NCCS Cancer Policy Roundtable Meeting Reinvigorating the Cancer - PDF document

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 NCCS Cancer Policy Roundtable Meeting Reinvigorating the Cancer Clinical Research Enterprise Peter C. Adamson, M.D. The Children’s Hospital of Philadelphia Success Rates for Drug Development 11% 5% Adapted from Nature Reviews: Drug Discovery, 3 (8): 711, 2004 1

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 NCI Cooperative Groups A Brief History History of NCI Cooperative Groups POG NCCTG IRSG NSABP GOG NWTSG RTOG SWOG CALGB ECOG CCG 1950 1960 1970 1980 1990 2

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 History of NCI Cooperative Groups IRSG NWTSG SWOG Pediat. Div. POG CALGB Pediat. Div. CCG 1955 1965 1975 1985 History of NCI Cooperative Groups Pediatric Oncology Group Children’s Oncology Group N ational INTERGROUP W ilms’ Rhabdomyosarcoma T umor STUDY GROUP S tudy G roup 2000 3

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Group Mergers • ECOG • RTOG • ACRIN • NSABP • GOG • CALGB • NCCTG • SWOG • ACOSOG New Drug Development Timelines NCI Expanding Infrastructure 4

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 New Drug Development Timeline Pre-Clinical Clinical R&D NDA Review Post-Marketing Testing, R&D Surveillance Average 18 mos Average 5 yrs Average 24 mos (1-3 yrs) (2-10 yrs) (2 mos-7yrs) Adverse Event Reporting Discovery Phase 1 Initial Surveys Synthesis Phase 2 Sampling & Purification Testing Phase 3 Animal Testing Inspections Short-term Long-term IND NDA NDA 30 Day Submitted Approved FDA Time Safety Review CTEP Therapeutics Development Specialty Resources Basic Resources /Other Phase I Program RAID (14 Phase 1 sites) Phase 0 - NExT Phase 1 Pediatric Phase 1 Expl IND Consortium CNS Consortia Phase 2 Program Pediatric, Adult Phase 2 (10 Phase 2 sites) *Other (Centers, SPORES, R21, R01, P01, etc.) Cooperative Groups Phase 3 *CCOPs *Non-CTEP Funded Resources Courtesy of Jeffrey Abrams, MD NCI-CTEP 5

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 New Drug Development Timelines Clinical Trials New Drug Development Timeline Pre-Clinical Clinical R&D NDA Review Post-Marketing Testing, R&D Surveillance Average 18 mos Average 5 yrs Average 24 mos (1-3 yrs) (2-10 yrs) (2 mos-7yrs) Adverse Event Reporting Discovery Phase 1 Initial Surveys Synthesis Phase 2 Sampling & Purification Testing Phase 3 Animal Testing Inspections Short-term Long-term IND NDA NDA 30 Day Submitted Approved FDA Time Safety Review 6

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Clinical Development Timeline � Rx Clinical Development Phase 3 Study Development Phase 2 Stdy D’vpt Phase 1 Time (Years) Concept to Trial Timeline Cooperative Group Response National Cancer Institute Central IRB Re-Review Concept Approved Process Takes up to 7 Years Courtesy of David Dilts 7

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 New Drug Development Timelines Investigator Perspective Academia Industry Scientific Review 8

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Concept Incubation Disease Cooperative Idea Committee Group Concept Review Review •Target •Competing Ideas •Scientific Mission •Drug •Research Landscape •Prioritization •Patient Population •Resources Concept to Trial Timeline Cooperative Group Response National Cancer Institute Central IRB Re-Review Concept Approved Courtesy of David Dilts 9

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 ���������������������������������������������������� Fail Early Sept-Oct 1998 Nov 1998 – July 1999 Aug 1999 - Present 10

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 “I have not failed, I have just found 10,000 ways that won’t work” Thomas Edison Clinical cancer research needs a system that can strategically fail early 11

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Cooperative Group Clinical Trials • Efficient • Effective Success Rates for Drug Development 11% 5% Adapted from Nature Reviews: Drug Discovery, 3 (8): 711, 2004 12

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Clinical Development Timeline � Rx Clinical Development Phase 3 Study Development Phase 2 Stdy D’vpt Phase 1 Time (Years) 13

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Study Design: Patient Flow Tumor shrinkage Continue open- � 25% label sorafenib (n=73) (n=79) Placebo* 12 weeks Sorafenib Tumor growth/ % Progression (n=33) 12-week run-in shrinkage <25% free 24 weeks (n=202) (n=69) Sorafenib 12 weeks (n=32) Tumor growth Off study � 25% (n=58) (n=51 † ) Disease status at 12 weeks unknown (n=9) *Placebo patients who progressed could cross over to sorafenib † Including 36 patients without bidimensional tumor measurements, but with radiological evidence of progression Courtesy of Mark Ratain, MD Progression Free Survival: Randomized Patients 1.00 Median PFS Sorafenib = 24 weeks Proportion of patients progression free Placebo = 12 weeks 0.75 Hazard ratio (S/P) = 0.44 p -value <0.000001 0.50 0.25 Sorafenib Placebo Censored observation 0 0 6 12 18 24 36 48 54 60 66 Time from randomization (weeks) Courtesy of Mark Ratain, MD 14

As Presented at the NCCS Cancer Policy Roundtable October 18-19, 2011 Smart Trials Smart Drugs 15