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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
197TiP - A phase 1/2 trial of selinexor combined with docetaxel for previously treated, advanced KRAS mutant non-small cell lung cancer (ID 244)
12:30 - 13:00 | Author(s): D..R. Camidge
Selinexor is an oral, reversible inhibitor of exportin-1 (XPO1), the major nuclear export protein responsible for nucleocytoplasmic transport of multiple tumor suppressor proteins and cell cycle regulators. Upregulation of XPO1 results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical and clinical trials. The most extensively studied SINE to date, selinexor (KPT-330; Karyopharm Therapeutics, Inc., Newton, MA), has demonstrated single-agent anticancer activity and synergistic effects in combination regimens against multiple cancer types. SINE may have particular relevance in KRAS-driven tumors, for which this treatment strategy demonstrates significant synthetic lethality. Thus, we designed a phase 1/2 study to assess the safety and tolerability of selinexor in combination with docetaxel in patients with previously treated, advanced KRAS mutant non-small cell lung cancer (NSCLC).
This is a multicenter, single-arm, open-label, non-blinded trial. Eligible patients are aged ≥18 years with advanced NSCLC and by central testing documenting presence of KRAS mutation (codons 12, 13, or 61). We will enroll 9–18 patients in the dose escalation cohort and 35 patients in the expansion cohort at five institutions with UT Southwestern as the primary coordinating center for this study. Dose escalation will be performed in a traditional 3 + 3 design. Patients will receive selinexor orally once weekly, with a lead in period of 1 week before chemotherapy initiation, in combination with standard doses of docetaxel given once every 3 weeks. Treatment will be administered in 21-day cycles. Dose limiting toxicities will be assessed based on the first cycle (7-day lead-in + 21-day cycle = 28 day) toxicity. The primary objective is to determine the safety and the maximum tolerated dose and recommended Phase 2 dose of selinexor administered with the standard dose of docetaxel. The sample size estimate is based on the exact one-sample binomial test for proportions. Enrollment will open in January 2018.
Clinical trial identification:
Legal entity responsible for the study:
University of Texas Southwestern Medical Center, Dallas, TX, USA
Karyopharm Therapeutics, Inc., Newton, MA
L. Horn: Has consulting for Abbvie, Astra Zeneca, Lilly, BMS, Merck, Roche-Genentech, Xcovery. D.E. Gerber: Research funding from Karyopharm. All other authors have declared no conflicts of interest.