VG161 / ViroGin Biotech, CNBG-Virogin Biotech - LARVOL DELTA

Oncolytic virus VG161 in combination with camrelizumab as second-line therapy in patients with advanced primary hepatocellular carcinoma: A phase Ib/IIa clinical study. (ASCO 2025) - P1/2 | "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 • Combination therapy • Metastases • Oncolytic virus • P1/2 data • Anemia • Hematological Disorders • Hepatocellular Cancer • Oncology • Solid Tumor • IL12A • IL15

Oncolytic virus VG161 in refractory hepatocellular carcinoma. (PubMed, Nature) - P1 | "This provides a new avenue for treatment and advances the field of oncolytic virus-based immunotherapies. ClinicalTrials.gov registration: NCT04806464 ."

Journal • Hepatocellular Cancer • Hepatology • Herpes Simplex • Liver Cancer • Oncology • Solid Tumor • IL12A • IL15

Clinical Study of VG161 in Subjects with Advanced Primary Liver Cancer (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd. | Trial completion date: Dec 2022 ➔ Dec 2024

Metastases • Trial completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Sinopharm's oncolytic virus VG161 receives breakthrough therapeutic designation [Google translation] (Sina Corp) - "Cailianshe reported on September 6 that the breakthrough therapy application for oncolytic virus VG161 submitted by Sinopharm's Sinopharm passed the review of the Center for Drug Evaluation (CDE) of the National Medical Products Administration and was officially included in the list of breakthrough therapies for the treatment of patients with advanced hepatocellular carcinoma (HCC) who have failed standard treatment, becoming the first oncolytic virus product in this disease field to receive CDE breakthrough therapy designation."

Breakthrough therapy • Hepatocellular Cancer

Clinical outcomes from a phase I clinical trial of a novel oncolytic virus VG161 in patients with hepatocellular carcinoma (HCC) refractory after 2 prior lines of therapy including checkpoint inhibitors (CPI). (ASCO 2024) - P1 | "VG161 was well tolerated and demonstrated comparable ORR and DCR with other CPIs data in 2L HCC. VG161 also prolonged survival in a subgroup of patients identified by prior treatment or gene signature, supporting further studies with enrichment of patients who may benefit from the treatment. The implications of pre/post VG161 CPI treatment on OS underscore a combination strategy for improving outcomes."

Checkpoint inhibition • Clinical • Clinical data • IO biomarker • Oncolytic virus • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • IL12A • IL15

An Open-Label, Multiple-Center, Phase IIa/IIb Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of VG161 as Monotherapy and in Combination With Nivolumab for Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - P2 | N=97 | Recruiting | Sponsor: Virogin Biotech Canada Ltd | Phase classification: P2a/2b ➔ P2 | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Oct 2025

Combination therapy • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • IDH1 • MSI

Clinical Study of VG161 Combined With Camrelizumab in Patients With Advanced Primary Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.

Metastases • New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • IL6 • NCAM1

Clinical Study of VG161 in the Treatment of Advanced Bone and Soft Tissue Sarcoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.

Metastases • New P2 trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

A clinical trial to evaluate the safety, tolerability and preliminary efficacy of VG161 in combination with Nivolumab in patients with advanced pancreatic cancer (SITC 2023) - P1/2 | "Moreover, patients were also more sensitive to subsequent immunosuppressive therapy. Conclusions VG161 can significantly improve the immune microenvironment and provide favorable conditions for the combination of nivolumab."

Clinical • Combination therapy • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • IL12A • IL15

A first-in-human study of VG161 in participants with advanced malignant tumours that have not responded to conventional therapies. (ANZCTR) - P1 | N=36 | Terminated | Sponsor: Virogin Biotech Australia Pty. Ltd. | Recruiting ➔ Terminated

Metastases • Trial termination • Oncology • Solid Tumor

Clinical Study of VG161 Combined With Nivolumab Injection in Patients With Advanced Metastatic Gastric Cancer (clinicaltrials.gov) - P1/2 | N=43 | Recruiting | Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.

Metastases • New P1/2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IL6 • NCAM1 • PD-L1

An Open-Label, Multiple-Center, Phase IIa/IIb Clinical Trial to Evaluate the Efficacy, Safety and Tolerability of VG161 as Monotherapy and in Combination With Nivolumab for Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - P2a/2b | N=97 | Recruiting | Sponsor: Virogin Biotech Canada Ltd | Not yet recruiting ➔ Recruiting | N=41 ➔ 97

Combination therapy • Enrollment change • Enrollment open • Monotherapy • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD4 • CD69 • CD8 • IDH1 • IL12A • IL15 • IL6 • MSI • NCAM1 • PD-1 • PD-L1 • TNFA

Combination of novel oncolytic herpesvirus with paclitaxel as an efficient strategy for breast cancer therapy. (PubMed, J Med Virol) - "The combination of PTX and VG161 is effective for repressing BC growth by inducing proinflammatory changes in the tumor microenvironment and reducing BC pulmonary metastasis. These data will provide a new strategy and valuable insight for oncolytic virus therapy applications in primary solid or metastatic BC tumors."

Journal • Oncolytic virus • Breast Cancer • Herpes Simplex • Oncology • Solid Tumor • CD4 • CD8 • IFNG

Pre-Existing HSV-1 Immunity Enhances Anticancer Efficacy of a Novel Immune-Stimulating Oncolytic Virus. (PubMed, Viruses) - "Moreover, VG161 efficacy in HLA-matched CD34+ humanized intrahepatic cholangiocarcinoma (ICC) patient-derived xenograft (PDX) models was also tested in multicycle treatment and was compared to standard chemotherapy for this type of cancer (gemcitabine). In conclusion, the anticancer efficacy of VG161 can be enhanced by pre-immunization with HSV-1 and multicycle administration when the virus is given intratumorally, indicating that pre-existing antiviral immunity might enhance OV-induced antitumor immunity. Our results suggest potential clinical benefits of HSV-1-based OV therapy in HSV-1-seropositive patients and multicycle administration of VG161 for long-term maintenance treatment."

IO biomarker • Journal • Oncolytic virus • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Herpes Simplex • Oncology • Solid Tumor • CD34

An Open-Label Phase I Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of VG161 in Patients with Advanced Primary Liver Cancer (SITC 2022) - P1 | "Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."

Clinical • P1 data • PK/PD data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CD69 • CD8 • IL12A • IL15

VG161 activates systemic anti-tumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes. (PubMed, J Med Virol) - "In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong anti-tumor potential. The more robusting anti-tumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials."

Journal • Oncolytic virus • Preclinical • Gastrointestinal Cancer • Hepatology • Herpes Simplex • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • Solid Tumor • CD8

Clinical Study of VG161 in Combination With Nivolumab in Subjects With Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=51 | Recruiting | Sponsor: Zhejiang University | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Cancer antigen 19-9 • CD19 • CD4 • CD8 • IFNG • IL6 • NCAM1 • PD-1 • TNFA

Newly Developed Oncolytic Herpes Simplex Viruses Expressing Multiple Immunomodulatory Transgenes Effectively Target AML Cells (ASH 2021) - "Moreover, PD-L1 expression was highly increased in AML patient cells when cultured with VG161 as compared to VG160 (2.7-fold) and this was further enhanced when co-cultured with VG161 and PBMC. Thus, we have demonstrated that newly developed oHSVs engineered with several immunomodulatory transgenes effectively target primitive AML cells, suggesting a potential treatment strategy for AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Herpes Simplex • Immune Modulation • Infectious Disease • Inflammation • Leukemia • Oncology • CASP3 • CASP8 • IL12A • IL15 • PD-1 • TNFRSF18

Clinical Study of VG161 in Combination With Nivolumab in Subjects With Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2; N=51; Not yet recruiting; Sponsor: Zhejiang University

Clinical • Combination therapy • New P1/2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Cancer antigen 19-9 • CD19 • CD4 • CD8 • IFNG • IL6 • NCAM1 • PD-1 • TNFA

[VIRTUAL] Initial results from a first in human trial incorporating accelerated dose titration of a novel immune stimulating oncolytic virus - VG161. (ASCO 2021) - "Single IT injection of VG161 up to 2×108 PFU/subject is safe and well tolerated, with no unexpected viral spread or shedding . The post-dose increase in cytokines and the transit regression of non-injected lesions imply the activation of anti-cancer immunity induced by VG161 . This holds potential for further dose optimization to assess the safety and efficacy."

IO biomarker • Oncolytic virus • P1 data • Oncology • Solid Tumor • IFNG • IL12A • IL15 • PD-L1 • TNFA

[VIRTUAL] Pre-existing HSV-1 Immunity enhances anti-cancer efficacy of a novel immune stimulating oncolytic virus - VG161 (AACR 2021) - "When the tumor reached 100-150 mm3, animals were divided into 4 groups (10 mice/group): vehicle control, positive control (oxaliplatin 5 mg/kg and gemcitabine 100 mg/kg), and 2 groups treated with VG161 at high dose (7.75×106 PFU) or low dose (3.10×105 PFU). The median time for 3-fold increase of tumor size is 41.5 days (95%CI: 32-58) in the vehicle control, 74 days (95%CI: 51-undefined) in high dose group, and not reached in low dose group (p<0.01). Repeated treatment (2-3 cycles) increased the anti-cancer efficacy of VG161.The anti-cancer efficacy of VG161 can be enhanced by pre-immunization of HSV-1 or multicycle administration when the virus is given by IT, suggesting potential clinical benefits of HSV-1 based OV therapy in HSV sero-positive patients and multicycle administration of VG161 for long term maintenance treatment."

Clinical • Oncolytic virus • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CD34 • IL12A • IL15

Clinical Study of VG161 in Subjects With Advanced Malignant Solid Tumors (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • IO biomarker • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL15 • NECTIN2 • PD-1 • PD-L1

Clinical Study of VG161 in Subjects With Advanced Primary Liver Cancer (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CD4 • IL15 • PD-1 • PD-L1

Clinical Study of VG161 in Subjects With Advanced Primary Liver Cancer (clinicaltrials.gov) - P1; N=44; Not yet recruiting; Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.

Clinical • New P1 trial • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CD4 • IL15 • PD-1 • PD-L1

Clinical Study of VG161 in Subjects With Advanced Malignant Solid Tumors (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.

Clinical • IO biomarker • New P1 trial • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL15 • NECTIN2 • PD-1 • PD-L1