1. Participating groups:
A randomized phase III trial of maintenance with Selinexor/ placebo after
combination chemotherapy for patients with advanced or
recurrent endometrial cancer.
Participating groups:
BGOG (Belgium, sponsor)
NSGO (Nordic Society of Gynecologic Oncology)
GINECO (France)
MITO (Italy), Candiolo Coordinator of 8 centers
AGO and NOGGO (Germany)
SAKK (Switzerland)
HECOG (Greece)
PI: Ignace Vergote, BGOG

2. Background and Rationale (1)
Advanced/recurrent Endometrial Cancer is still
a lethal disease > new drugs are needed

3. Exportin 1 XPO1 is frequently overexpressed in endometrial cancer
Background and Rationale (2)
Exportin 1 XPO1 is frequently overexpressed in endometrial cancer
Selinexor (KPT-330), is a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1) which impairs its activity of exporting out of the nucleus proapoptotic factors therefore
inducing apoptosis

4. Clinical activity in endometrial cancer:
The phase II SIGN trial (Endometrial Cancer cohort)
23 Endometrial Cancers (median previous treatments 2 (1–5)
DCR: 43%; ORR: 14%;. Median PFS : 12 wks ; 2 EC on SEL treatment >6 mos.
Toxicities:
Grade 1/2 drug-related adverse events (AEs) included:
nausea (56%), anorexia (47%), weight loss (44%) & fatigue (42%).
Grade 3 drug related AEs included: thrombocytopenia (11%), fatigue (10%), anemia (9%) , nausea (8%).
Grade 4 AEs were cataract (1pt) & hyponatremia (1pt).
Vergote et al ESMO 2016

5. Study Design Oral Selinexor 80 mg/weekly Until progression
Key inclusion criteria
Endometrial cancer (carcinosarcoma is allowed also)
No more than 2 lines for
metastatic disease
Must have received carboplatin paclitaxel earlier
PR or CR after last Carboplatin and Taxane
Tumor material available
Oral Selinexor
80 mg/weekly
Until progression
Placebo 80 mg
weekly
Primary endpoint: PFS
Secondary: PFS2 (successive treatment), OS,
Exploratory (ctDNA, plasma)
Patients: 126 (63 for each ARM)
MITO target: ?