A phase Ib/II study of oprozomib in patients with advanced multiple myeloma and Waldenstrom macroglobulinemia

Irene M. Ghobrial, Ravi Vij, David Siegel, Ashraf Badros, Jonathan Kaufman, Noopur Raje, Andrzej Jakubowiak, Michael R. Savona, Mihaela Obreja, Jesus G. Berdeja

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Purpose: The oral proteasome inhibitor oprozomib has shown preclinical antitumor activity. Here, we report phase Ib/II study results investigating single-agent oprozomib in patients with relapsed multiple myeloma and Waldenstrom € macroglobulinemia. Patients and Methods: The primary objectives were to determine the MTD, safety, and tolerability of oprozomib (phase Ib) as well as overall response rate (ORR; phase II). Oprozomib was administered once daily on days 1, 2, 8, and 9 (2/7 schedule) or days 1 to 5 (5/14 schedule) of a 14-day cycle. Results: In patients with multiple myeloma or Waldenstrom € macroglobulinemia (n ¼ 71), the determined MTDs were 300 mg/day (2/7 schedule) and 240 mg/day (5/14 schedule). Median oprozomib treatment duration for patients with multiple myeloma was 11.4 weeks (2/7 schedule, 240/ 300 mg/day), 5.4 weeks (5/14, 240 mg/day), and 10.1 weeks (5/14, 150/180 mg/day). For patients with Waldenstrom € macroglobulinemia, these values were 34.6 weeks (2/7 schedule, 240/300 mg/day) and 8.1 weeks (5/14 schedule, 240 mg/day). The most common grade 3 adverse events (AE) in phase Ib included gastrointestinal and hematologic AEs. Three AE-related deaths in phase II prompted enrollment into 2/7 and 5/14 step-up dosing schedules (240/300 mg/day and 150/180 mg/day, respectively). In phase II, ORRs in 95 response-eligible multiple myeloma patients were 41.0%, 28.1%, and 25.0% in the 2/7, 240/300-mg/day; 5/14, 150/180-mg/day; and 5/14, 240-mg/day cohorts, respectively. ORRs in 31 response-eligible Waldenstrom € macroglobulinemia patients were 71.4% and 47.1% for the 2/7 and 5/14 cohorts, respectively. Conclusions: This study demonstrated promising efficacy of single-agent oprozomib in patients with relapsed multiple myeloma and Waldenstrom € macroglobulinemia.

Original languageEnglish
Pages (from-to)4907-4916
Number of pages10
JournalClinical Cancer Research
Volume25
Issue number16
DOIs
StatePublished - Aug 15 2019

Fingerprint

Dive into the research topics of 'A phase Ib/II study of oprozomib in patients with advanced multiple myeloma and Waldenstrom <sup>€</sup> macroglobulinemia'. Together they form a unique fingerprint.

Cite this