Oncology immunotherapies have the potential to be effective in more tumor indications than a non-immunotherapy, as demonstrated by PD-1 (or PD-L1) immune checkpoint inhibitors such as pembrolizumab and nivolumab in recent years. Following the success of PD-1 (or PD-L1) inhibitors, a flood of next generation immunotherapies with different mechanisms of action (e.g., LAG3, CD40, ICOS, TIM-3, IDO1, GITR, STING, OX40, TIGIT) are being developed. While the expectation is high for these new immunotherapies, it is unrealistic to expect all of them to have the same success as the immune checkpoint inhibitors. In reality, they may be effective in a wide range of tumor indications, may be effective only in a few tumor indications, or may not be effective at all. Even if they are indeed as effective as the immune checkpoint inhibitors, it will be challenging to demonstrate their clinical benefit given the improved standard-of-care. It is imperative to apply innovative and cost-effective statistical strategies to the development of these new immunotherapies.
This tutorial will present the lessons and experiences learned from the development of the checkpoint inhibitors. It will also present statistical strategies on efficacy screening, design adaptation between Phase 2 and Phase 3, and adaptive biomarker enrichment design and platform/basket design for Phase 3 trials. Familiarity with multivariate normal distribution and an open mind are the only prerequisite for this tutorial.
Dr. Cong Chen is Director of Early Oncology Biostatistics at Merck & Co., Inc. He joined Merck in 1999 shortly before he graduated from Iowa State University, Ames, USA, with a Ph.D. in statistics. He has published over 60 papers and 6 book chapters on statistical methodologies for design and analysis of clinical trials, including new paradigms for biomarker directed clinical development and Phase II proof-of-concept studies. His most recent accomplishment includes playing a pivotal role in regulatory approval of KEYTRUDA, a paradigm changing anti-PD-1 immunotherapy, for multiple indications. He is a Fellow of American Statistical Association, an Associate Editor of Statistics in Biopharmaceutical Research, a member of Cancer Clinical Research Editorial Board and a co-leader of the DIA Small Population Work Stream.