9 November 2018 - - The first patient has been enrolled in a Phase 1 investigator-initiated clinical trial of tinostamustine, an investigational treatment, in patients with newly-diagnosed unmethylated O6-Methylguanine-DNA-methyltransferase glioblastoma multiforme (unmethylated nGBM), the most common and aggressive type of primary malignant brain tumo, US-based Purdue Pharma L.P. said.

Now open at The University of Texas MD Anderson Cancer Center, the open-label, non-randomized trial will investigate the safety profile, maximum tolerated dose, and efficacy of tinostamustine.

Glioblastoma is an incurable cancer with a very poor prognosis.

Median overall survival is only 15 months and survival rates have shown no notable improvement in the past 30 years.

The current standard of care for the disease includes surgery and postoperative radiation therapy with concurrent and adjuvant chemotherapy using temozolomide.

Prognosis is significantly worse for patients with the unmethylated MGMT form of glioblastoma because that tumor type is less likely to respond to currently available treaments.

Under current standard of care, the two-year overall survival rate was 46% in patients with MGMT-methylated nGBM versus 14% in patients with unmethylated nGBM.

The dual-acting therapy candidate tinostamustine, previously known as EDO-S101, is a novel and potentially first-in-class alkylating deacetylase inhibitor (AK-DACi) therapy.

Clinical research is underway to evaluate its ability to improve access to and break the DNA strands within cancer cells, and counteract the cancer cells' attempts to repair the DNA damage.

The potential utility of tinostamustine in the treatment of glioblastoma is supported by various pre-clinical data, and the molecule has shown anti-tumor activity in multiple in-vitro models of glioblastoma.

In a pharmacokinetic analysis of tinostamustine administered to murine models by IV bolus and continuous IV infusion, tinostamustine crossed the blood-brain barrier with central nervous system penetration of 16.5% and 13.8% for IV bolus and CIVI administrations, respectively.

CNS penetration with adequate therapeutic CNS concentration is essential for the treatment of brain tumors.

Tinostamustine is an investigational treatment and it is not approved for use in glioblastoma patients. Tinostamustine is also in development for a range of rare or difficult-to-treat blood cancers and advanced solid tumors.

The completion of the first-in-human Phase 1 dose escalation study of tinostamustine in patients with relapsed or refractory (difficult-to-treat) hematological malignancies for which there are no available therapies was announced recently, and a Phase 1/2 study in advanced solid tumors was initiated in 2017.

Tinostamustine is being developed in the US by Mundipharma EDO on behalf of Purdue Pharma.

Purdue Pharma L.P. develops and provides prescription medicines that meet the evolving needs of healthcare professionals, patients, and caregivers.

We were founded by physicians and we are currently led by a physician. Beyond our efforts to provide quality medications, Purdue is committed to supporting national, regional and local collaborations to drive innovations in patient care.

Privately held, Purdue is pursuing a pipeline of new medications and technologies through internal research and development and strategic industry partnerships.