Igor Espinoza-Delgado, M.D.Percy Ivy, M.D.
James A. Zwiebel, M.D.Investigational Drug Branch
Cancer Therapy Evaluation Program, NCI
Patricia LoRusso, D.O.Wayne State Cancer Center
ASCOJune 5, 2011
CTEP Young Investigator Meeting
Today’s Agenda
• CTEP overview & the Career Development LOI, James Zwiebel, MD
• Writing a competitive LOI, Percy Ivy, MD• LOI basics from a PI’s perspective, Patricia
LoRusso, DO • Elective rotation at CTEP for fellows and
faculty, Igor Espinoza-Delgado, MD
CTEP Overview
CTEP – FDA Concept ReviewNCI – Extramural Divisions
As of April 2004
Division ofCancer
Prevention
Peter G reenw ald ,M D
Division ofCancer
Contro l &PopulationSciences
Division ofCancerB io logy
Division ofCancer T reatm ent
and D iagnosis
Jim Doroshow ,M D
Division ofExtram uralActivities
NATIONAL CANCER INSTITUTE
Director
Andrew von Eschenbach, M D
Extram ural Divisions:
Com m unityO ncology and
Prevention T rialsResearch G roup
Cancer T herapyEvaluation
Program
Harold Varmus, M.D.
Radiation Radiation
Research Research
ProgramProgram
Division of Cancer Treatment and DiagnosisDivision of Cancer Treatment and DiagnosisJim Doroshow, MDJim Doroshow, MD
Office of the Director, DCTDOffice of the Director, DCTDBiometric Research BranchBiometric Research Branch
Cancer Cancer
Diagnosis Diagnosis
ProgramProgram
Cancer Cancer
Therapy Therapy
Evaluation Evaluation
ProgramProgram
Developmental Developmental
Therapeutics Therapeutics
ProgramProgram
CancerCancer
Imaging Imaging
ProgramProgram
Clinical
Grants
and
Contracts
BranchRoy Wu,
PhD
CANCER THERAPY EVALUATION PROGRAM
Jeffrey Abrams, MD
Operations & Informatics Branch
Steve Friedman, MHSA
Clinical
Investigations
Branch
Meg Mooney, MD
Regulatory
Affairs
Branch
Jan Casadei,
PhD
Investigational
Drug Branch
James Zwiebel, MD
Pharmaceutical
Management
Branch
Charles Hall, Jr., RPh, MBA
Clinical
Trials
Monitoring
Branch
Gary Smith, MT,
MGA
Broad Expertise of IDB Program Staff• IDB
– 12 full-time physicians committed to drug development– Staff are pro-active in identifying novel agents for clinical
development– Works with experts in the field
• Criteria for selection of novel agents– Novelty– Need – rare tumor indications, pediatric – Investigational combinations– Landscape – survey all agents in a class; avoid
duplicative development
InvestigationalInvestigationalTherapeutics 1Therapeutics 1
(Angiogenesis, (Angiogenesis, embryonic embryonic
pathways, apoptosis, pathways, apoptosis, cell death)cell death)
InvestigationalInvestigationalTherapeutics 2Therapeutics 2
(PI3K/AKT/mTOR, cell (PI3K/AKT/mTOR, cell cycle, microtubules, cycle, microtubules, proteosomes, c-met)proteosomes, c-met)
InvestigationalInvestigationalTherapeutics 3Therapeutics 3
(Angiogenesis, EGFR, (Angiogenesis, EGFR, imids, imids,
Immunotherapy, Immunotherapy, epigenetics)epigenetics)
Percy Ivy, MDPercy Ivy, MD(Associate Branch (Associate Branch
Chief)Chief)
John Wright, MD PhD John Wright, MD PhD (Associate Branch (Associate Branch
Chief)Chief)
Helen Chen, MD Helen Chen, MD (Associate Branch Chief)(Associate Branch Chief)
Pamela Harris, MD Pamela Harris, MD Alice Chen, MDAlice Chen, MD Igor Espinoza-Delgado, Igor Espinoza-Delgado, MDMD
Naoko Takebe, MD Naoko Takebe, MD PhDPhD
Austin Doyle, MDAustin Doyle, MD Howard Streicher, MDHoward Streicher, MD
Richard Piekarz, MD Richard Piekarz, MD PhDPhD
Investigational Drug BranchInvestigational Drug BranchJames Zwiebel, MD, ChiefJames Zwiebel, MD, Chief
SectionsSections
CTEP Therapeutics Development Program
Basic Resources Specialty Resources /Other
Phase 1
Phase 2
Phase 3
Adult U01 Phase 1 Program
Pediatric Phase 1 Consortium
CNS ConsortiaPediatric, NABTT,
NABTCN01
Phase 2 Program
Cooperative Groups
*CCOPs
*Other (Centers, SPORES, R21, R01, P01, etc.)
*Non-CTEP Funded Resources
Clinical Center,Cancer Centers, etc.
The Phase 2 N01 Network
Sydney, Australia
CTRG -Pacific Rim
Member Institutions and Consortia:29 NCI-designated Cancer CentersMD AndersonCalifornia Consortium
UC Davis, City of Hope, USC, U of PittU of Chicago
U of C network, U of Michigan, U of Maryland, College of Wisconsin
NY Phase 2 ConsortiumMontefiore, Weill Cornell, Mt Sinai, Columbia, North Shore, U Conn, Sydney
Mayo Phase 2 ConsortiumU of Wisconsin, Johns Hopkins, WayneState, Washington U, UCSF, CTRG (Pacific Rim), Mayo Arizona &Jacksonville, U of Colorado, U of Iowa
Memorial Sloan-KetteringPrincess Margaret Phase 2 Consortium
Hamilton, Kingston, London, Edmonton, McGill, Halifax, Sunnybrook,Vancouver, Roswell Park, Fox Chase
Ohio State UniversitySoutheast Phase 2 Consortium
Moffitt, UNC, Vanderbilt, Emory, Virginia Commonwealth, Medical University of South Carolina
To improve the lives of cancer patients To improve the lives of cancer patients
by finding better ways to treat, control by finding better ways to treat, control
and cure cancer.and cure cancer. – Extensive national program of cancer Extensive national program of cancer
research research
– Sponsor clinical trials to evaluate new anti-Sponsor clinical trials to evaluate new anti-
cancer agentscancer agents
– Particular emphasis on translational Particular emphasis on translational
research to elucidate molecular targets and research to elucidate molecular targets and
mechanisms of drug effects. mechanisms of drug effects.
The CTEP Mission
CTEP By Numbers
• Currently sponsors over 140 INDs
• Approx. 14,000 registered investigators at over
3,300 institutions
• Over 1000 active protocols
• 500 new protocols/year
• 25,000-30,000 patients accrued/year
CTEP’s Role in Drug Development
• Accelerate development of promising new agents
• Sources of agents:– Industry– Academia– NCI Experimental Therapeutics Program
• CTEP agreements with ~80 industry partners for 143 investigational agents
• ~10 new INDs filed each year
CTEP’s Role in Drug Development
• Broaden development in relevant tumor types– Industry focus on limited number of indications
dictated by market considerations
• Combinations of targeted agents a high priority– More than 100 trials initiated since 2000– Facilitated by the IP language in CTEP-industry
agreements
• Explore– Alternative methods of drug administration– Mechanism of Action/Proof of Principle/Biomarkers
From Bench to BedsideAGENTSAGENTS
STUDIESSTUDIES
NCI Industry Academia
CTEP
Letter of Intent
Investigators
CTEPReview of Review of DataData
Review of Review of DataData
DevelopmentDevelopmentPlan*Plan*
DevelopmentDevelopmentPlan*Plan*
SolicitationSolicitationSolicitationSolicitation
ApprovalApprovalApprovalApproval
DTPPreclinicalDevelopment
ClinicalDevelopment
CTA/CDACTA/CDACTA/CDACTA/CDA
Solicited, unsolicited LOIs
NExT Committee
IDSC
Solicitations for 2011-2012
Recently released:•ARQ 197 – c-met inhibitor (due July)•AMG 486 – Ang 1/2 inhibitor (completed)•TRC 105 – anti-endoglin (CD105) antibody (due 6/28)
Planned:• SCH-90077 - chk1 inhibitor• MK-1775 – wee-1 inhibitor• GSK 2118436 – mut. b-raf inhibitor• GSK 1120212 – mek inhibitor• TL32711 – smac mimetic IAP inhibitor• PCI-32765 – btk inhibitor
CTEP Career Development LOI
Program
Career Development LOI
Components:
1. Outreach
2. LOI prioritization
3. Mentorship and institutional support
Goal: To facilitate career development in translational cancer research
Outreach
• Education – Session at ASCO to increase awareness &
better understanding of CTEP & components of successful LOI
– Elective rotation at CTEP• LOI development
– Encourage investigators to interact with CTEP staff during LOI development and review process• Avoid pitfalls • Successfully address reviewers’ comments
Prioritization of solicited LOIs
• To provide junior faculty with a competitive advantage within the LOI review process:
• Award study to young investigator whose proposal is of similar quality as LOIs submitted by more senior, established investigators
Mentorship and institutional support
• Identify senior faculty mentor • Obtain institutional commitment for:
– Research nursing support– Date management and statistical support– Access to patients
• Prioritization of LOIs from young investigators may provide an incentive for institutional support
Submission requirements - 1
• Study proposals utilizing a CTEP-held IND agent and meeting the CTEP LOI evaluation criteria
• Junior faculty within 7 years of completion of training
• A major interest in clinical research and the intention to develop a career in that field
• Institutional track record in carrying out trials with investigational agents
Submission requirements - 2
• Letters of Commitment:– Institution:
• Support for the proposed study, e.g., research nursing staff, data monitoring, etc.
– Senior faculty member who will serve as a mentor:• provide expertise and oversight in the design and
conduct of the trial• confirm the feasibility of the proposed trial within the
institutional setting • make every reasonable effort to enable the PI to be able
to conduct clinical trial successfully
Information on CTEP
http://ctep.cancer.gov/
CTEP website