KEY TAKEAWAYS
- The CheckMate 9DW phase 3 trial aimed to investigate the efficacy and safety of NIVO plus IPI compared to LEN or SOR as 1L therapy for pts with uHCC.
- The primary endpoint was to determine OS.
- Researchers noticed a significant OS benefit and higher ORR with NIVO + IPI, suggesting its potential as a new 1L SOC for uHCC.
First-line (1L) therapies based on programmed death ligand 1 (PD-L1) inhibitors are standard of care (SOC) in unresectable hepatocellular carcinoma (uHCC) and demonstrate improved outcomes over sorafenib (SOR); however, prognosis remains poor, and there is an unmet need for alternative therapies with long-term benefits. Second-line nivolumab (NIVO) plus ipilimumab (IPI) demonstrated clinically meaningful efficacy and manageable safety in SOR-treated patients (pts) with hepatocellular carcinoma (HCC) in CheckMate 040, leading to its accelerated approval in the United States.
Peter Robert Galle and the team aimed to assess the efficacy and safety of NIVO + IPI compared to lenvatinib (LEN) or SOR as 1L therapy for pts with uHCC.
They performed an inclusive analysis of adult pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score of 5–6, and ECOG performance status 0–1. Pts were randomly assigned 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles) followed by NIVO 480 mg Q4W or the investigator’s choice of LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years.
The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1.
About 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333); among 325 pts treated in the LEN/SOR arm, 275 (85%) received LEN. After a median (range) follow-up of 35.2 (26.8–48.9) months (mo), median OS was 23.7 mo with NIVO + IPI vs 20.6 mo with LEN/SOR (HR, 0.79; 95% CI, 0.65–0.96; P = 0.0180), with respective 24-mo OS rates (95% CI) of 49% (44–55) vs 39% (34–45).
ORR was higher with NIVO + IPI (36%) vs LEN/SOR (13%; P< 0.0001); complete response was observed in 7% of pts with NIVO + IPI vs 2% with LEN/SOR. Median DOR was 30.4 mo with NIVO + IPI vs 12.9 mo with LEN/SOR.
The study concluded that NIVO + IPI exhibited a statistically significant OS benefit compared to LEN/SOR in previously untreated pta with uHCC, along with higher ORR and durable responses with a manageable safety profile. These findings advocate for the adoption of this combination as a potential new 1L standard of care for unresectable hepatocellular carcinoma.
The trial was sponsored by Bristol-Myers Squibb.
Source: https://meetings.asco.org/abstracts-presentations/234365
Clinical Trial: https://clinicaltrials.gov/study/NCT04039607
Galle P R, Decaens T, Kudo M, et al. (2024). “Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): First results from CheckMate 9DW.” Presented at ASCO 2024.
