FDA Rejects Rivoceranib/Camrelizumab in First-Line Unresectable HCC

The FDA has issued a third complete response letter (CRL) for the combination of rivoceranib and camrelizumab as a first-line systemic treatment for patients with unresectable or metastatic hepatocellular carcinoma (HCC), according to a news release from Elevar Therapeutics, Inc.¹

The agency rejected the new drug application (NDA) for the combination based on deficiencies observed during a cGMP inspection of a manufacturing site highlighted in the NDA. According to the press release, the FDA previously acknowledged “substantial clinical data” supporting the therapeutic regimen.

“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 [HCC] and to advancing the development of rivoceranib and camrelizumab,” Dong-Gun Kim, chief executive officer at Elevar Therapeutics, stated in the press release.¹ “We will engage with the FDA promptly to fully understand the agency's feedback and determine the most effective path forward.”

The tyrosine kinase inhibitor and PD-1 inhibitor combination was initially issued a CRL in May 2024, with the FDA citing manufacturing-related concerns.² The agency then issued another CRL in March 2025; at the time of the announcement, it was not specified why the second CRL was issued.³ The developers most recently resubmitted the NDA for the treatment combination in January 2026.⁴

What results have rivoceranib/camrelizumab demonstrated?

The NDA was supported by data from the pivotal, global, randomized, open-label phase 3 CARES-310 trial (NCT03764293), which compared rivoceranib plus camrelizumab against the standard of care, sorafenib (Nexavar), in patients with unresectable HCC.⁵ The combination showed a statistically significant and clinically meaningful improvement in the trial's dual primary end points of overall survival (OS) and progression-free survival (PFS).

The median OS was 23.8 months (95% CI, 20.6-27.2) with the combination vs 15.2 months (95% CI, 13.2-18.5) with sorafenib (HR, 0.64; 95% CI, 0.52-0.79; P <.0001). The median PFS was 5.6 months (95% CI, 5.5-7.4) vs 3.7 months (95% CI, 3.1-3.7), respectively (HR, 0.54; 95% CI, 0.44-0.67; P <.0001). Survival benefits were consistent across subgroups defined by etiology and geographic region.

What is the regulatory history of rivoceranib/camrelizumab in HCC?

After the FDA issued a CRL in May 2024 based on deficiencies from its inspection of the camrelizumab manufacturing facility and a second CRL in March 2025 requesting additional information, developers noted that neither CRL identified concerns regarding the clinical efficacy or safety of the combination. The developer resubmitted the NDA in January 2026, and the FDA accepted the resubmission for review later in the month, assigning a PDUFA date of July 23, 2026.⁶

What is the CARES-310 trial design?

CARES-310 enrolled 543 patients with unresectable HCC and randomly assigned them 1:1 to receive either the combination or sorafenib monotherapy. Patients in the experimental arm received camrelizumab at 200 mg intravenously every 2 weeks plus rivoceranib at 250 mg orally once daily; those in the comparator arm received sorafenib at 400 mg orally twice daily. Eligible patients had histologically or cytologically confirmed unresectable or metastatic HCC with no prior systemic therapy, at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and Child-Pugh class A liver function.

What are the safety findings for the combination?

The most common grade 3/4 treatment-related adverse events in the combination arm included hypertension (38%), increased aspartate aminotransferase level (17%), and increased alanine aminotransferase level (13%). Palmar-plantar erythrodysesthesia syndrome occurred in 12% of patients. One treatment-related death occurred in each arm due to multiple organ dysfunction syndrome in the combination group and respiratory failure/circulatory collapse in the sorafenib group.

References

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. News release. Elevar Therapeutics. July 10, 2026. Accessed July 10, 2026. https://tinyurl.com/2jdf9467
2. Announcement on receipt of complete response letter regarding camrelizumab for injection. News release. Jiangsu Hengrui Pharmaceuticals Co., Ltd. May 17, 2024. Accessed July 10, 2026. https://tinyurl.com/3kdz97k9
3. Ji-Yoon H. HLB, Antengene fail to gain U.S. FDA approval for liver cancer drug combo. News release. Chosun Biz. March 21, 2025. Accessed July 10, 2026. https://tinyurl.com/3jcd2j5m
4. Kim JH. HLB restarts FDA review with resubmitted liver cancer combo application. Korea Biomedical Review. January 26, 2026. Accessed July 10, 2026. https://tinyurl.com/3fddj45t
5. Qin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023;402(10408):1133-1146. doi:10.1016/S0140-6736(23)00961-3
6. 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. News release. Elevar Therapeutics. January 30, 2026. Accessed July 10, 2026. https://tinyurl.com/35kfv6nk