All Times EDT
Keywords: Non-proportional hazard, Delayed effect, MaxCombo, Robust power
Targeting the immune system to cure cancer has emerged as a promising treatment option for patients in recent years. Instead of targeting a tumor directly or destroying it with radiation, Immunotherapy boosts the body's natural defenses to fight cancer. However, this novel treatment poses new challenges in the study design and statistical analysis of clinical trials. A major challenge is the delayed onset of treatment effects due to the mechanism of immunotherapy which violates the proportional hazard (PH) assumption. The conventional log-rank test may suffer a significant power loss in such scenarios. It is known as the non-proportional hazard (NPH) problem. A suitable design for time to event data with potential NPH needs to be flexible enough to incorporate the uncertainty of NPH type and provide a robust inference. This presentation will focus on an alternative design approach for immune-oncology trials. The proposed design approach is based on a combination of multiple Fleming-Harrington WLR tests and is referred as the MaxCombo test. It chooses the best test adaptively depending on the underlying data. The main objective of the new design is to provide robust power for primary analysis under different NPH scenarios. The talk will provide the general design framework, sample size calculation, and evaluation of operating characteristics. In addition, a comparison of MaxCombo with other available approaches will be provided. Finally, It will reflect on further extensions of the MaxCombo test in group sequential design. A real-life example will be used for illustration.