Date: 2014-12-06
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Society of Hematology (ASH) 2014 Annual Meeting
Company: Triphase Accelerator (Canada - USA - CA) Celgene (USA - NJ)
Product: marizomib
Action
mechanism: proteasome inhibitor. Marizomib is a novel proteasome inhibitor that irreversibly targets and inhibits all three proteasome subunits, allowing for more durable and sustained responses.
Disease: multiple myeloma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 6, 2014, Triphase Accelerator announced preclinical study results demonstrating that marizomib and
pomalidomide (Pomalyst®) was synergistic in killing multiple myeloma cells. Combined doses of marizomib and pomalidomide inhibited tumor growth and prolonged survival in disease models of this hematologic cancer. The data were presented in a poster session at the American Society of Hematology (ASH) 2014 Annual Meeting in San Francisco.
Study Design and Results: Previous preclinical studies have shown that marizomib triggers synergistic anti-multiple myeloma activity in combination with lenalidomide. In this study, researchers examined the anti-multiple myeloma activity of a combination of marizomib and pomalidomide, which has immunomodulatory properties and, like lenalidomide, is an analogue of thalidomide. Researchers used in vitro models of multiple myeloma, including multiple myeloma cell lines, multiple myeloma cells from patients and blood cells from healthy donors, and in vivo models. 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 assessment of cell viability.
Results from the in vitro models showed that a significant decrease in viability of all cell lines and patient cells was observed 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 therapy was observed in multiple myeloma cells sensitive and resistant to conventional therapies (i.e., dexamethasone, doxorubicin and melphalan) and to novel therapies (i.e., bortezomib). Marizomib and pomalidomide also were shown to inhibit the proliferation of multiple myeloma cells and to block migration of multiple myeloma cells and angiogenesis. Results of the in vivo models demonstrated that combined doses of marizomib and pomalidomide inhibited tumor growth and prolonged survival and were not associated with any serious safety signals.
Triphase is currently evaluating marizomib in a Phase I study in combination with pomalidomide and dexamethasone in relapsed and refractory multiple myeloma. The Company plans to initiate a Phase I study of IV marizomib in glioblastoma (GBM) in early 2015. Triphase is also evaluating an oral formulation of marizomib in IND-enabling studies.
