The FDA has accepted a new drug application (NDA) for rivoceranib, a tyrosine kinase inhibitor (TKI), in combination with camrelizumab, a PD-1 inhibitor, as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). Elevar Therapeutics, the company behind the application, anticipates a Prescription Drug User Fee Act (PDUFA) target action date of May 16, 2024.
The NDA is based on data from the Phase 3 CARES 310 study (NCT03764293), a randomized, open-label, international trial involving 543 patients across 95 study sites in 13 countries. The study compared the combination of rivoceranib and camrelizumab against sorafenib, a standard first-line treatment for uHCC.
CARES 310 Study Results
The CARES 310 study demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) for the combination therapy. Patients treated with rivoceranib plus camrelizumab achieved a median OS of 22.1 months (95% CI, 19.1-27.2) compared to 15.2 months (95% CI, 13.0-18.5) for those treated with sorafenib (HR, 0.62; 95% CI, 0.49-0.80; P <.0001).
Progression-free survival (PFS) was also significantly improved in the combination arm, with a median PFS of 5.6 months (95% CI, 5.5-6.3) compared to 3.7 months (95% CI, 2.8-3.7) in the sorafenib arm (HR, 0.52; 95% CI, 0.41-0.65; P <.0001).
Furthermore, the confirmed objective response rate (ORR) was 25.4% (95% CI, 20.3%-31.0%) in the rivoceranib plus camrelizumab group, significantly higher than the 5.9% (95% CI, 3.4%-9.4%) observed in the sorafenib group.
Safety Profile
The most frequent grade 3 or higher treatment-related adverse events (TRAEs) in the combination therapy arm included hypertension (37.5%), aspartate aminotransferase increase (16.5%), and alanine transaminase increase (12.9%). In the sorafenib arm, the most common grade 3 or higher TRAEs were palmar-plantar erythrodysesthesia (15.2%) and hypertension (14.9%).
Implications for HCC Treatment
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, often occurring in individuals with chronic liver diseases. The current treatment landscape for unresectable HCC is limited, highlighting the urgent need for more effective therapies. The positive results from the CARES 310 study and the FDA's acceptance of the NDA suggest that the combination of rivoceranib and camrelizumab could represent a significant advancement in the first-line treatment of uHCC.
Saeho Chong, chief executive officer at Elevar, stated, "Rivoceranib plus camrelizumab has demonstrated the potential to improve the lives of those confronted with unresectable hepatocellular carcinoma. With the FDA’s acceptance of our new drug application, we are pleased to reach another milestone in the development of this combination therapy."
About Rivoceranib and Camrelizumab
Rivoceranib is a highly potent, oral TKI that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), a key regulator of tumor angiogenesis. Camrelizumab is a humanized monoclonal antibody that targets the programmed death-1 (PD-1) receptor, blocking the PD-1/PD-L1 signaling pathway and enhancing the immune response against cancer cells.
