The Global Coalition for Adaptive Research (GCAR) and Purdue Pharma have announced the activation of investigational tinostamustine in GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment–NCT03970447), an international adaptive platform trial designed to accelerate the identification of effective treatments for glioblastoma (GBM). Tinostamustine will be evaluated for the treatment of adult patients with newly diagnosed GBM across GBM AGILE. It will also be studied in a cohort of patients with recurrent GBM at select GBM AGILE sites.

GBM AGILE is a seamless phase-II/III study conducted under a master protocol enabling multiple therapies or combinations of therapies from different pharmaceutical companies to be evaluated simultaneously against a shared control arm. With its innovative design and efficient operational infrastructure, data from GBM AGILE can potentially be used as the foundation for a New Drug Application (NDA) and registrations to the US FDA and other health authorities. 

Dr. John de Groot, Neuro-Oncology Division Chief, Department of Neurosurgery, University of California, San Francisco and Dr. Shiao-Pei Weathers, Brain Tumor Section Chief, Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, are serving as the principal investigators for tinostamustine's evaluation in GBM AGILE. Dr. Timothy Cloughesy, Director, Neuro-Oncology Program and Distinguished Professor of Neurology at the University of California, Los Angeles, is the global principal investigator for the overall study.

"Glioblastoma remains one of the most aggressive and difficult-to-treat cancers we encounter in clinical practice. There is a pressing need to explore novel mechanisms of action in well-designed studies. GBM AGILE's adaptive platform design allows us to rigorously evaluate promising therapies like tinostamustine while generating high-quality data efficiently. The addition of tinostamustine strengthens our ability to investigate new approaches that may improve outcomes for patients with GBM," said Dr. John de Groot.

Tinostamustine is a first-in-class, new chemical entity that combines two potentially synergistic mechanisms of action: bifunctional DNA alkylating activity, which triggers apoptosis, and pan histone deacetylase inhibition (or HDAC inhibition), which, in addition to improving alkylating agent access to DNA, has been shown to disrupt oncogenic signaling pathways and enhance immune recognition of tumor cells. This dual mechanism may be particularly relevant in aggressive and treatment-resistant cancers like GBM, where both genomic instability and epigenetic dysregulation drive disease progression.

"Despite advances in oncology, outcomes for patients with glioblastoma remain poor. Participating in a global study like GBM AGILE gives patients access to innovative investigational therapies that would otherwise not be available outside of a clinical trial. The inclusion of tinostamustine offers hope and reflects the ongoing commitment to expanding meaningful treatment opportunities for this devastating disease," said Dr. Shiao-Pei Weathers. 

Tinostamustine has the potential to be a first-line treatment and is being investigated in patients with newly diagnosed GBM as an adjuvant therapy following standard treatment with surgery, chemotherapy and radiation, as well as in a limited cohort for patients in whom the disease has recurred following initial treatment.

"Activation of the first trial sites represents the culmination of years of hard work and dedication, scientific rigor, and partnership. It underscores our determination to apply sustained scientific and clinical investment to help deliver new treatments patients urgently need," said Dr. Craig Landau, President and CEO, Purdue.

 Since its launch in 2019, GBM AGILE has evaluated multiple investigational therapies and has screened more than 2,600 patients at approximately 60 trial locations in six countries.

"At GCAR, our mission is to rethink how therapies are developed for aggressive cancers like glioblastoma. Through master protocols and adaptive platform trials, we aim to streamline evaluation and accelerate decision-making. Our collaboration to evaluate tinostamustine represents an important step toward rapidly advancing new treatments in GBM AGILE and bringing new hope to patients," said Dr. Meredith Buxton, CEO and President, GCAR.