# Phase 1b/2a Trial of QBS-72S for the Treatment of Newly Diagnosed Glioblastoma Multiforme in Patients with Unmethylated MGMT Promoters

> **NIH NIH R44** · QUADRIGA BIOSCIENCES, INC. · 2021 · $1,368,236

## Abstract

PROJECT SUMMARY—With support from NCI-funded Phase I and Phase II SBIRs, Quadriga Biosciences
developed QBS-72S, a novel compound designed to treat glioblastoma multiforme (GBM), even in the 60% of
patients who are resistant to temozolomide (TMZ), the current standard of care. Preclinical studies demonstrated
QBS-72S meets the three requirements for a globally effective GBM treatment: 1) it has a cytotoxic mechanism
of action that is not affected by the DNA repair mechanisms responsible for resistance to TMZ, 2) it penetrates
the blood brain barrier (BBB), and 3) it targets GBM while sparing normal tissue. Further development and
commercialization of QBS-72S has the potential to deliver the first drug that is effective for improving
overall survival in all patients with GBM, including the majority of patients who are resistant to the
current standard of care. Resistance to TMZ in both newly-diagnosed and recurrent GBM occurs when O6-
methylguanine-DNA-methyltransferase (MGMT) repairs DNA damage produced by TMZ. QBS-72S circumvents
this resistance with a nitrogen mustard (N-mustard) that damages DNA by producing numerous inter-strand
crosslinks (ICLs) in actively dividing cells. The number of ICLs overwhelms repair mechanisms, and the reliance
on cellular division limits off-target toxicity. Many effective chemotherapeutics share these features, but most of
them are excluded by the BBB. In contrast, QBS-72S is selectively transported across the BBB by LAT-1, a
transporter that is also highly expressed in tumor cells but not in healthy tissues. These features make QBS-72S
an ideal candidate for treating GBM, and a first-in-humans study is underway to confirm safety and establish a
recommended Phase 2 dose. Following extensive discussions with NCI, Quadriga proposes to use this Phase
IIB SBIR to add QBS-72S as a new arm to the INdividualized Screening trial of Innovative Glioblastoma Therapy
(INSIGhT), an ongoing, multi-site, adaptive Phase 2 clinical trial designed to demonstrate the safety and efficacy
of novel therapeutics as replacements for TMZ in the current standard of care regimen. Aim. Evaluate the
effectiveness of QBS-72S in place of TMZ for improving overall survival and progression-free survival in
patients with newly diagnosed GBM with unmethylated MGMT promoters. Milestones: 1) recruit patients
and complete study—a) recruit up to 70 patients in the QBS-72S arm and up to 70 in the TMZ arm, b) QBS-72S
arm not dropped for futility, c) follow up with ³ 80% at 30 days post-treatment; 2) demonstrate efficacy—a) overall
survival hazard ratio ≥ 0.6 for QBS-72S (primary endpoint), b) progression-free survival hazard ratio ≥ 0.6 for
QBS-72S (secondary); 3) characterize safety—no unexpected dose-limiting toxicities; 4) determine whether
defined biomarkers predict QBS-72S benefit—exploratory; 5) complete data analysis, prepare Phase 3 protocol,
and submit IND amendment. Impact: Successful completion of these milestones is required to proceed to a
...

## Key facts

- **NIH application ID:** 10248080
- **Project number:** 2R44CA174129-04
- **Recipient organization:** QUADRIGA BIOSCIENCES, INC.
- **Principal Investigator:** Gordon M Ringold
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,368,236
- **Award type:** 2
- **Project period:** 2013-06-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248080

## Citation

> US National Institutes of Health, RePORTER application 10248080, Phase 1b/2a Trial of QBS-72S for the Treatment of Newly Diagnosed Glioblastoma Multiforme in Patients with Unmethylated MGMT Promoters (2R44CA174129-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10248080. Licensed CC0.

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