970P - A Phase 1 Study of Selinexor (S) in Combination with Paclitaxel (P) and Carboplatin (C) in Patients (pts) with Advanced Ovarian (OC) or Endometrial...

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Clinical research
Ovarian Cancer
Endometrial Cancer
Gynaecologic Malignancies
Basic Scientific Principles
Biological therapy
Presenter Vicky Makker
Citation Annals of Oncology (2017) 28 (suppl_5): v330-v354. 10.1093/annonc/mdx372
Authors V. Makker, N. Boucicaut, K.A. Cadoo, R. Grisham, D.M. Hyman, R. O'Cearbhail, A. Snyder Charen, W. Tew, M. Martin, C. Aghajanian
  • Medicine, Memorial Cloan Kettering Cancer Center, 10065 - New York/US



Selinexor (S) is an oral, first in class, inhibitor of exportin 1 (XPO1). In a Phase II clinical trial of pts with relapsed ovary cancer (OC) andendometrial cancer (EC), single agent S, demonstrated anti-cancer activity. In addition, clinical exploratory analysis has demonstrated S target engagement and a relationship between baseline circulating tumor cells and duration of response. Here we report results of a phase 1 study evaluating safety/tolerability of S combined with C and P in pts with advanced OC and EC or carcinosarcomas.


Patients (Pts) were enrolled using 3 + 3 dose escalation design for each regimen (reg). All pts with OC received 1 prior platinum (plt) therapy. Ptswith EC could be chemotherapy naïve or have received 1 prior plt therapy. Pts were enrolled to 1 of 4 regimens regardless of disease type as described in Table. Response was evaluated Q9 weeks (RECIST 1.1).


16 pts (12 EC, 3 OC, 1 endometrial carcinoma) were enrolled. 1 drug related DLT of G3 syncope occurred on Reg 2. Most common G2 AEs were hyperglycemia (43.8%), leukopenia (43.8%), anemia (31.3%). Most common Grade 3 and 4 AEs were anemia (62.5%), neutropenia (37.5%), lymphopenia (43.8%), neutropenia (31.3%) thrombocytopenia (12.5%). 50% of evaluable pts on Reg 1 and 2 were dose reduced due to S toxicity. One dose reduction of S on Reg 3. There were no dose reductions on Reg 4. 13 pts were evauble for efficacy: 2 CRs, 10 PRs, and 1 SD. Time on study ranged from 2–10.8 mos with 3 pts still on study.


Selinexor in combination with carboplatin and paclitacel (CP) chemotherapy in advanced OC, EC, and carcinosarcomas was well tolerated. The RP2Ds have been established at 30mg/m2twice weekly of S and 60 mg flat dose weekly in combination with CP chemotherapy. Given encouraging response, expansion cohorts for Regs 3/4 are planned. Frequent molecular alterations seen in the EC pts included: TP53, PIK3CA, and KRAS. Evaluation of S target engagement/correlatives of response will be discussed.Table:


Regimen #NRegimen details
14C AUC5 (day 1), P 175 mg/m2 (day 1) and S 30 mg/m2 (days 1, 4, 8, 11, 15, 18)
26C AUC5 (day 1), P 80 mg/m2 (days 1, 8, 15) and S 30 mg/m2 (days 1, 4, 8, 11, 15, 18)
33C AUC5 (day 1), P 80 mg/m2 (days 1, 8, 15) and S 60 mg (days 1, 8, 15)
43C AUC5 (day 1), P 175 mg/m2 (day 1) and S 60 mg (days 1, 8, 15)

Clinical trial identification


Legal entity responsible for the study

Memorial Sloan Kettering Cancer Center


Karyopharm Pharmaceuticals


All authors have declared no conflicts of interest.