PI-018 - FIRST-IN-HUMAN (FIH) HEALTHY VOLUNTEER (HV) STUDIES FOR ONCOLOGY THERAPEUTICS: A FRAMEWORK OF APPLICATION IN EARLY ONCOLOGY CLINICAL DEVELOPMENT.

J. Yang¹, L. Zhou², R. Mittapalli², M. Mach³, D. Yin²; ¹Pfizer, Bellevue, WA, USA, ²Pfizer, La Jolla, CA, USA, ³University of California, San Diego, La Jolla, CA, USA.

Background: Oncology FIH trials are often conducted in cancer patients due to the high unmet medical need, advanced nature of the disease and expected poor tolerability for cytotoxic agents. Even with the advent of molecularly targeted agents (MTAs) and immune-oncology (IO) agents, which have favorable safety profiles, FIH HV studies for oncology therapeutics have not been common. Here we proposed a framework describing several scenarios where an FIH HV study may be of value in early oncology development.

Methods: FIH HV studies reported for MTA and IO agents in the oncology area were reviewed. The impacts of HV studies on subsequent FIP studies were assessed from perspectives including benefit to patients (i.e., reducing patients receiving subtherapeutic dose levels), FIP starting dose selection, and accelerating the timeline. The conditions justifying the value of oncology FIH HV were summarized.

Results: Review of reported oncology FIH HV studies revealed that such studies could potentially add value through one or more of the following ways: increasing the FIP starting dose and reducing the number of patients receiving subtherapeutic dose levels; removing the need for monotherapy dose escalation in patients for agents with no expected monotherapy efficacy; addressing the uncertainty in predicted human PK/PD prior to FIP; and enabling development in both oncology and non-oncology indications. While FIH HV studies could generate valuable PK, PD and safety data, the decision of FIH HV in oncology needs to be made considering factors such as benefit to patients, impact on FIP study design, ability to extrapolate data between HVs and patients, and the overall resources and timeline.

Conclusion: Under specific conditions, FIH HV studies may provide opportunities to inform more efficient and optimal oncology Phase 1 trials in patients.