Keywords: Seamless Phase 2/3 Oncology Trial, Probability of Success, Go/No-Go Criteria, Optimal Interim Timing
In recent years, there is an increasing trend to conduct seamless phase 2/3 clinical trials for drug development in pharmaceutical industry due to the visible advantages compared with traditional approaches for separate phase 2 and 3 development. Innovative study designs have been proposed for seamless phase 2/3 trials which mainly focus on the traditional aspect of study design, such as how to control type I error rate, sample size re-estimation after phase 2 portion and how to make treatment selection at the end of phase 2 portion. However, there are still some questions unresolved such as how to determine go/no-go boundary and how to plan phase 2 portion sample size. In this paper, we discuss how to determine the phase 2 portion and phase 3 portion sample size as well as the corresponding go/no-go criteria for a seamless phase 2/3 oncology trial based on Probability of Success (PoS). In addition, we further expanded the methodology to include designs with an interim look within the phase 2 portion to speed up the go/no-go decision-making process. In case of overwhelming efficacy, this design would further shorten the overall trial duration. In case of inefficacy, this design can stop trial earlier without exposing more patients to inefficacious treatment.