Abstract Background: RZ-001 is an investigational targeted gene therapy, based on adenovirus-delivered, ribozyme-mediated RNA replacement of tumor-specific hTERT RNA with a new transcript expressing the suicide gene herpes simplex virus thymidine kinase (HSVtk). RZ-001 is administered via intratumoral injection in combination with oral VGCV, which is metabolized and activated by HSVtk resulting in inhibition of DNA replication and induction of apoptosis in HCC cells. The antitumor effect is further enhanced by the bystander effect and increased T-cell infiltration. Methods: The ongoing study enrolls patients with unresectable HCC (BCLC B or C) with hTERT (+) tumors who were refractory or unsuitable for TACE and had no prior systemic therapy. Patients received single dose of RZ-001 (Day1), followed by VGCV (900 mg BID, Days 2-22), atezolizumab and bevacizumab in every 3 weeks. 15 subjects are enrolled in each of 3 cohorts. After initial safety evaluation, cohort expansion and dose escalation proceeded in the absence of dose-limiting toxicities (DLT). Tumor response was assessed by RECIST v1. 1 and mRECIST, with exploratory immunologic biomarker analyses. Results: As of cutoff, 13 patients were enrolled. No DLT was observed. No grade 4-5 adverse events or grade ≥3 immune-related adverse events were reported. The best overall response rate of CR/PR was 54% (7/13) by mRECIST and increased to 75% (6/8) among patients treated for ≥ 12 weeks. Two patients achieved CR at Week 6; one maintained a durable CR through Week 30, while the other maintained CR until Week18 before discontinuation due to proteinuria, with objective response confirmed. In addition, one patient achieved a confirmed CR after converting from PR at Week 24, prior to later disease progression. The disease control rate (CR/PR/SD) at the first post-baseline tumor assessment was 92% (12/13). Conclusions: RZ-001 combined with VGCV, atezolizumab and bevacizumab was well tolerated and showed promising early efficacy in hTERT-positive HCC, suggesting a synergistic effect that may enhance antitumor responses when combined with a first-line standard therapy of Atezolizumab and Bevacizumab. Further enrollment is ongoing. Citation Format: Yong Han Paik, Yoon Jun Kim, Won Young Tak, Do Young Kim, Jeong Won Jang, Hyun Woong Lee, Young Sun Lee, Won Son, Ki Tae Yoon, Seong-Wook Lee, Sung Woo Hong, Eunjee Jeon. A phase 1b/2a, open-label, multicenter, randomized, dose escalation study evaluating the safety, tolerability and efficacy of RZ-001 in combination with valganciclovir (VGCV) and atezolizumab/bevacizumab in subjects with hepatocellular carcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT030.
Paik et al. (Fri,) studied this question.