A Bayesian adaptive phase I/II platform trial design for pediatric immunotherapy trials

Immunotherapy is the most promising new cancer treatment for various pediatric tumors and has resulted in an unprecedented surge in the number of novel immunotherapeutic treatments that need to be evaluated in clinical trials. Most phase I/II trial designs have been developed for evaluating only one candidate treatment at a time, and are thus not optimal for this task. To address these issues, we propose a Bayesian phase I/II platform trial design, which accounts for the unique features of immunotherapy, thereby allowing investigators to continuously screen a large number of immunotherapeutic treatments in an efficient and seamless manner. The elicited numerical utility is adopted to account for the risk-benefit trade-off and to quantify the desirability of the dose. During the trial, inefficacious or overly toxic treatments are adaptively dropped from the trial and the promising treatments are graduated from the trial to the next stage of development. Once an experimental treatment is dropped or graduated, the next available new treatment can be immediately added and tested. Extensive simulation studies have demonstrated the desirable operating characteristics of the proposed design.