KING: Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Participants With Recurrent Gliomas

• Sponsor: Karyopharm Therapeutics Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01986348
• Collaborator: (none)
• Enrollment: 76
• Locations: 6
• Arms: 4
• Actual Duration (Months): 70.7
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma; Glioma	Drug: Selinexor	Phase 2

Detailed Description

This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas.

Initially, the study included 2 arms: an exploratory Surgical Arm (Arm A) with sequential enrollment for participants who require surgery and a medical arm (Arm B) for participants who are not eligible for surgery.

Enrollment in Arm B was stopped to explore alternative dosing in Protocol Versions ≥ 4.0 to potentially improve tolerability. Four arms (Arms C, D, E, and F) were added to the Medical Arm in Protocol Version 4.0. Arms E and F were eliminated in protocol version 6.0 and no participants were ever enrolled in these arms.

Participants in the primary population enrolled under Protocol Version ≥ 4.0 will be randomized to Arm C and Arm D (approximately 30 participants per arm) to explore alternative dosing to potentially improve tolerability.

After screening and registration/randomization in the study, participants enrolling in Arm A or randomized to Arm C will receive 60 mg selinexor orally twice weekly. Participants randomized to Arm D will receive 80 mg selinexor orally weekly.

Participants will be treated until progression of disease or the development of unacceptable toxicities. All participants will then undergo the End of Treatment (EOT) visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study Evaluating the Efficacy and Safety of Selinexor (KPT-330) in Patients With Recurrent Gliomas
• Actual Study Start Date: Mar 3, 2014
• Actual Primary Completion Date: Jan 23, 2020
• Actual Study Completion Date: Jan 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Selinexor 60 mg and Surgery Participants who required surgery received up to 3 doses of oral selinexor tablets 60 milligrams (mg) twice weekly (BIW) on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until progression of disease (PD) or development of unacceptable toxicities.	Drug: Selinexor; One cycle is 28 days (4 weeks).; Other Names: KPT-330
Experimental: Arm B: Selinexor 50 mg/m^2 Participants who were not eligible for surgery received selinexor tablets 50 mg per square meter (mg/m^2) BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Drug: Selinexor; One cycle is 28 days (4 weeks).; Other Names: KPT-330
Experimental: Arm C: Selinexor 60 mg Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Drug: Selinexor; One cycle is 28 days (4 weeks).; Other Names: KPT-330
Experimental: Arm D: Selinexor 80 mg Participants who were not eligible for surgery received selinexor tablets 80 mg once weekly (QW) during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Drug: Selinexor; One cycle is 28 days (4 weeks).; Other Names: KPT-330

Outcome Measures

Primary Outcome Measures

1. 6-Month Progression-Free Survival (PFS) Rate [From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6)]

   The analysis of 6mPFS was performed by calculating the estimated survival probability of having PFS ≥ 6 months based on Kaplan-Meier method, where PFS was defined as the time from the start of study treatment until first documented progression based on Response Assessment in Neuro-Oncology (RANO) criteria, or death from any cause. Progressive disease occurs when either of the criteria was present: greater than or equal to (≥) 25 percentage (%) increase in T1 gadolinium enhancing disease, increase in T2/ Fluid-attenuated inversion recovery (FLAIR), detection of new lesions, or decreased clinical status.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Up to 71 months]

   The ORR was determined as percentage of participants who had either complete response (CR) or partial response (PR) using the RANO criteria. CR: No T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, no corticosteroid use and stable, or increasing clinical status. PR: ≥50% decrease in T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, stable or decreased use of corticosteroids, and stable or increased clinical status.

2. Overall Survival (OS) [From date of study treatment up to date of death (assessed up to 71 months)]

   The OS was calculated from the date of start of study treatment to the date of death. Participants who were still alive prior to the data cut-off for final efficacy analysis, or who dropout prior to study end, were censored on the day they were last known to be alive. The OS was estimated using Kaplan-Meier method.

3. Progression-free Survival (PFS) [From start of study treatment up to disease progression (assessed up to 71 months)]

   The PFS was calculated from the date of start of study treatment to the date of disease progression based on RANO criteria, or date of death should progression not have occurred. Progressive disease occurs when either of the criteria was present: ≥25% increase in T1 gadolinium enhancing disease, increased T2/FLAIR, detection of new lesions, or decreased clinical status.

4. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [From start of study treatment administration up to 71 months]

   An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as an AE that was fatal; life threatening (places the participant at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; and other important medical events. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study medication through 30 days following last dose or any event considered drug-related by the Investigator through the end of the study. TEAEs included both serious and non-serious TEAEs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathologically confirmed GBM (including all histologic variants) at first diagnosis with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide;

• 18 years of age or older

• Participants enrolling in the medical arm (Arms B, C and D) must be on a stable or decreasing dose of corticosteroids (or none) for at least 5 days prior to the baseline MRI;

• Measurable disease (according to RANO guidelines)

• Surgical arm (Arm A) must be predicted pre-operatively to have sufficiently sized tumor to be resected and provide tissue samples for exploratory assessments.

Exclusion Criteria:

• Markedly decreased visual acuity if attributed to other causes than GBM.

• Known active hepatitis A, B, or C

• Participants with coagulation problems and medically significant bleeding in the month prior to start of treatment (e.g., peptic ulcer, epistaxis, spontaneous bleeding). Prior history of DVT or PE is not exclusionary.

• Participants must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medications.

• Prior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any question of the definition of a direct VEGF/VEGFR inhibitor, consult Sponsor.

• Arms C and D only: body surface area < 1.2 m².

• < 24 days from prior temozolomide, < 6 weeks from nitrosourea, < 4 weeks from other chemotherapy or investigational agents prior to start of treatment within study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Dana Farber Cancer Institute, Center for Neuro-Oncology	Boston	Massachusetts	United States	02215
3	Columbia University, Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
4	The Phase I Unit, Dept. of Oncology, Rigshospitalet	Copenhagen		Denmark	DK-2100
5	University of Groningen Faculty of Medical Sciences, Medical Oncology	Groningen		Netherlands	9713 GZ
6	Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit	Rotterdam		Netherlands	3008AE

Sponsors and Collaborators

• Karyopharm Therapeutics Inc

Investigators

• Principal Investigator: Morten Mau-Sørensen, MD, Ph.D, The Phase I Unit, Dept. of Oncology, Rigshospitalet
• Principal Investigator: Andrew B Lassman, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol - Nov 13, 2015
• Statistical Analysis Plan - Mar 5, 2020

More Information

Publications

None provided.

• Responsible Party: Karyopharm Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT01986348
• Other Study ID Numbers: KCP-330-004
• First Posted: Nov 18, 2013
• Last Update Posted: Aug 2, 2021
• Last Verified: Jul 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: GBM; Glioblastoma; selinexor; KPT-330; Karyopharm; brain tumor; brain cancer; Glioma; Astrocytoma; Oligodendrogliomas; Oligo-astrocytomas
• Additional relevant MeSH terms: Glioblastoma; Glioma

Study Results

Participant Flow

Recruitment Details	This study was conducted at 6 sites across the United States of America, Denmark and Netherland between 03 March 2014 and 23 January 2020.
Pre-assignment Detail	A total of 76 participants were enrolled, randomized and treated in this study.

Arm/Group Title	Arm A: Selinexor 60 mg and Surgery	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg
Arm/Group Description	Participants who required surgery received up to 3 doses of oral selinexor tablets 60 milligrams (mg) twice weekly (BIW) on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until progression of disease (PD) or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 50 mg per square meter (mg/m^2) BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg once weekly (QW) during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Period Title: Overall Study
STARTED	8	24	14	30
COMPLETED	0	0	0	0
NOT COMPLETED	8	24	14	30

Baseline Characteristics

Arm/Group Title	Arm A: Selinexor 60 mg and Surgery	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg	Total
Arm/Group Description	Participants who required surgery received up to 3 doses of oral selinexor tablets 60 mg BIW on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Total of all reporting groups
Overall Participants	8	24	14	30	76
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.6 (6.70)	51.1 (13.04)	49.5 (12.36)	54.3 (11.98)	52.7 (11.99)
Sex: Female, Male (Count of Participants)
Female	1 12.5%	5 20.8%	5 35.7%	11 36.7%	22 28.9%
Male	7 87.5%	19 79.2%	9 64.3%	19 63.3%	54 71.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	3 10%	3 3.9%
Not Hispanic or Latino	8 100%	20 83.3%	8 57.1%	24 80%	60 78.9%
Unknown or Not Reported	0 0%	4 16.7%	6 42.9%	3 10%	13 17.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	1 3.3%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	8 100%	24 100%	8 57.1%	25 83.3%	65 85.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	6 42.9%	4 13.3%	10 13.2%

Outcome Measures

1. Primary Outcome

Title	6-Month Progression-Free Survival (PFS) Rate
Description	The analysis of 6mPFS was performed by calculating the estimated survival probability of having PFS ≥ 6 months based on Kaplan-Meier method, where PFS was defined as the time from the start of study treatment until first documented progression based on Response Assessment in Neuro-Oncology (RANO) criteria, or death from any cause. Progressive disease occurs when either of the criteria was present: greater than or equal to (≥) 25 percentage (%) increase in T1 gadolinium enhancing disease, increase in T2/ Fluid-attenuated inversion recovery (FLAIR), detection of new lesions, or decreased clinical status.
Time Frame	From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6)

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or PD. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery.

Arm/Group Title	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg
Arm/Group Description	Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Measure Participants	24	13	30
Number (95% Confidence Interval) [percentage of participants]	9.72 121.5%	7.69 32%	17.24 123.1%

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	The ORR was determined as percentage of participants who had either complete response (CR) or partial response (PR) using the RANO criteria. CR: No T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, no corticosteroid use and stable, or increasing clinical status. PR: ≥50% decrease in T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, stable or decreased use of corticosteroids, and stable or increased clinical status.
Time Frame	Up to 71 months

Outcome Measure Data

Analysis Population Description

mITT population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or disease progression. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery.

Arm/Group Title	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg
Arm/Group Description	Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Measure Participants	24	13	30
Number (95% Confidence Interval) [percentage of participants]	8.3 103.8%	7.7 32.1%	10.0 71.4%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	The OS was calculated from the date of start of study treatment to the date of death. Participants who were still alive prior to the data cut-off for final efficacy analysis, or who dropout prior to study end, were censored on the day they were last known to be alive. The OS was estimated using Kaplan-Meier method.
Time Frame	From date of study treatment up to date of death (assessed up to 71 months)

Outcome Measure Data

Analysis Population Description

mITT population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or disease progression. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery.

Arm/Group Title	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg
Arm/Group Description	Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Measure Participants	24	13	30
Median (95% Confidence Interval) [months]	10.51	8.48	10.15

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	The PFS was calculated from the date of start of study treatment to the date of disease progression based on RANO criteria, or date of death should progression not have occurred. Progressive disease occurs when either of the criteria was present: ≥25% increase in T1 gadolinium enhancing disease, increased T2/FLAIR, detection of new lesions, or decreased clinical status.
Time Frame	From start of study treatment up to disease progression (assessed up to 71 months)

Outcome Measure Data

Analysis Population Description

mITT population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or disease progression. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery.

Arm/Group Title	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg
Arm/Group Description	Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Measure Participants	24	13	30
Median (95% Confidence Interval) [months]	1.64	1.87	1.87

5. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as an AE that was fatal; life threatening (places the participant at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; and other important medical events. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study medication through 30 days following last dose or any event considered drug-related by the Investigator through the end of the study. TEAEs included both serious and non-serious TEAEs.
Time Frame	From start of study treatment administration up to 71 months

Outcome Measure Data

Analysis Population Description

Safety population consisted of all participants who had received any amount of study treatment.

Arm/Group Title	Arm A: Selinexor 60 mg and Surgery	Arm B: Selinexor 50 mg/m^2	Arm C: Selinexor 60 mg	Arm D: Selinexor 80 mg
Arm/Group Description	Participants who required surgery received up to 3 doses of oral selinexor tablets 60 mg BIW on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.	Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
Measure Participants	8	24	14	30
Participants with TEAEs	8 100%	24 100%	14 100%	30 100%
Participants with TESAEs	5 62.5%	7 29.2%	7 50%	7 23.3%

Adverse Events

Time Frame	From start of study treatment administration up to 71 months
Arm/Group Title	Arm A: Selinexor 60 mg and Surgery		Arm B: Selinexor 50 mg/m^2		Arm C: Selinexor 60 mg		Arm D: Selinexor 80 mg
Arm/Group Description	Participants who required surgery received up to 3 doses of oral selinexor tablets 60 mg BIW on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until PD or development of unacceptable toxicities.		Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.		Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.		Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities.
All Cause Mortality
	Arm A: Selinexor 60 mg and Surgery		Arm B: Selinexor 50 mg/m^2		Arm C: Selinexor 60 mg		Arm D: Selinexor 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		22/24 (91.7%)		10/14 (71.4%)		21/30 (70%)
Serious Adverse Events
	Arm A: Selinexor 60 mg and Surgery		Arm B: Selinexor 50 mg/m^2		Arm C: Selinexor 60 mg		Arm D: Selinexor 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)		7/24 (29.2%)		7/14 (50%)		7/30 (23.3%)
Gastrointestinal disorders
Diarrhoea	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
General disorders
Fatigue	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		0/30 (0%)
Asthenia	0/8 (0%)		0/24 (0%)		0/14 (0%)		1/30 (3.3%)
General physical health deterioration	0/8 (0%)		0/24 (0%)		0/14 (0%)		1/30 (3.3%)
Infections and infestations
Urinary tract infection	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Meningitis bacterial	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Pneumonia	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Staphylococcal infection	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Injury, poisoning and procedural complications
Acetabulum fracture	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Concussion	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Shunt malfunction	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Hyperglycaemia	0/8 (0%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Hyperlipasaemia	0/8 (0%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Hypophosphataemia	0/8 (0%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/8 (0%)		0/24 (0%)		0/14 (0%)		1/30 (3.3%)
Intracranial tumour haemorrhage	0/8 (0%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Nervous system disorders
Seizure	0/8 (0%)		1/24 (4.2%)		3/14 (21.4%)		2/30 (6.7%)
Syncope	0/8 (0%)		0/24 (0%)		0/14 (0%)		3/30 (10%)
Headache	0/8 (0%)		1/24 (4.2%)		1/14 (7.1%)		0/30 (0%)
Brain oedema	0/8 (0%)		0/24 (0%)		0/14 (0%)		1/30 (3.3%)
Cerebrospinal fluid leakage	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Cerebrovascular accident	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Dizziness	0/8 (0%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Pneumocephalus	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Psychiatric disorders
Confusional state	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Vascular disorders
Embolism	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Hypertension	0/8 (0%)		0/24 (0%)		0/14 (0%)		1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Arm A: Selinexor 60 mg and Surgery		Arm B: Selinexor 50 mg/m^2		Arm C: Selinexor 60 mg		Arm D: Selinexor 80 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		24/24 (100%)		14/14 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	6/8 (75%)		16/24 (66.7%)		6/14 (42.9%)		11/30 (36.7%)
Leukopenia	0/8 (0%)		7/24 (29.2%)		1/14 (7.1%)		14/30 (46.7%)
Neutropenia	1/8 (12.5%)		7/24 (29.2%)		2/14 (14.3%)		10/30 (33.3%)
Anaemia	2/8 (25%)		5/24 (20.8%)		1/14 (7.1%)		6/30 (20%)
Lymphopenia	2/8 (25%)		2/24 (8.3%)		0/14 (0%)		8/30 (26.7%)
Cardiac disorders
Tachycardia	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Ear and labyrinth disorders
Tinnitus	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		1/30 (3.3%)
Hypoacusis	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Endocrine disorders
Cushingoid	0/8 (0%)		4/24 (16.7%)		0/14 (0%)		0/30 (0%)
Inappropriate antidiuretic hormone secretion	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Eye disorders
Vision blurred	0/8 (0%)		6/24 (25%)		1/14 (7.1%)		4/30 (13.3%)
Dry eye	1/8 (12.5%)		1/24 (4.2%)		1/14 (7.1%)		1/30 (3.3%)
Eye pain	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Periorbital oedema	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		1/30 (3.3%)
Visual acuity reduced	0/8 (0%)		3/24 (12.5%)		0/14 (0%)		0/30 (0%)
Cataract	0/8 (0%)		0/24 (0%)		0/14 (0%)		3/30 (10%)
Gastrointestinal disorders
Nausea	6/8 (75%)		12/24 (50%)		9/14 (64.3%)		21/30 (70%)
Vomiting	1/8 (12.5%)		9/24 (37.5%)		5/14 (35.7%)		13/30 (43.3%)
Constipation	3/8 (37.5%)		8/24 (33.3%)		7/14 (50%)		7/30 (23.3%)
Diarrhoea	2/8 (25%)		3/24 (12.5%)		3/14 (21.4%)		6/30 (20%)
Dry mouth	1/8 (12.5%)		3/24 (12.5%)		2/14 (14.3%)		1/30 (3.3%)
Dyspepsia	0/8 (0%)		2/24 (8.3%)		1/14 (7.1%)		2/30 (6.7%)
Abdominal pain	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		3/30 (10%)
Stomatitis	0/8 (0%)		2/24 (8.3%)		1/14 (7.1%)		0/30 (0%)
Toothache	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
General disorders
Fatigue	5/8 (62.5%)		19/24 (79.2%)		11/14 (78.6%)		16/30 (53.3%)
Gait disturbance	5/8 (62.5%)		5/24 (20.8%)		3/14 (21.4%)		3/30 (10%)
Oedema peripheral	3/8 (37.5%)		1/24 (4.2%)		2/14 (14.3%)		3/30 (10%)
Malaise	1/8 (12.5%)		1/24 (4.2%)		3/14 (21.4%)		3/30 (10%)
Face oedema	0/8 (0%)		2/24 (8.3%)		2/14 (14.3%)		0/30 (0%)
Non-cardiac chest pain	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Pyrexia	1/8 (12.5%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Infections and infestations
Nasopharyngitis	0/8 (0%)		2/24 (8.3%)		1/14 (7.1%)		2/30 (6.7%)
Urinary tract infection	1/8 (12.5%)		0/24 (0%)		1/14 (7.1%)		3/30 (10%)
Upper respiratory tract infection	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		1/30 (3.3%)
Bronchitis	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Cystitis	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Influenza	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Pneumonia	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Injury, poisoning and procedural complications
Fall	1/8 (12.5%)		1/24 (4.2%)		1/14 (7.1%)		5/30 (16.7%)
Contusion	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Incision site pain	1/8 (12.5%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Spinal compression fracture	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Wound dehiscence	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Investigations
Weight decreased	1/8 (12.5%)		5/24 (20.8%)		6/14 (42.9%)		2/30 (6.7%)
Alanine aminotransferase increased	2/8 (25%)		1/24 (4.2%)		0/14 (0%)		5/30 (16.7%)
Aspartate aminotransferase increased	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		3/30 (10%)
Blood alkaline phosphatase increased	0/8 (0%)		0/24 (0%)		0/14 (0%)		3/30 (10%)
Metabolism and nutrition disorders
Decreased appetite	3/8 (37.5%)		12/24 (50%)		10/14 (71.4%)		8/30 (26.7%)
Hyponatraemia	4/8 (50%)		11/24 (45.8%)		3/14 (21.4%)		1/30 (3.3%)
Hypophosphataemia	3/8 (37.5%)		5/24 (20.8%)		0/14 (0%)		0/30 (0%)
Hyperglycaemia	0/8 (0%)		4/24 (16.7%)		1/14 (7.1%)		1/30 (3.3%)
Dehydration	1/8 (12.5%)		3/24 (12.5%)		0/14 (0%)		1/30 (3.3%)
Hypokalaemia	1/8 (12.5%)		2/24 (8.3%)		2/14 (14.3%)		0/30 (0%)
Hyperkalaemia	0/8 (0%)		3/24 (12.5%)		0/14 (0%)		1/30 (3.3%)
Hyperlipasaemia	2/8 (25%)		1/24 (4.2%)		0/14 (0%)		1/30 (3.3%)
Hypercreatininaemia	1/8 (12.5%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Hyperamylasaemia	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/8 (12.5%)		3/24 (12.5%)		4/14 (28.6%)		2/30 (6.7%)
Back pain	1/8 (12.5%)		0/24 (0%)		2/14 (14.3%)		2/30 (6.7%)
Myalgia	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Neck pain	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Osteoporosis	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Nervous system disorders
Dysgeusia	1/8 (12.5%)		10/24 (41.7%)		6/14 (42.9%)		4/30 (13.3%)
Headache	4/8 (50%)		5/24 (20.8%)		6/14 (42.9%)		5/30 (16.7%)
Dizziness	3/8 (37.5%)		6/24 (25%)		4/14 (28.6%)		2/30 (6.7%)
Memory impairment	1/8 (12.5%)		2/24 (8.3%)		2/14 (14.3%)		2/30 (6.7%)
Aphasia	1/8 (12.5%)		2/24 (8.3%)		0/14 (0%)		2/30 (6.7%)
Balance disorder	1/8 (12.5%)		1/24 (4.2%)		2/14 (14.3%)		1/30 (3.3%)
Dysarthria	0/8 (0%)		4/24 (16.7%)		0/14 (0%)		1/30 (3.3%)
Seizure	2/8 (25%)		1/24 (4.2%)		0/14 (0%)		2/30 (6.7%)
Haemorrhage intracranial	2/8 (25%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Hemiparesis	1/8 (12.5%)		2/24 (8.3%)		0/14 (0%)		1/30 (3.3%)
Neuropathy peripheral	1/8 (12.5%)		3/24 (12.5%)		0/14 (0%)		0/30 (0%)
Tremor	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		2/30 (6.7%)
Coordination abnormal	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		0/30 (0%)
Depressed level of consciousness	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		1/30 (3.3%)
Disturbance in attention	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		0/30 (0%)
Hemianopia homonymous	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
IIIrd nerve disorder	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Lethargy	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Motor dysfunction	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		0/30 (0%)
Paraesthesia	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Syncope	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Taste disorder	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Visual field defect	0/8 (0%)		1/24 (4.2%)		1/14 (7.1%)		0/30 (0%)
Ataxia	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Cerebrospinal fluid leakage	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Intracranial pressure increased	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		0/30 (0%)
Somnolence	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Upper motor neurone lesion	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Psychiatric disorders
Confusional state	2/8 (25%)		4/24 (16.7%)		1/14 (7.1%)		5/30 (16.7%)
Depression	1/8 (12.5%)		1/24 (4.2%)		2/14 (14.3%)		1/30 (3.3%)
Insomnia	0/8 (0%)		4/24 (16.7%)		1/14 (7.1%)		0/30 (0%)
Anxiety	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		1/30 (3.3%)
Abnormal behaviour	0/8 (0%)		0/24 (0%)		2/14 (14.3%)		0/30 (0%)
Mood altered	0/8 (0%)		1/24 (4.2%)		1/14 (7.1%)		0/30 (0%)
Personality change	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Renal and urinary disorders
Urinary incontinence	1/8 (12.5%)		3/24 (12.5%)		2/14 (14.3%)		3/30 (10%)
Pollakiuria	0/8 (0%)		2/24 (8.3%)		1/14 (7.1%)		1/30 (3.3%)
Reproductive system and breast disorders
Erectile dysfunction	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		3/24 (12.5%)		1/14 (7.1%)		4/30 (13.3%)
Dyspnoea	1/8 (12.5%)		1/24 (4.2%)		4/14 (28.6%)		2/30 (6.7%)
Oropharyngeal pain	2/8 (25%)		1/24 (4.2%)		0/14 (0%)		2/30 (6.7%)
Epistaxis	0/8 (0%)		3/24 (12.5%)		0/14 (0%)		0/30 (0%)
Nasal Congestion	1/8 (12.5%)		2/24 (8.3%)		0/14 (0%)		0/30 (0%)
Rhinitis allergic	0/8 (0%)		0/24 (0%)		0/14 (0%)		2/30 (6.7%)
Apnoea	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Pulmonary embolism	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/8 (0%)		2/24 (8.3%)		0/14 (0%)		4/30 (13.3%)
Pruritus	2/8 (25%)		1/24 (4.2%)		0/14 (0%)		2/30 (6.7%)
Dry skin	1/8 (12.5%)		0/24 (0%)		1/14 (7.1%)		1/30 (3.3%)
Rash maculo-papular	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		2/30 (6.7%)
Night sweats	0/8 (0%)		1/24 (4.2%)		1/14 (7.1%)		0/30 (0%)
Rash	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Purpura	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Vascular disorders
Hypotension	1/8 (12.5%)		0/24 (0%)		0/14 (0%)		6/30 (20%)
Flushing	1/8 (12.5%)		1/24 (4.2%)		0/14 (0%)		0/30 (0%)
Embolism	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)
Hypertension	0/8 (0%)		0/24 (0%)		1/14 (7.1%)		0/30 (0%)

Limitations/Caveats

Study was terminated due to Sponsor decision (all except 1 patient were off-treatment and 2 patients were in survival follow-up).

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Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.