1. AACR Genomics In Clinical Medicine Think Tank
NCI’s Precision Medicine Initiative for Oncology – Operationalizing Public- Private 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

2. NCTN as a Network in the Era of Precision Medicine
LAPS
Activated:
Lung-MAP (S1400) – led by SWOG
ALCHEMIST (A151216) – led by Alliance and ECOG-ACRIN
Exceptional Responders (9671) – open in NCTN and beyond
NCI MATCH –led by ECOG-ACRIN
In development:
NCI Pediatric MATCH – led by COG … It takes a network …

3. Key Aspects of NCI Precision Medicine Trials
Single IND – multiple company partners working together within NCI IP agreement framework
Public- private partnerships to extend the trials’ reach (FNIH, FOCR, Companies)
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
Correlative science: cfDNA, whole exome/genome, RNA seq

4. 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

5. NCI’s Early Therapeutics Clinical Trials Network (ETCTN)

6. NCI-Designated Cancer Centers (clinical)
(Red= clinical centers gaining ETCTN opportunity under new program)
This map shows in blue stars NCI CC’s that are part of ETCTN and in red stars NCI CC’s that are currently not affiliated with the NCI ETCTN program. Under this proposal, investigators in these cancer centers would now have the opportunity to propose original clinical study ideas to CTEP, and if approved, would have ETCTN sites and infrastructure available for accrual of patients. In addition, many of these centers would now be able to help us recruit patients with rare tumors to our studies.

7. Recently developed NCI IND agents
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
The program has many successes and our trials have contributed to FDA approval of the agents listed here.

8. Molecularly Targeted Combinations: Accrual Data
Active Studies : 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)

9. Common Data Sharing and IP Option Agreement Language
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
Network Groups
NCI/DCTD
Collaborator B
Investigational Agent B
Consortia
Agreements encompass multiple trials/studies of mutual interest
Framework accepted by Collaborators and Cancer Centers

10. 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