Download NCI Precision Medicine Trials - American Association for Cancer

NCI’s Precision Medicine Initiative for
Oncology – Operationalizing PublicPrivate Partnerships
Jeffrey S. Abrams M.D.
Associate Director, CTEP, DCTD
Acting Director for Clinical Research, DCTD
National Cancer Institute, NIH
AACR Genomics In Clinical Medicine
Think Tank
July 13-14, 2016
NCTN as a Network
in the Era of Precision Medicine
LAPS
Activated:
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Lung-MAP (S1400) – led by SWOG
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ALCHEMIST (A151216) – led by Alliance and ECOG-ACRIN
•
Exceptional Responders (9671) – open in NCTN and
beyond
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NCI MATCH –led by ECOG-ACRIN
In development:
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NCI Pediatric MATCH – led by COG
… It takes a network
…
NCI National Clinical Trials Network
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Key Aspects of NCI Precision Medicine Trials

Single IND – multiple company partners working together within NCI IP
agreement framework
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Public- private partnerships to extend the trials’ reach (FNIH, FOCR,
Companies)
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Biopsies, NGS & other diagnostic tests paid for either by NCI or by company
partners – trials are very expensive

New educational issues for clinicians and patients – significance of
diagnostic tests – somatic (variants, allelic fraction) and germline
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Correlative science: cfDNA, whole exome/genome, RNA seq
NCI Precision Medicine Trials: Lessons Learned
Multi-Lab Concordance for NGS testing is achievable
Assay turnaround time is adequate
Biopsies from sites nationwide are feasible
Central IRB is a critical component
Pre-screening is valuable
Multiple arms can be difficult to manage when new data
intrudes
 Adjuvant studies of rare variants are challenging
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NCI’s Early Therapeutics Clinical Trials Network (ETCTN)
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NCI-Designated Cancer Centers (clinical)
(Red= clinical centers gaining ETCTN opportunity under new program)
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Recently developed NCI IND agents
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Agents that have achieved FDA approval based in part on early development in CTEP collaborative early phase
programs
 Bortezomib- Mantle Cell Lymphoma
 Ipilumumab- Melanoma
 Lenalidomide and bortezomib- Multiple Myeloma
 Romidepsin- Peripheral T cell Lymphoma
 Sorafenib- Thyroid Cancer
 Ziv-aflibercept- Colorectal Cancer
 Dinutuximab (ch14.18)- Neuroblastoma
Pending FDA approval
 Nivolumab – Anal and Nasopharyngeal Cancer
 Pembrolizumab – Merkel Cell, Mycosis Fungoides
In pivotal trials based on development in CTEP program
 Cediranib and Oliparib- Ovarian Cancer
 Selumetinib- Uveal Melanoma
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Molecularly Targeted Combinations: Accrual Data
 Active Studies 2011-2016: 263
 97 Investigational/Investigational
 127 Investigational/Commercial
 39 Commercial New indication
 29 Trials in review using investigational combinations
 Total Accrual: 11,432 across all histologies (phase 1, phase 2,
and pilot studies only – ETCTN and Cooperative Group Network)
NCI /Cancer Therapy Evaluation Program (CTEP)
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NCI Drug Formulary Initiative: Industry-NCI/CTEP-Investigator Agreements
Common Data Sharing and IP Option Agreement Language
Funding Agreement/Protocol
Language or MTA (for non-clinical studies)
Simplified CRADA
Agreement
Institutions
Collaborator A
Investigational Agent A
Collaborator B
Investigational Agent B
NCI/DCTD
Network
Groups
Consortia
• Agreements encompass multiple trials/studies of mutual interest
• Framework accepted by Collaborators and Cancer Centers
NCI /Cancer Therapy Evaluation Program (CTEP)
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Recommendations
 What is the threshold (of rarity) that defines the need
for national scale investigation (NCTN or private
sector)?
 Nationwide screening effort is needed to find molecular
subtype – new cost sharing structure seems necessary (gov’t,
industry, philanthropy)
 Central IRBs are critical for multi-arm studies and for studies of
rare diseases – system depends on volunteers
 Multiple agents are available for the target – Medical system
needs a “bake-off” study to rationalize care
NCI /Cancer Therapy Evaluation Program (CTEP)
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