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 (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 not reached (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.