Document 4405

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
 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
 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
 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
 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
Created by a partnership of the CRI and LICR that leveraged complementary strengths and
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.
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
 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
 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.