994MO - The updated report of phase I trial of VG2025, a non-attenuated HSV-1 oncolytic virus expressing IL-12 and IL-15/Rα payloads, in patients with advanced solid tumors

Background

VG2025 is a non-attenuated HSV-1 Oncolytic virus (OV) with the payloads IL-12, IL-15, and IL-15Rα and a carcinoembryonic antigen (CEA) specific promoter for ICP27. Here, we report a first-in-human, open-label study to evaluate the safety and efficacy of VG2025 in patients (pts) with advanced solid tumors that progressed after standard of care, conducted in China.

Methods

3+3 Dose escalation design with 5 dose levels as intratumoral injections on days 1 and 15 of each 28-day cycle and 2 cohorts with multiple injection. The preliminary safety, efficacy (per RECIST v1.1), PK, viral shedding and immune biomarkers were analyzed.

Results

As of April 24, 2024, 23 pts received doses of 1.0x10ˆ8 PFU (d1 only) (n=3), 2.0x10ˆ8 PFU (n=3), 4.0x10ˆ8 PFU (n=3), 6.0x10ˆ8 PFU (n=5), 8.0x10ˆ8 PFU (n=3), 2.0 x10ˆ8 PFU on d1, 2, 3 (n=3) and 2.0x10ˆ8 PFU on d1, 2, 3, 15 (n=3) of each cycle. The longest duration of treatment was over 12 mons (1.0-12.0). 13 males and 10 females with a median age of 51.5 (43-73). 56.6% were PD(L)1 refractory, 30.5% had 2 prior lines of therapy, and 65.5% had 3 or more. The mean baseline CEA level was 28.1 (normal: 0.0-5.0 μg/L). Common tumor types included 6 CRC and 4 liver cancer. No DLTs were observed. TRAEs and Gr≥3 TRAEs were 91% and 48.0%, with pyrexia being the most common TRAE. 8 SAEs were reported unrelated to VG2025. No TRAEs led to dose reduction, discontinuation or death. No pts sample was positive for viral shedding. Of 24 evaluable pts, 3 PRs (in 1 ICC, 1 NEC and 1 breast cancer) and 8 SDs were reported. Tumor shrinkage was observed in non-injected lesions, demonstrating an abscopal effects. Nanostring analysis of paired biopsies from the PR pts demonstrated upregulation of integrin signaling pathway, antigen-presenting MHC (HLA-DQA1 and HLA-DRB1) and chemokine receptor (CMKLR1) genes, and also activation of CD8+ T cells. The dose escalation had been completed.

Conclusions

Intratumoral injection of VG2025 monotherapy has demonstrated anti-cancer activity with a well-tolerant safety profile in pts progressed after standard of care therapies, which support further investigation of the efficacy of VG2025 in potential indications such as TNBC, ICC, and duodenal adenocarcinoma.

Clinical trial identification

NCT05477849.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Virogin Biotech Co., Ltd.

Funding

Has not received any funding.

Disclosure

S. Rahimian, A. Qin, Y. Qiu, Q. Tan, R. Zhao: Financial Interests, Personal, Full or part-time Employment: Virogin Biotech (Shanghai) Ltd. All other authors have declared no conflicts of interest.