Skip to main content
Journal cover image

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

Publication ,  Journal Article
Kang, Y; Sundaramoorthy, P; Gasparetto, C; Feinberg, D; Fan, S; Long, G; Sellars, E; Garrett, A; Tuchman, SA; Reeves, BN; Li, Z; Liu, B ...
Published in: Ann Hematol
February 2023

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.

Duke Scholars

Published In

Ann Hematol

DOI

EISSN

1432-0584

Publication Date

February 2023

Volume

102

Issue

2

Start / End Page

369 / 383

Location

Germany

Related Subject Headings

  • Proteasome Inhibitors
  • Phosphotransferases (Alcohol Group Acceptor)
  • Multiple Myeloma
  • Mice
  • Immunology
  • Humans
  • Dexamethasone
  • Antineoplastic Combined Chemotherapy Protocols
  • Animals
  • 3201 Cardiovascular medicine and haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kang, Y., Sundaramoorthy, P., Gasparetto, C., Feinberg, D., Fan, S., Long, G., … Plasse, T. (2023). Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma. Ann Hematol, 102(2), 369–383. https://doi.org/10.1007/s00277-022-05056-7
Kang, Yubin, Pasupathi Sundaramoorthy, Cristina Gasparetto, Daniel Feinberg, Shengjun Fan, Gwynn Long, Emily Sellars, et al. “Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.Ann Hematol 102, no. 2 (February 2023): 369–83. https://doi.org/10.1007/s00277-022-05056-7.
Kang Y, Sundaramoorthy P, Gasparetto C, Feinberg D, Fan S, Long G, et al. Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma. Ann Hematol. 2023 Feb;102(2):369–83.
Kang, Yubin, et al. “Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.Ann Hematol, vol. 102, no. 2, Feb. 2023, pp. 369–83. Pubmed, doi:10.1007/s00277-022-05056-7.
Kang Y, Sundaramoorthy P, Gasparetto C, Feinberg D, Fan S, Long G, Sellars E, Garrett A, Tuchman SA, Reeves BN, Li Z, Liu B, Ogretmen B, Maines L, Ben-Yair VK, Smith C, Plasse T. Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma. Ann Hematol. 2023 Feb;102(2):369–383.
Journal cover image

Published In

Ann Hematol

DOI

EISSN

1432-0584

Publication Date

February 2023

Volume

102

Issue

2

Start / End Page

369 / 383

Location

Germany

Related Subject Headings

  • Proteasome Inhibitors
  • Phosphotransferases (Alcohol Group Acceptor)
  • Multiple Myeloma
  • Mice
  • Immunology
  • Humans
  • Dexamethasone
  • Antineoplastic Combined Chemotherapy Protocols
  • Animals
  • 3201 Cardiovascular medicine and haematology