Participating groups:

Presentazione sul tema: "Participating groups:"— Transcript della presentazione:

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: ?

6 Stato avanzamento SIENDO
Manca feedback dallo SPONSOR sulle questioni finanziarie contrattuali (da Novembre 2017) Già individuata CRO che seguira’ lo studio Già individuata compagnia assicurativa Da definizione bozza contrattuale tempo previsto per sottomissione a CEC (Coordinatore), AC (AIFA), CEP (periferici) 2-3 settimane. Realisticamente sottomissione prevista per 13/03/2018 (Riunione CE coordinatore) GRANT?