FDA Issues Complete Response Letter for Elevar's Rivoceranib-Camrelizumab Combination in First-Line HCC
核心洞察
The FDA issued a complete response letter for Elevar Therapeutics (搜索)' NDA for rivoceranib plus camrelizumab as first-line treatment for unresectable or metastatic hepatocellular carcinoma (搜索).
The CRL was related to deficiencies identified during a cGMP inspection of a manufacturing site listed on the rivoceranib NDA, not clinical data concerns.
The Phase 3 CARES-310 study demonstrated a median overall survival of 23.8 months, the longest reported among first-line HCC treatments to date.
FORT LEE, N.J. — Elevar Therapeutics (搜索), Inc., a majority-owned subsidiary of HLB Co., Ltd. (搜索), announced on July 10, 2026 that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding its new drug application (NDA) for the combination of rivoceranib and camrelizumab as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma (搜索) (HCC).
The FDA's decision was related to deficiencies identified during a cGMP inspection of a manufacturing site listed on the rivoceranib NDA. Notably, the agency did not cite concerns regarding the clinical efficacy or safety data supporting the application.
"The Company is reviewing the contents of the letter and intends to work closely with the FDA to determine the appropriate path forward. While we are disappointed by this outcome, we remain committed to patients with hepatocellular carcinoma (搜索) and to advancing the development of rivoceranib and camrelizumab," said Dong-Gun Kim, Chief Executive Officer of Elevar Therapeutics (搜索). "We will engage with the FDA promptly to fully understand the agency's feedback and determine the most effective path forward. Importantly, we continue to believe in the strength of the clinical data supporting this combination and remain committed to pursuing opportunities that may bring this treatment option to patients in need."
Robust Clinical Evidence from CARES-310
The NDA was supported by the global Phase 3 CARES-310 study, which demonstrated that the camrelizumab plus rivoceranib combination achieved a median overall survival of 23.8 months in patients with unresectable or metastatic HCC. This represents the longest overall survival reported to date among first-line treatments for HCC. Consistent efficacy was observed across multiple patient subgroups, with a manageable safety profile.
In December 2025, the final analysis of the CARES-310 study was published in The Lancet Oncology. Furthermore, prior to regulatory approval, the combination regimen was included as a first-line treatment option for HCC in the 2025 Barcelona Clinic Liver Cancer (BCLC) treatment strategy and European Society for Medical Oncology (ESMO) guidelines, formally recognizing its clinical value.
The Unmet Need in Hepatocellular Carcinoma
Hepatocellular carcinoma (搜索) is the most common type of liver cancer and most frequently develops in people with chronic underlying liver inflammation, which may arise from viral and non-viral causes. HCC typically carries a poor prognosis with limited treatment options and continues to represent a diagnosis with an ongoing urgent medical need. According to the American Cancer Society, more than 800,000 people worldwide are diagnosed with liver cancer each year, and it is a leading cause of cancer deaths, accounting for more than 700,000 annually.
Mechanism of Action and Global Development
Rivoceranib is a small-molecule tyrosine kinase inhibitor (TKI) and a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR (搜索)), a primary pathway for tumor angiogenesis. The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. It has received orphan drug designations in gastric cancer (U.S., EU, and South Korea), adenoid cystic carcinoma (U.S.), and HCC (U.S. and EU).
Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the PD-1 (搜索) receptor, blocking the PD-1/PD-L1 signaling pathway. Developed by Jiangsu Hengrui Pharmaceuticals (搜索) Company Ltd. (Hengrui Pharma), camrelizumab has been studied in more than 5,000 patients, with 50 clinical trials currently underway across a broad range of tumors. The FDA granted orphan drug designation to camrelizumab for advanced HCC in April 2021, and the EMA followed in August 2024.
The combination of rivoceranib and camrelizumab is already approved in China as a first-line treatment for unresectable HCC (January 2023) under Hengrui Pharma's license. In October 2023, Elevar licensed camrelizumab for commercialization from Hengrui Pharma worldwide, excluding Greater China and Korea.
Next Steps
Elevar Therapeutics (搜索) stated that it will engage with the FDA promptly to fully understand the agency's feedback and determine the most effective path forward. The company emphasized that the FDA has previously acknowledged the substantial clinical data supporting the application, and Elevar remains committed to pursuing opportunities that may bring this treatment option to patients in need.