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Clinical Trial Results:
A Phase II, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 (Selinexor) in Patients With Advanced Gynaecologic Malignancies

Summary
EudraCT number	2013-003650-24
Trial protocol	DK BE
Global end of trial date	29 Mar 2017

Results information
Results version number	v1(current)
This version publication date	20 May 2021
First version publication date	20 May 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

KCP-330-005

ISRCTN number

US NCT number

NCT02025985

WHO universal trial number (UTN)

Sponsor organisation name

Karyopharm Therapeutics Inc.

Sponsor organisation address

85 Wells Avenue, Newton MA, United States, 02459

Public contact

Clinical Trials Information, Karyopharm Therapeutics Inc., +1 617-658-0557, sharon@karyopharm.com

Scientific contact

Clinical Trials Information, Karyopharm Therapeutics Inc., +1 617-658-0557, sharon@karyopharm.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Mar 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Mar 2017

Was the trial ended prematurely?

Main objective of the trial

To determine the efficacy of Selinexor in subjects with advanced or metastatic gynaecological cancers by disease control rate.

Protection of trial subjects

The study was conducted in accordance with ethical principles that had their origin in the Declaration of Helsinki and were consistent with the International Council for Harmonisation Guideline for Good Clinical Practice, and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Apr 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 63

Country: Number of subjects enrolled

Denmark: 51

Worldwide total number of subjects

114

EEA total number of subjects

114

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted between 09-April-2014 and 29-March-2017.

Screening details

A total of 116 subjects were enrolled out of which 2 subjects discontinued the study before the start of the treatment (1 subject due to death and 1 subject due to other reason). Total 114 subjects started the study treatment.

Period 1 title

Overall (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW

Arm description

Subjects with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 milligram per meter square (mg/m^2) of selinexor oral tablets twice weekly (BIW) (doses at least 36 hours apart) with light meal and 120 milliliters (mL) of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets BIW were administrated if the subjects had no major toxicity. During dose reduction, subjects received a minimum dose of 35 mg/m^2 once weekly (QW). This treatment continued until progression of disease (PD) or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the subject, or non-compliance by the subject with protocol requirements.

Arm type

Experimental

Investigational medicinal product name

Selinexor

Investigational medicinal product code

KPT-330

Other name

XPOVIO, NEXPOVIO

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablets at doses of 50 mg/m^2 BIW and 60 mg/m^2 BIW. Treatment cycles were 4 weeks each i.e., 28 day cycle.

Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW

Arm description

Subjects with endometrial carcinoma who had received at least one line of chemotherapy for relapsed or advanced (Stage IVb, IIIc) disease received a dose of 50 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets BIW were administrated if the subjects had no major toxicity. During dose reduction, subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the subject, or non-compliance by the subject with protocol requirements.

Arm type

Experimental

Investigational medicinal product name

Selinexor

Investigational medicinal product code

KPT-330

Other name

XPOVIO, NEXPOVIO

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablets at doses of 50 mg/m^2 BIW and 60 mg/m^2 BIW. Treatment cycles were 4 weeks each i.e., 28 day cycle.

Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW

Arm description

Subjects with cervical carcinoma who had received at least one line of chemotherapy for relapsed or advanced (Stage IV) disease received a dose of 50 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets BIW were administrated if the subjects had no major toxicity. During dose reduction, subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the subject, or non-compliance by the subject with protocol requirements.

Arm type

Experimental

Investigational medicinal product name

Selinexor

Investigational medicinal product code

KPT-330

Other name

XPOVIO, NEXPOVIO

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablets at doses of 50 mg/m^2 BIW and 60 mg/m^2 BIW. Treatment cycles were 4 weeks each i.e., 28 day cycle.

Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW

Arm description

Subjects in Cohort A Schedule (Sch) 1 with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 35 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 6 weeks of treatment, a dose of 50 mg/m^2 of selinexor oral tablets BIW were administrated if the subjects had no major toxicity. During dose reduction, subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the subject, or non-compliance by the subject with protocol requirements.

Arm type

Experimental

Investigational medicinal product name

Selinexor

Investigational medicinal product code

KPT-330

Other name

XPOVIO, NEXPOVIO

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablets at doses of 35 mg/m^2 BIW, 50 mg/m^2 BIW, and 35 mg/m^2 QW. Treatment cycles were 4 weeks each i.e., 28 day cycle.

Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW

Arm description

Subjects in Cohort A Schedule (Sch) 2 with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 mg/m^2 of selinexor oral tablets QW (doses at least 5 days apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 6 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets QW were administrated if the subjects had no major toxicity. During dose reduction, subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the subject, or non-compliance by the subject with protocol requirements.

Arm type

Experimental

Investigational medicinal product name

Selinexor

Investigational medicinal product code

KPT-330

Other name

XPOVIO, NEXPOVIO

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Oral tablets at doses of 50 mg/m^2 QW, 60 mg/m^2 QW, and 35 mg/m^2 QW. Treatment cycles were 4 weeks each i.e., 28 day cycle.

Number of subjects in period 1	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Started	25	23	25	21	20
Modified Intent-to-treat(mITT)Population	23	22	25	21	20
Completed	0	0	0	0	0
Not completed	25	23	25	21	20
Consent withdrawn by subject	-	-	1	-	-
Death	21	20	23	20	17
Termination of study by Sponsor	4	3	1	1	3

Baseline characteristics

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Reporting group title

Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW

Reporting group description

Reporting group title

Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW

Reporting group description

Reporting group title

Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW

Reporting group description

Reporting group title

Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW

Reporting group description

Reporting group title

Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW

Reporting group description

Reporting group values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW	Total
Number of subjects	25	23	25	21	20	114
Age categorical
Units: Subjects
<=18 years	0	0	0	0	0	0
Between 18 and 65 years	17	6	20	13	14	70
>=65 years	8	17	5	8	6	44
Gender categorical
Units: Subjects
Female	25	23	25	21	20	114
Male	0	0	0	0	0	0
Ethnicity
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0
Not Hispanic or Latino	25	23	25	21	20	114
Unknown or Not Reported	0	0	0	0	0	0
Race
Units: Subjects
White	25	23	24	21	20	113
Other-unspecified	0	0	1	0	0	1

End points

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Reporting group title

Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW

Reporting group description

Reporting group title

Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW

Reporting group description

Reporting group title

Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW

Reporting group description

Reporting group title

Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW

Reporting group description

Reporting group title

Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW

Reporting group description

Primary: Percentage of Subjects With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

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End point title

Percentage of Subjects With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) ^[1]

End point description

Disease Control Rate (DCR) was defined as point estimate of the percentage of subjects who had complete response (CR), partial response (PR), or stable disease (SD) for at least 12 weeks, assessed according to RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters while on study. Subjects without documented disease progression were censored on date of last radiologic assessment. Analysis was modified intent-to-treat (mITT) population:all subjects who received at least 1 dose of study drug,had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

End point type

Primary

End point timeframe

Baseline up to 30 days after last dose administration, assessed after 6 weeks and 12 weeks (approximately 35 months)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive analyses was planned for this endpoint.

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	23	22	25	21	20
Units: percentage of subjects
number (confidence interval 95%)	30.4 (13.2 to 52.9)	36.4 (17.2 to 59.3)	24.0 (9.4 to 45.1)	33.3 (14.6 to 57.0)	30.0 (11.9 to 54.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Overall Response According to RECIST v1.1

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End point title

Percentage of Subjects With Overall Response According to RECIST v1.1

End point description

Overall Response Rate (ORR) was defined as the point estimate of the percentage of subjects who had CR or PR, assessed according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Analysis was performed on mITT population that included all subjects who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

End point type

Secondary

End point timeframe

Baseline up to the date of progression or recurrence (approximately 35 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	23	22	25	21	20
Units: percentage of subjects
number (confidence interval 95%)	8.7 (1.1 to 28.0)	13.6 (2.9 to 34.9)	4.0 (0.1 to 20.4)	9.5 (1.2 to 30.4)	15.0 (3.2 to 37.9)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria

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End point title

Percentage of Subjects With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria ^[2]

End point description

DCR was defined as the point estimate of the percentage of subjects who had CR, PR, or SD for at least 12 weeks, assessed according to GCIG response criteria (RECIST v1.1 and CA-125). Analysis was performed on GCIG evaluable population that included all subjects in the ovarian cancer cohort (Cohort A) who had received at least 1 dose of study drug, had measurable disease per RECIST at baseline or baseline CA-125 assessment, and had at least 1 post-baseline efficacy follow-up information (i.e., either post-baseline scan or CA-125 assessment). Data for this outcome measure was not planned to be collected and analysed for Cohort B and Cohort C, as pre-specified in protocol.

End point type

Secondary

End point timeframe

Baseline up to 30 days after last dose administration, assessed after 6 weeks and 12 weeks (approximately 35 months)

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this outcome measure were not planned to be collected and analysed for Cohort B and Cohort C, as pre-specified in protocol.

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	25	16	20
Units: percentage of subjects
number (confidence interval 95%)	16.0 (4.5 to 36.1)	23.8 (8.2 to 47.2)	20.0 (5.7 to 43.7)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Overall Response According to GCIG Response Criteria

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End point title

Percentage of Subjects With Overall Response According to GCIG Response Criteria ^[3]

End point description

ORR was defined as the point estimate of the percentage of subjects who had CR or PR, assessed according to GCIG response criteria (RECIST v1.1 and CA-125). Analysis was performed on GCIG evaluable population that included all subjects in the ovarian cancer cohort (Cohort A) who had received at least 1 dose of study drug, had measurable disease per RECIST at baseline or baseline CA-125 assessment, and had at least 1 post-baseline efficacy follow-up information (i.e., either post-baseline scan or CA-125 assessment). Data for this outcome measure were not planned to be collected and analysed for Cohort B and Cohort C, as pre-specified in protocol.

End point type

Secondary

End point timeframe

Baseline up to the date of progression or recurrence (approximately 35 months)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data for this outcome measure were not planned to be collected and analysed for Cohort B and Cohort C, as pre-specified in protocol.

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	25	21	20
Units: percentage of subjects
number (confidence interval 95%)	4.0 (0.1 to 20.4)	9.5 (1.2 to 30.4)	10.0 (1.2 to 31.7)

No statistical analyses for this end point

Secondary: Progression-free Survival (PFS) According to RECIST v1.1

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End point title

Progression-free Survival (PFS) According to RECIST v1.1

End point description

PFS was defined as the time from date of start of study therapy to the date of tumor disease progression (i.e., radiological only) or date of death due to any cause. Subjects without documented disease progression were censored at the time of last radiologic assessment. Subjects without any post baseline assessments were censored at date of start of study therapy. Analysis was performed on mITT population that included all subjects who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

End point type

Secondary

End point timeframe

From start of study drug administration until PD or discontinuation from the study or death, whichever occurred first (approximately 35 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	23	22	25	21	20
Units: days
median (confidence interval 95%)	79.0 (45.0 to 99.0)	86.5 (43.0 to 182.0)	44.0 (43.0 to 141.0)	85.0 (44.0 to 148.0)	44.5 (43.0 to 140.0)

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

OS was defined as time from the date of start of study therapy to the date of death due to any cause. Subjects who were alive at the time of the analysis or were lost to follow-up were censored at the day they were last known to be alive. Kaplan-Maier method was used for estimation. Analysis was performed on mITT population that included all subjects who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

End point type

Secondary

End point timeframe

From start of study treatment up to the date of death, assessed every 3 months (approximately 35 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	23	22	25	21	20
Units: days
median (confidence interval 95%)	172.0 (62.0 to 372.0)	226.0 (111.0 to 449.0)	152.0 (83.0 to 254.0)	348.0 (149.0 to 401.0)	173.0 (105.0 to 353.0)

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Survived at 12 and 24 Months

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End point title

Percentage of Subjects Who Survived at 12 and 24 Months

End point description

OS rate was reported as the percentage of subjects who were alive at 12 and 24 months. OS was defined as time from the date of start of study therapy to the date of death due to any cause. Subjects who were alive at the time of the analysis or are lost to follow-up were censored at the day they were last known to be alive. Survival rate were estimated by Kaplan-Maier method. Analysis was performed on mITT population that included all subjects who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

End point type

Secondary

End point timeframe

12 and 24 months

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	23	22	25	21	20
Units: percentage of subjects
number (confidence interval 95%)
12 months	34.8 (16.6 to 53.7)	31.8 (14.2 to 51.1)	13.2 (3.4 to 29.9)	33.3 (14.9 to 53.1)	25.0 (9.1 to 44.9)
24 months	21.7 (7.9 to 39.9)	13.6 (3.4 to 30.9)	4.4 (0.3 to 18.4)	19.0 (5.9 to 37.7)	15.0 (3.7 to 33.5)

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

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End point title

Number of Subjects With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

End point description

Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with use of medicinal product, whether or not related to medicinal product. Serious adverse event (SAE) was defined as AE that meets one or more of mentioned criteria, i.e., fatal, life threatening (places the subjects at immediate risk of death), required in-patient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. TEAE was defined as any AE (serious/non-serious) with onset or worsening of pre-existing condition on or after the first administration of study drug through 30 days after last dose or any event considered drug-related by the investigator through the end of study. Analysis was performed on safety population that included all subjects who had received any amount of study drug.

End point type

Secondary

End point timeframe

From start of study treatment up to 30 days after the last dose administration (approximately 35 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	25	23	25	21	20
Units: subjects
Subjects with TEAE	25	23	25	21	20
Subjects with TESAE	14	14	6	12	12

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

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End point title

Number of Subjects With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

End point description

AE:any unfavorable and unintended sign, symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. TEAE:any AE (serious/non-serious) with onset or worsening of a pre-existing condition on/after 1st study drug administration to 30 days after last dose or any event considered drug-related by investigator until end of study. Per NCI-CTCAE 4.03, Grade1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade3: severe or medically significant but not immediately life-threatening, hospitalisation/prolongation of existing hospitalisation indicated,disabling, limiting self-care ADL; Grade4:life-threatening consequence, urgent intervention indicated; Grade5:death related to AE. Safety population:all subjects who had received any amount of drug.

End point type

Secondary

End point timeframe

From start of study treatment up to 30 days after the last dose administration (approximately 35 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	25	23	25	21	20
Units: subjects
Mild (Grade 1)	0	0	0	0	0
Moderate (Grade 2)	3	3	5	5	7
Severe (Grade 3)	19	17	17	15	13
Life threatening (Grade 4)	3	2	2	1	0
Fatal (Grade 5)	0	1	1	0	0

No statistical analyses for this end point

Secondary: Quality of Life (QoL): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

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End point title

Quality of Life (QoL): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

End point description

EORTC QLQC30: Disease specific indication to rate overall QoL in cancer subjects, consists of 30 questions (Q) in 3 domains; 1) global health status (GHS), 2) functioning scales (FS) (physical, emotional, cognitive, social, role functioning), 3) symptom scales (SS) (fatigue, nausea, vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, financial difficulty). Of 30Q, 28Q were scored on scale of 1-4, (not at all, a little, quite a bit, and very much); remaining 2Q for GHS were scored on scale of 1-7, range ‘very poor' to 'excellent' to evaluate overall health and QoL. All scales and single-item measures range from 0-100, higher score=higher response level. Higher score for FS=high level of functioning, GHS=high QoL and SS=high level of symptoms/problems, respectively. Analysis was performed on mITT population. Here, 'Number of subjects analyzed'=subjects with available data for endpoint; ‘n' = subjects with available data for specified categories.

End point type

Secondary

End point timeframe

Baseline up to End of treatment (EOT) i.e., 30 days after last dose of study drug administration (up to 31 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	21	21	22	21	20
Units: scores on a scale
arithmetic mean (standard deviation)
GHS/QoL:Baseline(n=21,21,22,21,20)	52.8 ( 22.41 )	59.5 ( 20.63 )	60.2 ( 24.25 )	61.5 ( 22.89 )	57.5 ( 21.95 )
GHS/QoL:EOT (n=2,11,4,7,6)	-8.3 ( 11.79 )	-11.4 ( 29.88 )	-14.6 ( 10.49 )	-27.4 ( 31.81 )	-13.9 ( 15.52 )
FS/Physical function:Baseline(n=21,21,22,21,20)	69.5 ( 19.16 )	70.9 ( 21.54 )	66.1 ( 26.02 )	67.1 ( 21.14 )	70.7 ( 25.26 )
FS/Physical function:EOT(n=2,1,4,7,6)	-26.7 ( 28.28 )	-16.4 ( 27.55 )	-24.2 ( 21.32 )	-7.6 ( 16.97 )	-18.9 ( 14.25 )
FS/Role function:Baseline(n=21,21,22,21,20)	54.0 ( 29.77 )	59.5 ( 31.87 )	55.6 ( 35.49 )	59.5 ( 28.66 )	63.3 ( 34.45 )
FS/Role function:EOT(n=2,11,4,7,6)	-33.3 ( 47.14 )	-3.0 ( 49.90 )	-20.8 ( 36.96 )	-9.5 ( 39.51 )	-25.0 ( 9.13 )
FS/Emotional function:Baseline(n=21,21,22,21,20)	62.3 ( 24.81 )	69.8 ( 24.65 )	71.2 ( 23.81 )	74.2 ( 19.53 )	66.3 ( 23.33 )
FS/Emotional function:EOT(n=2,11,4,7,6)	-16.7 ( 11.79 )	-0.8 ( 38.27 )	12.5 ( 14.43 )	-13.9 ( 23.07 )	-2.8 ( 17.21 )
FS/Cognitive function:Baseline(n=21,21,22,21,20)	81.0 ( 22.54 )	86.5 ( 16.35 )	83.3 ( 25.20 )	83.3 ( 19.00 )	80.8 ( 23.12 )
FS/Cognitive function:EOT(n=2,11,4,7,6)	-33.3 ( 23.57 )	-6.1 ( 29.13 )	4.2 ( 20.97 )	-16.7 ( 38.49 )	0.0 ( 0.00 )
FS/Social function:Baseline(n=21,21,22,21,20)	61.1 ( 29.97 )	76.2 ( 32.31 )	72.7 ( 28.89 )	69.0 ( 30.86 )	77.5 ( 29.75 )
FS/Social function:EOT(n=2,11,4,7,6)	-33.3 ( 0.00 )	-6.1 ( 48.46 )	-20.8 ( 20.97 )	-7.1 ( 18.90 )	-30.6 ( 32.35 )
SS/Fatigue:Baseline(n=21,21,22,21,20)	46.6 ( 27.80 )	43.4 ( 27.42 )	44.9 ( 27.75 )	46.0 ( 27.28 )	41.7 ( 27.89 )
SS/Fatigue:EOT(n=2,11,4,7,6)	33.3 ( 47.14 )	6.1 ( 41.09 )	1.4 ( 17.20 )	23.8 ( 30.38 )	16.7 ( 11.65 )
SS/Nausea-vomiting:Baseline(n=21,21,22,21,20)	13.5 ( 24.51 )	17.5 ( 30.04 )	9.8 ( 15.99 )	5.6 ( 14.27 )	10.8 ( 21.81 )
SS/Nausea-vomiting:EOT(n=2,11,4,7,6)	8.3 ( 11.79 )	-0.0 ( 40.82 )	16.7 ( 19.25 )	9.5 ( 23.29 )	13.9 ( 16.39 )
SS/Pain:Baseline(n=21,21,22,21,20)	34.9 ( 27.84 )	37.3 ( 27.34 )	32.6 ( 27.93 )	31.0 ( 29.48 )	32.5 ( 26.75 )
SS/Pain:EOT(n=2,11,4,7,6)	-8.3 ( 11.79 )	-4.5 ( 21.20 )	4.2 ( 8.33 )	-2.4 ( 17.82 )	2.8 ( 26.70 )
SS/Dyspnoea:Baseline(n=21,21,22,21,20)	23.8 ( 31.87 )	30.2 ( 36.37 )	19.7 ( 30.27 )	33.3 ( 38.01 )	21.7 ( 29.17 )
SS/Dyspnoea:EOT(n=2,11,4,7,6)	50.0 ( 23.57 )	6.1 ( 32.72 )	8.3 ( 16.67 )	-0.0 ( 47.14 )	16.7 ( 18.26 )
SS/Insomnia:Baseline(n=21,21,22,21,20)	31.7 ( 34.12 )	36.5 ( 31.46 )	30.3 ( 32.38 )	20.6 ( 26.82 )	38.3 ( 29.17 )
SS/Insomnia:EOT(n=2,11,4,7,6)	-16.7 ( 23.57 )	-9.1 ( 30.15 )	-16.7 ( 33.33 )	-19.0 ( 26.23 )	5.6 ( 32.77 )
SS/Appetite loss:Baseline(n=21,21,22,21,20)	25.4 ( 31.46 )	34.9 ( 32.45 )	30.3 ( 36.96 )	23.8 ( 28.17 )	15.0 ( 27.52 )
SS/Appetite loss:EOT(n=2,11,4,7,6)	16.7 ( 23.57 )	0.0 ( 53.75 )	16.7 ( 43.03 )	33.3 ( 47.14 )	16.7 ( 34.96 )
SS/Constipation:Baseline(n=21,21,22,21,20)	27.0 ( 27.12 )	15.9 ( 24.99 )	15.2 ( 26.68 )	17.5 ( 30.95 )	11.7 ( 16.31 )
SS/Constipation:EOT(n=2,11,4,7,6)	0.0 ( 47.14 )	6.7 ( 43.89 )	8.3 ( 16.67 )	9.5 ( 31.71 )	-5.6 ( 13.61 )
SS/Diarrhoea:Baseline(n=21,21,22,21,20)	17.5 ( 30.95 )	9.5 ( 26.13 )	18.2 ( 24.62 )	18.3 ( 31.48 )	8.3 ( 14.81 )
SS/Diarrhoea:EOT(n=2,11,4,7,6)	0.0 ( 0.00 )	-3.0 ( 34.82 )	0.0 ( 27.22 )	23.8 ( 25.20 )	27.8 ( 32.77 )
SS/Financial difficulty:Baseline(n=21,21,22,21,20)	7.9 ( 17.97 )	4.8 ( 15.94 )	16.7 ( 26.73 )	9.5 ( 18.69 )	5.0 ( 12.21 )
SS/Financial difficulty:EOT(n=2,11,4,7,6)	16.7 ( 23.57 )	3.0 ( 17.98 )	0.0 ( 0.00 )	4.8 ( 29.99 )	-5.6 ( 13.61 )

No statistical analyses for this end point

Secondary: Number of Subjects With Individual Clinically Significant Abnormalities in Laboratory Tests

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End point title

Number of Subjects With Individual Clinically Significant Abnormalities in Laboratory Tests

End point description

Clinically significant laboratory tests abnormalities were analysed and reported for this outcome measure. Analysis was performed on safety population that included all subjects who had received any amount of study drug.

End point type

Secondary

End point timeframe

From start of study treatment up to 30 days after the last dose administration (approximately 35 months)

End point values	Part1: Cohort A-Ovarian Carcinoma: Selinexor upto 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Number of subjects analysed	23	22	25	21	20
Units: subjects	21	20	19	14	11

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From start of study treatment up to 30 days after last dose administration (approximately 35 months)

Adverse event reporting additional description

Analysis was performed on safety population that included all Subjects who had received any amount of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Part1:Cohort A-Ovarian Carcinoma:Selinexor up to 60 mg/m2 BIW

Reporting group description

Subjects with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets BIW were administrated if the Subjects had no major toxicity. During dose reduction, Subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the Subject, or non-compliance by the Subject with protocol requirements.

Reporting group title

Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW

Reporting group description

Subjects with endometrial carcinoma who had received at least one line of chemotherapy for relapsed or advanced (Stage IVb, IIIc) disease received a dose of 50 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets BIW were administrated if the Subjects had no major toxicity. During dose reduction, Subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the Subject, or non-compliance by the Subject with protocol requirements.

Reporting group title

Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW

Reporting group description

Subjects with cervical carcinoma who had received at least one line of chemotherapy for relapsed or advanced (Stage IV) disease received a dose of 50 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets BIW were administrated if the Subjects had no major toxicity. During dose reduction, Subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the Subject, or non-compliance by the Subject with protocol requirements.

Reporting group title

Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW

Reporting group description

Subjects with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 35 mg/m^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 6 weeks of treatment, a dose of 50 mg/m^2 of selinexor oral tablets BIW were administrated if the Subjects had no major toxicity. During dose reduction, Subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the Subject, or non-compliance by the Subject with protocol requirements.

Reporting group title

Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW

Reporting group description

Subjects with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 mg/m^2 of selinexor oral tablets QW (doses at least 5 days apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 6 weeks of treatment, a dose of 60 mg/m^2 of selinexor oral tablets QW were administrated if the Subjects had no major toxicity. During dose reduction, Subjects received a minimum dose of 35 mg/m^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the Subject, or non-compliance by the Subject with protocol requirements.

Serious adverse events	Part1:Cohort A-Ovarian Carcinoma:Selinexor up to 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Total subjects affected by serious adverse events
subjects affected / exposed	14 / 25 (56.00%)	14 / 23 (60.87%)	6 / 25 (24.00%)	12 / 21 (57.14%)	12 / 20 (60.00%)
number of deaths (all causes)	21	20	23	20	17
number of deaths resulting from adverse events	0	1	1	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial Tumour Haemorrhage
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep Vein Thrombosis
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Drain Placement
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Discomfort
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gait Disturbance
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General Physical Health Deterioration
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inflammation
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malaise
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural Effusion
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary Embolism
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femoral Neck Fracture
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Supraventricular Tachycardia
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aphasia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cognitive Disorder
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vision Blurred
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal Haemorrhage
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	4 / 20 (20.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Disorder
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal Obstruction
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstruction Gastric
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal Haemorrhage
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small Intestinal Obstruction
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	5 / 25 (20.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	5 / 5	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis Noninfective
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal Failure
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
Urinary Retention
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back Pain
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia Infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung Infection
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Respiratory Tract Infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary Tract Infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicella Zoster Virus Infection
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	2 / 25 (8.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	2 / 2	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	2 / 25 (8.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	2 / 2	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part1:Cohort A-Ovarian Carcinoma:Selinexor up to 60 mg/m2 BIW	Part1:CohortB-Endometrial Carcinoma:Selinexor upto 60mg/m2 BIW	Part1:CohortC-Cervical Carcinoma:Selinexor upto 60 mg/m2 BIW	Part2:CohortA-OvarianCarcinoma Sch.1:Selinexor upto 50mg/m2BIW	Part2:Cohort A-OvarianCarcinoma Sch.2:Selinexor upto 60mg/m2QW
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 25 (100.00%)	23 / 23 (100.00%)	25 / 25 (100.00%)	21 / 21 (100.00%)	20 / 20 (100.00%)
Vascular disorders
Deep Vein Thrombosis
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)
occurrences all number	0	1	1	3	1
Hot Flush
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	3 / 21 (14.29%)	2 / 20 (10.00%)
occurrences all number	0	1	2	3	2
Hypertension
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	1	0	1
Hypotension
subjects affected / exposed	2 / 25 (8.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	3 / 21 (14.29%)	0 / 20 (0.00%)
occurrences all number	2	2	0	3	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	7 / 25 (28.00%)	7 / 23 (30.43%)	5 / 25 (20.00%)	6 / 21 (28.57%)	3 / 20 (15.00%)
occurrences all number	7	7	5	6	3
Chills
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Face Oedema
subjects affected / exposed	2 / 25 (8.00%)	2 / 23 (8.70%)	2 / 25 (8.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences all number	2	2	2	1	0
Fatigue
subjects affected / exposed	12 / 25 (48.00%)	15 / 23 (65.22%)	15 / 25 (60.00%)	14 / 21 (66.67%)	14 / 20 (70.00%)
occurrences all number	12	15	15	14	14
General Physical Health Deterioration
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	2	0	1	1
Malaise
subjects affected / exposed	3 / 25 (12.00%)	3 / 23 (13.04%)	2 / 25 (8.00%)	1 / 21 (4.76%)	2 / 20 (10.00%)
occurrences all number	3	3	2	1	2
Oedema
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	0	0	0	1
Oedema Peripheral
subjects affected / exposed	3 / 25 (12.00%)	2 / 23 (8.70%)	2 / 25 (8.00%)	6 / 21 (28.57%)	2 / 20 (10.00%)
occurrences all number	3	2	2	6	2
Pyrexia
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	4 / 25 (16.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)
occurrences all number	3	1	4	3	1
Reproductive system and breast disorders
Vaginal Haemorrhage
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	1	1	2	1	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 25 (12.00%)	2 / 23 (8.70%)	3 / 25 (12.00%)	3 / 21 (14.29%)	5 / 20 (25.00%)
occurrences all number	3	2	3	3	5
Dyspnoea
subjects affected / exposed	6 / 25 (24.00%)	3 / 23 (13.04%)	6 / 25 (24.00%)	7 / 21 (33.33%)	4 / 20 (20.00%)
occurrences all number	6	3	6	7	4
Dyspnoea Exertional
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	1
Hiccups
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Oropharyngeal Pain
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1	1
Pleural Effusion
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0	0
Pulmonary Embolism
subjects affected / exposed	3 / 25 (12.00%)	2 / 23 (8.70%)	1 / 25 (4.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)
occurrences all number	3	2	1	2	1
Psychiatric disorders
Agitation
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0	0
Anxiety
subjects affected / exposed	3 / 25 (12.00%)	0 / 23 (0.00%)	3 / 25 (12.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	3	0	3	2	0
Confusional State
subjects affected / exposed	1 / 25 (4.00%)	2 / 23 (8.70%)	2 / 25 (8.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)
occurrences all number	1	2	2	2	1
Depression
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences all number	1	1	2	1	0
Hallucination
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	2 / 25 (8.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	0	2	0	0
Insomnia
subjects affected / exposed	7 / 25 (28.00%)	1 / 23 (4.35%)	5 / 25 (20.00%)	3 / 21 (14.29%)	0 / 20 (0.00%)
occurrences all number	7	1	5	3	0
Product issues
Device Occlusion
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	2 / 25 (8.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	2	0	0
Investigations
Weight Decreased
subjects affected / exposed	12 / 25 (48.00%)	13 / 23 (56.52%)	18 / 25 (72.00%)	11 / 21 (52.38%)	6 / 20 (30.00%)
occurrences all number	12	13	18	11	6
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	0	1
Humerus Fracture
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Procedural Pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	1
Nervous system disorders
Aphasia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Dizziness
subjects affected / exposed	7 / 25 (28.00%)	5 / 23 (21.74%)	6 / 25 (24.00%)	4 / 21 (19.05%)	2 / 20 (10.00%)
occurrences all number	7	5	6	4	2
Dysgeusia
subjects affected / exposed	7 / 25 (28.00%)	5 / 23 (21.74%)	11 / 25 (44.00%)	4 / 21 (19.05%)	6 / 20 (30.00%)
occurrences all number	7	5	11	4	6
Headache
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	3 / 25 (12.00%)	1 / 21 (4.76%)	4 / 20 (20.00%)
occurrences all number	3	1	3	1	4
Paraesthesia
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	2 / 25 (8.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	2	0	0
Peripheral Sensory Neuropathy
subjects affected / exposed	1 / 25 (4.00%)	4 / 23 (17.39%)	3 / 25 (12.00%)	0 / 21 (0.00%)	3 / 20 (15.00%)
occurrences all number	1	4	3	0	3
Somnolence
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0	0
Syncope
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	2	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	13 / 25 (52.00%)	11 / 23 (47.83%)	14 / 25 (56.00%)	9 / 21 (42.86%)	5 / 20 (25.00%)
occurrences all number	13	11	14	9	5
Neutropenia
subjects affected / exposed	2 / 25 (8.00%)	3 / 23 (13.04%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	3	0	0	0
Pancytopenia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Thrombocytopenia
subjects affected / exposed	12 / 25 (48.00%)	10 / 23 (43.48%)	13 / 25 (52.00%)	4 / 21 (19.05%)	1 / 20 (5.00%)
occurrences all number	12	10	13	4	1
Ear and labyrinth disorders
Auditory Disorder
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0	0
Ear Discomfort
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	1	0	0
Vertigo
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	1	1	1	1	1
Eye disorders
Cataract
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)
occurrences all number	0	1	0	2	1
Dry Eye
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	1
Vision Blurred
subjects affected / exposed	7 / 25 (28.00%)	8 / 23 (34.78%)	5 / 25 (20.00%)	7 / 21 (33.33%)	5 / 20 (25.00%)
occurrences all number	7	8	5	7	5
Visual Impairment
subjects affected / exposed	2 / 25 (8.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences all number	2	1	1	1	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 21 (9.52%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2	2
Abdominal Distension
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	3	1	2	2	0
Abdominal Pain
subjects affected / exposed	7 / 25 (28.00%)	1 / 23 (4.35%)	3 / 25 (12.00%)	5 / 21 (23.81%)	7 / 20 (35.00%)
occurrences all number	7	1	3	5	7
Abdominal Pain Lower
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1	1
Abdominal Pain Upper
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	2 / 25 (8.00%)	3 / 21 (14.29%)	5 / 20 (25.00%)
occurrences all number	0	0	2	3	5
Ascites
subjects affected / exposed	2 / 25 (8.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 21 (4.76%)	3 / 20 (15.00%)
occurrences all number	2	1	0	1	3
Constipation
subjects affected / exposed	7 / 25 (28.00%)	6 / 23 (26.09%)	6 / 25 (24.00%)	11 / 21 (52.38%)	7 / 20 (35.00%)
occurrences all number	7	6	6	11	7
Defaecation Urgency
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Diarrhoea
subjects affected / exposed	6 / 25 (24.00%)	7 / 23 (30.43%)	6 / 25 (24.00%)	10 / 21 (47.62%)	8 / 20 (40.00%)
occurrences all number	6	7	6	10	8
Dry Mouth
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)
occurrences all number	1	1	1	2	1
Dyspepsia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	4 / 20 (20.00%)
occurrences all number	0	0	1	0	4
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	1
Intestinal Obstruction
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Mouth Ulceration
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Nausea
subjects affected / exposed	22 / 25 (88.00%)	15 / 23 (65.22%)	17 / 25 (68.00%)	17 / 21 (80.95%)	15 / 20 (75.00%)
occurrences all number	22	15	17	17	15
Oesophageal Irritation
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Oesophageal Pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Oral Mucosal Blistering
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Stomatitis
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)
occurrences all number	3	1	1	3	1
Vomiting
subjects affected / exposed	18 / 25 (72.00%)	14 / 23 (60.87%)	11 / 25 (44.00%)	13 / 21 (61.90%)	12 / 20 (60.00%)
occurrences all number	18	14	11	13	12
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)
occurrences all number	1	0	0	0	2
Night Sweats
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	2 / 25 (8.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	0	0	2	2	0
Skin Fissures
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	0	0	0	2	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	4 / 25 (16.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	0	4	0	0
Haematuria
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	3 / 25 (12.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)
occurrences all number	1	0	3	1	0
Hydronephrosis
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0	0
Pollakiuria
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	4 / 25 (16.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	4	0	1
Polyurea
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	3 / 21 (14.29%)	0 / 20 (0.00%)
occurrences all number	1	1	2	3	0
Back Pain
subjects affected / exposed	2 / 25 (8.00%)	3 / 23 (13.04%)	4 / 25 (16.00%)	1 / 21 (4.76%)	4 / 20 (20.00%)
occurrences all number	2	3	4	1	4
Muscle Spasms
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1	1
Muscular Weakness
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	0	1	0	1
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	3 / 25 (12.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	0	3	1	1
Musculoskeletal Pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Osteoarthritis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	0	0	0	2	0
Pain In Extremity
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	0 / 25 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	0	2	0	1	1
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	0	0	1	2	0
Cystitis
subjects affected / exposed	2 / 25 (8.00%)	3 / 23 (13.04%)	1 / 25 (4.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	2	3	1	1	1
Device Related Infection
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	0	1
Helicobacter Infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Herpes Simplex
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Infection
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	0	1
Laryngitis
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0	0
Lung Infection
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	1	0	0
Nasopharyngitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	3 / 25 (12.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	0	0	3	2	0
Oral Candidiasis
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	0	1
Peritonitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Pneumonia
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	1	0	0	1
Respiratory Tract Infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Urinary Tract Infection
subjects affected / exposed	4 / 25 (16.00%)	2 / 23 (8.70%)	2 / 25 (8.00%)	2 / 21 (9.52%)	2 / 20 (10.00%)
occurrences all number	4	2	2	2	2
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	12 / 25 (48.00%)	18 / 23 (78.26%)	12 / 25 (48.00%)	16 / 21 (76.19%)	10 / 20 (50.00%)
occurrences all number	12	18	12	16	10
Dehydration
subjects affected / exposed	0 / 25 (0.00%)	4 / 23 (17.39%)	0 / 25 (0.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)
occurrences all number	0	4	0	3	1
Hyperglycaemia
subjects affected / exposed	2 / 25 (8.00%)	2 / 23 (8.70%)	1 / 25 (4.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)
occurrences all number	2	2	1	1	1
Hyperkalaemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)
occurrences all number	0	0	1	2	0
Hypoalbuminaemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1
Hypokalaemia
subjects affected / exposed	6 / 25 (24.00%)	8 / 23 (34.78%)	3 / 25 (12.00%)	5 / 21 (23.81%)	4 / 20 (20.00%)
occurrences all number	6	8	3	5	4
Hypomagnesaemia
subjects affected / exposed	3 / 25 (12.00%)	5 / 23 (21.74%)	3 / 25 (12.00%)	1 / 21 (4.76%)	3 / 20 (15.00%)
occurrences all number	3	5	3	1	3
Hyponatraemia
subjects affected / exposed	4 / 25 (16.00%)	5 / 23 (21.74%)	2 / 25 (8.00%)	2 / 21 (9.52%)	2 / 20 (10.00%)
occurrences all number	4	5	2	2	2
Hypophosphataemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

09 Sep 2014

1. Revised to specify that Carcinosarcomas were allowed. 2. Revised to specify that chemotherapy for relapsed or advanced (stage IIIc) disease was allowed for endometrium subjects. 3. Revised to define liver function and age at time of enrollment from >18 years to ≥18 years. 4. Revised to specify that subjects of childbearing potential must agree to use effective contraception during treatment and up to 3 months from last dose. 5. Expanded number of subjects in the ovarian cohort, to an additional 32 subjects. 6. Added overall survival to secondary objectives and removed it from exploratory objectives. 7. Removed male contraception text. 8. Revised PK sample collection to specify that samples for PK assessment will only be collected from subjects with impaired liver function. 9. Additional collection of CA-125 blood test for clinical chemistry for ovarian subjects only. 10. Removal of cell functionality biomarkers, pharmacodynamics. 11. Ophthalmological examination assessment was revised to specify that if a cataract is seen during the examination, the cataract will be graded according to the Lens Opacities Classification System (LOCS III). 12. Change in frequency of several assessments: They would be done at baseline and if clinically indicated. 13. Addition of optional PET scan at baseline. 14. Updated the electronic mail address to which the SAE forms would be sent to signsae@gso-hamburg.com. 15. Supportive care and prophylactic guidelines were updated based on recent Phase 1 clinical trial results and Investigator input. 16. Added Classification of Adverse Events by Causality. 17. The dose adjustment guidelines have been updated based on recent results of the Phase 1 clinical trials and new enrollment schedule added to this clinical trial. 18. Updated information related to the MTD to specify that escalating beyond 70 mg/m^2 BIW is prohibited in any study. 19. Added intra-subject dose escalation.

12 Nov 2014

1. Subjects with ovarian cancer must have had disease that was measurable according to RECIST or assessable according to the GCIG CA-125 criteria. 2. Receiving of a study drug within 3 weeks prior to Cycle 1 Day 1 was prohibited; however, participation in an anti-cancer study within 3 weeks prior to receiving study drug is acceptable. 3. Dosing schedule for Part 2 was revised. 4. CA-125 response definition was added. 5. Removed the acetaminophen restriction as ongoing clinical safety evaluations on the use of selinexor in combination with acetaminophen have not shown any significant clinical or laboratory abnormalities with doses of acetaminophen up to 1 gram and selinexor up to 55 mg/m^2 (approximately 80-100 mg). 6. Prophylactic and supportive care was revised. 7. Dose modification table was revised to include revised dose modification guidance for thrombocytopenia and nausea/emesis, and specified that guidance used for Grade 3 toxicities should also be used for toxicities that are Grade ≥ 3, table included specific guidance for Part 1 and Part 2 (Schedules 1 and 2). 8. Pre-specified dose/schedule modifications for adverse events (AEs) related to study drug for Part 2, Schedules 1 and 2 was revised. For both schedules, it is specified that upon the discontinuation of dosing, subjects would continue to be assessed. 9. Number of blood samples that will be collected for plasma proteins and PDn (whole blood RNA) for the convenience of subjects on the trial was revised. 10. Collection of blood for the assessment of CTCs as a direct correlation was made between the presence of CTC in the blood of subjects on this trial to their response was reactivated. 11. Collection of blood for PK assessments from the study as the already obtained PK data set from this and other Phase 1 and 2 studies is considered sufficient, and further evaluation of selinexor plasma analysis in this study is not required.

08 Jan 2016

1. Clarified the definitions of platinum refractory and platinum resistant in the inclusion criteria. 2. Clarified that dose escalation can occur if there is tolerability and no sign of progression after 12 weeks of treatment for patients in Parts 1 and 2. 3. Revised wording related to the number of subjects to specify that 21 and 32 evaluable patients are needed in Parts 1 and Part 2, respectively. 4. Consolidated and reformatted guidance for restricted and prohibited medications into one section. 5. Clarified that the overall survival objective will include overall survival rates at 12 and 24 months. 6. Clarified reasons for which the study could be discontinued. 7. Clarified primary and secondary parameters, including details of the efficacy evaluation. 8. Added total abstinence as a method of prevention of pregnancy. 9. Modified the definitions of the ITT population. 10. Added a provision to perform a primary analysis for submission in a CSR when patients are still on treatment, and subsequently perform a final analysis (to be reported in a final CSR) after all patients have completed treatment. 11. A table of GSH-, NAC-, and SAM-containing products was added as an appendix based on FDA feedback on a different protocol. 12. Clarified the timing of collection of AEs and SAEs. 13. Revised the window for assessments to be completed following 6 weeks of treatment for gynaecological cancers from ±5 days to ±7 days. 14. Added a baseline assessment for CA-125 to comply with CGIG CA-125 response criteria requirements. 15. The use of 20 mg tablets was added for increased tolerability based on the results of the ongoing Phase 1 studies. 16. Clarified that doses of selinexor must be at least 36 hours apart for twice weekly dosing and at least 5 days apart for once weekly dosing.

04 Aug 2016

1. Due to the termination of the Primary Treatment Phase of the study, a maintenance schedule had been added to allow the existing patients on the study to continue treatment with selinexor and/or survival follow-up. The revised Maintenance Phase included study treatment, schedule of assessments, supportive care, dose modification and data collection for separate Maintenance Phase database.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Phase II, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 (Selinexor) in Patients With Advanced Gynaecologic Malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Primary: Percentage of Subjects With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Secondary: Percentage of Subjects With Overall Response According to RECIST v1.1

Secondary: Percentage of Subjects With Overall Response According to RECIST v1.1

Secondary: Percentage of Subjects With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria

Secondary: Percentage of Subjects With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria

Secondary: Percentage of Subjects With Overall Response According to GCIG Response Criteria

Secondary: Percentage of Subjects With Overall Response According to GCIG Response Criteria

Secondary: Progression-free Survival (PFS) According to RECIST v1.1

Secondary: Progression-free Survival (PFS) According to RECIST v1.1

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Percentage of Subjects Who Survived at 12 and 24 Months

Secondary: Percentage of Subjects Who Survived at 12 and 24 Months

Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

Secondary: Number of Subjects With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

Secondary: Number of Subjects With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

Secondary: Quality of Life (QoL): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

Secondary: Quality of Life (QoL): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

Secondary: Number of Subjects With Individual Clinically Significant Abnormalities in Laboratory Tests

Secondary: Number of Subjects With Individual Clinically Significant Abnormalities in Laboratory Tests

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: A Phase II, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 (Selinexor) in Patients With Advanced Gynaecologic Malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Primary: Percentage of Subjects With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Secondary: Percentage of Subjects With Overall Response According to RECIST v1.1

Secondary: Percentage of Subjects With Overall Response According to RECIST v1.1

Secondary: Percentage of Subjects With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria

Secondary: Percentage of Subjects With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria

Secondary: Percentage of Subjects With Overall Response According to GCIG Response Criteria

Secondary: Percentage of Subjects With Overall Response According to GCIG Response Criteria

Secondary: Progression-free Survival (PFS) According to RECIST v1.1

Secondary: Progression-free Survival (PFS) According to RECIST v1.1

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Percentage of Subjects Who Survived at 12 and 24 Months

Secondary: Percentage of Subjects Who Survived at 12 and 24 Months

Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

Secondary: Number of Subjects With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

Secondary: Number of Subjects With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

Secondary: Number of Subjects With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

Secondary: Quality of Life (QoL): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

Secondary: Quality of Life (QoL): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

Secondary: Number of Subjects With Individual Clinically Significant Abnormalities in Laboratory Tests

Secondary: Number of Subjects With Individual Clinically Significant Abnormalities in Laboratory Tests

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 (Selinexor) in Patients With Advanced Gynaecologic Malignancies