BOIN12 ‐ PFS : A Bayesian Optimal Interval Phase I / II Design Incorporating Progression‐Free Survival Endpoint

ABSTRACT Modern oncology drug development is increasingly focused on identifying the optimal biological dose (OBD) rather than just the maximum tolerated dose (MTD). Early‐phase oncology trials have conventionally relied on short‐term endpoints, such as overall response rate (ORR), to evaluate efficacy. However, there is a growing perception that incorporating longer‐term endpoints, such as progression‐free survival (PFS), into early‐phase dose‐finding trials can provide more informative guidance for dose optimization. This study proposes a new design, BOIN12‐PFS, to identify the optimal dose based on PFS, short‐term efficacy, and toxicity. As an extension of the BOIN12 design, BOIN12‐PFS is expected to be comparatively straightforward to implement in clinical oncology dose‐finding trials. Simulation studies demonstrate that the BOIN12‐PFS design offers advantages over existing designs in terms of the probability of selecting the OBD, the average number of patients allocated to the OBD, reducing overdosing, and requiring a smaller total sample size across various realistic settings.