FDA Accepts Resubmission of NDA for Rivoceranib and Camrelizumab in Unresectable Hepatocellular Carcinoma
核心洞察
The FDA has accepted the resubmitted NDA for rivoceranib and camrelizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma (搜索).
The resubmission includes data from the Phase 3 CARES-310 study, which showed a median overall survival of 23.8 months with the combination.
The FDA has set a PDUFA target action date of March 20, 2025, for the rivoceranib and camrelizumab combination in uHCC (搜索).
The U.S. Food and Drug Administration (FDA) has accepted the resubmission of a New Drug Application (NDA) for rivoceranib, an oral VEGF tyrosine kinase inhibitor (TKI), in combination with camrelizumab, a PD-1 (搜索) inhibitor, as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma (搜索) (uHCC (搜索)). Elevar Therapeutics (搜索), the company seeking approval, announced the FDA's decision, with a Prescription Drug User Fee Act (PDUFA) target action date set for March 20, 2025.
The resubmission included data from the final analysis of the Phase 3 CARES-310 study, which was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study reported a median overall survival (mOS) of 23.8 months for patients with uHCC (搜索) treated with the combination of camrelizumab and rivoceranib, compared to 15.2 months for those treated with sorafenib (HR, 0.64; 95% CI, 0.52-0.79; 1-sided P < .0001). This marks the longest mOS reported for any treatment in a global Phase 3 trial for this patient population.
CARES-310 Trial Details
The CARES-310 trial was an international, randomized, open-label, Phase 3 study involving 543 patients with uHCC (搜索) who had not received prior systemic therapy. Patients were randomized 1:1 to receive either camrelizumab (190 mg intravenously every 2 weeks) plus rivoceranib (250 mg orally once daily) or sorafenib (400 mg orally twice daily).
The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and duration of response (DoR).
The final analysis of the CARES-310 study demonstrated clinically meaningful improvements in survival with the camrelizumab/rivoceranib combination. The OS rate at 24 months was 49.0% with the combination versus 36.2% with sorafenib, and 37.7% versus 24.8% at 36 months. Efficacy results were generally consistent across all patient subgroups, including those with viral and non-viral etiologies.
Safety and Efficacy
Safety data from the final analysis aligned with the interim OS analysis, with no new signals noted. Benefits in PFS, ORR, and DoR with the combination were also sustained after prolonged follow-up.
Chris Galloway, M.D., senior vice president of clinical and medical affairs at Elevar Therapeutics (搜索), stated, “We believe rivoceranib plus camrelizumab has the potential to change the clinical practice in the first-line setting for patients with advanced liver cancer. The results of the pivotal CARES-310 trial demonstrated significant improvements in overall survival, with a very manageable safety profile compared with currently approved uHCC (搜索) therapies.”
About Rivoceranib and Camrelizumab
Rivoceranib is a small-molecule tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptors (VEGFRs), a primary pathway for tumor angiogenesis. Camrelizumab is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1 (搜索)) receptor, blocking the PD-1/PD-L1 signaling pathway.
The combination of rivoceranib and camrelizumab is already approved in China as a first-line treatment for uHCC (搜索). Elevar Therapeutics (搜索) holds the global rights (excluding China) to rivoceranib and has partnered with HLB-LS in South Korea for its development and marketing.