1. Role of the Drug Project Team in Formulating the Initial Development Plan of NCI-IND agents Jeff Moscow, MD IDB, CTEP

2. 2 Overall Process of NCI-Sponsored Drug Development  Pharmaceutical Company X applies for CTEP collaboration through the NExT program to help develop Drug X  The NExT application proposes an envisioned collaboration in which NCI-sponsored clinical trials test Drug X in combination with specific CTEP IND agents  If Drug X is approved by NExT, an internal NCI committee makes a preliminary development plan, which is reviewed and approved by another internal NCI committee.  At this point, 2 things happen:  The Drug X Project Team is formed  CRADA negotiations with Pharmaceutical Company X are initiated.  Both processes have a 6 month deadline

3. 3 Why do pharmaceutical companies apply to NExT for NCI-sponsored development of their agents?  CTEP has access to novel agents from competitors- can act as an honest broker.  Companies realize that there are potential therapeutic indications that do not have high enough priority to compete for limited corporate resources  CTEP has a network of experienced clinical trialists and centralized clinical trial support systems  CTEP can expend public funds for clinical trials and regulatory support.

4. 4 Why does NCI help pharmaceutical companies develop their agents?  NCI recognizes that there is a significant public interest in finding indications for new oncology drugs beyond those that may be the most profitable.  NCI can advance the understanding of cancer biology and treatment through carefully designed clinical trials

5. 5 The Drug Project Team (1)  Leading extramural experts, together with intramural staff, formulate the initial NCI drug development plan.  Though the previous drug development plans (NExT application and preliminary internal plan) may be referenced, the Drug Project Team starts from a clean slate.  There are three major benefits:  Involvement of extramural community in development of the initial plan, instead of CTEP staff deciding on the plan.  Concurrent drug development planning with CRADA negotiations shortens the timeline  Eliminates the inefficient and frustrating process of preparing and reviewing unsolicited LOI’s

6. 6 The Drug Project Team (2)  A ‘quick team’ that is intended to be in existence for 6-12 weeks.  Has intramural and extramural participation  Three extramural roles: clinical scientists, translational scientists, and basic scientists  Two extramural scientists and the IDB drug monitor serve as co- chairs  All meetings are by webinar  Requires a commitment to participate in all meetings

7. 7 The Drug Project Team (3)  Since the concept is to recruit the most qualified experts to develop the initial development plan, only individuals, and not teams, may apply.  The exception is that YI’s can apply with a mentor.  For YI’s, the most important advice is: apply with a mentor. It is highly unlikely that a YI could be competitive without a mentor.  For potential mentors the most important advice is: apply with a YI. Preference is given to mentor/YI combinations, as training YI’s is an ETCTN program goal.

8. 8 The Drug Project Team (4)  PTMA is very simple form, and requires only the attachment of your NIH Biosketch.  Customize your personal statement to the Drug Project Team application.  The primary goal of the Drug Project team is to present a Drug Development plan to the IDSC.  Clinician scientist members of the Drug Project Team are anticipated to be the PI’s of the clinical trials that come out of the process.  Translational and basic scientists on the project team may also become members of the study teams for these trials.

9. 9 Responsibilities - DPT clinician scientists  Expected to actively participate in developing a comprehensive plan to be endorsed by the IDSC  Leaders (co-chairs) will present clinical information to the IDSC  Expected to lead or co-lead clinical trials that come out of the DPT planning process  Not guaranteed – selected clinical investigators that do not participate in team activities will be replaced  Should be from ETCTN-affiliated sites

10. 10 Responsibilities- DPT translational scientists  Expected to help develop biomarker endpoints for clinical studies  Expected to help select appropriate technology platforms, and to work out many details of biomarker selection and test qualification with CDP  May be eligible to apply for supplemental UM1 grant funds for selected projects.  Have the opportunity to incorporate the same biomarkers on the same platforms in multiple trials  Do not need to be from ETCTN-affiliated sites

11. 11 Responsibilities- DPT basic scientists  Expected to educate the team about the basic science behind the drug  Expected to help guide trial design based on underlying knowledge of mechanism of action of the agent  Expected to help guide biomarker selection  May perform experiments to help guide deliberations – will have access to NCI drugs  May be eligible to apply for supplemental UM1 grant funds for selected projects.  Do not need to be from ETCTN-affiliated sites

12. 12 Drug Project Team Outcomes (1)  Presentation to the Investigational Drug Steering Committee (IDSC)  IDSC is an advisory committee to CTEP. Recommendations are important but not binding  The IDSC has the following expertise: drug development, clinical pharmacology, clinical immunology, clinical trial design, omics, imaging, biostatistics, patient advocacy and HRQOL.  Members include Principal Investigators (PIs) of all phase I UM1 grants (including pediatric oncology) and all phase II N01 contracts; this includes all PIs from multi-PI sites.  IDSC votes by secret ballot on the Drug Project Team proposal

13. 13 Drug Project Team Outcomes (2)  If approved by the IDSC, the overall plan is presented to another internal committee for final approval.  If CRADA has been successfully negotiated, clinicians on the Drug Project Teams are invited to form study committees and submit LOI’s.

14. Open for discussion