FDA Review Restarts for Rivoceranib/Camrelizumab in Advanced HCC

A new drug application (NDA) and a biologics license application (BLA) have been resubmitted and accepted by the FDA for rivoceranib (formerly apatinib) and camrelizumab (SHR-1210), respectively, for first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC), marking the agency’s third formal review of the combination.¹

According to Elevar Therapeutics, sponsor of the rivoceranib NDA, the FDA will conduct an integrated review of the regimen, treating the agents as a single therapeutic unit. As such, the agency has assigned a Prescription Drug User Fee Act (PDUFA) target action date of July 23, 2026.

The resubmission follows a series of regulatory setbacks and aims to address previous manufacturing-related issues that resulted in complete response letters (CRLs) in May 2024 and March 2025.

“We will continue to work closely with Hengrui [camrelizumab BLA sponsor] to ensure full readiness throughout the FDA review process, including the inspection of relevant manufacturing facilities,” said Dong-Gun Kim, CEO of Elevar Therapeutics, in a news release.¹ “We will also maintain proactive communication with the FDA and remain focused on achieving a successful outcome.”

Clinical Efficacy: The CARES-310 Trial

Supporting data for the applications come from the completed phase 3 CARES-310 trial (NCT03764293), an international, randomized, open-label trial that evaluated the combination of rivoceranib, an oral VEGF tyrosine kinase inhibitor (TKI), and camrelizumab, an anti–PD-1 antibody, against the oral kinase inhibitor sorafenib (Nexavar).² In this trial, a total of 543 adult patients with unresectable or metastatic HCC were randomized 1:1 to receive either camrelizumab (200 mg intravenously every 2 weeks) plus rivoceranib (250 mg orally once daily) or sorafenib (400 mg orally twice daily).³

Final analysis data presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The Lancet Oncology showed clinically meaningful success in both primary end points of overall survival (OS) and progression-free survival (PFS), with consistent benefits across key subgroups. Crucially, the median OS reached 23.8 months (95% CI, 20.6-27.2) in the combination arm vs 15.2 months (95% CI, 13.2-18.5) in the sorafenib arm (HR, 0.64; 95% CI, 0.52-0.79; P <.0001), amounting to a 36% reduction in the risk of death.

Further, the median PFS was significantly prolonged with the combination at 5.6 months (95% CI, 5.5-7.4) compared with 3.7 months (95% CI, 2.8-3.7) with sorafenib (HR, 0.52; 95% CI, 0.41-0.65; P <.0001).

The safety profile was deemed manageable, with the most frequently occurring grade 3 or 4 treatment-related adverse events in the combination arm being hypertension (38%), palmar-plantar erythrodysaesthesia syndrome (12%), increased aspartate aminotransferase (17%), and increased alanine aminotransferase (14%).

A Potential New TKI-Based Combo in Practice

Prior to regulatory approval, several European clinical practice guidelines have included the combination as a first-line treatment option for unresectable HCC, including the 2025 Barcelona Clinic Liver Cancer treatment strategies and the European Society for Medical Oncology (ESMO) guidelines.¹

The addition of an oral TKI-based combination would provide a potential alternative for patients who may not be candidates for current regimens or those for whom a different mechanism of delivery is preferred. The FDA's next assessment of the manufacturing remediations and the robustness of the CARES-310 data will be critical for patients in the US in mid-2026.

REFERENCES

1. 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 February 3, 2026. https://tinyurl.com/2ufee9x4

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 January 30, 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