# Oncolytic Immunotherapy using Chimeric HSV C134: A Phase I Trial and Establishment of Response Indicators in Recurrent Glioma Patients

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $551,600

## Abstract

PROJECT SUMMARY: Gliomas are the most frequently occurring primary malignant brain tumors, with
glioblastoma multiforme (GBM) being one of the most fatal and treatment-refractory of all cancers. New
treatments are urgently needed. First-generation oncolytic Herpes Simplex Viruses (1st gen oHSVs) used in
Phase I clinical trials were safe and produced a 50% response rate however, only a minority of patients had a
durable anti-tumor response. Analysis of the 1st gen oHSV-treated glioma specimens shows that increased
antiviral and immunostimulatory activity in the tumor directly correlates with longer survival in the Phase Ib
study. The 1st Gen oHSVs were designed to restrict viral replication and therefore could not maintain infection
or sustain an antiviral immune response. To improve oHSV antitumor activity, we have developed a next-
generation oHSV, C134, with enhanced immunostimulatory activity. C134 is designed to activate antiviral
cellular pathways important for amplifying the immune response and to improve viral replication in tumor cells.
While it shares a similar safety profile as the 1st gen oHSVs, C134 has superior anti-tumor efficacy in pre-
clinical models. Murine studies also show that C134 more effectively induces T cell and antigen presenting cell
responses that are associated with improved patient survival in the Phase Ib studies.
We will test our hypothesis that “C134 is safe and induces immune activity that enhances the anti-tumor
response in patients with recurrent malignant glioma” by the following aims:
Aim 1: To conduct a Phase I clinical trial to determine a safe C134 (IND 17296) dose in patients with
recurrent malignant glioma. Hypothesis: Intratumoral administration of C134 is safe in patients with recurrent
malignant gliomas. We are ready to start our Phase I trial. Our clinical grade C134 has received regulatory
approval from the NIH-Recombinant DNA Council (RAC) and FDA-Investigational New Drug (IND#17296).
C134 will be intratumorally-administered to patients using a Continual Reassessment Method (CRM) design
and will be monitored for C134 safety and tolerability.
AIM 2 To monitor immune response changes associated with oHSV mediated anti-tumor responses
among C134-treated patients. Hypothesis: C134-induced antiviral and Th1 immune activity contribute to anti-
tumor efficacy and can be inferred from peripheral blood samples. Our past clinical trial results indicate that
oHSV-induced immune activity is associated with improved survival. We will therefore monitor patient's
peripheral blood (immunophenotyping and cytokine) after C134-treatment and define how immune response
changes relate to anti-tumor response. Studies will also examine how sustained viral activity and T cell clonal
changes contribute to the C134-anti-tumor response.
Impact: Successful completion of these studies is the first step in establishing an effective therapy for an
incurable tumor and would provide a way to monitor and potentially enhance the vir...

## Key facts

- **NIH application ID:** 10005926
- **Project number:** 5R01CA222903-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Kevin A Cassady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $551,600
- **Award type:** 5
- **Project period:** 2018-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005926

## Citation

> US National Institutes of Health, RePORTER application 10005926, Oncolytic Immunotherapy using Chimeric HSV C134: A Phase I Trial and Establishment of Response Indicators in Recurrent Glioma Patients (5R01CA222903-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10005926. Licensed CC0.

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