Document 6423362

Cancer Immunotherapy Trials Network (CITN)
Jedd D. Wolchok MD PhD
Steering Committee Member, CITN
Director, Cancer Vaccine Collaborative
Associate Chair, Dept of Medicine
Memorial Sloan-Kettering Cancer Center
Cancer Immunotherapy Trials Network
 CITN brings together cancer immunotherapists from 28 foremost
universities and cancer centers in North America
 To design & conduct innovative early phase immunotherapy trials for
patients with cancer.
 Innovative aspect
 CITN utilizes the collective experience and wisdom of “the field”
 To prioritize and conduct optimal trials:
 Likely to be more informative than trials that can be developed
and conducted by individual scientists and companies working in
isolation.
 Active collaboration with industry, foundations and not-for-profit entities
to design and co-fund trials
CITN Member Sites and PIs
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Baylor & Mt. Sinai - Palucka
Case Western Reserve -Triozzi
Dana Farber - Hodi
Dartmouth - Ernstoff
Duke - Lyerly
Emory - Waller
Fred Hutchinson - Thompson
MD Anderson - Cooper
Moffitt Cancer Center - Antonia
MSKCC - Wolchok
NCI Liaison – Schlom
New York University - Bhardwaj
Ohio State - Carson
Providence - Urba
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Roswell Park – Odunsi
Rush - Kaufman
Stanford – Levy
UCSD - Kipps
UCSF - Fong
U of Chicago - Gajewski
U of Miami - Rosenblatt
U of Minnesota - Miller
U of Pennsylvania - June
U of Pittsburgh - Ferris & Zarour
U of Toronto - Ohashi
U of Virginia - Slingluff
U of Wisconsin – Sondel
Yale - Sznol
Cancer Immunotherapy Trials Network
 Agents being developed were prioritized by a series of NCI
sponsored workshops to rank agents with high potential for use
in cancer therapy.
 Focus on agents with the greatest potential for broad usage by
multiple investigators in multiple different regimens.
 Processes & procedures for prioritization & for designing trials
could be used to organize other clinical trial disciplines.
Perceived Need
 Agents have been invented that can potentially cure cancer
patients
 Unlimited opportunities in immunotherapy, but too little focus and
limited resources
 >100 potential cancer vaccine targets
 >1000 combinations of agents, vaccines, antibodies & T cell therapy
regimens
 CITN has piloted methods for prioritization, recruited a “dream”
team of foremost immunotherapists and built an organization to
facilitate collaboration
 CITN can accelerate clinical development of immunotherapy
CITN: Strategy
 To use the collective strength of member sites to facilitate the
availability & testing of immunotherapy agents likely to benefit
cancer patients
 To focus on trials likely to achieve the optimal/quickest route to
 Proof of Concept
 Demonstration of patient benefit
 Regulatory approval
 To focus on agents & formulations likely to achieve broad
availability through commercialization
Brief History: NCI Prioritization Workshops
 NCI prioritization workshops
 “Immunotherapy Agents Workshop”
 Ranked top 20 agents out of 126 suggestions with known
substantial immunologic activity that have not been adequately
tested in cancer patients.
 “Cancer Antigen Pilot Prioritization Project”
 Ranked 75 target cancer antigens according to pre-determined
and pre-defined characteristics to focus on top 6
 “Immune Response Modifier Pathway Working Group”
 Developed criteria for combining agents with vaccines
 Broad input with more than 80 scientists involved)
Priority Agents with High Potential to
Benefit Patients with Cancer
 T cell growth factors (IL-7 & IL-15)
 Dendritic cell activators (Anti-CD40)
 Inhibitors of T cell checkpoint blockade (Anti-PD1)
 Dendritic cell growth factors (Flt3L)
 Vaccine adjuvants (IL-12)
 T cell stimulators (4-1-BB)
One Example: IL-7 – a Natural Occurring T cell Growth Factor
that Normally Functions to Maintain the Number of T cells
IL-7, as a drug, administered every other day for 14 days
can double and quadruple the total number of T cells in the blood
[Sportès (Mackall) et al J. Exp. Med. 1681:2007]
Current Study Focus
 Initial Cancer Focus
 Non-small cell lung cancer
 Pancreas cancer
 Melanoma
 Ovarian cancer
 Prostate cancer
 Trials to be initiated in Q1-Q2 2012
 IL15: Lung cancer & solid tumors
 Anti-CD40: Pancreas cancer
 Anti-PD1: Melanoma
Key Partners and Players
 27 foremost universities and comprehensive cancer centers
 Fred Hutchinson Cancer Research Center
 Central Operating and Statistical Center (COSC)
 Overall leadership, organizational infrastructure, statistical
design and protocol coordination
 Funding
 Biotech & Pharma
 Alignment of scientific, clinical and management resources
 GMP manufactured agents
 Co-design and co-fund trials
Key Partners and Players
 NCI
 Funding
 Cancer Therapy Evaluation Program (CTEP) – facilitates interactions with NCI
 CTMB (monitoring),
 Clinical Trials Support Unit (CTSU) – regulatory and data management,
 Biometrics Research Branch - assistance and review of data management,
 Biological Resources Branch (BRB) - assistance for accessing prioritized agents,
 Regulatory Affairs Branch (RAB) assists with investigational new drug (IND) applications
 Foundations & Non-profit Entities:
 Co-design to make innovative therapies available to cancer patients
 Co-fund to overcome financial barriers
A NEW MODEL OF CLINICAL DISCOVERY
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Created by a partnership of the CRI and LICR that leveraged complementary strengths and
resources
2001
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A coordinated global network dedicated to science-driven cancer vaccine testing and optimization,
composed of 19 academic trial sites closely linked with advanced immunological monitoring laboratories,
working in parallel to conduct early-phase clinical trials of multi-component therapeutic cancer vaccines.
A POWERFUL GLOBAL NETWORK
KEY CVC ACCOMPLISHMENTS
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49 completed, ongoing, or pending trials
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55 publications stemming from these studies
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Approximately 950 patients enrolled
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Developed monitoring tools and assays
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Largest survey of immunological response to single antigen NY-ESO-1
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Identified constructs capable of generating an integrated immune response to a known cancer antigen
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Tested and compared a broad array of TLR agonists as essential vaccine components
Conclusions
 Immunotherapy agents needed to treat and possibly cure
cancers have been invented & manufactured.
 Methods to prioritize immunotherapy agents, target antigens &
regimens have been piloted.
 The CITN provides an organized effort to conduct early phase
trials with a focus on trials likely to achieve the optimal/quickest
route to
 Proof of Concept
 Demonstration of patient benefit
 Regulatory approval
Conclusions
 CITN Vision – To have many immunotherapy agents with
proven biologic function broadly available for effective
cancer therapies.
 Vision can be accomplished by accelerating ongoing
collaborations between CITN investigators, industry,
foundations and not-for profit entities.