Elevar's Rivoceranib-Camrelizumab Combination Shows Significant Survival Benefit in Phase 3 Liver Cancer Trial
核心洞察
Elevar Therapeutics (搜索)' Phase 3 CARES-310 study published in The Lancet Oncology demonstrates that rivoceranib plus camrelizumab significantly improved overall survival compared to sorafenib in unresectable hepatocellular carcinoma (搜索) patients.
The combination therapy achieved a median overall survival of 23.8 months versus 15.2 months with sorafenib, representing a 36% reduction in death risk with manageable safety profile.
The company plans to resubmit its New Drug Application to the FDA for the combination therapy in January 2026, potentially offering a new first-line treatment option for liver cancer (搜索) patients.
Elevar Therapeutics (搜索) announced that the final analysis of its Phase 3 CARES-310 study has been published in The Lancet Oncology, demonstrating significant survival benefits for the combination of rivoceranib and camrelizumab as first-line therapy for unresectable hepatocellular carcinoma (搜索) (uHCC). The randomized, open-label international trial showed clinically meaningful survival improvement versus sorafenib, the current standard first-line treatment.
Trial Design and Patient Population
The CARES-310 study (NCT03764293) enrolled 543 patients across 95 study sites in 13 countries and regions between June 28, 2019, and March 24, 2021. The patient population was predominantly male (84%) and Asian (83%), with 272 patients receiving the camrelizumab-rivoceranib combination and 271 receiving sorafenib.
Primary Efficacy Results
At the final analysis conducted on June 14, 2023, the combination therapy demonstrated superior efficacy across key endpoints. Median overall survival reached 23.8 months (95% CI 20.6-27.2) with camrelizumab-rivoceranib compared to 15.2 months (13.2-18.5) with sorafenib, representing a hazard ratio of 0.64 (95% CI 0.52-0.79; one-sided p<0.0001).
The combination also showed improved progression-free survival, with a median of 5.6 months (95% CI 5.5-7.4) versus 3.7 months (95% CI 3.1-3.7) for sorafenib (HR 0.54 [95% CI 0.44-0.67]; one-sided p<0.0001). The median follow-up was 22.1 months in the combination group and 14.9 months in the sorafenib group.
Safety Profile
The combination therapy showed a manageable but distinct safety profile compared to sorafenib. The most common grade 3 or 4 treatment-related adverse events in the camrelizumab-rivoceranib group included hypertension (39% vs. 15% with sorafenib), increased aspartate aminotransferase (17% vs. 5%), and increased alanine aminotransferase (14% vs. 3%). Palmar-plantar erythrodysesthesia syndrome occurred in 12% of combination patients versus 16% of sorafenib patients.
Treatment-related serious adverse events were reported in 25% of patients receiving the combination compared to 7% with sorafenib. Treatment-related deaths occurred in one patient in each group, with multiple organ dysfunction syndrome in the combination arm and respiratory failure with circulatory collapse in the sorafenib arm.
Regulatory Path Forward
Elevar Therapeutics (搜索) plans to resubmit its New Drug Application to the U.S. Food and Drug Administration for the camrelizumab-rivoceranib combination in January 2026. Both drugs have received orphan drug designations for hepatocellular carcinoma (搜索) from the FDA and European Medicines Agency.
"Having our Phase 3 study final analysis published in a prestigious journal such as The Lancet Oncology is momentous for Elevar Therapeutics (搜索) and, even more so, for the global liver cancer (搜索) patient community," said Bryan Kim, chief executive officer of Elevar. "The data clearly showed the potential of our combination treatment of camrelizumab and rivoceranib, as it significantly improved survival compared to the standard treatment option."
Addressing Unmet Medical Need
Hepatocellular carcinoma (搜索) represents a significant global health burden, with more than 800,000 people worldwide diagnosed with liver cancer (搜索) annually and accounting for over 700,000 cancer deaths each year, according to the American Cancer Society. The disease typically has a poor prognosis with limited treatment options, representing an ongoing urgent medical need.
Drug Mechanisms and Development
Rivoceranib is a small-molecule tyrosine kinase inhibitor that potently inhibits vascular endothelial growth factor receptor (VEGFR (搜索)), a primary pathway for tumor angiogenesis. The drug has been studied in more than 6,000 patients worldwide and is currently approved in China for gastric cancer and, in combination with camrelizumab, for first-line treatment of uHCC.
Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1 (搜索)) receptor. Developed by Hengrui Pharma, the drug has been studied in more than 5,000 patients and is currently approved for eight indications in China. Elevar licensed camrelizumab for worldwide commercialization excluding Greater China and Korea in October 2023.