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|Ref Type||Journal Article|
|Authors||Harrison SJ, Mainwaring P, Price T, Millward MJ, Padrik P, Underhill CR, Cannell PK, Reich SD, Trikha M, Spencer A|
|Title||Phase I Clinical Trial of Marizomib (NPI-0052) in Patients with Advanced Malignancies Including Multiple Myeloma: Study NPI-0052-102 Final Results.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2016 Sep 15|
|Abstract Text||Marizomib (NPI-0052) is an irreversible proteasome inhibitor, derived from a marine actinomycete, with activity and specificity that is distinct from other proteasome inhibitors.Phase I study (NPI-0052-102) evaluated the MTD, pharmacokinetics, and pharmacodynamics of marizomib intravenously on two dosing schedules.Forty-two patients with advanced malignancies received Schedule A (0.1-0.9 mg/m(2) over 1-10 minutes on days 1, 8, 15 in 4-week cycles); 44 patients with relapsed and/or refractory multiple myeloma (RRMM) and other hematologic malignancies received Schedule B (0.075-0.6 mg/m(2) over 1 minute to 2 hours on days 1, 4, 8, 11, in 3-week cycles). The Schedule A recommended phase II dose was 0.7 mg/m(2) over 10 minutes; Schedule B was 0.5 mg/m(2) over 2 hours. The most common (>25% of patients) related adverse events were fatigue, nausea, diarrhea, and infusion site pain (Schedule A); and fatigue (Schedule B). Overall response rate of 11% was seen in 27 efficacy-evaluable RRMM Schedule B patients (1 very good partial response, 3 partial responses, 4 minimal responses, and 12 stable disease). One Schedule A patient with transformed marginal zone lymphoma had complete response. Marizomib has a short half-life (<30 minutes), with high volume of distribution (∼15-416 L) and clearance (∼0.9-22 L/minutes).Marizomib does not exhibit the severe peripheral neuropathy or hematologic toxicity observed with other proteasome inhibitors. Marizomib was generally well tolerated with low-dose dexamethasone, demonstrated activity in heavily pretreated RRMM patients, and warrants further evaluation. Clin Cancer Res; 22(18); 4559-66. ©2016 AACR.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||multiple myeloma||not applicable||Marizomib||Phase I||Actionable||In a Phase I trial, Marizomib (NPI-0052) treatment resulted in objective response in 14.8% (4/27) and stable disease in 44.4% (12/27) of patients with relapsed and/or refractory multiple myeloma (PMID: 27117181).||27117181|
|Unknown unknown||Advanced Solid Tumor||not applicable||Marizomib||Phase I||Actionable||In a Phase I trial, Marizomib (NPI-0052) treatment resulted in stable disease of short duration in 29% (7/24) of patients with advanced solid tumors (PMID: 27117181).||27117181|
|Unknown unknown||lymphoma||not applicable||Marizomib||Phase I||Actionable||In a Phase I trial, Marizomib (NPI-0052) treatment resulted in complete response lasting more than 10 treatment cycles in 7.1% (1/14) of lymphoma patients (PMID: 27117181).||27117181|