Nivolumab plus Ipilimumab versus Lenvatinib or Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: CheckMate 9DW Japanese Subgroup Analysis

Introduction: In the preplanned interim analysis of the phase 3 CheckMate 9DW trial, first-line nivolumab plus ipilimumab demonstrated significant overall survival (OS) benefit versus lenvatinib or sorafenib (hazard ratio [HR] = 0.79; 95% confidence interval [CI]: 0.65–0.96; p = 0.018) in patients with unresectable hepatocellular carcinoma (HCC). We present outcomes in Japanese patients from this trial. Methods: Patients with unresectable HCC without prior systemic therapy were randomized 1:1 to receive nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks (up to 4 doses, then nivolumab 480 mg every 4 weeks) or investigator’s choice of lenvatinib or sorafenib. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR); safety was an exploratory endpoint. Results: Fifty-six Japanese patients were randomized to nivolumab plus ipilimumab (n = 25) and lenvatinib or sorafenib (n = 31). After a median follow-up of 35.8 months (range: 28.2–45.3), median OS was not reached (NR) (95% CI: 16.9 months to not estimable [NE]) with nivolumab plus ipilimumab and 32.0 months (95% CI: 20.9–NE) with lenvatinib or sorafenib (HR = 0.64 [95% CI: 0.27–1.50]); 24- and 36-month OS rates were 70% versus 63% and 64% versus 40%, respectively. ORR per BICR with nivolumab plus ipilimumab was 56% (95% CI: 35–76) versus 16% (95% CI: 6–34) with lenvatinib or sorafenib. Median DOR was NR (95% CI: NE) and 11.1 months (95% CI: 6.4–NE), respectively. Grade 3/4 treatment-related adverse events occurred in 50% versus 65% of patients, respectively. There were no treatment-related deaths among Japanese patients. Conclusion: Consistent with the global population, first-line nivolumab plus ipilimumab showed clinically meaningful improvement in OS and ORR versus lenvatinib or sorafenib in Japanese patients with unresectable HCC, along with manageable safety. These results support nivolumab plus ipilimumab as a potential new first-line treatment for unresectable HCC in Japan.