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Activity Number: 410 - Bayesian Adaptive Designs and Novel Strategies for Dose Optimization in Cellular Therapy Drug Development
Type: Topic Contributed
Date/Time: Wednesday, August 10, 2022 : 10:30 AM to 12:20 PM
Sponsor: Biopharmaceutical Section
Abstract #322358
Title: The Ji3+3 Design for Cell/Gene Therapy Dose-Finding Trials with Joint Efficacy and Toxicity Outcomes
Author(s): Yuan Ji* and Xiaolei Lin
Companies: The University of Chicago and Fudan University
Keywords: Adaptive design; Immune Oncology; Non-monotone dose response; Rule-based design

Adoptive cell therapy (ACT), such as chimeric antigen receptor (CAR) T-cell therapy, has demonstrated promising therapeutic effects with potentially non-monotonic dose–response curves. Building upon the i3 + 3 design for cytotoxic agents (Liu et al., 2020), we propose a new method – joint i3 + 3 (Ji3 + 3) that takes into account of both safety and efficacy outcomes in making dosing recommendations. This allows for efficient dose escalation and identification of biological optimal dose of ACTs which may not be cytotoxic. The Ji3 + 3 design is rule based, easy to understand for clinicians, and is simple to implement. Simulation results show that Ji3 + 3 outperforms existing designs when monotonic dose–response assumption is violated, and still achieves comparable performance when the assumption holds. The simplicity and superior operating characteristics make Ji3 + 3 a good candidate for phase I/II ACT dose-finding trials in the clinical community when toxicity and efficacy are both considered as binary endpoints.

Authors who are presenting talks have a * after their name.

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