Oncolytic virus VG161 in combination with camrelizumab as second-line therapy in patients with advanced primary hepatocellular carcinoma: A phase Ib/IIa clinical study.

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Background: Advanced hepatocellular carcinoma has a rapid progression and poor prognosis. Although drugs have been approved as standard therapies, they are prone to recurrence and metastasis after treatment and have poor long-term efficacy, and improvement of their survival status has been an important therapeutic goal for advanced hepatocellular carcinoma. In addition to direct tumour lysis, VG161 carries IL-12, IL-15/15Rα, and PDL1B that can synergistically exert anti-tumour immune stimulatory effects. In this study we intended to evaluate the safety and efficacy of VG161 in combination with the PD-1 inhibitor Camrelizumab for the treatment of advanced hepatocellular carcinoma. Methods: This study was a multicentre, open-label, single-arm design Phase Ib/IIa clinical study in two phases. As of 31 December 2024, a total of 16 patients were enrolled. The first phase is a dose-escalation phase that explores safety in two dose levels using a standard 3+3 design. The second phase is a dose-expansion phase that evaluates the safety and efficacy of VG161 in combination with Camrelizumab in the treatment of hepatocellular carcinoma. Administration was 1.0*10^8 PFU of VG161 per dose, once daily, administered by intratumoural injection for 2 or 3 consecutive days on days 1-3 of each cycle; the dose of Camrelizumab was 3 mg/kg, intravenously, once per cycle. Camrelizumab was administered 21 days per cycle, 7 days after the first dose of VG161. Results: The 16 participants were all Asian, of Han Chinese ethnicity, 15 males and 1 female, with a mean age of 55.4 years. There were 1 patients in the second line and 15 patients in the third line and above. All participants had been treated with immune checkpoint inhibitor medication. All 16 participants did not achieve MTD, a total of 16 participants (100%) had at least 1 TEAE, 11 patients (68.8%) had a grade ≥3 TEAE, and the most common grade ≥3 TEAE was a decreased lymphocyte count (43.8%). The most common TEAEs associated with study drug were fever (81.3%), reactive capillary hyperplasia (62.5%), hypoalbuminaemia (62.5%), and anaemia (62.5%). 11 of 16 participants could be assessed for response. After a median follow-up of 7.8 (range 3.2 to 11.9), 2 participants achieved PR and 8 participants achieved SD with an ORR of 18.2%. The median PFS was 6.3 (95% CI 4.1, NA) and the 6-month OS rate was 87.5%. Conclusions: The combination of VG161 and Camrelizumab demonstrated excellent anti-tumour activity with an acceptable safety profile in patients with hepatocellular carcinoma who failed even first-line standard therapy. Administration of VG161 3*10^8 PFU plus Camrelizumab 3 mg/kg per cycle is identified as RP2D. Further clinical studies are ongoing. Clinical trial information: NCT06124001.