FDA issues Complete Response Letter to Elevar Therapeutics’ NDA for rivoceranib plus camrelizumab in advanced hepatocellular carcinoma, citing manufacturing deficiencies. Despite positive Phase 3 CARES‑310 data showing 23.8‑month median OS, U.S. review is delayed while global guidelines already recognize the regimen.
Written By: Disha Jadhao, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has issued a Complete Response Letter to Elevar Therapeutics regarding the New Drug Application for rivoceranib and the Biologics License Application (BLA) for Hengrui Pharma’s PD-1 inhibitor camrelizumab, which are under review as a first-line combination therapy for patients with unresectable or metastatic hepatocellular carcinoma (HCC). The agency cited deficiencies identified during a current Good Manufacturing Practice inspection at a manufacturing facility listed in the rivoceranib NDA.
The regulatory setback delays a potential new first-line treatment option for advanced liver cancer in the United States despite positive Phase 3 clinical data supporting the combination.
Manufacturing issue halts regulatory review
According to Elevar, the company is reviewing the FDA’s feedback and plans to work closely with the agency to determine the appropriate regulatory pathway. The company said it remains confident in the clinical evidence supporting the rivoceranib and camrelizumab combination and intends to address the manufacturing observations as quickly as possible.
Chief Executive Officer Dong-Gun Kim said the company remains committed to advancing the program for patients with hepatocellular carcinoma and will engage with the FDA to clarify the agency’s requirements before determining the next steps for resubmission.
Phase 3 CARES-310 study supported the NDA
The NDA was supported by results from the global Phase 3 CARES-310 trial (NCT03764293), which evaluated rivoceranib plus camrelizumab as first-line systemic therapy in patients with unresectable or metastatic HCC.
The combination achieved a median overall survival of 23.8 months, which Elevar described as the longest overall survival reported to date among first-line treatment regimens for advanced HCC. The study also demonstrated consistent efficacy across multiple patient subgroups while maintaining a manageable safety profile.
The final analysis of CARES-310 was published in The Lancet Oncology in December 2025, further strengthening the clinical evidence supporting the regimen.
Combination targets angiogenesis and immune checkpoint pathways
Rivoceranib is an oral tyrosine kinase inhibitor that selectively blocks vascular endothelial growth factor receptor (VEGFR), reducing tumor angiogenesis and limiting cancer progression. Camrelizumab is a humanized programmed death-1 (PD-1) immune checkpoint inhibitor that restores antitumor immune responses by blocking PD-1 signaling.
Combining VEGFR inhibition with PD-1 blockade has emerged as an established strategy for improving outcomes in advanced hepatocellular carcinoma by simultaneously disrupting tumor blood vessel formation and enhancing immune-mediated tumor control.
HCC remains the most common form of primary liver cancer and is frequently associated with chronic liver disease caused by viral hepatitis and other inflammatory liver disorders. More than 800,000 people are diagnosed with liver cancer globally each year, and the disease accounts for more than 700,000 deaths annually, underscoring the need for additional effective first-line therapies.
Guideline recognition and next regulatory steps
Although the FDA review has been delayed, the regimen has already received clinical recognition outside the United States. Before any U.S. approval, rivoceranib plus camrelizumab was incorporated into the 2025 Barcelona Clinic Liver Cancer (BCLC) treatment strategy and the European Society for Medical Oncology (ESMO) guidelines as a first-line treatment option for hepatocellular carcinoma.
The combination is also approved in China for first-line treatment of unresectable HCC. Elevar now plans to work with the FDA to resolve the manufacturing deficiencies before pursuing resubmission of the NDA, while continuing global development and commercialization efforts for the regimen outside China.
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About the Writer
Disha Sanjay Jadhao (LinkedIn) is a pharmacy graduate and healthcare writer with a strong interest in clinical documentation and simplifying healthcare information for better reader understanding. She is enthusiastic, adaptable, and eager to take on new challenges while contributing to clear, accurate, and engaging medical and pharmaceutical content.