FDA Accepts NDA for Rivoceranib and Camrelizumab in 1L Unresectable HCC

The FDA has accepted a new drug application (NDA) resubmission for the combination of rivoceranib and camrelizumab as a first-line systemic treatment for patients with unresectable hepatocellular carcinoma (HCC), according to a press release from the developer, Elevar Therapeutics.¹ The agency has assigned a Prescription Drug User Fee Act (PDUFA) target action date of July 23, 2026.

Previously, the NDA for this combination in the aforementioned patient population has received 2 complete response letters (CRLs) from the FDA, with the first coming in May 2024 and the second in March 2025.^2,3 The CRL issued by the FDA in May 2024 cited deficiencies related to the FDA’s inspection of the camrelizumab manufacturing facility, and in March 2025, the FDA requested more information on the treatment. The developer noted that the CRL did not identify any concerns regarding the clinical efficacy or safety of the combination therapy or the manufacturing process for rivoceranib.

“We will continue to work closely with Hengrui to ensure full readiness throughout the FDA review process, including the inspection of relevant manufacturing facilities,” stated Dong-Gun Kim, chief executive officer of Elevar Therapeutics, in the press release. “We will also maintain proactive communication with the FDA and remain focused on achieving a successful outcome.”

Clinical Efficacy

The submission is supported by data from the pivotal, global, randomized, open-label phase 3 CARES-310 trial (NCT03764293), which compared the combination of rivoceranib and camrelizumab against the standard of care, sorafenib (Nexavar).⁴ Rivoceranib is a small-molecule tyrosine kinase inhibitor that highly selectively inhibits VEGFR-2, while camrelizumab is a PD-1 blocking antibody. In the study, the combination demonstrated a statistically significant and clinically meaningful improvement in the dual primary end points of overall survival (OS) and progression-free survival (PFS).

According to the trial results, the median OS for patients receiving the combination therapy was 23.8 months (95% CI, 20.6-27.2) compared with 15.2 months (95% CI, 13.2-18.5) for those treated with sorafenib (HR, 0.64; 95% CI, 0.52-0.79; P <.0001). The median PFS also favored the combination arm at 5.6 months (95% CI, 5.5-7.4) vs 3.7 months (95% CI, 3.1-3.7) in the sorafenib arm (HR, 0.54; 95% CI, 0.44-0.67; P <.0001). These survival benefits were consistent across various subgroups, including those defined by etiology and geographical region.

Trial Breakdown

The CARES-310 study enrolled 543 patients who were randomly assigned 1:1 to receive either the combination or sorafenib monotherapy. The treatment regimen for the experimental arm consisted of camrelizumab administered at 200 mg via intravenous infusion every 2 weeks, combined with rivoceranib at 250 mg taken orally once daily. In the comparator arm, patients received sorafenib at 400 mg orally twice daily.

Patient sorting and eligibility required participants to have histologically or cytologically confirmed unresectable or metastatic HCC with no prior systemic therapy. Participants were required to have at least 1 measurable lesion per RECIST v1.1, an ECOG performance status of 0 or 1, and Child-Pugh class A liver function. The primary end points were OS and PFS as assessed by a blinded independent central review, while secondary endpoints included overall response rate, duration of response, and disease control rate.

Safety

Safety findings from the CARES-310 trial indicated that the combination was generally manageable, with a profile consistent with the known toxicities of each agent. The most common grade 3 or 4 treatment-related adverse events (TRAEs) in the combination arm included hypertension (38%), increased aspartate aminotransferase (17%), and increased alanine aminotransferase (13%). Palmar-plantar erythrodysesthesia syndrome was also observed in 12% of patients in the combination group. One patient each experienced treatment-related deaths in the combination regimen group and the sorafenib group, being due to multiple organ dysfunction syndrome, and respiratory failure and circulatory collapse, respectively.

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 2, 2026. https://tinyurl.com/35kfv6nk
2. Announcement on receipt of complete response letter regarding camrelizumab for injection. News release. Jiangsu Hengrui Pharmaceuticals Co Ltd. May 17, 2024. Accessed February 2, 2026. https://tinyurl.com/3kdz97k9
3. Heo JY. HLB, Antengene fail to gain U.S. FDA approval for liver cancer drug combo. Chosun Biz. March 21, 2025. Accessed February 2, 2026. https://tinyurl.com/3jcd2j5m
4. Camrelizumab combined with rivoceranib vs sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet Oncol. 2023;24(7):681-694. doi:10.1016/S1470-2045(23)00257-3
5. A study of camrelizumab (SHR-1210) in combination with rivoceranib (apatinib) as first-line therapy in patients with advanced HCC (CARES-310). ClinicalTrials.gov. Updated January 2026. Accessed February 2, 2026. https://tinyurl.com/ymndkrsp