All Times EDT
Keywords: dose-finding, BOIN, estimand
The clinical development of chimeric antigen receptor (CAR) T-cell immunotherapy for hematology malignancies has grown rapidly over the last several years. However, challenging questions remain regarding the immunobiology and development of these personalized therapies. For example, commonly used phase 1 oncology dose-finding trial designs enroll patients in cohorts and apply sequential decisions that determine the dose level for each cohort based on observed toxicity data only. Accrual is suspended after enrollment of each cohort of patients until all the patients in the current cohort have observed outcomes, with or without dose limiting toxicity. This type of cohort-based designs using only toxicity data can be inefficient for CAR-T trials. In late phase development of CAR-T trials, due to the complexity of CAR-T manufacturing process and use of bridging therapy, it is important to define and understand the trial objectives when comparing with a standard of care. In this abstract, we will discuss 1) the use of novel phase 1/2 dose-finding study designs (e.g., TITE-BOIN, BOIN12) for CAR-T cell trials; 2) the estimand framework for a phase 3 randomised trial.