Victor Moreno, Director of Clinical Research at START Madrid FJD, shared on LinkedIn:
“When a phase 1 trial enrols 395 patients, is it still really a phase 1 trial?
A new Lancet Oncology paper reports the development of SHR-A2102, a nectin-4-directed antibody–drug conjugate, across several pretreated solid tumors.
The study began with conventional dose escalation but grew to include multiple expansion cohorts across 39 hospitals.
It showed encouraging activity in breast, lung, esophageal and head and neck cancers, while grade 3–4 treatment-related adverse events occurred in 54% of patients.
Large expansion cohorts can identify tumor-specific signals and provide a more complete safety profile. But once a trial enrols hundreds of patients, its objectives go far beyond initial safety and dose finding.
At that scale, we should expect clearly defined cohort hypotheses, prospective statistical plans and tumor-specific dose optimisation – not simply more patients treated at one or two selected doses.
Calling a study ‘phase 1’ should describe its stage of development, not lower the evidentiary expectations applied to it.
Large expansion cohorts can accelerate development. But expansion is not the same as validation.”
Title: SHR-A2102, a nectin-4 directed antibody–drug conjugate, in patients with pretreated advanced solid tumors: a multicentre, single-arm, phase 1 trial
Authors: Runbo Zhong, Huangming Hong, Min Yan, Qiming Wang, Yan Zhang, Qiongyu Lan, Yongzhong Luo, Ling Zhang, Haipeng Xu, Sanxing Guo, Wei Guo, Jie Ma, Longzhen Zhang, Lin Wu, Zhigang Liu, Wei He, Yubei Sun, Kai Chen, Jiangqiong Huang, Guang Han, Weiqi Nian, Ming Zhang, Shengxiang Ren, Rong Qiao, Xiang Li, Meijing Yu, Jin Hu, Yanhua Huang, Li Song, Wei Shi, Hua Zhong.
You can also read: RP2 First-in-Human Study: Final Results of Oncolytic Immunotherapy in Advanced Solid Tumors
