Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma (XPORT-EC-042)

Karyopharm Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Endometrial Cancer

Treatments: Drug: Matching Placebo for selinexor; Drug: Selinexor

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT05611931

XPORT-EC-042

GOG-3083 (Other Identifier)

ENGOT-EN20 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v 1.1]) after completing at least 12 weeks of platinum-based therapy. A total of 276 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.

Enrollment: 276 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Patients must meet all of the following inclusion criteria in order to be eligible to participate in this study:

• Adults (Aged ≥ 18 years)
• Histologically confirmed endometrial cancer (endometrioid, serous, undifferentiated, or carcinosarcoma sub-types) that is TP53 wild type by central NGSHistologically confirmed EC including endometrioid, serous, undifferentiated, and carcinosarcoma
• Must have completed at least 12 weeks of platinum-based chemotherapy (with or without immune checkpoint inhibitors), with a confirmed partial or complete response according to RECIST v1.1
• Must be able to initiate C1D1 within 3-8 weeks after last platinum dose
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow function and organ function

Exclusion Criteria: Patients meeting any of the following exclusion criteria are not eligible to participate in this study:

• Uterine sarcomas, clear cell or small cell carcinoma with neuroendocrine differentiation
• Palliative radiotherapy administered within 14 days of intended C1D1
• Any gastrointestinal dysfunction that could interfere with the absorption of oral study therapy
• Serious psychiatric or medical conditions that could interfere with study participation or would make study involvement unreasonably hazardous
• Previous treatment with an XPO1 inhibitor
• Stable disease or disease progression after platinum-based chemotherapy
• Pregnancy, breastfeeding, or other legal/ethical restrictions to trial participation
• Known dMMR/MSI-H EC tumors that are medically eligible to receive an immune checkpoint inhibitor

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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276 participants in 2 patient groups, including a placebo group

Selinexor

Experimental group

Description:

Participants will receive a fixed dose of selinexor 60 milligrams (mg) oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle.

Treatment:

Drug: Selinexor

Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Treatment:

Drug: Matching Placebo for selinexor