A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with Relapsed/Refractory Multiple Myeloma.
Publication/Presentation Date
1-15-2019
Abstract
PURPOSE: The presence of hypoxia in the diseased bone marrow presents a new therapeutic target for multiple myeloma. Evofosfamide (formerly TH-302) is a 2-nitroimidazole prodrug of the DNA alkylator, bromo-isophosphoramide mustard, which is selectively activated under hypoxia. This trial was designed as a phase I/II study investigating evofosfamide in combination with dexamethasone, and in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.
PATIENTS AND METHODS: Fifty-nine patients initiated therapy, 31 received the combination of evofosfamide and dexamethasone, and 28 received the combination of evofosfamide, bortezomib, and dexamethasone. Patients were heavily pretreated with a median number of prior therapies of 7 (range: 2-15). All had previously received bortezomib and immunomodulators. The MTD, treatment toxicity, and efficacy were determined.
RESULTS: The MTD was established at 340 mg/m
CONCLUSIONS: Evofosfamide can be administered at 340 mg/m
Volume
25
Issue
2
First Page
478
Last Page
486
ISSN
1557-3265
Published In/Presented At
Laubach, J. P., Liu, C. J., Raje, N. S., Yee, A. J., Armand, P., Schlossman, R. L., Rosenblatt, J., Hedlund, J., Martin, M., Reynolds, C., Shain, K. H., Zackon, I., Stampleman, L., Henrick, P., Rivotto, B., Hornburg, K. T. V., Dumke, H. J., Chuma, S., Savell, A., Handisides, D. R., … Ghobrial, I. M. (2019). A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with Relapsed/Refractory Multiple Myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research, 25(2), 478–486. https://doi.org/10.1158/1078-0432.CCR-18-1325
Disciplines
Medicine and Health Sciences
PubMedID
30279233
Department(s)
Fellows and Residents
Document Type
Article