Phase i clinical trial of marizomib (NPI-0052) in patients with advanced malignancies including multiple myeloma: Study NPI-0052-102 final results

S.J. Harrison, P. Mainwaring, T. Price, Michael Millward, P. Padrik, C.R. Underhill, P.K. Cannell, S.D. Reich, M. Trikha, A. Spencer

    Research output: Contribution to journalArticlepeer-review

    54 Citations (Scopus)

    Abstract

    © 2016 American Association for Cancer Research.Purpose: Marizomib (NPI-0052) is an irreversible proteasome inhibitor, derived from a marine actinomycete, with activity and specificity that is distinct from other proteasome inhibitors. Experimental Design: Phase I study (NPI-0052-102) evaluated the MTD, pharmacokinetics, and pharmacodynamics of marizomib intravenously on two dosing schedules. Results: Forty-two patients with advanced malignancies received Schedule A (0.1-0.9 mg/m2 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/m2 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/m2 over 10 minutes; Schedule B was 0.5 mg/m2 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 (
    Original languageEnglish
    Pages (from-to)4559-4566
    Number of pages8
    JournalClinical Cancer Research
    Volume22
    Issue number18
    DOIs
    Publication statusPublished - 15 Sep 2016

    Fingerprint

    Dive into the research topics of 'Phase i clinical trial of marizomib (NPI-0052) in patients with advanced malignancies including multiple myeloma: Study NPI-0052-102 final results'. Together they form a unique fingerprint.

    Cite this