Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.

Autor: Kang Y; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA. yubin.kang@duke.edu., Sundaramoorthy P; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Gasparetto C; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Feinberg D; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Fan S; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Long G; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Sellars E; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Garrett A; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 5000, Durham, NC, DUMC 396127710, USA., Tuchman SA; Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Reeves BN; Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Li Z; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA., Liu B; Division of Hematology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Ogretmen B; Department of Biochemistry and Molecular Biology, and Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA., Maines L; Apogee Biotechnology Corporation, Hummelstown, PA, USA., Ben-Yair VK; RedHill Biopharma, Tel Aviv, Israel., Smith C; Apogee Biotechnology Corporation, Hummelstown, PA, USA., Plasse T; RedHill Biopharma, Tel Aviv, Israel.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2023 Feb; Vol. 102 (2), pp. 369-383. Date of Electronic Publication: 2022 Dec 03.
DOI: 10.1007/s00277-022-05056-7
Abstrakt: Multiple myeloma (MM) remains an incurable disease and there is an unmet medical need for novel therapeutic drugs that do not share similar mechanisms of action with currently available agents. Sphingosine kinase 2 (SK2) is an innovative molecular target for anticancer therapy. We previously reported that treatment with SK2 inhibitor opaganib inhibited myeloma tumor growth in vitro and in vivo in a mouse xenograft model. In the current study, we performed a phase I study of opaganib in patients with relapsed/refractory multiple myeloma (RRMM). Thirteen patients with RRMM previously treated with immunomodulatory agents and proteasome inhibitors were enrolled and treated with single-agent opaganib at three oral dosing regimens (250 mg BID, 500 mg BID, or 750 mg BID, 28 days as a cycle). Safety and maximal tolerated dose (MTD) were determined. Pharmacokinetics, pharmacodynamics, and correlative studies were also performed. Opaganib was well tolerated up to a dose of 750 mg BID. The most common possibly related adverse event (AE) was decreased neutrophil counts. There were no serious AEs considered to be related to opaganib. MTD was determined as at least 750 mg BID. On an intent-to-treat basis, one patient (7.7%) in the 500 mg BID dose cohort showed a very good partial response, and one other patient (7.7%) achieved stable disease for 3 months. SK2 is an innovative molecular target for antimyeloma therapy. The first-in-class SK2 inhibitor opaganib is generally safe for administration to RRMM patients, and has potential therapeutic activity in these patients. Clinicaltrials.gov: NCT02757326.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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