Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results.

3501 Background: Evidence supports use of nivolumab (N) in MSI-H mCRC. N, a fully human anti-PD-1 mAb and ipilimumab (I), a humanized anti-CTLA-4 mAb, have favorable safety & efficacy in other tumors. CheckMate-142, a phase 2 study, evaluates N ± I in pts with mCRC, MSI-H and non-MSI-H. Methods: Pts had ECOG PS 0–1, and intolerance/progression on ≥ 1 tx. MSI-H pts received N 3 mg/kg q2 wk (N3) or N 3 mg/kg + I 1 mg/kg q3 wk (N3+I1) x 4 doses followed by N3 until disease progression (PD) or other discontinuation. Initial evaluation of N+I at 3 doses was completed in non-MSI-H pts. Primary endpoint was investigator-reported ORR by RECIST 1.1; other endpoints were safety, OS, and PFS. Results: 33 (N3) and 26 (N3+I1) MSI-H pts, and 3 (N1+I1), 10 (N1+I3), and 10 (N3+I1) non-MSI-H pts were enrolled. 82% (N3) and 92% (N3+I1) of MSI-H and 100% of non-MSI-H pts had ≥ 2 prior regimens. 15% (N3) and 25% (N3+I1) of MSI-H pts had known BRAF V600E. 17 (52%; N3) and 19 (73%; N3+I1) MSI-H pts remain on tx. Efficacy results are shown in the Table. In MSI-H pts, tx-related adverse events (TRAEs) occurred in 26 (79%; N3) and 22 pts (85%; N3+I1); most common were diarrhea and fatigue (27% each; N3) and diarrhea (46%; N3+I1). Grade 3–4 TRAEs occurred in 7 (N3) and 8 pts (N3+I1). One pt on N3 had a Grade 5 TRAE (sudden death). In non-MSI-H pts median (95% CI) PFS was 1.4 mo (1.2–1.9; pooled N+I). Conclusions: N and N+I were well tolerated in most pts and demonstrated encouraging clinical activity and survival in MSI-H mCRC. This study is ongoing. Clinical trial information: NCT02060188.MSI-Ha efficacy. N3 (n = 33) N3+I1 (n = 26) ORR, n (%) 9 (27) 4 (15) CR 0 0 Confirmed PR 9 (27) 4 (15) SD 8 (24) 17 (65) PD 11 (33) 3 (12) Not determined/not reported 5 (15) 2 (8) Median duration of response (95% CI), mo NR (4.2–NE) NR (NE–NE) Median PFS (95% CI), mo 5.3 (1.4–NE) NR (NE–NE) 4-mo PFS rate,b % 55 80 Median OS (95% CI), mo 16.3 (8.3–NE) NR (NE–NE) 5-mo OS rate,c % 75 100 NR, not reached; NE, not estimable aBy local screen bPFS Kaplan-Meier plot estimate, N3 = 17/33 events, N3+I1 = 4/26 events cPFS Kaplan-Meier plot estimate, N3 = 11/33 events, N3+I1 = 0/26 events