Dr Kim on the CARES-310 Study of Rivoceranib Plus Camrelizumab in First-Line HCC

"Clearly [CARES-310] was a positive study… once the manufacturing issue is resolved, I believe that this regimen will [be] approved next year, [potentially] giving us more options to manage first-line HCC."

Richard Kim, MD, chief, Medical Gastrointestinal Oncology, senior member, Gastrointestinal Oncology Department, Moffitt Cancer Center; professor, oncology, University of South Florida College of Medicine, discusses the phase 3 CARES-310 trial (NCT03764293) evaluating rivoceranib plus camrelizumab as a first-line treatment for patients with unresectable or metastatic hepatocellular carcinoma (HCC).

In October, 2024, the FDA accepted the resubmission of the new drug application (NDA) for the VEGF TKI and PD-1 inhibitor combination for the treatment of patients within this population. The inital NDA submission for this combination was met with a complete response letter (CRL) from the FDA in May 2024, which cited deficiencies at the Hengrui Pharma facility where camrelizumab is manufactured, along with incomplete bioresearch monitoring inspections resulting from FDA travel restrictions.

The latest NDA submission was backed by data from CARES-310 trial, which enrolled 543 previously untreated patients with unresectable or metastatic HCC, Kim says. In this trial, patients were randomly assigned to receive the combination therapy or sorafenib (Nexavar) as the standard first-line TKI, Kim details.

Updated data from CARES-310 were presented at the 2024 ASCO Annual Meeting and showed improvements in survival and response rates with the combination vs sorafenib, Kim reported. The median overall survival (OS) of 23.8 months (95% CI, 20.6-27.2) with the combination compared with 15.2 months (95% CI, 13.2-18.5) in the sorafenib arm (HR, 0.64; 95% CI, 0.52-0.79; 1-sided P < .0001).

However, the combination therapy does present toxicity concerns, with a higher incidence of skin reactions and fatigue due to the addition of a TKI, Kim notes. Additionally, the trial was primarily conducted in Asia, Kim says, explaining that the predominance of Asian patients raises questions about generalizability, as most participants had hepatitis B-related HCC, differing from Western patient populations. Despite these limitations, FDA approval is anticipated once manufacturing issues are resolved, potentially offering another first-line treatment option for HCC next year, Kim concludes.