1. Pediatric Preclinical Testing Consortium
Malcolm A. Smith, MD, PhD
Cancer Therapy Evaluation Program, NCI
December, 2016

2. PPTC Primary Objective
The PPTC is designed to produce reliable preclinical in vivo data using genomically characterized patient-derived xenograft lines so that childhood cancer clinical researchers can better prioritize which agents to pursue in pediatric clinical trials. Effective prioritization of truly active agents for pediatric clinical testing is essential to future success in identifying more effective treatments for children with cancer.

3. History
Pediatric Preclinical Testing Program (PPTP) received two 5-year awards from NCI
PPTP awards were research contracts with Dr. Peter Houghton as PI
St. Jude Children’s Research Hospital
Nationwide Children’s Hospital
Systematic approach to preclinical testing with in vivo focus
More than 80 agents
More than 50 pharmaceutical companies
More than 70 publications

4. PPTC Niche Complementary to other research activities:
More basic research teams identify critical biological pathways and therapeutic targets
Individual laboratories focus on mechanism of action (primarily in vitro experiments)
Pharmaceutical companies develop agents for adult cancer markets
Clinical research teams prioritize agents for clinical evaluation
The PPTC develops robust preclinical dataset for candidate agents using genomically characterized childhood cancer xenograft lines

5. Pediatric Preclinical Testing Consortium (PPTC)
The PPTC is funded through a cooperative agreement.
Testing is performed by highly qualified research programs that focus on specific childhood cancers.
Coordination and data management/analysis is by the PPTC Coordinating Center.
NCI has specific responsibilities in providing scientific, technical, and regulatory assistance, advice, and coordination within the Consortium.
The NCI Program Director for PPTC is Dr. Malcolm Smith of Cancer Therapy Evaluation Program (CTEP)
Dr. Beverly Teicher serves as an NCI Steering Committee representative
NCI is responsible for negotiating Material Transfer Agreement (MTAs) with pharmaceutical companies.

6. PPTC Members Role Institution PI Coordinating Center
Research Triangle Institute (RTI)
Diana Severynse-Stevens, PhD
Sarcoma & Renal
Greehey Children’s Cancer Research Institute
Peter Houghton, PhD
Raushan Kurmasheva, PhD
Neuroblastoma
Children’s Hospital of Philadelphia
John Maris, MD
Osteosarcoma
Children’s Hospital at Montefiore
Richard Gorlick, MD
Leukemia
Children’s Cancer Institute Australia
Richard Lock, PhD
CNS
Baylor College of Medicine
Xiao-Nan Li, MD, PhD

7. Coordinating Center Name Position Diana Severynse-Stevens, PhD
Principal Investigator
Sudie Rowshan
Project Director
Cindy McClintock
Project Coordinator
Steve Erickson, PhD
Statistician
John Guo, PhD
Kevin Wilson
Data Management
Sophie Li

8. PPTC Organization

9. PPTC Funding Total funding of approximately $2.7 million per year
Testing of 6 to 10 new agents (or combinations of agents) annually across relevant, well-characterized preclinical models.
Limited funding for PK/PD studies

10. Evaluating Agents Through PPTC
Confidentiality agreement (if needed)
Application (see application at
Review by PPTC Steering Committee
Research Plan developed by PPTC
MTA with NCI (see
Provision of agent to PPTC Coordinating Center
In vivo testing and analysis of results at relevant Research Program(s)
Report for company with 8-12 months of drug receipt

11. Agents Tested by PPTC and Transitioned to the Clinic for Evaluation in Children with Cancer
Alisertib (MLN8237)
NTX-010
Selumetinib for BRAF-mutated low-grade astrocytoma
Rapalog plus standard chemotherapy (for rhabdomyosarcoma)
IGF-1R antibodies
Eribulin
Talazoparib (BMN 673) plus low-dose temozolomide

12. PPTC Material Transfer Agreements
Company executes MTA with CTEP/NCI for provision of agent for Pediatric Preclinical Testing Consortium only. No other uses of agent under this MTA.
NCI has executed MTAs with each of participating institutions and a collaboration agreement with the PPTC Coordinating Center
No significant modifications to MTAs are accepted from companies; terms of institution MTAs and company MTAs are consistent
Institution awards were based on acceptance of MTA terms

13. MTA Terms
Use agent as provided without making any modifications to agent or attempting to analyze compound provided
Institution indemnifies company for its use of material and data
Company indemnifies institution for its use of data resulting from the project
Reports provided to NCI at least quarterly
Company granted right to use all data and results for any purpose

14. Publications and IP Issues
45 day company review of all manuscripts and 10 day abstract review
Institution may not submit without written approval from CTEP to do so after any and all NCI and company comments are addressed
NCI IP Option to Collaborator included in Institution MTA and Coordinating Center Collaboration Agreement. Company receives non-exclusive royalty free license to any invention for commercial purposes, and first option to negotiate an exclusive or co-exclusive royalty bearing license for commercial purposes. Company will cover patent prosecution and maintenance costs. Company has 3 months to notify institution of interest in obtaining an exclusive license. Extended time period to decide if invention will be useful.
Unauthorized Use. Company receives a royalty-free exclusive or co-exclusive license. Company will cover patent prosecution and maintenance costs.