Summary

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 220 participants will be enrolled in the study and
randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.

Eligibility

1. At least 18 years of age at the time of signing informed consent.
2. Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinosarcoma.
3. TP53 wt assessed by next generation sequencing (NGS), evaluated by a central vendor.
4. Completed a single line, at least 12 weeks of platinum-based therapy (not including adjuvant or neoadjuvant therapy for Stage I-III disease) and achieved confirmed partial or complete response (PR or CR) by imaging, according to RECIST version 1.1. The participants should have received treatment for: Primary Stage IV disease, defined as:
5. had a primary or later debulking surgery during first-line platinum-based therapy with R0 resection (R0 resection indicates a macroscopic complete resection of all visible tumor) and achieved CR after at least 12 weeks platinum-based therapy, OR
6. had a primary or later debulking surgery during first-line platinum-based therapy with R1 resection (R1 resection indicates incomplete removal of all macroscopic disease) and achieved PR or CR after at least 12 weeks platinum-based chemotherapy, OR
7. had no surgery and achieved PR or CR after at least 12 weeks platinum-based chemotherapy OR At first relapse (i.e., relapse after primary therapy including surgery and/or chemotherapy and/or immunotherapy for Stage I-IV disease), defined as:
8. had Stage I - III disease at diagnosis and received, at initial diagnosis, adjuvant chemotherapy and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse,
9. had Stage I-III disease at diagnosis and did not receive adjuvant chemotherapy at initial diagnosis and relapsed later. Participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse, OR
10. had Stage IV disease at diagnosis and received initially chemotherapy with or without surgery and relapsed later. At the time of relapse, participants should have PR or CR after at least 12 weeks of platinum-based chemotherapy compared with the start of this chemotherapy at the time of relapse.
11. Previous treatment with anti-programmed cell death protein 1(PD-1) or anti-programmed death-ligand 1(PD-L1) monoclonal antibody and concomitant biologic agents (e.g., bevacizumab, trastuzumab) is allowed.
12. Must be able to initiate study drug 3 to 8 weeks after completion of their final dose of chemotherapy.
13. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
14. Participants must have adequate bone marrow function and organ function within 2 weeks before starting study drug as defined by the following laboratory criteria:
15. Hepatic function: total bilirubin up to less than (<) 3*upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (<=) 2.5*ULN in participants without liver metastasis. For participants with known liver involvement of their tumor: AST and ALT (<=) 5*ULN
16. Hematopoietic function within 1 week: Absolute neutrophil count (ANC) greater than or equal to (>=) 1.5*10^9/liter (L); platelet count >= 100*10^9/L; hemoglobin >= 9.0 gram per deciliter (g/dL) per local laboratory results
17. Renal function: estimated creatinine clearance (CrCl) of >= 20 milliliter per minute (mL/min), calculated using the standard local formula, as applicable
18. In the opinion of the Investigator, the participant must:
19. Have a life expectancy of at least 12 weeks, and
20. Be fit to receive investigational therapy
21. Premenopausal females of childbearing potential must have a negative pregnancy test (serum ß-human chorionic gonadotropin test) prior to the first dose of study drug. Female participants of childbearing potential must agree to use highly effective methods of contraception throughout the study and for 90 days following the last dose of study drug.
22. Written informed consent signed in accordance with federal, local, and institutional guidelines prior to the first screening procedure.

Treatment Sites in Georgia