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.