Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Adenocarcinoma

Melanoma

Prostatic Neoplasms

Glioblastoma

Carcinoma, Squamous Cell

Antipyretics

Analgesics

All Drugs and Chemicals

Hematinics

Acetaminophen

Liver Extracts

Analgesics, Non-Narcotic

Participants with colorectal cancer and liver metastasis received oral selinexor as single agent in 8 schedules, Schedule1: ≤12milligrams per meter square(mg/m\^2) 3 times weekly(TIW) during Weeks 1 and 3, twice weekly(BIW) during Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule2: \>12mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule3: ≥30mg/m\^2 BIW(Days 1 and 3) up to 8 doses/cycle(28 days/cycle); Schedule4: ≥20mg/m\^2 BIW(Days 1 and 2) up to 8 doses/cycle(28 days/cycle); Schedule5: ≥35mg/m\^2 BIW(Days 1 and 4) up to 8 doses(28 days/cycle); Schedule6: ≥20mg/m\^2 BIW(Days 1 and 4) after 500 mg(Week 1) to 1000 mg(Week 2 onwards) acetaminophen(given 1 hour prior to each selinexor dose) up to 8 doses/cycle (28 days/cycle); Schedule7: ≥50mg/m\^2 once weekly(QW) up to 4 doses/cycle(28 days per cycle); Schedule8: ≥45mg/m\^2 BIW(Days 1 and 3) up to 4 doses/cycle(21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants with castrate-resistant prostate cancer (CRPC) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants with glioblastoma multiforme (GBM) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants with Melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Participants in this study will receive selinexor orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m\^2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in 4-week (28 days for schedule 1 to 7) and 3-week (21 days for schedule 8) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.

Selinexor

Oral 500 mg (in Cycle 1, Week 1) to 1000 mg (in Cycle 1, Week 2 and onwards) of acetaminophen will be administered 1 hour prior to each selinexor dose up to 8 doses per cycle (28 days per cycle)

Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies.

This is a phase 1a and phase 1b, open-label, dose-escalation study to evaluate the safety and tolerability of selinexor and determine the RP2D in patients with solid tumor malignancies.

Safety Study of KPT-330 (Selinexor) in Patients With Advanced or Metastatic Solid Tumor Cancer

A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Advanced or Metastatic Solid Tumor Malignancies

An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria; is fatal, life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. Number of participants with TEAEs and TESAEs were reported.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A treatment-related AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product; the event had a causal relationship with the treatment or usage.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.

Evaluation of DLTs was only conducted in participants who participated in the Dose-escalation Phase. A DLT was defined as any of the following, considered possibly related to drug administration, occurring in the first 28 days (or 21 days for participants on Schedule 8) at the target dose (ie, for Schedule 2 this meant the first 4 weeks after the 12 mg/m2 run-in week): Missed selinexor doses due to drug-related toxicities, discontinuation of a participant due to a toxicity that was at least possibly related to study drug before completing Cycle 1.

The RP2D was the maximum tolerated dose (MTD) or less. MTD was defined as the next lower dose level below the one in which \>1 of 3 participants or ≥2 of 6 participants experienced DLT, provided that dose level was ≤25 percent (%) lower than the highest (intolerable) dose tested. If the projected MTD was \>25% lower than the highest dose tested, then an additional cohort of ≥3 participants was added at a dose that was intermediate between the intolerable dose and the next lower dose.

Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.

Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.

AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.

AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated). It was calculated as AUC0-t + Ct/kel, where: Ct = the last observed non-zero concentration and Kel = elimination rate constant.

t1/2 was defined as elimination half-life, it was calculated as ln(2)/kel, where In = natural logarithm and kel = elimination rate constant.

CL/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram).

Vd/F was calculated as Dose/(kel \* AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram).

BOR is response recorded from start of treatment until disease progression/recurrence. Best lesion response was defined by Recist Criteria V1 (for target and non-target lesions) and RANO criteria (for glioblastoma multiforme): complete response (CR)- disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to less than (\<) 10 mm; partial response (PR)- at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum longest diameter; stable disease (SD)- steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; progressive disease (PD): at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded since treatment started. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm, or appearance of one or more new lesions.

Objective response rate (ORR) was determined as percentage of participants who had either CR or PR, as defined by RECIST v1.1 (for solid tumors). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target/non target) must have reduction in short axis to \<10 mm and PR was defined as at least 30% decrease in sum of diameters of target lesions. ORR was calculated as a proportion and included a 2 sided 95% CI using the exact (Clopper-Pearson) method.

Duration of stable disease was defined as the time from the date of first dose to first documented radiologic evidence of disease recurrence or progression, as defined by RECIST v1.1 (for solid tumors) or RANO criteria (for GBM and AnaA).

Progression-free survival was calculated from the date of first dose of study treatment to first documented evidence of disease recurrence or progression or death due to any cause. Patients who are last known to be alive and without evidence of progression will be censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, patients are censored at the time of last evaluable disease assessment prior to the missed assessment. Progressive disease was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease.

OS was calculated from the date of first dose to date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropout prior to study end, were censored at the day they were last known to be alive. The OS was calculated using the Kaplan-Meier method.

Karyopharm Therapeutics Inc

As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.

Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m\^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Arm A (Colorectal Cancer)

Arm B (Gynecological Cancer)

Arm C (Squamous Cell Cancer)

Participants with CRPC received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Arm D (Castrate-resistant Prostate Cancer)

Participants with GBM received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Arm E (Glioblastoma Multiforme)

Participants with melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Arm F (Melanoma)

Arm G (Other Solid Tumors)

Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 milligrams per meter square (mg/m\^2) 3 times weekly (TIW) during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m\^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m\^2 once weekly (QW) up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Safety Population included all participants who received at least one dose of selinexor. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.

Jatin Shah

Participants with TEAEs

Participants with TESAEs

Safety population included all participants who received at least one dose of selinexor. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Participants with Treatment-related TEAEs

Participants with Treatment-related TESAEs

Number of Participants With Treatment-related Treatment-emergent Adverse Events

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Greater Than or Equal to Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

DLT Evaluable Population included all participants enrolled to the study during the dose-escalation phase who met the inclusion/exclusion criteria on first day of dosing and completed at least 1 cycle of therapy or experienced a DLT during the first cycle. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.

Number of Participants Who Experienced Dose Limiting Toxicity (DLT)

Participants with colorectal cancer with liver metastasis, gynecological cancer, squamous cell cancer, CRPC, GBM, melanoma, other solid tumors received oral selinexor as a single agent in eight schedules, schedule 1. ≤12 mg/m\^2 TIW in Weeks 1 and 3, BIW in Weeks 2 and 4, schedule 2. \>12 mg/m\^2 TIW in Weeks 1 and 3, BIW in Weeks 2 and 4, schedule 3. ≥ 30 mg/m\^2 BIW (Days 1 and 3), schedule 4. ≥20 mg/m\^2 BIW (Days 1 and 2), schedule 5. ≥35 mg/m\^2 BIW (Days 1 and 4), schedule 6. ≥20 mg/m\^2 BIW (Days 1 and 4), schedule 7. ≥50 mg/m\^2 once weekly (QW), schedule 8. ≥45 mg/m\^2 BIW (Days 1 and 3) until disease progression, death, or unacceptable toxicity.

Arms A to G: Overall Solid Tumor Malignancies

Safety Population included all participants who received at least one dose of selinexor. The data in terms of dose was reported as combined data for participants from all arms, pre-specified in protocol. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure.

Recommended Phase 2 Dose (RP2D)

Participants received 3 milligram per square meter (mg/m\^2) of selinexor for Cycle1 Day1.

Selinexor Dose: 3 mg/m^2

Participants received single oral dose of 6 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 6 mg/m^2

Participants received single oral dose of 12 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 12 mg/m^2

Participants received single oral dose of 16.8 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 16.8 mg/m^2

Participants received single oral dose of 20 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 20 mg/m^2

Participants received single oral dose of 23 mg/m\^2 Selinexor for Cycle1Day1.

Selinexor Dose: 23 mg/m^2

Participants received single oral dose of 28 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 28 mg/m^2

Participants received single oral dose of 30 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 30 mg/m^2

Participants received single oral dose of 35 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 35 mg/m^2

Participants received single oral dose of 39 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 39 mg/m^2

Participants received single oral dose of 40 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 40 mg/m^2

Participants received single oral dose of 45 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 45 mg/m^2

Participants received single oral dose of 50 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 50 mg/m^2

Participants received single oral dose of 55 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 55 mg/m^2

Participants received single oral dose of 58 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 58 mg/m^2

Participants received single oral dose of 65 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 65 mg/m^2

Participants received single oral dose of 70 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 70 mg/m^2

Participants received single oral dose of 80 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 80 mg/m^2

Participants received single oral dose of 85 mg/m\^2 Selinexor for Cycle1 Day1.

Selinexor Dose: 85 mg/m^2

Pharmacokinetic (PK) population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms where single participant was analyzed. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure.

Maximum Observed Plasma Concentration (Cmax) of Selinexor

Participants received 3 mg/m\^2 of selinexor for Cycle1 Day1.

Participants received single oral dose of 23 mg/m\^2 Selinexor for Cycle1 Day1.

PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and full range data was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure.

Time of Maximum Observed Concentration in Plasma (Tmax) of Selinexor

PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and % coefficient of variation was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure.

Area Under the Concentration Time Curve From the Time of Dosing to Time in Plasma (AUC0-t) of Selinexor

Area Under the Concentration Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Selinexor

PK population consisted of all participants who received selinexor, and had evaluable PK for at least one dosing occasion. Data for the PK parameters were planned and analyzed based on doses and full range was not evaluable for arms with single participant. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure.

Elimination Half-Life (t1/2) of Selinexor

Participants received single oral dose of 30 mg/m\^2 Selinexor for Cycle1Day1.

Apparent Total Body Clearance (CL/F) of Selinexor

Participants received 3 mg/m2 of selinexor for Cycle1Day1.

Selinexor Dose: 3 Milligram Per Square Meter (mg/m2)

Participants received single oral dose of 6 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 6 mg/m2

Participants received single oral dose of 12 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 12 mg/m2

Participants received single oral dose of 16.8 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 16.8 mg/m2

Participants received single oral dose of 20 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 20 mg/m2

Participants received single oral dose of 23 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 23 mg/m2

Participants received single oral dose of 28 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 28 mg/m2

Participants received single oral dose of 30 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 30 mg/m2

Participants received single oral dose of 35 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 35 mg/m2

Participants received single oral dose of 39 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 39 mg/m2

Participants received single oral dose of 40 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 40 mg/m2

Participants received single oral dose of 45 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 45 mg/m2

Participants received single oral dose of 50 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 50 mg/m2

Participants received single oral dose of 55 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 55 mg/m2

Participants received single oral dose of 58 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 58 mg/m2

Participants received single oral dose of 65 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 65 mg/m2

Participants received single oral dose of 70 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 70 mg/m2

Participants received single oral dose of 80 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 80 mg/m2

Participants received single oral dose of 85 mg/m2 Selinexor for Cycle1Day1.

Selinexor Dose: 85 mg/m2

Apparent Volume of Distribution of Selinexor (Vd/F)

Complete Response

Partial Response

Stable Disease

Progression (Objective)

Progressive Disease due to symptomatic deterioration

Not Evaluable

Efficacy Population included all participants registered to the study who had either completed 1 cycle of treatment or discontinued treatment prior to completing the first cycle due to documented disease progression, death related to disease, or treatment-related toxicity. As pre-specified in the study Protocol data were not collected per dose level. The limited data available based on cancer stratification as pre-specified in the protocol is presented.

Number of Participants With Best Overall Response (BOR)

Percentage of Participants With Objective Response

Duration of Stable Disease (SD)

Progression-free Survival (PFS)

Overall Survival (OS)

Participants with colorectal cancer with liver metastasis received oral selinexor as a single agent in eight schedules- Schedule 1: ≤12 milligrams per meter square (mg/m\^2) 3 times weekly (TIW) during Weeks 1 and 3, twice weekly (BIW) during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW(Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 6: ≥20 mg/m\^2 BIW (Days 1 and 4) after 500 mg (Cycle 1, Week 1) to 1000 mg (Cycle 1, Week 2 onwards) acetaminophen (given 1 hour prior to each selinexor dose) up to 8 doses/cycle(28 days/cycle); Schedule 7: ≥50 mg/m\^2 once weekly (QW) up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Spots Global Cancer Trial Database for Safety Study of KPT-330 (Selinexor) in Patients With Advanced or Metastatic Solid Tumor Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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