Designing Late-Stage Randomized Clinical Trials with Cancer Immunotherapy: Can We Make It Simpler?

The knowledge we have accumulated over the past few years in the field of cancer immunotherapy has prompted the research community to challenge the status quo of trial design and endpoint selection across all drug development phases. For the design of randomized phase III studies using overall survival (OS) as the primary endpoint in particular, the paradigm has shifted from the conventional approach based on a proportional hazards model to those that account for the unique survival kinetics observed in immuno-oncology trials, such as long-term survival and delayed clinical effect. These new approaches usually require complex modeling or simulations, as well as assumptions about the length of delay in clinical effect and the long-term survival rate, making the process of implementing these new designs challenging. Here, a late-stage randomized clinical trial design is proposed based on milestone survival to simplify the process of sample size determination while keeping OS as the primary endpoint. The new design also allows assessment in milestone survival and is unaffected by the uncertainty of the survival kinetics demonstrated by cancer immunotherapies. Cancer Immunol Res; 6(3); 250-4. ©2018 AACR. ©2018 American Association for Cancer Research.