Nivolumab in Patients with Advanced or Metastatic Malignancies, Including Rare Cancers: Results of CheckMate 627, an Adaptive Basket Design Clinical Trial

PURPOSE To report on CheckMate 627 (ClinicalTrials.gov identifier: NCT02832167 ), a phase II adaptive basket design trial of nivolumab in uncommon advanced/metastatic tumors. METHODS Adults with previously treated advanced/metastatic malignancies received nivolumab 240 mg once every 2 weeks for eight cycles, followed by nivolumab 480 mg once every 4 weeks. The primary end point was investigator-assessed objective response rate (ORR). In addition to observed ORRs, model-adjusted ORRs were estimated via Bayesian analysis in patients who completed ≥28 weeks of follow-up, to correct for variability inherent in multitumor studies. This adaptive model allowed for borrowing of information from other tumors demonstrating similar ORR and evaluation of nivolumab treatment effect versus historical standard-of-care (SOC) controls. Nivolumab was considered to have met the criteria for ORR superiority in a group if there was ≥80% posterior probability of ORR with nivolumab exceeding ORR with historical SOC control treatment in that group. RESULTS The study included 25 tumor groups (n = 239), with 24 groups included in the Bayesian ORR analysis (efficacy was reported but not modeled in the other group that contained a mix of tumor types). The poorly differentiated neuroendocrine tumor (PD-NET) group (n = 20) met the prespecified criterion for ORR superiority with a 93% probability of the model-adjusted ORR with nivolumab (22% [95% CI, 8 to 44]) exceeding the respective historical SOC ORR of 10.0%. The observed ORR was 30.0% (95% CI, 11.9 to 54.3). There were no new safety signals for nivolumab. CONCLUSION Nivolumab showed evidence of antitumor activity in patients with advanced/metastatic PD-NET in CheckMate 627. The results of this study support the use of an adaptive basket design for identification of rare cancers responsive to immunotherapy.