Abstract 3596: How many tumor indications should be initially studied in clinical development of next-generation immunotherapies

Abstract

Abstract An experimental oncology immunotherapy may have the potential to be effective in a large number of tumor indications. Once a recommended Phase II dose (RP2D) is determined, under resource constraint, a natural strategy is to conduct Phase II proof-of-concept (POC) trials in two waves. A cohort of potential tumor indications is selected for the first wave investigation and the second wave investigation in a different cohort of tumor indications is initiated only after the drug has been demonstrated to be effective in the first wave. Immunotherapy development is a dynamic environment with rapidly evolving mechanistic understanding, constant flow of new data and frequent changes in the competitive landscape. How many tumor indications should be investigated in the first wave given the uncertainties? We attempt to answer this question by maximizing a benefit-cost ratio, defined to be the expected number of effective tumor indications correctly identified in the two waves divided by the expected total sample size for the POC trials in the two waves and the total sample size for the Phase III trials triggered by those with a positive outcome in the first wave. It is found that the optimal number of the first wave POC trials is in a range of approximately three to six, which may vary with the resource constraint but is otherwise robust to the key factors we have considered. A recommendation is made on how much resource should be invested in the first wave. Citation Format: Cong Chen, Qiqi Deng, Linchen He, Devan Mehrotra, Eric H. Rubin, Robert A. Beckman. How many tumor indications should be initially studied in clinical development of next-generation immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3596. doi:10.1158/1538-7445.AM2017-3596