BE-BOIN: A Dose Optimization Design Accommodating Backfill and Late-Onset Toxicity

Date:	August 10, 2026
PMID:	42573944
Category:	N/A
Authors:	Kai Chen, Yixuan Zhao, Kentaro Takeda, Ying Yuan
Abstract:

The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), which optimizes the risk and benefit of treatments. The FDA's guidance emphasizes the importance of collecting sufficient toxicity and efficacy data across multiple doses and considering late-onset cumulative toxicity that often results in tolerability issues. To address these challenges, we propose the BE-BOIN (Backfill time-to-Event Bayesian Optimal INterval) design, which allows backfilling patients into safe and effective doses during dose escalation and accommodates late-onset toxicities. BE-BOIN enables the collection of additional safety and efficacy data to enhance the accuracy and reliability of OBD selection and supports real-time dose decisions for new patients. Our simulation studies show that BE-BOIN accurately identifies the MTD and OBD while significantly reducing trial duration.

---

Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center