Key Clinical Takeaways: 

• Design/Population: CheckMate 9DW is a randomized phase 3 trial evaluating first-line nivolumab plus ipilimumab versus lenvatinib or sorafenib in patients with previously untreated unresectable hepatocellular carcinoma. 
• Key Outcomes: After a median follow-up of 52.5 months, nivolumab plus ipilimumab continued to demonstrate an overall survival benefit, with higher 48-month survival rates, higher objective and complete response rates, and longer duration-of-response, compared with lenvatinib or sorafenib.
• Clinical Relevance: The sustained survival advantage, durable responses, and manageable safety profile observed at 4 years reinforce nivolumab plus ipilimumab as a standard-of-care first-line treatment option for patients with unresectable hepatocellular carcinoma.

According to updated results from the phase 3 CheckMate 9DW trial, first-line nivolumab plus ipilimumab continued to demonstrate sustained clinical efficacy with a manageable safety profile at 4 years among patients with unresectable hepatocellular carcinoma.

These findings were presented by Peter Galle, MD, PhD, University Medical Center Mainz, Mainz, Germany, at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.

In this trial, 668 previously untreated patients who were either ineligible for or had experienced disease progression after curative surgical or locoregional therapy were randomized 1:1 to receive 1 mg/kg of nivolumab plus 3 mg/kg of ipilimumab every 3 weeks for up to 4 cycles followed by 480 mg of nivolumab every 4 weeks (n = 335) or investigator’s choice of sorafenib or lenvatinib (n = 333) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Key secondary end points included objective response rate (ORR), duration of response, and safety.

At a median follow-up of 52.5 months, median OS was 23.7 months in the nivolumab plus ipilimumab arm and 20.6 months in the sorafenib or lenvatinib arm, with 48-month OS rates of 31% and 18%, respectively. The ORR was 36% in the nivolumab plus ipilimumab arm and 13% in the sorafenib or lenvatinib arm, and median duration of response was 34.3 months and 12.9 months, respectively.

Grade 3/4 treatment-related adverse events were reported in 136 patients in the nivolumab plus ipilimumab arm and in 138 patients in the sorafenib or lenvatinib arm. Treatment-related adverse events led to treatment discontinuation in 13% of patients receiving nivolumab plus ipilimumab and 6% of patients receiving sorafenib or lenvatinib.

“After 4 years of follow-up, [first-line nivolumab plus ipilimumab] continued to show sustained efficacy benefit [versus] [sorafenib or lenvatinib] in unresectable [hepatocellular carcinoma] and manageable safety with no new concerns,” concluded Dr Galle. “These results continue to support [nivolumab plus ipilimumab] as a standard-of-care treatment in these patients.”

Source: 

Galle PR, Sangro B, Decaens T, et al. Nivolumab plus ipilimumab vs lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (HCC): 4-year follow-up of CheckMate 9DW. Presented at ASCO Gastrointestinal Cancers Symposium. January 8 - 12, 2026; San Francisco, California. LBA479