Dedifferentiated Liposarcoma
Conditions
Keywords
Advanced unresectable dedifferentiated liposarcoma, selinexor, KCP-330, Karyopharm, Phase 2 / 3, dedifferentiated liposarcoma, Liposarcoma
Brief summary
This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2-3 study of patients diagnosed with advanced unresectable dedifferentiated liposarcoma. Approximately 342 total patients will be randomized to study treatment (selinexor or placebo).
Detailed description
In the Phase 2 portion of the study, 57 patients were randomized to selinexor (60 mg) or placebo at a 1:1 allocation ratio. In the Phase 3 portion of the study, approximately 285 patients will be randomized to selinexor (60 mg) or placebo with a 2:1 allocation ratio. Patients who progress during the blinded portion of the study will be unblinded and if receiving: * placebo, may cross over to open-label selinexor (60mg twice-weekly) * selinexor, will be withdrawn from further treatment and followed for survival Study treatment will be given twice-weekly on Day 1 and Day 3 during Weeks 1-6 of each six-week (42 day) cycle until disease progression or intolerability. Treatment will continue until one or more of the following occurs: * Disease progression, as defined by RECIST v1.1 Response Criteria * Clinical progression, as determined by the treating physician * Unacceptable adverse events (AEs) or failure to tolerate study treatment * Patient withdrawal * Patient discontinuation due to non-compliance
Interventions
DRUGSelinexor
Selinexor 60mg
DRUGPlacebo
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥12 years of age 2. Body surface area (BSA) ≥ 1.2 m2 3. Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment 4. Must have measurable disease per RECIST v1.1 Response Criteria 5. Radiologic evidence of disease progression within 6 months prior to randomization. If the patient received other intervening therapy after documented disease progression, further disease progression must be documented after the completion of the intervening therapy 6. Must have had at least 2 prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines) 7. If patient received any previous systemic therapy, the last dose must have been ≥ 21 days prior to randomization (or ≥ 5 half-lives of that drug, whichever is shorter) with all clinically significant therapy-related toxicities having resolved to ≤ Grade 1
Exclusion criteria
1. Patients with pure well-differentiated liposarcoma (WDLS), myxoid/round cell or pleomorphic tumor histologic subtypes 2. Known active hepatitis B (HepB), hepatitis C (HepC) or human immunodeficiency virus (HIV) infection 3. Known central nervous system metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months) | PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 | From the date of randomization in the Phase 3 open label period until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months) | PFS was defined as the time from the date of randomization in the Phase 3 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1 | From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 57 months) | PFS was defined as the time from date of randomization until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 | From date of randomization in the Phase 2 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 57 months) | PFS was defined as the time from date of randomization in the Phase 2 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 | From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months) | TTP was defined as the time from date of randomization until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1 | From date of randomization in the Phase 3 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months) | TTP was defined as the time from date of randomization in the Phase 3 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 | From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months) | TTP was defined as the time from date of randomization until ICR-determined PD as per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1 | From date of randomization in the Phase 2 open-label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months) | TTP was defined as the time from date of randomization in the Phase 2 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 3 Double Blind: Overall Response Rate (ORR) | From date of randomization until the documentation of CR or PR (up to 70 months) | ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR), per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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. |
| Phase 3 Open Label: Overall Response Rate (ORR) | From date of randomization in the Phase 3 open label period until the documentation of CR or PR (up to 70 months) | ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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. |
| Phase 2 Double Blind: Overall Response Rate (ORR) | From date of randomization until the documentation of CR or PR (up to 70 months) | ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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. |
| Phase 2 Open Label: Overall Response Rate (ORR) | From date of randomization in the Phase 2 open-label period until the documentation of CR or PR (up to 70 months) | ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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. |
| Phase 3 Double Blind: Duration of Response (DOR) | From first occurrence of CR or PR until the first date of PD (up to 70 months) | DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 3 Double Blind: Overall Survival (OS) | From date of randomization until death due to any cause, whichever occurred first (up to 70 months) | OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. |
| Phase 3 Double Blind: Time to Next Treatment (TTNT) | Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months) | TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first. |
| Phase 2 Double Blind: Time to Next Treatment (TTNT) | Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months) | TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first. |
| Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From start of study drug administration up to 70 months | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. |
| Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs | From start of study drug administration up to 70 months | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. |
| Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs | From start of study drug administration up to 70 months | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. |
| Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs | From start of study drug administration up to 70 months | An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs. |
| Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Baseline up to Day 1387 | The QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain); six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties); and global health status/quality of life (QoL). Most questions used a 4-point scale (from 1 'Not at all' to 4 'Very much'); 2 questions used a 7-point scale (from 1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. For the functional scales and the global health status/QoL, a higher score represents a better level of functioning (better health status); for the symptom scales/items, a higher score represents a higher level of symptomatology/problems (worse health status). |
| Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Baseline up to Day 379 | The QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain); six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties); and global health status/quality of life (QoL). Most questions used a 4-point scale (from 1 'Not at all' to 4 'Very much'); 2 questions used a 7-point scale (from 1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. For the functional scales and the global health status/QoL, a higher score represents a better level of functioning (better health status); for the symptom scales/items, a higher score represents a higher level of symptomatology/problems (worse health status). |
| Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment | From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 70 months) | PFS was defined as the time from date of randomization until the first date of PD, per RECIST version 1.1, or death due to any cause as defined by the Investigator based on clinical and/or radiologic criteria. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
| Phase 3 Open Label: Overall Survival (OS) | From date of randomization in phase 3 open label period until death due to any cause, whichever occurred first (up to 70 months) | OS was defined as the duration (in months) from the date of randomization in the Phase 3 open-label period to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. |
| Phase 2 Double Blind: Overall Survival (OS) | From the date of randomization until death due to any cause, whichever occurred first (up to 70 months) | OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. |
| Phase 2 Open Label: Overall Survival (OS) | From date of randomization in the Phase 2 open-label period until death due to any cause, whichever occurred first (up to 70 months) | OS was defined as the duration (in months) from the date of randomization in the Phase 2 open-label period to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier. |
Countries
Belgium, Canada, France, Germany, Israel, Italy, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 71 sites in the United States, Canada, Germany, Belgium, Israel, United Kingdom, France, Spain, Italy, and Sweden. A total of 342 participants were enrolled, out of which 57 participants were randomized to receive study treatment in Phase 2 and 285 participants randomized, of which 284 participants received study treatment in Phase 3.
Pre-assignment details
This study consisted of 2 phases (2 and 3), where participants were randomized to selinexor or placebo in double-blind treatment. Participants in the placebo group who had progressive disease (PD) during the phase 2 and 3 double-blinded treatment could crossover to open-label selinexor treatment.
Participants by arm
| Arm | Count |
|---|---|
| Phase 2 Double-blinded: Selinexor Participants received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle. | 27 |
| Phase 2 Double-blinded: Placebo Participants received a fixed blinding dose of placebo matched to Selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle. | 30 |
| Phase 3 Double-blinded: Selinexor Participants received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle. | 188 |
| Phase 3 Double-blinded: Placebo Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle. | 97 |
| Total | 342 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1: Double-blinded Period | Randomized but no treatment | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 2 Double-blinded: Selinexor | Phase 2 Double-blinded: Placebo | Phase 3 Double-blinded: Selinexor | Phase 3 Double-blinded: Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 13 Participants | 96 Participants | 51 Participants | 168 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 17 Participants | 92 Participants | 46 Participants | 174 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 7 Participants | 6 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 25 Participants | 149 Participants | 79 Participants | 278 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 32 Participants | 12 Participants | 46 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 9 Participants | 3 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 34 Participants | 13 Participants | 50 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 23 Participants | 20 Participants | 139 Participants | 80 Participants | 262 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 74 Participants | 33 Participants | 130 Participants |
| Sex: Female, Male Male | 15 Participants | 19 Participants | 114 Participants | 64 Participants | 212 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 18 / 27 | 25 / 30 | 127 / 187 | 67 / 97 | 20 / 24 | 43 / 63 |
| other Total, other adverse events | 27 / 27 | 29 / 30 | 186 / 187 | 94 / 97 | 24 / 24 | 62 / 63 |
| serious Total, serious adverse events | 4 / 27 | 6 / 30 | 73 / 187 | 18 / 97 | 13 / 24 | 25 / 63 |
Outcome results
Primary
Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1
PFS was defined as the time from date of randomization until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
Population: The Phase 2 Intent-to-Treat Population (Ph2-ITT) consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1 | 3.02 Months |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1 | 2.76 Months |
p-value: 0.605195% CI: [0.5357, 2.4778]Log Rank
Primary
Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
PFS was defined as the time from date of randomization in the Phase 2 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization in the Phase 2 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 57 months)
Population: The Phase 2 Open-Label Population (Ph2-OL) consisted of all participants in Phase 2 who were randomized to placebo in the blinded phase, entered open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 | 1.38 Months |
Primary
Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
Population: Phase 3 Intent-to-Treat Population (Ph3-ITT) consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 2.83 Months |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 2.07 Months |
p-value: 0.011495% CI: [0.5191, 0.9509]Log Rank
Primary
Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1
PFS was defined as the time from the date of randomization in the Phase 3 open-label period until the first date of IRC-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From the date of randomization in the Phase 3 open label period until the first date of disease progression, or death due to any cause whichever occurred first (up to 57 months)
Population: The Phase 3 Open-Label Population (Ph3-OL) consisted of all participants in Phase 3 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Progression-free Survival (PFS) as Per RECIST Version 1.1 | 2.73 Months |
Secondary
Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Population: The Phase 2 Safety Population (Ph2-SAF) consisted of all participants in Phase 2 who had received at least one dose of blinded study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 27 Participants |
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 4 Participants |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 29 Participants |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 6 Participants |
Secondary
Phase 2 Double Blind: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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.
Time frame: From date of randomization until the documentation of CR or PR (up to 70 months)
Population: The Ph2-ITT consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Overall Response Rate (ORR) | 0 Percentage of participants |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Overall Response Rate (ORR) | 0 Percentage of participants |
Secondary
Phase 2 Double Blind: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From the date of randomization until death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph2-ITT consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Overall Survival (OS) | 17.31 Months |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Overall Survival (OS) | 16.07 Months |
Secondary
Phase 2 Double Blind: Time to Next Treatment (TTNT)
TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first.
Time frame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months)
Population: The Ph2-ITT consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Time to Next Treatment (TTNT) | 4.96 Months |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Time to Next Treatment (TTNT) | 2.92 Months |
Secondary
Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization until ICR-determined PD as per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph2-ITT consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 | 3.02 Months |
| Phase 3 Double-blinded: Placebo | Phase 2 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 | 2.76 Months |
Secondary
Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Population: The Ph2-OL consisted of all participants in Phase 2 who were randomized to placebo in the blinded phase, entered open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 13 Participants |
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 24 Participants |
Secondary
Phase 2 Open Label: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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.
Time frame: From date of randomization in the Phase 2 open-label period until the documentation of CR or PR (up to 70 months)
Population: The Ph2-OL consisted of all participants in Phase 2 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor. Data could not be evaluated due to no CR or PR events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Overall Response Rate (ORR) | Participants who achieved CR | 0 Percentage of participants |
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Overall Response Rate (ORR) | Participants who achieved PR | 0 Percentage of participants |
Secondary
Phase 2 Open Label: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization in the Phase 2 open-label period to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From date of randomization in the Phase 2 open-label period until death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph2-OL consisted of all participants in Phase 2 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Overall Survival (OS) | 8.90 Months |
Secondary
Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization in the Phase 2 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization in the Phase 2 open-label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph2-OL consisted of all participants in Phase 2 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 2 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1 | 1.38 Months |
Secondary
Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
The QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain); six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties); and global health status/quality of life (QoL). Most questions used a 4-point scale (from 1 'Not at all' to 4 'Very much'); 2 questions used a 7-point scale (from 1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. For the functional scales and the global health status/QoL, a higher score represents a better level of functioning (better health status); for the symptom scales/items, a higher score represents a higher level of symptomatology/problems (worse health status).
Time frame: Baseline up to Day 1387
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Global Health Status | 33.33 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Cognitive Functioning | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Fatigue | -22.22 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Insomnia | 33.33 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Constipation | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Diarrhoea | 33.33 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Physical Functioning | 20.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Role Functioning | 16.67 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Emotional Functioning | 8.33 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Social Functioning | 50.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Nausea and Vomiting | 16.67 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Pain | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Dyspnoea | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Appetite Loss | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Financial Difficulties | -66.67 Score on a Scale |
Secondary
Phase 3 Double Blind: Duration of Response (DOR)
DOR was defined as the time from first occurrence of CR or PR until the first date of PD per RECIST version 1.1 or death. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From first occurrence of CR or PR until the first date of PD (up to 70 months)
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment. Here, overall number of participants analyzed signifies those who had CR and PR in specified group/arm and phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Duration of Response (DOR) | 7.39 Months |
Secondary
Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Population: The Phase 3 Safety Population (Ph3-SAF) consisted of all participants in Phase 3 who had received at least one dose of blinded study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 187 Participants |
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 73 Participants |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 94 Participants |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 18 Participants |
Secondary
Phase 3 Double Blind: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR), per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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.
Time frame: From date of randomization until the documentation of CR or PR (up to 70 months)
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Overall Response Rate (ORR) | 2.7 Percentage of participants |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Overall Response Rate (ORR) | 0 Percentage of participants |
Secondary
Phase 3 Double Blind: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From date of randomization until death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Overall Survival (OS) | 10.38 Months |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Overall Survival (OS) | 12.71 Months |
Secondary
Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment
PFS was defined as the time from date of randomization until the first date of PD, per RECIST version 1.1, or death due to any cause as defined by the Investigator based on clinical and/or radiologic criteria. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 70 months)
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment | 2.89 Months |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Progression-free Survival (PFS) as Per Investigator Assessment | 1.87 Months |
Secondary
Phase 3 Double Blind: Time to Next Treatment (TTNT)
TTNT was defined as time since randomization until the first new antineoplastic therapy or death due to any cause, whichever occurs first.
Time frame: Time from randomization to the first new antineoplastic therapy or death due to any cause (up to 70 months)
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Time to Next Treatment (TTNT) | 5.42 Months |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Time to Next Treatment (TTNT) | 3.22 Months |
Secondary
Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 | 2.83 Months |
| Phase 3 Double-blinded: Placebo | Phase 3 Double Blind: Time-to-Progression (TTP) as Per RECIST Version 1.1 | 2.10 Months |
Secondary
Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30)
The QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of patients with cancer. QLQ-C30 contains 30 questions that include five functional scales (physical, role, emotional, social, and cognitive functioning); three symptom scales (fatigue, nausea/vomiting and pain); six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties); and global health status/quality of life (QoL). Most questions used a 4-point scale (from 1 'Not at all' to 4 'Very much'); 2 questions used a 7-point scale (from 1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to a 0-100 scale. For the functional scales and the global health status/QoL, a higher score represents a better level of functioning (better health status); for the symptom scales/items, a higher score represents a higher level of symptomatology/problems (worse health status).
Time frame: Baseline up to Day 379
Population: The Ph3-OL consisted of all participants in Phase 3 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Physical Functioning | -40.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Role Functioning | -33.33 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Pain | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Global Health Status | -16.67 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Emotional Functioning | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Social Functioning | -50.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Cognitive Functioning | -16.67 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Fatigue | 66.67 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Nausea and Vomiting | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Dyspnoea | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Insomnia | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Appetite Loss | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Constipation | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Diarrhoea | 0.00 Score on a Scale |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Change From Baseline in Quality-of-life Questionnaire 30 Item (QLQ-C30) | Financial Difficulties | 100.00 Score on a Scale |
Secondary
Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to 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. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 70 months
Population: The Ph3-OL consisted of all participants in Phase 3 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 63 Participants |
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 25 Participants |
Secondary
Phase 3 Open Label: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR or PR, per RECIST v.1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in 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.
Time frame: From date of randomization in the Phase 3 open label period until the documentation of CR or PR (up to 70 months)
Population: The Ph3-OL consisted of all participants in Phase 3 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Overall Response Rate (ORR) | 3.2 Percentage of participants |
Secondary
Phase 3 Open Label: Overall Survival (OS)
OS was defined as the duration (in months) from the date of randomization in the Phase 3 open-label period to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time frame: From date of randomization in phase 3 open label period until death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph3-OL consisted of all participants in Phase 3 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Overall Survival (OS) | 10.18 Months |
Secondary
Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1
TTP was defined as the time from date of randomization in the Phase 3 open-label period until ICR-determined PD per RECIST version 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: From date of randomization in the Phase 3 open label period until the first date of PD or death due to any cause, whichever occurred first (up to 70 months)
Population: The Ph3-OL consisted of all participants in Phase 3 who were randomized to placebo in the blinded phase, entered the open-label period, and received at least one dose of open-label selinexor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 3 Double-blinded: Selinexor | Phase 3 Open Label: Time-to-Progression (TTP) as Per RECIST Version 1.1 | 2.73 Months |