TG6002 / Transgene, Tasly - LARVOL DELTA

TG6002 oncolytic vaccinia virus and chemotherapy synergy: a promising strategy for pancreatic ductal adenocarcinoma. (PubMed, Front Microbiol) - "TG6002 also expresses the suicide gene FCU1, which efficiently converts the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic agent 5-fluorouracil (5-FU)...Additionally, we investigated the therapeutic potential of combining TG6002 with standard chemotherapeutic agents, including gemcitabine and components of the FOLFIRI regimen (irinotecan and oxaliplatin)...In a xenograft model, systemic delivery of TG6002 with 5-FC, combined with either oxaliplatin or irinotecan, resulted in superior antitumor effects compared to monotherapy. In summary, our findings suggest that the systemic administration of TG6002 with 5-FC, in combination with irinotecan and oxaliplatin, represents a promising therapeutic strategy for PDAC patients."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase I Clinical Trial of Intrahepatic Artery Delivery of TG6002 in Combination with Oral 5-Fluorocytosine in Patients with Liver-Dominant Metastatic Colorectal Cancer (Clin Cancer Res) - P1/2a | N=15 | NCT04194034 | Sponsor: Transgene | "Successful IHA delivery of replication-competent TG6002 was achieved, as demonstrated by the virus within tumor biopsies. Functional transcription of the FCU1 transgene indicates viral replication within the tumor, with higher plasma 5-fluorouracil associated with patients receiving the highest dose of TG6002....Moreover, an increase in the number and frequency of T-cell receptor clones against both cancer antigens and neoantigens, with elevated functional activity, may be associated with improved anticancer activity. Despite these findings, no clinical efficacy was observed."

P1 data • Colorectal Cancer

A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer. (PubMed, Clin Cancer Res) - "In summary, these data demonstrate delivery of OV to tumour via IHA administration, associated with viral replication and significant peripheral immune activation. Collectively, the data supports the need for future studies using IHA administration of OVs."

Journal • P1 data • Colorectal Cancer • Hepatology • Oncology • Solid Tumor • CALR

[PREPRINT] A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer (medRxiv) - P1/2 | N=15 | NCT04194034 | Sponsor: Transgene | "Successful IHA delivery of replication-competent TG6002 was achieved, as demonstrated by virus within tumour biopsies. Functional transcription of the FCU1 transgene indicates viral replication within the tumour, with higher plasma concentrations of 5-fluorouracil (5-FU) associated with patients receiving the highest dose of TG6002. IHA delivery of TG6002 correlated with a robust systemic peripheral immune response to virus with activation of peripheral blood mononuclear cells, associated with a proinflammatory cytokine response and release of calreticulin, potentially indicating immunogenic cell death. Gene Ontology analyses of differentially-expressed genes reveal a significant immune response at the transcriptional level in response to treatment."

P1 data • Preprint • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A viral attack on brain tumors: the potential of oncolytic virus therapy. (PubMed, J Neurovirol) - "Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors."

Journal • Oncolytic virus • Review • Brain Cancer • Gene Therapies • Oncology • Solid Tumor

Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors. (PubMed, Mol Ther Oncolytics) - "Viral replication, 5-fluorouracil synthesis, and tumor microenvironment changes were more frequently observed with higher TG6002 doses. This study confirmed the replicative properties, targeted chemotherapy synthesis, and reversion of the immunosuppressive tumor microenvironment in dogs with spontaneous malignant tumors treated with TG6002 and 5-fluorocytosine."

Journal • Oncolytic virus • Immunology • Oncology • Solid Tumor

Study of TG6002 (VV TK-RR-FCU1) in Combination With 5-FC in Patients With Advanced Gastro-intestinal Tumors. (clinicaltrials.gov) - P1/2 | N=51 | Terminated | Sponsor: Transgene | N=101 ➔ 51 | Trial completion date: Sep 2023 ➔ Feb 2023 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2022 ➔ Feb 2023; Study has been terminated after Phase I part on 23 February 2023

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of Intrahepatic Arterial Infusion of TG6002 in Combination With 5-FC in Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2a | N=15 | Terminated | Sponsor: Transgene | N=75 ➔ 15 | Trial completion date: Sep 2023 ➔ Feb 2023 | Recruiting ➔ Terminated; Study has been terminated after Phase I part on 23 February 2023

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liver-dominant metastatic colorectal cancer (AACR 2023) - "TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion)...The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively..."

Clinical • IO biomarker • Metastases • Oncolytic virus • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Transgene to Present Multiple Posters Highlighting the Potential of its Exciting Immunotherapy Pipeline at AACR 2023 (Businesswire) - "New Phase I data confirm high immunogenicity and promising efficacy profile of TG4050, an individualized neoantigen cancer vaccine developed by Transgene in collaboration with NEC Corporation...Transgene...will be presenting eight posters on its clinical and preclinical immunotherapies at the AACR (American Association for Cancer Research) Annual Meeting 2023, which will take place in Orlando, Florida, USA, April 14 – 19."

Clinical data • Preclinical • Trial status • Anal Carcinoma • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Ovarian Cancer • Penile Cancer • Solid Tumor • Vaginal Cancer • Vulvar Cancer

Updated data of biodistribution and activity of oncolytic virus TG6002 after intravenous administration in patients with advanced gastrointestinal carcinomas (ESMO 2022) - P1/2 | "In terms of safety, a single dose-limiting toxicity was observed among these 30 pts consisting of a disseminated pustular rash in one pt treated at the dose of 3x10 9 pfu. Conclusions The updated data of TG6002.02 trial at higher doses of TG6002 confirmed the favourable safety profile of the TG6002/5-FC combination and the effective expression of the FCU1 transgene in tumor cells."

Clinical • IO biomarker • Oncolytic virus • Gastrointestinal Cancer • Oncology • Solid Tumor

Transgene Confirms the Potential of the Intravenous Route of its Invir.IO Oncolytic Viruses against Solid Tumors with TG6002 Phase I Data Presented at ESMO Congress 2022 (Businesswire) - P1/2 | N=101 | NCT03724071 | Sponsor: Transgene | "Transgene...announces positive confirmatory data from the Phase I trial evaluating TG6002 administered intravenously (IV) in combination with oral 5-FC in patients with advanced gastrointestinal carcinomas....TG6002 demonstrated good tolerability when administered weekly or on days 1,3 and 5. No major toxicities limiting the dose escalation process or the intensification of the schedule of administration were observed. Onset of a neutralizing antibody response is not associated with a decreased biological activity of the product. TG6002 is able to reach the tumor, replicate, and express its payload after IV administration....The two IV administration schedules display different characteristics, that can both be leveraged in upcoming clinical trials....Additional data will be produced from the Phase I program and will be presented at a scientific congress in H1 2023."

P1 data • Gastrointestinal Cancer • Oncology • Solid Tumor

Positive Readouts for Transgene’s Clinical Stage Candidates Generated by its Two Innovative Platforms, with Further Clinical Data Expected in the Second Half of 2022 (Businesswire) - "TG4001 – Results from the interim analysis of the randomized Phase II trial in HPV-positive anogenital cancers to be released in Q4 2022; TG4050 (myvac® platform) – New positive Phase I data presented at AACR and ASCO - Additional data from the two Phase I trials to be communicated in H2 2022; TG6002 – Phase I data confirming the potential of the intravenous administration of Transgene’s Invir.IO™ oncolytic viruses will be presented at ESMO 2022 on September 11 at 12 pm CET; BT-001 (Invir.IO™ platform) – Initial Phase I data demonstrated good tolerability and first signs of antitumor activity - Phase Ib (BT-001 in combination with pembrolizumab) expected to start in the second half of 2022."

P1 data • P2 data • Anal Carcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Ovarian Cancer • Solid Tumor

Transgene Confirms the Potential of Its Two Innovative Platforms and Expects Significant Clinical Results in 2022 (Businesswire) - "TG4050 (myvac): Additional data to be presented at AACR 2022 in April...TG4001: Interim analysis expected in Q4 2022.... BT-001 (Invir.IO): IND approval for Phase I/IIa trial in the US, ongoing enrollment in Europe...The next clinical update on the ongoing Phase I trial is expected in the second quarter of 2022...TG6002: End of Phase I expected in mid-2022....The Phase I trial evaluating TG6002 administered intravenously is expected to be completed by mid-2022. Comprehensive translational data will be presented in the fourth quarter of 2022."

IND • P1 data • P1/2 data • Anal Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] Pre-Clinical Trial of T601 Oncolytic Virus for High-Grade Glioma via Intra-Tumoral Injection (EANO 2021) - "In summary, T601 exhibited efficient anti-tumoral function and acceptable side effect. T601 treatment prolonged the survival period of GBM mice with acceptable neurotoxicity, demonstrating that T601 contains necessary criterial for intra-tumoral injection. Ultimately, this project provided basic reference information of dose for future clinical trial."

Oncolytic virus • Preclinical • Brain Cancer • Glioma • Oncology • Solid Tumor

Transgene’s Two Innovative Platforms Progressing Well - Financial Visibility Extended Until End 2023 (Businesswire) - “The Phase I clinical trials assessing TG4050 are enrolling patients in the US and in Europe (UK and France) with: ovarian cancer, and head and neck cancers…The first data from the two ongoing Phase I clinical trials are expected in the second half of November 2021. Transgene expects to communicate safety and immunogenicity (T cell induction) data…TG6002 is also being evaluated in a Phase I/IIa clinical trial where it is being given by intrahepatic artery infusion in patients with advanced colorectal cancer with liver metastases…First Phase I data expected mid-2022…Research and Development (R&D) expenses amounted to €15.3 million in the first half of 2021 compared to €13.8 million for the same period in 2020, reflecting the ramp up of manufacturing activities.”

Commercial • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Ovarian Cancer

[VIRTUAL] Bioavailability and activity of oncolytic virus TG6002 after intravenous administration in patients with advanced gastrointestinal carcinomas (ESMO 2021) - P1/2 | "TG6002 localized to the tumor after IV administration in patients with advanced GI cancers and persisted selectively in tumors while expressing its transgene of interest. These data support the relevance of this route of administration in oncolytic virotherapy."

Clinical • IO biomarker • Oncolytic virus • Gastrointestinal Cancer • Oncology • Solid Tumor

PLK1/NF-κB feedforward circuit antagonizes the mono-ADP-ribosyltransferase activity of PARP10 and facilitates HCC progression. (PubMed, Oncogene) - "PLK1, an important regulator for cell mitosis, directly interacts with and phosphorylates PARP10 at T601...Clinically, the expression levels of PLK1 and phosphor-p65 show an inverse correlation with PARP10 expression in human HCC tissues. These findings are the first to uncover a PLK1/PARP10/NF-κB signaling circuit that underlies tumorigenesis and validate PLK1 inhibitors, alone or with NF-κB antagonists, as potential effective therapeutics for PARP10-expressing HCC."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Transcriptional activity of FIGLA, NEUROG2, and EGR1 transcription factors associated with polymorphisms in the proximal regulatory region of GPR54 gene in cattle. (PubMed, Anim Reprod Sci) - "Two luciferase-based promoters, ATC and CCT, which contain three single nucleotide polymorphisms (SNPs), A/C-794, T/C-663, and C/T-601, in the GPR54 PRR, were analyzed to evaluate gene expression and activation of different promoters by FIGLA, NEUROG2, and EGR1...The ATC-activating effects of NEUROG2 and EGR1 were markedly greater (12.91- and 8.41-fold; P < 0.01) than CCT-activating effects. The polymorphisms, CCT and ATC, of the cattle GPR54 affect the activity of transcription factors, therefore, have an important effect on production of GPR54 mRNA transcript."

Journal • NEUROG1

Safety, Tolerability and Pharmacokinetics Characteristics of Recombinant Oncolytic Vaccinia Virus Injection T601 as a Single Drug or in Combination With Oral Flucytosine (5-FC), in Patients With Advanced Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=69; Recruiting; Sponsor: Tasly Tianjin Biopharmaceutical Co., Ltd.

Clinical • Combination therapy • New P1/2 trial • Oncolytic virus • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Transgene Presents Data From Phase I Clinical Trial Confirming the Potential of the Oncolytic Virus TG6002 (Businesswire) - P1, N=60; NCT03724071; Sponsor: Transgene; "Transgene...announces the presentation of data from a Phase I study combining intravenous (IV) oncolytic virus TG6002 and oral 5-FC in patients with advanced gastrointestinal carcinomas...The data also demonstrate that the chemotherapy agent 5-FU is produced in the tumor across the three dose-level cohorts (3x108 pfu, 1x109 pfu and 3x109 pfu). 5-FU results from the local conversion of the pro-drug 5-FC (administered orally) allowed by the in-tumor expression of the proprietary FCU1 gene that has been integrated within the genome of TG6002....Direct evidence of TG6002 in the tumor, after intravenous administration, which remains active and effectively express FCU1 gene selectively in tumor tissue...TG6002 is well tolerated and no major toxicities limiting the dose escalation process were observed."

P1 data • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of TG6002 (VV TK-RR-FCU1) in Combination With 5-FC in Patients With Advanced Gastro-intestinal Tumors. (clinicaltrials.gov) - P1/2; N=101; Recruiting; Sponsor: Transgene; N=60 ➔ 101; Trial completion date: Dec 2021 ➔ Sep 2023; Trial primary completion date: Dec 2020 ➔ Sep 2022

Enrollment change • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

[VIRTUAL] Oncolytic virus TG6002 locates to tumors after intravenous infusion and induces tumor-specific expression of a functional pro-drug activating enzyme in patients with advanced gastrointestinal carcinomas (AACR 2021) - "Objective: TG6002 is a vaccinia virus deleted for Thymidine Kinase/Ribonucleotide Reductase and encoding the FCU1 enzyme that converts 5-Fluorocytosine (5-FC) to 5-Fluorouracil (5-FU). TG6002 was detected by qPCR in plasma and was rapidly cleared with no patients showing trace of the virus beyond 3 hours after administration. On day 5, despite very scarce availability of biomaterial, the virus was detected in tumoral tissue in 1/3 and 2/7 patients of the LD and HD cohorts, respectively. 5-FC to 5-FU conversion was detected in tumor of all patients and the highest tumor concentrations of 5-FU (65 and 227 pg/mg of tissue, respectively) were found in 2 of the 3 patients in which virus was detected in the tumor."

Clinical • IO biomarker • Late-breaking abstract • Oncolytic virus • Ampulla of Vater Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Oncolytic viruses as a promising therapeutic strategy against the detrimental health impacts of air pollution: The case of glioblastoma multiforme. (PubMed, Semin Cancer Biol) - "Engineered adenoviruses (i.e., DNX-2401, DNX-2440, CRAd8-S-pk7 loaded Neural stem cells), herpes simplex virus type 1 (i.e., HSV-1 C134, HSV-1 rQNestin34.5v.2, HSV-1 G207, HSV-1 M032), measles virus (i.e., MV-CEA), parvovirus (i.e., ParvOryx), poliovirus (i.e., Poliovirus PVSRIPO), reovirus (i.e., pelareorep), moloney murine leukemia virus (i.e., Toca 511 vector), and vaccinia virus (i.e., vaccinia virus TG6002) as possible life-changing alleviations for GBM have been discussed. We believe that the article will significantly appeal to a broad readership of virologists, oncologists, neurologists, environmentalists, and those who work in the field of (bio)energy. Policymakers may also use it to establish better health policies and regulations about air pollution and (bio)fuels exploration, production, and consumption."

Clinical • Journal • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Hematological Malignancies • Herpes Simplex • Immunology • Infectious Disease • Inflammation • Leukemia • Oncology • Solid Tumor

Transgene Presents Initial Phase I Data of TG6002, Highlighting the Potential of the Intravenous Administration of Its Oncolytic Viruses (Businesswire) - P1, N=60; NCT03724071; Sponsor: Transgene; "Transgene...today announces initial promising results from a Phase I study combining intravenous (IV) oncolytic virus TG6002 and oral 5-FC in patients with advanced gastrointestinal carcinomas...These results will be presented at the American Association for Cancer Research (AACR) virtual meeting taking place from April 10-15, 2021....TG6002 infects tumors after intravenous administration, remains active and effectively express FCU1 gene selectively in tumor tissue...None of the patients presented clinical signs of extra-tumoral dissemination of the virus suggesting a high tumor specificity of the viral replication...Title of the poster: 'Oncolytic virus TG6002 locates to tumors after intravenous infusion and induces tumor-specific expression of a functional pro-drug activating enzyme in patients with advanced gastrointestinal carcinomas'"

P1 data • Gastrointestinal Cancer • Oncology • Solid Tumor