Voyager-V1

P1, N=34, Active, not recruiting, Mayo Clinic | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jun 2024 --> Aug 2023

P1, N=20, Recruiting, Mayo Clinic

P2, N=87, Recruiting, Vyriad, Inc. | Trial primary completion date: Mar 2024 --> Dec 2024

P1/2, N=70, Recruiting, Vyriad, Inc. | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=120, Recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Apr 2032 | Trial primary completion date: Dec 2024 --> Dec 2028

P1, N=34, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=77 --> 34

The optimal systemic therapy beyond first line platinum and etoposide is not established...If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163.

An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

P1, N=77, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting

P1, N=77, Recruiting, Mayo Clinic | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

The 30 minute infusion rate was considered the best as its PK provides the highest Cmax and AUC with no significant CRS differences among other groups. IL-6 and IFNα markers at hour 4 indicate a likely CRS and hour 24 provides a possible prediction of the grade. Cmax and AUC were also highest at 1.7e11 TCID50.

In the TCL cohort: at DL4 Group A (no Ruxolitinib), 12 pts were registered, but only 11 pts were treated (mycosis fungoides (MF) N=3; ALK- ALCL N=1; PTCL-NOS N=2; AITL N=4; Nodal PTCL, TFH N=2; ages 33-79)... These updated results of single agent VSV-IFNβ-NIS which include pts with PTCL treated at the highest dose level and a dose expansion cohort demonstrates not only the safety of VSV-IFNβ-NIS but also a strong efficacy signal in pts with PTCL with impressive durable responses. Two expansion cohorts at DL4 have been added (20 additional PTCL, 10 B-cell lymphoma pts) to obtain additional data on tolerability and efficacy and biomarkers of response in these pts. Clinical trial information: NCT03017820.

P2, N=87, Recruiting, Vyriad, Inc. | N=152 --> 87

P1/2, N=70, Recruiting, Vyriad, Inc. | N=40 --> 70 | Trial completion date: Sep 2023 --> Dec 2023 | Trial primary completion date: Sep 2023 --> Dec 2023

The optimal systemic therapy beyond first line platinum and etoposide is not established...If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163.

The optimal systemic therapy beyond first line platinum and etoposide is not established...RESULTS The NEC expansion cohort will seek to enroll 10 patients. If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study.CONCLUSIONS Trial is currently enrolling patients.

P1/2, N=40, Recruiting, Vyriad, Inc. | Trial completion date: Jun 2023 --> Sep 2023 | Trial primary completion date: Aug 2022 --> Sep 2023

P1, N=72, Suspended, Mayo Clinic | Trial completion date: Mar 2022 --> Apr 2023 | Recruiting --> Suspended | Trial primary completion date: Mar 2022 --> Apr 2023

P2, N=152, Recruiting, Vyriad, Inc. | Trial completion date: Mar 2023 --> Mar 2025 | Trial primary completion date: Mar 2022 --> Mar 2024

P1, N=76, Completed, Vyriad, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Apr 2022

Further clinical testing is warranted. (This trial is registered at www.clinicaltrials.gov as NCT03017820).

Current anti-myeloma therapies (conventional chemotherapies, immunomodulatory drugs i.e., thalidomide and its' analogues, proteasome inhibitors, monoclonal antibodies, and radiotherapy) initially substantially debulk tumour burden, but after a period of remission 'plateau phase' disease invariably relapses due to tumour recrudescence from foci of minimal residual disease (MRD) and accumulating drug resistance...This review will discuss the potential use of oncolytic virus (OV) therapies in the treatment of myeloma. Specifically, it will focus on preclinical studies using DNA viruses (adenovirus (Ad), vaccinia virus (VV), myxoma virus (MYXV), and herpes simplex virus (HSV)), RNA viruses (reovirus (reo), coxsackie virus, measles virus (MV) and bovine viral diarrhoea virus (BVDV), and vesicular stomatitis virus (VSV)), and on four types of viruses (VV, reo, MV-NIS and VSV-IFNβ-NIS) that have been assessed clinically in a small number of myeloma patients.

Oral ruxolitinib was administered for 5 days as IFNβ toxicity mitigation leading to normalization of AST and platelets. Analysis of the correlative data supports that intravenous Voyager-V1 therapy can recruit diverse antitumor effector mechanisms to impact tumor response in pts with heavily pretreated TCL. Importantly, intratumoral virus amplification, which results in high circulating concentrations of IFNβ, does not necessarily lead to tumor regression perhaps because of defective immune cell recruitment and/or activation in some tumors but not in others. This will be further evaluated in future study participants by performing CTL assays on fresh, rather than frozen PBMC.

P1/2, N=40, Recruiting, Vyriad, Inc. | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Aug 2021 --> Aug 2022

In this patient population acceptable tolerability was observed at the higher dose with 30 min duration, thus the RP2D is 1x 1011 over 30 mins. Trial Registration NCT02923466

A single intravenous dose of VSVIFN -NIS up to 1.7x1011 is safe in heavily pre-treated patients with hematologic malignancies and appears to be most effective as a single agent at DL 4, especially in patients with TCL. Future trials of combination strategies with immune-modulatory drugs are currently being planned.

P1, N=76, Active, not recruiting, Vyriad, Inc. | Recruiting --> Active, not recruiting | N=143 --> 76

P1, N=72, Recruiting, Mayo Clinic | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Mar 2021 --> Mar 2022

P1/2, N=40, Recruiting, Vyriad, Inc. | Phase classification: P1 --> P1/2

P1, N=40, Recruiting, Vyriad, Inc. | N=23 --> 40 | Trial completion date: Jul 2021 --> Jun 2022 | Trial primary completion date: Mar 2021 --> Aug 2021

P1, N=23, Recruiting, Vyriad, Inc. | Trial completion date: Mar 2021 --> Jul 2021 | Trial primary completion date: Nov 2020 --> Mar 2021

P2, N=152, Recruiting, Vyriad, Inc. | Not yet recruiting --> Recruiting

P1, N=72, Recruiting, Mayo Clinic | Trial completion date: Mar 2020 --> Mar 2021 | Trial primary completion date: Mar 2020 --> Mar 2021

P2, N=152, Not yet recruiting, Vyriad, Inc.