Design of a Phase I Drug Combination Study with Adaptive Allocation Based on Dose-Limiting Toxicity Attribution.

ABSTRACT: Background: This article describes the adaptation of a Phase I drug combination method to incorporate dose-limiting toxicity (DLT) attribution in dose assignments. The study is motivated by the Embolden trial (NCT03240211), a Phase Ib, multicenter trial at the UVA Comprehensive Cancer Center evaluating pembrolizumab with pralatrexate (Arm A), decitabine (Arm C), or both (Arm B) in relapsed/refractory peripheral and cutaneous T cell lymphomas. Methods: While Arms A and C used monotherapy dose escalation, Arm B required simultaneous escalation of both agents, integrating drug-specific DLT attribution to guide dosing. Results: We adapted the partial order continual reassessment method (POCRM) to incorporate this attribution, ensuring appropriate de-escalation of the offen

SUBMITTER: Wages NA 

PROVIDER: S-EPMC11940839 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature