Selinexor Clinical Trials

What Is Selinexor?

Selinexor is an FDA-approved medication for multiple myeloma. It is a first-in-class, oral selective exportin 1 (XPO1) inhibitor. Selinexor works by blocking the nuclear export protein XPO1, which causes tumor suppressor proteins to build up inside cancer cells. This action also inhibits the production of oncoprotein messenger RNAs (mRNAs), selectively leading to the death of cancer cells.

Currently, selinexor is approved for use in patients with multiple myeloma, particularly in cases of relapsed or refractory disease, or after other treatments have failed. It is also being investigated in a wide range of other cancers, including acute myeloid leukemia, myelofibrosis, and various lymphomas.

Uses and Conditions Under Study

Selinexor is being studied for its potential to treat a variety of cancers, often leveraging its mechanism of inhibiting XPO1 to target cancer cell growth and survival.

• Multiple Myeloma: Selinexor is extensively studied for multiple myeloma, including relapsed and refractory forms. This plasma cell disorder is characterized by the abnormal growth of plasma cells in the bone marrow. Selinexor's ability to accumulate tumor suppressor proteins within these cells makes it a promising treatment. There are 39 trials investigating selinexor for multiple myeloma.
• Acute Myeloid Leukemia (AML): AML is a fast-growing cancer of the blood and bone marrow. Selinexor is being explored as a treatment option for AML, including secondary AML, due to its ability to induce cancer cell death. A total of 20 trials are focused on selinexor for various forms of acute myeloid leukemia.
• Myelofibrosis: This is a rare bone marrow disorder that disrupts the body's normal production of blood cells. Selinexor is under investigation for myelofibrosis in 5 trials, aiming to address the abnormal cell proliferation characteristic of the disease.
• Endometrial Cancer: This type of cancer originates in the lining of the uterus. Selinexor's mechanism of action, by inhibiting XPO1 and promoting tumor suppressor protein accumulation, is being evaluated in 4 trials for its effectiveness in treating endometrial cancer.
• Lymphoma: Lymphoma is a cancer that begins in infection-fighting cells of the immune system, called lymphocytes. Selinexor is being studied in 3 trials for different types of lymphoma, including B-cell non-Hodgkin lymphoma, where it may help by disrupting cancer cell survival pathways.

Dosing

Selinexor is an oral medication, typically taken by mouth. The specific dosage and frequency can vary depending on the condition being treated and the study phase.

In early phase trials, selinexor has been studied at various weekly doses, including 20 mg, 40 mg, and 60 mg, administered once weekly (Days 1, 8, 15, and 22 of a cycle). Other regimens have explored doses such as 80 mg once weekly. Some studies have also investigated twice-weekly (BIW) dosing.

Dosages expressed per body surface area (BSA) have also been explored, such as approximately 55 mg/m² (ranging from 60 to 120 mg based on BSA) or 60 mg (equivalent to 35 mg/m²). For specific conditions like ovarian, endometrial, or cervical carcinoma, doses up to 60 mg/m² twice weekly or 60 mg/m² once weekly have been studied. These various dosing strategies are being evaluated to determine the most effective and well-tolerated regimen across different cancer types.

Side Effects

In clinical trials, patients taking Selinexor experienced various side effects. These trials included up to 403 patients in the Selinexor treatment arms and compared outcomes to patients receiving a placebo.

• Decreased appetite was reported by 68.1% of patients on Selinexor, compared to 20.5% on placebo.
• Nausea affected 62.8% of patients taking Selinexor, while 25.4% of patients on placebo experienced it.
• Fatigue occurred in 53.8% of patients on Selinexor, versus 35.4% on placebo.
• Vomiting was reported by 50.8% of patients taking Selinexor, compared to 12.6% on placebo.
• Weight decreased in 44.9% of patients on Selinexor, while 7.1% on placebo experienced weight loss.
• Thrombocytopenia (low platelet count) was observed in 39.2% of patients receiving Selinexor, compared to 5.5% on placebo.
• Anemia (low red blood cell count) affected 37.7% of patients on Selinexor, versus 15.0% on placebo.
• Diarrhea was reported by 29.3% of patients taking Selinexor, compared to 12.2% on placebo.
• Constipation occurred in 28.3% of patients on Selinexor, versus 18.8% on placebo.

Other common side effects included hyponatremia (low sodium levels) in 26.3% of Selinexor patients (8.9% on placebo), dysgeusia (altered taste) in 26.2% of Selinexor patients (4.7% on placebo), and asthenia (lack of energy) in 24.3% of Selinexor patients (7.9% on placebo).

Clinical Trial Results

Advanced or Metastatic Solid Tumor Cancer (NCT01607905)

In a safety study of Selinexor for advanced or metastatic solid tumors, the recommended Phase 2 dose was determined to be 35 mg/m^2. The study also evaluated various clinical outcomes across different cancer types:

• For gynecological cancer patients, the median overall survival was 491 days, with a median progression-free survival of 119 days.
• Patients with castrate-resistant prostate cancer had a median overall survival of 354 days and a median progression-free survival of 127 days.
• For other solid tumors, the median overall survival was 290 days, with a median progression-free survival of 88 days.
• Objective response rates varied by cancer type: 15.0% for gynecological cancer, 14.3% for melanoma, 2.2% for other solid tumors, and 1.8% for colorectal cancer. No objective responses were observed in squamous cell cancer, castrate-resistant prostate cancer, or glioblastoma multiforme.

Recurrent Gliomas (NCT01986348)

A study in patients with recurrent gliomas evaluated Selinexor at different doses. The overall response rate was 10.0% for patients receiving 80 mg, 8.3% for 50 mg/m^2, and 7.7% for 60 mg. The 6-month progression-free survival rate was highest at 17.24% for the 80 mg dose. Median overall survival ranged from 8.48 months (60 mg) to 10.51 months (50 mg/m^2).

Advanced Gynecologic Malignancies (NCT02025985)

In a study of female patients with advanced gynecologic malignancies, Selinexor was evaluated across different cohorts and schedules. For ovarian carcinoma, a schedule of up to 50 mg/m^2 twice weekly (BIW) resulted in a median overall survival of 348 days and an overall response rate of 9.5%. Another schedule for ovarian carcinoma (up to 60 mg/m^2 once weekly, QW) showed a 15.0% overall response rate. For endometrial carcinoma, the overall response rate was 13.6%, with a median progression-free survival of 86.5 days.

Relapsed AML in Older Patients (NCT02088541)

This study investigated Selinexor (60 mg, equivalent to 35 mg/m^2) in older patients with relapsed Acute Myeloid Leukemia (AML). Patients treated with Selinexor achieved an overall response rate of 13.6% and a disease control rate of 50.8%. The median overall survival for Selinexor patients was 94 days. The median disease-free survival for those who achieved complete remission or complete remission with incomplete hematologic recovery was 175 days.

Richter's Transformation (NCT02138786)

In a study for Richter's Transformation, Selinexor treatment resulted in an overall response rate of 4% and a disease control rate of 28.0%. The median duration of progression-free survival was 38 days.

Currently Recruiting Trials

Selinexor is currently being investigated in numerous clinical trials for a variety of conditions, primarily focusing on different types of cancer. These studies aim to understand its effectiveness and safety, often in combination with other therapies or as a maintenance treatment.

• A Phase 1 study, NCT07200102, is enrolling 20 participants with multiple myeloma to evaluate Selinexor as a maintenance therapy after CAR-T cell treatment. This trial is sponsored by Washington University School of Medicine.
• For patients with relapsed or refractory multiple myeloma, a large Phase 3 study, NCT07579234, is comparing F182112 against standard of care, which includes Selinexor-based regimens, in 261 participants.
• Another Phase 3 trial, NCT07138209, is comparing QLS32015 monotherapy to Selinexor and Dexamethasone, or Pomalidomide and Dexamethasone, for relapsed or refractory multiple myeloma, with an enrollment target of 228 participants.
• Researchers are also exploring Selinexor's role in predicting treatment response. Study NCT07514052, a multicenter prospective study with 127 participants, seeks to identify predictive biomarkers for Selinexor-based therapy in relapsed/refractory multiple myeloma.
• Beyond multiple myeloma, Selinexor is being studied for other challenging conditions. A Phase 2/3 trial, NCT07369739, is combining Golidocitinib with Selinexor for CAEBVD (Chronic Active EBV Infection), targeting 28 participants.
• In lymphoma, NCT06966154 is a Phase 1/2 study evaluating Tislelizumab in combination with Golidocitinib and Selinexor for relapsed/refractory Natural Killer/T-cell Lymphoma (NKTCL), aiming for 68 participants.
• For relapsed or refractory diffuse large B-cell lymphoma, a Phase 3 study, NCT07011056, is comparing Purinostat Mesylate for injection against Selinexor, with an enrollment of 390 participants.
• Selinexor monotherapy is being investigated in NCT05980806, a Phase 2 trial for JAK inhibitor-naïve myelofibrosis patients with moderate thrombocytopenia, with a target of 58 participants.
• In solid tumors, NCT05611931 is a Phase 3 study evaluating Selinexor as maintenance therapy in 276 participants with p53 wild-type, advanced or recurrent endometrial carcinoma.
• A Phase 1/2 trial, NCT05432804, is testing the addition of Selinexor to temozolomide for recurrent glioblastoma, with an enrollment target of 97 participants.

Where to Participate

Clinical trials involving Selinexor are widely accessible, with studies actively recruiting across 302 sites in 153 cities and 44 states. This broad reach helps ensure that patients in various regions have the opportunity to participate.

The top cities with multiple recruiting sites include:

• Los Angeles, California (12 sites)
• New York, New York (12 sites)
• Atlanta, Georgia (7 sites)
• St Louis, Missouri (7 sites)
• Cincinnati, Ohio (6 sites)
• Memphis, Tennessee (6 sites)
• Chicago, Illinois (6 sites)
• Boston, Massachusetts (6 sites)
• Houston, Texas (6 sites)
• Pittsburgh, Pennsylvania (5 sites)

Eligibility for these trials generally includes individuals aged 12-99 years, of all genders. Healthy volunteers are not eligible to participate, but children are included in some studies.

Development Timeline

The clinical development journey for Selinexor began on May 30, 2012. Since then, a robust pipeline has emerged, with a total of 181 trials initiated, enrolling over 12,734 participants to date. A significant driving force behind this development has been Karyopharm Therapeutics Inc., sponsoring 32 of these studies.

Early investigations explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted to oncology, where Selinexor has been extensively studied across various cancer types. The development has progressed through multiple phases, with the majority of studies being Phase 2 (76 trials), followed by Phase 1 (36 trials) and Phase 1/Phase 2 (36 trials). There are also 15 Phase 3 trials underway, indicating advanced stages of research for several indications.

Selinexor's pipeline has expanded to address a wide range of challenging cancers, including multiple myeloma (both newly diagnosed and relapsed/refractory forms), various lymphomas (such as Diffuse Large B-cell Lymphoma, Central Nervous System Lymphoma, and NK/T-cell Lymphoma), acute myeloid leukemia, myelofibrosis, endometrial carcinoma, ovarian cancer, and sarcomas. The latest study is set to begin on May 12, 2026, demonstrating ongoing commitment to exploring Selinexor's potential.