Combination of nivolumab (nivo) + ipilimumab (ipi) in the treatment of patients (pts) with deficient DNA mismatch repair (dMMR)/high microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC): CheckMate 142 study.

3531 Background: Nivo, a fully human anti-PD-1 mAb, provided an ORR of 31%, durable responses (median DOR not reached), and a 12-mo OS rate of 73.8% in pts with dMMR/MSI-H mCRC (Overman M, et al. 2017). Preliminary analysis of nivo + ipi, a humanized anti-CTLA-4 mAb, demonstrated manageable safety and promising efficacy in pts with dMMR/MSI-H mCRC (Overman M, et al . 2016). Here we report interim safety and efficacy of nivo + ipi in this pt population from the Checkmate 142 study (NCT02060188). Methods: Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥1 prior line of therapy received nivo 3 mg/kg + ipi 1 mg/kg q3w × 4 doses followed by nivo 3 mg/kg q2w until discontinuation due to disease progression or other reason. Primary endpoint was investigator-reported ORR by RECIST 1.1. Other endpoints included DOR, PFS, OS, safety, and tolerability. Results: 27 pts with dMMR/MSI-H mCRC treated with nivo + ipi received the first dose ≥6 mo prior to the database lock (DBL; Sept 2016). Of these pts, 93% received ≥2 prior lines of therapy. At the time of DBL, 44% of pts remained on treatment, and 14 pts had discontinued therapy due to disease progression (n=8) or TRAEs (n=6). ORR was 41% and disease control rate (DCR) was 78% (Table). The median time to response was 2.7 mo, and 82% of responses (9/11) were ongoing at 6 mo. The medians for DOR, PFS and OS had not been reached. Grade 3–4 TRAEs occurred in 10 pts (37%).TRAEs leading to discontinuation included acute kidney injury, increased transaminases, necrotizing myositis, sarcoidosis, dyspnea, and thrombocytopenia (1 each). No deaths were attributed to therapy. Conclusions: Initial analysis ofnivo + ipi in pts with ≥6-mo follow-up demonstrated a manageable safety profile and clinical activity characterized by a high DCR and encouraging survival benefit. This study is ongoing, and updated efficacy and biomarker analyses of ≈80 pts with ≥6-mo follow-up will be presented. Clinical trial information: NCT02060188. [Table: see text]