A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results

作者：Spencer Andrew; Harrison Simon; Zonder Jeffrey; Badros Ashraf; Laubach Jacob; Bergin Krystal; Khot Amit; Zimmerman Todd; Chauhan Dharminder; Levin Nancy; MacLaren Ann; Reich Steven D.; Trikha Mohit; Richardson Paul^*

来源：British Journal of Haematology, 2018, 180(1): 41-51.

DOI：10.1111/bjh.14987

• marizomib
• proteasome inhibitor
• pomalidomide
• low-dose dexamethasone
• relapsed/refractory multiple myeloma

Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0.3-0.5 mg/m(2)) was administered over 2h on days 1, 4, 8, 11; POM (3-4 mg) on days 1-21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1-10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0.5mg/m(2) MRZ was determined to be the RP2D. The most common treatment-related >= Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.

• 出版日期2018-1