"Patients with relapsed and refractory multiple myeloma urgently need new options to treat this otherwise fatal hematologic cancer," said
"These data provide a strong rationale for clinical trials of a combination of marizomib and pomalidomide to increase response, overcome drug resistance and improve outcomes in patients with relapsed and refractory multiple myeloma," said
Triphase is currently evaluating marizomib in a Phase I study in combination with pomalidomide and dexamethasone in relapsed and refractory multiple myeloma. Marizomib is also being evaluated in an ongoing Phase II clinical trial in combination with dexamethasone in a highly refractory multiple myeloma population, including patients refractory to carfilzomib. Study Design and Results Previous preclinical studies have shown that marizomib triggers apoptosis (cell death) in multiple myeloma cells resistant to bortezomib and induces synergistic anti-multiple myeloma activity in combination with the immunomodulatory agent lenalidomide. This new study evaluated the anti-multiple myeloma activity of a combination of marizomib and pomalidomide, which has immunomodulatory properties, using multiple myeloma cell lines, multiple myeloma cells from patients, and blood cells from healthy donors. The multiple myeloma cells were pretreated with a control or with pomalidomide for 24 hours, and marizomib was then added for an additional 24 hours, followed by analysis of cell viability.
Results showed a significant decrease in viability of all cell lines in response to treatment with combined marizomib and pomalidomide compared with either agent alone. The synergistic anti-multiple myeloma activity of these agents was confirmed by a separate method of evaluating combination chemotherapy. The cytotoxicity of the marizomib/pomalidomide combination treatment also was observed in multiple myeloma cells resistant to bortezomib. Additionally, marizomib and pomalidomide were shown to overcome the cytoprotective effects of the bone marrow.
The marizomib abstract is available at abstracts.asco.org. Details of the poster presentation follow. Abstract Title: Effect of combination of proteasome inhibitor marizomib and immunomodulatory agent pomalidomide on synergistic cytotoxicity in multiple myeloma (Abstract #8588, Poster Board #275) Date/Time:
About Marizomib Marizomib is a novel, highly potent proteasome inhibitor that irreversibly targets and inhibits all three proteasome subunits, allowing for more durable and sustained responses. Triphase is developing marizomib in both intravenous (IV) and oral formulations as a potential best-in-class proteasome inhibitor for hematologic malignancies and solid tumors. Marizomib has demonstrated activity in a Phase I study in patients with multiple myeloma refractory to lenalidomide or bortezomib. An IV formulation has been evaluated in more than 230 patients in four Phase I studies in patients with solid and hematologic malignancies, either as a single agent or in combination with dexamethasone or an HDAC inhibitor.
Triphase is currently evaluating the IV formulation in an ongoing Phase II clinical trial in combination with dexamethasone in a highly refractory multiple myeloma population, including those refractory to carfilzomib; it is also being tested in a Phase I study in combination with pomalidomide and dexamethasone in relapsed and refractory multiple myeloma. Triphase is evaluating an oral formulation of marizomib in IND-enabling studies. The Company has received orphan drug designation from the
Worldwide, an estimated 750,000 people are living with multiple myeloma.1 An estimated 103,000 new cases are diagnosed annually, accounting for about 1 percent of all cancers diagnosed and 12 percent of all hematologic cancers diagnosed.2 About Triphase Triphase is a private drug development accelerator with a primary focus on oncology and operations in
Keywords for this news article include: Antineoplastics, Pharmaceuticals, Cancer, Hormones, Oncology, Immunology, Leukocytes, Blood Cells, Bone Marrow, Chemotherapy, Lenalidomide, Plasma Cells, B-Lymphocytes,
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