Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC)

Abstract

Background: In previously chemotherapy-treated patients with MSI-H/dMMR mCRC from the phase II CheckMate-142 trial, NIVO +low-dose IPI (1 mg/kg) provided durable clinical benefit (investigator-assessed [INV] objective response rate [ORR] 55%, median duration of response [DOR] not reached, 12-month overall survival [OS] rate 85%) and manageable safety. Here we report the first results of the efficacy and safety of NIVO + low-dose IPI as a first-line (1L) therapy for patients with MSI-H/ dMMR mCRC from CheckMate-142. Methods: Patients with no prior treatment for MSI-H/dMMR mCRC were treated with NIVO 3 mg/kg every 2 weeks (Q2W) +low-dose IPI every 6 weeks (Q6W) until disease progression. The primary endpoint was ORR (INV; RECIST v1.1). Results: Of 45 patients, 51% were male and median age was 66 years. Median follow-up (time from first dose to data cut-off) was 13.8 months (range 9-19). The ORR and disease control rate (DCR) were 60% and 84%, respectively, with a 7% complete response rate (Table). Median DOR was not reached. At 12 months, progression-free survival (PFS) and OS rates were 77% and 83%, respectively. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 16% of patients and 7% of patients had any grade TRAEs leading to discontinuation. Any grade select immune-mediated TRAEs affecting the hepatic (13%), gastrointestinal (11%), pulmonary (2%), and renal (2%) systems resolved in 100% of patients, while those affecting the skin (33%) and endocrine (24%) systems resolved in 45% and 60% of patients, respectively. Conclusions: NIVO (Q2W) + low-dose IPI (Q6W) demonstrated robust and durable clinical benefit and was well-tolerated as a 1L treatment for MSI-H/dMMR mCRC. These results suggest that NIVO+ low-dose IPI may represent a new treatment option for these patients. (Table Presented) .