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