Inclusion Criteria:
1. Female, at least 18 years of age at the time of informed consent.
2. Histological confirmed endometrial cancer of the endometrioid, serous, or
undifferentiated type. Carcinosarcoma of the uterus is also allowed.
3. Completed a single line of at least 12 weeks of taxane-platinum combination therapy
for Stage IV disease or at first relapse and is in partial or complete remission
according to RECIST v1.1. This includes patients who received taxane-platinum
combination therapy for primary Stage IV disease and patients who received
taxane-platinum combination therapy for recurrent (i.e., relapse after primary therapy
for early stage disease including surgery and/or adjuvant therapy) disease.
4. Must be able to initiate study drug 5 to 8 weeks after completion of their final dose
of chemotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Patients must have adequate bone marrow function and organ function within 2 weeks
before starting study drug as defined by the following laboratory criteria:
1. Hepatic function: total bilirubin up to 1.5 x upper limit of normal (ULN);
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN in
patients without liver metastasis. For patients with known liver involvement of
their tumor: AST and ALT ≤5 x ULN.
2. Hematopoetic function: Absolute neutrophil count (ANC) ≥1.5 x 109/L; platelet
count ≥100 x 109/L; hemoglobin ≥9.0 g/dL.
3. Renal function: estimated creatinine clearance (CrCl) of ≥30 mL/min, calculated
using the Cockroft Gault formula.
7. In the opinion of the Investigator, the patient must:
1. Have a life expectancy of at least 12 weeks, and
2. Be fit to receive experimental therapy
8. Premenopausal females of childbearing potential must have a negative pregnancy test
(serum β-human chorionic gonadotropin test) prior to the first dose of study drug.
Female patients of childbearing potential must agree to use highly effective methods
of contraception throughout the study and for 3 months following the last dose of
study drug.
9. Written informed consent in accordance with federal, local, and institutional
guidelines. The patient must provide informed consent prior to the first screening
procedure.
Exclusion Criteria:
Patients meeting any of the following exclusion criteria are not eligible to enroll in this
study:
1. Has any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear
cell carcinomas.
2. Received a blood or platelet transfusion during 4 weeks prior to randomization.
3. Being treated with a concurrent cancer therapy.
4. Previous treatment with an XPO1 inhibitor.
5. Previous treatment with anti-PD-1 or anti-PD-L1 immunotherapy (e.g., pembrolizumab).
6. Concurrent treatment with an investigational agent or participation in another
clinical trial.
7. Patients who received any systemic anticancer therapy including investigational agents
or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to
C1D1. Palliative radiotherapy may be permitted for symptomatic control of pain from
bone metastases in extremities, provided that the radiotherapy does not involve target
lesions, and the reason for the radiotherapy does not reflect progressive disease
(PD).
8. Major injuries or surgery within 14 days prior to C1D1 and/or planned surgery during
the on-treatment study period.
9. Previous malignant disease, except patients with other malignant disease, for which
the patient has been disease-free for at least 3 years. Concurrent other malignant
disease except for curatively treated carcinoma in situ of the cervix or basal cell
carcinoma of the skin.
10. Any life-threatening illness, medical condition or organ system dysfunction which, in
the investigator's opinion, could compromise the patient's safety or compliance with
the protocol.
11. Known contraindications to selinexor.
12. Known uncontrolled hypersensitivity to the investigational drug, or to its excipients.
13. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging.
14. Persistent Grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy, with
the exception of alopecia.
15. Active brain metastases (e.g., stable for <8 weeks, no adequate previous treatment
with radiotherapy and/or surgery, symptomatic, requiring treatment with
anti-convulsants. Corticoid therapy is allowed if administered as stable dose for at
least 1 month before randomization).
16. Known unstable cardiovascular function:
1. Symptomatic ischemia, or
2. Uncontrolled clinically significant conduction abnormalities (i.e., ventricular
tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or
asymptomatic left anterior fascicular block /right bundle branch block will not
be excluded), or
3. Congestive heart failure of New York Heart Association Class ≥3, or
4. Myocardial infarction within 3 months
17. Females who are pregnant or actively breastfeeding.
18. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics,
antivirals, or antifungals within 1 week prior to first dose; however, prophylactic
use of these agents is acceptable even if parenteral.
19. Active hepatitis C and/or B infection.
20. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other
GI disease or GI dysfunction that could interfere with absorption of study drug. A
history of bowel obstruction requiring a nasogastric tube or intravenous infusion
during the past 2 months is not allowed (except when this obstruction is caused by
surgery or other non-malignant causes).
21. Psychiatric illness or substance use that would prevent the patient from giving
informed consent or being compliant with the study procedures.
22. Patients unwilling or unable to comply with the protocol.
23. Persons who have been committed to an institution by official or judicial order.
24. Patients with dependency on the Sponsor, Investigator or study site.
