Marizomib is a novel brain-penetrant proteasome inhibitor in development for patients with glioblastoma and relapsed and/or refractory multiple myeloma
Toronto and San Diego, CA (GLOBE NEWSWIRE) - Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through clinical Phase 2 proof-of-concept, today announced positive full enrollment results from its multicenter, open label, Phase 1 study evaluating marizomib (MRZ) in combination with bevacizumab (BEV) in patients with WHO grade IV malignant glioma. The study results were presented at the Society of Neuro Oncology meeting today in Scottsdale, Arizona. Triphase separately announced on November 17, 2016 that Celgene acquired the assets relating to MRZ.
“These results continue to demonstrate the potential benefit of both the combination therapy of MRZ and BEV, as well as MRZ monotherapy, for recurrent glioma," said Daniela Bota, M.D., medical director of Neuro-Oncology and associate professor of neurology at the University of California, Irvine, and lead investigator of the study. “As we reported for our interim results, adding the expansion cohort of monotherapy with MRZ was extremely helpful in achieving robust results, and we think we may have established an optimal dosing regimen.”
The Phase 1 open-label dose-escalation study included three dose escalation cohorts plus an expansion cohort, for a total of 36 recurrent glioma patients receiving MRZ on days 1, 8, and 15, with standard dose of bevacizumab (BEV at 10mg/kg) on days 1 and 15, of a 28-day cycle. The MRZ+BEV combination was well tolerated with no dose limiting toxicity at 0.8 mg/m2, which was the highest dose of MRZ evaluated in this study.
The Response Rate (by Response Assessment in Neuro-Oncology (RANO) criteria) was 42% (14/33) in efficacy evaluable patients, with 34% of patients achieving six months progression-free survival (PFS) and 55% achieving nine months overall survival (OS). The 6 and 9 months PFS in patients with unmethylated MGMT – a marker of poor prognosis and resistance to standard-of-care in glioblastoma - were 34% and 23%, respectively. These data are comparable to PFS in all patients (34% PFS 6 months, 22% PFS 9 months), suggesting a potentially unique clinical benefit of MRZ+BEV in this difficult to treat segment of glioblastomas. To date, the 9 months OS in unmethylated MGMT patients is 44%, with data collection continuing for most patients.
In an ongoing Phase 2 (MRZ monotherapy) portion of the study, a total of 15 recurrent glioma patients have been enrolled to date, receiving 0.8 mg/m2 MRZ on days 1, 8, and 15 of a 28-day cycle. MRZ monotherapy in these patients has resulted in a partial remission in 1 patient, and stable disease in 2 additional patients, demonstrating activity of MRZ as a single agent. Based on these data, the study will continue enrollment up to 30 total patients. MRZ is generally well tolerated in combination with BEV and as monotherapy. The most common study treatment-related adverse events across both phases of the study include fatigue, headache, nausea, diarrhea, dysphonia, hypertension, vomiting, hallucination and weakness.
“These clinical proof of concept results further support the value of MRZ as a potential treatment for recurrent glioma,” said Mohit Trikha, Ph.D., Chief Scientific Officer and head of Triphase Accelerator Research and Development. “Equally as important for Triphase Accelerator, these results were instrumental to Celgene’s decision to acquire the compound.”
Marizomib is a novel, brain-penetrant proteasome inhibitor, which inhibits all three proteasome subunits.
Triphase Accelerator is developing marizomib in both intravenous (IV) and oral formulations as a proteasome inhibitor for hematologic malignancies and solid tumors. The IV formulation has been evaluated in more than 300 patients in multiple clinical studies in patients with solid and hematologic malignancies, either as a single agent or in combination with dexamethasone, a histone deacetylase inhibitor, or an immunomodulatory drug.
The company is currently evaluating marizomib in a proof-of-concept clinical study in combination with bevacizumab (Avastin®) in patients with Grade IV malignant glioma (glioblastoma), and has received Orphan Drug designation for marizomib in glioblastoma in the United States from the FDA. In addition, Triphase Accelerator is currently developing marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, and has received Orphan Drug designation for marizomib in multiple myeloma in the United States and the European Union. Triphase Accelerator is also evaluating an oral formulation in preclinical studies.
Marizomib has not been approved for any use in any country.
About Triphase Accelerator
Triphase Accelerator is a private drug development company with a primary focus on oncology and with operations in Toronto and San Diego. Triphase Accelerator is dedicated to advancing novel compounds through Phase 2 proof-of-concept clinical studies using a unique, science-based, high-quality model that is faster and more cost-effective than traditional pharmaceutical and biotech industry drug development approaches. Triphase Accelerator was spun out of the Ontario Institute for Cancer Research (OICR), with support from the Fight Against Cancer Innovation Trust (FACIT), MaRS Innovation and MaRS. It has a strategic relationship with Celgene for marizomib. For more information, visit www.triphaseco.com or LinkedIn.
© Copyright 2016, GlobeNewswire, Inc. All Rights Reserved.