Frontline nivolumab plus ipilimumab ups OS, ORR in patients with uHCC

The combination of nivolumab and ipilimumab (NIVO + IPI) significantly improves overall survival (OS) and objective response rate (ORR) compared with lenvatinib or sorafenib (LEN/SOR) in the first-line setting for patients with unresectable hepatocellular carcinoma (uHCC), based on the CheckMate 9DW expanded analyses presented at ASCO GI 2025.

At a median follow-up of 35.2 months, patients treated with NIVO + IPI achieved a significantly longer median OS than those treated with LEN/SOR (23.7 vs 20.6 months; hazard ratio, 0.79; p=0.018). [ASCO GI 2025, abstract 520]

Moreover, the OS rates were higher among patients on the combination regimen than those on LEN/SOR at 24 (49 percent vs 39 percent) and 36 (38 percent vs 24 percent) months.

As per the BICR* assessment, ORR was also significantly higher in the NIVO + IPI arm vs the LEN/SOR arm (36 percent vs 13 percent; p<0.0001), with complete and partial response rates of 7 percent vs 2 percent and 29 percent vs 11 percent, respectively.

At the 24-week landmark, the median OS for patients with complete or partial responses was not reached in the combination arm and was 28.3 months in the LEN/SOR arm. “In both treatment arms, objective response by BICR was associated with improved OS outcomes,” said lead author Dr Masatoshi Kudo from Kindai University Hospital in Osaka, Japan.

Across all subgroups, the BICR-assessed ORR was consistently higher with NIVO + IPI than with LEN/SOR (36.1 percent vs 13.2 percent).

“Taken together, NIVO + IPI demonstrated a statistically significant and clinically meaningful OS [and ORR] benefit vs LEN/SOR in patients with uHCC [who were] naive to systemic therapy,” Kudo noted.

The phase III CheckMate 9DW trial included 668 patients with uHCC who were randomized in a 1:1 ratio to receive NIVO 1 mg/kg + IPI 3 mg/kg IV Q3W for up to 4 cycles, then NIVO 480 mg Q4W (NIVO + IPI arm: n=335, median age 65 years) or LEN 8 or 12 mg PO QD or SOR 400 mg PO BID (LEN/SOR arm: n=333, median age 66 years). Patients continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, or a maximum treatment duration of 2 years for the NIVO + IPI arm only.

In terms of safety, the majority of treatment-related adverse events were grade 1 or 2 and did not result in treatment discontinuation.

However, most treatment-related deaths occurred in 12 patients in the NIVO + IPI arm, of which nine patients had severe and underlying liver disease, compared with three patients in the LEN/SOR arm.

According to Kudo, the safety of NIVO + IPI was consistent with the known safety profile of the regimen.

“Overall, these results demonstrated the efficacy and manageable safety of NIVO + IPI in uHCC and further support its use as a new first-line standard of care treatment option in this setting,” Kudo concluded.