Cho Juhee, Bok Haesook, Jo Taeyoun, Ahn Sohyun
Department of Biohealth Regulatory Science, Graduate School, Sung Kyun Kwan University, 2066 Seobu-Ro, Jangan-Gu Suwon-Si, Suwon, Kyunggi-Do, 16419, Republic of Korea.
College of Pharmacy, Sook Myung Women's University, Cheongpa-ro 47-gil 100, Yongsan-Ku, Seoul, Korea, Seoul, 04310, Republic of Korea.
Ther Innov Regul Sci. 2025 Jun 21. doi: 10.1007/s43441-025-00830-x.
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.
自2000年以来，抗癌疗法的研发在癌症研究和监管方面发生了变化。对癌症生物学的深入理解，再加上分子生物学和技术的进步，催生了具有多种作用机制的新型抗癌药物。本研究旨在分析2013年至2024年期间美国食品药品监督管理局（FDA）批准的抗癌药物一期临床试验设计的趋势和主要特征。在2013年至2024年期间批准的143种抗癌药物中，靶向疗法是最常见的药物类别，有86种获批。值得注意的是，双特异性T细胞衔接器的获批数量最近有所增加。肺癌和白血病的初始适应症数量均最多，各有24种和21种药物。一期研究的主要目标被认为是确定剂量限制性毒性（DLT）、最大耐受剂量（MTD）和推荐的二期剂量（RP2D），次要目标则侧重于观察抗肿瘤反应，而不考虑药物类别。抗癌药物一期临床试验的总体设计特点可描述为“非随机化”“开放”“无对照”和“无缝剂量扩展”。在2013年至2024年的研究期间，3+3剂量递增设计似乎仍然是最常用的方法。
