Second-line NIVO + IPI combo sustains response, OS benefit in aHCC

The combination of nivolumab 1 mg/kg (NIVO1) and ipilimumab 3 mg/kg (IPI3) every 3 weeks followed by NIVO 240 mg every 2 weeks in the second-line setting continues to confer durable response and overall survival (OS) benefit in patients with advanced hepatocellular carcinoma (aHCC), according to 5-year data from the CheckMate 040* trial presented at ESMO GI 2022.

This multicentre, open-label trial involved 148 patients (median age 60 years) with aHCC who were previously treated with sorafenib. They were randomized in a 1:1:1 ratio to receive four doses of NIVO1 + IPI3 Q3W (arm A; n=50), four doses of NIVO 3 mg/kg (NIVO3) + IPI 1 mg/kg (IPI1) Q3W (arm B; n=49), or NIVO3 Q2W + IPI1 Q6W (arm C; n=49). Patients in both arms A and B were subsequently given a flat dose of NIVO 240 mg Q2W. All patients continued treatment until unacceptable toxicity or disease progression. [ESMO GI 2022, abstract SO-12]

After a minimum follow-up of 60 months, high objective response rates, as per investigator’s assessment, were sustained across all treatment arms (34.0 percent, 27.0 percent, and 29.0 percent in arms A, B, and C, respectively, with a median duration of response of 51.2, 15.2, and 21.7 months, respectively.

During the primary analysis, median OS rates were 22.8 [arm A], 12.5 [arm B], and 12.8 months [arm C], which were all maintained over this 60-month long-term follow-up (22.2, 12.5, and 12.7 months, respectively).

Five-year OS rates were 29.0 percent, 19.0 percent, and 21.0 percent in arms A, B, and C, respectively, with a trend toward a more favourable OS in arm A.

The researchers also found that the 6-month landmark analysis of median OS by best overall response was better among responders vs nonresponders across all treatment arms (Arm A: not reached vs 15.6 months; Arm B: not reached vs 12.5 months; and arm C: 63.2 vs 19.5 months).

Grade 3/4 immune-mediated adverse events, such as hepatitis, pneumonitis, and rash, occurred more frequently in arm A than arms B and C, but most resolved following treatment according to standard algorithms, noted the researchers.

Overall, the safety profile was manageable and no new safety signals were observed across all treatment arms even after this longer follow-up of 5 years, the researchers said.

The initial results of the phase I/II CheckMate 040 study led to US FDA approval of the regimen comprising NIVO1 + IPI3 Q3W for four doses followed by NIVO 240 mg Q2W for sorafenib-treated patients with aHCC. [JAMA Oncol 2020;6:e204564]

“[With this extended follow-up,] second-line NIVO1 + IPI3 Q3W, 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,” said the researchers.

“[Our] results further support the use of NIVO1 + IPI3 as second-line treatment for patients with advanced aHCC who have previously received sorafenib,” they noted.

*CheckMate 040: An immunotherapy study to evaluate the effectiveness, safety, and tolerability of nivolumab or nivolumab in combination with other agents in patients with advanced liver cancer