Relative Bioavailability/Bioequivalence of Different Formulations of Selinexor, the Impact of Hepatic Impairment on Selinexor Pharmacokinetics, Tolerability and Antitumor Activity of Selinexor Combination Treatment

Sponsor
Karyopharm Therapeutics Inc
Study ID
NCT04256707
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Colorectal Cancer (CRC)
  • Non-Small Cell Lung Carcinoma (NSCLC)
  • Other Solid Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Selinexor 100 mg — DRUG
    100-mg 2 formulations: * 5 × 20-mg tablets (Tablet A) * 1 × 100-mg tablet (Tablet B)
  • Docetaxel — DRUG
    75 mg/m\^2 IV
  • Pembrolizumab — DRUG
    200 mg IV
  • FOLFIRI — DRUG
    FOLFIRI: * Irinotecan 180 mg/m\^2 * Leucovorin 400 mg/m\^2 * 5-FU 400 mg/m\^2 bolus * 5-FU 2400 mg/m\^2 IV
  • Selinexor 40 mg — DRUG
    \- 2 × 20-mg tablets (Tablet A)
  • Selinexor 80 mg — DRUG
    \- 4 × 20-mg tablets (Tablet A)
  • Selinexor 60 mg — DRUG
    \- 3× 20-mg tablets (Tablet A)

Study Details

This is a Phase 1/2, two-part, multi-arm, open-label study in patients with normal Hepatic Function (HF), with either Non-small cell lung cancer (NSCLC), who have had 1-2 prior lines of treatment, with 1 line containing a checkpoint Inhibitor (CPI); or patients with normal HF, with colorectal cancer (CRC) who have had 1-3 prior lines (KRAS wild-type \[WT\]) or 1-2 prior lines (mutant KRAS) of treatment with no CPI; or patients with impaired HF, with any solid tumor, who have had at least 1 prior line of treatment. The study will comprise 2 treatment periods (monotherapy and combination therapy). The purposes of this study, during Monotherapy period, are: (1) to determine the relative bioavailability of the 100 milligrams (mg) (Tablet B) and 20 mg (Tablet A) tablets of selinexor at 100 mg once weekly (QW) dose in patients with normal hepatic function; and (2) to assess the PK of selinexor after a single dose of 40 mg (2 × 20 mg), among patients with moderate and severe hepatic impairment, relative to 100 mg (5 × 20 mg), among patients with normal hepatic function; and, during the Combination therapy period, to assess the preliminary anti-tumor activity of selinexor in combination with docetaxel in patients with NSCLC and with pembrolizumab or folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) in patients with CRC.

Key Dates

Start date
Jan 14, 2020
Status verified
Mar 2025
Primary completion
Jul 31, 2024
Completion
Jul 31, 2024

Study Design

Enrollment
126 participants (actual)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Monotherapy: Normal Hepatic Function (Selinexor)
    (Closed for Enrollment) Cohort 1: * Week 1: selinexor 5 x 20-mg tablet daily; * Week 2: selinexor 1 x 100-mg tablet daily Cohort 2: * Week 1: selinexor 1 x 100-mg tablet daily; * Week 2: selinexor 5 x 20-mg tablet daily.
  • Experimental: Monotherapy: Impaired Hepatic Function (Selinexor)
    Cohort 3: Patients with Moderate Hepatic Impairment with any Solid Tumors; \- Selinexor 2 x 20-mg tablet once weekly (QW). Cohort 4: Patients with Severe Hepatic Impairment with any Solid Tumors; \- Selinexor 2 x 20-mg tablet QW.
  • Experimental: Combination Therapy: NSCLC Arm A: (Selinexor + Docetaxel)
    (Closed for Enrollment) Selinexor 60 mg oral dose QW and docetaxel 75 mg/m\^2 intravenously (IV) once every 3 weeks (Non-small cell lung cancer \[NSCLC\] patients).
  • Experimental: Combination Therapy: CRC Arm B: (Selinexor + Pembrolizumab)
    (Closed for Enrollment) Selinexor 80 mg oral does QW and pembrolizumab 200 mg IV every 3 weeks (Colorectal cancer \[CRC\] Patients).
  • Experimental: Combination Therapy: CRC Arm C: (Selinexor + FOLFIRI)
    (Closed for Enrollment) Cohort 1: Selinexor 40 mg oral dose Days 1, 3, 15 and 18 in a 28-day cycle and FOLFIRI (irinotecan 180 mg/m\^2; leucovorin 400 mg/m\^2; 5- fluorouracil (5-FU) 400 mg/m\^2 bolus then 5-FU 2400 mg/m\^2 continuous over 46-48 hours; IV on Day 1 and 15 in a 28-day cycle) (CRC Patients). Cohort 2: Selinexor 80 mg oral dose Days 1 and 15 in a 28-day cycle and FOLFIRI (irinotecan 180 mg/m\^2; leucovorin 400 mg/m\^2; 5-FU 400 mg/m\^2 bolus then 5-FU 2400 mg/m\^2 continuous over 46-48 hours; IV on Day 1 and 15 in a 28-day cycle) (CRC Patients).

Primary Outcome Measure

Monotherapy Period: Area Under the Concentration-Time Curve from Time Zero to Time of Last Concentration (AUC 0-t) of Selinexor in Patients with Normal, Moderate and Severe Hepatic Function [ Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24, 30, and 48 hours post-dose on Days 1 and 8 ]

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