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

Purpose: To better understand the relevance of genomic characteristics of NSCLC for the management of advanced NSCLC in Chinese patients, the phase II 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. Methods: CLUSTER was an open-label, umbrella design study with four treatment arms. Capmatinib (METi), ceritinib (ALKi), binimetinib (MEKi), and alpelisib (PI3Kai) monotherapies were investigated in previously treated patients with advanced NSCLC and matched genetic alterations. The primary endpoint for all treatment arms was overall response rate (ORR) per RECIST v1.1. Although not a predefined endpoint, a post-hoc analysis of the overall anti-tumor activity in all treated patients enrolled in the study was also performed. Results: 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. The overall anti-tumor activity in all treated patients showed encouraging results. Conclusion: 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 ClinicalTrials.gov, NCT02276027 Registered 27 October 2014 - Retrospectively registeredhttps://clinicaltrials.gov/ct2/show/NCT02276027