SIENDO Study in Endometrial Cancer Hits Enrollment Milestone

All 248 patients with endometrial cancer have been enrolled in the phase 3 SIENDO clinical trial.

The phase 3 SIENDO clinical trial has completed its enrollment of 248 patients with endometrial cancer, according to a press release by Karyopharm Therapeutics Inc.1

SIENDO is a prospective, multicenter, double-blind, placebo-controlled, randomized study (NCT03555422). The study aims to show that selinexor [Xpovio], a first-in-class oral selective inhibitor of the nuclear export compound, is effective and safe for the treatment of patients with advanced or recurrent endometrial patients. Selinexor selectively binds to nuclear protein exportin 1 and inhibits its export. It also blocks the nuclear export of tumor suppressor, growth regulatory, and anti-inflammatory proteins.1,2

"There is a clear and significant need for treatments that help extend remission or delay disease progression following front-line chemotherapy treatment in patients with endometrial cancer," said Sharon Shacham, PhD, chief scientific officer of Karyopharm, in a press release. "Completing enrollment in the phase 3 SIENDO study is an important step toward our goal of delivering a novel, front-line maintenance therapy for patients and positive data from this study will further reinforce our views on the therapeutic potential of selinexor in solid tumor indications. We anticipate reporting top-line data from this event-driven study by the end of this year or early next year."

SIENDO is ongoing in 18 areas of the United States, as well as centers in Canada, Europe, Asia, and the Middle East. With patients randomized 2:1 to receive either selinexor or placebo, SIENDO is exploring progression-free survival as its primary end point. The secondary end points of the study include PFS by blinded independent central review, disease-specific survival, overall survival, time to first subsequent treatment, PFS after subsequent treatment, time to second subsequent treatment, disease control rate, health-related quality of life, and the percentage of patients with treatment-emergent adverse events.

Selinexor will be administered orally at 80 mg in patients with a body mass index (BMI) less than 20 kg/m2 on days 1, 8, 15, and 22 of each 28-day cycle. Matching placebo in the comparator arm will be administered in 4 80-mg tablets or 3 60-mg tablets.

The study is including female patients aged 18 years and older with histologically confirmed disease. Patients are required to be able to start selinexor 5 to 8 weeks after completing chemotherapy, have an ECOG performance status of 0 or 1, and e adequate bone marrow, organ, hepatic, and renal function. All patients must also have a life expectancy of at least 12 weeks and be fit for experimental therapy.

Selinexor is FDA approved in combination with dexamethasone (Ozurdex) for the treatment of adult patients with relapsed refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody. The drug also holds several other indications for the treatment of hematologic malignancies. The SIENDO is 1 of many ongoing studies to investigate the efficacy of selinexor in patients with solid tumors.1

Although its efficacy in endometrial cancer is yet to be determined, the drug’s label warns about adverse events like thrombopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, embryo-fetal toxicity, and cataract.

References:

Karyopharm completes patient recruitment in phase 3 SIENDO study of selinexor in patients with endometrial cancer. News release. Karypharm Therapeutics. December 2, 2021. Accessed December 6, 2021. https://bit.ly/3Eu29vP

Maintenance with selinexor/placebo after combination chemotherapy in participants with endometrial cancer [SIENDO] (ENGOT-EN5). Clinicaltrials.gov. Accessed December 6, 2021. https://bit.ly/3DrCBh