TORONTO and SAN DIEGO (June 4, 2016) — Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, today announced positive results from its Phase 1 proof-of-concept study evaluating marizomib in combination with bevacizumab in patients with WHO grade IV malignant glioma.
These results were presented in a poster session during the American Society for Clinical Oncology (ASCO) annual meeting in Chicago on June 4, 2016.
“These results confirm our original hypothesis that this combination therapy is a viable treatment for recurrent glioma, and they are essential to our determining an appropriate Phase 2 dose as we continue the development of marizomib (MRZ),” 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. “The expansion cohort was extremely helpful in our achieving robust results, and we believe we understand optimal dosing and look forward to continuing to further evaluate MRZ.”
The open-label, dose-escalation study, included three dose escalation cohorts, plus an expansion cohort, for a total of 36 patients receiving MRZ at day 1, day 8, and day 15, each with standard dose of bevacizumab (BEV at 10mg/kg) on days 1 and 15 of a 28 day cycle. MRZ+BEV combination was well tolerated with no DLTs at 0.8mg/m2, which was the highest dose of MRZ that was evaluated in this study. At the time of data cut off on May 17, 2016, 31 patients were efficacy evaluable and 25 of those patients achieved clinical benefit. Response rate was 45% (14/31) in efficacy evaluable patients and 39% (14/36) in the intent to treat population. Five patients achieved a deep response in that the tumor area was 0 mm2 by MRI. In fact, 16 patients are active as of the data cutoff date and the study continues. The trial has been amended to include a monotherapy arm to evaluate single agent activity and safety of MRZ.
“We continue to be encouraged by these results, and plan to initiate a new trial to evaluate the safety and activity of MRZ in newly diagnosed glioma patients,” said Mohit Trikha, Ph.D., chief scientific officer and head of Triphase Accelerator. “The safety and tolerability results we have seen, along with the encouraging responses, continue to demonstrate what we have believed to be the value in developing marizomib as a potential new treatment for glioma patients.”
Marizomib is a novel, irreversible, potent and brain-penetrant proteasome inhibitor, which inhibits all three proteasome subunits, thus providing superior potency, specificity, and duration of proteasome inhibition, and potentially improved clinical activity. Triphase Accelerator is developing marizomib in both intravenous (IV) and oral formulations as a potential best-in-class 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.
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.