Nivolumab plus ipilimumab and cobimetinib in previously treated microsatellite-stable/DNA mismatch repair-proficient metastatic colorectal cancer: the phase II CheckMate 142 trial

Background: Immune checkpoint inhibitors (ICIs) have shown limited efficacy in patients with microsatellite-stable/DNA mismatch repair-proficient (MSS/pMMR) metastatic colorectal cancer (CRC). Based on data suggesting antitumor synergy between ICIs and MEK inhibitors, the phase II CheckMate 142 trial evaluated the combination of nivolumab, ipilimumab, and cobimetinib in a cohort of patients with previously treated MSS/pMMR metastatic CRC. Patients and methods: Patients received nivolumab (3 mg/kg every 2 weeks), ipilimumab (1 mg/kg every 6 weeks), and cobimetinib [60 mg daily in 28-day cycles (21 days on/7 days off)]. The primary endpoint was investigator-assessed objective response rate (ORR) using RECIST v1.1. Results: = 9), and median [95% confidence interval (CI)] progression-free survival was 1.5 (1.4-2.6) months. Median (95% CI) overall survival was 8.2 (2.2-13.9) months. Twenty-five patients (83%) had ≥1 treatment-related adverse event (TRAE), 9 (30%) had a grade 3-4 TRAE, and 3 (10%) discontinued treatment due to TRAEs. Conclusions: The combination of nivolumab, ipilimumab, and cobimetinib had limited clinical activity in patients with previously treated MSS/pMMR mCRC. Further investigation of this regimen is not warranted.