TY - JOUR
T1 - A phase Ib/II study of oprozomib in patients with advanced multiple myeloma and Waldenstrom € macroglobulinemia
AU - Ghobrial, Irene M.
AU - Vij, Ravi
AU - Siegel, David
AU - Badros, Ashraf
AU - Kaufman, Jonathan
AU - Raje, Noopur
AU - Jakubowiak, Andrzej
AU - Savona, Michael R.
AU - Obreja, Mihaela
AU - Berdeja, Jesus G.
N1 - Funding Information:
R. Vij is a consultant/advisory board member for Amgen, Celgene, Bristol-Myers Squibb, Takeda, Janssen, Karypopharm, and Sanofi and reports receiving commercial research grants from Takeda, Celgene, and Bristol-Myers Squibb. D. Siegel reports receiving speakers bureau honoraria from and is a consultant/ advisory board member for Amgen. J. Kaufman is a consultant/advisory board member for Celgene, Takeda, Bristol-Myers Squibb, Janssen, Karyopharm, TG Therapeutics, and Incyte. N. Raje is a consultant/advisory board member for Amgen, Celgene, Janssen, Takeda, and Bristol-Myers Squibb. A. Jakubowiak is a consultant/advisory board member for Amgen, Celgene, AbbVie, Bristol-Myers Squibb, Janssen, Juno, Karyopharm, SkylindeDX, and Takeda. M.R. Savona has ownership interest (including patents) in Karyopharm, is a consultant/advisory board member for Celgene, Karyopharm, Incyte, TG Therapeutics, Takeda, Amgen, and Astex, and reports receiving commercial research grants from Incyte, Takeda, TG Therapeutics, Sunesis, and Astex. J.G. Berdeja is a consultant/advisory board member for Takeda, Bristol-Myers Squibb, Karyopharm, CRISPR Therapeutics, Kite Pharma, and Servier and reports receiving commercial research grants from AbbVie, Amgen, Bluebird, Bristol-Myers Squibb, Celgene, Genentech, Glenmark, Janssen, Novartis, Poseida, Sanofi, Takeda, and Teva. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
The authors wish to thank all the patients, families, caregivers, research nurses, study coordinators, and support staff who contributed to this study. Medical writing and editorial assistance was provided by Andrew Gomes and Sachi Yim of BlueMomentum, an Ashfield Company, part of UDG Healthcare PLC, and funded by Amgen Inc. This study was supported by Amgen Inc.
Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2019/8/15
Y1 - 2019/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070695297&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-3728
DO - 10.1158/1078-0432.CCR-18-3728
M3 - Article
C2 - 31142508
AN - SCOPUS:85070695297
VL - 25
SP - 4907
EP - 4916
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 16
ER -