anthony tolcher director of clinical research institute for drug development ctrc, san antonio tx

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Phase I Drug Development: Early Indications of Antitumor Activity for Sarcoma Patients and Opportunities for Progress Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

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Phase I Drug Development: Early Indications of Antitumor Activity for Sarcoma Patients and Opportunities for Progress. Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX. Phase-1-ologist. Pronounced: faez ·won·ole·geest Definition: - PowerPoint PPT Presentation

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Page 1: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Phase I Drug Development:Early Indications of Antitumor Activity

for Sarcoma Patients and Opportunities for Progress

Anthony TolcherDirector of Clinical Research

Institute for Drug DevelopmentCTRC, San Antonio TX

Page 2: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Phase-1-ologist

Pronounced: faez·won·ole·geest

Definition:1small curious creature that inhabits Texas, Ohio,

California, and occasionally Arizona.

2Exhibits animated activity when exposed to novel chemical structures or mechanisms of action

3Becomes ecstatic if one patient in 40 has response

Page 3: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Conventional Wisdom

• Focus on main indications– Breast, lung, colon, maybe prostate

• Smaller pharma- quickest route to NDA– unmet need, or accelerated approval

• Serendipity versus screening– Apriori, cannot predict activity– If we fail to have sarcoma patients, it is hard for us to

convince sponsors to explore sarcoma as an indication

Page 4: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

May 18 2004 Sep 15 2004

AP23573- Phase I

Page 5: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

AP23573 Phase I

34 yr old female with GIST Refractory to Gleevec, ET743 and others

Page 6: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Activity in Phase I Meaningful for Some Agents

Regulatory Success from phase I activity

• Iressa: NSCLC activity phase I – colon intended as indication– Contrast Tarceva

• Irinotecan: persistent SD in colorectal

• Gemcitabine: pancreas

Page 7: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Integrated Proliferation/Apoptosis Targets

Adapted from Johnstone et al. Cell. 2002.

DR4/5

TRAIL

TRM1ETR2

YM155Oblimersen

CCI 779AP23573

R115777

TNTC

Page 8: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Current Phase I Targets

• Survivin– MFH

• TRAIL R1• TRAIL R2

– Durable SD

• PDGFR• c-Met• Multi-targeted TKi• Integrins

• mTOR• IGFR

– Considerable literature

• PARP• Kinesin 1 inhibitors• Aurora Kinase

Inhibitors• Polo kinase inhibitors• C-myc

Page 9: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Opportunities for Strategic Collaborations

• Sarcoma patients account for 10% or less of IDD phase I population (500 yr)

• Serendipity or screening?– Can we increase “chance” to see activity– Known targets in sarcoma subtypes– Direct patients to studies

• Early identification of activity, rapid dissemination to phase II through affiliation

Page 10: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Create a Relationship

1. Activity seen in phase I (sarcoma pt)

2. Rapid access network of phase II sarcoma investigators to conduct study

• Accrual remains a serious concern

• Need to be “problem-free”• Quality of data remains the key

Page 11: Anthony Tolcher Director of Clinical Research Institute for Drug Development CTRC, San Antonio TX

Referrals

• This is key– Early Screen / serendipity– 40% of our patients come from southern USA– Good performance status, adequate organ

function

• Help from patient advocates– Opportunities for patients looking for expt

options