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 Anti-Cancer Agents & Biologic Therapy
Drug Development
Ovarian Cancer
Endometrial Cancer
Gynaecologic Malignancies
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

Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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:

970P

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

NCT02269293

Legal entity responsible for the study

Memorial Sloan Kettering Cancer Center

Funding

Karyopharm Pharmaceuticals

Disclosure

All authors have declared no conflicts of interest.