FDA Sets PDUFA Date for Rivoceranib/Camrelizumab Resubmission After Third CRL in Unresectable HCC

The FDA has acknowledged the receipt of a resubmission of a new drug application (NDA) for rivoceranib in combination with camrelizumab as first-line systemic treatment for unresectable or metastatic hepatocellular carcinoma (HCC), according to a news release from Elevar Therapeutics.¹ The agency assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 9, 2027.

The resubmission follows 3 complete response letters (CRLs) the combination has received since 2024. The FDA will review the NDA together with Jiangsu Hengrui Pharmaceuticals’ resubmitted biologics license application (BLA) for camrelizumab under an integrated review.

“The results from the CARES-310 study [NCT03764293] support our continued evaluation of the combination of camrelizumab and rivoceranib as a potential first-line therapy to improve outcomes for patients facing limited treatment options in unresectable hepatocellular carcinoma, which we continue to keep top of mind while navigating the regulatory landscape,” said Dong-Gun Kim, chief executive officer of Elevar Therapeutics.¹ “We are pleased to receive classification of this NDA resubmission, jointly with Hengrui’s BLA resubmission for camrelizumab and will work closely with the FDA as it reviews the applications.”

What is the regulatory history of the rivoceranib/camrelizumab application?

Elevar resubmitted the NDA on October 9, 2026, after the FDA issued the third CRL on July 10, 2026.^1,2 The CRL came ahead of a July 23, 2026, PDUFA date, and was based on deficiencies found during a current good manufacturing practice (cGMP) inspection of a manufacturing site highlighted in the NDA.

Days later, the FDA issued a voluntary action indicated close-out letter for the cGMP inspection of the Jiangsu Hengrui facility in China where rivoceranib is produced. HLB and Elevar said the classification would not directly and negatively affect the FDA’s review of pending applications.³

The FDA’s first CRL for the combination, given in May 2024, cited manufacturing concerns, according to an announcement from Hengrui.⁴ The second CRL, in March 2025, did not specify its deficiencies, according to a news report that cited HLB chairman Jin Yang-gon.⁵

Neither rivoceranib nor camrelizumab is approved in the US.

What data support the application?

The application is supported by the phase 3 CARES-310 trial, which randomly assigned 543 patients with previously untreated unresectable or metastatic HCC 1:1 to camrelizumab (200 mg intravenously every 2 weeks) plus rivoceranib (250 mg orally once daily; n = 272) or sorafenib (Nexavar; 400 mg orally twice daily; n = 271) at 95 sites across 13 countries and regions. The final analysis of the trial was published in The Lancet Oncology.⁶ The coprimary end points were progression-free survival (PFS), assessed by a blinded independent review committee per RECIST 1.1, and overall survival (OS).

At the final analysis (data cutoff, June 14, 2023), 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; one-sided P < .0001), at a median follow-up of 22.1 months and 14.9 months, respectively. 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; one-sided P < .0001), and the objective response rate was 27% vs 6%.

Treatment-related adverse effects of grade 3 or higher occurred in 81% of patients in the combination arm and 54% of patients in the sorafenib arm. The most common were hypertension (38% vs 15%), palmar-plantar erythrodysesthesia syndrome (12% vs 16%), increased aspartate aminotransferase (17% vs 5%), and increased alanine aminotransferase (14% vs 3%). Treatment-related serious adverse effects occurred in 25% vs 7% of patients. One treatment-related death occurred in each arm.

The trial was open label, and most patients were from Asia (83%) and had hepatitis B virus–related disease (76%).

Rivoceranib is an oral VEGF receptor 2 tyrosine kinase inhibitor, and camrelizumab is an anti–PD-1 antibody.

“Hepatocellular carcinoma remains a major cause of cancer-related mortality worldwide,” Arndt Vogel, MD, PhD, said in the release.¹ “Despite advances in treatment, there remains a need for additional therapeutic options for patients with advanced HCC.” Vogel is a scientist in the Division of Gastroenterology and Hepatology at Toronto General Hospital Research Institute, and a medical oncologist at UHN-Princess Margaret Cancer Centre at the University of Toronto in Canada.

References

1. Elevar Therapeutics announces FDA assignment of PDUFA date for rivoceranib and camrelizumab NDA resubmission. News release. Elevar Therapeutics. November 4, 2026. Accessed November 5, 2026. https://tinyurl.com/59h9cey4
2. 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 November 5, 2026. https://tinyurl.com/2jdf9467
3. FDA hurdle cleared for liver cancer drug application: HLB. The Korea Herald. July 15, 2026. Accessed November 5, 2026. https://tinyurl.com/mr24enb3
4. Announcement on receipt of complete response letter regarding camrelizumab for injection. News release. Jiangsu Hengrui Pharmaceuticals. May 17, 2024. Accessed November 5, 2026. https://tinyurl.com/3kdz97k9
5. 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 November 5, 2026. https://tinyurl.com/3jcd2j5m
6. 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