Trial Outcomes & Findings for Selinexor Treatment of Refractory Myeloma (NCT NCT02336815)

Last Updated: 2023-01-26

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

202 participants

Primary outcome timeframe

Baseline until disease progression/discontinuation from the study, or death, whichever occurred first (maximum duration of 17 months)

Results posted on

2023-01-26

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	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 multiple myeloma (MM) (i.e. 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 the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 milligrams (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).	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 post oral (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).
Overall Study STARTED	79	123
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	79	123

Reasons for withdrawal

Reasons for withdrawal
Measure	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 multiple myeloma (MM) (i.e. 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 the anti-CD38 mAb daratumumab) received, two dosing schedules (1) selinexor 80 milligrams (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).	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 post oral (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).
Overall Study Disease Progression	45	70
Overall Study Adverse Event	18	39
Overall Study Physician Decision	11	4
Overall Study Withdrawal by Subject	3	2
Overall Study Lost to Follow-up	1	3
Overall Study Other	1	5

Baseline Characteristics

Selinexor Treatment of Refractory Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 n=79 Participants 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).	Part 2 n=123 Participants 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).	Total n=202 Participants Total of all reporting groups
Age, Continuous	62.9 years STANDARD_DEVIATION 8.79 • n=5 Participants	64.5 years STANDARD_DEVIATION 9.41 • n=7 Participants	63.9 years STANDARD_DEVIATION 9.18 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	52 Participants n=7 Participants	94 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	71 Participants n=7 Participants	108 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=5 Participants	97 Participants n=7 Participants	172 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	17 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	21 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) White	62 Participants n=5 Participants	86 Participants n=7 Participants	148 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
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 Interval 18.7 to 35.0	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=16 Participants 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).	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).
Part 1: Duration of Response (DoR) Per IMWG as Assessed by IRC	6.2 Months Interval 3.6 to 9.8	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=32 Participants 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).	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).
Part 2: Duration of Response (DoR) Per IMWG as Assessed by an IRC	4.4 Months Interval 3.7 to 10.8	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Part 1: Percentage of Participants With Clinical Benefit Rate (CBR) ) Per IMWG as Assessed by IRC	31.6 Percentage of Participants Interval 21.6 to 43.1	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
Part 2: Percentage of Participants With Clinical Benefit Rate (CBR) Per IMWG as Assessed by IRC	39.3 Percentage of Participants Interval 30.6 to 48.6	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=25 Participants 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).	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).
Part 1: Duration of Clinical Benefit Per IMWG as Assessed by IRC	5.6 Months Interval 4.4 to 10.3	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=48 Participants 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).	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).
Part 2: Duration of Clinical Benefit Per IMWG as Assessed by IRC	3.8 Months Interval 3.2 to 10.9	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
Part 2: Disease Control Rate (DCR)	44.3 Percentage of Participants Interval 35.3 to 53.5	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Part 1: Progression Free Survival (PFS) Per IMWG as Assessed by IRC	4.7 Months Interval 3.3 to 7.6	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
Part 2: Progression Free Survival (PFS) Per IMWG as Assessed by IRC	3.7 Months Interval 2.8 to 4.7	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Part 1: Time to Progression (TTP) Per IMWG as Assessed by IRC	5.5 Months Interval 3.3 to 10.7	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
Part 2: Time to Progression (TTP) Per IMWG as Assessed by IRC	4.1 Months Interval 3.0 to 6.2	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Part 1: Time to Next Treatment (TTNT)	2.6 Months Interval 1.8 to 4.2	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
Part 2: Time to Next Treatment (TTNT)	3.2 Months Interval 2.6 to 3.8	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Part 1: Overall Survival (OS)	7.3 Months Interval 5.8 to 10.9	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=122 Participants 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).	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).
Part 2: Overall Survival (OS)	8.4 Months Interval 6.2 to 11.2	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=107 Participants 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).	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).
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 19.20	—
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: 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 15.50	—
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: 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: 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: 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: 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: 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: 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: 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 Standard Deviation NA Standard deviation was not estimated due to single participant.	—
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 Standard Deviation NA Standard deviation was not estimated due to single participant.	—
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 Standard Deviation NA Standard deviation was not estimated due to single participant.	—
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 Standard Deviation NA Standard deviation was not estimated due to single participant.	—
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 Standard Deviation NA Standard deviation was not estimated due to single participant.	—
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 Standard Deviation NA Standard deviation was not estimated due to single participant.	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	Part 2 n=123 Participants 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).
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	115 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	Part 2 n=123 Participants 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).
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	110 Participants

SECONDARY outcome

Timeframe: 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.

CL/F of selinexor in plasma was reported.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Apparent Clearance (CL/F) of Selinexor in Plasma	16.6 Liters/Hour Standard Deviation 2.8	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 2 n=79 Participants 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).	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).
Volume of Distribution (V/F) of Selinexor in Plasma	145.6 Liter Standard Deviation 28.2	—

Adverse Events

Part 1

Serious events: 45 serious events

Other events: 79 other events

Deaths: 20 deaths

Part 2

Serious events: 78 serious events

Other events: 123 other events

Deaths: 28 deaths

Serious adverse events

Other adverse events

Additional Information

Jatin Shah, MD

Karyopharm Therapeutics Inc.

Phone: (617) 658-0600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Part 1 n=79 participants at risk 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).	Part 2 n=123 participants at risk 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 post oral (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).
Blood and lymphatic system disorders Thrombocytopenia	73.4% 58/79 • Number of events 58 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	74.0% 91/123 • Number of events 91 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Blood and lymphatic system disorders Anaemia	46.8% 37/79 • Number of events 37 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	65.0% 80/123 • Number of events 80 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Blood and lymphatic system disorders Neutropenia	29.1% 23/79 • Number of events 23 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	39.8% 49/123 • Number of events 49 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Blood and lymphatic system disorders Leukopenia	25.3% 20/79 • Number of events 20 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	33.3% 41/123 • Number of events 41 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Blood and lymphatic system disorders Lymphopenia	13.9% 11/79 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	16.3% 20/123 • Number of events 20 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Cardiac disorders Tachycardia	11.4% 9/79 • Number of events 9 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	3.3% 4/123 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Eye disorders Vision blurred	12.7% 10/79 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	10.6% 13/123 • Number of events 13 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Gastrointestinal disorders Nausea	75.9% 60/79 • Number of events 60 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	71.5% 88/123 • Number of events 88 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Gastrointestinal disorders Diarrhoea	44.3% 35/79 • Number of events 35 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	46.3% 57/123 • Number of events 57 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Gastrointestinal disorders Vomiting	46.8% 37/79 • Number of events 37 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	38.2% 47/123 • Number of events 47 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Gastrointestinal disorders Constipation	26.6% 21/79 • Number of events 21 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	22.0% 27/123 • Number of events 27 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Gastrointestinal disorders Abdominal pain	8.9% 7/79 • Number of events 7 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	9.8% 12/123 • Number of events 12 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Fatigue	69.6% 55/79 • Number of events 55 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	62.6% 77/123 • Number of events 77 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Pyrexia	12.7% 10/79 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	14.6% 18/123 • Number of events 18 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Asthenia	6.3% 5/79 • Number of events 5 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	15.4% 19/123 • Number of events 19 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Oedema peripheral	6.3% 5/79 • Number of events 5 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	11.4% 14/123 • Number of events 14 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Chills	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	3.3% 4/123 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Malaise	2.5% 2/79 • Number of events 2 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	6.5% 8/123 • Number of events 8 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
General disorders Gait disturbance	0.00% 0/79 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	5.7% 7/123 • Number of events 7 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Infections and infestations Upper respiratory tract infection	12.7% 10/79 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	13.8% 17/123 • Number of events 17 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Infections and infestations Pneumonia	3.8% 3/79 • Number of events 3 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.1% 10/123 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Infections and infestations Urinary tract infection	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	3.3% 4/123 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Injury, poisoning and procedural complications Fall	5.1% 4/79 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	10.6% 13/123 • Number of events 13 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Investigations Weight decreased	49.4% 39/79 • Number of events 39 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	49.6% 61/123 • Number of events 61 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Investigations Alanine aminotransferase increased	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	10.6% 13/123 • Number of events 13 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Investigations Aspartate aminotransferase increased	3.8% 3/79 • Number of events 3 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.9% 11/123 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Decreased appetite	54.4% 43/79 • Number of events 43 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	55.3% 68/123 • Number of events 68 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hyponatraemia	43.0% 34/79 • Number of events 34 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	36.6% 45/123 • Number of events 45 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hyperglycaemia	20.3% 16/79 • Number of events 16 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	12.2% 15/123 • Number of events 15 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hypokalaemia	6.3% 5/79 • Number of events 5 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	19.5% 24/123 • Number of events 24 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Dehydration	19.0% 15/79 • Number of events 15 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.1% 10/123 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hypocalcaemia	8.9% 7/79 • Number of events 7 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	10.6% 13/123 • Number of events 13 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hypomagnesaemia	12.7% 10/79 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.1% 10/123 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hypophosphataemia	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	6.5% 8/123 • Number of events 8 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hypercreatininaemia	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	4.9% 6/123 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hypercalcaemia	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	4.1% 5/123 • Number of events 5 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Metabolism and nutrition disorders Hyperkalaemia	1.3% 1/79 • Number of events 1 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.1% 10/123 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Back pain	11.4% 9/79 • Number of events 9 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.1% 10/123 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Bone pain	8.9% 7/79 • Number of events 7 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.9% 11/123 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Hypercreatinaemia	11.4% 9/79 • Number of events 9 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	4.9% 6/123 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Arthralgia	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	4.9% 6/123 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Muscle spasms	5.1% 4/79 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	6.5% 8/123 • Number of events 8 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Muscular weakness	7.6% 6/79 • Number of events 6 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	3.3% 4/123 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 4/79 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	3.3% 4/123 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Nervous system disorders Dizziness	15.2% 12/79 • Number of events 12 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	15.4% 19/123 • Number of events 19 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Nervous system disorders Headache	12.7% 10/79 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.9% 11/123 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Nervous system disorders Dysgeusia	12.7% 10/79 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.1% 10/123 • Number of events 10 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Nervous system disorders Peripheral neuropathy	8.9% 7/79 • Number of events 7 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	6.5% 8/123 • Number of events 8 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Psychiatric disorders Insomnia	13.9% 11/79 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	17.9% 22/123 • Number of events 22 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Psychiatric disorders Confusional state	11.4% 9/79 • Number of events 9 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	8.9% 11/123 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Psychiatric disorders Anxiety	5.1% 4/79 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	6.5% 8/123 • Number of events 8 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	29.1% 23/79 • Number of events 23 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	22.8% 28/123 • Number of events 28 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Respiratory, thoracic and mediastinal disorders Cough	15.2% 12/79 • Number of events 12 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	14.6% 18/123 • Number of events 18 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	13.9% 11/79 • Number of events 11 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	10.6% 13/123 • Number of events 13 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Respiratory, thoracic and mediastinal disorders Productive cough	5.1% 4/79 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	2.4% 3/123 • Number of events 3 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)
Skin and subcutaneous tissue disorders Alopecia	5.1% 4/79 • Number of events 4 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)	2.4% 3/123 • Number of events 3 • Baseline to 30 days after last dose of study treatment (maximum duration of 18 months)