New FDA draft Guidance on Expansion Cohorts

Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics Guidance for Industry

The purpose of this guidance is to provide advice to sponsors regarding the design and conduct of first-in-human (FIH) clinical trials intended to efficiently expedite the clinical development of cancer drugs, including biological products, through multiple expansion cohort trial designs. These are trial designs that employ multiple, concurrently accruing patient cohorts, where individual cohorts assess different aspects of the safety, pharmacokinetics, and anti-tumor activity of the drug.

The key points of the guidance are:

  • FIH should be in patients’ population with no available therapies, patient population for expansion cohorts always need to be justified
  • Multiple expansion cohort trials usually better with drugs where CMC changes can be more easily controlled/bridged – e.g. small molecules
  • Products with steep toxicity indices and high inter-/intra-patient variable PK not suitable
  • Strong emphasis on prespecified statistical design of expansion cohorts – randomized, non-randomized and corresponding analyses required
  • If sponsor adds a disease specific cohort and intends to further develop the specific indication then a new IND should be submitted
  • In exceptional cases expansion cohorts can be used for regulatory filing, but need high quality incl. IRC, optimal dose determined, prespecified statistical plan
  • Reminder to asses need for ID exemption assessment when IVD/biomarker used
  • Need for IDMC, central IRB preferred
  • Pre-IND meeting recommended and sponsor can request FDA a meeting (TC) within the 30-day review period
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