FDA issued a complete response letter (CRL) for Elevar Therapeutics' new drug application seeking approval of the combination of rivoceranib and camrelizumab as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma.

The rejection was not based on clinical data, which FDA has previously acknowledged as substantial, but rather on manufacturing deficiencies identified during a current good manufacturing practice (cGMP) inspection of a production site listed on the rivoceranib application.¹

Dong-Gun Kim, chief executive officer of Elevar Therapeutics, says the company is reviewing the letter and plans to engage promptly with FDA to understand the agency's feedback and chart a path forward. "While we are disappointed by this outcome, we remain committed to patients with hepatocellular carcinoma and to advancing the development of rivoceranib and camrelizumab," Kim said. "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."

Why was the application rejected?

The CRL stemmed from manufacturing issues rather than any question of clinical efficacy or safety. FDA identified deficiencies during a cGMP inspection of a manufacturing site listed on the rivoceranib application, a procedural hurdle that has derailed other drug applications in recent years and can typically be resolved through remediation without requiring new clinical trials.¹

What is the clinical case for the combination?

The application was built on the global Phase III Cares-310 study, which evaluated the camrelizumab plus rivoceranib regimen in patients with unresectable or metastatic hepatocellular carcinoma. The combination achieved a median overall survival of 23.8 months, marking the longest overall survival reported to date among first-line treatments for the disease.² The combination held consistent efficacy across multiple patient subgroups and along with a manageable safety profile.²

The clinical data has already drawn recognition outside of the FDA process, as prior to the U.S. regulatory decision, the combination was included as a first-line treatment option for hepatocellular carcinoma in both the 2025 Barcelona Clinic Liver Cancer treatment strategy and European Society for Medical Oncology guidelines.²

What are the treatments?

Rivoceranib is a small-molecule tyrosine kinase inhibitor that potently targets vascular endothelial growth factor receptor, a primary pathway for tumor angiogenesis. The drug has been studied in more than 6,000 patients across solid tumor indications and has received orphan drug designations in gastric cancer, adenoid cystic carcinoma and hepatocellular carcinoma across the U.S. and EU.¹ It was the first TKI approved in gastric cancer in China in 2014 and is approved in combination with camrelizumab as a first-line treatment for unresectable hepatocellular carcinoma.¹

Camrelizumab is a humanized monoclonal antibody targeting the PD-1 receptor, developed by Hengrui Pharma and studied in more than 5,000 patients. It holds eight approved indications in China across hepatocellular carcinoma, Hodgkin's lymphoma, lung cancer, esophageal cancer and nasopharyngeal carcinoma.¹ FDA granted camrelizumab orphan drug designation for advanced hepatocellular carcinoma in April 2021.

Why is this important?

FDA’s decision to issue Elevar a CRL comes on the heels of the agency’s decision to halt the release of CRL’s following a citizen’s petition being filed against the agency, asking for FDA to reform how it releases the letters.

The agency currently has a deadline of October 17, 2026 to respond to the petition, and has yet to release an official response.

Sources

1. Elevar Therapeutics Receives FDA Complete Response Letter for Combination of Rivoceranib and Camrelizumab as a First-line Treatment for Unresectable or Metastatic Hepatocellular Carcinoma Elevar Therapeutics July 10, 2026 https://www.globenewswire.com/news-release/2026/07/10/3325659/0/en/elevar-therapeutics-receives-fda-complete-response-letter-for-combination-of-rivoceranib-and-camrelizumab-as-a-first-line-treatment-for-unresectable-or-metastatic-hepatocellular-ca.html
2. Elevar Therapeutics Announces FDA Acceptance of New Drug Application Resubmission for Rivoceranib in Combination with Camrelizumab as a First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma Elevar Therapeutics January 30, 2026 https://www.globenewswire.com/news-release/2026/1/30/3229623/0/en/Elevar-Therapeutics-Announces-FDA-Acceptance-of-New-Drug-Application-Resubmission-for-Rivoceranib-in-Combination-with-Camrelizumab-as-a-First-line-Systemic-Treatment-for-Unresectab.html