Camrelizumab/Rivoceranib Maintains Survival Benefits in uHCC

Human Liver Anatomy: © nerthuz - stock.adobe.com

Camrelizumab (SHR-1210), a PD-1 inhibitor, given in combination with rivoceranib (Apatinib), an oral tyrosine kinase inhibitor, sustained favorable long-term survival results vs sorafenib (Nexavar) when used in the frontline for patients with unresectable hepatocellular carcinoma (uHCC), according to findings from the phase 3 CARES-310 study (NCT03764293).¹

This final analysis comes 16 months after the completion of the interim analysis, which followed the data cutoff date of February 8, 2022. Camrelizumab with rivoceranib led to clinically meaningful survival improvements, with a median overall survival (OS) of 23.8 months (95% CI, 20.6-27.2) vs sorafenib at 15.2 months (95% CI, 13.2-18.5), respectively (HR, 0.64; 95% CI, 0.52-0.79; 1-sided P <.0001). Further, the OS rate with camrelizumab and rivoceranib was 49.0% vs 36.2% with sorafenib at 24 months, and 37.7% vs 24.8% at 36 months.

These OS benefits seen with the camrelizumab/rivoceranib combination were generally consistent across subgroups, regardless of geographical region, race and etiology.

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

The combination also produced a manageable safety profile. These extended follow-up data further confirmed the favorable benefit-to-risk profile of this combination and support its use as a potential new first-line treatment option for uHCC.

Additional findings will be presented at the 2024 American Society of Clinical Oncology Annual Meeting on June 1.

“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 hepatocellular carcinoma,” said Saeho Chong, chief executive officer of Elevar, in the press release. “These data confirm that the novel combination therapy represents a clinically differentiated improvement to the standard of care in first-line treatments for uHCC.”

About the Phase 3 CARES-301 Trial

CARES 310 is a randomized, open-label, international, phase 3 study. A total of 543 patients with unresectable or metastatic HCC were included in the trial if they had not received prior systemic therapy. The study was conducted at 95 study sites across 13 countries/regions.²

Enrolled patients were those with histopathologically or cytologically confirmed advanced HCC who had no previous systematic treatment for 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.

Once enrolled, patients were randomly assigned in a 1:1 fashion and given either the combination of camrelizumab and rivoceranib or sorafenib. Camrelizumab was administered 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, and sorafenib was administered at a dose of 400 mg orally twice daily.

The co-primary end points of the study included OS and progression-free survival (PFS). Secondary end points consisted of objective response rate and duration of response.

The combination previously demonstrated a median OS of 22.1 months (95% CI, 19.1-27.2) vs 15.2 months (95% CI, 13.0-18.5) with sorafenib, and median PFS rates were 5.6 months (95% CI, 5.5-6.3) compared with 3.7 months (95% CI, 2.8-3.7; HR, 0.52; 95% CI, 0.41-0.65; P <.0001).³ Additionally, the confirmed ORR for camrelizumab plus rivoceranib was 25.4% (95% CI, 20.3-31.0) vs 5.9% (95% CI, 3.4-9.4) with sorafenib.

For safety, 99% of patients treated in the camrelizumab/rivoceranib arm had at least 1 any-grade adverse event (AE), as well as 99% of patients given sorafenib.⁴ Grade 3 or higher AEs were seen in 88% of patients in the combination arm vs 68% of patients in the sorafenib arm, respectively.

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, Inc. May 30, 2024. Accessed May 30, 2024. https://tinyurl.com/bddn45mw

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 May 30, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03764293

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, Inc. July 17, 2023. Accessed May 30, 2024. https://tinyurl.com/h5fy64xt

4. Qin S, Chan SL, Gu S, et al. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. Published online July 24, 2023. doi:10.1016/S0140-6736(23)00961-3