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DESIGN OF A DISEASE SPECIFIC MASTER PROTOCOL Jeff Allen, PhD Executive Director Friends of Cancer Research.

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Presentation on theme: "DESIGN OF A DISEASE SPECIFIC MASTER PROTOCOL Jeff Allen, PhD Executive Director Friends of Cancer Research."— Presentation transcript:

1 DESIGN OF A DISEASE SPECIFIC MASTER PROTOCOL Jeff Allen, PhD Executive Director Friends of Cancer Research

2 Current Challenges Each potential new therapy is typically tested independently from other therapies seeking to treat the same condition For every new trial, the protocol must be reviewed by a number of oversight entities new phase III trials requires an average of 36 administrative or regulatory approvals and averages more than 2 years Approximately 4% of adult cancer patients enroll in clinical trials inability to meet accrual goals is a frequent factor causing trials to close, wasting time, money, and limited patient resources New therapies molecularly targeted against specific mutations may be present in only a fraction of the patient population

3 Design of a Disease-Specific Master Protocol 2012 Friends/Brookings Conference on Clinical Cancer Research

4 Major elements Setting: Setting: Squamous cell carcinoma (SCCA), advanced stage, 2 nd line therapy Agents: Agents: Candidate drugs must demonstrate biologic activity against a measurable target with a proposed predictive biomarker Study design: Study design: Multi-arm randomized, controlled phase II/III master registration protocol. Each arm able to open and close independent of other arms

5 Screening Archival FFPE tumor-common broad testing analytically validated platform suitable for registration purposes Molecule–specific tests, to include IHC, fresh core needle biopsy as appropriate Protocol arm powered for central test+ cases, with subsequent bridging studies as per FDA clearance. Goal is to develop each molecule with a companion diagnostic to support clinical use

6 Trial Structure Primary Endpoint: Primary Endpoint: Each arm independently powered for OS; interim analysis for PFS. Positive results at “rolling” interim analysis (no temporary closure) determine if a protocol arm proceeds to phase III portion. Goal Goal: minimum of 4 arms open at any time, to ascertain a reasonable chance for patients to be “biomarker positive”. Marker-negative patients enter common control group treated with SoC (vs anti-PD1 agent) to establish annotated repository

7 Trial operations Operations Management: Operations Management: Neutral 3 rd party - FNIH in collaboration with NCI Cooperative Groups Independent Drug/Biomarker Selection Committee Independent Drug/Biomarker Selection Committee: evaluates each drug-marker pair for suitability Oversight Committee Oversight Committee: Comprised of leaders from NCI, Academia, FDA, industry, advocates, to ensure operational efficacy

8 CT* TT=Targeted therapy, CT=chemotherapy (docetaxel or gemcitabine), E=erlotinib MASTER PROTOCOL Biomarker C TT C+CT CT* Endpoint (Interim PFS) OS Biomarker Β TT B CT* Endpoint (Interim PFS) OS Biomarker A TT A CT* Endpoint (Interim PFS) OS CNB/CLIA Biomarker Profiling Biomarker D TT D+E E* Endpoint (Interim PFS) OS Anti PD1 Unkn-Negbiomarker Courtesy of: Vali Papadimitrakopoulou

9 R a n d o m i z a ti o n Complete Accrual Study Design Within Each Biomarker- defined Subgroup Phase II Analysis 56 PFS events Final Analysis 210 OS events Phase III Interim Analyses Based on OS Futility established Stop 12 months follow-up Courtesy of: Mary Redman

10 Master Protocol over time Additional drug/biomarker combinations dropped and added to study

11 Benefits of a Master Protocol Enrollment Efficiency: Enrollment Efficiency: Grouping these studies under a single trial reduces the overall screen failure rate Operational Efficiency: Operational Efficiency: single master protocol can be amended as needed as drugs enter and exit the study Consistency: Consistency: every drug entered into the trial would be tested in the identical manner Predictability: Predictability: If pre-specified efficacy and safety criteria are met, the drug and accompanying companion diagnostic will be approved Patient Benefit: Patient Benefit: offers the advantage of bringing safe and effective drugs to patients sooner than they might otherwise be available.

12 Expert Working Group Roy Herbst – Yale University David Gandara – UC Davis Ellen Sigal – Friends of Cancer Research Vali Papadimitrakopoulou – MD Anderson Fred Hirsch – University of Colorado Mary Redman - Fred Hutchinson Cancer Center Jeff Abrams – National Cancer Institute Jack Welch – National Cancer Institute Shakun Malik – Food and Drug Administration David Wholley – Foundation for the NIH Eric Rubin – Merck Richard Gaynor – Eli Lilly David Chang - Amgen

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