49: Statistical designs to account for patient heterogeneity in cell therapy cancer clinical trials

Music City Center 

This presentation describes a novel phase I statistical trial design developed to enhance the safety and efficiency of cell therapies in oncology by specifically addressing patient heterogeneity and dose-feasibility encountered in such therapies. Traditional dose-finding methods do not accommodate specific challenges encountered in cell-therapy trials, like patients not being able to receive their intended dose due to manufacturing limitations or specific groups of patients being more prone to toxicity than others. To address these issues, we incorporate statistical models that allow for the adaptive updating of dose levels based on real-time patient-data concerning both toxicity and dose-feasibility. Our design aims to calculate groups specific Feasible Maximum Tolerated Doses (FMTDs), by sharing toxicity data between groups and utilizing data observed at unplanned dose levels. We present simulation results showing the operating characteristics across multiple possible clinical scenarios and apply our design to the motivating trial. We also illustrate how sharing data between patient groups can simultaneously improve efficiency and avoid undesirable trial results like reversals.

Statistical trial design

cancer clinical trial

biostatistics

patient heterogeneity 

Biopharmaceutical Section