Subgroup analyses of patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) treated with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line (1L) therapy:Two-year clinical update.

Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up, 29.0 months [range, 24.2–33.7]) (Lenz et al. J Clin Oncol 2020;38:Abstract 4040; NCT02060188). Objective response rate (ORR) per investigator (INV) was achieved in 69% of pts (95% CI, 53–82); progressive disease rate was 13%. Median progression-free survival (PFS) and overall survival (OS) were not reached. Median duration of treatment was 19.1 months (95% CI, 11.1–29.0). Grade 3–4 treatment-related adverse events (TRAEs) occurred in 22% of pts. We present the post hoc subgroup analyses of efficacy and safety outcomes in pts from the same follow-up based on demographics and baseline disease characteristics. Methods: Pts with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. ORR (primary endpoint, RECIST v1.1) and PFS were assessed per INV. Post hoc subgroup analyses of efficacy (by ECOG performance status [PS], stage at initial diagnosis, primary tumor location, and BRAF/KRAS mutation status) and safety (by age and ECOG PS) are presented. Results: Among 45 treated pts, efficacy (Table) and safety were generally consistent across evaluated subgroups. ORR was similar in pt subgroups by BRAF/KRAS mutation status, stage at initial diagnosis, primary tumor location, and ECOG PS (Table). Median PFS and OS were not reached (NR) in evaluated subgroups after a minimum follow-up of 24.2 months (Table). Incidence of grade 3–4 TRAEs for subgroups by age and ECOG PS were consistent with the overall population. Conclusions: NIVO + low-dose IPI demonstrated robust, durable clinical benefit; was well tolerated with 2-year follow-up; and was consistent in evaluated subgroups in 1L MSI-H/dMMR mCRC.