Developers Resubmit NDA for Camrelizumab Combo in Unresectable Liver Cancer

Supporting data for the resubmitted NDA came from the phase 3 CARES-310 trial (NCT03764293) assessing treatment with camrelizumab/rivoceranib vs sorafenib among patients with unresectable HCC.

A new drug application (NDA) for frontline camrelizumab plus rivoceranib in unresectable hepatocellular carcinoma (HCC) has been resubmitted to the FDA, according to a press release from the developers, Elevar Therapeutics, Inc.¹

The developers’ resubmission of the NDA follows receipt of a complete response letter (CRL) from the FDA for camrelizumab/rivoceranib in May 2024.² At the time, the regulatory agency noted manufacturing deficiencies at the Hengrui Pharma facility—the site where camrelizumab is produced—as well as incomplete Bioresearch Monitoring (BIMO) clinical inspections based on agency travel restrictions. The CRL did not highlight any problems associated with the data supporting the clinical use of the combination therapy or the manufacturing facility for rivoceranib.

At a Type A meeting hosted in July 2024, the regulatory agency confirmed that developers had sufficiently responded to the issues related to the Hengrui facility. Following this meeting, developers were eligible to resubmit the NDA for camrelizumab/rivoceranib without further delay, with full BIMO inspections taking place thereafter.

“Elevar’s timely resubmission of the NDA for the combination of camrelizumab and rivoceranib marks a critical milestone in our mission to bring a novel combination therapy for [patients with unresectable HCC] and healthcare providers. HCC remains an area of significant unmet medical need,” Saeho Chong, PhD, chief executive officer at Elevar Therapeutics, said in the press release.¹ “We are eager to work with the FDA in the coming months as we focus on the commercialization of our combination therapy.”

Supporting data for the resubmitted NDA came from the phase 3 CARES-310 trial (NCT03764293) assessing treatment with camrelizumab/rivoceranib vs sorafenib (Nexavar) among patients with unresectable HCC. Investigators presented updated findings from the CARES-310 trial in a poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.³

Data showed a median overall survival (OS) of 23.8 months (95% CI, 20.6-27.2) with the camrelizumab combination and 15.2 months (95% CI, 13.2-18.5) with sorafenib monotherapy (HR, 0.64; 95% CI, 0.52-0.79; P <.0001). In each respective arm, the OS rates were 76.6% vs 60.9% at 12 months, 49.0% vs 32.6% at 24 months, and 37.7% vs 24.8% at 36 months. Additionally, an OS benefit with camrelizumab-based treatment extended to most patient subgroups based on characteristics such as geographical region and race.

Camrelizumab/rivoceranib yielded a median progression-free survival (PFS) of 5.6 months (95% CI, 5.5-7.4) compared with 3.7 months (95% CI, 3.1-3.7) in the sorafenib arm (HR, 0.54; 95% CI, 0.44-0.67; P <.0001). The objective response rate (ORR) in each respective arm was 26.8% (95% CI, 21.7%-32.5%) vs 5.9% (95% CI, 3.4%-9.4%), and the median duration of response (DOR) was 17.5 months (95% CI, 9.3-not reached [NR]) vs 9.2 months (95% CI, 5.3-NR), respectively.

Any-grade treatment-related adverse effects (TRAEs) in the camrelizumab/rivoceranib and sorafenib arms included hypertension (69.5% vs 43.5%), aspartate aminotransferase increases (54.5% vs 37.5%), proteinuria (49.6% vs 27.1%), and alanine aminotransferase increases (47.4% vs 30.1%), respectively. Overall, investigators observed no new safety signals at the time of this analysis.

In the global, open-label CARES-310 study, 543 patients were randomly assigned 1:1 to receive camrelizumab at 200 mg intravenously every 2 weeks plus rivoceranib at 250 mg orally once a day (n = 272) or sorafenib at 400 mg orally twice a day (n = 271).

The trial’s primary end points were PFS and OS. ORR was a key secondary end point. Patients with unresectable or metastatic HCC, Barcelona Clinic Liver Cancer stage B or C disease, no prior systemic therapy, an ECOG performance status of 0 or 1, Child-Pugh A disease, and 1 or more measurable lesions per RECIST v1.1 criteria were eligible for enrollment on the trial.

References

1. Elevar Therapeutics resubmits new drug application to FDA for combination of camrelizumab plus rivoceranib as first-line treatment option for unresectable hepatocellular carcinoma boosted by CARES-310 leading overall survival analysis. News release. Elevar Therapeutics, Inc. September 23, 2024. Accessed September 24, 2024. https://tinyurl.com/mtsxc5c5
2. Announcement on receipt of complete response letter regarding camrelizumab for injection. News release. Jiangsu Hengrui Pharmaceuticals Co., Ltd. May 17, 2024. Accessed September 24, 2024. https://tinyurl.com/3kdz97k9
3. Vogel A, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma: final overall survival analysis of the phase 3 CARES-310 study. J Clin Oncol. 2024;42(suppl 16):4110. doi:10.1200/JCO.2024.42.16_suppl.4110