# A Phase 2 biomarker driven, Study of DB107, a Retroviral Replicating Vector, Combined With 5-FC in Patients with Recurrent Glioblastoma or Anaplastic Astrocytoma

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $204,520

## Abstract

PROJECT SUMMARY
 High-grade gliomas are the most common primary brain tumors in adults that continue to have poor
median 5-year survival rates despite maximal safe resection and chemoradiation. Over the last 20 years, the
standard treatment for high-grade gliomas has not changed drastically; therefore, attention has shifted to
developing virotherapies to improve outcomes from this lethal disease. Viral based gene therapies are preferred
biological agents that selectively deliver transgenes to tumor cells and are not permissible in normal cells. The
first clinical candidate retroviral replicating vector (RRV) (DB107, vocimagene amiretrorepvec) delivers a
transgene, cytosine deaminase, to convert the non-toxic prodrug 5-fluorocytosine (5-FC) to an intracellular
chemotherapeutic, 5-fluorouracil. Recently, phase III randomized clinical trials (Toca 5, NCT02414165) using
the first clinical candidate DB107 (formerly named Toca511) demonstrated an improvement in survival in a select
subgroup of patients with a novel biomarker, DGM7 compared to patients receiving standard of care alone (SOC)
(18.3 vs. 12.0 months, HR: 0.5, p<0.0167). Since DGM7 is highly predictive of a positive response to retroviral
gene therapy, we are conducting a Phase II, biomarker-driven trial to a priori identify “responders” to DB107+5-
FC. Additionally, we have previously shown that DB107+5-FC suppresses myeloid derived suppressor cells and
recruits tumor infiltrating CD8+ T-cells. Therefore, we hypothesize that DB107+5-FC will not only improve
outcomes in patients with recurrent high-grade gliomas, but will also induce a robust anti-tumor immune
response. To non-invasively characterize the immune response, we plan to employ an multiplex immuno-ELISA
in treated patients before and after exposure to DB107+5-FC. Additionally, we will validate these in vivo immuno-
ELISA signatures with single-nuclei RNA-seq of HGG ex vivo. The fundamental goal of this study is to 1)
prospectively validate DGM7 as a novel biomarker to identify patients who will respond to DB107 and 2)
comprehensively characterize the anti-tumor immune response after viral-based gene therapy through serum-
based ELISA and transcriptomic approaches. The proposed clinical trial may not only validate clinical DGM7 as
a prognostic marker for DB107 in recurrent high-grade gliomas but also set the foundation for the clinical
translation of biomarker-driven clinical trials in neuro-oncology.

## Key facts

- **NIH application ID:** 10888393
- **Project number:** 5R21CA282543-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Ashish Harish Shah
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,520
- **Award type:** 5
- **Project period:** 2023-07-14 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888393

## Citation

> US National Institutes of Health, RePORTER application 10888393, A Phase 2 biomarker driven, Study of DB107, a Retroviral Replicating Vector, Combined With 5-FC in Patients with Recurrent Glioblastoma or Anaplastic Astrocytoma (5R21CA282543-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10888393. Licensed CC0.

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