Analysis of Phase I Clinical Trial Design of Anti-Cancer Agents

Since 2000, there have been cancer research and regulatory changes in the development of anti-cancer therapies. The broadening understanding of cancer biology, coupled with advances in molecular biology and technology, has led to the development of new cancer drugs with diverse mechanisms of action. This study aims to analyze the trends and major features of Phase 1 clinical trial designs for anti-cancer agents approved by the U.S. FDA between 2013 and 2024. Out of the 143 anticancer drugs approved between 2013 and 2024, targeted therapies were the most common drug class, accounting for 86 approvals. Notably, there has been a recent increase in the approval of bi-specific T-cell engagers. Lung cancer and leukemia each had the highest number of initial indications, with 24 and 21 drugs for each. It was considered that the primary objective of phase I study was to determine DLT (Dose-Limiting Toxicity), MTD (Maximum Tolerated Dose), and RP2D (Recommended Phase 2 Dose), with secondary objectives focusing on observing antitumor responses, regardless of drug class. The overall design features of Phase I clinical trials for anticancer drugs can be described as ‘non-randomized,’ ‘open,’ ‘without comparison,’ and ‘seamless dose expansion’. During the research period from 2013 to 2024, the 3 + 3 dose escalation design has seemed remained the most commonly used approach.