Multicenter phase 1 trial of ipilimumab, nivolumab, and panitumumab for KRAS/NRAS/BRAF WT microsatellite stable metastatic colorectal cancer

The EGFR targeting monoclonal antibody panitumumab is standard therapy for patients with KRAS/NRAS/BRAF wild-type (WT) microsatellite stable (MSS) metastatic colorectal cancer (mCRC). A multicenter phase 2 trial in the USA evaluated the combination of ipilimumab, nivolumab, and panitumumab for these patients. The study included 56 patients after at least one previous line of therapy, but no previous anti-EGFR or immune checkpoint inhibitor. The overall response rate was 32.1% (95% CI 21.4-45.2; n=18). The median progression-free survival was 6.0 months (95% CI 5.5-7.4), and the median overall survival was 17.4 months (14.2-27.5). With a median follow-up of 43.3 months, four patients (7.1%) remain alive without progression, including two patients with liver metastases. There was one treatment-related grade 5 myocarditis. The authors conclude that the combination of panitumumab, ipilimumab, and nivolumab demonstrated an acceptable response rate among patients with KRAS/NRAS/BRAF WT MSS mCRC.