Role of the Drug Project Team in Formulating the Initial Development Plan

of NCI-IND agents

Jeff Moscow, MDIDB, CTEP

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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

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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.

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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

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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

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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

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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.

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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.

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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

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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

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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

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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

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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.

Open for discussion