Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with, and inhibiting, the nuclear export protein, XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.
Selinexor, also know as XPOVIO, has only been approved by the United States Food and Drug Administration (FDA) in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval.
Additionally, the FDA has accepted for filing Karyopharm’s supplemental New Drug Application (sNDA) seeking accelerated approval for oral XPOVIO tablets for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL), not otherwise specified, who have received at least two prior therapies. The FDA granted Karyopharm’s request for Priority Review and assigned a user fee goal date of June 23, 2020 under the Prescription Drug User-Fee Act (PDUFA).
Selinexor has been granted orphan designation by FDA for both multiple myeloma and DLBCL.
Selinexor is also currently being evaluated in ongoing Phase 2 and 3 clinical studies in patients with a variety of hematologic and solid tumor malignancies. In these settings, selinexor is an investigational medicine and has not been approved by The United States Food and Drug Administration (FDA), Health Canada, the European Medicines Agency (EMA), nor any other regulatory agency.
Please see below to learn more about selinexor’s ongoing clinical development:
Selinexor in Hematologic Malignancies
Selinexor is currently being studied in two ongoing Karyopharm-sponsored clinical studies in patients with multiple myeloma: The BOSTON study and the STOMP study
BOSTON (Bortezomib, Selinexor and dexamethasone) is a pivotal, randomized Phase 3 study of selinexor in combination with bortezomib and low-dose dexamethasone compared to bortezomib and low-dose dexamethasone in patients with multiple myeloma who have had one to three prior lines of therapy. Importantly, in the selinexor arm of the study, both selinexor and bortezomib are administered once per week while in the control arm, bortezomib is administered at its currently indicated twice per week schedule.
This study started enrolling patients in 2017 and Karyopharm announced the completion of enrollment in January 2019. Top-line results from this study were announced on March 2, 2020 and the full study results were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. Based on the data from the BOSTON study, Karyopharm submitted a supplemental New Drug Application to the FDA for XPOVIO® (selinexor) as a treatment for patients with multiple myeloma after at least one prior line of therapy .
To learn more about the BOSTON study please visit clinicaltrials.gov
STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) is a Phase 1b/2 study evaluating selinexor and low-dose dexamethasone in combination with one of several standard approved therapies, including Revlimid® (lenalidomide), Pomalyst® (pomalidomide), Velcade® (bortezomib), Kyprolis® (carfilzomib), or Darzalex® (daratumumab), in patients with relapsed or refractory multiple myeloma. Additionally, a new arm to this study was added in 2018 to study the combination of selinexor and Revlimid® in newly diagnosed patients with multiple myeloma.
To learn more about the STOMP study please visit clinicaltrials.gov.
Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited
Revlimid® and Pomalyst® are registered trademarks of Celgene Corporation
Kyprolis® is a registered trademark of Onyx Pharmaceuticals, Inc.
Darzalex® is a registered trademark of Janssen Biotech, Inc.
Diffuse Large B-Cell Lymphoma (DLBCL)
Selinexor is currently being studied in an ongoing clinical study in patients with DLBCL: The SADAL study
SADAL (Selinexor Against Diffuse Aggressive Lymphoma) is an open label, Phase 2b study evaluating patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue.
This study completed enrollment in October 2018 and top-line results were presented at the American Society of Hematology 2018 Annual Meeting.
Based on the SADAL study, the FDA has accepted for filing Karyopharm’s supplemental New Drug Application (sNDA) seeking accelerated approval for oral XPOVIO tablets for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL), not otherwise specified, who have received at least two prior therapies. The FDA granted Karyopharm’s request for Priority Review and assigned a user fee goal date of June 23, 2020 under the Prescription Drug User-Fee Act (PDUFA).
To learn more about the SADAL study please visit clinicaltrials.gov
Selinexor Studies in Solid Tumors
Selinexor is also currently being studied in patients with a variety of solid tumors, including:
- Liposarcoma (The SEAL study): A Phase 3 randomized, multicenter, double-blind, placebo-controlled study evaluating selinexor in patients with advanced unresectable dedifferentiated liposarcoma.
- Endometrial Cancer (The SIENDO study): A study evaluating once weekly selinexor as a maintenance therapy versus placebo in patients with endometrial cancer after first- or second-line chemotherapy
- Glioma (The KING study): An open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of selinexor in patients with recurrent gliomas