The phase 3 SIENDO study, which is evaluating maintenance selinexor in endometrial cancer, has been recommended by the Data and Safety Monitoring Board to continue as previously planned without the need to add additional patients to the trial or amend the study protocol, following a prespecified interim futility analysis.
The phase 3 SIENDO study (NCT03555422), which is evaluating maintenance selinexor (Xpovio) in endometrial cancer, has been recommended by the Data and Safety Monitoring Board to continue as previously planned without the need to add additional patients to the trial or amend the study protocol, following a prespecified interim futility analysis.
"We are very excited that the SIENDO study has passed its planned futility analysis and that the study will continue as planned," said Sharon Shacham, PhD, MBA, president and chief scientific officer of Karyopharm, the developer of selinexor. "We believe this is an encouraging development for the study, and more importantly, for patients and families in need of novel treatment options for advanced or recurrent endometrial cancer.”
The ongoing, multicenter trial is evaluating the efficacy and safety of selinexor as a frontline maintenance therapy in patients with advanced or recurrent endometrial cancer. Topline results are expected in the second half of 2021.
In July 2019, the FDA granted an accelerated approval to selinexor for use in combination with dexamethasone as a treatment for 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. Selinexor is also indicated for adult patients with relapsed/refractory diffuse large B-cell lymphoma, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 prior lines of systemic therapy.
In the placebo-controlled, randomized, phase 3 SIENDO trial, investigators are enrolling patients with primary stage IV or recurrent endometrial cancer who had a partial or complete response following a single line, of at least 12 weeks, of standard taxane-platinum combination therapy.
Patients are randomized 2:1 to receive either maintenance selinexor or placebo, both at 80 mg weekly, until disease progression. The expected enrollment is 248 patients; approximately 109 patients have been enrolled as of the date of the planned futility analysis.
To be eligible for enrollment, patients must also be at least 18 years old; have histological confirmed endometrial cancer of the endometrioid, serous, or an undifferentiated subtype, or carcinoma sarcoma of the uterus; an ECOG performance status of 0 to 1; and have adequate bone marrow function and organ function within 2 weeks before starting the study drug, among other criteria.
Those with any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear cell carcinomas; receive a blood or platelet transfusion during 4 weeks prior to randomization; are being treated with concurrent cancer therapy; had received prior treatment with an XPO1 inhibitor, PD-1/PD-L1 inhibitor, or concurrent treatment with an investigational agent in another trial; have active brain metastases; have known unstable cardiovascular function; and have active hepatitis B and/or C infection are excluded from enrolling on the study.
The primary end point is investigator-assessed progression-free survival (PFS); the goal is to demonstrate a hazard ratio of 0.6. Secondary end points include PFS as assessed 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 treatment-emergent adverse events.
“There are currently no approved therapies in the maintenance setting for patients with advanced endometrial cancer, making the future trial results from the SIENDO study, particularly important,” Shacham concluded. “We expect to report topline data from this study in the second half of 2021."
Karyopharm announces ongoing phase 3 SIENDO study of Xpovio (selinexor) in patients with endometrial cancer passes planned interim futility analysis: Data and Safety Monitoring Board recommends the study should proceed as planned without any modifications. News release. Karyopharm. November 25, 2020. Accessed November 25, 2020. https://bit.ly/2HAtKTY.