Clinical Evaluation of M1-c6v1 Oncolytic Virus Combined with Camrelizumab and Apatinib in Advanced Hepatocellular Carcinoma

Abstract PURPOSE: This study evaluated the safety, tolerability, and preliminary efficacy of M1-c6v1, an oncolytic virus, combined with the immune checkpoint inhibitors (ICIs) camrelizumab and the vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib in advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This single-arm, investigator-initiated, open-label clinical trial enrolled patients with advanced HCC (NCT04665362). Patients received M1-c6v1 (1×10⁹ CCID50) intravenously for 5 days every 28 days, camrelizumab (200 mg) intravenously biweekly, and apatinib (250 mg) orally daily. Treatment continued for up to 1 year or until disease progression, intolerability, or withdrawal. Primary endpoints were safety and tolerability, while secondary endpoints assessed efficacy based on tumor response, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirteen patients were enrolled, with 84.6% having hepatitis B virus (HBV)-related HCC and 76.9% presenting with tumors >10 cm. The treatment was well-tolerated, with 92.15% of adverse events (AEs) being grade 1 or 2. The most common AEs included influenza-like symptoms and transient cytopenia. No viral shedding was detected in all secretions and excretions collected from subjects. In 10 patients evaluable for efficacy, the overall response rate (ORR) was 70% (7/10), with 7 partial responses (PR) according to mRECIST. The median OS and PFS was 15.4 and 8.9 months respectively. CONCLUSION: The combination of M1-c6v1 with camrelizumab and apatinib demonstrates an acceptable safety profile and promising efficacy in advanced HCC.