Elevar resubmits its rivoceranib-camrelizumab NDA for advanced liver cancer after a third FDA CRL, following Phase 3 survival benefits in CARES-310.
Written By: Mayuresh Salvi, PharmD
Reviewed By: Pharmacally Editorial Team
Elevar Therapeutics has resubmitted its New Drug Application (NDA) for rivoceranib plus camrelizumab as first-line treatment for unresectable or metastatic hepatocellular carcinoma (HCC), following a third Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) in July 2026. The combination demonstrated a median overall survival of 23.8 months in the Phase 3 CARES-310 trial, but repeated regulatory setbacks have delayed its potential U.S. approval.
Third CRL Extends a Multi-Year Regulatory Review
Elevar originally submitted the NDA in May 2023. The FDA issued its first CRL in May 2024, citing manufacturing facility inspection deficiencies involving camrelizumab and incomplete clinical site inspections. After a subsequent resubmission, the application received a second CRL in March 2025. Elevar resubmitted the NDA in January 2026, but the FDA issued another CRL in July 2026.
The latest CRL cited deficiencies identified during a current good manufacturing practice (cGMP) inspection of a facility listed in the rivoceranib NDA. Elevar resubmitted the application on October 9, 2026, following discussions with the FDA and its development partner, Hengrui Pharma.
The company has not publicly detailed all corrective actions included in the latest resubmission or provided a new target action date. The regulatory history indicates that manufacturing and inspection requirements have been important obstacles to approval. However, the reasons for individual CRLs should be distinguished rather than treated as identical, and the public disclosures do not establish that every outstanding regulatory concern has been resolved.
CARES-310 Demonstrated a Significant Survival Advantage
The NDA is supported by CARES-310, a global Phase 3 study comparing first-line rivoceranib plus camrelizumab with sorafenib in patients with unresectable or metastatic HCC.
The combination achieved a median overall survival (mOS) of 23.8 months, compared with 15.2 months for sorafenib. The hazard ratio for death was 0.64 (95% confidence interval [CI], 0.52–0.79; p<0.0001), corresponding to a 36% lower hazard of death during the study period.
The study also demonstrated a progression-free survival benefit, and results across multiple patient subgroups were generally consistent. The final analysis was published in The Lancet Oncology in December 2025.
These findings support the clinical value of combining antiangiogenic therapy with immune checkpoint inhibition in advanced HCC. The survival advantage is clinically meaningful, although efficacy alone cannot resolve manufacturing, inspection or other regulatory requirements governing approval.
Dual Mechanism Targets Angiogenesis and Immune Evasion
Rivoceranib is an oral tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptors (VEGFRs), which contribute to the formation of blood vessels that supply tumors. Camrelizumab is a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), a checkpoint that can suppress antitumor immune responses.
By targeting tumor angiogenesis and immune evasion, the combination uses complementary mechanisms to control disease. Both agents have established development histories in China, where rivoceranib, known as apatinib, has been approved for gastric cancer and the combination has been approved for unresectable or metastatic HCC. Camrelizumab is also approved for several cancer indications in China.
The combination was included as a first-line treatment option for advanced HCC in the 2025 Barcelona Clinic Liver Cancer treatment strategy and European Society for Medical Oncology guidelines. These recommendations reflect the clinical evidence but do not confer U.S. marketing authorization.
FDA Review Will Determine the Next Milestone
HCC is the most common form of primary liver cancer and frequently develops in people with chronic liver disease. Advanced disease remains associated with substantial mortality, making effective first-line systemic treatments an important clinical need.
For Elevar, the October resubmission represents another attempt to translate the CARES-310 survival benefit into U.S. regulatory approval. The FDA’s assessment will determine whether the company’s response adequately addresses the deficiencies raised in July. Until the agency completes its review, the timing and outcome of a potential U.S. approval remain uncertain.
Reference
Elevar Therapeutics Resubmits New Drug Application to FDA for Combination of Camrelizumab plus Rivoceranib for Use as a First-line Treatment Option for Unresectable or Metastatic Hepatocellular Carcinoma, Elevar Therapeutics, 14 October 2026
About the Writer
Mayuresh Sunil Salvi (Linkedin) is a PharmD professional and healthcare writer with a strong interest in pharmacovigilance, drug safety, and emerging medical research. He is passionate about exploring new drug discoveries, clinical research, and advances in evidence-based medicine. His interests also include ward rounds, prescription audits, and treatment analysis to support rational pharmacotherapy and improved patient care.