The U.S. Food and Drug Administration (FDA) declined to approve rivoceranib plus camrelizumab as first-line therapy for unresectable hepatocellular carcinoma (HCC), marking the second rejection for the combination’s regulatory submission.
The FDA issued a complete response letter (CRL) to rivoceranib’s drugmaker HLB Group on March 20, according to Korean news sources, who cited a video announcement by the company’s chairman, Jin Yang-gon. The CRL did not specify what deficiencies regulators found and added that Antengene Corporation – the Chinese-based maker of camrelizumab – will contact the FDA to address specific issues, Yang-gon said.
The regulatory decision marks the second CRL the combination has received in the past year. In May 2024, the FDA sent a CRL for the combination, citing Good Manufacturing Practice issues at a camrelizumab manufacturing facility and incomplete clinical inspections due to travel restrictions during the COVID-19 pandemic.
Elevar Therapeutics, a majority-owned subsidiary of HLB Group, announced in September that it had resubmitted its new drug application. The latest application was based on the results of the phase 3 CARES-310 clinical trial, which was published in the Journal of Clinical Oncology and presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting.
The international, open-label, study included 543 patients with unresectable HCC. Patients were randomly assigned in a 1:1 manner to receive either camrelizumab plus rivoceranib or sorafenib.
Results showed that the median overall survival (OS) was 23.8 months in the camrelizumab plus rivoceranib group (95% confidence interval [CI], 20.6–27.2) compared with 15.2 months in the sorafenib group (95% CI, 13.2–18.5; hazard ratio [HR] = 0.64; 1-sided P<0.0001). The OS rate with camrelizumab plus rivoceranib was 49.0% versus 36.2% at 24 months, and 37.7% vs. 24.8% at 36 months, respectively.
Safety data aligned with the interim OS analysis, with no new signals noted. The OS benefits with camrelizumab plus rivoceranib were consistent across subgroups, races, and locations, the authors reported.
Camrelizumab is an anti-PD-1 antibody that is administered intravenously. Rivoceranib is a kinase inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR-2). Neither drug is approved in the United States.
