Data reveals positive preliminary results for investigational agent tinostamustine as a potential first-in-class treatment for glioblastoma.
Stamford, Conn. November 19, 2025 – Purdue Pharma L.P. (“Purdue”) announced positive preliminary results from a Phase 1 study of tinostamustine in MGMT promoter-unmethylated (uMGMT) glioblastoma (GBM), a form of aggressive brain cancer with a subset of patients that do not respond or respond poorly to standard-of-care therapy. Tinostamustine was shown to be tolerable at doses of 80 to 100 mg/m², with side effects similar to other anti-neoplastic agents and preliminary signs of efficacy. The results will be shared as a poster at the 2025 Neuro-Oncology Societies Meeting on November 22 in Honolulu, Hawaii. The results were also presented in October at the 2025 European Association for Neuro-Oncology (EANO) meeting.
Glioblastoma is a fast-growing cancer that occurs in the brain. It is very challenging to treat and there is no cure.1 Most treatments seek to remove or shrink the tumor to help reduce symptoms and prolong survival.1 As many as 15,000 people in the U.S. are diagnosed with glioblastoma each year,2 and nearly 60% of those patients have uMGMT GBM.3
Tinostamustine is an investigational, potential first-in-class, new chemical entity that combines two potentially synergistic mechanisms of action, bifunctional alkylating activity and pan histone deacetylase inhibition (or HDAC inhibition). Tinostamustine has the potential to be a first-line treatment for GBM.
“Newly diagnosed patients with GBM, especially those with uMGMT, experience limited if any survival benefit from current pharmacologic treatment approaches,” said Julie Ducharme, Vice President and Chief Scientific Officer, Purdue. “These Phase 1 findings show that tinostamustine can be administered safely following standard chemoradiation. We are encouraged by these results and look forward to advancing tinostamustine through the Phase 2/3 GBM AGILE trial (Glioblastoma Adaptive Global Innovative Learning Environment – NCT03970447), a global adaptive clinical trial for glioblastoma patients led by the Global Coalition for Adaptive Research (GCAR).”
In September 2025, Purdue entered into an agreement to include tinostamustine in GBM AGILE, a pioneering, international adaptive platform trial designed to streamline the clinical trial process and accelerate the evaluation of treatments for glioblastoma. It is led by GCAR, a non-profit corporation and is supported by a global network of clinicians, researchers, biostatisticians, and patient advocacy organizations.
In the current study, the Phase 1, open-label, multicenter dose-escalation trial (NCT05432375) evaluated the safety, tolerability, and preliminary efficacy of tinostamustine following chemoradiation with temozolomide (RT/TMZ), the standard-of-care chemotherapy for GBM. Eligible patients were adults with confirmed uMGMT GBM who had completed RT/TMZ in the past 5 weeks and without disease progression. Tinostamustine was administered as a one-hour intravenous infusion on Day 1 of each 21-day cycle, beginning at 80 mg/m² and escalating to 100 mg/m² using a standard 3+3 design.
Ten patients were enrolled, nine of whom were evaluable for safety and efficacy. The median patient age was 63 years, and most were male. Three patients received tinostamustine at 80 mg/m² without experiencing dose-limiting toxicities (DLTs). Among the six patients treated at 100 mg/m², one experienced a DLT of prolonged low-grade thrombocytopenia. Grade ≥3 treatment-related adverse events were reported in both cohorts, including anemia and hematologic toxicities. Overall, tinostamustine’s side effect profile was considered manageable, and 100 mg/m² was established as the maximum tolerated dose (MTD) per the study protocol.
“Glioblastoma is one of the most devastating cancers, and patients with uMGMT GBM face especially limited treatment options,” said Craig Landau, MD, President and CEO, Purdue. “The data generated to date are encouraging and represent a meaningful step forward for tinostamustine, that if successfully developed and ultimately approved by FDA, would provide hope and potential benefit for affected patients and their families. We are encouraged by these preliminary results and committed to advancing innovative science that can transform lives. Tinostamustine reflects the kind of bold innovation we strive for across our pipeline, and we look forward to continuing this important work with urgency and purpose.”
While not designed to demonstrate efficacy, exploratory analyses of progression-free and overall survival outcomes showed encouraging signals of clinical activity. Details of these findings will be presented at the scientific meeting. The forthcoming evaluation in the GBM AGILE trial will advance the understanding of tinostamustine’s potential in treating glioblastoma.
This press release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that tinostamustine will successfully complete development or gain FDA approval.
About Purdue Pharma L.P.
Purdue and its subsidiaries develop, manufacture and market medications to meet the evolving needs of healthcare professionals, patients, and caregivers. Purdue and its subsidiaries focus on balancing innovative science with clinically effective, compassionate care. The Company’s goals are to serve patients who rely on its medicines, pursue public health initiatives intended to help abate the opioid crisis, advance its pipeline of branded and generic medications, and introduce medicines that will help save and improve lives.
About Imbrium Therapeutics L.P.
Imbrium is a clinical-stage biopharmaceutical company dedicated to advancing medical science through the development of important new pharmacologic and biologic therapeutics. We are pursuing oncology chemotherapeutics, treatments for disorders of the central nervous system, and non-opioid approaches to the management of pain. As a subsidiary of Purdue Pharma L.P., Imbrium strives to develop and bring to market new medicines that serve the unmet needs of patients, physicians and health systems worldwide. We have built a robust and diversified pipeline of investigational drug candidates, and we actively collaborate with industry and academic partners to identify and advance future impactful medicines. For more information, please visit www.imbriumthera.com
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Reference
- Glioblastoma (GBM). https://my.clevelandclinic.org/health/diseases/17032-glioblastoma. Accessed September 24, 2025.
- Glioblastoma Brain Tumor Information. (n.d.). Glioblastoma Foundation. https://glioblastomafoundation.org/patients/glioblastoma-brain-tumor-information
- Liu, D., Yang, T., Ma, W., Wang, Y. (2022). Clinical strategies to manage adult glioblastoma patients without MGMT hypermethylation. Journal of Cancer, 13(1), 354-363. https://doi.org/10.7150/jca.63595.