Rivoceranib Plus Camrelizumab Maintains Frontline Survival Benefit in Unresectable HCC

The combination of rivoceranib and camrelizumab continued to show a significant improvement in overall survival (OS) vs sorafenib (Nexavar) alone as frontline therapy in patients with advanced, unresectable hepatocellular carcinoma (HCC), according to the final analysis of the phase 3 CARES-310 trial (NCT03764293), findings from which will be presented in a poster presentation at the 2024 ASCO Annual Meeting.¹

With an additional 16 months of follow-up from the interim analysis, which was conducted after data cutoff on February 8, 2022, the median OS was 23.8 months (95% CI, 20.6-27.2) with the combination (n = 272) vs 15.2 months (95% CI, 13.2-18.5) with sorafenib (n = 271) alone (HR, 0.64; 95% CI, 0.52-0.79; 1-sided P < .0001). The 24- and 36-month OS rates with the combination were 49.0% and 37.7%, respectively, vs 36.2% and 24.8% with sorafenib, respectively. Comparable OS benefits were observed with the combination across subgroups, irrespective of geographical region, race, and etiology.

“The CARES-310 final OS analysis confirmed statistically superior and clinically meaningful survival improvement with a manageable safety profile for the combination of camrelizumab and rivoceranib as a first-line treatment for patients suffering from unresectable HCC,” Saeho Chong, chief executive officer of Elevar, stated in a news release. “These data confirm that the novel combination therapy represents a clinically differentiated improvement to the standard of care in first-line treatments for unresectable HCC.”

The open-label, international phase 3 CARES-310 trial enrolled 543 patients with unresectable or metastatic HCC who had not received prior systemic therapy. Patients were randomly assigned 1:1 to receive intravenous camrelizumab 190 mg every 2 weeks plus oral rivoceranib 250 mg once daily, or oral sorafenib 400 mg twice daily.

The coprimary end points of the study were OS and progression-free survival (PFS). Secondary end points included objective response rate (ORR) and duration of response (DOR).

The median follow-up for the final analysis was 22.1 months in the combination arm and 14.9 months in the sorafenib arm, at which point 159 (58.5%) and 192 (70.8%) survival events had occurred in the combination and monotherapy arms, respectively. A total of 199 (73.2%) and 209 (77.1%) PFS events also occurred in the combination and monotherapy arms, respectively. Median PFS remained unchanged from the interim analysis, at 5.6 months (95% CI, 5.5-7.4) and 3.7 months (95% CI, 3.1-3.7) in the combination and monotherapy arms, respectively (HR, 0.54; 95% CI, 0.44-0.67; P < .0001).²

The ORR was 26.8% (95% CI, 21.7%-32.5%) with camrelizumab plus rivoceranib vs 5.9% (95% CI, 3.4-9.4) with sorafenib, and the median DOR was 17.5 months (95% CI, 9.3-not reached [NR]) vs 9.2 months (95% CI, 5.3-NR), respectively.

Following the completion of frontline therapy 36% of patients in the combination arm and 42% of those in the sorafenib arm received subsequent targeted therapy; 17% and 36% of patients in the combination and monotherapy arms received immunotherapy, respectively.

Safety data were comparable to those reported in the interim analysis.

“The CARES-310 landmark analysis reported the longest median OS for any treatment in a global phase 3 trial in the unresectable HCC setting,” Ahmed Omar Kaseb, MD, professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, added in the news release. “The combination of camrelizumab and rivoceranib shows distinct promise to advance the standard of care for patients suffering with unresectable HCC.”¹

The FDA had previously accepted for review a new drug application seeking approval of the combination as frontline therapy for patients with unresectable HCC.³

References

1. Elevar Therapeutics reports landmark median overall survival of 23.8 months in first-Line treatment for unresectable hepatocellular carcinoma. News release. Elevar Therapeutics. May 30, 2024. Accessed May 30, 2024. https://elevartherapeutics.com/2024/05/30/elevar-therapeutics-landmark-overall-survival/
2. Vogel A, Chan SL, Ren Z, et al. Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): 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
3. 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 May 30, 2024. 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/