Elevar Therapeutics, a subsidiary of HLB Co., Ltd., announced that the U.S. Food and Drug Administration (FDA) has accepted the resubmission of the New Drug Application (NDA) for rivoceranib in combination with camrelizumab for the first-line treatment of unresectable or metastatic hepatocellular carcinoma (uHCC). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date for March 20, 2025.
The resubmission is based on data from the Phase 3 CARES-310 study, which demonstrated a significant improvement in overall survival (OS). Chris Galloway, M.D., senior vice president of clinical and medical affairs at Elevar Therapeutics, highlighted the manageable safety profile of the combination compared to existing uHCC therapies.
CARES-310 Study Results
The CARES-310 study, an international, randomized, open-label trial, involved 543 patients with uHCC who had not previously received systemic treatment. The final analysis, presented at the 2024 ASCO Annual Meeting, showed a median overall survival (mOS) of 23.8 months for the rivoceranib and camrelizumab combination, compared to 15.2 months for sorafenib. This represents the longest mOS reported in a global Phase 3 trial for uHCC.
The combination therapy's OS rate was 49.0% at 24 months and 37.7% at 36 months, compared to 32.6% and 24.8% for sorafenib, respectively. These benefits were consistent across subgroups, including geographical regions, races, and etiologies, indicating broad applicability of the treatment.
Mechanism of Action and Clinical Significance
Rivoceranib is a small-molecule tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptors (VEGFRs), targeting tumor angiogenesis. Camrelizumab is a humanized monoclonal antibody that targets the programmed death-1 (PD-1) receptor, enhancing the immune response against cancer cells. The combination of these two agents provides a dual approach by inhibiting tumor growth and stimulating the immune system.
The CARES-310 study was the first to demonstrate significant progression-free survival (PFS) and overall survival (OS) benefits with an immunotherapy combined with an anti-angiogenic TKI over standard TKIs as a first-line treatment for uHCC. The extended follow-up data confirmed the favorable benefit-to-risk profile of the combination, supporting its potential as a new first-line treatment option.
Current Landscape and Unmet Needs
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and often develops in individuals with chronic liver inflammation. HCC generally has a poor prognosis with limited treatment options, representing an ongoing urgent medical need. The combination of rivoceranib and camrelizumab addresses this need by offering a more effective and tolerable treatment option compared to existing therapies.
Elevar Therapeutics holds the global rights (excluding China) to rivoceranib and has partnered with HLB-LS in South Korea for its development and marketing.
