A 2-in-1 adaptive phase 2/3 design for expedited oncology drug development.

We propose an adaptive design that allows us to expand an ongoing Phase 2 trial into a Phase 3 trial to expedite a drug development program with fewer patients. Rather than the usual practice of increasing sample size with a less positive interim outcome, here we propose maintaining sample size with such a result and wait for fully mature data. The final Phase 2 data may be negative, may warrant a larger Phase 3 trial, or, in the extreme, could provide a definitively positive outcome. If the interim outcome is more positive, the trial continues to an originally planned larger sample size for a definitive Phase 3 evaluation. All patients from the study are used for inference regardless of the interim expansion decision. We show that no penalty needs to be paid in order to control the overall Type I error of the study, under a mild assumption that is expected to generally hold in practice. The proposed design may be considered an alternative approach to sample size adjustment for ongoing trials. As such, the use of an intermediate endpoint for adaptive decision is a unique feature of the design. A hypothetical example is provided for illustration purpose.