Journal de biométrie et biostatistique

Challenges and Innovations in Phase I Dose-Finding Designs for Molecularly Targeted Agents and Cancer Immunotherapies

Abstract

Jun Yin and Shihao Shen

Phase I oncology trials are designed to identify a safe dose with an acceptable toxicity profile. In traditional phase I dose-finding design, the dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle. The recent development of molecularly targeted agents and cancer immunotherapies call for new innovations in phase I designs, because of prolonged treatment cycles often involved. Various phase I designs using toxicity and efficacy endpoints from multiple treatment cycles have been developed for these new treatment agents. Here, we will review the novel endpoints and designs for the phase I oncology clinical trials.