क्लिनिकल परीक्षण जर्नल
खुला एक्सेस

अमूर्त

General Principles and Confirmatory Trial Design of the Co-Development of Anticancer Drugs for Use in Combination

Huiyao Huang, Yu Tang, Dandan Cui, Xinyu Meng, Dawei Wu, Meiruo Liu, Shuhang Wang, Xiyan Li, Xin Wang, Yue Yu, Lanwei Guo, Yuan Fang, Ning Jiang, Huilei Miao, Peiwen Ma, Bing he Xu, Ning Li

The emergence of immunotherapy has caused a wave of co-development of anticancer drugs globally, and some unreasonable or unwarranted combination of anticancer drugs was observed. Combining regulatory guidance with case studies, this study aims to clarify key generally applicable principles in the co-development of combination therapy, when it’s appropriate to start a confirmatory trial, possible scenarios and main determinants of the most efficient confirmatory trial design. Biological rationale for the combination, adequate safety profile of each individual drug and the combination, added efficacy of the combination and attribution of each individual drug, are three golden basic principles for anticancer combination therapy. Before initiation of a confirmatory trial, a powered factorial study supporting the superiority of the combination over individual drug and standard-of-care is recommended. The appropriate design of pivotal study is generally a class-by-class determination, mainly based on whether there is a similar drug approved for the more active drug, what has been previously demonstrated about the effects of the combination and the individual drugs, the feasibility of monotherapy and standard-of-care alone treatment arms, the best practice and other factors.