The U.S. Food and Drug Administration (FDA) has accepted the resubmission of the new drug application (NDA) for rivoceranib, an oral VEGF-TKI, in combination with camrelizumab, a PD-1 inhibitor, as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma (uHCC). Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., made the announcement, with the FDA assigning a Prescription Drug User Fee Act (PDUFA) target action date of March 20, 2025.
The resubmission included the final analysis of the Phase 3 CARES-310 study, which was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. The study reported a median overall survival (mOS) of 23.8 months, which is the longest mOS reported in a global Phase 3 trial for patients with uHCC. This confirms that the combination of camrelizumab and rivoceranib shows sustained long-term survival benefits as a first-line treatment.
CARES-310 Study Details
The CARES-310 study is an international, randomized, open-label, Phase 3 trial involving 543 patients with uHCC who had not previously received systemic treatment. It was the first study to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with immunotherapy plus an anti-angiogenic tyrosine kinase inhibitor (TKI) over standard TKI as first-line treatment for uHCC. The final analysis showed that median OS was significantly prolonged with camrelizumab plus rivoceranib compared to sorafenib (23.8 months vs. 15.2 months; hazard ratio [HR] 0.64; 1-sided p < 0.0001).
Chris Galloway, M.D., senior vice president of clinical and medical affairs at Elevar Therapeutics, 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... Elevar is committed to working with the FDA to bring this combination to market for patients and healthcare providers."
Impact on Hepatocellular Carcinoma Treatment
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, with over 800,000 people diagnosed each year worldwide, causing more than 830,000 deaths annually. HCC typically has a poor prognosis with limited treatment options, highlighting an urgent medical need. The data from the CARES-310 study suggest that the combination of rivoceranib and camrelizumab has the potential to benefit a global uHCC population, with consistent efficacy observed across patients with both viral and non-viral etiologies.
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) receptor. The combination aims to limit tumor growth and disease progression through complementary mechanisms of action.
Camrelizumab is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), and in combination with chemotherapy for the treatment of non-small cell lung cancer, esophageal squamous cell carcinoma, and nasopharyngeal carcinoma in the first-line setting.
