Abstract 83P
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.
Resources from the same session
519P - Final results and subgroup analysis of ORIENTAL: A phase IIIB study of durvalumab plus platinum-etoposide in first-line treatment of Chinese patients with extensive-stage small-cell lung cancer (ES-SCLC)
Presenter: Ying Cheng
Session: Poster Display
Resources:
Abstract
520P - Role of atezolizumab in controlling CNS progression in ES-SCLC
Presenter: Yoon Namgung
Session: Poster Display
Resources:
Abstract
521P - Camrelizumab combined with chemotherapy and apatinib as first-line therapy for extensive-stage small cell lung cancer: A phase II, single-arm, exploratory research
Presenter: Yanbin Zhao
Session: Poster Display
Resources:
Abstract
522P - Durvalumab plus etoposide and carboplatin for extensive-stage small cell lung cancer with mild idiopathic interstitial pneumonia
Presenter: Ichiro Nakachi
Session: Poster Display
Resources:
Abstract
523P - Camrelizumab plus apatinib as maintenance treatment in patients with extensive-stage small cell lung cancer who were responding or stable after standard first-line chemotherapy (CAMERA): Results from a single-arm, phase II trial
Presenter: Qi Wang
Session: Poster Display
Resources:
Abstract
524P - Treatment pattern and overall survival by lines of therapy among patients with advanced small cell lung cancer in Taiwan
Presenter: Kelly Huang
Session: Poster Display
Resources:
Abstract
525P - Development of diagnostic prediction score for malignant pleural effusion in lung cancer: MPE-Lung score
Presenter: Chaichana Chantharakhit
Session: Poster Display
Resources:
Abstract
526P - Burden and trends of tracheal, bronchus, and lung (TBL) cancer in Southeast Asia, East Asia, and Oceania from 1990-2019, and its projection of deaths to 2040: A benchmarking analysis
Presenter: Monika Chhayani
Session: Poster Display
Resources:
Abstract
527P - Efficacy of intraventricular chemotherapy with pemetrexed for leptomeningeal metastasis from lung adenocarcinoma: A retrospective study
Presenter: Fang Cun
Session: Poster Display
Resources:
Abstract
528P - Socioeconomic determinants of access to standard-of-care treatments in advanced and metastatic NSCLC in Hong Kong: A territory-wide study
Presenter: Ka Man Cheung
Session: Poster Display
Resources:
Abstract