Multiple Myeloma
Conditions
Keywords
Multiple myeloma, Karyopharm, KPT-330, Selinexor, Refractory, Bortezomib, Carfilzomib, Lenalidomide, Pomalidomide, Dexamethasone, STORM, Daratumumab
Brief summary
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd) dosed twice weekly in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or quad refractory MM (Part 1 only).
Detailed description
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg plus dexamethasone 20 mg (Sd), both dosed twice weekly in each four-week cycle, in patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab and refractory to prior treatment with glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and daratumumab. This study consists of two parts: * Part 1 enrolled patients with both quad-refractory MM and penta-refractory MM. * Part 2 will enroll patients with penta-refractory MM only.
Interventions
DRUGSelinexor
Fixed oral dose of 80 mg twice weekly (e.g., Monday and Wednesday or Tuesday and Thursday, etc.)
DRUGDexamethasone
20 mg was given with each dose of Selinexor.
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Measurable MM based on modified IMWG guidelines. Defined by at least one of the following: 1. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA 2. Urinary M-protein excretion ≥ 200 mg/24 hours 3. Free Light Chain (FLC) ≥ 100 mg/L, provided that the FLC ratio is abnormal 4. If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative Ig levels by nephelometry or turbidimetry are acceptable * Must have previously received ≥ 3 anti-MM regimens including: an alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a glucocorticoid. There is no upper limit on the number of prior therapies provided that all other inclusion/
Exclusion criteria
are met. * MM refractory to previous treatment with one or more glucocorticoids, parenteral PI (i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), and the anti-CD38 mAb, daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC) | Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months) | IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (\>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to lesser than (\<) 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and lesser than or equal to (\<=) 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells in bone marrow biopsy by immunohistochemistry). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC | First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months) | IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>= 5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC | Baseline up to a maximum of 13 months | IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry). |
| Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC | Baseline up to a maximum of 17 months | IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry). |
| Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC | First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months) | IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC | First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months) | IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 2: Disease Control Rate (DCR) | Every 12 weeks until progressive disease or death due to any cause, up to 17 months | DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: CR as defined+Normal FLC ratio+Absence of clonal cells by immunohistochemistry). |
| Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC | From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months) | IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC | From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months) | IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC | From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months) | IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC | First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months) | IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method. |
| Part 1: Time to Next Treatment (TTNT) | From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 13 months) | TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method. |
| Part 2: Time to Next Treatment (TTNT) | From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 17 months) | TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method. |
| Part 1: Overall Survival (OS) | From start of study treatment to death (maximum duration of 13 months) | OS was defined as the duration (in months) from start of study treatment 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. Analysis was performed using Kaplan-Meier method. |
| Part 2: Overall Survival (OS) | From start of study treatment to death (maximum duration of 17 months) | OS was defined as the duration (in months) from start of study treatment 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. Analysis was performed using Kaplan-Meier method. |
| Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Baseline, Day 1 of Cycle 2 to Cycle 20 (up to a maximum of 17 months) | FACT-MM combines the general version of the FACT (FACT-G) with a MM-specific sub-scale (14 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI); total of 41 items) is the primary measurement of interest, comprised of the Physical and Functional sub-scales plus the MM-specific sub-scale. Each item is rated on a 5-point Likert scale, ranging from 0 (Not at all) to 4 (Very much), therefore the TOI has a score ranging from 0 to 120. Higher scores indicated improvement in well being. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) | 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. Treatment-emergent events are events between first dose of study drug and up to last dose of study treatment + 30 days (inclusive) that were absent before treatment or that worsened relative to pre-treatment state. |
| Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | Baseline to 30 days after last dose of study treatment (maximum duration of 18 months) | 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. |
| Apparent Clearance (CL/F) of Selinexor in Plasma | Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose | CL/F of selinexor in plasma was reported. |
| Volume of Distribution (V/F) of Selinexor in Plasma | Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose | Vz/F of selinexor in plasma was reported. |
| Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC | From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months) | IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method. |
Countries
Austria, Belgium, France, Germany, Greece, United States
Participant flow
Recruitment details
Part 1 of the study was conducted at 32 sites in the United States and Part 2 of the study was conducted at 59 sites in France, Germany, Belgium, Greece, Austria and United States. Enrollment in both parts was between from 26 May 2015 (first participant first visit)) and 26 July 2019 (last participant last visit).
Pre-assignment details
A total of 202 participants were enrolled in the study, out of which 79 participants were treated in Part 1 and 123 participants were treated in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Participants with quad-exposed, double-class-refractory (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, but not an anti-CD38 mab) and penta-exposed, triple-class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly on Days 1 and 3 for 3 weeks of each 4-week cycle (2) selinexor 80 mg plus low-dose dexamethasone 20 mg (Sd) twice-weekly continuously in 4-week cycles; until disease progression, death, or unacceptable toxicity (maximum duration of approximately 13 months). | 79 |
| Part 2 Participants who previously had received more than 3 anti-MM regimens and had penta-exposed, triple class-refractory MM (i.e. previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an IMiD, a PI, and the anti-CD38 mAb daratumumab) received, selinexor 80 mg PO plus low-dose dexamethasone 20 mg Sd twice-weekly on Days 1 and 3 until disease progression, death, or unacceptable toxicity (maximum duration of approximately 17 months). | 123 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 39 |
| Overall Study | Disease Progression | 45 | 70 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Other | 1 | 5 |
| Overall Study | Physician Decision | 11 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Part 2 | Total | Part 1 |
|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 9.41 | 63.9 years STANDARD_DEVIATION 9.18 | 62.9 years STANDARD_DEVIATION 8.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 11 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 97 Participants | 172 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 19 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 35 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 10 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) White | 86 Participants | 148 Participants | 62 Participants |
| Sex: Female, Male Female | 52 Participants | 94 Participants | 42 Participants |
| Sex: Female, Male Male | 71 Participants | 108 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 79 | 28 / 123 |
| other Total, other adverse events | 79 / 79 | 123 / 123 |
| serious Total, serious adverse events | 45 / 79 | 78 / 123 |
Outcome results
Primary
Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC)
IRC assessed ORR per 2016 IMWG criteria: Percentage of participants who experienced Partial response (PR): greater than or equal to (\>=) 50 percent (%) reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to lesser than (\<) 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and lesser than or equal to (\<=) 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells in bone marrow biopsy by immunohistochemistry).
Time frame: Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)
Population: Modified intent-to-treat (mITT) population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Data was not planned to be collected and analyzed for Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2 | Part 2: Percentage of Participants With Overall Response Rate (ORR) Per International MyelomaWorking Group (IMWG) as Assessed by an Independent Review Committee (IRC) | 26.2 Percentage of Participants |
Secondary
Apparent Clearance (CL/F) of Selinexor in Plasma
CL/F of selinexor in plasma was reported.
Time frame: Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose
Population: Pharmacokinetic (PK) set included all participants in Part 1 who received at least 1 dose of investigational product in this study. Data was not planned to be collected and analyzed for Part 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 2 | Apparent Clearance (CL/F) of Selinexor in Plasma | 16.6 Liters/Hour | Standard Deviation 2.8 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
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. Treatment-emergent events are events between first dose of study drug and up to last dose of study treatment + 30 days (inclusive) that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | 75 Participants |
| Part 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAE) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | 115 Participants |
Secondary
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
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.
Time frame: Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 2 | Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | 69 Participants |
| Part 2 | Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (TEAEs) of Grade 3/4, Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 | 110 Participants |
Secondary
Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC
IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 13 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC | 5.6 Months |
Secondary
Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC
IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 gram per deciliter (g/dL); Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 13 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC | 6.2 Months |
Secondary
Part 1: Overall Survival (OS)
OS was defined as the duration (in months) from start of study treatment 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. Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to death (maximum duration of 13 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 1: Overall Survival (OS) | 7.3 Months |
Secondary
Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC
IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).
Time frame: Baseline up to a maximum of 13 months
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2 | Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC | 31.6 Percentage of Participants |
Secondary
Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC
IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 13 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC | 4.7 Months |
Secondary
Part 1: Time to Next Treatment (TTNT)
TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 13 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 1: Time to Next Treatment (TTNT) | 2.6 Months |
Secondary
Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC
IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 13 months)
Population: Safety population consisted of all participants, who had received at least 1 dose of study treatment (partial or complete) and had any post-baseline safety information.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC | 5.5 Months |
Secondary
Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire
FACT-MM combines the general version of the FACT (FACT-G) with a MM-specific sub-scale (14 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI); total of 41 items) is the primary measurement of interest, comprised of the Physical and Functional sub-scales plus the MM-specific sub-scale. Each item is rated on a 5-point Likert scale, ranging from 0 (Not at all) to 4 (Very much), therefore the TOI has a score ranging from 0 to 120. Higher scores indicated improvement in well being.
Time frame: Baseline, Day 1 of Cycle 2 to Cycle 20 (up to a maximum of 17 months)
Population: mITT population set. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure at given time points. Data was not planned to be collected and analyzed for Part 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Baseline | 67.5 Score on a Scale | Standard Deviation 19.2 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C2D1 | -6.1 Score on a Scale | Standard Deviation 18.43 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C3D1 | -8.5 Score on a Scale | Standard Deviation 15.5 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C4D1 | -9.1 Score on a Scale | Standard Deviation 16.79 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C5D1 | -6.9 Score on a Scale | Standard Deviation 12.06 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C6D1 | -8.3 Score on a Scale | Standard Deviation 15.07 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C7D1 | -7.5 Score on a Scale | Standard Deviation 19.26 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C8D1 | -15.4 Score on a Scale | Standard Deviation 24.59 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C9D1 | -4.7 Score on a Scale | Standard Deviation 14.84 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C10D1 | -4.0 Score on a Scale | Standard Deviation 5.29 |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C11D1 | 3.0 Score on a Scale | — |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C12D1 | 3.0 Score on a Scale | — |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C13D1 | -23.0 Score on a Scale | — |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C14D1 | 14.0 Score on a Scale | — |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C15D1 | 1.0 Score on a Scale | — |
| Part 2 | Part 2: Change From Baseline in Health-related Quality of Life (HRQL) Score Based on Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) Questionnaire | Trial Outcomes Index Score: Change at C16D1 | 4.0 Score on a Scale | — |
Secondary
Part 2: Disease Control Rate (DCR)
DCR was defined as the percentage of participants who achieved stable disease (SD) or better (MR, PR, VGPR, CR, sCR) for a minimum of 12 weeks. Stable disease (SD): Not recommended for use as an indicator of response; stability of disease was best described by providing the time to progression (TTP) estimates. MR: \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: CR as defined+Normal FLC ratio+Absence of clonal cells by immunohistochemistry).
Time frame: Every 12 weeks until progressive disease or death due to any cause, up to 17 months
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Data was not planned to be collected and analyzed for Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2 | Part 2: Disease Control Rate (DCR) | 44.3 Percentage of Participants |
Secondary
Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC
IRC assessed duration of clinical benefit per 2016 IMWG criteria: Duration from first response (at least MR) to time of IRC-determined PD or death due to disease progression, whichever occurs first. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: First response subsequently confirmed to disease progression, or death, whichever occurred first (maximum duration of 17 months)
Population: miTT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC | 3.8 Months |
Secondary
Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC
IRC assessed DoR per 2016 IMWG criteria: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of progressive disease (PD) or death due to any cause. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>= 5 g/dL; Urine M-protein (absolute increase must be \>= 200 mg per 24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: First response subsequently confirmed to disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC | 4.4 Months |
Secondary
Part 2: Overall Survival (OS)
OS was defined as the duration (in months) from start of study treatment 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. Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to death (maximum duration of 17 months)
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 2: Overall Survival (OS) | 8.4 Months |
Secondary
Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC
IRC assessed CBR per 2016 IMWG criteria: Percentage of participants with a confirmed minimal response (MR) or better (PR, VGPR, CR or sCR) before confirmed disease progression or initiating new MM treatment. Minimal response (MR): \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%. Partial response (PR): \>= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>= 90% or to \< 200 mg per 24 hours; Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 hours; Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or stringent complete response (sCR): CR as defined+Normal free light chain (FLC) ratio+Absence of clonal cells by immunohistochemistry).
Time frame: Baseline up to a maximum of 17 months
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 2 | Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC | 39.3 Percentage of Participants |
Secondary
Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC
IRC assessed PFS per 2016 IMWG criteria: Duration from start of study treatment until IRC-determined progressive disease (PD) or death from any cause, whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 17 months)
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC | 3.7 Months |
Secondary
Part 2: Time to Next Treatment (TTNT)
TTNT was defined as the duration from start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurred first. Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to start of next anti-MM treatment or death due to disease progression, whichever occurs first (maximum duration of 17 months)
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 2: Time to Next Treatment (TTNT) | 3.2 Months |
Secondary
Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC
IRC assessed TTP per 2016 IMWG criteria: Duration from start of study treatment until PD or death due to PD (per IRC), whichever occurred first. Progressive disease (PD): Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>=1 g/dL if the lowest M-component was \>= 5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg/24 hours). Analysis was performed using Kaplan-Meier method.
Time frame: From start of study treatment to progression of disease or death, whichever occurred first (maximum duration of 17 months)
Population: mITT population consisted of Part 2 participants with penta-refractory MM who met all eligibility criteria and received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 | Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC | 4.1 Months |
Secondary
Volume of Distribution (V/F) of Selinexor in Plasma
Vz/F of selinexor in plasma was reported.
Time frame: Cycle 1: Day 1: Pre-dose, 1, 2 and 4 hours post-dose; Day 8 and 15: Pre-dose and 1 hour post-dose; Cycle 2: Day 1: Predose, 1, 2 and 4 hours post-dose
Population: Pharmacokinetic (PK) set included all participants in Part 1 who received at least 1 dose of investigational product in this study. Data was not planned to be collected and analyzed for Part 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 2 | Volume of Distribution (V/F) of Selinexor in Plasma | 145.6 Liter | Standard Deviation 28.2 |