Theriva™ Biologics’ oncolytic viruses have the potential to treat a broad range of difficult-to-treat tumor types and may be combined with a variety of cancer therapies.
In the on-going VIRAGE Phase 2 clinical trial in patients with PDAC, VCN-01 is being tested in combination with standard-of-care chemotherapy gemcitabine/nab-paclitaxel. VCN-01 was also administered with the checkpoint inhibitor durvalumab in a Phase 1 study in patients with HNSCC and is currently being evaluated in combination with huCART-meso cells in an investigator-sponsored study in patients with either pancreatic cancer or ovarian cancer.
The diversity of tumor types and coadministered cancer treatments highlight the broad anticipated utility of Theriva’s systemic, selective, and stroma-degrading oncolytic viruses.
Clinical Trial Overview
VIRAGE trial (EudraCT 2022-000897-24) is multi-center, open label, randomized, 2-parallel arm, Phase IIb study evaluating intravenous VCN-01 in combination with first-line standard-of-care chemotherapy (SoC) in patients with newly-diagnosed metastatic pancreatic adenocarcinoma. Approximately 92 patients in about 25 sites across Spain, Germany and the USA will be randomized in a 1:1 ratio into one of two treatment arms:
Nab-paclitaxel and gemcitabine 28-day cycles as SoC (no VCN-01).
Up to two doses of VCN-01 administrated in combination with nab-paclitaxel and gemcitabine cycles as SoC.
The first dose of VCN-01will be administered 7-days prior to the first dose of the first cycle of nab-paclitaxel and gemcitabine SoC. The second dose of VCN-01 is scheduled to be administered approximately 3 months later, 7-days prior to the first dose of the fourth cycle of nab-paclitaxel and gemcitabine SoC.
The primary endpoints for the study are overall survival and the safety and tolerability of VCN01. Secondary endpoints include progression-free survival/time-to-progression, objective response rate, and changes in the tumor biomarker Ca19.9. Exploratory measures include patient quality of life and measures of VCN-01 biodistribution, mechanism of action, and immune response.
Sponsor: VCN Bioscience S.L. (a wholly-owned subsidiary of Theriva Biologics, Inc.)
ICO-VCN-H&N-2018 (NCT03799744) is a phase I trial to evaluate the safety, tolerability, and potential antitumor activity of intravenous VCN-01 oncolytic adenovirus in combination with durvalumab (MEDI4736) in subjects with recurrent/metastatic squamous cell carcinoma of the head and heck. The study evaluates escalating single doses of VCN-01 combined with a fixed dose of durvalumab. In Arm I, VCN-01 is administered on the same day as the first dose of durvalumab (concomitant schedule) while in Arm II VCN-01 is administered 2-weeks prior to the first dose of durvalumab (delayed schedule).
Sponsor: Institut Català d’Oncologia
UPCC#03821 (NCT05057715) is a phase I trial to evaluate the safety and feasibility of intravenous injection of VCN-01 oncolytic adenovirus in combination with huCART-meso cells in patients with either pancreatic cancer or ovarian cancer. The study evaluates escalating single doses of VCN-01 administered 14 days prior to intravenous infusion of huCART-meso cells. An optional cohort administering huCART-meso cells 10-days prior to VCN-01 is also included.
Sponsor: University of Pennsylvania
FSJD-RTB-2015 (NCT03284268) is a phase 1 clinical trial evaluating the safety and potential activity of intravitreal VCN-01 oncolytic adenovirus in children with refractory retinoblastoma. The study is evaluating escalating doses of VCN-01 administered by 2 intravitreal injections separated by 14 days.
Sponsor: Fundació Sant Joan de Déu
Study CO20/134663 (EudraCT 2020-003405-59, ISRCTN51762486) is a phase I trial to determine the safety of IV VCN-01 in patients with high-grade primary or secondary brain tumors and to evaluate the potential for systemically administered VCN-01 to reach tumors in the brain of these patients. In this trial, patients will be administered a single IV dose of VCN-01 approximately 8-15 days prior to scheduled surgical resection of their brain tumor. VCN-01 levels will be measured in resected brain tumor samples.
Sponsor: The University of Leeds.
NCT04692181 is a phase 1b/2a clinical trial evaluating the safety, tolerability and potential systemic absorption of oral SYN-004 into the systemic circulation of adult allogeneic hematopoietic cell transplant recipients who develop fever after conditioning therapy and are treated with either IV β-lactam antibiotics meropenem (MER), piperacillin tazobactam (PIP/TAZO), or cefepime (FEP). The trial is also designed to evaluate potential protective effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients, including prevention of acute graft-versus host disease (aGVHD). The trial is expected to enroll up to 36 participants in three sequential IV beta-lactam antibiotic cohorts. Safety and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee that will make a recommendation on whether to proceed to the next IV beta-lactam antibiotic.
Sponsor: Washington University in St. Louis