CLUSTER: A biomarker-integrated targeted therapy study in patients with advanced non-small cell lung cancer

Abstract The CLUSTER umbrella trial simultaneously investigated the efficacy of multiple targeted therapies in Chinese patients with advanced non-small cell lung cancer and pre-specified genetic alterations. Patients were assigned to receive capmatinib (METi), ceritinib (ALKi), binimetinib (MEKi), or alpelisib (PI3Kαi) matched to their genetic alteration. The overall response rate (ORR) and safety of each treatment were determined. Ceritinib met the pre‑specified statistical threshold for efficacy with an ORR of 73%, whereas an ORR of 19% and 9% were attained with capmatinib and binimetinib, respectively. Although not a predefined endpoint, a post-hoc analysis of the overall anti-tumor activity in all treated patients showed encouraging results. Despite the limited number of patients in some of the treatment arms and the stringent criteria for preliminary activity, these findings confirm the feasibility of conducting biomarker-integrated studies in China, and warrant the implementation of further umbrella trials to simultaneously evaluate the efficacy of multiple targeted treatments. Trial registration number : NCT02276027