FDA Receives NDA Resubmission for Rivoceranib Plus Camrelizumab in Frontline Unresectable or Metastatic HCC

A new drug application (NDA) has been resubmitted to the FDA, seeking the approval of camrelizumab plus rivoceranib for the first-line systemic treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC).¹

The resubmission was filed on October 9, 2026, in response to a third complete response letter (CRL) issued in July 2026.

The NDA is supported by data from the global phase 3 CARES-310 trial (NCT03764293), in which camrelizumab plus rivoceranib produced a median overall survival (OS) of 23.8 months (95% CI, 20.6-27.2) vs 15.2 months (95% CI, 13.2-18.5) for sorafenib (Nexavar) at a median follow-up of 22.1 months (HR, 0.64; 95% CI, 0.52-0.79; P < .0001) in the final analysis.² Median progression-free survival (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). The final analysis was published in The Lancet Oncology in December 2025, and results were generally consistent across prespecified subgroups.^1,2

"Following submission of our response to the [CRL], we look forward to continued engagement with the FDA as it reviews the NDA for this combination therapy, which demonstrated positive OS and PFS results and a manageable safety profile in the CARES-310 study," Dong-Gun Kim, chief executive officer of Elevar Therapeutics, stated in the news release.¹

What is the regulatory history of the NDA?

The October 2026 filing marks the fourth submission of the NDA for the combination in this indication. The FDA issued an initial CRL on May 16, 2024, citing current good manufacturing practice (cGMP) deficiencies at the Hengrui Pharma facility responsible for producing camrelizumab, as well as incomplete bioresearch monitoring clinical inspections that were constrained by FDA travel restrictions.³ Following a resubmission, the agency issued a second CRL in March 2025 for reasons that were not publicly disclosed.

Elevar resubmitted the NDA again in January 2026.¹ In July 2026, the FDA issued a third CRL, which cited cGMP deficiencies identified during an inspection of a manufacturing site listed in the application; the letter raised no new concerns about the efficacy or safety data from CARES-310.³ According to Elevar, the current resubmission follows work with the FDA and Hengrui Pharma to address that CRL.¹

What is the mechanism of action of rivoceranib plus camrelizumab?

Rivoceranib is an oral, small-molecule TKI that selectively inhibits VEGFRs, a primary pathway for tumor angiogenesis. Camrelizumab is a humanized monoclonal antibody that binds to the PD-1 receptor, blocking PD-1/PD-L1 signaling. Elevar holds global rights to rivoceranib outside China and licensed camrelizumab, for use in combination with rivoceranib in HCC, from Hengrui Pharma in October 2023 for commercialization worldwide excluding Greater China and South Korea.

How was the CARES-310 trial designed?

The randomized, open-label, international, multicenter phase 3 CARES-310 trial enrolled 543 patients with unresectable or metastatic HCC who had not received prior systemic therapy.²

Patients were randomly assigned 1:1 to receive camrelizumab at 200 mg intravenously every 2 weeks plus oral rivoceranib at 250 mg once daily, or oral sorafenib at 400 mg twice daily.

OS and blinded independent review committee–assessed PFS per RECIST 1.1 criteria served as the co-primary end points.

What is the safety profile of rivoceranib plus camrelizumab?

Safety in CARES-310 was manageable and consistent with the known profiles of each agent. The most common grade 3 or higher treatment-related adverse effects (TRAEs) in the combination arm included hypertension (38.2%), increased aspartate aminotransferase levels (17.3%), increased alanine aminotransferase levels (14.0%), and palmar-plantar erythrodysesthesia (12.1%).

TRAEs led to discontinuation of camrelizumab in 17.6% of patients, discontinuation of rivoceranib in 16.9%, and discontinuation of both agents in 4.4%.

References

1. Elevar Therapeutics resubmits new drug application to FDA. News release. Elevar Therapeutics. October 14, 2026. Accessed October 14, 2026. https://www.globenewswire.com/news-release/2026/10/14/3380931/0/en/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-h.html
2. Qin S, Gu S, Chan SL, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study. Lancet Oncol. 2025;26(12):1598-1611. doi:10.1016/S1470-2045(25)00543-1
3. FDA issues third CRL for rivoceranib plus camrelizumab in first-line HCC over additional manufacturing concerns. OncLive. Published July 13, 2026. Accessed October 14, 2026. https://www.onclive.com/view/fda-issues-third-crl-for-rivoceranib-plus-camrelizumab-in-first-line-hcc-over-additional-manufacturing-concerns