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Hung Trinh on Expansion Cohorts in First-in-Human Oncology Trials by FDA

Hung Trinh/LinkedIn

Jan 21, 2025, 16:04

Hung Trinh on Expansion Cohorts in First-in-Human Oncology Trials by FDA

Hung Trinh, CMC/MFG Consultant and Managing Director at Vertex Biopharm Consulting, shared a post on LinkedIn:

“FDA: ‘Expansion Cohorts: Use in First-in-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics Guidance for Industry’

What are typical number of patients should be enrolled in the expansion cohort study for solid tumors?

A. Assessing Safety of Recommended Phase 2

Dose Expansion cohorts can be intended to further evaluate safety beyond the initial dose-escalation portion of a trial. These studies should be supported by detailed information on available safety and PK data from the dose-escalation phase and a summary of safety data from other expansion cohorts, if available.

In situations when there is a narrow therapeutic index and dose-limiting toxicities have been observed in the dose escalation phase that may be fatal or result in serious morbidity, FDA strongly recommends that expansion be delayed until sufficient data are available to determine the recommended phase 2 dose to help ensure subjects safety

B. Evaluating Preliminary Antitumor Activity

Information to support expansion cohorts assessing disease-specific cohort antitumor activity should include the following:

A scientific rationale for inclusion of each population within a cohort based on proposed mechanism of action of the drug, any antitumor activity data and data regarding acceptability of risks in the proposed population(s) considering the natural history and underlying comorbidities, as well as lack of satisfactory alternative therapy
A statistical analysis plan for the cohort that includes justification of the maximum sample size and stopping rules for lack of activity, to minimize the number of subjects exposed to an ineffective drug (e.g., generally limited to 40 subjects with solid tumors based on a Simon two-stage model13 or 20 subjects with hematological malignancies when the rarity of the hematological malignancy may support initiation of efficacy trials based on smaller efficacy databases)
Updated safety experience from the dose-escalation portion and other expansion cohorts, as available.”

Hung Trinh on Expansion Cohorts in First-in-Human Oncology Trials by FDA

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Hung Trinh on Expansion Cohorts in First-in-Human Oncology Trials by FDA