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AzTrials

Non-Small Cell Lung Carcinoma (NSCLC)Phase 1/2SPRINTNCT04256707

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

A Phase 1/2 study testing Selinexor 100 mg, Docetaxel and Pembrolizumab in people with Non-Small Cell Lung Carcinoma (NSCLC) and Colorectal Cancer (CRC), run by Karyopharm Therapeutics Inc at 11 sites in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Selinexor 100 mg, Docetaxel and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
11 sitesIsrael
Study dates
9 Feb 2020to 31 Jul 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Common inclusion criteria for all patients:
  • Are greater than or equal to [≥] 18 years of age at the time of informed consent.
  • 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).
  • Willing to provide written informed consent in accordance with federal, local, and institutional guidelines and comply with all requirements of the study.
  • 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):
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  • 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.
  • Must have either normal hepatic function, or moderate or severe hepatic impairment (as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria:
  • 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.
  • MHI arm: ≥1 week of documented moderate hepatic impairment (total bilirubin >1.5-3 × ULN, any level of AST).
  • SHI arm: ≥1 week of documented severe hepatic impairment (total bilirubin >3-10 × ULN, any level of AST).
  • For Combination Therapy Part only:
  • Previous treatment lines (adjuvant or neoadjuvant therapy is not counted as one line of systemic therapy):
  • 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)
  • 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.
  • Arm C: For patients with CRC participating in the combination arm with FOLFIRI, 1-2 prior lines of systemic therapy are allowed.
  • Arm B and C in CRC: patient with CRC who are not candidates for curative resection of metastatic lesions.
  • Must have hepatic function as follows:
  • 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.
  • 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.

Who cannot join

  • Common exclusion criteria for all patients:
  • Have inadequate hematopoietic function defined as (without transfusion or growth factor support within 7 days prior to first dose):
  • 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).
  • For Arms A-C: ANC <1.5 × 10^9/L; PLT <100 × 10^9/L; or Hb <10 g/dL.
  • 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.
  • 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]).
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  • Ongoing infection requiring parenteral antibiotics, antivirals, or antifungals on Day 1 dosing.
  • All patients: on Day 1 dosing.
  • Prior exposure to a SINE compound or selinexor.
  • Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
  • 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.
  • 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.
  • Had last dose of previous anti-cancer therapy ≤14 days prior to Day 1 dosing.
  • Palliative radiotherapy >14 days prior to the study is allowed.
  • 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).
  • 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.
  • 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).
  • Female patients who are pregnant or breastfeeding.
  • For Monotherapy Part only (BA/BE and HI arms):
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of:
  • ≥3 for patients to be enrolled into the S20-100 or S100-20 arms of the study.
  • ≥4 for patients to be enrolled into the MHI and SHI arms of the study.
  • For MHI and SHI arms: ANC <1 × 10^9/L; PLT <75 × 10^9/L; or Hb <8 g/dL.
  • 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.
  • Inability or unwillingness to undergo a series of PK sampling.
  • For Combination Therapy Part only:
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3 for Arms A and B and ECOG PS ≥2 for Arm C.
  • Arm B patients with CRC who are to receive pembrolizumab:
  • 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.
  • Patients with controlled diabetes mellitus and patients with endocrinopathies on stable hormone replacement therapy, are eligible for the trial.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Israel11 sites

  • University Hospital Assuta Ashdod

    Ashdod, 7747629

  • Soroka University Medical Center

    Beersheba, 84101

  • Oncology Department Hillel Yaffe Medical Center

    Hadera, 38100

  • Rambam Health Care Campus

    Haifa, 3109601

  • Shaarei Zedek Medical Center

    Jerusalem, 9103102

  • Hadassah Ein Karem University Hospital

    Jerusalem, 91120

  • Meir Medical Center

    Kfar Saba, 4428164

  • Galilee Medical Center

    Nahariya, 22100

  • Rabin Medical Center

    Petah Tikva, 49100

  • Tel-Aviv Sourasky Medical Center

    Tel Aviv, 64239

  • Sheba Medical Center

    Tel HaShomer, 5265601

Other trials in Israel

About this study

Official title: Open-Label, Phase 1/2 Study Evaluating the Relative Bioavailability/Bioequivalence of Different Formulations of Selinexor, the Impact of Hepatic Impairment on Selinexor Pharmacokinetics, and the Tolerability and Antitumor Activity of Selinexor Combination Treatment (SPRINT)

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.

Read the 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.

Being tested
Selinexor 100 mg, Docetaxel, Pembrolizumab, FOLFIRI, Selinexor 40 mg
Keywords
Non-small cell lung carcinoma, Selinexor, Docetaxel, Colorectal cancer, KPT-330, Bioequivalence, Relative bioavailability, Pharmacokinetics, Other Solid Tumors
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Selinexor 100 mgDrug

    Also called Xpovio®

    100-mg 2 formulations:

    • 5 × 20-mg tablets (Tablet A)
    • 1 × 100-mg tablet (Tablet B)

  • DocetaxelDrug

    Also called Taxotere®

    75 mg/m^2 IV

  • PembrolizumabDrug

    Also called Keytruda®

    200 mg IV

  • FOLFIRIDrug

    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 mgDrug

    Also called Xpovio®

    • 2 × 20-mg tablets (Tablet A)

  • Selinexor 80 mgDrug

    Also called Xpovio®

    • 4 × 20-mg tablets (Tablet A)

  • Selinexor 60 mgDrug

    Also called Xpovio®

    • 3× 20-mg tablets (Tablet A)
Study groups in NCT04256707
Study groupRoleWhat they receive
Monotherapy: Normal Hepatic Function (Selinexor)Experimental(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.
Receives: Drug: Selinexor 100 mg
Monotherapy: Impaired Hepatic Function (Selinexor)ExperimentalCohort 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.
Receives: Drug: Selinexor 40 mg
Combination Therapy: NSCLC Arm A: (Selinexor + Docetaxel)Experimental(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).
Receives: Drug: Docetaxel; Drug: Selinexor 60 mg
Combination Therapy: CRC Arm B: (Selinexor + Pembrolizumab)Experimental(Closed for Enrollment) Selinexor 80 mg oral dose QW and pembrolizumab 200 mg IV every 3 weeks (Colorectal cancer [CRC] Patients).
Receives: Drug: Pembrolizumab; Drug: Selinexor 80 mg
Combination Therapy: CRC Arm C: (Selinexor + FOLFIRI)Experimental(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).
Receives: Drug: FOLFIRI; Drug: Selinexor 40 mg; Drug: Selinexor 80 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    AUC0-t was defined as the total-drug area under the concentration-time curve from time zero to time of last concentration measured.

    Measured: 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. 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

    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.

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

    Cmax was defined as maximum observed plasma total-drug concentration of selinexor.

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

    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.

    Measured: Up to 25 months

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

    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.

    Measured: From start of study drug administration up to survival follow-up (up to 25 months)

Secondary outcomes (17)

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

    Tmax was defined as time to the maximum observed concentration of selinexor.

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

    Lambda z was defined as the terminal elimination rate constant of selinexor.

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

    t1/2 was defined as the terminal elimination half-life of selinexor.

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

    CL/F was defined as the apparent clearance of selinexor.

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

    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.

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

    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.

    Measured: At 3 and 8 hours post-dose on Days 1 and 8

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

    Cmax,u was defined as the maximum observed free-drug concentration of Selinexor, calculated as Cmax * Fu.

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

    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.

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

    CLu/F was defined as the apparent free-drug clearance of selinexor.

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

    Vu/F was defined as the apparent free-drug volume of distribution of selinexor.

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

    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.

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

    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.

    Measured: 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)

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

    DCR was calculated as the percentage of participants for whom the best overall response (BOR) was determined as CR, PR, or at least 12 continuous weeks of stable disease as assessed by RECIST v1.1 (Arms A, C), and iRECIST (Arm B), before Investigator had determined PD or initiating a new antineoplastic therapy. 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.

    Measured: Up to 25 months

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

    OS was defined as time since the starting date of the combination therapy until death due to any cause.

    Measured: Time since the starting date of combination therapy until death due to any cause (up to 25 months)

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

    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 can 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.

    Measured: From start of study drug administration up to survival follow-up (up to 4 months)

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

    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 can 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.

    Measured: From start of study drug administration up to survival follow-up (up to 25 months)

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

    ORR was defined as the proportion of participants who achieve an Investigator-determined BOR of PR or 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.

    Measured: Up to 25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2020
  2. Study start9 Feb 2020
  3. Primary completion31 Jul 2024
  4. Study completion31 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Two-part study (monotherapy period and combination therapy period).
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04256707
Sponsor's protocol ID
KCP-330-027
Acronym
SPRINT
Status last verified
Sep 2026
First submitted
3 Feb 2020
Last updated
9 Oct 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Selinexor 100 mg, Docetaxel and Pembrolizumab in people with Non-Small Cell Lung Carcinoma (NSCLC) and Colorectal Cancer (CRC), run by Karyopharm Therapeutics Inc at 11 sites in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04256707.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.

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