Work

Dose-finding designs for cell therapy cancer clinical trials evaluating drug-combinations

Year: 2025

Type: article

Abstract: Cell therapies have taken hold as a promising modality of treatment for multiple types of cancer. Despite this, their efficacy as a monotherapy has been limited, driving interest in their possible role as part of a drug combination. This paper introduces a novel dose-finding design for phase I cancer trials assessing drug combinations where one of the drugs is a cell therapy. Our design adapts the partial order continual reassessment method (POCRM) to account for late-onset dose-limiting toxicities (DLT) and feasibility concerns due to complexities related to manufacturing the cell therapy product. We illustrate our design on a proposed trial to assess the combination of a Rituximab-based bispecific antibody activated T cell product and Nivolumab for the treatment of high-grade B-cell lymphoma. We also provide simulation results that demonstrate our design's ability to accurately identify the feasible maximum tolerated dose combination (FMTDC) while managing late-onset DLTs and feasibility concerns. Our methodology aims to improve the phase I drug combination landscape for cell therapy cancer clinical trials.

Source: Contemporary Clinical Trials

DOI: 10.1016/j.cct.2025.107894

Authors: Evan M. Bagley, Nolan A. Wages

Institutions: Medical University of South Carolina, Virginia Commonwealth University

Language: English

Topic: Statistical Methods in Clinical Trials

Subfield: Statistics and Probability

Field: Mathematics

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,140