# Clinical evaluation of combination oncolytic viro-immunotherapy for solid tumors

> **NIH NIH R44** · VYRIAD, INC. · 2020 · $823,919

## Abstract

PROJECT SUMMARY/ABSTRACT .
Non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) are leading cause of cancer death
globally. Immune checkpoint inhibitors (CPIs), which block tumor immune-evasion signals and activate T-cell
mediated antitumor immunity, have demonstrated clinical efficacy and are approved for several cancers
including NSCLC and HCC. Despite this broad spectrum of activity, less than 50% of patients receive any
sustained benefit from these compounds. Moreover the majority of patients who achieve a response will
relapse within a year. There is an unmet clinical need for therapeutic approaches that overcome resistance
and enhance efficacy of CPI therapies. Pharmacodynamics monitoring has been incorporated into clinical trials
to define mechanisms of resistance to CPI therapy, indicating that tumors with low levels of immune infiltration,
or `cold' tumors, tend to respond poorly to checkpoint inhibition. Oncolytic virotherapy uses engineered viruses
to destroy tumor cells and promote antitumor immunity. Several oncolytic virotherapies have been evaluated
clinically with the recent approval of an oncolytic Herpesvirus (T-VEC) to treat advanced melanoma. Vyriad is
developing Vesicular stomatitis virus (VSV), a potent oncolytic virotherapy platform, as an intravenous therapy
for advanced cancer. VSV-IFNβ-NIS, an engineered recombinant VSV, has demonstrated potent preclinical
efficacy and is currently being tested in a clinical trial for intravenous therapy of patients with advanced cancer.
Preclinical studies demonstrate that VSV selectively amplifies in and kills tumor cells resulting in rapid and
durable tumor remission following single-shot intravenous therapy in murine tumor models. Intravenous VSV
therapy also elicits intratumoral CD8+ T-cell infiltration. The addition of PD-1/PD-L1 blockade extends duration
of T-cell infiltration to significantly enhance tumor remission in a murine colorectal tumor model. These data
indicate that oncolytic tumor destruction promotes influx of T-cells, while local immunosuppressive signals can
be blocked by checkpoint inhibitors to promote activation and amplification of antitumor T-cell responses.
These synergistic interactions have the potential to overcome both primary and acquired resistance to single-
agent checkpoint inhibitor therapy. Our goal is to clinically advance the combination oncolytic viro-
immunotherapy approach to treat patients with CPI refractory NSCLC and HCC. This goal is addressed in
this SBIR Fast-track proposal by combining Vyriad's expertise in oncolytic virotherapy development with the
world-class expertise of the Mayo Clinic Early Cancer Therapeutics Program. The proposed clinical study will
provide critical feasibility and efficacy signals and indicate mode of action to support rapid advancement of this
combination oncolytic viro-immunotherapy approach to treat CPI refractory cancer.

## Key facts

- **NIH application ID:** 10018816
- **Project number:** 5R44CA233024-03
- **Recipient organization:** VYRIAD, INC.
- **Principal Investigator:** Shruthi Naik
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $823,919
- **Award type:** 5
- **Project period:** 2018-09-18 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018816

## Citation

> US National Institutes of Health, RePORTER application 10018816, Clinical evaluation of combination oncolytic viro-immunotherapy for solid tumors (5R44CA233024-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10018816. Licensed CC0.

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