SEAL: Selinexor in Advanced Liposarcoma

• Sponsor: Karyopharm Therapeutics Inc (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02606461
• Collaborator: (none)
• Enrollment: 342
• Locations: 71
• Arms: 4
• Anticipated Duration (Months): 70.9
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a randomized, multicenter, double-blind, placebo-controlled, Phase 2-3 study of patients diagnosed with advanced unresectable dedifferentiated liposarcoma. Approximately 342 total patients will be randomized to study treatment (selinexor or placebo).

Condition or Disease	Intervention/Treatment	Phase
Dedifferentiated Liposarcoma	Drug: Selinexor; Drug: Placebo	Phase 2/Phase 3

Detailed Description

In the Phase 2 portion of the study, 57 patients were randomized to selinexor (60 mg) or placebo at a 1:1 allocation ratio.

In the Phase 3 portion of the study, approximately 285 patients will be randomized to selinexor (60 mg) or placebo with a 2:1 allocation ratio.

Patients who progress during the blinded portion of the study will be unblinded and if receiving:

• placebo, may cross over to open-label selinexor (60mg twice weekly)

• selinexor, will be withdrawn from further treatment and followed for survival

Study treatment will be given twice weekly on Day 1 and Day 3 during Weeks 1-6 of each six-week (42 day) cycle until disease progression or intolerability.

Treatment will continue until one or more of the following occurs:

• Disease progression, as defined by RECIST v1.1 Response Criteria

• Clinical progression, as determined by the treating physician

• Unacceptable Adverse events (AEs) or failure to tolerate study treatment

• Patient withdrawal

• Patient discontinuation due to non-compliance

Study Design

• Study Type: Interventional
• Actual Enrollment: 342 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2-3, Multicenter, Randomized, Double-blind Study of Selinexor (KPT-330) Versus Placebo in Patients With Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)
• Actual Study Start Date: Jan 4, 2016
• Actual Primary Completion Date: Oct 28, 2020
• Anticipated Study Completion Date: Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2 Double-blinded: Selinexor Participants received a fixed blinding dose of 60 milligrams (mg) selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until progressive disease (PD).	Drug: Selinexor; Selinexor 60mg; Other Names: KPT-330
Experimental: Phase 3 Double-blinded: Selinexor Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Drug: Selinexor; Selinexor 60mg; Other Names: KPT-330
Placebo Comparator: Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD in double-blinded treatment period. Participants in the placebo group who had PD during the Phase 2 double-blinded treatment, will be elected to cross over to open-label selinexor.	Drug: Placebo; Other Names: sugar pill
Placebo Comparator: Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity. Participants in the placebo group who had PD during the Phase 3 double-blinded treatment, will be elected to cross over to open-label selinexor.	Drug: Placebo; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version. 1.1 [From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 56 months)]

   Progression-free survival (PFS) was defined as the time from the date of randomization until the first date of IRC-confirmed PD per RECIST version. 1.1, or death due to any cause. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions.

2. Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1 [From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 56 months)]

   Progression-free survival (PFS) was defined as the time from date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Secondary Outcome Measures

1. Phase 3 Double Blind: Overall Survival (OS) [From date of randomization until death due to any cause, whichever occurred first (up to 56 months)]

   OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.

2. Phase 2 Double Blind: Overall Survival (OS) [From the date of randomization until death due to any cause, whichever occurred first (up to 56 months)]

   OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.

3. Phase 3 Double Blind: Time to Progression (TTP) as Per RECIST Version 1.1 [From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 56 months)]

   TTP was defined as the time from date of randomization until determined progressive disease (PD) as per RECIST version. 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

4. Phase 2 Double Blind: Time to Progression (TTP) as Per RECIST Version 1.1 [From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 56 months)]

   TTP was defined as the time from date of randomization until determined progressive disease (PD) as per RECIST version. 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

5. Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [From start of study drug administration up to 56 Months]

   Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.

6. Phase 2 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [From start of study drug administration up to 56 Months]

   Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.

7. Phase 3 Double Blind: Change From Baseline in Quality-of-Life Questionnaire 30 Item (QLQ-C30) [Baseline up to Day 1135]

   The QLQ-C30 was a 30-item questionnaire developed to assess the quality of life of cancer patients. QLQ-C30 contains 30 questions that include five functional scales: physical, role, emotional, social, and cognitive functioning; three symptom scales (fatigue, nausea/vomiting and pain), six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/quality of life (QoL) scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. A negative change from baseline score indicates less functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients ≥12 years of age

2. Body surface area (BSA) ≥ 1.2 m2

3. Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment

4. Must have measurable disease per RECIST v1.1 Response Criteria

5. Radiologic evidence of disease progression within 6 months prior to randomization. If the patient received other intervening therapy after documented disease progression, further disease progression must be documented after the completion of the intervening therapy

6. Must have had at least two (2) prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines)

7. If patient received any previous systemic therapy, the last dose must have been ≥ 21 days prior to randomization (or ≥ 5 half-lives of that drug - whichever is shorter) with all clinically significant therapy- related toxicities having resolved to less than or equal to Grade 1

Exclusion Criteria:

1. Patients with pure Well-differentiated Liposarcoma (WDLS), myxoid/round cell or pleomorphic tumor histologic subtypes.

2. Known active Hepatitis B (HepB), Hepatitis C (HepC) or human immunodeficiency virus (HIV) infection.

3. Known central nervous system metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	University of California, Los Angeles	Los Angeles	California	United States	90095
3	Sarcoma Oncology Center	Santa Monica	California	United States	90403
4	Stanford University	Stanford	California	United States	94305
5	University of Colorado-Denver	Denver	Colorado	United States	80202
6	Yale Cancer Center	New Haven	Connecticut	United States	06520-8032
7	Mayo Clinic	Jacksonville	Florida	United States	32224
8	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
9	Johns Hopkins	Baltimore	Maryland	United States	21231
10	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
11	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
12	University of Michigan	Ann Arbor	Michigan	United States	48109
13	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
14	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
15	Columbia University Medical Center	New York	New York	United States	10032
16	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
17	Northwell Health Physicians Partners	New York	New York	United States	11042
18	Duke Institute of Cancer	Durham	North Carolina	United States	27710
19	James Cancer Center, Ohio State University	Columbus	Ohio	United States	43210-1240
20	Oregon Health and Science	Portland	Oregon	United States	97239
21	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19106
22	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
23	University of Pittsburgh Medical Center (UPMC)	Pittsburgh	Pennsylvania	United States	15232
24	Vanderbilt	Nashville	Tennessee	United States	37232
25	MD Anderson	Houston	Texas	United States	77030
26	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
27	UZ Brussel	Brussels		Belgium	1090
28	UCL Saint-Luc	Brussels		Belgium	1200
29	UZ Gent	Ghent		Belgium	9000
30	Cross Cancer Center - Alberta Health Services	Edmonton	Alberta	Canada	T6G1Z2
31	The Ottawa Hospital Cancer	Ottawa	Ontario	Canada
32	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
33	McGill University	Montréal	Quebec	Canada	H4A3J1
34	Institut Bergonie	Bordeaux,		France	33076
35	Oscar Lambret Center	Lille Cedex 307		France	59020
36	Centre Leon Berard	Lyon Cedex		France	96373
37	Timone University Hospital	Marseille Cedex 5		France	13385
38	Institut Régional du Cancer de Montpellier (ICM)	Montpellier		France	34298
39	CLCC Antoine Lacassagne	Nice		France	06789
40	Institut Curie	Paris		France	75248
41	Institut Claudius Regaud	Toulouse		France	31059
42	Institut Gustave Roussy	Villejuif		France	94110
43	Helios Hospital Berlin-Buch	Berlin		Germany	13125
44	Technische Universitaet Dresden Med. Fakultaet Carl Gustav Carus Med. Klinik u. Poliklinik I	Dresden		Germany	01307
45	National Center for Tumor Diseases, Univeristy Hospital Heidelberg	Heidelberg		Germany	69120
46	University Hospital Mannheim	Mannheim		Germany	68167
47	Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie Klinikum rechts der Isar der TU Muenchen	Muenchen		Germany	81675
48	Soroka University Medical Center	Be'er Sheva		Israel	84101
49	Hadassah Medical Center	Jerusalem		Israel	91120
50	Rabin Medical Center	Petach Tikva		Israel	4941492
51	Sheba Medical Center	Ramat Gan		Israel	52621
52	Tel Aviv Sourasky Medical	Tel Aviv		Israel	64239
53	Assaf Harofe Medical Center	Zerifin		Israel	7030000
54	Candiolo Cancer Institute	Candiolo		Italy	10060
55	Istituto Nazionale dei Tumori, Milan	Milano		Italy	20133
56	U.O.C. Oncologia Medica Oncology Department	Palermo		Italy	90127
57	Policlinico Universitario Campus Biomedico	Roma		Italy	00128
58	"Germans Trias Pujol" University Hospital	Badalona		Spain	41013
59	Vall d´hebron University Hospital	Barcelona		Spain	08035
60	Hospital Sant Pau Barcelona	Barcelona		Spain	08041
61	Hospital ICO Bellvitge	Barcelona		Spain	08908
62	Hospital Universitario Clínico San Carlos	Madrid		Spain	28040
63	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
64	Hospital La Fe Valencia	Valencia		Spain	46026
65	Sahlgrenska Universitetssjukhuset	Göteborg		Sweden	413 45
66	Skane University Hospital	Lund		Sweden	221 85
67	Onkologiska Kliniken	Stockholm		Sweden	171 76
68	Cambridge University Hospitals NHS Foundation Trust	Cambridge		United Kingdom	CB2 0QQ
69	University College London Hospitals	London		United Kingdom	NW1 2BU
70	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SW3 6JJ
71	The Christie	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• Karyopharm Therapeutics Inc

Investigators

• Study Director: Michael Kauffman, MD, Ph.D, Karyopharm Therapeutics Inc

Study Documents (Full-Text)

• Study Protocol - May 21, 2020
• Statistical Analysis Plan - Sep 20, 2020

More Information

Publications

None provided.

• Responsible Party: Karyopharm Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT02606461
• Other Study ID Numbers: KCP-330-020; 2015-003594-14
• First Posted: Nov 17, 2015
• Last Update Posted: Dec 7, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Karyopharm Therapeutics Inc: Advanced unresectable dedifferentiated liposarcoma; selinexor; KCP-330; Karyopharm; Phase 2 / 3; dedifferentiated liposarcoma; Liposarcoma
• Additional relevant MeSH terms: Liposarcoma

Study Results

Participant Flow

Recruitment Details

Participants were enrolled at 71 sites in the United States, Canada, Germany, Belgium, Israel, United Kingdom, France, Spain, Italy, and Sweden. This study consisted of 2 Phases (2 and 3), where participants were randomized to selinexor or placebo in double-blind treatment and has the option to cross over to open-label selinexor from placebo group of both phases based on progressive disease (PD).

Pre-assignment Detail

A total of 57 participants were enrolled, randomized, and received study treatment in Phase 2 and 285 participants were enrolled and randomized in Phase 3, of which 284 participants received study treatment in this study. Participants in the placebo group who had PD during the Phase 2 and 3 double-blinded treatment, could crossover to open-label selinexor treatment. Data was reported based on primary analysis cut-off date (30-Sep-2020) for double-blinded treatment period only.

Arm/Group Title	Phase 2 Double-blinded: Selinexor	Phase 2 Double-blinded: Placebo Followed by Open Label- Selinexor	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo Followed by Open Label- Selinexor
Arm/Group Description	Participants received a fixed blinding dose of 60 milligrams (mg) selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD in double-blinded treatment period. Participants in the placebo group who had PD during the Phase 2 double-blinded treatment, will be elected to cross over to open-label selinexor.	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity. Participants in the placebo group who had PD during the Phase 3 double-blinded treatment, will be elected to cross over to open-label selinexor.
Period Title: Overall Study
STARTED	27	30	188	97
Treated	27	30	187	97
Open Label	0	24	0	57
COMPLETED	0	0	0	0
NOT COMPLETED	27	30	188	97

Baseline Characteristics

Arm/Group Title	Phase 2 Double-blinded: Selinexor	Phase 2 Double-blinded: Placebo	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo	Total
Arm/Group Description	Participants received a fixed blinding dose of 60 milligram (mg) selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.	Total of all reporting groups
Overall Participants	27	30	188	97	342
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	19 70.4%	17 56.7%	92 48.9%	46 47.4%	174 50.9%
>=65 years	8 29.6%	13 43.3%	96 51.1%	51 52.6%	168 49.1%
Sex: Female, Male (Count of Participants)
Female	12 44.4%	11 36.7%	74 39.4%	33 34%	130 38%
Male	15 55.6%	19 63.3%	114 60.6%	64 66%	212 62%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.4%	3 10%	7 3.7%	6 6.2%	18 5.3%
Not Hispanic or Latino	25 92.6%	25 83.3%	149 79.3%	79 81.4%	278 81.3%
Unknown or Not Reported	0 0%	2 6.7%	32 17%	12 12.4%	46 13.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 7.4%	5 16.7%	9 4.8%	3 3.1%	19 5.6%
Native Hawaiian or Other Pacific Islander	1 3.7%	0 0%	2 1.1%	0 0%	3 0.9%
Black or African American	1 3.7%	2 6.7%	3 1.6%	1 1%	7 2%
White	23 85.2%	20 66.7%	139 73.9%	80 82.5%	262 76.6%
More than one race	0 0%	3 10%	34 18.1%	13 13.4%	50 14.6%
Unknown or Not Reported	0 0%	0 0%	1 0.5%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Phase 3 Double Blind: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version. 1.1
Description	Progression-free survival (PFS) was defined as the time from the date of randomization until the first date of IRC-confirmed PD per RECIST version. 1.1, or death due to any cause. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions.
Time Frame	From the date of randomization until the first date of disease progression, or death due to any cause whichever occurred first (up to 56 months)

Outcome Measure Data

Analysis Population Description

Phase 3 Intent-to-Treat Population (Ph3-ITT) consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.

Arm/Group Title	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.
Measure Participants	188	97
Median (95% Confidence Interval) [Months]	2.83	2.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 3 Double-blinded: Selinexor, Phase 3 Double-blinded: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0114
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.7026
	Confidence Interval	(2-Sided) 95%; 0.5191 to 0.9509
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Phase 2 Double Blind: Progression-free Survival (PFS) as Per RECIST Version 1.1
Description	Progression-free survival (PFS) was defined as the time from date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST version 1.1, or death due to any cause. PD was defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time Frame	From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 56 months)

Outcome Measure Data

Analysis Population Description

The Phase 2 Intent-to-Treat Population (Ph2-ITT) consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.

Arm/Group Title	Phase 2 Double-blinded: Selinexor	Phase 2 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 milligram (mg) selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.
Measure Participants	27	30
Median (95% Confidence Interval) [Months]	3.02	2.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 3 Double-blinded: Selinexor, Phase 3 Double-blinded: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6051
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio, log
	Estimated Value	1.1521
	Confidence Interval	(2-Sided) 95%; 0.5357 to 2.4778
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Phase 3 Double Blind: Overall Survival (OS)
Description	OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time Frame	From date of randomization until death due to any cause, whichever occurred first (up to 56 months)

Outcome Measure Data

Analysis Population Description

The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.

Arm/Group Title	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.
Measure Participants	188	97
Median (95% Confidence Interval) [Months]	9.99	12.91

4. Secondary Outcome

Title	Phase 2 Double Blind: Overall Survival (OS)
Description	OS was defined as the duration (in months) from the date of randomization to death from any cause. Participants last known to be alive were censored at the date of discontinuation from the study, or database cut date, whichever was earlier.
Time Frame	From the date of randomization until death due to any cause, whichever occurred first (up to 56 months)

Outcome Measure Data

Analysis Population Description

The Ph2-ITT consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.

Arm/Group Title	Phase 2 Double-blinded: Selinexor	Phase 2 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.
Measure Participants	27	30
Median (95% Confidence Interval) [Months]	17.31	16.07

5. Secondary Outcome

Title	Phase 3 Double Blind: Time to Progression (TTP) as Per RECIST Version 1.1
Description	TTP was defined as the time from date of randomization until determined progressive disease (PD) as per RECIST version. 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time Frame	From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 56 months)

Outcome Measure Data

Analysis Population Description

The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment.

Arm/Group Title	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.
Measure Participants	188	97
Median (95% Confidence Interval) [Months]	2.83	2.10

6. Secondary Outcome

Title	Phase 2 Double Blind: Time to Progression (TTP) as Per RECIST Version 1.1
Description	TTP was defined as the time from date of randomization until determined progressive disease (PD) as per RECIST version. 1.1, or death due to disease progression, whichever occurred first. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time Frame	From date of randomization until the first date of PD or death due to any cause, whichever occurred first (up to 56 months)

Outcome Measure Data

Analysis Population Description

The Ph2-ITT consisted of all participants randomized to study treatment in Phase 2, regardless of whether or not they received study treatment.

Arm/Group Title	Phase 2 Double-blinded: Selinexor	Phase 2 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.
Measure Participants	27	30
Median (95% Confidence Interval) [Months]	3.02	2.76

7. Secondary Outcome

Title	Phase 3 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.
Time Frame	From start of study drug administration up to 56 Months

Outcome Measure Data

Analysis Population Description

The Phase 3 Safety Population (Ph3-SAF) consisted of all participants in Phase 3 who had received at least one dose of blinded study treatment.

Arm/Group Title	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.
Measure Participants	187	97
Participants with TEAEs	187 692.6%	94 313.3%
Participants with Serious TEAEs	71 263%	18 60%

8. Secondary Outcome

Title	Phase 2 Double Blind: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.
Time Frame	From start of study drug administration up to 56 Months

Outcome Measure Data

Analysis Population Description

The Phase 2 Safety Population (Ph2-SAF) consisted of all participants in Phase 2 who had received at least one dose of blinded study treatment.

Arm/Group Title	Phase 2 Double-blinded: Selinexor	Phase 2 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.
Measure Participants	27	30
Participants with TEAEs	27 100%	29 96.7%
Participants with Serious TEAEs	4 14.8%	6 20%

9. Secondary Outcome

Title	Phase 3 Double Blind: Change From Baseline in Quality-of-Life Questionnaire 30 Item (QLQ-C30)
Description	The QLQ-C30 was a 30-item questionnaire developed to assess the quality of life of cancer patients. QLQ-C30 contains 30 questions that include five functional scales: physical, role, emotional, social, and cognitive functioning; three symptom scales (fatigue, nausea/vomiting and pain), six single-item symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/quality of life (QoL) scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. A negative change from baseline score indicates less functioning.
Time Frame	Baseline up to Day 1135

Outcome Measure Data

Analysis Population Description

The Ph3-ITT consisted of all participants randomized to study treatment in Phase 3, regardless of whether or not they received study treatment. Here, "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Phase 3 Double-blinded: Selinexor	Phase 3 Double-blinded: Placebo
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.	Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.
Measure Participants	1	0
Global health status	-16.67 (NA)
Physical Functioning	-6.67 (NA)
Role Functioning	-33.33 (NA)
Emotional Functioning	-25.00 (NA)
Social Functioning	0.00 (NA)
Cognitive Functioning	-16.67 (NA)
Fatigue	33.33 (NA)
Nausea and Vomiting	0.00 (NA)
Pain	0.00 (NA)
Dyspnoea	0.00 (NA)
Insomnia	-33.33 (NA)
Appetite Loss	0.00 (NA)
Constipation	0.00 (NA)
Diarrhoea	-33.33 (NA)
Financial Difficulties	33.33 (NA)

Adverse Events

Time Frame	From start of study drug administration up to 56 Months
Adverse Event Reporting Description	The Ph2-SAF and Ph3-SA consisted of all participants who had received at least one dose of blinded study treatment in Phase 2 and Phase 3 respectively. The Phase 3 Open-label population (Ph3-OL) and Phase 2 Open-label Population (Ph2-OL) consisted of all participants in Phase 3 and Phase 2 respectively, who were randomized to placebo in blinded phase, entered open-label period and received at least one dose of open-label selinexor.
Arm/Group Title	Phase 2 Double-blinded: Selinexor		Phase 2 Double-blinded: Placebo		Phase 3 Double-blinded: Selinexor		Phase 3 Double-blinded: Placebo		Phase 2 Open-label: Selinexor		Phase 3: Open-label: Selinexor
Arm/Group Description	Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.		Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 13 months until PD.		Participants received a fixed blinding dose of 60 mg selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 38 months until PD.		Participants received a fixed blinding dose of placebo matched to selinexor twice weekly on Day 1 and 3 during each 6 Week cycle (42 days) up to 14 months until PD or development of unacceptable toxicity.		Participants received open-label selinexor 60 mg twice-weekly during Weeks 1-6 of each 6-week cycle (42-day), based on the decision by Investigator in collaboration with the sponsor, on the clinical judgment if the participants derive benefit from continued treatment with selinexor.		Participants received open-label selinexor 60 mg twice-weekly during Weeks 1-6 of each 6-week cycle (42-day), based on the decision by Investigator in collaboration with the sponsor, on the clinical judgment if the participants derive benefit from continued treatment with selinexor.
All Cause Mortality
	Phase 2 Double-blinded: Selinexor		Phase 2 Double-blinded: Placebo		Phase 3 Double-blinded: Selinexor		Phase 3 Double-blinded: Placebo		Phase 2 Open-label: Selinexor		Phase 3: Open-label: Selinexor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/27 (59.3%)		25/30 (83.3%)		105/187 (56.1%)		58/97 (59.8%)		20/24 (83.3%)		35/57 (61.4%)
Serious Adverse Events
	Phase 2 Double-blinded: Selinexor		Phase 2 Double-blinded: Placebo		Phase 3 Double-blinded: Selinexor		Phase 3 Double-blinded: Placebo		Phase 2 Open-label: Selinexor		Phase 3: Open-label: Selinexor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/27 (14.8%)		6/30 (20%)		71/187 (38%)		18/97 (18.6%)		13/24 (54.2%)		24/57 (42.1%)
Blood and lymphatic system disorders
Anaemia	1/27 (3.7%)		0/30 (0%)		3/187 (1.6%)		0/97 (0%)		1/24 (4.2%)		2/57 (3.5%)
Thrombocytopenia	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		2/57 (3.5%)
Cardiac disorders
Cardiac failure	0/27 (0%)		1/30 (3.3%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Atrial fibrillation	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Cardiac ventricular thrombosis	0/27 (0%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Cardiac arrest	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
Eye disorders
Cataract	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
Retinal tear	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
Gastrointestinal disorders
Abdominal pain	0/27 (0%)		0/30 (0%)		6/187 (3.2%)		1/97 (1%)		0/24 (0%)		1/57 (1.8%)
Nausea	0/27 (0%)		0/30 (0%)		4/187 (2.1%)		0/97 (0%)		3/24 (12.5%)		0/57 (0%)
Small intestinal obstruction	0/27 (0%)		1/30 (3.3%)		2/187 (1.1%)		2/97 (2.1%)		2/24 (8.3%)		2/57 (3.5%)
Vomiting	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		1/97 (1%)		2/24 (8.3%)		0/57 (0%)
Upper gastrointestinal haemorrhage	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Anastomotic ulcer haemorrhage	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Constipation	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Diarrhoea	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Dysphagia	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Enterocutaneous fistula	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Gastritis	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Gastrointestinal haemorrhage	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Intestinal obstruction	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		2/57 (3.5%)
Intra-abdominal haemorrhage	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Large intestinal obstruction	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Obstruction gastric	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Rectal haemorrhage	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Rectal obstruction	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Ileus	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Large intestine perforation	0/27 (0%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
Stomatitis	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
General disorders
General physical health deterioration	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Fatigue	0/27 (0%)		1/30 (3.3%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Multiple organ dysfunction syndrome	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Oedema peripheral	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		1/57 (1.8%)
Pain	1/27 (3.7%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Pyrexia	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		1/24 (4.2%)		0/57 (0%)
Sudden death	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Complication associated with device	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Hepatobiliary disorders
Bile duct obstruction	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Hyperbilirubinaemia	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Infections and infestations
Pneumonia	0/27 (0%)		2/30 (6.7%)		3/187 (1.6%)		0/97 (0%)		2/24 (8.3%)		1/57 (1.8%)
Bronchitis viral	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Cellulitis	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		1/97 (1%)		0/24 (0%)		1/57 (1.8%)
Influenza	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Sepsis	0/27 (0%)		1/30 (3.3%)		0/187 (0%)		2/97 (2.1%)		1/24 (4.2%)		1/57 (1.8%)
Urinary tract infection	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		1/97 (1%)		0/24 (0%)		1/57 (1.8%)
Device related infection	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Escherichia infection	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Febrile infection	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Lung abscess	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Peritonitis	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Pneumonia klebsiella	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Septic shock	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Upper respiratory tract infection	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Bronchitis	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Respiratory syncytial virus infection	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Bacteraemia	0/27 (0%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Injury, poisoning and procedural complications
Anastomotic ulcer haemorrhage	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Clavicle fracture	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Fall	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Head injury	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Hip fracture	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Limb injury	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Spinal fracture	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Wound complication	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Fracture	1/27 (3.7%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Investigations
Transaminases increased	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Ejection fraction decreased	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Metabolism and nutrition disorders
Decreased appetite	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		1/97 (1%)		0/24 (0%)		1/57 (1.8%)
Dehydration	1/27 (3.7%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
Hyperglycaemia	1/27 (3.7%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Hyponatraemia	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Malnutrition	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Hypocalcaemia	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Musculoskeletal and connective tissue disorders
Back pain	0/27 (0%)		0/30 (0%)		0/187 (0%)		2/97 (2.1%)		1/24 (4.2%)		0/57 (0%)
Muscular weakness	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Musculoskeletal pain	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Pain in extremity	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Tumour pain	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Cancer pain	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Nervous system disorders
Syncope	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Cerebrovascular accident	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Dizziness	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Lethargy	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Cerebral ischaemia	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Product Issues
Device breakage	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Psychiatric disorders
Mania	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Suicide attempt	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Confusional state	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Delirium	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		1/24 (4.2%)		0/57 (0%)
Renal and urinary disorders
Acute kidney injury	0/27 (0%)		1/30 (3.3%)		2/187 (1.1%)		1/97 (1%)		0/24 (0%)		2/57 (3.5%)
Haematuria	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Renal failure	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Renal impairment	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Urinary tract obstruction	0/27 (0%)		0/30 (0%)		0/187 (0%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
Hydronephrosis	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/27 (0%)		0/30 (0%)		3/187 (1.6%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Pulmonary embolism	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		1/97 (1%)		0/24 (0%)		3/57 (5.3%)
Chronic obstructive pulmonary disease	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		1/97 (1%)		0/24 (0%)		1/57 (1.8%)
Pneumothorax	0/27 (0%)		0/30 (0%)		2/187 (1.1%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Acute respiratory failure	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Pulmonary oedema	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Hypoxia	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Dyspnoea	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		1/97 (1%)		1/24 (4.2%)		0/57 (0%)
Respiratory failure	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		1/24 (4.2%)		1/57 (1.8%)
Vascular disorders
Venous thrombosis	0/27 (0%)		0/30 (0%)		1/187 (0.5%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Deep vein thrombosis	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		1/24 (4.2%)		2/57 (3.5%)
Embolism	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		1/57 (1.8%)
Other (Not Including Serious) Adverse Events
	Phase 2 Double-blinded: Selinexor		Phase 2 Double-blinded: Placebo		Phase 3 Double-blinded: Selinexor		Phase 3 Double-blinded: Placebo		Phase 2 Open-label: Selinexor		Phase 3: Open-label: Selinexor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/27 (100%)		29/30 (96.7%)		186/187 (99.5%)		94/97 (96.9%)		24/24 (100%)		56/57 (98.2%)
Blood and lymphatic system disorders
Anaemia	16/27 (59.3%)		9/30 (30%)		87/187 (46.5%)		22/97 (22.7%)		10/24 (41.7%)		22/57 (38.6%)
Thrombocytopenia	11/27 (40.7%)		2/30 (6.7%)		71/187 (38%)		5/97 (5.2%)		11/24 (45.8%)		24/57 (42.1%)
Leukopenia	9/27 (33.3%)		1/30 (3.3%)		26/187 (13.9%)		1/97 (1%)		5/24 (20.8%)		11/57 (19.3%)
Neutropenia	8/27 (29.6%)		1/30 (3.3%)		37/187 (19.8%)		1/97 (1%)		6/24 (25%)		11/57 (19.3%)
Lymphopenia	0/27 (0%)		0/30 (0%)		12/187 (6.4%)		4/97 (4.1%)		0/24 (0%)		5/57 (8.8%)
Cardiac disorders
Sinus tachycardia	0/27 (0%)		0/30 (0%)		6/187 (3.2%)		5/97 (5.2%)		0/24 (0%)		6/57 (10.5%)
Tachycardia	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)
Ear and labyrinth disorders
Vertigo	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Eye disorders
Vision blurred	8/27 (29.6%)		2/30 (6.7%)		41/187 (21.9%)		3/97 (3.1%)		9/24 (37.5%)		7/57 (12.3%)
Cataract	2/27 (7.4%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Photopsia	2/27 (7.4%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Vitreous floaters	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		3/24 (12.5%)		0/57 (0%)
Gastrointestinal disorders
Nausea	24/27 (88.9%)		10/30 (33.3%)		150/187 (80.2%)		38/97 (39.2%)		20/24 (83.3%)		40/57 (70.2%)
Vomiting	15/27 (55.6%)		4/30 (13.3%)		92/187 (49.2%)		12/97 (12.4%)		14/24 (58.3%)		27/57 (47.4%)
Abdominal pain	6/27 (22.2%)		8/30 (26.7%)		43/187 (23%)		30/97 (30.9%)		5/24 (20.8%)		12/57 (21.1%)
Constipation	6/27 (22.2%)		8/30 (26.7%)		71/187 (38%)		23/97 (23.7%)		6/24 (25%)		14/57 (24.6%)
Diarrhoea	8/27 (29.6%)		4/30 (13.3%)		75/187 (40.1%)		17/97 (17.5%)		7/24 (29.2%)		16/57 (28.1%)
Abdominal distension	2/27 (7.4%)		1/30 (3.3%)		11/187 (5.9%)		6/97 (6.2%)		2/24 (8.3%)		0/57 (0%)
Dyspepsia	0/27 (0%)		0/30 (0%)		18/187 (9.6%)		6/97 (6.2%)		0/24 (0%)		4/57 (7%)
Dry mouth	0/27 (0%)		0/30 (0%)		11/187 (5.9%)		1/97 (1%)		2/24 (8.3%)		3/57 (5.3%)
Gastrooesophageal reflux disease	0/27 (0%)		0/30 (0%)		11/187 (5.9%)		1/97 (1%)		0/24 (0%)		0/57 (0%)
General disorders
Fatigue	15/27 (55.6%)		14/30 (46.7%)		96/187 (51.3%)		31/97 (32%)		18/24 (75%)		32/57 (56.1%)
Oedema peripheral	3/27 (11.1%)		3/30 (10%)		30/187 (16%)		12/97 (12.4%)		3/24 (12.5%)		10/57 (17.5%)
Pyrexia	1/27 (3.7%)		4/30 (13.3%)		18/187 (9.6%)		9/97 (9.3%)		0/24 (0%)		7/57 (12.3%)
Influenza like illness	1/27 (3.7%)		3/30 (10%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Malaise	3/27 (11.1%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		3/24 (12.5%)		0/57 (0%)
Non-cardiac chest pain	0/27 (0%)		2/30 (6.7%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Chills	0/27 (0%)		0/30 (0%)		10/187 (5.3%)		7/97 (7.2%)		2/24 (8.3%)		0/57 (0%)
General physical health deterioration	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Asthenia	0/27 (0%)		0/30 (0%)		58/187 (31%)		10/97 (10.3%)		0/24 (0%)		10/57 (17.5%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/27 (3.7%)		2/30 (6.7%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)
Infections and infestations
Urinary tract infection	5/27 (18.5%)		3/30 (10%)		11/187 (5.9%)		8/97 (8.2%)		3/24 (12.5%)		4/57 (7%)
Rhinitis	2/27 (7.4%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Sinusitis	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Upper respiratory tract infection	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Investigations
Weight decreased	14/27 (51.9%)		0/30 (0%)		79/187 (42.2%)		9/97 (9.3%)		15/24 (62.5%)		23/57 (40.4%)
Blood alkaline phosphatase increased	6/27 (22.2%)		7/30 (23.3%)		14/187 (7.5%)		10/97 (10.3%)		3/24 (12.5%)		5/57 (8.8%)
Alanine aminotransferase increased	6/27 (22.2%)		2/30 (6.7%)		16/187 (8.6%)		5/97 (5.2%)		3/24 (12.5%)		6/57 (10.5%)
Aspartate aminotransferase increased	3/27 (11.1%)		2/30 (6.7%)		11/187 (5.9%)		5/97 (5.2%)		2/24 (8.3%)		7/57 (12.3%)
Activated partial thromboplastin time prolonged	0/27 (0%)		4/30 (13.3%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		4/57 (7%)
Blood creatine phosphokinase increased	3/27 (11.1%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Electrocardiogram QT prolonged	2/27 (7.4%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
International normalised ratio increased	0/27 (0%)		2/30 (6.7%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Blood lactate dehydrogenase increased	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		3/24 (12.5%)		0/57 (0%)
Metabolism and nutrition disorders
Decreased appetite	15/27 (55.6%)		5/30 (16.7%)		113/187 (60.4%)		21/97 (21.6%)		14/24 (58.3%)		31/57 (54.4%)
Hyponatraemia	9/27 (33.3%)		6/30 (20%)		51/187 (27.3%)		8/97 (8.2%)		10/24 (41.7%)		11/57 (19.3%)
Hyperglycaemia	9/27 (33.3%)		3/30 (10%)		21/187 (11.2%)		8/97 (8.2%)		2/24 (8.3%)		6/57 (10.5%)
Hypercreatininaemia	4/27 (14.8%)		5/30 (16.7%)		40/187 (21.4%)		13/97 (13.4%)		7/24 (29.2%)		7/57 (12.3%)
Hypoalbuminaemia	4/27 (14.8%)		5/30 (16.7%)		10/187 (5.3%)		8/97 (8.2%)		0/24 (0%)		5/57 (8.8%)
Hypokalaemia	2/27 (7.4%)		4/30 (13.3%)		20/187 (10.7%)		5/97 (5.2%)		0/24 (0%)		0/57 (0%)
Hypomagnesaemia	3/27 (11.1%)		3/30 (10%)		23/187 (12.3%)		2/97 (2.1%)		3/24 (12.5%)		0/57 (0%)
Hypocalcaemia	4/27 (14.8%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)
Hypophosphataemia	3/27 (11.1%)		1/30 (3.3%)		11/187 (5.9%)		3/97 (3.1%)		0/24 (0%)		7/57 (12.3%)
Hypochloraemia	3/27 (11.1%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		3/24 (12.5%)		0/57 (0%)
Hyperkalaemia	0/27 (0%)		2/30 (6.7%)		13/187 (7%)		2/97 (2.1%)		4/24 (16.7%)		3/57 (5.3%)
Dehydration	0/27 (0%)		0/30 (0%)		11/187 (5.9%)		3/97 (3.1%)		3/24 (12.5%)		3/57 (5.3%)
Hyperuricaemia	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)
Musculoskeletal and connective tissue disorders
Back pain	4/27 (14.8%)		3/30 (10%)		23/187 (12.3%)		12/97 (12.4%)		4/24 (16.7%)		7/57 (12.3%)
Arthralgia	3/27 (11.1%)		0/30 (0%)		8/187 (4.3%)		5/97 (5.2%)		0/24 (0%)		0/57 (0%)
Muscular weakness	2/27 (7.4%)		0/30 (0%)		11/187 (5.9%)		2/97 (2.1%)		3/24 (12.5%)		5/57 (8.8%)
Muscle spasms	0/27 (0%)		0/30 (0%)		12/187 (6.4%)		3/97 (3.1%)		0/24 (0%)		0/57 (0%)
Myalgia	0/27 (0%)		0/30 (0%)		8/187 (4.3%)		7/97 (7.2%)		0/24 (0%)		0/57 (0%)
Pain in extremity	0/27 (0%)		0/30 (0%)		11/187 (5.9%)		4/97 (4.1%)		0/24 (0%)		4/57 (7%)
Flank pain	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)
Nervous system disorders
Dysgeusia	10/27 (37%)		2/30 (6.7%)		51/187 (27.3%)		4/97 (4.1%)		6/24 (25%)		10/57 (17.5%)
Dizziness	7/27 (25.9%)		3/30 (10%)		42/187 (22.5%)		6/97 (6.2%)		4/24 (16.7%)		10/57 (17.5%)
Headache	4/27 (14.8%)		3/30 (10%)		23/187 (12.3%)		3/97 (3.1%)		3/24 (12.5%)		7/57 (12.3%)
Taste disorder	3/27 (11.1%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		5/57 (8.8%)
Sciatica	2/27 (7.4%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Anxiety	0/27 (0%)		2/30 (6.7%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)
Syncope	0/27 (0%)		0/30 (0%)		11/187 (5.9%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Memory impairment	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Psychiatric disorders
Insomnia	2/27 (7.4%)		1/30 (3.3%)		21/187 (11.2%)		4/97 (4.1%)		2/24 (8.3%)		0/57 (0%)
Confusional state	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Depression	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		5/57 (8.8%)
Renal and urinary disorders
Haematuria	3/27 (11.1%)		0/30 (0%)		6/187 (3.2%)		6/97 (6.2%)		0/24 (0%)		0/57 (0%)
Micturition urgency	2/27 (7.4%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Pollakiuria	2/27 (7.4%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Proteinuria	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	4/27 (14.8%)		3/30 (10%)		29/187 (15.5%)		7/97 (7.2%)		7/24 (29.2%)		7/57 (12.3%)
Epistaxis	3/27 (11.1%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Nasal congestion	3/27 (11.1%)		1/30 (3.3%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Dyspnoea	0/27 (0%)		3/30 (10%)		34/187 (18.2%)		11/97 (11.3%)		7/24 (29.2%)		10/57 (17.5%)
Oropharyngeal pain	1/27 (3.7%)		2/30 (6.7%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		0/57 (0%)
Pleural effusion	0/27 (0%)		2/30 (6.7%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Aspiration	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Pulmonary embolism	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Dyspnoea exertional	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		3/57 (5.3%)
Skin and subcutaneous tissue disorders
Night sweats	3/27 (11.1%)		0/30 (0%)		13/187 (7%)		0/97 (0%)		2/24 (8.3%)		0/57 (0%)
Rash	0/27 (0%)		0/30 (0%)		5/187 (2.7%)		5/97 (5.2%)		2/24 (8.3%)		0/57 (0%)
Vascular disorders
Hypertension	5/27 (18.5%)		3/30 (10%)		21/187 (11.2%)		10/97 (10.3%)		3/24 (12.5%)		5/57 (8.8%)
Hypotension	4/27 (14.8%)		3/30 (10%)		23/187 (12.3%)		3/97 (3.1%)		3/24 (12.5%)		5/57 (8.8%)
Hot flush	0/27 (0%)		0/30 (0%)		0/187 (0%)		0/97 (0%)		0/24 (0%)		4/57 (7%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.