Cancer Immunotherapy - Society for Immunotherapy of Cancer
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Cancer Immunotherapy - Society for Immunotherapy of Cancer
T Understanding RESO URCE Cancer Immunotherapy Published in partnership with FREE tankee o PAT I ENT CONTENT REVIEWED BY A DISTINGUISHED MEDICAL ADVISORY BOARD PRP PATIENT RESOURCE PUBLISHING ® 2014 Immunotherapy A.indd 1 9/17/2014 9:27:04 AM ABOUT THE Society for Immunotherapy of Cancer The Society for Immunotherapy of Cancer (SITC) is the world’s leading member-driven organization specifically dedicated to professionals working in the field of cancer immunology and immunotherapy. Established in 1984, SITC is a 501(c)(3) not-for-profit organization with a growing constituency of more than 800 academic, government, industry, clinical and basic scientists and medical professionals from around the world. SITC’s mission is to improve cancer patient outcomes by advancing the science, development and application of cancer immunology and immunotherapy through core values of interaction/integration, innovation, translation and leadership in the field. Learn more at www.sitcancer.org. 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Uhlig Publisher Linette Atwood Co-Editor-in-Chief Charles M. Balch, MD, FACS Co-Editor-in-Chief Michael B. Atkins, MD 14 Talking With Your Doctor About Immunotherapy 15 Advocacy & Financial Resources 16 Clinical Trials in Cancer Immunotherapy 33 Glossary of Terms: The Immune System and Immunotherapy Understanding Cancer Immunotherapy Advisory Board Charles M. Balch, MD, FACS Professor of Surgery, University of Texas Southwestern Medical Center Editor-in-Chief, Patient Resource LLC Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center Professor of Oncology and Medicine, Georgetown University School of Medicine Past President, SITC Bernard A. Fox, PhD Harder Family Endowed Chair for Cancer Research, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center Past President, SITC Chair, World Immunotherapy Council Howard L. Kaufman, MD, FACS Chief Surgical Officer, Associate Director for Clinical Science, Rutgers Cancer Institute of New Jersey President-Elect, SITC John M. Kirkwood, MD Usher Professor of Medicine, Dermatology and Translational Science, Co-Director, Melanoma and Skin Cancer Program, University of Pittsburgh Cancer Institute Member, SITC Co-Editor-in-Chief John M. Kirkwood, MD Senior Vice President Debby Easum Vice President, Operations Leann Sandifar Managing Editor Matt Smithmier Writer Dana Schneider PATI EN T R ESOU RCE CA NCER GU I DE Co-Editor-in-Chief Bernard A. Fox, PhD Co-Editor-in-Chief Howard L. Kaufman, MD, FACS Graphic Designer Michael St. George Production Manager Jennifer Hiltunen Vice Presidents, Amy Galey Business Development Stephanie Kenney Account Executive Kathy Hungerford Office Address 8455 Lenexa Drive Overland Park, KS 66214 For Additional Information [email protected] Advisory Board Visit our website at PatientResource.com to read bios of our medical and patient advisory board. For Additional Copies: To order additional copies of Patient Resource Cancer Guide: Understanding Cancer Immunotherapy, visit www.patientresource.com, call 913-725-1600, or email [email protected]. Editorial Submissions: Editorial submissions should be sent to [email protected]. Disclaimer: Information presented in Patient Resource Cancer Guide: Understanding Cancer Immunotherapy is not intended as a substitute for the advice given by your health care provider. 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The publisher is not engaged in rendering medical or other professional services. The publication of advertisements, whether paid or not, and survivor stories is not an endorsement. If medical or other expert assistance is required, the services of a competent professional person should be sought. © 2014 Patient Resource LLC. All rights reserved. PRP PATIENT RESOURCE PUBLISHING® For reprint information, email [email protected]. Pati entRes ource .c om 2014 Immunotherapy A.indd 1 1 9/17/2014 9:27:23 AM IMMUNOTHERAPY in the news Source: The New York Times, Los Angeles Times You may have heard about a new and innovative cancer treatment called immunotherapy. These treatments have given doctors new ways to fight cancer. Reports from mainstream media show results that are nothing short of miraculous: patients going into remission, many living longer and some even thought to be cured. Some of the agents for this treatment are so new, in fact, that many of these results come from patients participating in clinical trials, the research studies of drugs or treatment combinations that are not yet FDA-approved. What is this immunotherapy? Is it a cure, can I get it, and will it work for me? Is it true there are no side effects? Simply stated, immunotherapy is a type of treatment that uses your own immune system to attack your cancer. Just as the immune system attacks foreign germs, such as bacteria and viruses, it can also attack cancer cells. This rids the body of defective or abnormal cells, whether infected by a virus or changed because of cancer. Basically, “immuno” (from the immune system) + “therapy” (treatment) = “immunotherapy.” Cancer cells are cells that have originated from the tissues of the body that have damaged DNA and therefore grow out of control. Because they come from the body, however, these cells can trick your immune system into thinking they aren’t a threat by 2 2014 Immunotherapy A.indd 2 turning off the immune response or stopping the immune functions that might otherwise destroy them. Immunotherapy uses different ways to reverse those tricks, allowing the immune system to respond as it should and attack the cancer. Recent breakthroughs have been made specifically in the treatment of melanoma and prostate cancer and have begun to show promise in the treatment of lung, kidney, cervical, head and neck, and several other types of cancer. You may have recently heard about immunotherapy drugs such as pembrolizumab (Keytruda), interleukin 2 (Proleukin), sipuleucel-T (PROVENGE), ipilimumab (Yervoy) and nivolumab. These drugs are types of immunotherapy that focus on re-engaging different parts of the immune system to combat cancer. Studies of patients with advanced melanoma have shown that they are living longer, with up to 20 percent showing no signs of cancer years after treatment has been completed. Many of the patients treated in these trials had already tried other aggressive forms of treatment and had only a few remaining options. The results have been unprecedented in the history of melanoma treatment, and immunotherapy has quickly moved into the spotlight. As far as side effects: Most cancer treatments have the potential for side effects, and immunotherapy is no different. However, because immunotherapy is unlike other treatments, so is your body’s response. In fact, some patients experience only minimal side effects, if any. Because immunotherapy affects the immune system, however, some patients have suffered from a range of immune-related adverse effects that have needed immediate attention. The good news is that most of the side effects commonly associated with immunotherapy are readily treatable if recognized early. Immunotherapy and the immune system are both very complicated, and scientists are learning more about both every day. If you or someone you know is considering this type of treatment, it’s important to understand as much as you can so you can make informed decisions about your comprehensive cancer care. n P a t i e n t Reso ur ce.co m 9/17/2014 9:27:27 AM UNDERSTANDING THE BASICS of immunotherapy I mmunotherapy is a type of cancer treatment that seeks to stimulate your own immune system to fight cancer. Because cancer cells have the ability to evade the immune system by using a number of clever techniques (see page 6), the application of immunotherapy is based on understanding these techniques and using them to restore the immune system’s ability to destroy tumors. Immunotherapy is a rapidly evolving field, different from any previous “standard” cancer treatments, such as chemotherapy, radiation therapy and surgery. Chemotherapy uses drugs to kill rapidly multiplying cells, which includes cancer cells but sometimes healthy tissue as well. The destruction of healthy cells and tissues often leads to the side effects commonly associated with chemotherapy, including hair loss, nausea and vomiting, and low blood cell counts. Radiation therapy, which targets a specific region of the body, uses high-energy X-rays to destroy cancer cells. While often very effective, it’s not guaranteed to kill all of the cancer cells and usually involves the destruction of nearby healthy tissue as well. Surgery to remove a tumor, although common, can be invasive and may leave behind cancer cells that have the potential to develop into new tumors. Targeted therapy goes after specific mutations in the DNA of cancer cells. Although targeted therapy has been shown to produce a dramatic response against cancer cells without harming normal cells, this type of treatment doesn’t always totally destroy the cancer. Cancer cells have the ability to adapt and develop alternative ways to grow, essentially becoming resistant to the treatment over time. Tumors may shrink or disappear, but remaining cells that are able to adapt may begin growing again. Immunotherapy is fundamentally different because it focuses on activating the immune system to fight cancer, wherever it may be, and uses the body’s own immune cells and mechanisms to destroy the cancer. HISTORY OF IMMUNOTHERAPY Immunotherapy is a cancer treatment more than 100 years in the making, beginning most notably with Dr. William B. Coley, who worked with patients and multiple physicians to study how cancer tumors reacted to bacterial infections. He treated cancer patients with inoperable tumors by injecting a combination of bacteria, which became known as Coley’s Toxins, directly into their tumors. His results showed that this treatment shrank the tumors and sometimes even cured the patient. He believed that the body’s increased response to the bacteria also helped fight off the cancer. In the modern era, Dr. Donald Morton was an early proponent of immunotherapy and particularly cancer vaccines. His work with Bacillus Calmette-Guerin (BCG) for melanoma eventually led to the use – and eventual approval – of BCG for bladder cancer, the first successful immunotherapy treatment against a human tumor. Pati entRes ource .c om 2014 Immunotherapy A.indd 3 Because the immune system can be activated broadly against cancer cells throughout the body, it’s more difficult for cancer cells to hide from therapy or develop mechanisms to escape destruction. Immunotherapy also has the potential to remain effective for long intervals far beyond the end of treatment, a feature called “memory.” This feature is the same one that allows a tetanus vaccine, for example, to remain effective for many years. In cancer patients, this effect can lead to long-term, cancer-free remission and increased overall survival. Because it’s less likely that immunotherapy will affect healthy tissues and cells, side effects may be less common and either less severe or more easily treatable. As with any treatment, however, there are still associated risks that should be discussed with your doctor (see page 14). Immunotherapy may be an option alone or in combination with other treatments, including traditional treatments and other immunotherapies. Several different immunotherapy strategies are currently being studied or used as cancer treatment: n Monoclonal antibodies (mAbs) are engineered antibodies that target specific cancer cell antigens (proteins on the surface of cancer cells) or receptors on the surface of immune cells. n Non-specific immune stimulation involves giving the immune system a general boost to improve overall function and response, without targeting the cancer cells specifically. n Cancer vaccinations are vaccines created from either modified viruses or the patient’s own tumor or immune cells and engineered to direct immune cells to the cancer cells. Oncolytic virus immunotherapy is the use of viruses to directly infect only tumor cells and induce an immune response against the infected cancer. n Immune-checkpoint inhibitors target the immune checkpoints, which are a series of immune system “brakes,” and disengage them to make the immune response stronger. n Adoptive T cell transfer (T cell therapy) involves extracting immune cells from the patient, activating them outside the body using cancer tissues or T cell stimulants, and then multiplying them in the lab before injecting them back into the patient. n 3 9/17/2014 9:27:29 AM THE IMMUNE SYSTEM and how it works A better understanding of how the specific immunotherapy strategies may work starts with a basic knowledge of the immune system and how it interacts with cancer. The immune system is the body’s natural defense against infection and disease, responsible for protecting the host from substances that can cause harm, such as bacteria and viruses (sometimes called “germs”). The cells of the immune system continually circulate through the body, monitoring for invaders. These invaders can be recognized by their “antigens,” which are tiny proteins on their surface. Every cell or substance has its own specific antigens, and the body’s cells carry “self ” antigens that are specific to that one person. Cells bearing self antigens typically pose no threat. Invading germs, however, carry “non-self ” antigens because they did not originate in the body (see Figure 1). The immune system is designed to recognize this kind of antigen as harmful and respond appropriately. The immune system and its responses can be broken down into two subsystems: innate immunity and adaptive immunity. Innate immunity refers to the system that finds the invaders and sounds the alarm. Adaptive immunity refers to the system that creates the battle plan and launches the attack. Innate immune cells are responsible for gathering information about the invader and sharing it with the cells of the adaptive immune system. The innate immune system can also begin a very general attack, but because the adaptive immune system can’t “see” the threat until the innate cells share the information, FIGURE 1 Invader Self antigen Immune cell Non-self antigen ©Patient Resource LLC 4 2014 Immunotherapy A.indd 4 FIGURE 2 NORMAL IMMUNE RESPONSE Immune cells Antigen Antigenpresenting cells Invader (bacteria) Skinned knee: First barrier of protection is broken. An invader enters the body through the cut, where immune cells have begun to gather to protect the body. The immune cells begin to destroy and digest the invader and its antigens. ©Patient Resource LLC Some of the immune cells transform into antigen-presenting cells that tell the T cells about the invader. it’s important that they communicate as soon as possible. This allows the adaptive cells to start figuring out how to effectively fight the specific invader. Most immune cells release messengers called cytokines to help them communicate with other immune cells and regulate the immune system response. has been identified, B cells will work rapidly to produce antibodies against the invading germs, which can eliminate bacteria. Viruses like to hide inside normal cells and may be difficult for the immune system to “see,” but T cells are designed to detect abnormal Attacking a normal enemy Antigen-presenting cell (APC) When you skin your knee, you break the immune system’s first barrier, the skin, and harmful substances can easily enter the body (see Figure 2). Luckily, as soon as the injury occurs, immune cells that have been circulating in your body start to gather at the site and call other immune cells to help defend the body against invasion. Any bacteria or foreign substance that enters should be recognized by the immune cells as an invader. Innate immune cells known as natural killer cells begin to destroy the invaders with a general attack. Although this attack can kill some, it may not be able to destroy all of them or may be unable to prevent them from multiplying. Meanwhile, other immune cells start to eat the invaders and their foreign antigens. This “eating” causes the immune cells to transform into antigen-presenting cells (APCs). The APCs continue to gather information, which they then present to the primary immune cells of the adaptive immune system – the B and T cells. Once an antigen FIGURE 3 Antigen Naïve (inactive) T cell MHC T cell receptor Antigen-presenting cell presents antigen to naïve T cell, known as Signal 1. Antigen-presenting cell (APC) Antigen Activated T cell T cell receptor MHC Co-stimulatory molecules T cell recieves co-stimulatory signal to fully activate, known as Signal 2. ©Patient Resource LLC P a t i e n t Reso ur ce.co m 9/17/2014 9:27:35 AM fragments inside normal cells. Before these T cells have been told what to attack, they’re known as “naïve” T cells. In order for the APCs to effectively communicate with and activate the naïve T cells, they must connect through protein molecules on their surfaces. A specific molecule on the APC, called the Major Histocompatibility Complex (MHC) molecule, must successfully connect to the receptor on the T cell (see Figure 3). This first interaction is sometimes referred to as Signal 1. This connection allows the T cell to finally “see” the antigen and recognize it as a threat. Before a T cell can become fully activated, however, a second connection between additional molecules is necessary to confirm that the T cell still needs to launch an attack against the invader. This second signal is known as the co-stimulatory signal, or Signal 2. If a T cell receives Signal 1 but not Signal 2, it will die, ending the possibility of attacking the threat. If the T cell receives both signals, it will now be able to recognize the invader and destroy it. This fully activated T cell then multiplies to develop an army of T cells equipped with the necessary mechanisms to recognize and destroy the threat (see Figure 4). After multiple generations of immune cells have been created by the same immune response, some T cells transform into “regulatory” T cells, which are responsible for slowing and eventually shutting down the immune response FIGURE 5 Tumor cell FIGURE 4 T CELL PROLIFERATION Activated T cells When a T cell receives both signals to fully activate, the cell multiplies. ©Patient Resource LLC once the threat has been eliminated. Other T cells may become “memory” T cells, which can stay alive for many months or even years to fight off the same invader. This is the basis of immune protection against disease and explains why we don’t get the same diseases twice, such as measles or chicken pox. Because cancer cells are created by the body, the normal methods used to find and fight foreign invaders are not always effective. Attacking cancer Because cancer cells are created by the body, the normal methods used to find and fight foreign invaders are not always effective. If the body can’t distinguish the tumor cells from normal cells, the tumor cells may go completely unrecognized. However, a major feature of cancer cells is changes in their DNA, which can lead to abnormal proteins that are not found in normal, noncancerous cells. These abnormal proteins can often be recognized by the immune system much like the immune system can recognize viral proteins in normal cells. Because the T cells are responsible for eliminating most viral infections, they have been the primary focus of recent research. If the immune system detects cancer, the APCs must share that information with the T cells (see Figure 5). T cells are HOW THE IMMUNE SYSTEM ATTACKS CANCER Tumor antigens APC Naïve T cell Activated T cell Activated T cell Destroyed tumor cell Tumor cell Tumor cells release tumor antigens. APCs gather tumor antigens and prepare to present to naïve T cells. T cells are activated by the APC. Activated T cells find the tumor cells with the same tumor antigens and destroy them. ©Patient Resource LLC Pati entRes ource .c om 2014 Immunotherapy A.indd 5 5 9/17/2014 9:27:39 AM THE IMMUNE SYSTEM the primary players in the fight against cancer and their ability to activate and attack cancer is at the heart of immunotherapy research. These cells communicate with each other through a network of cell signaling. When the molecules on an APC connect to receptors on the T cell, the result is either a positive signal or a negative signal. Positive signals tell the T cell to activate and multiply. Negative signals tell the T cell to shut down. A T cell can only function properly if it recognizes the cancer as harmful, receives the proper signals to fully activate, and then gets continued approval to launch and maintain an attack. The delicate balance of these positive and negative signals regulates the strength and duration of the immune attack, keeping the attack going until the threat has been eliminated, then helping to shut it down once it’s no longer necessary (see Figure 6). However, cancer cells are able to take control of this normal mechanism that the body uses to shut off the immune response. This means that even if the immune system recognizes the cancer, it may not be able to successfully start the attack or maintain it long enough to eliminate the threat. One specific area of research focuses on the cancer cells’ ability to trick the immune FIGURE 6 APC T cell MHC T cell receptor Tumor antigen + + + Co-stimulatory molecules The positive and negative signals help to regulate the strength and duration of the immune response. system into prematurely engaging “checkpoint pathways.” Checkpoint pathways are part of the system of checks and balances that allow the immune cells to evaluate their attack at multiple stages; pathways THE 3 E’s 1 CANCER vs. THE BODY 2 ©Patient Resource LLC essentially function as the brakes when the response is no longer necessary. By engaging the brakes, the cancer shuts down the attack response and is able to continue growing. Recent research has shown that Elimination – In the elimination phase, the immune system recognizes and eliminates cancer cells. This phase suggests that our bodies may be regularly introduced to cancerous changes and that our immune systems are capable of handling and eliminating them. In the 1950s, researchers thought the immune sys- tem did two things: it protected your body against bacteria and viruses, and it looked for abnormal cells and killed them before they could become tumors. Called the cancer immunosurveillance theory, it was initially rejected. In the last 10 years, however, studies have shown that immune cells are indeed important in the prevention of cancer. Although tumors may develop in a functioning immune system, the way a tumor grows and develops is influenced by the body’s immune response. Based on this new evidence, the theory has been refined and renamed “cancer immunoediting” and confirmed by the mouse tumor studies conducted by Dr. Robert Schreiber. The three E’s of Dr. Schreiber’s theory of cancer immunoediting are elimination, equilibrium and escape: 6 2014 Immunotherapy A.indd 6 Equilibrium – If the cancer cells are not eliminated immediately, they may exist in a delicate balance between growth and suppression by the immune system. During equilibrium, the body’s immune system is able to keep the cancer cells under control but is unable to eradicate them completely. In this phase, a tumor may remain dormant for an indeterminate amount of time, completely unrecognized by medical testing. According to the theory, however, the constant interactions between the tumor cells and the T cells of the adaptive immune system may actually lead to tumors that can adapt to the immune response and are no longer susceptible to an immune attack. Tumors that have successfully adapted to the immune response can no longer be controlled and move on to the third phase. 3 Escape – The escape phase refers to the disruption of equilibrium (balance) that leads to immunosuppression, allowing the dormant tumors to escape immune control and begin growing in an environment of immune “tolerance.” It’s at this point that the clinical symptoms of cancer begin to emerge. Tumors in the escape phase use a number of mechanisms that alter the body’s immune response in such a way that actually allows them to grow. P a t i e n t Reso ur ce.co m 9/17/2014 9:27:42 AM TOLERATING CANCER HOW CANCER CELLS EVADE DETECTION If you suffer from an allergy – pollen, for example – you might see your doctor for periodic allergy shots. These shots work much like a vaccine: As the amount of the particular allergen is injected in increasing doses over a series of visits, your body begins to develop a tolerance to pollen. This type of therapy can eventually lead to decreased symptoms from a pollen exposure, or even may eliminate your symptoms altogether. Because your body no longer recognizes pollen as an invader, the immune system stops attacking it. blocking the effect of these checkpoint pathways can restore the activity of tumor-directed immune cells. Recent breakthroughs in immunotherapy research have involved two checkpoint pathways, the CTLA-4 immune checkpoint pathway and the PD-1/PD-L1 immune checkpoint pathway (see Figure 7). FIGURE 7 Cancer often uses this same trick. In early stages, cancer cells may shed proteins into your body. As these proteins circulate through your bloodstream, you begin to develop a tolerance. And once that tolerance exists, your body may not recognize these cancer cells as a threat. Then, just like the pollen, the cancer cells may be safe from an immune system attack. Immunotherapy seeks to reverse this tolerance, to once again identify the cancer cells as a threat and a target for destruction. CHECKPOINT PATHWAYS APC MHC T cell receptor + The delicate balance of these positive and negative signals regulates the strength and duration of the immune attack. Pati entRes ource .c om 2014 Immunotherapy A.indd 7 + - CTLA-4 CTLA-4 checkpoint pathway When the CTLA-4 molecule connects instead of other molecules, a negative signal is sent to the T-cell. T cell Tumor cell Tumor antigen MHC The longer the exposure to the tumor, the more reduced the immune response becomes. And the longer cancer cells are subjected to a weakened immune response, the more they’re able to adapt, and the easier it is to manipulate immune cells. It’s as if the tumor recruits the body’s own immune cells to turn around and fight off the attack, using the very mechanisms put in place for protection. Immunotherapy research focuses on finding these different ways tumors manipulate the immune system to reduce its effectiveness, with the goal of allowing the immune system to react to the cancer for as long as necessary to destroy all of the tumor cells. n T cell Tumor antigen T cell receptor + PD-L1 PD-1 PD-1 checkpoint pathway ©Patient Resource LLC When PD-1 connects to PD-L1, a negative signal is sent to the T cell to inactivate. 7 9/17/2014 9:27:46 AM TYPES OF IMMUNOTHERAPY C ancer immunotherapy targets the different stages of the anticancer immune response that appear to be easily influenced and manipulated by tumors. Several immunotherapy strategies have been created to help stimulate and re-engage the immune system, including treatments to help the immune cells recognize and destroy cancer cells. by strategy FIGURE 2 DELIVERING THERAPEUTIC AGENTS TO CANCER CELLS WITH MONOCLONAL ANTIBODIES Chemotherapy drug Monoclonal antibody (mAb) FIGURE 1 Monoclonal antibody A monoclonal antibody (mAb) carrying chemotherapy targets specific cancer cells and attaches to the surface. ©Patient Resource LLC The tumor cell engulfs the mAb. Monoclonal antibody with attached therapeutic agent Monoclonal antibodies (mAbs) One of the body’s natural immune responses to foreign substances is the creation of antibodies specific to the antigens found on the surface of invaders and damaged or infected cells. Monoclonal antibodies are manmade antibodies engineered to target specific tumor antigens. They work in a few different ways: nFlagging targeted cancer cells for destruction – The mAb can act as a flag that attaches to molecules or parts found only on the surface of specific cancer cells, marking them for destruction by other immune cells. nBlocking growth signals and receptors – Some mAbs are engineered to block the mechanisms that cancer cells use to grow. These mAbs work in a variety of ways, including blocking certain pathways that allow the cancer to thrive, or destroying the blood supply for the tumor. Cancer cells rely on these blood vessels to deliver oxygen and nutrients; blocking them deprives the cancer cell of resources, which can help to slow or stop growth. As the mAb is digested, the toxic particles are released, causing cell death from within. ©Patient Resource LLC nDelivering other therapeutic agents directly to targeted cancer cells – The mAbs can be engineered to carry cancer drugs or radiation particles directly to cancer cells. When a mAb is combined with a chemotherapy drug or specific toxin, it travels through the system until it reaches the targeted cancer cell, then attaches to its surface. The tumor cell then engulfs the mAb and begins to break it down internally. This releases the chemotherapy drug or toxin, inducing cell death from within. Basically, the tumor cell inadvertently causes its own death. This di- >> TIMELINE OF IMMUNOTHERAPY 1890 Dr. Coley creates the first immunotherapy treatment when he injects bacteria directly into inoperable tumors to stimulate an immune response that also fights the cancer. 8 2014 Immunotherapy A.indd 8 1956 Tumor-specific cell antigens are discovered. 1973 Dendritic cells are identified as “antigen-presenting cells” (APCs). 1978 Bacillus Calmette-Guerin is first studied for bladder cancer; interleukin-2 (IL-2) is discovered. 1978 Tumor-specific monoclonal antibodies (mAbs) are discovered. 1984 Society for Immunotherapy of Cancer (formerly SBT) is founded. 1985 Adoptive T cell transfers are studied as a possible cancer treatment. rect form of delivery typically damages only the targeted cells. Combining mAbs with radiation particles, called radioimmunotherapy, allows for radiation to be delivered in lower doses over a longer period of time directly to specific cancer cells, leaving the majority of surrounding cells undamaged. These radiation-tagged mAbs may also be helpful in determining the diagnosis or spread of certain cancers by using a special imaging device to detect where the radioactive particles accumulate in the body. 1985 Results from IL-2 and lymphokineactivated killer cell (LAK) cell therapy in various tumors are first reported. 1986 The Extramural IL-2/LAK Working Group is formed with funding from the National Cancer Institute to confirm results of the high-dose IL-2/ LAK cell regimen in the treatment of melanoma and renal cell cancer. P a t i e n t Reso ur ce.co m 9/17/2014 9:27:49 AM Chemical messengers called cytokines can also be attached to a mAb, which is then called an immunocytokine. This agent delivers cytokines to the tumor cells to help promote a normal immune response. This therapy is being tested in clinical trials right now. A number of monoclonal antibodies are currently available to treat several different cancers, and clinical trials are currently testing new ones for nearly every type of cancer. Approved monoclonal antibodies include: • Breast cancer: trastuzumab (Herceptin), ado-trastuzumab (Kadcyla) • Chronic lymphocytic leukemia: obinutuzumab (Gazyva), alemtuzumab (Campath), rituximab (Rituxan), ofatumumab (Arzerra) • Colorectal cancer: bevacizumab (Avastin), cetuximab (Erbitux), panitumumab (Vectibix) • Gastric cancer: trastuzumab (Herceptin), ramucirumab (Cyramza) • Hodgkin lymphoma: brentuximab vedotin (Adcetris) • Kidney cancer: bevacizumab (Avastin) • Lung cancer: bevacizumab (Avastin) • Melanoma: ipilimumab (Yervoy), pembrolizumab (Keytruda) • Non-Hodgkin lymphoma: rituximab (Rituxan), ibritumomab (Zevalin) Notable mAbs in clinical trials include: • bavituximab (breast cancer, liver cancer, lung cancer, melanoma, pancreatic cancer, rectal cancer) • blinatumomab (ALL, non-Hodgkin lymphoma, gastric cancer, lung cancer) • Ch14.18 (neuroblastoma) • MT110 (colorectal cancer, gastric cancer, lung cancer) • nivolumab (melanoma) • rilotumumab (fallopian cancer, gastric cancer, lung cancer, ovarian cancer) • selectikine (melanoma) 1988 First results from tumor-infiltrating lymphocytes (TIL) therapy are reported. 1990 Bacillus Calmette-Guerin is approved for treatment of bladder cancer. 1990 First treatment with genetically modified TIL. 1991 Granulocyte macrophage-colony stimulating factor (GMCSF), sargramostim Pati entRes ource .c om 2014 Immunotherapy A.indd 9 FIGURE 3 APC FIGURE 4 MHC Tumor T cell receptor antigen T cell T cell T cell receptor Tumor cell MHC Tumor antigen PD-1 CTLA-4 APC MHC Tumor antigen T cell receptor PD-L1 T cell Monoclonal antibody blocking the connection Immune checkpoint inhibitors Immune checkpoint pathways are the specific connections between molecules on the surfaces of cells – specifically between antigen-presenting cells and T cells, or between T cells and tumor cells – that help regulate the immune response. Some tumor cells have proteins on their surface that bind to activated immune cells, inhibiting their function. This connection effectively puts the brakes on the attack (known as tumorinduced immunosuppression). Understanding how to block certain immune checkpoint pathways is an important focus of current research. Immune checkpoint inhibitors are drugs that block the checkpoint from being engaged, which essentially turns the immune response back (Leukine), is approved to boost white blood cell counts. 1992 High-dose IL-2 is approved to treat metastatic kidney cancer. T cell receptor Tumor antigen CTLA-4 CTLA-4 checkpoint pathway T cell PD-1 MHC Tumor cell PD-L1 Monoclonal antibody PD-1 checkpoint blocking the connection pathway ©Patient Resource LLC on. Immune checkpoint inhibitors currently being studied for use in the treatment against cancer include: nAnti-CTLA-4: CTLA-4 is a protein receptor found on the surface of T cells. When engaged by molecules on the surface of antigen-presenting cells, CTLA-4 is capable of suppressing the immune system response (known as “downregulating”). Anti-CTLA-4 antibodies block the connection necessary to engage this protein, allowing the T cells to continue their response against the cancer cells, rather than shutting it down (see Figure 3). nAnti-PD-1: The PD-1 checkpoint pathway is CTLA-4’s checkpoint pathway backup. When the PD-1 receptors on the surface of T cells connect with the PD-L1 molecules on the surface of cancer cells, signals are sent to the T 1996 Interferon alfa2b is approved for the adjuvant treatment of high-risk melanoma. cell malignancies. 1998 IL-2 is approved to treat metastatic melanoma. 1997 The first monoclonal antibody, rituximab (Rituxan), is approved to treat B- 1998 The monoclonal antibody drug trastuzumab (Herceptin) is approved to treat breast cancer. 1999 Denileukin diftitox (Ontak), a fusion of IL-2 and diphtheria toxin, is approved. >> 2000 Gemtuzumab ozogamicin (Mylotarg), which combines a 9 9/17/2014 9:27:53 AM TYPES OF IMMUNOTHERAPY cells to dampen the response. Anti-PD-1 drugs block the connection necessary to engage this protein, allowing the T cells to continue their response against the cancer cells. nAnti-PD-L1: Cancer cells have the ability to make certain molecules appear on the surface, including PD-L1 and PD-L2 of the PD-1 checkpoint pathway. These molecules bind to the PD-1 on the T cells and turn them off, preventing attack of the cancer cell. In addition to researching PD-1 inhibitors, scientists are also researching blocking the PD-L1 molecule (see Figure 4, page 9). These checkpoint pathway blockers stop the negative signals associated with certain checkpoint pathways, but researchers are also studying ways to increase the positive signals between cells that can promote stronger immune responses. For example, studies have shown that engaging certain stimulatory receptors with the use of monoclonal antibodies enhances the number and activity of certain T cells. This increases the amount of positive signals and decreases the impact of the negative signals. Clinical trials are also studying the use of both types of treatment at the same time. FDA-approved immune checkpoint inhibitors include: • Melanoma: ipilimumab (Yervoy), pembrolizumab (Keytruda) Notable immune checkpoint inhibitors in clinical trials include: • ipilimumab (Yervoy) (non-small cell lung cancer, prostate cancer) • MPDL-3280A (advanced melanoma, lung cancer, kidney cancer, bladder cancer) • nivolumab (advanced melanoma, lung cancer, kidney cancer, head and neck cancer) • pembrolizumab (MK-3475) (lung cancer, kidney cancer, head and neck cancer) >> >> TABLE 1 IMMUNOTHERAPY TREATMENTS BY CANCER TYPE Cancer FDA-approved treatments Major clinical trials Bladder • Bacillus Calmette-Guerin • MPDL-3280A Blood cancers • alemtuzumab (Campath) • brentuximab vedotin (Adcetris) • ibritumomab (Zevalin) • interferon alfa-2a (Roferon-A) • obinutuzumab (Gazyva) • ofatumumab (Arzerra) • rituximab (Rituxan) • Adoptive T cell therapy • Anti-PD-1/PD-L1 treatments • BioVaxID • blinatumomab • Chimeric antigen receptors (CARs) Breast cancer • ado-trastuzumab emtansine (Kadcyla) • trastuzumab (Herceptin) • bavituximab • NeuVax Kidney cancer • bevacizumab (Avastin) • High-dose interleukin-2 • IFN-alfa • Combination treatments (ipilimumab/nivolumab) • MPDL-3280A • nivolumab Lung cancer (NSCLC) • bevacizumab (Avastin) • bavituximab • blinatumomab • ipilimumab (Yervoy) • MPDL-3280A • MT110 Melanoma • High-dose interleukin-2 • High-dose interferon alfa • ipilimumab (Yervoy) • pegylated interferon alfa-2b • pembrolizumab (Keytruda) • Adoptive T cell therapy • bavituximab • Combination treatments (ipilimumab/nivolumab) • nivolumab • selectikine • talimogene laherparepvec (TVEC) Prostate cancer • sipuleucel-T (PROVENGE) • sipuleucel-T/Pca combination treatments • Toll-like receptor (TLR) ligands (adjuvant therapy) • tremelimumab (hepatocellular cancer, mesothelioma) • Combination ipilimumab/nivolumab (advanced melanoma, kidney cancer, non-small cell lung cancer) Non-specific immune stimulation Non-specific immune stimulation involves giving the immune system an overall boost. This is achieved by exposing the body to certain molecules capable of activating immune cells, such as T cells, resulting in an increased immune response. This type can be used alone or in combination with other treatments in order to produce increased and longer lasting immune responses. Different types of non-specific immune stimulation include: • nivolumab • pembrolizumab (MK-3475) • rilotumumab immunotherapy – Cytokines are the messengers of the immune system, aiding in communication between immune cells and playing a big role in the full activation of an adaptive immune response. Cytokine immunotherapy treatments involve introducing large amounts of cytokines to the immune system to promote specific immune responses. There are several cytokines currently being studied in the treatment against cancer, including interleukin, interferon and GM-CSF: • Interleukins are cytokines that help regulate the activation of certain immune cells. These proteins have been successfully recreated in a lab and developed into the drug IL-2. There are also several molecules siminCytokine TIMELINE OF IMMUNOTHERAPY monoclonal antibody and a toxin from the bacteria Micromonospora echinospora, is approved for acute myeloid leukemia. 2002 Ibritumomab tiuxetan (Zevalin), a 10 2014 Immunotherapy A.indd 10 monoclonal antibody with a radioisotope, is approved for some nonHodgkin lymphomas. 2003 Tositumomab and Iodine I 131 tositumomab (Bexxar), a monoclonal antibody- based, radioimmunotherapeutic regimen for the treatment of CD-20 positive, follicular non-Hodgkin lymphoma, is approved. 2004 Monoclonal anti-vascular endo- thelial growth factor antibody bevacizumab (Avastin) is approved for metastatic colorectal cancer. 2004 Cetuximab (Erbitux), an antiepidermal growth factor receptor monoclonal antibody, is approved. 2006 Panitumumab (Vectibix), a monoclonal anti-epidermal growth factor receptor antibody, is approved. 2009 Anti-CD20 monoclonal antibody ofatumumab (Arzerra) is approved for chronic lymphocytic leukemia. 2010 Gemtuzumab ozogamicin is discontinued due to safety P a t i e n t Reso ur ce.co m 9/17/2014 9:27:53 AM FIGURE 5 lar to IL-2 in clinical development, including IL-7, IL-12, IL-15 and IL-21. • Interferons are cytokines that boost the ability of certain immune cells to attack cancer cells. These proteins have been successfully re-created in a lab and developed into the drug IFN-alfa. • GM-CSF (granulocyte-macrophage colony stimulating factor) are cytokines that stimulate the bone marrow, promoting immune and blood cell growth and dendritic cell development. GM-CSF has been successfully re-created in a lab, developed into the drug sargramostim (Leukine) and is currently being used to boost white blood cell count after chemotherapy treatment. Some studies have suggested a benefit with sargramostim alone or in combination with other immunotherapy agents for patients with advanced melanoma, but this has not yet been confirmed in randomized clinical trials. bacteria – One approved treatment for bladder cancer is actually an altered tuberculosis vaccine called intravesical Bacillus Calmette-Guerin (BCG). BCG is bacteria that have been modified to ensure they will not spread disease. Treatment causes inflammation in the bladder that guides the immune response to the bladder cancer cells. nToll-like receptor agonists – The immune system often detects germs through a series of receptors called toll-like receptors that are found on the surface of most immune cells. When patterns in bacteria or viruses are “seen” by these toll-like receptors, they produce a signal that activates the immune cell to attack. Several of these specialized receptors have been evaluated for use in cancer, and one such agent, imiquimod (Aldara, Zyclara), binds to the toll-like receptors 7 and 8, resulting in an immune response that kills cancer nModified concerns and lack of benefit. advanced prostate cancer. 2010 The first therapeutic cancer vaccine, sipuleucel-T (PROVENGE), a dendritic cell vaccination, is approved to treat 2011 Ipilimumab (Yervoy), a monoclonal antibody targeted to a T cell checkpoint protein, is approved to treat melanoma. Pati entRes ource .c om 2014 Immunotherapy A.indd 11 DENDRITIC (or APC) CELL VACCINES 4 The APCs are injected back into the patient, where they activate T cells so they can find and fight the cancer cells. Antigen-presenting cells 3 This transforms them into APCs. 1 The patient’s own immune cells are extracted from the body. Immune cells 2 These cells are sent to a lab. ©Patient Resource LLC cells in patients with basal cell skin cancers and possibly other early-stage skin cancers. Current FDA-approved non-specific immune stimulators include: • IFN-alfa (kidney cancer, melanoma, certain leukemias and lymphomas, Kaposi sarcoma) • IL-2 (kidney cancer, melanoma) • Bacillus Calmette-Guerin (bladder cancer) • imiquimod (Aldara, Zyclara) (early-stage skin cancer) Notable non-specific immune stimulators in clinical trials include: • montanide (used concurrently with cancer vaccinations in the treatment of several cancers) • Toll-like receptor (TLR) ligands as adjuvant therapy with therapeutic cancer vaccines (brain, kidney, lung, colon, pancreatic, prostate, ovarian, breast) • sargramostim (Leukine) used as adjuvant 2011 Pegylated interferon (PEG-Intron) is approved for adjuvant therapy of selected melanoma patients. 2012 Several clinical studies of T cell checkpoint inhibitors targeting PD-1 and PD-L1 demonstrate therapeutic activity in many types of cancer. 2013 The combination of two agents targeting CTLA-4 and PD-1 checkpoints therapy with therapeutic cancer vaccinations (prostate and pancreatic cancer) Cancer vaccines There are two types of cancer vaccines: prophylactic vaccines used to prevent the viruses that cause cancers and therapeutic vaccines used to treat existing cancers. Currently, prophylactic vaccinations are available for the human papillomavirus (HPV), the cause of most cervical cancers, and hepatitis B (HBV), a known risk factor for liver cancer. Therapeutic cancer vaccinations include several types: nTumor cell vaccines (autologous) – Autologous tumor cell vaccinations are made from your own tumor cells, extracted directly from the tumor or from the blood and treated with radiation to prevent spreading. This allows each patient to have a customized vaccine that includes antigens from the patient’s own cancer cells. They are modified in a lab to make them safer and more susceptible demonstrate remarkable activity in a melanoma clinical trial. 2013 The first Phase III trial of oncolytic virus immunotherapy shows improvement in the long-term response rate in patients with melanoma. 2014 Pembrolizumab (Keytruda) is the first PD-1 inhibitor to gain FDA approval to treat advanced melanoma. 11 9/17/2014 9:27:55 AM TYPES OF IMMUNOTHERAPY to immune attack, then injected back into the body. Allogeneic tumor cell vaccinations are another option; the cells or tissues used to make the vaccination come from a donor. This method is typically easier and less expensive, but a difference in effectiveness between the two has not yet been determined. nAntigen (or peptide) vaccines – These are made from the proteins or pieces of proteins (peptides) expressed on only the surface of tumor cells rather than the entire cancer cell. These vaccinations are specific to a certain type of cancer but are not patient-specific. nDendritic (or APC) cell vaccines – Dendritic cell vaccinations are made from white blood cells that are extracted from the patient and sent to a lab, where they are exposed to chemicals that turn them into dendritic cells. These dendritic cells are then exposed to cancer cells and tumor antigens so that they begin preparing the antigen material for presentation before being injected back into the body (see Figure 5, page 11). These matured APCs activate the T cells in the body with the tumor antigens they need to recognize the abnormal cancer cells as a threat. Any cells that release that specific antigen are then targeted and destroyed. Sipuleucel-T (PROVENGE) is an FDA-approved drug consisting of chemically activated dendritic cells exposed to the prostate cancer antigen expressed by most prostate cancer cells as well as the cytokine GM-CSF. These matured APCs are injected into the body to help train the immune system to recognize and destroy the cancer cells that express that antigen. nVector-based vaccines – Vector-based vaccines are made from altered viruses or bacteria that are injected into the body to create an immune response, both specific FIGURE 6 12 2014 Immunotherapy A.indd 12 >> Oncolytic virus immunotherapy uses natural or modified viruses to directly attack and kill tumor cells while simultaneously starting an immune response. One of the most-studied approaches uses a modified, weakened version of the herpes simplex virus called talimogene laherparepvec (TVEC). TVEC is a safer herpes virus that contains the gene for GM-CSF. The virus targets only specific cancer cells, infects them and replicates continuously within the cell until it explodes (see Figure 6). This kills the cell and releases the GM-CSF protein implanted with the virus to promote an overall immune system boost against the cancer. The immune response can then eliminate cancer cells that have not been infected with the virus. FDA approved cancer vaccinations include: • Cervarix (cervical-cancer-causing HPV) • Gardasil (cervical-cancer-causing HPV) • Hepatitis B vaccine (liver cancer risk factor hepatitis B) • sipuleucel-T (PROVENGE) (prostate cancer) – dendritic cell vaccination (DCVac) Notable cancer vaccinations in clinical trials include: • BioVaxID (non-Hodgkin lymphoma and mantle cell lymphoma) • CDX-110 (brain cancer) • CRS-207 and GVAX Pancreas combination (pancreatic cancer) • • • • • • DCVax (brain cancer) GVAX Pancreas (pancreatic cancer) HyperAcute-Pancreas (pancreatic cancer) Imprime PGG (colorectal cancer) NeuVax (breast cancer) sipuleucel-T (PROVENGE) (in combination with other treatments) • TVEC (metastatic melanoma) Adoptive T cell transfer Adoptive T cell transfer focuses on manipulating the body’s own T cells to fight cancer. Immune cells are collected from the patient, engineered to recognize specific cancer cells, and then infused back into the patient. The modified T cells seek and destroy the cancer cells that carry those specific antigens. The three methods of adoptive T cell transfer include: • Collecting a sample from the actual tumor and multiplying the tumorinfiltrating T cells in a laboratory • Taking T cells from the bloodstream and genetically altering them to attack cancer cells that have specific antigens • Taking T cells from the body and modifying them with special receptors, called chimeric antigen receptors (CARs), that recognize specific proteins found on the surface of cancer cells. The CAR T cells bind to the cancer cells that have those proteins and then destroy them. This type of immunotherapy treatment is still investigational and available only through clinical trials. Studies have shown promise in the treatment of leukemia, lymphoma, metastatic melanoma, neuroblastoma and synovial cell sarcoma. n ONCOLYTIC VIRUS IMMUNOTHERAPY Engineered oncolytic viruses find specific cancer cells... ©Patient Resource LLC and overall. Tumor-specific vectors are genetically modified to target specific cancer cells in such a way that trains the immune system to recognize and destroy them. One vector-based vaccine currently being studied to treat leukemia is an HIV virus (modified to no longer cause disease). ...infect them and begin to multiply inside. The viruses continue to multiply.... ...until the cancer cell ruptures, releasing cancer-fighting viruses and immune-stimulating antigens. P a t i e n t Reso ur ce.co m 9/17/2014 9:28:03 AM SURVIVOR STORY Steven Silverstein Survivor Dedicated Himself to Giving Back After Melanoma Steven Silverstein is a 58-year-old Stage IV melanoma survivor. His disease was initially dismissed, but after his eventual diagnosis and a few different treatment options, he was given an immunotherapy drug that saved his life. Steven spent 34 years working in the lighting industry, but in 2013, he sold his company and began devoting his time to the Melanoma Research Foundation, the Department of Defense Cancer Funding Program, The Valley Hospital and other organizations. Steven and his wife, Ava, have been married for 30 years and have two daughters and a dog. When he can find the time, Steven enjoys photography, cycling, skiing and golf. T here has been no moment in my life more horri- ble than the moment I was confronted with a cancer diagnosis. The instant in which I learned I had Stage IV melanoma will stick with me forever; however, I’ve since moved past the disease both physically and emotionally. Let’s first jump back to the beginning. My story began about 11 years ago during a routine visit to the dermatologist when I pointed out a lesion on my face. The doctor said it was nothing, but he arranged to have a plastic surgeon remove it anyway upon my request. The plastic surgeon confirmed it was nothing and decided it wasn’t even worth sending to the lab for testing. The following summer, I developed some swelling under my jaw. A needle biopsy revealed melanoma, and a full-body scan uncovered liver metastasis. Because my cancer had initially gone undiagnosed, it had already progressed into Stage IV disease. The news of my diagnosis left me shocked, devastated and overwhelmed. I had always been a proactive, sun-educated individual who visited the dermatologist annually. I was at a wonderful stage of family life, and I had just returned from a weeklong trip full of hiking and rock climbing only to be told I had just 12 to 18 months to live. I met with several oncologists to get multiple opinions. I also developed an inner team of personal advisers, which consisted of several knowledgeable family members and friends. They helped me reflect upon and analyze the massive amounts of information I was receiving from medical professionals. Ultimately, I opted for a full neck dissection to remove the cancer from my lymph nodes. Even though the doctors and I knew it wouldn’t cure my disease due to the liver metastasis, we wanted to remove as much of the tumor load as possible. Following surgery, I unsuccessfully attempted to join a clinical trial, so I instead started a chemotherapy regimen that included the drugs temozolomide (Temodar) and thalidomide (Thalomid). I also tried chemoembolization to attempt to slow the cancer growth; a catheter was inserted into my liver and drugs blasted specific sites. Pati entRes ource .c om 2014 Immunotherapy A.indd 13 In addition to the traditional treatments, I also started acupuncture, began eating an organic diet, got plenty of exercise and rest, and enlisted the services of a psychiatrist. As time went on and no treatment had proved effective, it became clear that I was nearing the end of my options. We decided it was time to try interleukin-2 (IL-2) despite its notorious side effects, which can include flu-like symptoms, nausea, skin sensitivity, kidney reactions, digestive tract inflammation and more. Was it fun? Hardly. But it wasn’t as bad as its reputation, and in the hands of an experienced team, led by Dr. Howard Kaufman, all of these symptoms were manageable. Additionally, the chance of being cured was well worth the discomfort. About five months after starting IL-2, the progress of my disease had stopped and there was no further evidence of active metabolic activity. I was thrilled, but I wanted to be vigilant about staving off recurrence, so I followed up that treatment with a three-year regimen of injections with the then-experimental drug sargramostim (Leukine). I also had follow-up PET and CT scans every three months for five years and every six months thereafter, ceasing by the end of the eighth year. These days, I’m doing great. I’m approaching my 11th anniversary of being cancer-free, and I’m fortunate to have no lasting physical effects. All that’s left is a new awareness and a calling to give back to the cancer community. A while back, I began to get involved with the Melanoma Research Foundation (MRF), and soon I was on the board, learning about and gaining insights into the world of cancer research. All those years ago when I was lying in a hospital bed, fighting and hoping for the best, I was overwhelmed with questions like, “How are drugs and cures developed?” and “Why does it take so long?” Now, as chair of MRF, I understand the answers to those questions, and I do what I can to share my knowledge with those currently engaged in their own battles. I also discuss with them the treatment process, the breaking news and trends in the field, where to get help, and other important issues surrounding family, friends, physical condition and mental attitude. My hope is that they take comfort in knowing there’s an entire community dedicated to supporting their needs and eradicating melanoma. n 13 9/17/2014 9:28:05 AM TALKING WITH YOUR DOCTOR about immunotherapy B e sure to discuss the prospect of immunotherapy with your doctor to see if it’s the best treatment option for your particular diagnosis, or if there’s any added benefit to including immunotherapy as a part of your comprehensive cancer care. Below are some topics you should discuss and information to help you begin the conversation. Also included are other suggested questions you may want to ask if you’re considering immunotherapy as a treatment: What makes immunotherapy so different? Immunotherapy activates your body’s own immune cells to find and attack cancer cells. Every day the immune system fights off viruses and infections, but because cancer is so similar to normal cells, the immune system’s typical response may not work. Different types of immunotherapy trigger the body’s immune system in different ways to find and destroy the cancer. >> Is it like chemotherapy? No. Immunotherapy is a completely different method of treatment. Unlike chemotherapy, which uses powerful drugs to kill rapidly multiplying cells, immunotherapy focuses on re-engaging the immune system so that it recognizes and kills only specific cancer cells. >> What are the possible side effects? With immunotherapy, cancer cells are targeted and destroyed by the body’s own immune system rather than by drugs or radiation. Because of this, damage to healthy tissue is often less than with other therapies. This means immunotherapy doesn’t normally cause many of the side effects commonly associated with standard cancer treatments. However, flu-like symptoms, infusion reactions, rashes, and moderate to severe diarrhea have been reported with the use of some immunotherapy drugs. And because immunotherapy can activate the immune system, there is a risk that certain immunotherapy drugs may cause more serious autoimmune reactions, known as immune-related adverse events (IRAEs), when the immune system reacts against normal body organs. However, most side effects associated with immunotherapy are easily manageable if treated early, so be sure to talk >> 14 2014 Immunotherapy A.indd 14 to your doctor about what to expect before treatment begins, and carefully monitor how you feel during and after treatment. Is immunotherapy right for me? Some immunotherapy treatments are patient-specific and depend on the exact type of cancer you have, and your doctor will need to determine your eligibility based on treatment criteria. Participation in an immunotherapy clinical trial will also have specific qualification guidelines, which may include diagnosis, general health and treatment history. Because cancer immunotherapy is dependent on a functioning immune system, it will likely be important that you not have any autoimmune disorders and are not taking any chronic immunosuppressive medications. Be sure to discuss all of your available treatment options with your doctor to determine the best treatment for your specific diagnosis. Immunotherapy may be considered as treatment alone or in combination with other treatments and immunotherapies. >> your treatments in a specific facility on a very strict regimen. Some treatments require hospitalization, while others can be given safely in an outpatient clinic or doctor’s office. How long until we know whether treatment is effective? Immunotherapy is a different form of cancer treatment, so measuring results can also be different. The effectiveness of standard treatments is typically measured in both progression-free survival and overall survival. With chemotherapy, an increase in tumor size or the presence of new tumors is considered disease progression and often means the treatment isn’t working. With immunotherapy, however, the immune system needs time to mount an effective immune attack, which may result in a delayed response. During this time, tumors may continue to grow or new tumors may appear before the body can effectively target and destroy the cancer cells. As a result, many immunotherapy treatments may not show >> How do I get started? doctor should discuss any FDA-approved immunotherapy >>drugsYouthatandareyourapplicable to your diagnosis, as well as any available clinical trials within a reasonable traveling distance for you. The National Cancer Institute (NCI) maintains a list of current clinical trials that can be accessed at www.clinicaltrials.gov. Once you have determined your best options, do your research and talk to your doctor about any additional questions you have so you can make informed decisions throughout the treatment process. How are immunotherapy treatments administered? Your treatment regimen will depend on the treatment you receive. For example, the immunotherapy cancer vaccine sipuleucel-T (PROVENGE) requires biweekly visits – one for collecting the immune cells and another for the intravenous vaccination injection – over the course of three weeks. Typically, immunotherapy treatments are given intravenously and may require specialized centers with physicians and staff members who have been trained in the delivery of specific immunotherapy drugs. If you’re participating in a clinical trial, you may be required to receive >> a significant increase in progression-free survival but over time may offer more longlasting and life-extending benefits. The duration of your treatment will depend on the specific treatment type and your individual response to the medication. Some patients may need to continue treatments over an extended period of time in order to keep the immune system engaged. Some immunotherapy treatments, however, have shown responses that last beyond the end of treatment. You should discuss your response with your doctor and remember that sometimes progress may take several weeks or even months. n P a t i e n t Reso ur ce.co m 9/17/2014 9:28:06 AM ADVOCACY & FINANCIAL RESOURCES Cancer education Academy of Oncology Nurse Navigators.......................................................... www.aonnonline.org Alex’s Lemonade Stand Foundation for Childhood Cancer..........................www.alexslemonade.org American Cancer Society...........................................................................................www.cancer.org American Society of Clinical Oncology (patient website).........................................www.cancer.net Association of Community Cancer Centers...................................................... www.accc-cancer.org CANCER101........................................................................................................ www.cancer101.org CancerCare......................................................................................................... www.cancercare.org CancerGuide..................................................................................................... www.cancerguide.org The Cancer Project......................................................................................... www.cancerproject.org CancerQuest..................................................................................................... www.cancerquest.org The Center for Cancer Support & Education..............................................www.centerforcancer.org Centers for Disease Control and Prevention................................................................. www.cdc.gov The Gathering Place....................................................................................... www.touchedbycancer.org GetPalliativeCare.org................................................................................www.getpalliativecare.org Global Resource for Advancing Cancer Education.......................................... www.cancergrace.org The Hope Light Foundation...................................................................... www.hopelightproject.com LIVESTRONG Foundation..................................................................................... www.livestrong.org National Cancer Institute......................................................................................... www.cancer.gov National Comprehensive Cancer Network...................................................................www.nccn.org OncoLink..................................................................................................................www.oncolink.org PearlPoint Cancer Support...................................................................................www.pearlpoint.org Pine Street Foundation...................................................................... www.pinestreetfoundation.org R.A. Bloch Cancer Foundation Inc.....................................................................www.blochcancer.org Scott Hamilton CARES Initiative......................................................................... www.scottcares.org Union for International Cancer Control..........................................................................www.uicc.org U.S. National Library of Medicine...........................................................................www.nlm.nih.gov Wellness Place..............................................................................................www.wellnessplace.org Caregivers & support 4th Angel Mentoring Program...............................................................................www.4thangel.org American Self-Help Group Clearinghouse................................................... www.selfhelpgroups.org Bloch Cancer Hotline.....................................................................................................800-433-0464 Buddy Kemp Caring House..........................................................www.presbyterian.org/buddykemp CANCER101........................................................................................................ www.cancer101.org Cancer Action...............................................................................................www.canceractionkc.org Cancer and Careers................................................................................. www.cancerandcareers.org CancerCare......................................................................................................... www.cancercare.org Cancer Connection............................................................................. www.thecancerconnection.org Cancer Hope Network.......................................................................... www.cancerhopenetwork.org Cancer Information and Counseling Line.......................................................................800-525-3777 Cancer Really Sucks!.............................................................................. www.cancerreallysucks.org Cancer Support Community.........................................................www.cancersupportcommunity.org Cancer Support Community Open to Options counseling program...............................888-793-9355 Cancer Survivors Network..................................................................................http://csn.cancer.org Cancer Survivors On Line............................................................................www.cancersurvivors.org Cancer Wellness Center.............................................................................www.cancerwellness.org Caregiver Action Network......................................................................... http://caregiveraction.org CaringBridge....................................................................................................www.caringbridge.org The Center for Cancer Support & Education..............................................www.centerforcancer.org Center to Advance Palliative Care................................................................................www.capc.org The Children’s Treehouse Foundation..............................................www.childrenstreehousefdn.org Cleaning for a Reason...........................................................................www.cleaningforareason.org Cuddle My Kids.............................................................................................. www.cuddlemykids.org Family Caregiver Alliance..................................................................................... www.caregiver.org Fighting Chance........................................................................................... www.fightingchance.org Friend for Life Cancer Support Network............................................................. www.friend4life.org The Gathering Place..................................................................................www.touchedbycancer.org Guam Cancer Care....................................................................................http://guamcancercare.org Guide Posts of Strength Inc.................................................................................www.cancergps.org The Hope Light Foundation...................................................................... www.hopelightproject.com Imerman Angels.......................................................................................... www.imermanangels.org The LGBT Cancer Project – Out With Cancer..................................................... www.lgbtcancer.org LIVESTRONG Foundation..................................................................................... www.livestrong.org LivingWell Cancer Resource Center................................................................www.livingwellcrc.org Lotsa Helping Hands.............................................................................www.lotsahelpinghands.com MyLifeLine.org Cancer Foundation...................................................................... www.mylifeline.org The Patient Partner Project.......................................................... www.thepatientpartnerproject.org PearlPoint Cancer Support.................................................................................. www.pearlpoint.org Pati entRes ource .c om 2014 Immunotherapy A.indd 15 SHARE Caregiver Circle for Family and Friends ...........................www.sharecancersupport.org/share-new/support/for_partners_and_caregivers Strike Out Cancer.......................................................................................www.strikeoutcancer.com Turning Point.................................................................................................www.turningpointkc.org The Ulman Cancer Fund for Young Adults......................................................... http://ulmanfund.org Visiting Nurse Associations of America...................................................................... www.vnaa.org Vital Options International................................................................................ www.vitaloptions.org Walk With Sally.............................................................................................www.walkwithsally.org Wellness Place..............................................................................................www.wellnessplace.org Well Spouse Association...................................................................................www.wellspouse.org weSPARK (Cancer Support Center)........................................................................ www.wespark.org Wonders & Worries.............................................................................www.wondersandworries.org Chemotherapy Chemocare.com................................................................................................www.chemocare.com The Chemotherapy Foundation.................................................. www.chemotherapyfoundation.com Complementary programs & alternative medicine The Annie Appleseed Project......................................................... www.annieappleseedproject.org Believe Big.......................................................................................................... www.believebig.org The Cancer Project......................................................................................... www.cancerproject.org The Center for Mind-Body Medicine......................................................................... www.cmbm.org Exceptional Cancer Patients............................................................................. www.ecap-online.org Kansas City Healing Touch...........................................................www.kansascityhealingproject.org National Center for Complementary and Alternative Medicine........................ www.nccam.nih.gov Office of Cancer Complementary and Alternative Medicine...........................www.cancer.gov/cam Society for Oncology Massage................................................................................... www.s4om.org Stewart’s Caring Place: Cancer Wellness Center............................... www.stewartscaringplace.org Touch, Caring and Cancer........................................................................www.partnersinhealing.net Financial assistance American Cancer Society...........................................................................................www.cancer.org American Kidney Fund....................................................................................... www.kidneyfund.org BenefitsCheckUp........................................................................................www.benefitscheckup.org Bringing Hope Home..............................................................................www.bringinghopehome.org CancerCare..........................................................................................www.cancercare.org/financial Cancer Financial Assistance Coalition................................................................ www.cancerfac.org The CHAIN Fund............................................................................................ www.thechainfund.com HealthWell Foundation..................................................................... www.healthwellfoundation.org LIVESTRONG Foundation..................................................................................... www.livestrong.org Medicare...............................................................................................................www.medicare.gov Native American Cancer Research................................................................. www.natamcancer.org NeedyMeds...................................................................................................... www.needymeds.com Partnership for Prescription Assistance..................................................................... www.pparx.org Patient Access Network Foundation............................................................www.panfoundation.org Patient Advocate Foundation:....................................................................www.patientadvocate.org Patient Services Inc................................................................................www.patientservicesinc.org RxAssist...................................................................................................................www.rxassist.org RxHope.....................................................................................................................www.rxhope.com Social Security Administration...................................................................................... www.ssa.gov The Social Security and Disability Resource Center................................................. www.ssdrc.com State Health Insurance Assistance Program.......................................................... www.shiptalk.org Stupid Cancer...................................................................................................www.stupidcancer.org Immunotherapy TheAnswertoCancer.org........................................................................ www.theanswertocancer.org Cancer Research Institute........................................................................... www.cancerresearch.org Society for Immunotherapy of Cancer...................................................................www.sitcancer.org Mental health services American Psychosocial Oncology Society Helpline.......................................................866-276-7443 Pain management American Chronic Pain Association........................................................................ www.theacpa.org Cancer Pain Research Consortium..................................admin@cancerpainresearchconsortium.org LIVESTRONG Foundation..................................................................................... www.livestrong.org National Foundation for the Treatment of Pain..............................................................www.nih.gov Painfromcancer.org..................................................................................... www.painfromcancer.org U.S. Pain Foundation............................................................................... http://uspainfoundation.org 15 9/17/2014 9:28:06 AM CLINICAL TRIALS in cancer immunotherapy P rior to approval, new drugs being tested for safety and effectiveness are called “investigational” or “experimental” medications. Clinical trials are the controlled studies of these investigational drugs. The main goal of clinical trials is to validate a drug’s safety and effectiveness, but they also help determine a variety of other factors, including the drug’s associated side effects and recommended dosages. The results of clinical trials help the Food and Drug Administration (FDA) decide whether to approve the drugs and release them for public use. In some cases, patients may want to participate in a clinical trial to gain access to certain medications before they’re officially approved by the FDA. Patients who participate in clinical trials are offered a number of benefits, including early access to potentially revolutionary new medications, playing an important role in advancing medical research, and receiving the very best standard of care with close monitoring by experts in the field. Cancer immunotherapy clinical trials study ways to treat cancer through immunotherapy. There are currently hundreds of clinical trials in various stages studying innovative immunotherapy drugs as new treatments, in combination with other ANAL - BREAST treatments or as new uses for already approved treatments. Without patient participation in clinical trials, the immunotherapy treatments that exist today wouldn’t be available. To qualify for a clinical trial, each patient must meet certain eligibility criteria. Cancer type, overall health and treatment history may be considerations depending on the type or phase of the trial. Because cancer immunotherapy is dependent on immune system function, a properly functioning immune system is often a qualifying factor for immunotherapy clinical trials. The clinical trial staff will be able to determine whether you are eligible to participate in a specific trial. Current clinical trials with open recruitment as of Aug. 21, 2014, are displayed on the following pages. (See www.clinicaltrials.gov for a complete and current list of trials.) Each trial is either “Recruiting” or “Not yet recruiting,” which means the studies are either actively recruiting participants or getting ready to start the recruiting process. The NCT number is a unique identification code assigned to each clinical study that is registered on the website. You can find more information about a specific clinical trial by entering the trial record number into the search box located at the top of the Web page. CANCER IMMUNOTHERAPY CLINICAL TRIALS BY DISEASE Includes all studies categorized as immunotherapy cancer trials by the U.S. National Institutes of Health at www.clinicaltrials.gov ANAL Title Cancer Type Treatment Location NCT Number A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human PapillomavirusAssociated Cancers Cervical Cancer, Oropharyngeal Cancer, Vaginal Cancer, Anal Cancer, Penile Cancer Drug: fludarabine; Drug: cyclophosphamide; Biological: Young TIL; Drug: aldesleukin MD NCT01585428 Title Cancer Type Treatment Location NCT Number Evaluation for NCI Surgery Branch Clinical Studies Synovial Cell Cancer, Melanoma, Colorectal Cancer, Lung Cancer, Bladder Cancer MD NCT00001823 A Study of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer Transitional Cell Carcinoma of Bladder, Urethra Cancer, Ureter Cancer, Malignant Tumor of Renal Pelvis Drug: cisplatin; Drug: gemcitabine; Biological: ALT-801 AZ; CA; FL; GA; IA; IL; KS; LA; MI; MO; NC; NY; OK; PA NCT01326871 A Study of ALT-801 in Patients With Bacillus Calmette-Guerin (BCG) Failure Non-Muscle Invasive Bladder Cancer Non-muscle Invasive Bladder Cancer Biological: ALT-801; Drug: gemcitabine AL; CA; FL; NC; OK; PA NCT01625260 A Phase I/II Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT Bladder Cancer Biological: HS-410; Biological: Placebo; Biological: BCG CA; CO; IL; IN; KS; MA; MD; NC; SC; TX NCT02010203 Study of Bacillus Calmette-Guerin (BCG) Combined With PANVAC Versus BCG Alone in Adults With High Grade Non-Muscle Invasive Bladder Cancer Who Failed At Least 1 Course of BCG Bladder Cancer Biological: TICE Bacillus Calmette-Guerin (BCG); Biological: PANVAC MD; NJ NCT02015104 A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG-naive Non-Muscle Invasive Bladder Cancer Non-muscle Invasive Bladder Cancer Biological: ALT-803 HI NCT02138734 Safety and Efficacy of CG0070 Oncolytic Virus Regimen in Patients With High Grade Non-Muscle Invasive Bladder Cancer Bladder Cancer, High Grade, Non Muscle Invasive Biological: oncolytic adenovirus expressing GM-CSF AZ NCT02143804 BLADDER 16 2014 Immunotherapy - Clinical Trials Section.indd 16 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:06 AM BRAIN Title Cancer Type Treatment Location NCT Number Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer Glioblastoma Multiforme, Glioblastoma, GBM, Grade IV Astrocytoma, Glioma, Brain Cancer, Brain Tumor Drug: Dendritic cell immunotherapy AR; CA; CO; DC; FL; GA; IL; IN; KS; MA; MI; MN; MO; NC; NJ; NY; OH; PA; RI; SC; TN; TX; WA NCT00045968 Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma Brain and Central Nervous System Tumors, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer Biological: Autologous immunoglobulin idiotype-KLH conjugate vaccine; Biological: sargramostim; Drug: methotrexate; Drug: thiotepa; Radiation: Radiation therapy TX NCT00621036 Basiliximab in Treating Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Targeted Immunotherapy and Temozolomide-Caused Lymphopenia Malignant Neoplasms Brain Biological: RNA-loaded dendritic cell vaccine; Drug: basiliximab NC NCT00626483 A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors Malignant Glioma, Recurrent Ependymoma Biological: AdV-tk; Drug: valacyclovir; Radiation: Radiation IL; MA NCT00634231 Cellular Immunotherapy Study for Brain Cancer Gliomas, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Mixed Glioma, Glioblastoma Multiforme, Malignant Meningioma Drug: alloreactive CTL CA NCT01144247 Dendritic Cell Vaccine for Patients With Brain Tumors Glioma, Anaplastic Astrocytoma, Anaplastic Astro-oligodendroglioma, Glioblastoma Biological: autologous tumor lysate-pulsed DC vaccination; Biological: Tumor lysatepulsed DC vaccination + 0.2% resiquimod; Biological: Tumor-lysate pulsed DC vaccination + adjuvant polyICLC CA NCT01204684 Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Medulloblastoma, Neuroectodermal Tumor Biological: TTRNA-xALT; Biological: TTRNA-DCs FL NCT01326104 White Blood Cells With Anti-EGFR-III for Malignant Gliomas Malignant Glioma, Glioblastoma, Brain Cancer Biological: Anti-EGFRvIII CAR transduced PBL; Drug: aldesleukin; Drug: fludarabine; Drug: cyclophosphamide MD NCT01454596 Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors Multiple Cancer Types Biological: DEC-205-NY-ESO-1 fusion protein vaccine; Drug: sirolimus; Other: laboratory biomarker analysis NY NCT01522820 Immune Reconstitution in Oncology Patients Following Autologous Stem Cell Transplant Solid Tumor, Brain Tumor, Lymphoma Other: Blood samples obtained TN NCT01540175 Study to Evaluate the Effects of Imiquimod and Tumor Lysate Vaccine Immunotherapy in Adults With High Risk or Recurrent/Post-Chemotherapy WHO Grade II Gliomas High Risk WHO Grade II Glioma, Recurrent/Post-Chemotherapy WHO Grade II Glioma Biological: Tumor lysate vaccine; Drug: imiquimod PA NCT01678352 Phase I Study of a Dendritic Cell Vaccine for Patients With Either Newly Diagnosed or Recurrent Glioblastoma Glioblastoma, Glioblastoma Multiforme, Glioma, Astrocytoma, Brain Tumor Biological: Dendritic cell vaccination, in addition to standard temozolomide chemotherapy and involved field radiation therapy; Biological: Dendritic cell vaccination, with optional bevacizumab treatment for patients previously treated with bevacizumab CA NCT02010606 Efficacy Study of Oral Arginine to Improve Immune Function in Glioblastoma Multiforme Glioblastoma Multiforme Drug: arginine in powder form VA NCT02017249 A Study of ICT-121 Dendritic Cell Vaccine in Recurrent Glioblastoma Recurrent Glioblastoma Biological: ICT-121 DC vaccine CA NCT02049489 Safety and Efficacy Study of SL-701, a Glioma-Associated Antigen Vaccine To Treat Recurrent Glioblastoma Multiforme Adult Brain Glioblastoma, Glioblastoma Multiforme Biological: SL-701; imiquimod cream 5%; Leukine 150 micrograms; Drug: imiquimod cream 5%; Drug: Leukine 150 micrograms AZ; IL; MA; MI; NY NCT02078648 RESIST: Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine Brain Cancer, Brain Neoplasm, Primary, Brain Neoplasms, Recurrent, Brain Tumor, Cancer of the Brain Biological: PEPIDH1M vaccine NC NCT02193347 DNX-2401 With Interferon Gamma (IFN-y) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors Glioblastoma, Gliosarcoma Drug: Single intratumoral injection of DNX2401; Drug: interferon gamma AR; FL; OH; TX NCT02197169 Genetically Modified T cells in Treating Patients With Recurrent or Refractory Malignant Glioma Multiple Cancer Types Biological: IL13Ra2-specific, hingeoptimized, 41BB-costimulatory CAR/ truncated CD19-expressing T lymphocytes; Other: Laboratory biomarker analysis; Other: Quality-of-life assessment CA NCT02208362 Title Cancer Type Treatment Location NCT Number Collection of Blood From Patients With Cancer Prostate Cancer, Breast Cancer, Colon Cancer, Lung Cancer, Liver Cancer MD NCT00034216 Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Women With HER2/ Neu-Negative Metastatic Breast Cancer Breast Cancer MI NCT01022138 BREAST Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 17 Biological: HER2Bi-armed activated T cells; Drug: cyclophosphamide; Other: Laboratory biomarker analysis 17 9/17/2014 9:16:06 AM CLINICAL TRIALS BREAST - HEAD & NECK BREAST (CONTINUED) Title Cancer Type Treatment Location NCT Number Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or Stage III Breast Cancer Undergoing Surgery Breast Cancer Biological: HER2Bi-armed activated T cells; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Other: laboratory biomarker analysis; Procedure: neoadjuvant therapy; Procedure: Therapeutic conventional surgery MI NCT01147016 Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer Neoplasms, Breast Biological: GSK Biologicals’ recombinant WT1 AR; DE; FL; MA; Antigen-Specific Cancer Immunotherapeutic MI; NC; OR; SC; (ASCI) GSK2302024A; Biological: Placebo TN; TX; WA NCT01220128 Vaccine Therapy in Treating Patients With Metastatic Solid Tumors Malignant Solid Tumor, Breast Cancer, Malignant Tumor of Colon, GIST, Ovarian Cancer Biological: HER2 vaccine OH NCT01376505 Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms Other: ²¹²Pb-TCMC-Trastuzumab, Biological: trastuzumab AL; CA NCT01384253 Toll-like Receptor (TLR) 7 Agonist, Cyclophosphamide, and Radiotherapy for Breast Cancer With Skin Metastases Breast Cancer, Metastatic Breast Cancer, Recurrent Breast Cancer Radiation: Radiation; Drug: imiquimod; Drug: cyclophosphamide NY NCT01421017 A Phase I Study To Evaluate The Antitumor Activity And Safety Of AVX901 HER2+ Cancer Biological: AVX901 NC NCT01526473 Pilot Study of a Breast Cancer Vaccine Plus Poly-ICLC for Breast Cancer Breast Cancer Biological: 9 Peptides from HER2/neu, CEA, & CTA + poly-ICLC VA NCT01532960 Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax Breast Cancer Drug: Herceptin; Drug: NeuVax vaccine; Drug: GM-CSF CA; DC; HI; IN; MD; OR; PA; TX; VA; WA NCT01570036 Vaccine Therapy and Trastuzumab With or Without Polysaccharide-K in Treating Patients With Stage IV HER2 Positive Breast Cancer HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer Biological: HER2/neu intracellular domain protein; Biological: trastuzumab; Other: placebo; Biological: polysaccharide-K; Other: laboratory biomarker analysis WA NCT01922921 Exemestane and Cyclophosphamide for Metastatic Breast Cancer Metastatic Beast Cancer Drug: exemestane; Drug: cyclophosphamide NY NCT01963481 Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion Malignant Pleural Effusion, Lung Cancer, Mesothelioma, Breast Cancer, Ovarian Cancer Biological: AdV-tk + valacyclovir PA NCT01997190 A Phase I Trial of NY-ESO-1 With GLA-SE in Patients With Unresectable or Metastatic Cancer Melanoma, Ovarian Cancer, Sarcoma, Non-Small Cell Lung Cancer, Breast Cancer Biological: IDC-G305 AZ; FL; MI; NY NCT02015416 Increased Frequency of AlloStim™ Dosing in Combination With Cryoablation in Metastatic Breast Cancer Patients Metastatic Breast Cancer Biological: AlloStim; Procedure: Cryoablation CA NCT02018419 DC Vaccine for Patients With Ductal Carcinoma In Situ Breast Cancer, DCIS Biological: HER2 pulsed dendritic cell vaccine PA NCT02061332 HER2 Pulsed DC Vaccine to Prevent Recurrence of Invasive Breast Cancer Post Neoadjuvant Chemotherapy Breast Cancer Biological: HER2 pulsed dendritic cell vaccine PA NCT02061423 HER2 Pulsed DC Vaccine to Prevent Recurrence of Invasive Breast Cancer Breast Cancer Biological: HER2 pulsed dendritic cell vaccine PA NCT02063724 A Phase I Safety Study of Intradermal ID-LV305 in Patients With Locally Advanced, Relapsed or Metastatic Cancer Expressing NY-ESO-1 Breast Cancer, Melanoma, Non-Small Cell Lung Cancer, Ovarian Cancer, Sarcoma Biological: ID-LV305 CT; MA; MN; TX; WA NCT02122861 Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T cell Costimulatory Molecules (MVA-Brachyury-TRICOM) Lung Cancer, Breast Cancer, Prostate Cancer, Tumors (Others) Biological: MVA-brachyury-TRICOM MD NCT02179515 Title Cancer Type Treatment Location NCT Number A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers Cervical Cancer, Oropharyngeal Cancer, Vaginal Cancer, Anal Cancer, Penile Cancer Drug: fludarabine; Drug: cyclophosphamide; Biological: Young TIL; Drug: aldesleukin MD NCT01585428 ADXS11-001 High Dose HPV+ Cervical Cancer Effects of Immunotherapy, Metastatic/ Recurrent Cervical Cancer, Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Squamous Cell Carcinoma, Cervical Small Cell Carcinoma, Stage III Cervical Cancer, Stage IVA Cervical Cancer, Stage IVB Cervical Cancer Biological: ADXS11-001 GA NCT02164461 CERVICAL 18 2014 Immunotherapy - Clinical Trials Section.indd 18 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:06 AM COLORECTAL Title Cancer Type Location NCT Number Evaluation for NCI Surgery Branch Clinical Studies Synovial Cell Cancer, Melanoma, Colorectal Cancer, Lung Cancer, Bladder Cancer Treatment MD NCT00001823 Collection of Blood From Patients With Cancer Prostate Cancer, Breast Cancer, Colon Cancer, Lung Cancer, Liver Cancer MD NCT00034216 A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers Metastatic Colorectal Cancer, Metastatic Gastric Cancer, Metastatic Pancreatic Cancer, Metastatic Hepatocellular Carcinoma, Metastatic Cholangiocarcinoma Biological: Young TIL; Drug: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine MD NCT01174121 Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes Metastatic Cancer, Metastatic Melanoma, Renal Cancer, Colorectal Cancer, Ovarian Cancer, Lung Cancer Genetic: Anti-VEGFR2 CAR CD8 plus PBL; Drug: cyclophosphamide; Drug: aldesleukin; Drug: fludarabine MD NCT01218867 Vaccine Therapy in Treating Patients With Metastatic Solid Tumors Malignant Solid Tumor, Breast Cancer, Malignant Tumor of Colon, GIST, Ovarian Cancer Biological: HER2 vaccine OH NCT01376505 Anti-CD3 x Anti-Erbitux® Armed Activated T Cells (Phase Ib) for Gastrointestinal (GI Cancer) Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm, Malignant Neoplasm of Large Intestine, Malignant Tumor of Colon, Colon Carcinoma, Cancer of Colon, Pancreatic Cancer Drug: FOLFOX6; Biological: EGFRBi armed ATC infusions MI NCT01420874 Immunotherapy With CEA(6D) VRP Vaccine (AVX701) in Patients With Stage III Colorectal Cancer Stage III Colon Cancer Biological: AVX701 NC NCT01890213 Title Cancer Type Treatment Location NCT Number INCB024360 Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Stage IIIA Fallopian Tube Cancer, Stage IIIA Ovarian Epithelial Cancer, Stage IIIA Primary Peritoneal Cavity Cancer, Stage IIIB Fallopian Tube Cancer, Stage IIIB Ovarian Epithelial Cancer, Stage IIIB Primary Peritoneal Cavity Cancer, Stage IIIC Fallopian Tube Cancer, Stage IIIC Ovarian Epithelial Cancer, Stage IIIC Primary Peritoneal Cavity Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Primary Peritoneal Cavity Cancer Drug: IDO1 inhibitor INCB024360; Procedure: Therapeutic conventional surgery; Other: Laboratory biomarker analysis MN; NY NCT02042430 Title Cancer Type Treatment Location NCT Number MAGE-A3/HPV 16 Vaccine for Squamous Cell Carcinoma of the Head and Neck Squamous Cell Carcinoma of the Head and Neck Biological: MAGE-A3; Biological: HPV-16 vaccine MD NCT00257738 Vitamin D - Celecoxib Therapy Mouth Neoplasms Drug: celecoxib; Drug: 1,25-dihydroxyvitamin D3 SC + celecoxib; Drug: 1,25-dihydroxyvitamin D3 NCT00953849 Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas Lung Cancer, Esophageal Cancer, Malignant Pleural Mesothelioma, Sarcoma, Thymic Carcinoma Biological: Allogeneic tumor cell vaccine (K562); Drug: celecoxib; Drug: cyclophosphamide MD NCT01143545 TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck Multiple Cancer Types Drug: TLR8 agonist VTX-2337; Biological: cetuximab; Other: Laboratory biomarker analysis; Other: pharmacogenomic studies WA NCT01334177 Safety Study of HPV DNA Vaccine to Treat Head and Neck Cancer Patients HPV-related Head and Neck Cancer Biological: pNGVL-4a-CRT/E7 (detox) DNA vaccine MD NCT01493154 A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers Cervical Cancer, Oropharyngeal Cancer, Vaginal Cancer, Anal Cancer, Penile Cancer Drug: fludarabine; Drug: cyclophosphamide; Biological: Young TIL; Drug: aldesleukin MD NCT01585428 A Phase II Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract Head and Neck Squamous Cell Carcinoma Drug: tadalafil; Drug: Placebo MD NCT01697800 Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-Small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer Multiple Cancer Types Biological: Recombinant interleukin-15, Other: Pharmacological study; Other: Laboratory biomarker analysis CA; MD; MN; WA; WI NCT01727076 Window of Opportunity Trial of ADXS 11-001 Vaccination Prior to Robotic Surgery of HPV-Positive Oropharyngeal Cancer Head and Neck Cancer, Squamous Cell Carcinoma of the Head and Neck, Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma Biological: ADXS11-001 (ADXS-HPV) NY NCT02002182 FALLOPIAN TUBE HEAD & NECK Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 19 19 9/17/2014 9:16:07 AM CLINICAL TRIALS HEAD & NECK - LEUKEMIA/LYMPHOMA/MULTIPLE MYELOMA HEAD & NECK (CONTINUED) Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum Lung Cancer, Esophageal Cancer, Malignant Pleural Mesothelioma, Sarcoma, Thymic Carcinoma Biological: H1299 lysate vaccine; Drug: cyclophosphamide; Drug: celecoxib MD NCT02054104 Study of HPV Specific Immunotherapy in Patients With HPV Associated Head and Neck Squamous Cell Carcinoma Head and Neck Squamous Cell Cancer Biological: 1.1 mL of VGX-3100 and INO-9012 delivered via IM EP PA NCT02163057 Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer Kidney Cancer Biological: Anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil MD NCT00003553 Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes Metastatic Cancer, Metastatic Melanoma, Renal Cancer, Colorectal Cancer, Ovarian Cancer, Lung Cancer Genetic: Anti-VEGFR2 CAR CD8 plus PBL; Drug: cyclophosphamide; Drug: aldesleukin; Drug: fludarabine MD NCT01218867 Phase III Trial of Autologous Dendritic Cell Immunotherapy (AGS-003) Plus Standard Treatment of Advanced Renal Cell Carcinoma (RCC) Advanced Renal Cell Carcinoma, Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma Drug: Standard treatment; Biological: AGS-003 AK; AZ; CA; CO; CT; FL; GA; IA; ID; IL; IN; KS; KY; LA; MA; MD; MI; MN; MO; NC; NE; NH; NJ; NM; NY; OH; OK; OR; PA; RI; SC; TN; TX; UT; VA; WA; WI NCT01582672 Reference Group Trial for The ONE Study End-stage Renal Failure, Kidney Graft Rejection Other: Blood drawing for immune monitoring and questionnaires CA; MA NCT01656135 PET Quantitative Assessments of Solid Tumor Response to Immune Checkpoint Blockade Therapy Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC) Radiation: PET/CT imaging with [18F] 2-deoxy-2-(18F)fluoro-D-glucose (FDG) MD NCT01666353 High Dose IL-2 and Stereotactic Ablative Body Radiation Therapy for Metastatic Renal Cancer Metastatic Clear Cell Renal Cell Carcinoma Drug: IL-2; Radiation: Stereotactic ablative body radiation therapy TX NCT01896271 Vaccine Therapy Before Surgery in Treating Patients With Localized Kidney Cancer Recurrent Renal Cell Cancer, Stage I Renal Cell Cancer, Stage II Renal Cell Cancer Biological: Renal cell carcinoma/CD40L RNAtransfected autologous dendritic cell vaccine AGS-003; Procedure: Therapeutic conventional surgery; Other: Laboratory biomarker analysis NY NCT02170389 A Rollover Protocol for Subjects Previously Treated With AGS-003 Renal Cell Carcinoma Drug: AGS-003 GA; IN; MN; NC; VA NCT01482949 Title Cancer Type Treatment Location NCT Number Anti-CD3 x Anti-Erbitux® Armed Activated T Cells (Phase Ib) for Gastrointestinal (GI Cancer) Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm, Malignant Neoplasm of Large Intestine, Malignant Tumor of Colon, Colon Carcinoma, Cancer of Colon, Pancreatic Cancer Drug: FOLFOX6; Biological: EGFRBi armed ATC infusions MI NCT01420874 KIDNEY LARGE INTESTINE LEUKEMIA /LYMPHOMA /MULTIPLE MYELOMA Title Cancer Type Treatment Location NCT Number Biological Therapy in Treating Patients at High-Risk or With Lymphoma, Lymphoproliferative Disease, or Malignancies Leukemia, Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific Biological: Allogeneic Epstein-Barr virusspecific cytotoxic T lymphocytes NY NCT00002663 Xcellerated T Cells™ for Non-Hodgkin Lymphoma (NHL) Patients Non-Hodgkin Lymphoma Drug: Xcellerated T Cells CA; CO; GA; MA; MD; MO; NJ; OH, OR; SC; TX; WA NCT00081783 HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplasia, Chronic Myeloid Leukemia, Histiocytosis Drug: Chemotherapy and antibodies; Device: Miltenyi Biotec CliniMACS; Procedure: Allogeneic stem cell transplantation TN NCT00145626 Rituximab, Vaccine Therapy, and GM-CSF in Treating Patients With Non-Hodgkin Lymphoma Lymphoma Biological: Autologous immunoglobulin idiotype-KLH conjugate vaccine; Biological: rituximab; Biological: sargramostim TN NCT00258336 Allogeneic Blood Stem Cell Transplantation and Adoptive Immunotherapy for Hodgkin Disease Hodgkin Disease Drug: gemcitabine; Drug: fludarabine; Drug: melphalan; Drug: antithymocyte globulin; Procedure: Allogeneic stem cell infusion; Drug: tacrolimus; Drug: filgrastim (G-CSF); Drug: methotrexate TX NCT00385788 20 2014 Immunotherapy - Clinical Trials Section.indd 20 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:07 AM LEUKEMIA /LYMPHOMA /MULTIPLE MYELOMA (CONTINUED) Title Cancer Type Treatment Location NCT Number Safety Study of CAT-8015 Immunotoxin in Patients With HCL With Advance Disease Leukemia, Hairy Cell Leukemia, HCL Drug: Immunotoxin therapy; Drug: CAT-8015 immunotoxin; Procedure: Biological therapy CA; IL; MD NCT00462189 Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma Brain and Central Nervous System Tumors, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine; Biological: sargramostim; Drug: methotrexate; Drug: thiotepa; Radiation: Radiation therapy TX NCT00621036 Autologous and Allogeneic Transplant for Relapsed Lymphoma Non-Hodgkin Lymphoma, Hodgkins Disease Drug: fludarabine and busulfan; Drug: fludarabine, busulfan and ATG NY NCT00802113 Neukoplast (NK-92) for the Treatment of Refractory or Relapsed Acute Myeloid Leukemia Acute Myeloid Leukemia Biological: Neukoplast (NK-92) PA NCT00900809 Phase I Study of B Cell Malignancies Using T Cells Expressing an Anti-CD19 Chimeric Receptor: Assessment of the Impact of Lymphocyte Depletion Prior to T Cell Transfer Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Large Cell Lymphoma Drug: fludarabine; Drug: cyclophosphamide; Biological: Anti-CD19-CAR PBL MD NCT00924326 Safety and Efficacy Study of Immunotherapy With Rituximab and Interleukin-2 in Patients With Non-Hodgkin Lymphoma High Risk Non-Hodgkin Lymphoma Biological: rituximab; Biological: interleukin-2 PA NCT00994643 Administration of Anti-CD19-chimeric-antigen-receptortransduced T Cells From the Original Transplant Donor to Patients With Recurrent or Persistent B cell Malignancies After Allogeneic Stem Cell Transplantation B Cell Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, B Cell Lymphoma Procedure: Allogeneic stem cell transplant; Biological: Anti-CD19-chimericantigen receptor-traduced T cell; Drug: cyclophosphamide; Drug: pentostatin MD NCT01087294 Blockade of PD-1 in Conjunction With the Dendritic Cell/ AML Vaccine Following Chemotherapy Induced Remission Acute Myelogenous Leukemia, AML Biological: DC AML vaccine; Drug: CT-011 MA NCT01096602 Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/ Refractory, Aggressive NHL Non-Hodgkin Lymphoma, NHL, Aggressive NHL, Diffuse Large B cell Lymphoma Drug: veltuzumab and 90Y-epratuzumab tetraxetan; Drug: 90Y-epratuzumab tetraxetan; Drug: veltuzumab DE; FL; IN; MN; NY; PA NCT01101581 A Phase II Study of Ofatumumab-Based Induction Chemoimmunotheraphy Followed by Consolidation Ofatumumab Immunotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Small Lymphocytic Lymphoma, CLL (Chronic Lymphocytic Leukemia) Drug: fludarabine phosphate; Biological: ofatumumab; Drug: cyclophosphamide MD NCT01145209 Immunotherapy for Asymptomatic Phase Lymphoplasmacytic Lymphoma Lymphoma Biological: DNA Vaccine TX NCT01209871 Th1/Tc1 Immunotherapy Following Stem Cell Transplantation in Multiple Myeloma Multiple Myeloma Procedure: Adoptive immunotherapy; Drug: Th1/Tc1 product MD; NJ NCT01239368 Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma Advanced Myeloma Biological: Prevnar-pneumococcal conjugate vaccine (PCV); Other: Activated/costimulated autologous T cell; Drug: lenalidomide; Biological: MAGE-A3, Hiltonol (Poly-ICLC) MD; PA NCT01245673 Trial of Daily Pulse Interleukin-2 With Famotidine in Acute Myelogenous Leukemia Acute Myelogenous Leukemia Drug: interleukin-2 NC NCT01289678 Trial of Low-Dose MTX and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma Follicular Lymphoma Drug: Low-dose methotrexate and Bexxar MI NCT01389076 A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, NonHodgkin, Lymphoma, T-Cell Drug: brentuximab vedotin; Drug: rituximab AL; CA; CO; FL; GA; IL; MA; MN; MO; NJ; NV; NY; OH; OR; SC; TX; VA; WA NCT01421667 Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant Mantle Cell Lymphoma Biological: ofatumumab; Other: ofatumumab + bendamustine NJ; NY NCT01437709 Yttrium-90-labeled Daclizumab With Chemotherapy and Stem Cell Transplant for Hodgkin s Lymphoma Hodgkin Lymphoma Radiation: 111In-daclizumab; Radiation: 90Y-daclizumab MD NCT01468311 Phase II Ofatumumab/Methylprednisolone Followed by Ofatumumab/Lenalidomide for Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma Drug: High-dose methylprednisolone (HDMP); Drug: ofatumumab; Drug: lenalidomide FL NCT01496976 Immune Reconstitution in Oncology Patients Following Autologous Stem Cell Transplant Solid Tumor, Brain Tumor, Lymphoma Other: Blood samples obtained TN NCT01540175 Continuous Infusion of rhIL-15 for Adults With Advanced Cancer Carcinoma, Lymphoma Biological: rhIL-15 MD NCT01572493 Phase I/II Study of hLL1-DOX in Relapsed NHL and CLL Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia Drug: hLL1-DOX (IMMU-115) DE; FL; IN; MA; NJ; TX NCT01585688 Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma ALL, B Cell Lymphoma, Leukemia, Large Cell Lymphoma, Non-Hodgkin Lymphoma Biological: Anti-CD19-CAR MD NCT01593696 Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 21 21 9/17/2014 9:16:07 AM CLINICAL TRIALS LEUKEMIA/LYMPHOMA/MULTIPLE MYELOMA LEUKEMIA /LYMPHOMA /MULTIPLE MYELOMA (CONTINUED) Title Cancer Type Treatment Location NCT Number Laboratory-Treated T Cells in Treating Patients With HighRisk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant Multiple Cancer Types Biological: WT1-sensitized T cells; Biological: aldesleukin; Other: laboratory biomarker analysis WA NCT01640301 A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia B Cell Leukemia Biological: Autologous CD19 CAR+ EGFTt + T cells WA NCT01683279 Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma Mantle Cell Lymphoma, Diffuse Large Cell Lymphoma, Burkitts Lymphoma, T Cell Lymphomas, Acute Myeloid Leukemia/Acute Lymphoblastic Leukemia Biological: Cellular immunotherapy RI NCT01685606 Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma Recurrent Childhood Acute B-lymphoblastic Leukemia, Recurrent Childhood B-lymphoblastic Lymphoma Drug: dexamethasone; Drug: vincristine sulfate; Biological: rituximab; Drug: clofarabine; Drug: cyclophosphamide; Drug: etoposide; Biological: aldesleukin; Drug: pegaspargase; Drug: methotrexate; Drug: mercaptopurine; Drug: cytarabine; Drug: mitoxantrone; Drug: teniposide; Drug: vinblastine; Biological: Natural killer cell infusion; Other: Laboratory biomarker analysis; Drug: Therapeutic hydrocortisone; Procedure: Allogeneic hematopoietic stem cell transplantation TN NCT01700946 Phase III Frontline Therapy Trial in Patients With Advanced Classical Hodgkin Lymphoma Hodgkin Lymphoma Drug: brentuximab vedotin; Drug: doxorubicin; Drug: bleomycin; Drug: vinblastine; Drug: dacarbazine AL; AZ; CA; CO; DC; FL; IL; IN; MA; MD; MI; MN; MO; NC; ND; NE; NJ; NM; NV; NY; OH; PA; SC; TN; TX; UT; WA; WI; WV NCT01712490 A Study of Brentuximab Vedotin in Adults Age 60 and Above With Newly Diagnosed Hodgkin Lymphoma (HL) Hodgkin Disease Drug: brentuximab vedotin; Drug: dacarbazine AL; AZ; CA; CO; FL; GA; IL; MD; NE; NY; OR; TX; VA; WA NCT01716806 Phase I Dose Escalation Study of IMMU-114 in Relapsed or Refractory NHL and CLL Non-Hodgkin Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma Drug: IMMU-114 OH NCT01728207 ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T cell Lymphomas Large-Cell Anaplastic Lymphoma, Non-Hodgkin Lymphoma, T Cell Lymphoma Drug: brentuximab vedotin; Drug: doxorubicin; Drug: prednisone; Drug: vincristine; Drug: cyclophosphamide AL; CA; CT; FL; IA; KS; MA; MD; MI; MN; MO; NJ; NY; OH; OK; PA; TN; TX; VA; WA NCT01777152 Autologous T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia Relapsed B-Cell Acute Lymphoblastic Leukemia Procedure: Leukapheresis or collection of PBMCs; Drug: cyclophosphamide; Biological: Modified T cells MA; NY NCT01860937 Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia Multiple Cancer Types Biological: Anti-CD19-CAR lentiviral vectortransduced autologous T lymphocytes; Other: Laboratory biomarker analysis WA NCT01865617 Allogeneic Stem Cell Transplantation With Adoptive Immunotherapy in Epstein-Barr Virus Positive Recurrent/ Refractory Hodgkin Lymphoma Hodgkin Lymphoma Biological: Allogeneic donor-derived LMPspecific cytotoxic T-lymphocyte NY NCT01636388 Study of Brentuximab Vedotin Combined With Bendamustine in Patients With Hodgkin Lymphoma Hodgkin Disease Drug: brentuximab vedotin; Drug: bendamustine AL; CA; CO; IL; IN; MA; MI; MN; NE; NY; OH; SC; TX; VA NCT01874054 Safety Study of CAT-8015 Immunotoxin in Patients With CLL, PLL or SLL With Advance Disease Leukemia Drug: Immunotoxin therapy; Drug: CAT-8015 immunotoxin; Procedure: Biological therapy CA; IL, MD NCT00457860 Collect Long-term Data on Subjects Following Participation in Previous EMD 531444 (L-BLP25 or BLP25 Liposome Vaccine) Clinical Trials Non-Small Cell Lung Cancer, Multiple Myeloma Biological: tecemotide; Other: No intervention MA NCT01423760 22 2014 Immunotherapy - Clinical Trials Section.indd 22 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:07 AM LEUKEMIA /LYMPHOMA /MULTIPLE MYELOMA (CONTINUED) Title Cancer Type Treatment Location NCT Number A Safety Study of SGN-CD33A in AML Patients Acute Myelogenous Leukemia, Acute Myeloid Leukemia Drug: SGN-CD33A AL; CA; FL; MA; NY; OH; UT; WA NCT01902329 Study of Brentuximab Vedotin Combined With RCHOP in Front-line Treatment of Patients With Diffuse Large B cell Lymphoma (DLBCL) B Cell Lymphoma, Diffuse Large B Cell Lymphoma Drug: brentuximab vedotin; Drug: rituximab; Drug: vincristine; Drug: cyclophosphamide; Drug: prednisone; Drug: doxorubicin AZ; CA; CO; MN; MO; NJ; OH; OR; TX; UT; VA; WA NCT01925612 Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma EBV Extranodal NK-T-Cell Lymphoma Biological: CMD-003 CA; DC; MA; MN; NJ; NY; OH; OR; PA; TN; TX NCT01948180 A Pediatric and Young Adult Trial of Genetically Modified T Cells Directed Against CD19 for Relapsed/Refractory CD19+ Leukemia CD19+ Leukemia Biological: Patient-derived CD19 specific CAR T cells also expressing an EGFRt WA NCT02028455 Central Memory Enriched T Cells Following Stem Cell Transplant in Treating Patients With Recurrent B-Cell Non-Hodgkin Lymphoma Multiple Cancer Types Biological: autologous CD19CAR-CD28CD3zeta-EGFRt-expressing Tcm-enriched T cells; Other: Laboratory biomarker analysis CA NCT02051257 Immunotherapy Following Reduced Intensity Conditioning and Allogeneic Stem Cell Transplant for Poor Risk CD30+ Hodgkin Lymphoma Patients Hodgkin Lymphoma Drug: brentuximab vedotin; Procedure: Allogeneic stem cell transplantation; Drug: Reduced intensity conditioning NY NCT02098512 A Study of ALT-803 in Patients With Relapsed or Refractory Multiple Myeloma Relapsed or Refractory Multiple Myeloma Biological: ALT-803 MN NCT02099539 A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas Neuroblastoma, Lymphoma, High-risk Tumor Device: CD133+ selected autologous stem cell infusion; Biological: IL-2; Biological: hu14.18K322A; Drug: busulfan; Drug: melphalan; Biological: GM-CSF; Drug: carmustine; Drug: etoposide; Drug: cytarabine; Drug: carboplatin; Device: Haploidentical natural killer cell infusion; Biological: G-CSF; Drug: etoposide phosphate TN NCT02130869 Cellular Immunotherapy After Cyclophosphamide in Treating Patients With High-Risk Acute Lymphoblastic Leukemia B cell Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia Drug: cyclophosphamide; Biological: autologous CD19CAR-CD28-CD3zeta-EGFRtexpressing Tcm-enriched T cells; Other: Laboratory biomarker analysis CA NCT02146924 Cellular Immunotherapy Following Cyclophosphamide in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia or B-Cell Prolymphocytic Leukemia Post-transplant Lymphoproliferative Disorder, Prolymphocytic Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Waldenström Macroglobulinemia Drug: cyclophosphamide; Biological: Autologous CD19CAR-CD28-CD3zeta-EGFRtexpressing Tcm-enriched T cells; Other: Laboratory biomarker analysis CA NCT02153580 A Phase Ib/II Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL Chronic Lymphocytic Leukemia Drug: IPI-145; Drug: fludarabine; Drug: cyclophosphamide; Drug: rituximab MA NCT02158091 Genetically Modified T cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Acute Myeloid Leukemia Drug: cyclophosphamide; Biological: AntiCD123-CAR/CD28-costimulatory, retroviral vector-transduced autologous T lymphocytes; Other: Laboratory biomarker analysis CA NCT02159495 Micro Needle Array-Doxorubicin (MNA-D) in Patients With Cutaneous T cell Lymphoma (CTCL) Cutaneous T Cell Lymphoma Drug: Micro needle array-doxorubicin (MNA-D) PA NCT02192021 Study of T Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma Plasma-Cell Myeloma, Multiple Myeloma Drug: cyclophosphamide; Drug: fludarabine; Biological: Anti-BCMA CAR T cells MD NCT02215967 Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 23 23 9/17/2014 9:16:07 AM CLINICAL TRIALS LIVER - MELANOMA LIVER Title Cancer Type Collection of Blood From Patients With Cancer Prostate Cancer, Breast Cancer, Colon Cancer, Lung Cancer, Liver Cancer A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers Metastatic Colorectal Cancer, Metastatic Gastric Cancer, Metastatic Pancreatic Cancer, Metastatic Hepatocellular Carcinoma, Metastatic Cholangiocarcinoma Title Cancer Type Evaluation for NCI Surgery Branch Clinical Studies Treatment Location NCT Number MD NCT00034216 Biological: Young TIL; Drug: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine MD NCT01174121 Treatment Location NCT Number Synovial Cell Cancer, Melanoma, Colorectal Cancer, Lung Cancer, Bladder Cancer MD NCT00001823 Collection of Blood From Patients With Cancer Prostate Cancer, Breast Cancer, Colon Cancer, Lung Cancer, Liver Cancer MD NCT00034216 Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and GM-CSF in Treating Patients With Recurrent, Refractory, or Metastatic Non-Small Cell Lung Cancer Lung Cancer Biological: EGFRBi-armed autologous activated T cells; Biological: aldesleukin; Biological: sargramostim RI NCT00569296 Expression Analysis of Specific Markers in Non-Small Cell Lung Cancer or Melanoma Non-Small Cell Lung Cancer Procedure: Collection of tumor and blood samples CA; IL; MO; UT NCT00685750 Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas Lung Cancer, Esophageal Cancer, Malignant Pleural Mesothelioma, Sarcoma, Thymic Carcinoma Biological: Allogeneic tumor cell vaccine (K562); Drug: celecoxib; Drug: cyclophosphamide MD NCT01143545 Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes Metastatic Cancer, Metastatic Melanoma, Renal Cancer, Colorectal Cancer, Ovarian Cancer, Lung Cancer Genetic: Anti-VEGFR2 CAR CD8 plus PBL; Drug: cyclophosphamide; Drug: aldesleukin; Drug: fludarabine MD NCT01218867 Randomized Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy Malignant Pleural Mesothelioma Biological: WT-1-vaccine Montanide + GM-CSF; Biological: Montanide adjuvant + GM-CSF NY NCT01265433 Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer Non-Small Cell Lung Carcinoma Biological: TG4010; Drug: Placebo AZ; KS; KY; MD; MO; NC; OH; PA; TX NCT01383148 Combination Immunotherapy of GM.CD40L Vaccine With CCL21 in Lung Cancer Lung Cancer, Adenocarcinoma Biological: GM.CD40L.CCL21 vaccinations; Biological: GM.CD40L cells vaccinations FL NCT01433172 Combination Vaccine Immunotherapy (DRibbles) for Patients With Definitively-Treated Stage III Non-Small Cell Lung Cancer Non-Small Cell Lung Cancer Carcinoma Drug: cyclophosphamide; Biological: DRibble vaccine; Drug: imiquimod; Drug: GM-CSF; Biological: HPV vaccine OR NCT01909752 PET Quantitative Assessments of Solid Tumor Response to Immune Checkpoint Blockade Therapy Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC) Radiation: PET/CT imaging with [18F] 2-deoxy-2-(18F)fluoro-D-glucose (FDG) MD NCT01666353 Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma Malignant Pleural Mesothelioma Biological: Vaccine plus chemotherapy CA; FL; IL; MD; PA NCT01675765 Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-Small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer Multiple Cancer Types Biological: Recombinant interleukin-15; Other: Pharmacological study; Other: Laboratory biomarker analysis CA; MD; MN; WA; WI NCT01727076 Immunotherapy Study in Progressive or Relapsed Non-Small Cell Lung Cancer Non-Small Cell Lung Cancer, Progression of Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer Recurrent Drug: docetaxel; Biological: HyperAcute-Lung Immunotherapy; Drug: gemcitabine; Drug: pemetrexed CA; CT; FL; IL; IN; KS; MO; MS; NE; NY; OH; TN; VA; WI NCT01774578 Combination of gp96-Ig Vaccine, Theophylline and Oxygen for the Treatment of Patients With Advanced, Relapsed or Metastatic Non-Small Cell Lung Cancer Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma Biological: gp96-Ig vaccine; Drug: theophylline; Other: Oxygen; Procedure: Immunologic evaluation FL NCT01799161 A Study to Demonstrate the Benefit of a New Kind of Anti-cancer Treatment [Preferentially Expressed Antigen of Melanoma (PRAME) Immunotherapy] for Patients With Non-Small Cell Lung Cancer (NSCLC), After Removal of Their Tumor Non-Small Cell Lung Cancer Biological: Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302032A; Biological: Placebo DE; IL; MN; NJ; NY; PA; WA NCT01853878 Phase II Study of Adjuvant WT-1 Analog Peptide Vaccine in MPM Patients After MSK10-134 Malignant Pleural Mesothelioma Biological: WT-1-vaccine Montanide + GM-CSF; Biological: Montanide adjuvant + GM-CSF NY; TX NCT01890980 LUNG 24 2014 Immunotherapy - Clinical Trials Section.indd 24 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:08 AM LUNG (CONTINUED) Title Cancer Type Treatment Location NCT Number Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion Malignant Pleural Effusion, Lung Cancer, Mesothelioma, Breast Cancer, Ovarian Cancer Biological: AdV-tk + valacyclovir PA NCT01997190 A Phase Ib Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-Small Cell Lung Cancer NSCLC, Non-Small Cell Lung Cancer, Lung Cancer Drug: MEDI4736; Drug: tremelimumab CA; CT; FL; NY NCT02000947 A Phase I Trial of NY-ESO-1 With GLA-SE in Patients With Unresectable or Metastatic Cancer Melanoma, Ovarian Cancer, Sarcoma, Non-Small Cell Lung Cancer, Breast Cancer Biological: IDC-G305 AZ; FL; MI; NY NCT02015416 A Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy or Immunotherapy in Participants With Lung Cancer (MK-3475-021/KEYNOTE-021) Non-Small Cell Lung Carcinoma Drug: pembrolizumab; Drug: paclitaxel; Drug: carboplatin; Biological: bevacizumab; Drug: pemetrexed; Biological: ipilimumab; Drug: erlotinib; Drug: gefitinib MI; OH; PA; TX NCT02039674 Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum Lung Cancer, Esophageal Cancer, Malignant Pleural Mesothelioma, Sarcoma, Thymic Carcinoma Biological: H1299 lysate vaccine; Drug: cyclophosphamide; Drug: celecoxib MD NCT02054104 A Phase II Study of Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer Non Small Cell Lung Cancer Drug: viagenpumatucel-L; Drug: metronomic cyclophosphamide; Drug: Physician’s Choice Regimen (vinorelbine, erlotinib, gemcitabine; paclitaxel, docetaxel) CA; MA; MO; OH; PA; TX NCT02117024 A Phase I Safety Study of Intradermal ID-LV305 in Patients With Locally Advanced, Relapsed or Metastatic Cancer Expressing NY-ESO-1 Breast Cancer, Melanoma, Non-Small Cell Lung Cancer, Ovarian Cancer, Sarcoma Biological: ID-LV305 CT; MA; MN; TX; WA NCT02122861 Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T cell Costimulatory Molecules (MVA-Brachyury-TRICOM) Lung Cancer, Breast Cancer, Prostate Cancer, Tumors (Others) Biological: MVA-brachyury-TRICOM MD NCT02179515 Study of Combined Ionizing Radiation and Ipilimumab in Metastatic Non-Small Cell Lung Cancer (NSCLC) Non-Small Cell Lung Cancer (NSCLC) Drug: ipilimumab; Radiation: Radiotherapy (IMRT) NY NCT02221739 Collect Long-term Data on Subjects Following Participation in Previous EMD 531444 (L-BLP25 or BLP25 Liposome Vaccine) Clinical Trials Non-Small Cell Lung Cancer, Multiple Myeloma Biological: tecemotide; Other: No intervention MA NCT01423760 Title Cancer Type Treatment Location NCT Number Evaluation for NCI Surgery Branch Clinical Studies Synovial Cell Cancer, Melanoma, Colorectal Cancer, Lung Cancer, Bladder Cancer MD NCT00001823 Multiple Class I Peptides & Montanide ISA 51 VG w Escalating Doses of Anti-PD-1 Antibody BMS936558 Melanoma (Skin) Biological: NY-ESO-1; Biological: BMS936558; Biological: gp100:280-288(288V); Drug: montanide FL NCT01176474 Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes Metastatic Cancer, Metastatic Melanoma, Renal Cancer, Colorectal Cancer, Ovarian Cancer, Lung Cancer Genetic: Anti-VEGFR2 CAR CD8 plus PBL; Drug: cyclophosphamide; Drug: aldesleukin; Drug: fludarabine MD NCT01218867 Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal Sarcoma, Melanoma, Epithelial Malignancies, Pleural Malignancy Biological: Epigenetically modified autologous tumor; Drug: cyclophosphamide; Drug: celecoxib MD NCT01341496 RADVAX: A Stratified Phase I/II Dose Escalation Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Metastatic Melanoma Metastatic Melanoma Drug: ipilimumab; Radiation: Stereotactic body radiation therapy PA NCT01497808 Vemurafenib and White Blood Cell Therapy for Advanced Melanoma Metastatic Cancer, Melanoma Drug: vemurafenib; Drug: Young TIL; Drug: cyclophosphamide; Drug: fludarabine; Drug: aldesleukin MD NCT01585415 Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma Metastatic Melanoma Drug: High-dose interleukin-2 (IL-2); Procedure: ACT with TIL infusion; Drug: vemurafenib; Drug: Lymphodepletion FL NCT01659151 PET Quantitative Assessments of Solid Tumor Response to Immune Checkpoint Blockade Therapy Melanoma, Renal Cell Carcinoma (RCC), Non-Small Cell Lung Cancer (NSCLC) Radiation: PET/CT imaging with [18F] 2-deoxy2-(18F)fluoro-D-glucose (FDG) MD NCT01666353 HD IL-2 + Vemurafenib in Patients With BRAF Mutation Positive Metastatic Melanoma Metastatic Melanoma Drug: vemurafenib + HD IL-2 AZ; CA; FL; GA; IA; IL; IN; LA; MI; MN; NH; NJ; NY; OH; OR; PA NCT01683188 Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma Metastatic Melanoma Drug: ipilimumab; Other: Radiation therapy and ipilimumab NY NCT01689974 Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-Small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer Multiple Cancer Types Biological: Recombinant interleukin-15; Other: Pharmacological study; Other: Laboratory biomarker analysis CA; MD; MN; WA; WI NCT01727076 Treatment of Advanced Melanoma With MK-3475 and Peginterferon Melanoma Drug: MK-3475; Drug: peginterferon alfa-2b PA NCT02112032 MELANOMA Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 25 25 9/17/2014 9:16:08 AM CLINICAL TRIALS MELANOMA - OVARIAN MELANOMA (CONTINUED) Title Cancer Type Treatment Location Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma Melanoma Drug: talimogene laherparepvec plus ipilimumab; Drug: ipilimumab AZ; CA; FL; IA; IL; IN; NCT01740297 KY; MN; NC; NJ; NY; OH; TN; UT NCT Number Dendritic Cell Activating Scaffold in Melanoma Melanoma Biological: WDVAX MA NCT01753089 Combined BRAF-Targeted Therapy & Immunotherapy for Melanoma Melanoma Drug: vemurafenib; Drug: aldesleukin MA NCT01754376 Detection of Immune Cell Infiltration Into Melanomas Treated by PV-10, a Feasibility Study Melanoma Drug: PV-10; Procedure: Surgery FL NCT01760499 Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutationpositive Melanoma Metastatic or Unresectable Cutaneous Melanoma Drug: MEK162; Drug: dacarbazine AL; AR; CA; CO; DC; FL; IA; IL; IN; MA; MD; ME; MI; MN; MO; NC; NE; NH; NJ; NV; NY; OH; OR; PA; TN; TX NCT01763164 Aldesleukin Imaging in Viewing Tumor Growth in Patients With Stage IV Melanoma Receiving Ipilimumab Therapy Recurrent Melanoma, Stage IV Melanoma Procedure: Scintigraphy; Other: Laboratory biomarker analysis; Biological: Technetium Tc 99 hydrazinonicotinamide-tricine-linked interleukin-2 MN NCT01789827 Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma Drug: cyclophosphamide; Drug: fludarabine phosphate; Biological: Therapeutic tumor infiltrating lymphocytes; Biological: aldesleukin; Other: Laboratory biomarker analysis WA NCT01807182 NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma Unresectable or Metastatic Melanoma Biological: ipilimumab; Biological: NY-ESO-1 protein vaccine; Biological: NY-ESO-1 OLP4 vaccine NY; PA; VA NCT01810016 The Effects of Vemurafenib on Immunity in Patients With Melanoma Melanoma Drug: vemurafenib DC NCT01813214 Autologous Dendritic Cell-Tumor Cell Immunotherapy for Metastatic Melanoma Stage IV Melanoma, Stage III Melanoma Biological: Autologous dendritic cell-tumor cell immunotherapy (DC-TC); Biological: Autologous PBMCs in GM-CSF (MC) CA NCT01875653 Dendritic Cell Vaccines + Dasatinib for Metastatic Melanoma Metastatic Melanoma Biological: DC vaccine; Drug: dasatinib PA NCT01876212 INCB024360 and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma Multiple Cancer Types Drug: IDO1 inhibitor INCB024360; Biological: MELITAC 12.1 peptide vaccine; Other: Laboratory biomarker analysis GA; NC; NH; VA NCT01961115 A Phase I Trial of NY-ESO-1 With GLA-SE in Patients With Unresectable or Metastatic Cancer Melanoma, Ovarian Cancer, Sarcoma, Non-Small Cell Lung Cancer, Breast Cancer Biological: IDC-G305 AZ; FL; MI; NY NCT02015416 Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 Melanoma Drug: cyclophosphamide; Procedure: CD8+ T cells; Drug: interleukin-2; Drug: ipilimumab TX NCT02027935 Vemurafenib:Radiation Use During Vemurafenib Treatment Melanoma Drug: vemurafenib UT NCT02042040 Immunotherapy Study for Patients With Stage IV Melanoma Stage IV Melanoma, Metastatic Melanoma Drug: HyperAcute-Melanoma (HAM) immunotherapy; Drug: ipilimumab NC; TN NCT02054520 Phase II Study of CD62L+-Derived T Lymphocytes Transduced With a T Cell Receptor Recognizing the NYESO-1 Antigen and Aldesleukin Following Lymphodepletion in Patients With NY-ESO-1 Expressing Melanoma Metastatic Cancer, Metastatic Melanoma Biological: Anti-NY ESO-1 TCR CD62L+ cells; Drug: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine MD NCT02062359 Study of IDO Inhibitor in Combination With Ipilimumab for Adult Patients With Metastatic Melanoma Metastatic Melanoma, Stage III Melanoma, Stage IV Melanoma Drug: indoximod; Drug: ipilimumab GA; NC; NH; VA NCT02073123 Study of Cell Transfer Therapy for Metastatic Melanoma Using 4-1BB Tumor Infiltrating Lymphocytes Plus IL-2 Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Melanoma, Skin Cancer Drug: interleukin-2; Drug: fludarabine; Drug: cylcophosphamide; Genetic: 41BB selected tumor infiltrating lymphocytes MD NCT02111863 Safety and Efficacy Study of Vemurafenib and High-dose Interferon Alfa-2b in Melanoma Melanoma Drug: High-dose interferon alfa-2b; Drug: vemurafenib PA NCT01943422 A Phase I Safety Study of Intradermal ID-LV305 in Patients With Locally Advanced, Relapsed or Metastatic Cancer Expressing NY-ESO-1 Breast Cancer, Melanoma, Non-Small Cell Lung Cancer, Ovarian Cancer, Sarcoma Biological: ID-LV305 CT; MA; MN; TX; WA NCT02122861 CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301 in Treating Patients With Stage IIB-IV Melanoma Multiple Cancer Types Biological: recombinant flt3 ligand; Biological: DEC-205/NY-ESO-1 fusion protein CDX-1401; Biological: neoantigen-based Melanoma-polyICLC vaccine; Other: laboratory biomarker analysis; Other: pharmacological study NH; NY NCT02129075 26 2014 Immunotherapy - Clinical Trials Section.indd 26 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:08 AM MELANOMA (CONTINUED) Title Cancer Type Treatment Location NCT Number Adoptive Therapy Using Antigen-Specific CD4 T-Cells Melanoma, Sarcoma Drug: ipilimumab; Drug: cyclophosphamide; Biological: CD4+ T cells TX NCT02210104 Multiple Antigen-Engineered DC Vaccine for Melanoma Melanoma Biological: DC Vaccine + IFN; Biological: AdVTMM2/DC vaccination PA NCT01622933 Neoadjuvant Combination Therapy With Ipilimumab and HighDose IFN-a2b for Melanoma Melanoma Drug: Administration of ipilimumab10mg/kg; Drug: Administration of ipilimumab 3mg/ kg + HDI PA NCT01608594 Aldesleukin With or Without Ziv-Aflibercept in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed By Surger Recurrent Melanoma Stage III-IV Melanoma Biological: ziv-aflibercept; Biological: aldesleukin; Other: Laboratory biomarker analysis CA, CO, GA, IL, IN, MI, MN, NH, NY, OH, PA, TN, VA NCT01258855 Title Cancer Type Treatment Location NCT Number 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow Neuroblastoma Biological: 3F8/GM-CSF immunotherapy plus 13-Cis-Retinoic acid NY NCT01183897 Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma Neuroblastoma Drug: zoledronic acid; Biological: aldesleukin AL NCT01404702 Study of Donor Derived, Multi-virus-specific, Cytotoxic T-Lymphocytes for Relapsed/Refractory Neuroblastoma Neuroblastoma Biological: Tri-virus specific cytotoxic T cells MO NCT01460901 Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma Recurrent Neuroendocrine Carcinoma of the Skin, Stage IV Neuroendocrine Carcinoma of the Skin Radiation: Radiation therapy; Biological: Recombinant interferon beta; Biological: MCPyV TAg-specific polyclonal autologous CD8-positive T cell vaccine; Biological: aldesleukin; Other: Laboratory biomarker analysis WA NCT01758458 3rd Generation GD-2 Chimeric Antigen Receptor and iCaspase Suicide Safety Switch, Neuroblastoma, GRAIN Neuroblastoma Genetic: iC9-GD2 T cell lymphocytes TX NCT01822652 Phase II STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma Procedure: Allogeneic HCT; Drug: Donor NK cell infusion WI NCT02100891 Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for HighRisk Neuroblastoma Neuroblastoma Biological: Anti-GD2 3F8 monoclonal antibody; Drug: GM-CSF (granulocyte-macrophage colony-stimulating factor); Drug: oral isotretinoin NY NCT02100930 Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma Multiple Cancer Types Biological: aldesleukin; Biological: OKT3/ humanized 3F8 bispecific antibody-activated T lymphocytes; Biological: sargramostim; Other: Laboratory biomarker analysis MI; NY NCT02173093 Isotretinoin With or Without Monoclonal Antibody Ch14.18, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma Disseminated Neuroblastoma|Localized Resectable Neuroblastoma|Localized Unresectable Neuroblastoma|Regional Neuroblastoma|Stage 4S Neuroblastoma Drug: isotretinoin|Biological: sargramostim|Biological: dinutuximab|Biological: aldesleukin|Other: laboratory biomarker analysis|Other: qualityof-life assessment|Other: pharmacological study AL; AR; AZ; CA; CO; NCT00026312 CT; DC; DE; FL; GA; HI; IA; IL; IN; KY; LA; MA; MD; ME; MI; MN; MO; MS; NC; ND; NE; NH; NJ; NM; NV; NY; OH; OK; OR; PA; RI; SC; SD; TN; TX; UT; VA; VT; WA; WI; WV 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of First Remission After Non-Myeloablative Therapy in Patients With High-Risk Neuroblastoma Neuroblastoma Drug: 3F8 and 13-cis-retinoic acid NY NCT01183429 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma Neuroblastoma Biological: 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid NY NCT01183897 Title Cancer Type Treatment Location NCT Number Trial of Adjuvant FANG Vaccine for High Risk Stage III/IV Ovarian Cancer Ovarian Cancer Biological: FANG FL; NH; TX; WA NCT01309230 Vaccine Therapy in Treating Patients With Metastatic Solid Tumors Malignant Solid Tumour, Breast Cancer, Malignant Tumor of Colon, GIST, Ovarian Cancer Biological: HER2 vaccine OH NCT01376505 Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms Other: ²¹²Pb-TCMC-trastuzumab; Biological: trastuzumab AL; CA NCT01384253 Treating Cancer With Anti-mesothelin Modified Lymphocytes Metastatic Cancer, Pancreatic Cancer, Mesothelioma, Ovarian Drug: fludarabine; Biological: anti-mesothelin CAR; Drug: cyclophosphamide; Drug: aldesleukin MD NCT01583686 NEUROENDOCRINE OVARIAN Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 27 27 9/17/2014 9:16:08 AM CLINICAL TRIALS OVARIAN - PROSTATE OVARIAN (CONTINUED) Title Cancer Type Treatment Location NCT Number How Our Immune System Can Help Fight Cancer Ovarian Cancer Drug: carboplatin & paclitaxel; Biological: carboplatin & paclitaxel & oregovomab CT; IN NCT01616303 Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes Metastatic Cancer|Metastatic Melanoma|Renal Cancer|Colorectal Cancer|Ovarian Cancer|Lung Cancer Genetic: Anti-VEGFR2 CAR CD8 plus PBL|Drug: Cyclophosphamide|Drug: Aldesleukin|Drug: Fludarabine MD NCT01218867 A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer Platinum Sensitive Ovarian Cancer Drug: Active comparator: Niraparib|Drug: placebo CT; IN NCT01616303 Autologous Dendritic Cell-Tumor Cell Immunotherapy for Advanced Epithelial Ovarian Carcinomas Stage III Ovarian Carcinoma, Stage IV Ovarian Carcinoma, Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma Biological: ovapuldencel-T; Biological: MC: Autologous PBMCs in GM-CSF CA NCT02033616 A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer Platinum Sensitive Ovarian Cancer Drug: Active comparator: Niraparib|Drug: placebo AZ; CA; CT; FL; GA; IL; IN; MA; MN; NC; NJ; NM; NY; OH; OK; PA; RI; TN; TX; WA NCT01847274 Intrapleural AdV-tk Therapy in Patients With Malignant Pleural Effusion Malignant Pleural Effusion, Lung Cancer, Mesothelioma, Breast Cancer, Ovarian Cancer Biological: AdV-tk + valacyclovir PA NCT01997190 A Controlled Study of the Effectiveness of Oregovomab (Antibody) Plus Chemotherapy in Advanced Ovarian Cancer Ovarian Neoplasms Drug: carboplatin & paclitaxel; Biological: carboplatin & paclitaxel & oregovomab CT; IN NCT01616303 INCB024360 Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Multiple Cancer Types Drug: IDO1 inhibitor INCB024360; Procedure: Therapeutic conventional surgery; Other: Laboratory biomarker analysis MN; NY NCT02042430 A Phase I Safety Study of Intradermal ID-LV305 in Patients With Locally Advanced, Relapsed or Metastatic Cancer Expressing NY-ESO-1 Breast Cancer, Melanoma, Non-Small Cell Lung Cancer, Ovarian Cancer, Sarcoma Biological: ID-LV305 CT; MA; MN; TX; WA NCT02122861 Title Cancer Type Treatment Location NCT Number A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers Metastatic Colorectal Cancer, Metastatic Gastric Cancer, Metastatic Pancreatic Cancer, Metastatic Hepatocellular Carcinoma, Metastatic Cholangiocarcinoma Biological: Young TIL; Drug: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine MD NCT01174121 Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms Other: ²¹²Pb-TCMC-trastuzumab; Biological: trastuzumab AL; CA NCT01384253 Anti-CD3 x Anti-Erbitux® Armed Activated T Cells (Phase Ib) for Gastrointestinal (GI Cancer) Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm, Malignant Neoplasm of Large Intestine, Malignant Tumor of Colon, Colon Carcinoma, Cancer of Colon, Pancreatic Cancer Drug: FOLFOX6; Biological: EGFRBi armed ATC infusions MI NCT01420874 Treating Cancer With Anti-Mesothelin Modified Lymphocytes Metastatic Cancer, Pancreatic Cancer, Mesothelioma, Ovarian Drug: fludarabine; Biological: Antimesothelin CAR; Drug: cyclophosphamide; Drug: aldesleukin MD NCT01583686 Pancreatic Tumor Cell Vaccine (GVAX), Low Dose Cyclophosphamide, Fractionated Stereotactic Body Radiation Therapy (SBRT), and FOLFIRINOX Chemotherapy in Patients With Resected Adenocarcinoma of the Pancreas Pancreatic Cancer Drug: cyclophosphamide; Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine; Radiation: Stereotactic body radiation (SBRT); Drug: FOLFIRINOX MD NCT01595321 Immunotherapy Study in Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer Pancreatic Cancer, Pancreatic Carcinoma Non-resectable, Locally Advanced Malignant Neoplasm Drug: FOLFIRINOX; Biological: algenpantucel-L immunotherapy; Radiation: 5-FU chemoradiation; Drug: gemcitabine; Drug: capecitabine; Drug: nab-paclitaxel AZ; CA; CT; FL; IL; IN; KS; MI; MN; NC; NY; OH; OK; OR; PA; TN; TX; WA; WI NCT01836432 A Phase II, Multicenter Study of FOLFIRINOX Followed by Ipilimumab With Allogenic GM-CSF Transfected Pancreatic Tumor Vaccine in the Treatment of Metastatic Pancreatic Cancer Metastatic Pancreatic Adenocarcinoma Drug: ipilimumab; Biological: Vaccine; Drug: FOLFIRINOX MD NCT01896869 Chemoimmunotherapy and Radiation in Pancreatic Cancer Locally Advanced Malignant Neoplasm Drug: tadalafil; Drug: gemcitabine; Radiation: Radiation; Procedure: Pancreaticoduodenectomy OR NCT01903083 PANCREATIC 28 2014 Immunotherapy - Clinical Trials Section.indd 28 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:09 AM PANCREATIC (CONTINUED) Title Cancer Type Treatment Location NCT Number A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine Pancreatic Cancer Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine MD NCT01088789 Combination Chemotherapy With or Without Oregovomab Followed By Stereotactic Body Radiation Therapy and Nelfinavir Mesylate in Treating Patients With Locally Advanced Pancreatic Cancer Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer, Stage III Pancreatic Cancer Drug: gemcitabine hydrochloride; Drug: leucovorin calcium; Biological: oregovomab; Drug: nelfinavir mesylate; Radiation: Stereotactic body radiation therapy; Procedure: Therapeutic conventional surgery; Other: Laboratory biomarker analysis; Drug: fluorouracil NE NCT01959672 Safety and Efficacy of Combination Listeria/GVAX Pancreas Vaccine in the Pancreatic Cancer Setting 2nd-line, 3rd-line and Greater Metastatic Pancreatic Cancer Biological: GVAX Pancreas vaccine; Biological: CRS-207; Drug: gemcitabine, capecitabine, 5-FU, irinotecan or erlotinib; Drug: cyclophosphamide AZ; CA; CO; FL; IL; MD; MO; NC; NY; OR; PA; TN; VA; WA NCT02004262 Title Cancer Type Treatment Location NCT Number A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers Cervical Cancer, Oropharyngeal Cancer, Vaginal Cancer, Anal Cancer, Penile Cancer Drug: fludarabine; Drug: cyclophosphamide; Biological: Young TIL; Drug: aldesleukin MD NCT01585428 Title Cancer Type Treatment Location NCT Number Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms Other: ²¹²Pb-TCMC-trastuzumab; Biological: trastuzumab AL; CA NCT01384253 INCB024360 Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Multiple Cancer Types Drug: IDO1 inhibitor INCB024360; Procedure: Therapeutic conventional surgery; Other: Laboratory biomarker analysis MN; NY NCT02042430 Title Cancer Type Treatment Location NCT Number Collection of Blood From Patients With Cancer Prostate Cancer, Breast Cancer, Colon Cancer, Lung Cancer, Liver Cancer MD NCT00034216 Phase II Study of Adenovirus/PSA Vaccine in Men With Recurrent Prostate Cancer After Local Therapy APP21 Recurrent Prostate Cancer Biological: Adenovirus/PSA vaccine IA NCT00583752 Adoptive Transfer of Autologous T Cells Targeted to Prostate Specific Membrane Antigen (PSMA) for the Treatment of Castrate Metastatic Prostate Cancer (CMPC) Prostate Cancer Biological: Engineered autologous T cells; Drug: cyclophosphamide NY NCT01140373 A Randomized, Double-blind, Phase III Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer Prostate Cancer Metastatic Biological: PROSTVAC-V; Biological: PROSTVAC-F; Drug: GM-CSF; Other: GM-CSF Placebo; Biological: Placebo AK; CA; CO; DC; FL; NCT01322490 IA; ID; IL; IN; LA; MA; MD; MN; MO; NC; ND; NE; NJ; NV; NY; OH; OR; PA; SC; TN; TX; UT; VA; VT; WA; WI; WV Sipuleucel-T, CT-011, and Cyclophosphamide for Advanced Prostate Cancer Prostatic Neoplasms Drug: CT-011 (Anti-PD1 Antibody); Other: Sipuleucel-T (PROVENGE); Drug: cyclophosphamide GA NCT01420965 Phase III Study of ProstAtak Immunotherapy With Standard Radiation Therapy for Localized Prostate Cancer Prostate Cancer Biological: ProstAtak(AdV-tk) + valacyclovir; Biological: Placebo + valacyclovir AZ; CO; MA; MD; NM; NY; PA; TX NCT01436968 C11-Sodium Acetate PET/CT Imaging for Metastatic Disease in Intermediate-to-high Risk Prostate Adenocarcinoma Prostate Cancer, Prostate Adenocarcinoma Drug: C11-sodium acetate AZ NCT01530269 Ipilimumab and GM-CSF Immunotherapy for Prostate Cancer Prostate Cancer Drug: ipilimumab; Drug: GM-CSF CA NCT01530984 Combining Ipilimumab With Abiraterone Acetate Plus Prednisone in Chemotherapy and Immunotherapy-naïve Patients With Progressive Metastatic Castration-resistant Prostate Cancer Prostate Cancer Drug: ipilimumab IL; NY; OR NCT01688492 A Neoadjuvant Study of Androgen Ablation Combined With Cyclophosphamide and GVAX Vaccine for Localized Prostate Cancer Prostate Cancer Adenocarcinoma in Situ Drug: degarelix acetate; Drug: cyclophosphamide; Drug: GVAX MD NCT01696877 Monitoring Anti-Prostate Cancer Immunity Following Stereotactic Body Radiotherapy (SBRT) Oligometastatic Prostate Cancer MN NCT01777802 A Randomized Phase II Trial of Combining Sipuleucel-T With Immediate vs. Delayed CTLA-4 Blockade for Prostate Cancer Prostate Cancer CA; TX NCT01804465 PENILE PERITONEAL PROSTATE Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 29 Drug: sipuleucel-T treatment; Drug: ipilimumab 29 9/17/2014 9:16:09 AM CLINICAL TRIALS PROSTATE - VAGINAL PROSTATE (CONTINUED) Title Cancer Type Treatment Location NCT Number Sipuleucel-T With or Without Radiation Therapy in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer Adenocarcinoma of the Prostate, Bone Metastases, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Soft Tissue Metastases, Stage IV Prostate Cancer Biological: sipuleucel-T; Radiation: External beam radiation therapy; Other: Laboratory biomarker analysis CA; UT NCT01807065 Sipuleucel-T and Stereotactic Ablative Body Radiation (SABR) for Metastatic Castrate-resistant Prostate Cancer (mCRPC) Metastatic Castrate-resistant Prostate Cancer, mCRPC Drug: sipuleucel-T; Radiation: Stereotactic ablative body radiation TX NCT01818986 Enzalutamide With or Without Vaccine Therapy for Advanced Prostate Cancer Prostate Cancer Biological: PROSTVAC-F/TRICOM; Biological: PROSTVAC-V/TRICOM; Drug: enzalutamide (Xtandi) MD NCT01867333 Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer Prostate Cancer Biological: PROSTVAC-F/TRICOM; Biological: PROSTVAC-V/TRICOM; Drug: enzalutamide (Xtandi) MD NCT01875250 Biological Therapy With or Without Vaccine Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer Biological: glycosylated recombinant human interleukin-7; Other: laboratory biomarker analysis CA; GA; NH; NY; WA NCT01881867 Combining Ipilimumab, Degarelix, and Radical Prostatectomy in Men With Newly Diagnosed Metastatic Castration Sensitive Prostate Cancer or Ipilimumab and Degarelix in Men With Biochemically Recurrent Castration Sensitive Prostate Cancer After Radical Prostatectomy Metastatic Castration Sensitive Prostate Cancer Drug: degarelix; Drug: ipilimumab; Procedure: Radical prostatectomy NY NCT02020070 Dendreon Lymph Node Biopsy in Metastatic CastrateResistant Prostate Cancer Prostate Cancer Drug: sipuleucel-T; Procedure: Lymph node biopsy NC NCT02036918 PET/MR Assessment of Sipuleucel-T Treatment for Metastatic Castration Resistant Prostate Cancer Prostate Cancer Device: PET/CT; Device: PET/MRI NY NCT02042053 Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T cell Costimulatory Molecules (MVA-Brachyury-TRICOM) Lung Cancer, Breast Cancer, Prostate Cancer, Tumors (Others) Biological: MVA-brachyury-TRICOM MD NCT02179515 Title Cancer Type Treatment Location NCT Number A Study of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer Transitional Cell Carcinoma of Bladder, Urethra Cancer, Ureter Cancer, Malignant Tumor of Renal Pelvis Drug: cisplatin; Drug: gemcitabine; Biological: ALT-801 AZ; CA; FL; GA; IA; IL; KS; LA; MI; MO; NC; NY; OK; PA NCT01326871 Title Cancer Type Treatment Location NCT Number Evaluation for NCI Surgery Branch Clinical Studies Synovial Cell Cancer, Melanoma, Colorectal Cancer, Lung Cancer, Bladder Cancer MD NCT00001823 Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas Lung Cancer, Esophageal Cancer, Malignant Pleural Mesothelioma, Sarcoma, Thymic Carcinoma Biological: Allogeneic tumor cell vaccine (K562); Drug: celecoxib; Drug: cyclophosphamide MD NCT01143545 Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal Sarcoma, Melanoma, Epithelial Malignancies, Pleural Malignancy Biological: Epigenetically modified autologous tumor; Drug: cyclophosphamide; Drug: celecoxib MD NCT01341496 Autologous T Cells and Cyclophosphamide in Treating Patients With Soft Tissue Sarcoma That is Metastatic or Cannot Be Removed By Surgery Adult Liposarcoma, Adult Synovial Sarcoma, Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma Drug: cyclophosphamide; Biological: NY-ESO-1-specific T cells; Other: Laboratory biomarker analysis WA NCT01477021 A Phase I Trial of NY-ESO-1 With GLA-SE in Patients With Unresectable or Metastatic Cancer Melanoma, Ovarian Cancer, Sarcoma, Non-Small Cell Lung Cancer, Breast Cancer Biological: IDC-G305 AZ; FL; MI; NY NCT02015416 Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum Lung Cancer, Esophageal Cancer, Malignant Pleural Mesothelioma, Sarcoma, Thymic Carcinoma Biological: H1299 lysate vaccine; Drug: cyclophosphamide; Drug: celecoxib MD NCT02054104 Phase II STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma Procedure: Allogeneic HCT; Drug: Donor NK cell infusion WI NCT02100891 RENAL PELVIS SARCOMA 30 2014 Immunotherapy - Clinical Trials Section.indd 30 P a t i e n t Reso ur ce.co m 9/17/2014 9:16:09 AM SARCOMA (CONTINUED) Title Cancer Type Treatment Location NCT Number A Phase I Trial of T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Children and Young Adults With Nonneuroblastoma, GD2+ Solid Tumors Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Ewing Sarcoma, Melanoma Other: Anti-GD2.28.z.OX40.ICD9 (anti-GD2 CAR) retroviral transduced autologous peripheral blood lymphocytes); Drug: AP1903 dimerizing agent MD NCT02107963 A Phase I Safety Study of Intradermal ID-LV305 in Patients With Locally Advanced, Relapsed or Metastatic Cancer Expressing NY-ESO-1 Breast Cancer, Melanoma, Non-Small Cell Lung Cancer, Ovarian Cancer, Sarcoma Biological: ID-LV305 CT; MA; MN; TX; WA NCT02122861 Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma Desmoplastic Small Round Cell Tumor, Disseminated Neuroblastoma, Metastatic Childhood Soft Tissue Sarcoma, Metastatic Ewing Sarcoma/ PNET, Metastatic Osteosarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/ PNET, Recurrent Melanoma, Recurrent Neuroblastoma, Recurrent Osteosarcoma Biological: aldesleukin; Biological: OKT3/ humanized 3F8 bispecific antibody-activated T lymphocytes; Biological: sargramostim; Other: Laboratory biomarker analysis MI; NY NCT02173093 Adoptive Therapy Using Antigen-Specific CD4 T-Cells Melanoma, Sarcoma Drug: ipilimumab; Drug: cyclophosphamide; Biological: CD4+ T cells TX NCT02210104 Title Cancer Type Treatment Location NCT Number Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma Brain and Central Nervous System Tumors, Lymphoma, Lymphoproliferative Disorder, Small Intestine Cancer Biological: Autologous immunoglobulin idiotype-KLH conjugate vaccine; Biological: sargramostim; Drug: methotrexate; Drug: thiotepa; Radiation: Radiation therapy TX NCT00621036 A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers Metastatic Colorectal Cancer, Metastatic Gastric Cancer, Metastatic Pancreatic Cancer, Metastatic Hepatocellular Carcinoma, Metastatic Cholangiocarcinoma Biological: Young TIL; Drug: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine MD NCT01174121 Title Cancer Type Treatment Location NCT Number A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers Metastatic Colorectal Cancer, Metastatic Gastric Cancer, Metastatic Pancreatic Cancer, Metastatic Hepatocellular Carcinoma, Metastatic Cholangiocarcinoma Biological: Young TIL; Drug: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine MD NCT01174121 Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms Other: ²¹²Pb-TCMC-trastuzumab; Biological: trastuzumab AL; CA NCT01384253 SMALL INTESTINE STOMACH URETER Title Cancer Type Treatment Location NCT Number A Study of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer Transitional Cell Carcinoma of Bladder, Urethra Cancer, Ureter Cancer, Malignant Tumor of Renal Pelvis Drug: cisplatin; Drug: gemcitabine; Biological: ALT-801 AZ; CA; FL; GA; IA; IL; KS; LA; MI; MO; NC; NY; OK; PA NCT01326871 Title Cancer Type Treatment Location NCT Number A Study of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer Transitional Cell Carcinoma of Bladder, Urethra Cancer, Ureter Cancer, Malignant Tumor of Renal Pelvis Drug: cisplatin; Drug: gemcitabine; Biological: ALT-801 AZ; CA; FL; GA; IA; IL; KS; LA; MI; MO; NC; NY; OK; PA NCT01326871 Title Cancer Type Treatment Location NCT Number A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers Cervical Cancer, Oropharyngeal Cancer, Vaginal Cancer, Anal Cancer, Penile Cancer Drug: fludarabine; Drug: cyclophosphamide; Biological: Young TIL; Drug: aldesleukin MD NCT01585428 URETHRA VAGINAL Pati entRes ource .c om 2014 Immunotherapy - Clinical Trials Section.indd 31 31 9/17/2014 9:16:09 AM CLINICAL TRIALS MISCELLANEOUS MISCELLANEOUS Title Cancer Type Treatment Location NCT Number Immunotherapy of the Paraneoplastic Syndromes Paraneoplastic Syndromes Drug: tacrolimus (FK506) NY NCT00378326 Study of Cytokines in Children With Opsoclonus-Myoclonus Syndrome Opsoclonus-myoclonus Syndrome IL NCT00806182 Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid Tumors Neoplasms, Tumors, Solid Tumors, Metastatic Cancer Biological: EGFRBi-armed autologous activated T cells RI NCT01081808 Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis Hemophagocytic Lymphohistiocytosis Drug: ATG, rabbit; Drug: etoposide; Drug: intrathecal methotrexate; Drug: hydrocortisone AZ; CA; FL; LA; MA; OH; PA; TX NCT01104025 Natural History Study of SCID Disorders SCID, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis, ADA Deficiency, XSCID AL; CA; CO; DC; FL; GA; IL; LA; MA; MD; MI; MN; MO; NC; NJ; NY; OH; OR; PA; TX; UT; WA; WI NCT01186913 Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal Sarcoma, Melanoma, Epithelial Malignancies, Pleural Malignancy MD NCT01341496 Patients Treated for SCID (1968-2010) SCID, ADA-SCID, XSCID, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis AL; CA; CO; DC; FL; GA; IL; LA; MA; MD; MI; MN; MO; NC; NJ; NY; OH; OR; PA; TX; UT; WA; WI NCT01346150 Human Placental-Derived Stem Cell Transplantation Mucopolysaccharidosis I, Mucopolysaccharidosis VI, Adrenoleukodystrophy, Niemann-Pick Disease, Metachromatic Leukodystrophy, Wolman Disease, Krabbe’s Disease, Gaucher’s Disease, Fucosidosis, Batten Disease, Severe Aplastic Anemia, Diamond-Blackfan Anemia, Amegakaryocytic Thrombocytopenia, Myelodysplastic Syndrome, Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia Drug: Human placental derived stem cell NY; UT NCT01586455 Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis Lupus Nephritis Biological: BMS-188667; Drug: mycophenolate mofetil; Drug: prednisone; Biological: Placebo matching with BMS-188667 AL; CA; FL; GA; LA; MA; NC; NJ; NY; OH; TN; TX; UT; VA NCT01714817 Ipilimumab and Imatinib Mesylate in Advanced Cancer Advanced Cancers Drug: ipilimumab; Drug: imatinib mesylate TX NCT01738139 Immunotherapy for Recurrent Ependymomas in Children Treatment for Recurrent Ependymomas Using HLA-A2 Restricted Tumor Antigen Peptides in Combination With Imiquimod Recurrent Ependymoma Biological: HLA-A2 restricted synthetic tumor antigen; Drug: imiquimod; Genetic: Reverse transcriptase-polymerase chain reaction; Other: Enzyme-linked immunosorbent assay; Other: Flow cytometry; Other: Immunohistochemistry staining method; Other: Laboratory biomarker analysis PA NCT01795313 Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores to Treat Patients With Solid Tumors That Have Not Responded to Standard Therapies Solid Tumor Malignancies Biological: Clostridium novyi-NT spores IL; MD; MI; MO; NY; OH; TX NCT01924689 Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NYESO-1 Murine TCR-Gene Engineered Lymphocytes Metastatic Cancers Other Than Melanoma That Express ESO Antigen Biological: Anti-NY-ESO-1 mTCR PBL; Drug: cyclophosphamide; Drug: fludarabine; Biological: aldesleukin MD NCT01967823 Patients Treated for Chronic Granulomatous Disease (CGD) Since 1995 Granulomatous Disease, Chronic CA; DC; FL; GA; LA; MA; MD; MI; MO; NC; NJ; NY; OH; OR; PA; TX; UT; WA; WI NCT02082353 Phase I/II Study of the Treatment of Metastatic Cancer That Expresses MAGE-A3 Using Lymphodepleting Conditioning Followed by Infusion of HLA-DP0401/0402 Restricted Anti-MAGE-A3 TCR-Gene Engineered Lymphocytes and Aldesleukin Metastatic Cancer That Express the MAGE-A3-DP4 Antigen MD NCT02111850 32 2014 Immunotherapy - Clinical Trials Section.indd 32 Biological: Epigenetically modified autologous tumor; Drug: cyclophosphamide; Drug: celecoxib Biological: Anti-MAGE-A3-DP4 TCR; Drug: cyclophosphamide; Drug: fludarabine; Drug: aldesleukin P a t i e n t Reso ur ce.co m 9/17/2014 9:16:09 AM GLOSSARY OF TERMS The immune system and immunotherapy Adaptive immunity – A subsystem of the overall immune system composed of specialized cells that eliminate infection and disease. This is the part of the immune system that creates a battle plan and launches a specific attack against every threat. This system is also characterized by a “memory” response that allows the immune system to work for prolonged periods of time. Antibody – A protein created by B cells in direct response to specific antigens. An antibody attaches itself to its respective antigen, marking it for other immune cells to “see” and destroy. Antigen – A protein on the surface of every cell or substance that alerts the immune system and causes the production of antibodies. Antigen-presenting cells (APCs) – Special cells that digest harmful materials in the body to “show” to the T cells so they recognize what to attack. Apoptosis – A process in which cells self-destruct, which helps regulate and limit the lifespan of cells. This process often does not work in cancer cells. B cells – Immune cells responsible for producing antibodies for specific antigens that will bind to the antigens and mark them for destruction by other immune cells. Cancer cells – Cells with damaged DNA that results in changes in normal cell growth and division. New cancer cells grow uncontrollably and old cancer cells don’t die when they should, resulting in a malignant tumor. Cancer cells can also spread to other parts of the body and grow. Co-stimulatory signal – The second stimulation required for T cells to become fully activated (Signal 2). CTLA4 (cytotoxic T lymphocyte associated antigen 4) – A protein receptor found on the surface of T cells. This protein is part of the CTLA4 checkpoint pathway, which can shut down the immune system response in its early stages by either preventing the positive signal necessary for activation or sending negative signals to inactivate the T cell. Certain cancer cells have the ability to engage this checkpoint, which puts the brakes on the immune response. Cytokines – Proteins released by immune cells to communicate with other immune cells; certain cytokines, such as interferon and interleukin, help regulate specific immune system functions. Cytotoxic T cell – A type of T cell that destroys virally infected cells and cancer cells through direct contact or via a chemical signal. To keep cytotoxic T cells in check, their activity is reduced by regulatory T cells when they are no longer necessary; this helps prevent damage to healthy tissue (autoimmune disease). Dendritic cell (DC) – A type of antigen-presenting cell responsible for processing antigen material and presenting it to the T cells for activation. DCs are also able to help regulate other immune cells. Downregulation – Reducing either the overall immune system response or the specific responses of certain immune cells. GM-CSF (Granulocyte-macrophage colony stimulating factor) – A cytokine protein responsible for stimulating bone marrow and promoting the growth of immune cells, especially dendritic cells. GM-CSF is currently used to restore white blood cells that have been depleted in chemotherapy patients, and is being studied as a possible immunotherapy treatment. Pati entRes ource .c om 2014 Immunotherapy A.indd 33 Immune cells – The cells of the immune system that are involved in defending the body against infectious disease and foreign invaders. may include certain proteins or molecules on the surface of the cancer cells; they are meant to stimulate an immune response just as naturally produced antibodies do. Immune checkpoint inhibitors – Drugs that block the activation of specific immune checkpoint pathways. Natural killer cells – White blood cells that contain enzymes that kill virally infected cells and tumor cells. They also communicate with T cells to help regulate their development and response. These cells are part of the innate immune response. Immune checkpoint pathways – The system of checks and balances in place to prevent over-activation of the immune system. Different pathways function at different stages of the immune system response to help regulate the length and intensity of the T cell activity; engaging an immune checkpoint typically results in shutting down the immune system response. Immunosuppression – Preventing the immune system from launching a successful attack to protect the body against infection and disease. Immunotherapy – An innovative type of cancer treatment that focuses on using the body’s own immune system to fight cancer. Immune-related adverse events (IRAEs) – Autoimmune reactions that occur as a result of boosting the immune system. Severe reactions may include colitis, dermatitis and hepatitis. Innate immunity – A subsystem of the overall immune system that detects and eliminates infection and disease and activates adaptive immunity. This is the part of the immune system that finds the threat and sounds the alarm. Interferon – A protein released by immune cells that helps regulate different immune cell activity; types of interferon include alfa, beta and gamma. Different types help regulate different functions, including prompting increased T cell activity, stimulating natural killer cells or affecting certain cell functions that influence tumor cell growth. Man-made versions of the IFN-alfa protein are currently FDA-approved to treat certain types of cancer. Interleukins – A set of proteins produced by T cells that helps regulate the production of certain immune cells, how they function during an immune response, and their production of cytokines. The man-made version of interleukin-2 (IL-2 or aldesleukin [Proleukin]), is currently FDA-approved to treat metastatic melanoma and metastatic renal cell carcinoma. Other interleukins are under study for possible cancer-fighting ability. Ligands – Protein molecules on the surface of a cell that bind to the receptor on the surface of another cell. Most ligands are signal-triggering molecules, which means they send out immune cell signals when engaged by a receptor. These signals help to regulate specific immune system functions. Major Histocompatibility Complex (MHC) – A set of molecules on the surface of certain immune cells that influences the interaction with other immune cells by displaying the cells’ antigens. Antigen-presenting cells present digested antigens to T cells through the MHC molecules on their surface; this allows the T cell to “see” the antigen and recognize it as foreign. The MHC–T cell receptor (TCR) connection is the first signal necessary to activate the T cell to respond to a tumor. Memory cells – T cells and B cells from a specific immune reaction that continue to circulate through the body even after the infection is resolved. They “remember” specific antigens and can multiply rapidly upon subsequent exposure, creating an immediate immune response already trained to eliminate the threat. Neutrophil – A type of white blood cell responsible for responding quickly to the site of injury or infection. Neutrophils contribute to acute inflammation and are the primary component of pus. Oncolytic virus – Viruses that have the ability to infect and multiply within cancer cells, leading to cell death. These viruses are tumor-selective, may be engineered or naturally occurring, and can be used to target and destroy specific tumor cells and initiate an immune response against the infected cancer cells. PD-1 (programmed cell death-1) – The receptor in the PD-1 checkpoint pathway that sends negative signals to the T cell when it connects to a PD-L1 or PD-L2 ligand. These negative signals normally slow down or stop the immune response when it’s no longer necessary. Certain cancer cells have the ability to influence the engagement of this checkpoint, which puts the brakes on the immune response. Proliferation – Cell division and development (growth). Receptors (immune receptors) – Proteins on the surface of immune cells that bind to ligands on the surface of other immune cells; this connection typically results in immune cell signaling that regulates specific immune system functions. Regulatory T cells – T cells that help maintain the necessity, strength and duration of an immune response by regulating T cell activity. They shut down the other T cells at the end of an immune reaction. Certain tumor cells have the ability to increase regulatory T cell activity, which decreases the overall immune response. Signal 1, Signal 2 – The primary and secondary cell signals necessary for the immune system to activate. Signal 1 is the Major Histocompatibility Complex (MHC) / Antigen-T cell receptor (TCR) interaction between the antigen-presenting cell and the T cell; Signal 2 can be any number of connections formed by the molecules and receptors on the surfaces of both the APC and the T cell. T cells – Adaptive immune cells responsible for recognizing specific antigens during antigen presentation; T cells are the major players in the immune system’s fight against cancer. Their activation and activity are two of the main focuses in immunotherapy research. T cell receptors (TCRs) – Molecules found only on the surface of T cells. TCRs must bind to special molecules on the surface of antigen-presenting cells before they can receive information about the threat. This connection is the first signal necessary to activate the T cell to respond to the tumor. Tumor microenvironment – The area surrounding a tumor inside which normal cells, molecules and blood vessels help sustain the tumor. The microenvironment contributes to the behavior, proliferation and spread of the tumor; the tumor itself is capable of affecting its own microenvironment. Upregulate – Increasing either the overall immune system response or the specific responses of certain immune cells. Monoclonal antibodies (mAbs) – Man-made antibodies engineered to target specific parts of cancer cells, which 33 9/17/2014 9:28:06 AM This patient education guide was produced with support from: 2014 Immunotherapy A.indd 1 9/17/2014 9:28:07 AM