Delving into the Latest Updates on Recombinant Human IL12/15-PDL1B Herpes simplex type I oncolytic virus(Vero cell)(Virogin) with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

Recombinant Human IL12/15-PDL1B Herpes Simplex Type I Oncolytic Virus, recombinant human IL12/15-PDL1B HSV-1 oncolytic virus Injection, 重组人IL12/15-PDL1B单纯疱疹I型溶瘤病毒

+ [3]

Target

IL-12R x IL-15Rα x PDL1

Mechanism

IL-12R stimulants(Interleukin-12 receptor stimulants), IL-15Rα agonists(Interleukin-15 receptor subunit alpha agonists), PDL1 inhibitors(Programmed death-ligand 1 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication

Intrahepatic CholangiocarcinomaOsteosarcomaBile Duct Neoplasms+ [8]

Inactive Indication-

Originator Organization

Virogin Biotech Ltd.Startup

Active Organization

CNBG-Virogin Biotech (Shanghai) Ltd.

Virogin Biotech Ltd.Startup

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationFast Track (US), Orphan Drug (US), Breakthrough Therapy (CN)

Login to view timeline

Safety Run-in Cohort (cohort 1):
10 patients will be treated with IT injection of VG161 in the cohort 1 at dose level of 1.0x10E8 PFU x 3 days.
Monotherapy Cohorts (Cohort 2 and 3) Cohort 2 (HCC) This part is a single-agent, single one-dose level and single-arm design. Approximately 39 subjects will be enrolled in the study to receive VG161. In the first stage, 21 subjects will be enrolled. If there is only 1 or fewer subjects has been observed with objective response and no more than 12 (<13) subjects have PFS longer than 3 months, the trial will be stopped. Otherwise, this study will continue to enter the second stage, and 18 additional subjects will be added, and the total number of trial subjects will reach 39.
Cohort 3 (ICC) This part is a single-agent, single one-dose level and single-arm design. The trial will be carried out in two periods. In the first period, a total of 20 subjects will be enrolled. If there is only 1 or fewer response case in the 20 subjects, the trial will be stopped to investigate the efficacy of the IP, otherwise, subjects will continue to enter the second period, and 13 additional subjects will be added, and the total number of trial cases will reach 33.
Cohort 4 (ICC and HCC) Combination with Nivolumab Combination cohort and subjects will receive VG161 at the same schedule as the monotherapy cohorts and 240 mg of intravenous Nivolumab on days 8 and 15 of each treatment cycle. The Nivolumab dose can be changed to 480 mg every 4 weeks after cycle one based on investigator's discretion.

Start Date24 Jan 2024

Sponsor / Collaborator

Virogin Biotech Ltd.Startup

CTR20233149 / RecruitingPhase 1/2

VG161联合卡瑞利珠单抗治疗晚期原发性肝细胞癌患者的开放的Ib/IIa 期临床试验

[Translation] An open phase Ib/IIa clinical trial of VG161 combined with camrelizumab in patients with advanced primary hepatocellular carcinoma

Ib期主要目的：评价VG161连续多次肿瘤内注射给药联合卡瑞利珠单抗治疗晚期原发性肝细胞癌患者的安全性和耐受性，探索联合治疗最适合的II期推荐剂量（RP2D）。次要目的： 1）初步评价VG161联合卡瑞利珠单抗治疗晚期原发性肝细胞癌患者的抗肿瘤活性；2）监测药效学相关的免疫学指标变化； 3）评价I型单纯疱疹病毒抗体滴度水平对VG161安全性、有效性的影响。IIa期主要目的：评价VG161连续多次肿瘤内注射给药联合卡瑞利珠单抗治疗晚期原发性肝细胞癌患者的有效性，主要观察指标是客观缓解率（ORR）。次要目的：1）评价联合治疗有效性的次要观察指标，包括疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）；2）监测药效学相关的免疫学指标变化；3）进一步评价 VG161联合卡瑞利珠单抗治疗的安全性。4）评价I型单纯疱疹病毒抗体滴度水平对VG161安全性、有效性的影响

[Translation]

The main purpose of Phase Ib is to evaluate the safety and tolerability of VG161 combined with carrelizumab in the treatment of patients with advanced primary hepatocellular carcinoma, and to explore the most suitable Phase II recommended dose (RP2D) for combined treatment. Secondary objectives: 1) Preliminary evaluation of the anti-tumor activity of VG161 combined with carrelizumab in the treatment of patients with advanced primary hepatocellular carcinoma; 2) Monitor changes in immunological indicators related to pharmacodynamics; 3) Evaluate the impact of herpes simplex virus type I antibody titer on the safety and efficacy of VG161. The main purpose of Phase IIa is to evaluate the effectiveness of VG161 combined with carrelizumab in the treatment of patients with advanced primary hepatocellular carcinoma, with the primary observation index being the objective response rate (ORR). Secondary objectives: 1) Evaluate secondary observation indicators of the effectiveness of combined treatment, including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR); 2) Monitor changes in immunological indicators related to pharmacodynamics; 3) Further evaluate the safety of VG161 combined with carrelizumab. 4) Evaluate the impact of herpes simplex virus type I antibody titer on the safety and efficacy of VG161

Start Date04 Dec 2023

Sponsor / Collaborator

CNBG-Virogin Biotech (Shanghai) Ltd.

NCT06124001 / Not yet recruitingPhase 1/2

An Open-label Phase Ib/IIa Clinical Trial of VG161 Combined With Camrelizumab in the Treatment of Advanced Primary Hepatocellular Carcinoma

VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 injection.This study will be conducted in combination with camrelizumab in patients with advanced advanced primary hepatocellular carcinoma who have received at least one first-line treatment regimen. This is an open-label study divided into two parts.
Part 1: This part is an escalating dose trial to explore the safety of the combination and determine the recommended safe dose of the combination.
Part 2: This part is an extension trial to investigate the preliminary efficacy of the combination at a safe dose.

Start Date30 Nov 2023

Sponsor / Collaborator

CNBG-Virogin Biotech (Shanghai) Ltd.

100 Clinical Results associated with Recombinant Human IL12/15-PDL1B Herpes simplex type I oncolytic virus(Vero cell)(Virogin)

Login to view more data

100 Translational Medicine associated with Recombinant Human IL12/15-PDL1B Herpes simplex type I oncolytic virus(Vero cell)(Virogin)

Login to view more data

100 Patents (Medical) associated with Recombinant Human IL12/15-PDL1B Herpes simplex type I oncolytic virus(Vero cell)(Virogin)

Login to view more data

5

Literatures (Medical) associated with Recombinant Human IL12/15-PDL1B Herpes simplex type I oncolytic virus(Vero cell)(Virogin)

01 May 2023·Journal of Medical Virology

Combination of novel oncolytic herpesvirus with paclitaxel as an efficient strategy for breast cancer therapy

Article

Author: Leng, Qi ; Zhong, Guansheng ; Ding, Jun ; Yi, Ming ; Zhao, Ronghua ; Zhang, Chaomei ; Jia, Weiguo ; Dai, Zhijun ; WeiyangLou ; Deng, Xinyue ; Shen, Yinan ; Dong, Chenfang ; Zhao, Bin ; Xue, Dixuan

AbstractBackgroundNew strategies are needed to improve the treatment of patients with breast cancer (BC). Oncolytic virotherapy is a promising new tool for cancer treatment but still has a limited overall durable antitumor response. A novel replicable recombinant oncolytic herpes simplex virus type 1 called VG161 has been developed and has demonstrated antitumor effects in several cancers. Here, we explored the efficacy and the antitumor immune response of VG161 cotreatment with paclitaxel (PTX) which as a novel oncolytic viral immunotherapy for BC.MethodsThe antitumor effect of VG161 and PTX was confirmed in a BC xenograft mouse model. The immunostimulatory pathways were tested by RNA‐seq and the remodeling of tumor microenvironment was detected by Flow cytometry analysis or Immunohistochemistry. Pulmonary lesions were analyzed by the EMT6‐Luc BC model.ResultsIn this report, we demonstrate that VG161 can significantly represses BC growth and elicit a robust antitumor immune response in a mouse model. The effect is amplified when combined with PTX treatment. The antitumor effect is associated with the infiltration of lymphoid cells, including CD4+ T cells, CD8+ T cells, and NK cells (expressing TNF and IFN‐γ), and myeloid cells, including macrophages, myeloid‐derived suppressor cells, and dendritic cell cells. Additionally, VG161 cotreatment with PTX showed a significant reduction in BC lung metastasis, which may result from the enhanced CD4+ and CD8+ T cell‐mediated responses.ConclusionsThe 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.

01 Jan 2023·Journal of Medical Virology

VG161 activates systemic antitumor immunity in pancreatic cancer models as a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes

Article

Author: Wang, Meng ; Liang, Tingbo ; Song, Wei ; Bai, Xueli ; Lin, Danni ; Wu, Zongsong ; Guo, Sida ; Zhang, Xiaozhen ; Jia, Weiguo ; Ding, Jun ; Zhao, Ronghua ; Sheng, Jianpeng ; Wang, Zijun ; Yang, Zifan ; Lou, Yufeng ; Pan, Xinping ; Murad, Yanal ; Li, Yuwei ; Shen, Yinan

AbstractThe VG161 represents the first recombinant oncolytic herpes simplex virus type 1 carrying multiple synergistic antitumor immuno‐modulating factors. Here, we report its antitumor mechanisms and thus provide firm theoretical foundation for the upcoming clinical application in pancreatic cancer. Generally, the VG161‐mediated antitumor outcomes were analyzed by a collaboration of techniques, namely the single‐cell sequencing, airflow‐assisted desorption electrospray ionization‐mass spectrometry imaging (AFADSI‐MSI) and nanostring techniques. In vitro, the efficacy of VG161 together with immune checkpoint inhibitors (ICIs) has been successfully shown to grant a long‐term antitumor effect by altering tumor immunity and remodeling tumor microenvironment (TME) metabolisms. Cellular functional pathways and cell subtypes detected from patient samples before and after the treatment had undergone distinctive changes including upregulated CD8+ T and natural killer cells. More importantly, significant antitumor signals have emerged since the administration of VG161 injection. In conclusion, VG161 can systematically activate acquired and innate immunity in pancreatic models, as well as improve the tumor immune microenvironment, indicative of strong antitumor potential. The more robusting antitumor outcome for VG161 monotherapy or in combination with other therapies on pancreatic cancer is worth of being explored in further clinical trials.

Viruses

Pre-Existing HSV-1 Immunity Enhances Anticancer Efficacy of a Novel Immune-Stimulating Oncolytic Virus

Article

Author: Sun, Yi ; Zhao, Ronghua ; Lee, I-Fang ; Ding, Jun ; Samudio, Ismael ; Liu, Xiaohu ; Jia, William Wei-Guo ; Murad, Yanal M.

Oncolytic viruses (OVs) can specifically replicate in the host and cause cancer cell lysis while inducing an antitumor immune response. The aim of this study is to investigate the impact of either pre-existing immunity against herpes simplex virus type-1 (HSV-1) or multicycle treatment with OVs on anticancer efficacy of VG161, an HSV-1 OV in phase 2 clinical trial. VG161 efficacy was tested in CT26 mouse models by comparing the efficacy and immune response in naïve mice or in mice that were immunized with VG161. 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). The HSV-1-immunized mice significantly inhibited tumor growth in VG161-treated mice compared to control naïve treated mice. RNA expression profiling and ELISPOT analyses indicated changes in the tumor’s immune profile in the immunized and treated group compared to naïve and treated mice, as well as enhanced T cell function depicted by higher numbers of tumor specific lymphocytes, which was enhanced by immunization. In the ICC PDX model, repeated treatment of VG161 with 2 or 3 cycles seemed to increase the anticancer efficacy of VG161. 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.

100 Deals associated with Recombinant Human IL12/15-PDL1B Herpes simplex type I oncolytic virus(Vero cell)(Virogin)

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Liver Cancer	Phase 3	CN	Virogin Biotech Ltd.Startup	23 Apr 2021
Intrahepatic Cholangiocarcinoma	Phase 2	US	Virogin Biotech Ltd.Startup	24 Jan 2024
Osteosarcoma	Phase 2	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	27 Jul 2023
Metastatic gastric adenocarcinoma	Phase 2	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	06 Mar 2023
Metastatic gastroesophageal adenocarcinoma	Phase 2	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	06 Mar 2023
Metastatic Gastric Carcinoma	Phase 2	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	17 Nov 2022
Bile Duct Neoplasms	Phase 2	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	14 May 2022
Hepatocellular Carcinoma	Phase 2	-	Virogin Biotech Ltd.Startup	04 Feb 2022
Primary Malignant Liver Neoplasm	Phase 1	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	16 Mar 2021
Advanced Malignant Solid Neoplasm	Discovery	CN	CNBG-Virogin Biotech (Shanghai) Ltd.	24 Mar 2021

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04806464 (ASCO2024) Manual	Phase 1	Hepatocellular Carcinoma Second line	44	VG161	-	Positive	24 May 2024
NCT04806464 (ASCO2024) Manual	Phase 1	Hepatocellular Carcinoma Second line	44	VG161 (HCC)	(cylpncxsdj) = viprreokac kafophdxqc (iciebevyna ) View more	Positive	24 May 2024
NCT05162118 (766, SITC2023)	Phase 1/2	Advanced Pancreatic Adenocarcinoma	13	VG161 + Nivolumab	vqmdvrxtit(tiurtqtdpa) = lsqrkrnkmx izwbagerdd (upjmdkidfp )	Positive	02 Nov 2023
NCT04806464 (694, SITC2022)	Phase 1	Primary Malignant Liver Neoplasm PD-L1 \| PD-1 \| CD69 ... View more	11	VG161	yktwshqsvd(gyuxutjbgb) = wduwwsojuz yqlghjfcbe (eevrynyduj ) View more	Positive	07 Nov 2022