FDA Accepts NDA for Rivoceranib Plus Camrelizumab in Unresectable HCC

The FDA has accepted for review a new drug application seeking the approval of rivoceranib in combination with camrelizumab as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC).¹

The NDA is supported by data from the phase 3 CARES 310 study (NCT03764293), which showed that rivoceranib plus camrelizumab provided a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared with sorafenib (Nexavar) in the first-line treatment of patients with unresectable HCC.

Treatment with the doublet resulted in a median OS of 22.1 months (95% CI, 19.1-27.2) compared with 15.2 months (95% CI, 13.0-18.5) with sorafenib (HR, 0.62; 95% CI 0.49-0.80; 1-sided P < .0001). Furthermore, the median PFS was 5.6 months (95% CI, 5.5-6.3) and 3.7 months (95% CI, 2.8-3.7) with the combination and sorafenib, respectively (HR, 0.52; 95% CI, 0.41-0.65; 1-sided P < .0001). Additionally, patients treated with the combination achieved a confirmed objective response rate (ORR) of 25.4% (95% CI 20.3%-31.0%) vs 5.9% (95% CI, 3.4%-9.4%) with sorafenib.

The FDA assigned a target action date of May 16, 2024, under the Prescription Drug User Fee Act.

“Rivoceranib plus camrelizumab has demonstrated the potential to improve the lives of those confronted with unresectable HCC carcinoma,” Saeho Chong, chief executive officer of Elevar Therapeutics, stated in a news release. “With the FDA’s acceptance of our new drug application, we are pleased to reach another milestone in the development of this combination therapy. We look forward to working closely with the FDA during this review process and are focused on making the combination commercially available as quickly as possible should we gain approval.”

CARES is a randomized, open-label, international, multicenter, phase 3 that enrolled patients at least 18 years of age with histopathologically or cytologically confirmed advanced HCC who had not received previous systematic treatment for their disease.² Patients needed to have at least 1 measurable lesion per RECIST v1.1 criteria and have Barcelona Clinic Liver Cancer stage B or C disease. They could not be suitable for surgical or local therapy or they must have progressed following surgical and/or local therapy. Other key inclusion criteria included having an ECOG performance status of 0 or 1, Child-Pugh class A disease, and a life expectancy of at least 12 weeks.

Key exclusion criteria included known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma, or lamellar cell carcinoma; another active malignant tumor except HCC within 5 years; moderate-to-severe ascites with clinical symptoms; a history of gastrointestinal hemorrhage within 6 months prior to the start of study treatment; abdominal fistula, gastrointestinal perforation, or intraperitoneal abscess within 6 months prior to the start of study; known genetic or acquired hemorrhage or thrombotic tendency, or thrombosis or a thromboembolic event within 6 months prior to the start of study.

The study enrolled 543 patients who were randomly assigned to receive the combination of rivoceranib and camrelizumab or sorafenib alone.

OS and PFS served as the co-primary end points. Secondary end points included time to progression, ORR, disease control rate, duration of response, and safety.

Rivoceranib plus camrelizumab was approved by China’s National Medical Products Administration as a first-line treatment for patients with liver cancer in February 2023.¹

References

1. Elevar Therapeutics announces FDA acceptance for filing of new drug application for rivoceranib in combination with camrelizumab as a first-line treatment for unresectable hepatocellular carcinoma. News release. Elevar Therapeutics. July 17, 2023. Accessed July 17, 2023. https://elevartherapeutics.com/2023/07/17/elevar-therapeutics-announces-fda-acceptance-for-filing-of-new-drug-application-for-rivoceranib-in-combination-with-camrelizumab-as-a-first-line-treatment-for-unresectable-hepatocellular-carcinoma/
2. A study to evaluate SHR-1210 in combination with apatinib as first-line therapy in patients with advanced HCC. ClinicalTrials.gov. Updated June 22, 2023. Accessed July 17, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03764293