FDA Sets April 2027 Decision Date for Rivoceranib Combo in HCC

Following the fourth resubmission of applications to the FDA for rivoceranib plus camrelizumab as first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC), the FDA has assigned a Prescription Drug User Fee Act (PDUFA) target date of April 9, 2027, for the new drug application (NDA).¹

Elevar Therapeutics announced that the FDA acknowledged receipt of its resubmitted NDA for rivoceranib, an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, in combination with camrelizumab, a PD-1 inhibitor. The NDA was resubmitted on October 9, 2026, alongside a biologics license application (BLA) resubmission for camrelizumab from Hengrui Pharma. The FDA will review both applications through an integrated review process for the combination regimen.

“[HCC] remains a major cause of cancer-related mortality worldwide,” Arndt Vogel, MD, PhD, of Toronto General Hospital Research Institute and Princess Margaret Cancer Centre at the University of Toronto, stated in a news release. “Despite advances in treatment, there remains a need for additional therapeutic options for patients with advanced HCC… the FDA’s continued review represents an important regulatory milestone as the potential role of this investigational combination in HCC continues to be evaluated.”

Supporting Evidence: CARES-310

The applications are supported by findings from CARES-310 (NCT03764293), a global, randomized, open-label, phase 3 trial evaluating rivoceranib plus camrelizumab compared with sorafenib (Nexavar) as first-line treatment for patients with unresectable HCC.² The study enrolled 543 patients, with 272 assigned to the combination arm and 271 assigned to sorafenib.

According to the final overall survival (OS) analysis published in The Lancet Oncology, median OS was 23.8 months (95% CI, 20.6-27.2) with rivoceranib plus camrelizumab compared with 15.2 months (95% CI, 13.2-18.5) with sorafenib, representing a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.52-0.79; P < .0001).³ Median follow-up was 22.1 months and 14.9 months, respectively. The 24-month OS rates were 49.0% with the combination and 36.2% with sorafenib, while 36-month OS rates were 37.7% and 24.8%, respectively.

Median progression-free survival was 5.6 months with the combination compared with 3.7 months with sorafenib (HR, 0.54; 95% CI, 0.44-0.67). Objective response rates were 26.8% and 5.9%, respectively. Safety findings were consistent with the earlier analysis, with no new safety signals identified.

Regulatory Considerations and Clinical Context

The resubmissions address concerns previously raised by the FDA in a complete response letter issued in July 2026. The companies submitted additional information in response to the agency's feedback, with the latest regulatory action following efforts to resolve the previously identified manufacturing issues.

Rivoceranib, also known as apatinib, received approval in China for gastric cancer in October 2014 and in combination with camrelizumab for unresectable or metastatic HCC in January 2023. If approved by the FDA, the regimen would provide another first-line systemic treatment option for US patients with unresectable or metastatic HCC.

FAQs

What is the FDA’s target action date for rivoceranib plus camrelizumab in HCC?

The FDA assigned a Prescription Drug User Fee Act target date of April 9, 2027, for the resubmitted new drug application (NDA) for rivoceranib in combination with camrelizumab as first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC).

What applications are under review?

Elevar Therapeutics resubmitted the NDA for rivoceranib on October 9, 2026. Hengrui Pharma resubmitted the biologics license application for camrelizumab the same day. The FDA will review both through an integrated process for the combination regimen.

What are rivoceranib and camrelizumab?

Rivoceranib, also known as apatinib, is an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI). Camrelizumab is a PD-1 inhibitor.

Why were the applications resubmitted?

The resubmissions respond to concerns the FDA raised in a complete response letter issued in July 2026. The companies submitted additional information in response to the agency’s feedback, following efforts to resolve previously identified manufacturing issues.

What trial supports the applications?

The applications are supported by the global, randomized, open-label, phase 3 CARES-310 trial (NCT03764293), which compared rivoceranib plus camrelizumab with sorafenib (Nexavar) as first-line treatment for unresectable HCC. The study enrolled 543 patients: 272 in the combination arm and 271 in the sorafenib arm.

What were the overall survival results in CARES-310?

In the final analysis, median overall survival (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. This represents a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.52-0.79; P < .0001). The 24-month OS rates were 49.0% vs 36.2%, and the 36-month OS rates were 37.7% vs 24.8%.

How did the combination perform on progression-free survival and response?

Median progression-free survival was 5.6 months with the combination vs 3.7 months with sorafenib (HR, 0.54; 95% CI, 0.44-0.67). Objective response rates were 26.8% vs 5.9%.

Were there new safety concerns?

No. Safety findings were consistent with the earlier analysis, and no new safety signals were identified.

Is the combination approved anywhere?

Yes. In China, rivoceranib plus camrelizumab was approved for unresectable or metastatic HCC in January 2023. Rivoceranib alone was approved there for gastric cancer in October 2014.

What would FDA approval mean for patients?

If approved, the regimen would add another first-line systemic treatment option for US patients with unresectable or metastatic HCC.

REFERENCES

1. Elevar Therapeutics announces FDA PDUFA date for resubmitted new drug application for rivoceranib in combination with camrelizumab for ise as a first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma. News release. Elevar Therapeutics. November 4, 2026. Accessed November 6, 2026. https://tinyurl.com/4yuam8f6

2. A study to evaluate SHR-1210 in combination with apatinib as first-line therapy in patients with advanced HCC. ClinicalTrials.gov. Updated February 6, 2024. Accessed November 6, 2026. https://clinicaltrials.gov/study/NCT03764293

3. 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 Oncol. 2023;402(10408):1133-1146. doi:10.1016/s0140-6736(23)00961-3‌