Background: Nivolumab (NIVO) provided durable responses (investigator-assessed [INV] ORR, 31%) and disease control (DCR, 69%) in pretreated pts with dMMR/MSI-H mCRC in CheckMate-142 (NCT02060188; Overman et al Lancet Oncol 2017). An interim analysis of the NIVO + ipilimumab (IPI) combination cohort of CheckMate-142 reported a preliminary ORR of 55% and manageable safety profile in a subset of pts (n = 84) with dMMR/MSI-H mCRC and ≥ 6 mo of follow-up (André et al ASCO 2017). Here we report for the first time efficacy and safety from the complete population (N = 119) of the NIVO + IPI cohort of CheckMate-142, which is the largest single-study report of an immunotherapy regimen in pts with dMMR/MSI-H mCRC. Methods: Pts with dMMR/MSI-H mCRC received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W. Primary endpoint was ORR (INV; RECIST 1.1). Other endpoints were DOR, PFS, OS, and safety/tolerability. Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. Median follow-up was 13.4 mo. The ORR was 55% and DCR was 80% (Table). Notably, ORR in pts with a BRAF mutation was 55%. Among all responders, median DOR was not reached (NR), with 94% of responses ongoing at data cutoff. Tumor burden was reduced from baseline in 77% of pts. The 9-mo PFS and OS rates were 76% and 87%, respectively. Gr 3–4 TRAEs occurred in 32% of pts; 13% (any gr) and 10% (gr 3–4) of pts had TRAEs that led to discontinuation. No treatment-related deaths were reported. Results including a similar follow-up of the NIVO arm will also be presented. Conclusions: In the largest cohort of dMMR/MSI-H pts treated with an immunotherapy regimen, NIVO + IPI built on the efficacy reported with NIVO monotherapy, demonstrating enhanced clinical benefit and manageable safety, and may represent a new standard of care in pts with dMMR/MSI-H mCRC. Clinical trial information: NCT02060188

NE = not estimable

^aCR + PR + SD ≥ 12 wk