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 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 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 • Created by a partnership of the CRI and LICR that leveraged complementary strengths and resources 2001 • 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 • 49 completed, ongoing, or pending trials • 55 publications stemming from these studies • Approximately 950 patients enrolled • Developed monitoring tools and assays • Largest survey of immunological response to single antigen NY-ESO-1 • Identified constructs capable of generating an integrated immune response to a known cancer antigen • 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.
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