A review of seamless phase I/II trial designs towards oncology dose optimization with examples of clinical pharmacology considerations in early drug development
Sep 2026· European Journal of Clinical Pharmacology· Vol 82· 0 citations· 57 references
Medicine
TL;DR
This review article focuses on seamless Phase I/II designs for dose optimization in oncology and provides practical CP consideration examples in evaluating modern designs and ensures essential features to inform CP packages are included as part of the trial design in a cross-functional team setting.
Overall, DO can be effectively implemented at multiple stages of clinical development and should balance statistical rigor, development speed, practical feasibility, and the suitability of the endpoints used for dose selection.
An-Nan Deng, Xiao-Chen Zhu, Hai-Yang Sheng et al.· Clinical pharmacology and th...· 0 citations
Background Adaptive Phase I/II designs can jointly use toxicity and efficacy information to guide dose allocation and regimen selection. These designs are particularly relevant for oncology drug-combination trials, where the optimal regimen may not coincide with the maximum tolerated dose. Methods We conducted a struct...
Jun-Ying Wang, Song Wu, Jie Yang· Frontiers in Oncology· 0 citations
Historically, phase I oncology trials were designed with the focus to find the highest tolerable dose. However, given the FDA's acknowledgment that the highest tolerable dose might not be the dose which is optimal biologically, there is an increased emphasis the development of designs that explore the dose-toxicity and...
Connor Celum, Evan M. Bagley Statistics Department, California State University et al.· 0 citations
The FDA's Project Optimus CALLS for randomized exploration of multiple doses to better refine selection of the optimal biologic dose (OBD). Project FrontRunner encourages the use of randomized controlled trials earlier in the drug development process. We propose a seamless three-stage trial design that addresses both g...
Emily C. Zabor, Sneha Govande, Wen-Wee Ma et al.· Pharmaceutical statistics· 0 citations
The US Food and Drug Administration's Project Optimus has initiated a paradigm shift in oncology drug development from “more is better” to “less is more.” Methodological development for combination therapy trials remains limited due to their complex dose‐combination space and the need to integrate multi‐source data, in...
Ying-Jie Qiu, Ming-Yue Li· Statistics in Medicine· 0 citations
Background/AimsPhase II trials with a safety lead-in (SLI), allowing one or two dose de-escalations based on toxicities from the first several patients at a dose, are increasingly common in oncology. Despite increased demand, formal evaluation of SLI designs remains limited to dose selection without evaluating the perf...
Emily N. Potts, Marie Ferron, L. Biard et al.· Clinical Trials· 0 citations
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