SO-12 Nivolumab (NIVO) plus ipilimumab (IPI) combination therapy in patients with advanced hepatocellular carcinoma (aHCC): 5-year results from CheckMate 040

NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) followed by NIVO 240 mg Q2W demonstrated an objective response rate (ORR) of 32% and median overall survival (mOS) of 22.8 months in sorafenib-treated patients with aHCC from CheckMate 040, which led to accelerated approval in the United States in this population. 1 We present 5-year long-term follow-up results from the CheckMate 040 NIVO+IPI cohort. 1. Yau T, et al. JAMA Oncol. 2020;6(11):e204564. 148 patients were randomized 1:1:1 to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Efficacy assessments included ORR and duration of response (DOR) by investigator assessment (INV) and blinded independent review (BICR) per RECIST v1.1 and OS. Landmark analysis was performed by response status at 6 months to determine post-landmark survival outcomes. Safety and tolerability and the association of biomarkers with survival were also evaluated. Data cutoff was November 9, 2021. At minimum follow-up of 60 months, ORR by INV was 34% in arm A, 27% in arm B, and 29% in arm C (BICR: 32%, 31%, 31%, respectively). Durable responses were achieved across treatment arms, with median DOR (range) by INV of 51.2 months (8.3–62.2) in arm A, 15.2 months (4.2–59.3) in arm B, and 21.7 months (2.8–65.0) in arm C (BICR: 17.5 months [4.6–58.1], 22.2 months [4.2–59.3], 16.6 months [4.1–62.3], respectively). mOS (95% CI) remained at 22.2 months (9.4–54.8) in arm A, 12.5 months (7.6–16.4) in arm B, and 12.7 months (7.4–30.5) in arm C; 36-month OS rates were 42%, 26%, and 30%, respectively; 60-month OS rates were 29%, 19%, and 21%, respectively. mOS (95% CI) at the landmark timepoint of 6 months was meaningfully longer for responders (not reached in arms A and B, 63.2 [31.2–not estimable] in arm C) vs non-responders (arm A 15.6, [9.0–29.6]; arm B, 12.5 [8.0–14.2]; arm C, 19.5 [8.6–30.5] months). No new treatment-related adverse events (TRAEs) were reported with longer follow-up. There was 1 additional discontinuation due to TRAE (in arm B) and no new discontinuations due to immune-mediated adverse events (IMAEs) since the primary analysis. IMAEs were more frequently reported in arm A than in arms B or C. Most IMAEs resolved when treated using established algorithms, with median time to resolution between 0.1 and 39.1 weeks across organ categories and treatment arms. After 5 years, second-line NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) followed by NIVO 240 mg Q2W (arm A) continued to provide durable and clinically meaningful responses with long-term survival benefit in patients with aHCC. Responses also remained durable in arms B and C. All 3 arms had manageable safety profiles, and no new safety signals were identified with longer follow-up.