Rivoceranib Plus Camrelizumab Shows Promise in First-Line HCC Treatment
Key Insights
The CARES-310 trial demonstrated that rivoceranib plus camrelizumab significantly improved overall survival in patients with unresectable or metastatic hepatocellular carcinoma (search) (HCC (search)).
Patients receiving the combination therapy had a median overall survival of 23.8 months, compared to 15.2 months for those treated with sorafenib.
The FDA is reviewing the new drug application (NDA) for the rivoceranib and camrelizumab combination, with potential approval expected following resolution of manufacturing issues.
The combination of rivoceranib and camrelizumab has emerged as a promising first-line treatment for patients with unresectable or metastatic hepatocellular carcinoma (search) (HCC (search)), according to data from the phase 3 CARES-310 trial. The study's findings suggest a significant improvement in overall survival compared to the current standard treatment, sorafenib.
The CARES-310 trial, a phase 3 study, enrolled 543 previously untreated patients with unresectable or metastatic HCC (search). Participants were randomized to receive either the combination therapy of rivoceranib and camrelizumab or sorafenib, a standard first-line TKI. Updated data presented at the 2024 ASCO Annual Meeting revealed a median overall survival (OS) of 23.8 months (95% CI, 20.6-27.2) in the combination arm, compared to 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).
Regulatory Status and Manufacturing
The FDA accepted the resubmission of the new drug application (NDA) for the VEGF (search) TKI and PD-1 (search) inhibitor combination in October 2024. An initial NDA submission faced a complete response letter (CRL) from the FDA in May 2024 due to deficiencies at the Hengrui Pharma facility, where camrelizumab is manufactured, and incomplete bioresearch monitoring inspections resulting from FDA travel restrictions. Dr. Richard Kim, chief of Medical Gastrointestinal Oncology at Moffitt Cancer Center, anticipates potential FDA approval next year once these manufacturing issues are resolved.
Safety and Tolerability
While the combination therapy demonstrated significant efficacy, it also presented toxicity concerns. Patients receiving rivoceranib plus camrelizumab experienced a higher incidence of skin reactions and fatigue compared to those treated with sorafenib. These adverse events may require careful management and monitoring.
Considerations for Generalizability
It is important to note that the CARES-310 trial was primarily conducted in Asia, with a majority of participants having hepatitis B-related HCC (search). This raises questions about the generalizability of the findings to Western patient populations, where the etiology of HCC may differ. Further studies may be needed to confirm the efficacy and safety of this combination in diverse populations.
Despite these limitations, the CARES-310 trial provides compelling evidence for the potential of rivoceranib plus camrelizumab as a new first-line treatment option for HCC (search). With anticipated FDA approval pending resolution of manufacturing issues, this combination could offer a valuable alternative for managing this challenging cancer.