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Clin Cancer Res. 2019 Aug 15;25(16):4907-4916. doi: 10.1158/1078-0432.CCR-18-3728. Epub 2019 May 29.

A Phase Ib/II Study of Oprozomib in Patients with Advanced Multiple Myeloma and Waldenström Macroglobulinemia.

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Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
Myeloma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
Multiple Myeloma Service, University of Maryland School of Medicine, Baltimore, Maryland.
Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Emory University, Atlanta, Georgia.
Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
Myeloma Program, University of Chicago Medical Center, Chicago, Illinois.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Department of Biostatistics, Amgen Inc., Thousand Oaks, California.
Myeloma Research, Sarah Cannon Research Institute, Nashville, Tennessee.



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 Waldenström macroglobulinemia.


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.


In patients with multiple myeloma or Waldenström macroglobulinemia (n = 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 Waldenström 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 Waldenström macroglobulinemia patients were 71.4% and 47.1% for the 2/7 and 5/14 cohorts, respectively.


This study demonstrated promising efficacy of single-agent oprozomib in patients with relapsed multiple myeloma and Waldenström macroglobulinemia.

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