FDA Accepts NDA Resubmission of Rivoceranib and Camrelizumab in HCC

• The FDA has accepted the resubmission of a new drug application (NDA) for the combination of rivoceranib (Apatinib) and camrelizumab (SHR-1210) as a first-line systemic treatment in unresectable or metastatic hepatocellular carcinoma (uHCC).
• Rivoceranib is an oral VEGF tyrosine kinase inhibitor (TKI), and camrelizumab is a PD-1 inhibitor.
• The Prescription Drug User Fee Act (PDUFA) target action date has been set for March 20, 2025.

The resubmission of the NDA for rivoceranib, an oral VEGF TKI, in combination with camrelizumab, a PD-1 inhibitor, has been accepted by the FDA as a potential first-line systemic treatment for patients with uHCC.¹

In the resubmission, data from the final analysis of the phase 3 CARES-310 study (NCT03764293) that were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting were included. In the trial, the median overall survival (mOS) was 23.8 months with the combination vs 15.2 months (95% CI, 13.2-18.5) with sorafenib (Nexavar; HR, 0.64; 95% CI, 0.52-0.79; 1-sided P <.0001). This marks the longest mOS for any treatment in a global phase 3 trial in this patient population.

The efficacy results were generally unchanging across all patient subgroups, suggesting the combination's potential for the treatment of uHCC. Consistent efficacy was also observed among patients with both viral and nonviral etiologies.

“We believe rivoceranib plus camrelizumab has the potential to change the clinical practice in the first-line setting for patients with advanced liver cancer. The results of the pivotal CARES-310 trial demonstrated significant improvements in overall survival, with a very manageable safety profile compared with currently approved uHCC therapies. Elevar is committed to working with the FDA to bring this combination to market for patients and healthcare providers,” said Chris Galloway, MD, senior vice president of clinical and medical affairs at Elevar Therapeutics, in a press release.

A PDUFA target action date of March 20, 2025, has been assigned.

Prior Data From the CARES-310 Study

CARES-310 was an international, randomized, open-label, phase 3 trial evaluating the combination of rivoceranib and camrelizumab in uHCC at 95 study sites across 13 countries/regions.² There were 543 patients with unresectable or metastatic HCC included in the trial if they had not received prior systemic therapy.

Patients were required to have histopathologically or cytologically confirmed advanced HCC, at least 1 measurable lesion, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ function. Following enrollment, patients were randomly assigned in a 1:1 fashion to receive camrelizumab via intravenous infusion at a dose of 190 mg every 2 weeks along with oral rivoceranib at a dose of 250 mg given once daily or sorafenib at a dose of 400 mg orally twice daily.

OS and progression-free survival (PFS) served as the coprimary end points of the study. Secondary end points were objective response rate and duration of response.

In the primary analysis with a data cutoff date of May 10, 2021, and the interim analysis with a data cutoff date of February 8, 2022, significant improvements in PFS were seen with the combination when compared with sorafenib.¹

In the final analysis of the phase 3 study, the combination of camrelizumab and rivoceranib led to clinically meaningful survival improvements. The OS rate with the camrelizumab/rivoceranib combination was 49.0% vs 36.2% with sorafenib at 24 months, and 37.7% vs 24.8% at 36 months. With camrelizumab/rivoceranib, the OS benefits were generally consistent across subgroups, regardless of geographical region, race, and etiology.

After prolonged follow-up, there were also benefits observed for PFS, objective response rate, and duration of response with the experimental combination.

For safety, no new signals were noted, and the combination of camrelizumab with rivoceranib continued to demonstrate clinically meaningful improvement in survival vs sorafenib in the final analysis.

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, Inc. October 21, 2024. Accessed October 21, 2024. https://tinyurl.com/mp9tkz63

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 October 21, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03764293