Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma: NPI-0052-101 Part 1

Paul G. Richardson, Todd M. Zimmerman, Craig C. Hofmeister, Moshe Talpaz, Asher A. Chanan-Khan, Jonathan L. Kaufman, Jacob P. Laubach, Dharminder Chauhan, Andrzej J. Jakubowiak, Steven Reich, Mohit Trikha, Kenneth C. Anderson

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Marizomib (MRZ) is a novel, irreversible proteasome inhibitor in clinical development for the treatment of relapsed or relapsed and refractory multiple myeloma (RRMM). MRZ inhibits the 3 proteolytic activities of the 20S proteasome with specificity distinct from bortezomib and carfilzomib. Study NPI-0052-101 Part 1 enrolled relapsed or RRMM patients into an open-label, dose-escalation design to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of MRZ administered intravenously on 2 different schedules: schedule A (0.025-0.7 mg/m2 once weekly on days 1, 8, and 15 of 4-week cycles) and schedule B (0.15-0.6 mg/m2 twice weekly on days 1, 4, 8, and 11 of 3-week cycles; concomitant dexamethasone was allowed with schedule B). Patients had received an average of 4.9 and 7.3 prior treatment regimens (schedules A and B, respectively). MRZ schedule A was administered to 32 patients, and the RP2D was established as 0.7 mg/m2 infused over 10 minutes. Schedule B was administered to 36 patients, and the RP2D was determined to be 0.5 mg/m2 infused over 2 hours. The most common (>20% of patients) related adverse events were fatigue, headache, nausea, diarrhea, dizziness, and vomiting. Six patients achieved clinical benefit responses (defined as minimal response or better), including 5 partial responses (1 patient on schedule A and 4 on schedule B; 3 of these 4 patients received concomitant dexamethasone). MRZ was generally well tolerated, and results suggest activity in previously treated RRMM patients. Combination studies using pomalidomide and dexamethasone are now underway. The trial was registered at as #NCT00461045.

Original languageEnglish (US)
Pages (from-to)2693-2700
Number of pages8
Issue number22
StatePublished - Jun 2 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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