83P - The updated report of phase I trial of VG2025, a non-attenuated HSV-1 oncolytic virus expressing IL-12 and IL-15/RA 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-15Ra and a Carcinoembryonic Antigen (CEA) specific promoter for ICP27. Here, we reported 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 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. Preliminary safety, efficacy (per RECIST v1.1), PK, viral shedding and the immune biomarkers were analyzed.

Results

The preliminary findings of this study were presented at ASCO 2023, here we present updated results of additional dose levels. As of Aug 8, 2023, 14 pts received doses of 1.0x10ˆ8 PFU (n=3), 2.0x10ˆ8 PFU (n=3), 4.0x10ˆ8 PFU (n=3), and 6.0x10ˆ8 PFU (n=5) of each cycle. The longest duration of treatment was more than 11 cycles and the treatment is still ongoing. There were 11 males and 3 females with a median age of 51.5 (41-74). 57.1% were PD(L)1 refractory, 28.6% had 2 prior lines of therapy, and 64.3% had 3 or more prior lines of therapy. The mean CEA level was 29.1 (normal range of 0-5 μg/L). Tumor types included 4 CRC, 2 Duodenal adenocarcinoma, 2 HCC, 2 Pancreatic cancer, 1 NSCLC, 1 ICC, 1 NEC and 1 Neuroendocrine cancer. No DLTs were observed. The incidence of TRAEs and Gr≥3 TRAEs were 92.9% and 50.0%, with fever being the most common TRAE. 4 pts had 7 SAEs, which were unrelated to VG2025. No TRAEs led to dose reduction or treatment discontinuation. No pts had positive viral shedding. Of 9 evaluable pts, the ORR was 22.2% (with 2 PRs: 1 ICC pt and 1 NEC pt) and the DCR was 77.8%. The PR pts showed meaningful reductions in CEA levels. Tumor shrinkage was also observed in non-injected lesions, demonstrating an abscopal effect. 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 activation of CD8+ T cells.

Conclusions

Monotherapy with VG2025 demonstrated activity with a well-tolerant safety profile in pts with advanced solid tumors that progressed after standard of care therapy.

Clinical trial identification

NCT05477849.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Virogin Biotech Co., Ltd.

Funding

Has not received any funding.

Disclosure

Y. Shen, T. Liang: Financial Interests, Personal, Coordinating PI: Virogin. S. Rahimian, A. Qin, Y. Qiu, Q. Tan, R. Zhao: Financial Interests, Personal, Full or part-time Employment: Virogin. All other authors have declared no conflicts of interest.