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NCT04256707 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2026-10-09

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Monotherapy: Area Under the Concentration-Time Curve From Time Zero to Time of Last Concentration (AUC 0-t) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-Inf) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Maximum Plasma Concentration (Cmax) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Combination Therapy (Arms: A and B): Overall Response Rate (ORR) as Assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

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outcome · POSTED

Combination Therapy (Arm C): Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · POSTED

Monotherapy: Time to Maximum Observed Concentration (Tmax) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Terminal Elimination Rate Constant (Lambda z) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Terminal Half-Life (t1/2) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Apparent Clearance (CL/F) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Apparent Volume of Distribution (Vd/F) of Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment

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outcome · POSTED

Monotherapy: Percent Fraction Unbound (fu) of Selinexor (Tablet A) in Plasma Protein

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outcome · POSTED

Monotherapy: Maximum Free-Drug Concentration (Cmax,u) of Free Selinexor (Tablet A) in Plasma

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outcome · POSTED

Monotherapy: Area Under the Free-Drug Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCu) of Free Selinexor (Tablet A) in Plasma

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outcome · POSTED

Monotherapy: Apparent Free-drug Clearance (CLu/F) of Free Selinexor (Tablet A) in Plasma

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outcome · POSTED

Monotherapy: Apparent Free-drug Volume of Distribution (Vu/F) of Free Selinexor (Tablet A) in Plasma

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outcome · POSTED

Combination Therapy (Arms: A, B and C): Progression-free Survival (PFS)

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outcome · POSTED

Combination Therapy (Arms: A, B and C): Duration of Response (DOR)

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outcome · POSTED

Combination Therapy (Arms: A, B and C): Disease Control Rate (DCR)

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outcome · POSTED

Combination Therapy (Arms: A, B and C): Overall Survival (OS)

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outcome · POSTED

Monotherapy: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · POSTED

Combination Therapy (Arms: A and B): Number of Participants With TEAEs

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outcome · POSTED

Combination Therapy (Arm C): Percentage of Participants With ORR as Assessed by RECIST 1.1

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Key Inclusion Criteria: Common inclusion criteria for all patients: 1. Are greater than or equal to \[≥\] 18 years of age at the time of informed consent. 2. Have histologically confirmed solid tumor (any type of advanced or metastatic solid tumor for the Hepatic Impairment Arm of the Monotherapy Part), advanced or metastatic NSCLC or CRC and evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1 or iRECIST criteria, as applicable). 3. Willing to provide written informed consent in accordance with federal, local, and institutional guidelines and comply with all requirements of the study. 4. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective (dual methods of) contraception throughout the study and for 4 months following the last dose of study drug (childbearing potential excludes: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy or hysterectomy); and male patients must use an effective barrier method of contraception throughout the study and for 4 months following the last dose of study drug if sexually active. Male patients must agree not to donate sperm during the study treatment period. For the Monotherapy Part only (bioavailability/bioequivalence \[BA/BE\] and hepatic impairment \[HI\] arms): 5. Have received at least 1 line of systemic anticancer treatment unless there is no first-line standard of care therapy or standard of care therapy is contraindicated (adjuvant or neoadjuvant therapy is not counted as one line of systemic therapy). Patients must have failed prior standard curative therapy for their disease, must be intolerant to or be ineligible for any potentially curative approved treatment, irrespective of line of therapy. 6. Must have either normal hepatic function, or moderate or severe hepatic impairment (as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria: 1. S20-100 and S100-20 arms: normal hepatic function (total bilirubin and aspartate aminotransferase \[AST\] less than or equal to \[≤\] upper limit of normal \[ULN\]). Note: Patients with mild hepatic dysfunction (total bilirubin greater than \[\>\] 1 to 1.5 × ULN or AST \> ULN) may be included if liver function tests are stable for the past 3 months and enrollment is approved in writing by the Sponsor's Medical Monitor. 2. MHI arm: ≥1 week of documented moderate hepatic impairment (total bilirubin \>1.5-3 × ULN, any level of AST). 3. SHI arm: ≥1 week of documented severe hepatic impairment (total bilirubin \>3-10 × ULN, any level of AST). For Combination Therapy Part only: 7. Previous treatment lines (adjuvant or neoadjuvant therapy is not counted as one line of systemic therapy): 1. Arm A: For patients with NSCLC, have received 1-2 prior lines of systemic anti-cancer treatment with 1 regimen including an anti-PD-1/L1 monoclonal antibody (mAb) 2. Arm B: For patients with RAS mutant CRC, 1-2 prior lines of systemic treatments, and no prior anti- programmed cell death protein 1/L1 monoclonal antibody (anti-PD-1/L1 mAb). * KRAS WT: have 1-3 prior lines of systemic treatments. * KRAS mutant (at least 50 percent \[%\] of patients): 1-2 prior lines of systemic treatments. 3. Arm C: For patients with CRC participating in the combination arm with FOLFIRI, 1-2 prior lines of systemic therapy are allowed. 4. Arm B and C in CRC: patient with CRC who are not candidates for curative resection of metastatic lesions. 8. Must have hepatic function as follows: 1. Arm A (combination with docetaxel): Patients with NSCLC who are to receive docetaxel and have bilirubin ≤ ULN, and AST and/or alanine transaminase (ALT) ≤ 1.5 x ULN. 2. Arm B and C: total bilirubin ≤ 1.5 × ULN and AST ≤ 2.5 x ULN, AST ≤ 2.5 x ULN; for Arm B, unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin must be ≤ 4 x ULN. Key Exclusion Criteria: Common exclusion criteria for all patients: 1. Have inadequate hematopoietic function defined as (without transfusion or growth factor support within 7 days prior to first dose): 1. For S20-100 or S100-20 arms: absolute neutrophil count (ANC) \<1.5 × 10\^9/liter (L); platelet count (PLT) \<100 × 10\^9/L; or hemoglobin (Hb) \<10 gram per deciliter (g/dL). 2. For Arms A-C: ANC \<1.5 × 10\^9/L; PLT \<100 × 10\^9/L; or Hb \<10 g/dL. 2. Have inadequate renal function defined as a calculated creatinine clearance (CrCl) of: a. all patients: \<20 mL/min using the formula of Cockcroft and Gault. 3. Have any other medical condition especially any gastrointestinal (GI) dysfunctions or GI disease that could interfere with the absorption of selinexor (e.g., inability to swallow or retain oral medications, malabsorption syndrome, a history of GI surgery which may result in intestinal blind loop, significant gastroparesis, unresolved nausea, vomiting, or diarrhea \[National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade \>1\]). 4. Ongoing infection requiring parenteral antibiotics, antivirals, or antifungals on Day 1 dosing. a. All patients: on Day 1 dosing. 5. Prior exposure to a SINE compound or selinexor. 6. Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as: 1. Not recovered from major surgery ≤21 days for Arms A, B, and C prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted. 2. Have ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade \>1. Patients with any of the following will not be excluded: immune checkpoint-related endocrinopathies that are well controlled with hormonal supplements, patients with electrolyte abnormalities that are well-managed with supplementation, patients with Grade 2 lymphopenia, or patients with alopecia of any grade. In specific cases, patients whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor. 3. Had last dose of previous anti-cancer therapy ≤14 days prior to Day 1 dosing. 4. Palliative radiotherapy \>14 days prior to the study is allowed. 5. Received investigational drugs in other clinical trials within 28 days, or 5 half-lives of the investigational drug (whichever is shorter), prior to Cycle 1 Day 1 (C1D1). 7. Serious active psychiatric or active medical condition that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous for Arms A-C. 8. Known allergy to selinexor (all patients), docetaxel (NSCLC Arm A only), pembrolizumab (CRC arm B only), 5-FU, leucovorin, or irinotecan (CRC Arm C only). 9. Female patients who are pregnant or breastfeeding. For Monotherapy Part only (BA/BE and HI arms): 10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of: 1. ≥3 for patients to be enrolled into the S20-100 or S100-20 arms of the study. 2. ≥4 for patients to be enrolled into the MHI and SHI arms of the study. 11. For MHI and SHI arms: ANC \<1 × 10\^9/L; PLT \<75 × 10\^9/L; or Hb \<8 g/dL. 12. Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosing OR strong CYP3A inducers ≤14 days prior to Day 1 dosing. 13. Inability or unwillingness to undergo a series of PK sampling. For Combination Therapy Part only: 14. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3 for Arms A and B and ECOG PS ≥2 for Arm C. 15. Arm B patients with CRC who are to receive pembrolizumab: 1. Had a diagnosis of immunodeficiency or are receiving systemic steroid therapy (\>10 milligram per day \[mg/day\] of prednisone or equivalent) or any other form of immunosuppressive therapy. 2. Patients with controlled diabetes mellitus and patients with endocrinopathies on stable hormone replacement therapy, are eligible for the trial. 3. Have active autoimmune disease requiring systemic treatment during the past 2 years. Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted. Note: The Investigator needs to evaluate the patient's medical history to confirm that they are eligible to receive the combination with pembrolizumab per these criteria. 4. For patients with CRC who have received live-attenuated vaccine against an infectious disease (e.g., nasal spray influenza vaccine) ≤14 days prior to the intended C1D1 of the Combination Therapy. 16. Arm C: Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Note: for patients who are initially enrolled onto the BA/BE arm in the monotherapy part and plan to switch to combination therapy after completing the planned dosing and PK sample collection, dose interruption between the Monotherapy Part and the Combination Therapy Part is allowed for recovery from AEs. Patients requiring \>21 days to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for documented approval to continue to the Combination Therapy Part if inclusion/exclusion criteria are met. Experiencing PD during the Monotherapy Part does not constitute exclusion from the Combination Therapy Part.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    (Closed for Enrollment) S20-100 arm: * Week 1: selinexor 5 x 20-mg tablet once weekly (QW). * Week 2: selinexor 1 x 100-mg tablet QW. S100-20 arm: * Week 1: selinexor 1 x 100-mg tablet QW. * Week 2: selinexor 5 x 20-mg tablet QW.
    intervention Names
    1. Drug: Selinexor 100 mg
    label
    Monotherapy: Normal Hepatic Function (Selinexor)
    type
    EXPERIMENTAL
  2. description
    Cohort 1: Patients with Moderate Hepatic Impairment with any Solid Tumors. - Selinexor 2 x 20-mg tablet QW. Cohort 2: Patients with Severe Hepatic Impairment with any Solid Tumors. \- Selinexor 2 x 20-mg tablet QW.
    intervention Names
    1. Drug: Selinexor 40 mg
    label
    Monotherapy: Impaired Hepatic Function (Selinexor)
    type
    EXPERIMENTAL
  3. description
    (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).
    intervention Names
    1. Drug: Docetaxel
    2. Drug: Selinexor 60 mg
    label
    Combination Therapy: NSCLC Arm A: (Selinexor + Docetaxel)
    type
    EXPERIMENTAL
  4. description
    (Closed for Enrollment) Selinexor 80 mg oral dose QW and pembrolizumab 200 mg IV every 3 weeks (Colorectal cancer \[CRC\] Patients).
    intervention Names
    1. Drug: Pembrolizumab
    2. Drug: Selinexor 80 mg
    label
    Combination Therapy: CRC Arm B: (Selinexor + Pembrolizumab)
    type
    EXPERIMENTAL
  5. description
    (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).
    intervention Names
    1. Drug: FOLFIRI
    2. Drug: Selinexor 40 mg
    3. Drug: Selinexor 80 mg
    label
    Combination Therapy: CRC Arm C: (Selinexor + FOLFIRI)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Monotherapy: Normal Hepatic Function (Selinexor)
    description
    100-mg 2 formulations: * 5 × 20-mg tablets (Tablet A) * 1 × 100-mg tablet (Tablet B)
    name
    Selinexor 100 mg
    other Names
    1. Xpovio®
    type
    DRUG
  2. arm Group Labels
    1. Combination Therapy: NSCLC Arm A: (Selinexor + Docetaxel)
    description
    75 mg/m\^2 IV
    name
    Docetaxel
    other Names
    1. Taxotere®
    type
    DRUG
  3. arm Group Labels
    1. Combination Therapy: CRC Arm B: (Selinexor + Pembrolizumab)
    description
    200 mg IV
    name
    Pembrolizumab
    other Names
    1. Keytruda®
    type
    DRUG
  4. arm Group Labels
    1. Combination Therapy: CRC Arm C: (Selinexor + FOLFIRI)
    description
    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
    name
    FOLFIRI
    type
    DRUG
  5. arm Group Labels
    1. Combination Therapy: CRC Arm C: (Selinexor + FOLFIRI)
    2. Monotherapy: Impaired Hepatic Function (Selinexor)
    description
    \- 2 × 20-mg tablets (Tablet A)
    name
    Selinexor 40 mg
    other Names
    1. Xpovio®
    type
    DRUG
  6. arm Group Labels
    1. Combination Therapy: CRC Arm B: (Selinexor + Pembrolizumab)
    2. Combination Therapy: CRC Arm C: (Selinexor + FOLFIRI)
    description
    \- 4 × 20-mg tablets (Tablet A)
    name
    Selinexor 80 mg
    other Names
    1. Xpovio®
    type
    DRUG
  7. arm Group Labels
    1. Combination Therapy: NSCLC Arm A: (Selinexor + Docetaxel)
    description
    \- 3× 20-mg tablets (Tablet A)
    name
    Selinexor 60 mg
    other Names
    1. Xpovio®
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
SEQUENTIAL
intervention Model Description
Two-part study (monotherapy period and combination therapy period).
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
80
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    AUC0-t was defined as the total-drug area under the concentration-time curve from time zero to time of last concentration measured.
    measure
    Monotherapy: Area Under the Concentration-Time Curve From Time Zero to Time of Last Concentration (AUC 0-t) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  2. description
    AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated), calculated as AUC0-last + Ct/λ, where: Ct = the last quantifiable concentration and λ is terminal elimination rate constant.
    measure
    Monotherapy: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-Inf) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  3. description
    Cmax was defined as maximum observed plasma total-drug concentration of selinexor.
    measure
    Monotherapy: Maximum Plasma Concentration (Cmax) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  4. description
    Overall response rate (ORR) was defined as the percentage of participants who achieved an Investigator-determined best overall response (BOR) of partial response (PR) or complete response (CR) as assessed by RECIST or iRECIST before disease progression or initiating a new antineoplastic treatment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) might have reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentage of participants who achieved ORR were reported.
    measure
    Combination Therapy (Arms: A and B): Overall Response Rate (ORR) as Assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
    time Frame
    Up to 25 months
  5. description
    Adverse event (AE): Any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were any event that was not present prior to the initiation of study treatment, or any event already present that worsened in either intensity or frequency following exposure to study treatment.
    measure
    Combination Therapy (Arm C): Number of Participants With Treatment-emergent Adverse Events (TEAEs)
    time Frame
    From start of study drug administration up to survival follow-up (up to 25 months)
secondary Outcomes
  1. description
    Tmax was defined as time to the maximum observed concentration of selinexor.
    measure
    Monotherapy: Time to Maximum Observed Concentration (Tmax) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  2. description
    Lambda z was defined as the terminal elimination rate constant of selinexor.
    measure
    Monotherapy: Terminal Elimination Rate Constant (Lambda z) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  3. description
    t1/2 was defined as the terminal elimination half-life of selinexor.
    measure
    Monotherapy: Terminal Half-Life (t1/2) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  4. description
    CL/F was defined as the apparent clearance of selinexor.
    measure
    Monotherapy: Apparent Clearance (CL/F) of Total Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  5. description
    Vd/f was defined as the apparent volume of distribution, calculated as Dose/ (λz\*AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight.
    measure
    Monotherapy: Apparent Volume of Distribution (Vd/F) of Selinexor in Participants With Normal, Moderate and Severe Hepatic Impairment
    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
  6. description
    Fu represents the unbound fraction, which is the portion of the drug in the bloodstream that is unbound to plasma proteins. Mean percent fraction unbound of selinexor (Tablet A) in plasma, calculated by averaging the percent fraction unbound measurements obtained at 3 and 8 hours post-dose on Days 1 and 8.
    measure
    Monotherapy: Percent Fraction Unbound (fu) of Selinexor (Tablet A) in Plasma Protein
    time Frame
    At 3 and 8 hours post-dose on Days 1 and 8
  7. description
    Cmax,u was defined as the maximum observed free-drug concentration of Selinexor, calculated as Cmax \* Fu.
    measure
    Monotherapy: Maximum Free-Drug Concentration (Cmax,u) of Free Selinexor (Tablet A) in Plasma
    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
  8. description
    AUCu was defined as free-drug area under the concentration-time curve from time zero to infinity (extrapolated), calculated as (AUC0-last + Ct/λz) \* Fu, where: Ct = the last observed nonzero concentration.
    measure
    Monotherapy: Area Under the Free-Drug Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCu) of Free Selinexor (Tablet A) in Plasma
    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
  9. description
    CLu/F was defined as the apparent free-drug clearance of selinexor.
    measure
    Monotherapy: Apparent Free-drug Clearance (CLu/F) of Free Selinexor (Tablet A) in Plasma
    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
  10. description
    Vu/F was defined as the apparent free-drug volume of distribution of selinexor.
    measure
    Monotherapy: Apparent Free-drug Volume of Distribution (Vu/F) of Free Selinexor (Tablet A) in Plasma
    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
  11. description
    PFS was defined as the time from the starting date of the combination therapy until the date of first progressive disease (PD) determined by PI per Response Evaluation Criteria in Solid Tumors (RECIST) for Arm A and B or Immunotherapeutic Response Evaluation Criteria in Solid Tumors (iRECIST) for Arm C, or death due to any cause, whichever occurred first.
    measure
    Combination Therapy (Arms: A, B and C): Progression-free Survival (PFS)
    time Frame
    Time from starting date of combination therapy until the date of first PD or death due to any case, whichever occurs first (up to 25 months)
  12. description
    DOR was defined for participants with partial response (PR) or complete response (CR) as the duration from the date of first PR or better to the date of first PD or death due to any cause, whichever occurred first. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) might have reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    measure
    Combination Therapy (Arms: A, B and C): Duration of Response (DOR)
    time Frame
    Date of first PR or better to the date of first PD or death due to any cause, whichever occurs first (up to 25 months)
Full study description
brief Summary
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.
detailed Description
Up to 120 patients will be enrolled, of which, 20 with normal HF will be able to continue from Monotherapy to Combination therapy and up to 106 patients with normal HF will receive combination therapy in total. Patients with impaired hepatic function can only participate in the Monotherapy part of the study. Monotherapy Period: For the Monotherapy Period of Study KCP-330-027, patients with normal hepatic function (n=20), will be allocated to one of two test formulation treatment arms, and will receive a cross-over once weekly oral dosing, with either 1x100 mg or 5x20 mg selinexor, for 2 weeks, and then will have the option to move on to the combination treatment part of the study. Patients with either moderately or severely impaired hepatic functions will be treated with 2x20 mg selinexor weekly (with an option to increase the dose every 3 weeks by 20 mg increments, up to 80 mg). For the assessment of hepatic impairment, participants with any type of advanced or metastatic solid tumor who have moderate or severe hepatic impairment will be enrolled in Moderate Hepatic Impairment (MHI) (n=8) and Severe Hepatic Impairment (SHI) (n=6) arms, respectively and will be treated with 2 × 20 mg selinexor, weekly. For Weeks 1 and 2, following an overnight fast of at least 10 hours, patients will be fed a standard low-fat meal 30 minutes prior to administration of once weekly selinexor. Patients should finish the meal in 30 minutes or less; however, selinexor dose should be administered 30 minutes after start of the meal. Blood sampling for selinexor PK analyses will be collected ≤10 minutes (m) pre selinexor dose, and at 15m (±5m), 30m (±5m), 1 hour (h) (±5m), 1.5h (±5m), 2h (±10m), 3h (±10m), 4h (±10m), 5h (±10m), 6h (±10m), 8h (±20m), 10h (±20m; optional), 24h (±1h), 30h (±1h), and 48h (±2h) post selinexor dose. Practitioners must record the actual clock time for selinexor dose, and each sample drawn. If a patient experiences emesis during the first 6 hours of the PK sampling, the PK results for that week will be excluded from the PK analysis dataset, and all testing timepoints must be re-collected during the following week (in this case, the same dosing formulation should be repeated on the following week, and other dosing formulation will be given the week after that). Patients who will complete the Monotherapy Period will be reassessed for continuation to the Combination Therapy Period, as long as their Hepatic Function remains normal. If a patient experiences significant toxicity related to selinexor and can't start the combination therapy immediately following monotherapy, dose interruption and weekly retesting are allowed for up to 21 days after the end of Monotherapy treatment visit. Patients requiring \>21 days to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for documented approval to continue to the Combination Therapy Period. Reassessment may be extended then and following Medical Monitor approval up to 28 days. Combination Therapy Period: In the combination treatment period of the study, patients with normal hepatic functions will be allocated to one of 3 arms (with Arm C divided into 2 cohorts): Arm A (n= up to 40): Patients with NSCLC who have had up to 2 lines of prior systemic treatment with 1 line containing a CPI will receive 60 mg selinexor weekly, in combination with docetaxel 75 milligrams per meter square (mg/m\^2) once every 3 weeks; Arm B (n= up to 40): Patients with CRC (KRAS WT) who have had up to 3 lines of prior systemic treatment or patients with CRC (KRAS mutant \[KRAS Mut\]) who have had up to 2 lines of prior systemic treatment, with no lines containing a checkpoint inhibitor (CPI) will receive 80 mg selinexor weekly, in combination with pembrolizumab 200 mg once every 3 weeks; Arm C (n\<=26): Patients with CRC (regardless of KRAS status) who have had up to 2 lines of prior systemic treatment (regardless of CPI use) will receive either: (Cohort 1) selinexor 40 mg on days 1, 3, 15 and 18 in 28-day cycle + FOLFIRI; or (Cohort 2) selinexor 80 mg on days 1 and 15 in 28-day cycle + FOLFIRI. Combination Therapy Period Patients will receive combination treatment until progressive disease (PD) or intolerable toxicity. During both study periods, safety will be assessed through continuous reporting of adverse events (AEs), treatment-emergent adverse events (TEAEs), regularly scheduled clinical laboratory tests (hematologic and chemical), and physical examinations. Tumor assessment will be performed with either computed tomography (CT) or magnetic resonance imaging (MRI) (CT with contrast preferred; for each patient, the imaging method should remain the same throughout the study). Following treatment, patients will come in for a safety visit (approximately 30 days after the last dose of combination therapy) and will be followed for up to 2 years after that. Patients who discontinued due to PD will be followed for survival, and patients who discontinued for reasons other than PD will have tumor assessments until PD or until the start of new anti-neoplastic therapy, after which they will be followed for survival.
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