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The FDA granted orphan drug designation to tinostamustine for malignant glioma.
The FDA has granted orphan drug designation to tinostamustine as a potential therapeutic option for patients with malignant glioma, according to an announcement from Purdue Pharma.1
Tinostamustine is a potential first-in-class agent featuring 2 mechanisms of action that could work in a synergistic tandem: bifunctional alkylating activity and pan histone deacetylase (HDAC) inhibition.
“As many as 15,000 people in the US are diagnosed with glioblastoma each year. Unfortunately, there is limited survival benefit with existing treatment options,” Julie Ducharme, vice president and chief scientific officer at Purdue Pharma, stated in a news release. “This recognition from FDA is an important milestone in our mission of advancing innovative science in areas of serious, unmet medical need. We look forward to further investigating tinostamustine, which has shown promise in early trials.”
FDA Orphan Drug Designation for Tinostamustine in Malignant Glioma
In September 2025, Purdue Pharma reached an agreement with the Global Coalition for Adaptive Research to evaluate tinostamustine as part of the phase 2/3 GBM AGILE trial (NCT03970447), which is examining multiple therapies in patients with newly diagnosed and recurrent glioblastoma.2,3 Evaluation of the agent in the study is contingent on FDA approval of trial protocol following an investigational new drug application submission.2
GBM AGILE is a response-adaptive randomization platform trial intended to examine different therapies in patients with glioblastoma with the intention of identifying potentially effective therapy options for this patient population, including treatments among various subtypes of the malignancy.3
To enroll, patients with newly diagnosed disease must be at least 18 years of age with histologically confirmed grade IV glioblastoma per surgical resection or biopsy. Patients are required to have a Karnofsky performance status of at least 60% within 14 days of randomization. Patients with newly diagnosed glioblastoma are being excluded if they received any prior treatment for glioma, have extensive leptomeningeal disease, or have a QTc greater than 450 msec for male patients or a QTc greater than 470 msec for female patients. Patients with a history of another malignancy in the 2 years prior to enrollment, with a disease-free interval of less than 2 years, are being excluded; however, those with prior history of in situ cancer or basal/squamous cell skin cancer are allowed to enroll.
Patients with recurrent disease need to be at least 18 years of age with histologically confirmed grade IV glioblastoma at first or second recurrence after receiving prior standard, control, or experimental therapies, with recurrent disease confirmed by disease progression per slightly modified Response Assessment in Neuro-Oncology criteria. Notably, prior radiation therapy is required for this subset. Other key inclusion criteria for patients with recurrent disease include 2 scans to confirm progression and a Karnofsky performance status of at least 70%. Exclusion criteria mirror the exclusion criteria for the newly diagnosed population, with the addition of early disease progression within 3 months (or 12 weeks) of the completion of radiation therapy; receipt of more than 2 prior lines for chemotherapy; and any prior treatment with lomustine, agents in any experimental arm, and bevacizumab (Avastin) or other VEGF/VEGFR-targeted agent.
In GBM AGILE, all experimental therapies are being evaluated in 2 stages. Stage 1 is an adaptively randomized screening stage to compare the treatment against a common control, and this stage will continue in each cohort until it reaches maximum sample size (n = 200), is ended for futility, or displays unacceptable safety. Treatments deemed eligible to advance to stage 2 will then be investigated in a fixed-randomization expansion cohort (n = 50).
Overall survival is serving as the trial’s primary end point. Secondary end points include progression-free survival, overall response rate, and duration of response.
“Behind every designation like this are real people, patients and families, facing the devastating reality of malignant gliomas, especially glioblastoma,” Craig Landau, MD, president and chief executive officer of Purdue Pharma, added in a news release.1 “We are deeply committed to pursuing this medicine that has the potential to bring hope where few options exist today. Tinostamustine represents a step forward in our efforts to help address the urgent and unmet needs of those affected by these aggressive cancers.”
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