A Phase 3 Randomized, Controlled, Open-label Study of Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)
Phase: PHASE3
Conditions: Multiple Myeloma
Sponsor: Karyopharm Therapeutics Inc

Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 1 
Version 4.0 
CLINICAL STUDY PROTOCOL 
KCP-330-023 
A PHASE 3 RANDOMIZED, CONTROLLED, OPEN-LABEL 
STUDY OF SELINEXOR, BORTEZOMIB, AND 
DEXAMETHASONE (SVD) VERSUS BORTEZOMIB AND 
DEXAMETHASONE (VD) IN PATIENTS WITH RELAPSED OR 
REFRACTORY MULTIPLE MYELOMA (RRMM) 
Study Name: BOSTON: Bortezomib, Selinexor, and Dexamethasone in Patients with 
Multiple Myeloma 
Study Number: 
KCP-330-023 
Study Phase: 
3 
Investigational Product: 
Selinexor (KPT-330) 
EudraCT Number: 
2016-003957-14 
Indication: 
Relapsed or refractory multiple myeloma (RRMM) 
Sponsor: 
Karyopharm Therapeutics Inc. 
85 Wells Avenue 
Newton, MA 02459 USA 
Tel. + (617) 658-0600 
Protocol Date and Version: 
18 November 2016, Version 1.0 
22 February 2017, Version 2.0 (Amendment 1) 
06 April 2017, Version 3.0 (Amendment 2) 
17 August 2018, Version 4.0 (Amendment 3) 
CONDUCT 
In accordance with the ethical principles that originate from the Declaration of Helsinki and 
that are consistent with International Council for Harmonisation (ICH) guidelines on Good 
Clinical Practice (GCP) and regulatory requirements as applicable. 
CONFIDENTIAL INFORMATION 
This document is the sole property of Karyopharm Therapeutics Inc. (Karyopharm). This 
document and any and all information contained herein has to be considered and treated as 
strictly confidential. This document shall be used only for the purpose of the disclosure herein 
provided. No disclosure or publication shall be made without the prior written consent of 
Karyopharm. 

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Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 3 
Version 4.0 
INVESTIGATOR’S AGREEMENT 
I have read and understand the contents of this clinical protocol for Study KCP-330-023 dated 
17 August 2018 and will adhere to the study requirements as presented, including all statements 
regarding confidentiality. In addition, I will conduct the Study in accordance with current Good 
Clinical Practice, ICH E6, and applicable FDA regulatory requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Institution 
 
 
 
 
 
 
 
 
Date 

Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 4 
Version 4.0 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................12 
2. 
PROTOCOL SYNOPSIS ...........................................................................................17 
3. 
STUDY SCHEMATICS AND SCHEDULE OF ASSESSMENTS AND 
DOSING FOR STUDY KCP-330-023 .......................................................................22 
3.1. 
Schedules of Visits for In-clinic Dosing and MM Evaluations ..................................29 
3.2. 
Dose Schedules ...........................................................................................................31 
4. 
INTRODUCTION ......................................................................................................35 
4.1. 
Multiple Myeloma ......................................................................................................35 
4.1.1. 
Disease Background ...................................................................................................35 
4.1.2. 
MM Treatment ............................................................................................................35 
4.2. 
Selinexor .....................................................................................................................35 
4.2.1. 
Selinexor Mechanism of Action .................................................................................35 
4.2.2. 
Selinexor Pharmacodynamics and Dosing Frequency ...............................................36 
4.2.3. 
Selinexor Pharmacokinetics ........................................................................................36 
4.2.4. 
Selinexor Metabolism/Drug-drug Interactions ...........................................................37 
4.2.5. 
Selinexor Nonclinical Combination with Dexamethasone and Proteasome 
Inhibitors .....................................................................................................................37 
4.2.6. 
Overall Clinical Experience with Selinexor ...............................................................38 
4.2.6.1. 
Study KCP-330-017 (STOMP) ...................................................................................39 
4.2.7. 
Potential Risks of Selinexor ........................................................................................40 
4.2.7.1. 
Reproductive Risks for Selinexor ...............................................................................41 
4.3. 
Bortezomib and Dexamethasone (Vd) ........................................................................41 
4.4. 
Study and Dose Rationale ...........................................................................................41 
4.4.1. 
Study Rationale ...........................................................................................................41 
4.4.2. 
Dose Rationale ............................................................................................................42 
4.4.2.1. 
Bortezomib QW Dose Rationale ................................................................................43 
5. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................44 
5.1. 
Objectives ...................................................................................................................44 
5.1.1. 
Primary Objective .......................................................................................................44 
5.1.2. 
Secondary Objectives .................................................................................................44 
5.1.3. 
Exploratory Objectives ...............................................................................................44 
5.1.4. 
Pharmacokinetic Objective .........................................................................................45 

Investigational Product (KPT-330)  
 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 5 
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5.2. 
Endpoints ....................................................................................................................45 
5.2.1. 
Primary Endpoint ........................................................................................................45 
5.2.2. 
Secondary Efficacy Endpoints ....................................................................................45 
5.2.2.1. 
Key Secondary Efficacy Endpoints ............................................................................45 
5.2.2.2. 
Non-Key Secondary Efficacy Endpoints ....................................................................45 
5.2.3. 
Secondary Safety Endpoints .......................................................................................46 
5.2.3.1. 
Key Secondary Safety Endpoint .................................................................................46 
5.2.3.2. 
Non-Key Secondary Safety Endpoints .......................................................................46 
5.2.4. 
Secondary HR-QoL Endpoint .....................................................................................46 
5.2.5. 
Exploratory Endpoints ................................................................................................46 
5.2.6. 
PK Endpoints ..............................................................................................................46 
6. 
INVESTIGATIONAL PLAN .....................................................................................47 
6.1. 
Overall Study Design and Plan ...................................................................................47 
6.2. 
Crossover ....................................................................................................................49 
6.3. 
Data Safety Monitoring Board ....................................................................................50 
6.4. 
Independent Review Committee .................................................................................50 
7. 
STUDY POPULATION SELECTION ......................................................................51 
7.1. 
Study Population .........................................................................................................51 
7.2. 
Inclusion Criteria ........................................................................................................51 
7.3. 
Exclusion Criteria .......................................................................................................52 
8. 
REGISTRATION AND RANDOMIZATION ...........................................................55 
8.1. 
Screening and Registration .........................................................................................55 
8.1.1. 
Study Patient Number .................................................................................................55 
8.1.2. 
Rescreening .................................................................................................................55 
8.1.3. 
Screen Failures ............................................................................................................55 
8.1.4. 
Replacement of Patients .............................................................................................55 
8.2. 
Randomization to Study Treatment ............................................................................55 
8.3. 
Blinding Procedures ....................................................................................................56 
9. 
DISCONTINUATION CRITERIA ............................................................................57 
9.1. 
Early Termination of the Study ..................................................................................57 
9.2. 
Discontinuation of Study Treatment and/or Withdrawal of Patients from the 
Study ...........................................................................................................................57 
9.3. 
End of Study Definition ..............................................................................................58 

Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 6 
Version 4.0 
10. 
STUDY TREATMENTS ............................................................................................59 
10.1. 
Treatments Administered ............................................................................................59 
10.1.1. 
Study Treatments ........................................................................................................59 
10.2. 
Dose Schedules and Administration ...........................................................................59 
10.2.1. 
Labeling ......................................................................................................................59 
10.2.2. 
Dispensing Directions .................................................................................................59 
10.2.3. 
Dosing Information .....................................................................................................59 
10.2.3.1. 
Dosing Sequence and Timing .....................................................................................59 
10.2.3.2. 
Selinexor .....................................................................................................................59 
10.2.3.3. 
Bortezomib .................................................................................................................60 
10.2.3.4. 
Dexamethasone ...........................................................................................................60 
10.2.4. 
Dose Schedules for Evaluation ...................................................................................60 
10.2.4.1. 
SVd Arm .....................................................................................................................60 
10.2.4.2. 
Vd Arm .......................................................................................................................60 
10.2.4.3. 
SVdX Patients .............................................................................................................61 
10.2.4.4. 
SdX Patients ................................................................................................................61 
10.2.5. 
Selinexor Dose Escalation ..........................................................................................61 
10.2.6. 
Duration of Treatment and Follow-up ........................................................................61 
10.3. 
Supportive Care for All Patients .................................................................................61 
10.3.1. 
Required 5-HT3 Antagonists ......................................................................................61 
10.3.2. 
Recommended Supportive Care .................................................................................62 
10.3.3. 
Infection ......................................................................................................................62 
10.3.4. 
Glucocorticoid Side Effects ........................................................................................62 
10.3.5. 
Overdose .....................................................................................................................62 
10.4. 
Dose Modifications .....................................................................................................62 
10.4.1. 
Selinexor Dose Reduction Guidelines ........................................................................63 
10.4.1.1. 
Selinexor Dose Adjustment in the Setting of Infection ..............................................67 
10.4.1.2. 
Conditions Not Requiring Selinexor Dose Reduction ................................................67 
10.4.2. 
Dose Modifications for Overlapping Toxicities .........................................................68 
10.4.3. 
Bortezomib Dose Modifications .................................................................................68 
10.4.4. 
Dexamethasone Dose Modifications ..........................................................................68 
10.5. 
Missed or Vomited Doses ...........................................................................................68 

Investigational Product (KPT-330)  
 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 7 
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10.5.1. 
Missed Doses of Study Treatments (Selinexor, Bortezomib, and 
Dexamethasone) .........................................................................................................68 
10.5.2. 
Vomited Doses of Selinexor .......................................................................................69 
10.6. 
Sponsor-supplied Study Treatment Accountability ....................................................69 
10.7. 
Compliance .................................................................................................................69 
10.8. 
Contraception Requirements and Concomitant Medications .....................................70 
10.8.1. 
Contraception Requirements ......................................................................................70 
10.8.2. 
Non-study-related Concomitant Medication and Treatment ......................................70 
10.8.2.1. 
Permitted Concomitant Medication ............................................................................71 
10.8.2.2. 
Use of Blood Products ................................................................................................71 
10.8.2.3. 
Radiation Treatment ...................................................................................................71 
10.8.3. 
Restrictions for Study Treatment ................................................................................71 
10.8.3.1. 
Restrictions for Selinexor ...........................................................................................71 
10.8.3.2. 
Restrictions for Bortezomib and Dexamethasone ......................................................71 
10.8.4. 
Prohibited Medications ...............................................................................................72 
11. 
ASSESSMENTS .........................................................................................................73 
11.1. 
Informed Consent .......................................................................................................73 
11.2. 
Demographic and Baseline Characteristics Assessments ...........................................73 
11.2.1. 
Demographics .............................................................................................................73 
11.2.2. 
Medical History ..........................................................................................................73 
11.3. 
Efficacy Assessments .................................................................................................73 
11.3.1. 
Multiple Myeloma Disease Assessments ...................................................................73 
11.3.1.1. 
SPEP ...........................................................................................................................78 
11.3.1.2. 
UPEP ...........................................................................................................................78 
11.3.1.3. 
Quantitative Immunoglobulin Levels .........................................................................78 
11.3.1.4. 
Serum FLC ..................................................................................................................78 
11.3.1.5. 
β2 microglobulin .........................................................................................................78 
11.3.1.6. 
LDH ............................................................................................................................78 
11.3.1.7. 
Skeletal Survey ...........................................................................................................78 
11.3.1.8. 
Clinical Plasmacytoma Assessment ...........................................................................79 
11.3.1.9. 
Bone Marrow Aspirate ...............................................................................................79 
11.3.1.10. Bone Marrow Core (Trephine) Biopsy .......................................................................80 
11.4. 
Pharmacokinetic and Pharmacodynamic Procedures .................................................80 

Investigational Product (KPT-330)  
 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
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11.4.1. 
Pharmacokinetic Endpoints ........................................................................................80 
11.4.2. 
Pharmacodynamic Studies ..........................................................................................81 
11.4.2.1. 
Bone Marrow Aspirates for PDn ................................................................................81 
11.5. 
Safety Assessments .....................................................................................................81 
11.5.1. 
Clinical Safety Assessments .......................................................................................81 
11.5.1.1. 
Weight, Height, and BSA ...........................................................................................81 
11.5.1.2. 
Physical Examination, Vital Signs, and ECOG Performance Status ..........................81 
11.5.1.3. 
Electrocardiography ....................................................................................................82 
11.5.1.4. 
Ophthalmic Examination ............................................................................................82 
11.5.1.5. 
Concomitant Medications ...........................................................................................83 
11.5.1.6. 
Adverse Events ...........................................................................................................83 
11.5.2. 
Laboratory Safety Assessments ..................................................................................83 
11.5.2.1. 
Clinical Laboratory Tests ...........................................................................................83 
11.5.2.2. 
Pregnancy Testing ......................................................................................................84 
11.6. 
QoL Assessments ........................................................................................................84 
11.7. 
Other Assessments ......................................................................................................85 
11.7.1. 
C-reactive Protein and Collection of Information on Antineoplastic Therapy ...........85 
11.7.2. 
Nutritional Consultation .............................................................................................85 
11.7.3. 
Telephone Contacts ....................................................................................................85 
11.7.4. 
Durability of Response and Survival Follow-up Visit(s) ...........................................85 
12. 
SAFETY DEFINITIONS, RECORDING, AND REPORTING ................................86 
12.1. 
Adverse Events ...........................................................................................................86 
12.1.1. 
Definitions ..................................................................................................................86 
12.1.2. 
Recording of Adverse Events .....................................................................................86 
12.1.2.1. 
Laboratory Test Abnormalities ...................................................................................87 
12.1.2.2. 
Adverse Events of Special Interest .............................................................................87 
12.1.2.3. 
Other Adverse Events .................................................................................................87 
12.1.3. 
Adverse Event Severity ..............................................................................................88 
12.1.4. 
Adverse Event Causality .............................................................................................88 
12.2. 
Serious Adverse Events ..............................................................................................88 
12.2.1. 
Events that Do Not Meet the Definition of a Serious Adverse Event ........................89 
12.2.2. 
Recording of Serious Adverse Events ........................................................................89 
12.2.3. 
Reporting of Serious Adverse Events .........................................................................89 

Investigational Product (KPT-330)  
 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
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12.2.4. 
Suspected Unexpected Serious Adverse Reactions ....................................................90 
12.3. 
Procedures for Handling Special Situations ...............................................................90 
12.3.1. 
Pregnancy and Breastfeeding .....................................................................................90 
12.3.2. 
Overdose, Abuse, Misuse, Medication Errors, and Occupational Exposure ..............91 
12.3.2.1. 
Overdose .....................................................................................................................91 
12.3.2.2. 
Abuse, Misuse, or Medication Error ...........................................................................92 
12.3.2.3. 
Occupational Exposure ...............................................................................................92 
13. 
STATISTICAL METHODS .......................................................................................93 
13.1. 
General Considerations ...............................................................................................93 
13.2. 
Determination of Sample Size ....................................................................................93 
13.2.1. 
Interim Analyses .........................................................................................................93 
13.2.1.1. 
Interim Analysis of PFS for Sample Size Re-estimation ............................................93 
13.2.1.2. 
Interim Analysis of PFS for Futility or Superiority ....................................................94 
13.3. 
Analysis Populations ..................................................................................................94 
13.3.1. 
Intent-to-Treat Population ..........................................................................................94 
13.3.2. 
Per-protocol Population ..............................................................................................94 
13.3.3. 
SVdX (Crossover from Vd) Population .....................................................................94 
13.3.4. 
SdX (Crossover from Vd) Population ........................................................................95 
13.3.5. 
Safety Population ........................................................................................................95 
13.4. 
Data Analysis and Presentation ..................................................................................95 
13.4.1. 
Procedures for Handling Missing Data .......................................................................95 
13.4.2. 
Patient Disposition ......................................................................................................95 
13.4.3. 
Demographic Characteristics ......................................................................................96 
13.4.4. 
Baseline Characteristics and Medical History ............................................................96 
13.5. 
Efficacy Analysis ........................................................................................................96 
13.5.1. 
Primary Analysis for PFS ...........................................................................................96 
13.5.2. 
Analyses of the Key Secondary Endpoints .................................................................97 
13.5.2.1. 
Overall Response Rate ................................................................................................97 
13.5.2.2. 
Incidence of Any Grade ≥2 Peripheral Neuropathy Events .......................................98 
13.5.2.3. 
Response Rate for Responses ≥VGPR Based on the IRC’s Assessment ...................98 
13.5.3. 
Analyses of the Non-Key Secondary Effiacy Endpoints ............................................98 
13.5.4. 
Exploratory Analyses ..................................................................................................99 
13.6. 
Pharmacokinetic Analysis ........................................................................................100 

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Clinical Study Protocol: KCP-330-023 
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13.7. 
Safety Analysis .........................................................................................................100 
13.7.1. 
Analysis of the Key Secondary Safety Endpoint ......................................................101 
13.7.1.1. 
Peripheral Neuropathy Events ..................................................................................101 
13.7.2. 
Analyses of the Non-Key Secondary Safety Endpoints ...........................................101 
13.7.2.1. 
Study Treatment Exposure .......................................................................................101 
13.7.2.2. 
Adverse Events .........................................................................................................101 
13.7.2.3. 
Clinical Laboratory Data ..........................................................................................102 
13.7.2.4. 
Vital Signs and Physical Examinations ....................................................................102 
13.7.2.5. 
Electrocardiogram .....................................................................................................102 
13.7.2.6. 
Ophthalmological Examinations ..............................................................................102 
13.7.2.7. 
Concomitant Medications .........................................................................................103 
13.8. 
QoL Analyses ...........................................................................................................103 
13.9. 
Changes in the Conduct of the Study or Planned Analyses ......................................103 
14. 
ADMINISTRATIVE MATTERS ............................................................................104 
14.1. 
Regulatory and Ethical Compliance .........................................................................104 
14.2. 
Ethics Committees ....................................................................................................104 
14.3. 
Regulatory Authority Approval ................................................................................104 
14.4. 
Protocol Adherence ..................................................................................................104 
14.5. 
Amendments to the Protocol ....................................................................................104 
14.6. 
Informed Consent .....................................................................................................104 
14.7. 
Patient Confidentiality and Disclosure .....................................................................105 
14.8. 
Study Documentation, Data Collection and Storage, and Study Monitoring 
and Auditing Procedures ...........................................................................................105 
14.8.1. 
Study Documentation, Record Keeping, and Retention of Documents ...................105 
14.8.2. 
Study Monitoring and Auditing Procedures .............................................................106 
14.9. 
Disclosure of Information .........................................................................................106 
14.10. 
Discontinuation of the Study ....................................................................................106 
14.11. 
Study Report and Publication Policy ........................................................................107 
15. 
LIST OF REFERENCES ..........................................................................................108 
APPENDIX 1. PROTOCOL AMENDENT: RATIONALES AND SUMMARY OF 
CHANGES ...............................................................................................................112 
  
 

Investigational Product (KPT-330)  
 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
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Page 11 
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LIST OF TABLES 
Table 1: 
Abbreviations and Definitions of Terms ....................................................................12 
Table 2: 
Schedule of Assessments for Study KCP-330-023 ....................................................22 
Table 3: 
Unique Visits Required for Crossover to SVdX or SdX: Separate OR 
Combined Visits .........................................................................................................28 
Table 4: 
SVd Arm: Schedule of Visits for In-clinic Dosing and MM Evaluations ..................29 
Table 5: 
Vd Arm: Schedule of Visits for In-clinic Dosing and MM Evaluations ....................29 
Table 6: 
SVdX Treatment: Schedule of Visits for In-clinic Dosing and MM 
Evaluations .................................................................................................................30 
Table 7: 
SdX Treatment: Schedule of Visits for In-clinic Dosing and MM Evaluations .........30 
Table 8: 
SVd Arm/SVdX Treatment Dose Schedule; 5-Week (35-Day) Cycle .......................31 
Table 9: 
Dose Schedule for Vd Arm Cycles 1 through 8; 3-Week (21-day) Cycle .................32 
Table 10: Dose Schedule for Vd Arm Cycles ≥9; 5-Week (35-day) Cycle ................................32 
Table 11: Dose Schedule for SdX Patients; 5-Week (35-Day) Cycle ........................................33 
Table 12: KCP-330-017 Best Responses in Evaluable SVd Patients as of 05 June 2018 ..........39 
Table 13: In-clinic Dosing and MM Evaluations .......................................................................48 
Table 14: Revised International Staging System for Multiple Myeloma ...................................56 
Table 15: Pre-specified Dose Modifications for AEs Related to Selinexor ...............................63 
Table 16: Supportive Care and Selinexor Dose Adjustment Guidelines for AEs Related 
to Selinexor .................................................................................................................64 
Table 17: International Myeloma Working Group Response Criteria, Myeloma 
(Kumar, 2016) .............................................................................................................74 
Table 18: Collection Time Points for Bortezomib and Selinexor PK ........................................80 
Table 19:  Clinical Laboratory Tests ...........................................................................................83 
 
LIST OF FIGURES 
Figure 1: 
Study KCP-330-023 Overview ...................................................................................34 
 

Investigational Product (KPT-330)  
 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
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1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Definitions of Terms 
Abbreviation or Specialist Term 
Explanation 
5-HT3 
5-hydroxytryptamine 
ACS 
American Cancer Society 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
AOA 
American Optometric Association 
API 
active pharmaceutical ingredient 
ASCT 
autologous stem-cell transplantation 
AST 
aspartate aminotransferase 
AUC 
area under the concentration versus time curve 
AUC0-∞ 
area under the concentration versus time curve from the time of 
dosing extrapolated to infinity 
BIW 
twice weekly 
bort 
bortezomib 
BP 
blood pressure 
BSA 
body surface area 
C 
visit for in-clinic dosing only 
CA 
chromosomal abnormalities 
CBC 
complete blood count 
CI 
confidence interval 
CIPN20 
Chemotherapy-induced Peripheral Neuropathy 
Cmax 
maximum plasma concentration 
CMH 
Cochran-Mantel-Haenszel 
CR 
complete response 
CRAB features 
calcium elevation, renal failure, anemia, lytic bone lesions 
CrCl 
creatinine clearance 
CRM1 
chromosome region maintenance protein 1 
CSR 
clinical study report 

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Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 14 
Version 4.0 
Abbreviation or Specialist Term 
Explanation 
iFISH 
interphase fluorescence in situ hybridization 
IMWG 
International Myeloma Working Group 
IRB 
Institutional Review Board 
IRC 
Independent Review Committee 
ISS 
International Staging System 
ITT 
intent-to-treat 
IV 
intravenous 
Karyopharm 
Karyopharm Therapeutics Inc. 
KPT-330 
selinexor 
KM 
Kaplan-Meier 
LDH 
lactate dehydrogenase 
M 
visit for MM disease assessments only 
mAb 
monoclonal antibody 
MAP 
maximum a posteriori 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
minutes 
MM 
multiple myeloma 
MR 
minimal response 
MRD 
minimal residual disease 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NGF 
next generation flow 
NGS 
next generation sequencing 
NHL 
non-Hodgkin’s lymphoma 
ORR 
overall response rate 
ORR1 
overall response rate during SVdX treatment 
OS 
overall survival 
PD 
progressive disease 
PDn 
pharmacodynamics 
PE 
physical examination 

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Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 16 
Version 4.0 
Abbreviation or Specialist Term 
Explanation 
SPEP 
serum protein electrophoresis 
Study Manual 
Manual for the study site that may include any of the following: 
Laboratory Manual, Pharmacy Manual, Investigator Binder, 
Case Report Form Guidelines, Interactive Response 
Technologies User Guidelines, and any other site materials that 
are generated for the study such as Imaging Guidelines, etc. 
SUSAR 
suspected unexpected serious adverse reaction 
SVd 
selinexor plus bortezomib plus low-dose dexamethasone 
SVdX 
SVd treatment after crossover  
TEAE 
treatment-emergent adverse event 
t½  
elimination (terminal) half-life 
TLS 
tumor lysis syndrome 
tmax  
time to peak plasma concentration 
TSP 
tumor suppressor protein 
TTNT 
time-to-next-treatment 
TTR 
time to response 
ULN 
upper limit of normal 
UPEP 
urine protein electrophoresis 
URL 
uniform resource locator 
USA 
United States of America 
Vd 
bortezomib plus low-dose dexamethasone 
VGPR 
very good partial response 
WBC 
white blood cell 
X 
visit for in-clinic dosing and multiple myeloma disease 
assessment 
XPO1 
exportin 1 

Investigational Product (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 17 
Version 4.0 
2.
PROTOCOL SYNOPSIS
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Study Phase: 
Phase 3 
Title of Study: 
A Phase 3 Randomized, Controlled, Open-label Study of Selinexor, Bortezomib, and Dexamethasone 
(SVd) versus Bortezomib and Dexamethasone (Vd) in Patients with Relapsed or Refractory Multiple 
Myeloma (RRMM) 
Study Name:  
BOSTON: Bortezomib, Selinexor, and Dexamethasone in Patients with Multiple Myeloma 
Protocol Number: KCP-330-023 
Indication: Relapsed or refractory multiple myeloma (RRMM) 
Overall Study Design: This Phase 3, 2-arm, randomized, active comparator-controlled, open-label, 
multicenter study will compare the efficacy and health-related quality of life (HR-QoL) and assess the 
safety of selinexor plus bortezomib (Velcade® or generic equivalent) plus low-dose dexamethasone 
(SVd) versus bortezomib plus low-dose dexamethasone (Vd) in adult patients with RRMM who have 
received 1 to 3 prior anti-multiple myeloma (MM) regimens. After progressive disease (PD) is 
confirmed by the Independent Review Committee (IRC), patients in the Vd Arm may cross over to a 
regimen that includes selinexor: 1) SVd treatment (SVdX) for patients who are able to tolerate continued 
bortezomib, or 2) selinexor and dexamethasone treatment (SdX) for patients who have significant 
tolerability issues with bortezomib. Patients who cross over will be referred to as SVdX patients or SdX 
patients, respectively. 
The study overview is presented in the figure below. 
Abbreviations: IA = interim analysis; IRC = Independent Review Committee; ITT = intent-to-treat; PD = progressive disease; 
PFS = progression-free survival; SdX= selinexor plus low-dose dexamethasone treatment after crossover; SVd = selinexor plus 
bortezomib plus low-dose dexamethasone; SVdX = SVd treatment after crossover; Vd = bortezomib plus low-dose 
dexamethasone. 

Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 18 
Version 4.0 
Study Rationale: 
This study is based on preliminary supportive data from patients with relapsed MM treated with SVd in 
Study KCP-330-017 (STOMP; NCT02343042) demonstrating that SVd has very high levels of 
anti-myeloma activity, even in patients with proteasome-inhibitor (PI)-refractory disease, with relatively 
low adverse event (AE) rates. The majority of patients in Study KCP-330-017 (STOMP) were treated 
with once weekly (QW) bortezomib. 
Crossover of patients on the control arm (Vd Arm) to SVdX will allow for direct assessment of 
selinexor’s ability to restore sensitivity in PI-resistant MM. 
The QW regimen of SVd, based on Study KCP-330-017 (STOMP), provides for a considerable 
reduction (~40%) in overall bortezomib dose versus the control arm (Vd Arm) that, in addition to the 
relatively low dose of selinexor, may be associated with better tolerability (eg, peripheral neuropathy) 
compared with second-line Vd and Vd-based combination regimens. Thus, this SVd regimen could 
serve a current and rapidly growing unmet medical need in patients with RRMM, providing for 
increased response rates and durability of response over Vd, with improved tolerability with respect to 
peripheral neuropathy-associated untoward effects of bortezomib. 
Objectives: 
Primary 
Disease response will be assessed according to the International Myeloma Working Group (IMWG) 
response criteria based on Kumar (Kumar 2016). 
• 
To compare progression-free survival (PFS) based on the IRC’s disease outcome assessments in 
patients randomized to the SVd Arm versus the Vd Arm 
Secondary 
• 
To compare the overall response rate (ORR) (≥ partial response [PR]) based on the IRC’s 
response outcome assessments in patients randomized to the SVd Arm versus the Vd Arm 
• 
To compare the incidence of any Grade ≥2 peripheral neuropathy events in patients randomized 
to the SVd Arm versus patients randomized to the Vd Arm 
• 
To compare the number of patients with response ≥ very good partial response (VGPR), 
≥ complete response (CR), ≥ stringent complete response (sCR), or minimal residual disease 
(MRD) negative (for patients who achieve CR or sCR) in patients randomized to the SVd Arm 
versus the Vd Arm 
• 
To compare overall survival (OS) in all patients randomized to the SVd Arm versus the Vd Arm 
• 
To compare the duration of response (DOR) in patients randomized to the SVd Arm versus the 
Vd Arm 
• 
To determine ORR1 (ORR during SVdX treatment only) 
• 
To determine PFS1 (PFS during SVdX treatment only) 
• 
To compare time-to-next-treatment (TTNT) in patients randomized to the SVd Arm versus the 
Vd Arm who receive post-SVd/Vd/SVdX/SdX treatment 
• 
To compare time-to-response (TTR) in patients randomized to the SVd Arm versus the Vd Arm 
• 
To assess the safety and tolerability of treatment with SVd versus Vd in patients with RRMM 

Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 19 
Version 4.0 
• 
To compare patient-reported peripheral neuropathy as measured by the European Organization 
for Research and Treatment of Cancer (EORTC) Chemotherapy-induced Peripheral Neuropathy 
(QLQ-CIPN20) instrument in patients randomized to the SVd Arm versus the Vd Arm 
Endpoints:  
Primary Endpoint 
• 
PFS, defined as time from date of randomization until the first date of PD, per IMWG response 
criteria, or death due to any cause, whichever occurs first. For the purposes of PFS 
determination, PD will be determined by the IRC. 
Key Secondary Efficacy Endpoints 
• 
ORR, defined as any response ≥PR (ie, PR, VGPR, CR, or sCR) based on the IRC’s response 
outcome assessments, according to the IMWG response criteria. All changes in MM disease 
assessments will be based on baseline MM disease assessments. 
• 
Response rates at any time prior to PD or death due to any cause, pooled and separately for the 
following responses: ≥VGPR, ≥CR, ≥sCR, or MRD negative (for patients who achieve CR or 
sCR) 
Non-Key Secondary Efficacy Endpoints 
• 
OS, defined as time to death or lost to follow-up, measured from the date of randomization until 
death due to any cause or until lost to follow-up, for all patients 
• 
DOR, defined as the duration of time from first occurrence of IRC-confirmed response ≥PR 
until the first date of IRC-confirmed PD or death due to any cause, whichever occurs first 
• 
ORR1 (ORR for SVdX patients only) 
• 
PFS1 (PFS for SVdX patients only), defined as the duration of time from date of first dose of 
SVd treatment after crossover from the Vd Arm until the first date of PD, or death due to any 
cause 
• 
TTNT, defined as duration of time from date of last dose of study treatment until the date of first 
dose of post-SVd/Vd/SVdX/SdX treatment 
• 
TTR, defined as duration of time from randomization until the date of first documented response 
(≥PR) per IMWG response criteria 
• 
PFS2 (PFS for patients who receive post-SVd/Vd/SVdX treatment), defined as the duration of 
time from the date of first dose of post-SVd/Vd/SVdX treatment until the first date of PD on 
post SVd/Vd/SVdX treatment, or death due to any cause 
Key Secondary Safety Endpoint 
• 
Incidence of any Grade ≥2 peripheral neuropathy events in patients randomized to the SVd Arm 
versus patients randomized to the Vd Arm. The incidence of any Grade ≥2 peripheral 
neuropathy events will be compared between the SVd Arm and the Vd Arm (using only events 
that occurred prior to crossover) as a secondary endpoint using the safety population. 
Non-Key Secondary Safety Endpoints 
• 
Safety and tolerability of study treatment based on AE reports, physical examination results 
(including vital signs), Eastern Cooperative Oncology Group (ECOG) performance status score, 

Investigational Product (KPT-330)  
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 20 
Version 4.0 
12-lead electrocardiogram (ECG) results, ophthalmic examination results, and clinical 
laboratory results 
Secondary HR-QoL Endpoint 
• 
Patient-reported peripheral neuropathy, as measured by the EORTC QLQ-CIPN20 instrument 
Study Location:  
Approximately 120 global investigative sites are planned. 
Number of Patients (planned):  
Approximately 364 patients will be randomized. The number of patients enrolled may be adjusted based 
on the results of the interim analysis (IA) for sample size re-estimation (first IA). 
Study Population: This study will enroll patients ≥18 years of age with RRMM who have received 1 to 
3 prior anti-MM regimens and who meet all of the inclusion criteria and none of the exclusion criteria.  
Randomization:  
Patients (~364) will be randomized to 1 of 2 treatment arms (SVd or Vd) in a 1:1 allocation, as follows: 
• 
SVd Arm (~182): selinexor + bortezomib (QW) + dexamethasone  
• 
Vd Arm (~182): bortezomib (Cycles 1-8 [twice weekly], Cycles ≥9 [QW]) + dexamethasone  
Randomization will be stratified based on the following stratification factors and will maintain the 1:1 
allocation between treatment arms (SVd, Vd) within each of the stratification categories: 
• 
Prior PI therapies (Yes or No) 
• 
Number of prior anti-MM regimens (1 versus >1) 
• 
Revised International Staging System (R-ISS) stage based on screening results (R-ISS Stage III 
versus R-ISS Stage I or II) (Palumbo 2015).  
It is planned to randomize patients within individual countries in a 1:1 allocation to SVd:Vd.  
Test Product, Dose, and Mode of Administration:  
SVd Arm: 
• 
Selinexor will be given as a fixed oral 100 mg dose (five 20 mg tablets) on Days 1, 8, 15, 22, 
and 29 of each 35-day cycle. 
• 
Bortezomib will be given at a dose of 1.3 mg/m2 SC on Days 1, 8, 15, and 22 of each 35-day 
cycle. 
• 
Dexamethasone will be given as an oral 20 mg dose on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 
30 of each 35-day cycle. 
Vd Arm: 
• 
Bortezomib will be given at a dose of 1.3 mg/m2 SC on Days 1, 4, 8, and 11 of each 21-day 
cycle for the first 8 cycles. For Cycles ≥9, bortezomib will be given at a dose of 1.3 mg/m2 SC 
on Days 1, 8, 15, and 22 of each 35-day cycle. 
• 
Dexamethasone will be given as an oral 20 mg dose on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 
21-day cycle for the first 8 cycles. For Cycles ≥9, dexamethasone will be given as an oral 20 mg 
dose on Days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each 35-day cycle. 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 22 
Version 4.0 
3. 
STUDY SCHEMATICS AND SCHEDULE OF ASSESSMENTS AND DOSING FOR 
STUDY KCP-330-023 
Table 2: Schedule of Assessments for Study KCP-330-023 
Activity/Assessmenta 
Section 
Screeningb 
C1 
C1 
Phone Call 
MM Disease 
Assessment 
Visits 
(Table 13) 
In-clinic Dosing 
Visits 
(> C1D2) 
(Table 13) 
EoT 
Visitc 
Safety 
Follow-
up Call 
Durability of 
Response and 
Survival 
Follow-up 
Visitd 
D -28 to -1 
D1e 
D3f 
(selinexor-
containing 
regimens 
only) 
See Table 4, 
Table 5, 
Table 6, and 
Table 7  
See Table 4, 
Table 5, 
Table 6, and 
Table 7  
≤14 
Days 
Post-
Last 
Dose 
30 days 
after last 
dose of 
treatment 
Every 
3 months 
until 
End-of-Study 
Section 11.7.4 
 
 
 
± 2 daysg 
± 2 days 
 
+ 7 days 
± 14 days 
ICFh 
11.1 
X 
 
 
 
 
 
 
 
Patient History 
Inclusion/Exclusion 
7.2/ 7.3  
X 
 
 
 
 
 
 
 
Demographics 
11.2.1 
X 
 
 
 
 
 
 
 
Medical History 
11.2.2 
X 
 
 
 
 
 
 
 
Clinical Assessments 
Height 
11.5.1.1 
X 
 
 
 
 
 
 
 
Weight 
11.5.1.1 
X 
X 
 
 
Xi 
(D1 of each 
cycle only) 
X 
 
 
BSAj 
11.5.1.1 
X 
X 
 
 
 
 
 
 
Vital signsk 
11.5.1.2 
X 
X 
 
Xl 
X 
X 
 
 
Complete PE 
11.5.1.2 
X 
 
 
 
 
X 
 
 
Symptom-directed 
PE 
11.5.1.2 
 
Perform if 
clinically 
indicated  
 
Perform if clinically indicated 
 
 
Perform if 
clinically 
indicated 
ECOG 
11.5.1.2 
X 
 
 
 
X 
(D1 of each 
cycle only) 
X 
 
 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 23 
Version 4.0 
Activity/Assessmenta 
Section 
Screeningb 
C1 
C1 
Phone Call 
MM Disease 
Assessment 
Visits 
(Table 13) 
In-clinic Dosing 
Visits 
(> C1D2) 
(Table 13) 
EoT 
Visitc 
Safety 
Follow-
up Call 
Durability of 
Response and 
Survival 
Follow-up 
Visitd 
D -28 to -1 
D1e 
D3f 
(selinexor-
containing 
regimens 
only) 
See Table 4, 
Table 5, 
Table 6, and 
Table 7  
See Table 4, 
Table 5, 
Table 6, and 
Table 7  
≤14 
Days 
Post-
Last 
Dose 
30 days 
after last 
dose of 
treatment 
Every 
3 months 
until 
End-of-Study 
Section 11.7.4 
 
 
 
± 2 daysg 
± 2 days 
 
+ 7 days 
± 14 days 
Ophthalmic 
examination 
11.5.1.4  
Xm 
 
Perform if clinically indicated 
X 
 
 
12-lead ECGn 
11.5.1.3  
Xm 
 
Perform if clinically indicated 
X 
 
 
Laboratory Assessments                                                              May be performed more frequently if clinically indicated, or at the Investigator’s discretion. 
Urinalysis 
11.5.2.1 
Xm 
 
 
 
X 
 
 
CBC with 
differential 
11.5.2.1 
Xo 
 
X 
X 
(C1D8 only) 
X 
 
 
Complete serum 
chemistry 
11.5.2.1 
X 
X 
 
X 
X 
(C1D8 only) 
X 
 
 
Coagulation tests 
11.5.2.1 
Xm 
 
 
 
X 
 
 
Pregnancy test (if 
applicable)p 
11.5.2.2 
X 
 
 
 
X 
(D1 of each 
cycle only) 
X 
 
 
C-reactive protein 
11.7.1 
Xm 
 
 
 
X 
 
 
PK at Selected Investigational Sites (up to 25 patients per arm) 
Vd Arm subset: 
Blood draws for 
bortezomib PK 
testing  
11.4  
 
 
 
X 
(C2D11 only)q 
 
 
 
SVd Arm subset: 
Blood draws for 
bortezomib and 
selinexor PK testing  
11.4  
 
 
 
X 
(C2D15 only)q 
 
 
 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 24 
Version 4.0 
Activity/Assessmenta 
Section 
Screeningb 
C1 
C1 
Phone Call 
MM Disease 
Assessment 
Visits 
(Table 13) 
In-clinic Dosing 
Visits 
(> C1D2) 
(Table 13) 
EoT 
Visitc 
Safety 
Follow-
up Call 
Durability of 
Response and 
Survival 
Follow-up 
Visitd 
D -28 to -1 
D1e 
D3f 
(selinexor-
containing 
regimens 
only) 
See Table 4, 
Table 5, 
Table 6, and 
Table 7  
See Table 4, 
Table 5, 
Table 6, and 
Table 7  
≤14 
Days 
Post-
Last 
Dose 
30 days 
after last 
dose of 
treatment 
Every 
3 months 
until 
End-of-Study 
Section 11.7.4 
 
 
 
± 2 daysg 
± 2 days 
 
+ 7 days 
± 14 days 
Multiple Myeloma Disease Assessmentsg, r 
SPEP with serum 
protein 
immunofixations 
11.3.1.1 
X 
X 
 
X 
 
X 
 
X 
UPEP (24-hr urine) 
and urine protein 
immunofixations 
11.3.1.2 
X 
X 
 
X 
 
X 
 
X 
Quantitative Ig levels 
11.3.1.3 
X 
X 
 
X 
 
X 
 
X 
Serum FLCs 
11.3.1.4 
X 
X 
 
X 
 
X 
 
X 
β2-microglobulin 
11.3.1.5 
X 
 
 
 
 
X 
 
 
LDH 
11.3.1.6 
Xo 
 
 
 
X 
 
 
Skeletal surveyt 
11.3.1.7 
X 
 
 
Frequency determined by the 
Investigator 
X 
 
Perform if 
clinically 
indicated 
Clinical 
plasmacytoma 
assessments, u 
11.3.1.8 
X 
X 
 
Perform if 
clinically 
indicated 
 
X 
 
Perform if 
clinically 
indicated 
Bone marrow 
aspiratev 
11.3.1.9 
 
X 
 
 
At the time of response for the MRD test for 
patients who achieve CR or sCR 
 
Perform if 
clinically 
indicated 
Bone marrow core 
(trephine) biopsyw 
11.3.1.10 
 
 
 
At the time of response to confirm CR or 
sCR 
 
 
HR-QoLx 
11.6  
X 
 
 
 
X  
(D1 of each 
cycle only) 
X 
 
 
Randomization 
8.2  
Prior to dosing of Vd/SVd 
 
 
 
 
 
 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 26 
Version 4.0 
d After discontinuation of SVd, Vd, SVdX, or SdX if feasible and clinically indicated, MM evaluations should be performed every 3 months for patients who 
have not progressed to assess durability of response. If MM evaluations cannot be performed, at a minimum, a telephone call will be made to the patient (or the 
patient’s family) to assess the survival status, status of the patient’s MM, and overall medical condition of the patient and collect information on any 
antineoplastic therapies used after discontinuation of study treatment (see Section 11.7.4). 
e SVdX/SdX patients will return to Cycle 1 for SVdX/SdX treatment. See Table 3. 
f Only for patients being treated with selinexor-containing regimens: Telephone call with patient to evaluate supportive care medications, concomitant 
medications, and AEs, and to adjust supportive care as appropriate. The telephone contact with the patient must take place on C1D3. 
g The window of ± 2 days for MM disease assessments that fall on in-clinic dosing visits may be extended to ± 7 days for MM disease assessments that fall on a 
day when dosing in the clinic is not required (eg, C10D29). 
h ICF must be signed before any study-specific procedures are performed. 
i If the patient’s weight fluctuates substantially from baseline (ie, >20%) during treatment, BSA should be recalculated. 
j BSA will be calculated on C1D1 to determine the volume of bortezomib to be administered and to ensure that no patient receives a dose of selinexor 
>70 mg/m2. 
k BP and pulse rate should be measured after the patient has been in a supine or sitting position for 5 minutes. BP should be assessed on the same arm throughout 
the study. Vital signs do not need to be repeated if they are performed as part of the physical examination.  
l If the visit for MM disease assessments occurs on the same day as the in-clinic dosing visit, vital signs should only be performed once. 
m The following assessments may be performed between Day -28 and prior to administration of study treatment on C1D1: ophthalmic examination, 12-lead ECG, 
urinalysis, coagulation tests, C-reactive protein, and nutritional consultation. 
n Patients must rest for at least 5 minutes prior to the ECG recording. 
o CBC with differential and LDH may be performed between Day -7 and administration of study treatment on C1D1. 
p For females of childbearing potential; negative serum hCG pregnancy test must be obtained within 3 days before the first dose of study treatment. Pregnancy 
testing (serum hCG or urine) is also required for females of childbearing potential prior to dosing on Day 1 of Cycles ≥2 while on treatment (a negative 
pregnancy test must be documented prior to administration of study drug) and at the EoT Visit (serum hCG). Pregnancy testing may also be performed as 
clinically indicated during the study. 
q Perform blood draws for PK analysis at the time points in Table 18. PK sampling for bortezomib will be performed for up to 25 patients in the Vd Arm and PK 
sampling for bortezomib and selinexor will be performed for up to 25 patients in the SVd Arm at selected investigational sites that can accommodate patients 
for up to 4 hours. Details for PK sample collection and processing can be found in the Study Manual. 
r Patients randomized to the SVd Arm who have IRC-confirmed PD while they are on SVd treatment will discontinue SVd treatment, proceed to the EoT Visit, 
and be followed for survival. Patients randomized to the Vd Arm who have IRC-confirmed PD while they are on Vd treatment and meet the criteria in 
Section 6.2 may cross over to a regimen that includes selinexor (Table 3): 1) SVd treatment (SVdX) for patients who are able to tolerate continued bortezomib, 
or 2) selinexor and dexamethasone treatment (SdX) for patients who have significant tolerability issues with bortezomib. Patients who do not elect to cross over 
to SVdX or SdX from the Vd Arm will discontinue treatment, proceed to the EoT Visit, and be followed for survival. 
s Samples for MM disease assessments on C1D1 must be collected either on Day -1 or predose on C1D1 for baseline values. For patients who achieve CR or 
sCR, confirmatory samples for SPEP with serum protein immunofixation, quantitative Ig, and serum FLC must be collected in duplicate at the time of response 
and the duplicate samples must be provided to the central laboratory. A confirmatory 24-hour urine sample must also be collected and an aliquot will be 
provided to the central laboratory for UPEP with urine protein immunofixation. Refer to the Study Manual for details. 
t A baseline skeletal survey is to be performed within 45 days prior to C1D1. Skeletal imaging does not need to be repeated in Cycle 1. Skeletal survey results 
will be read by the local laboratory. 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 28 
Version 4.0 
Patients who cross over to SVdX or SdX after IRC-confirmed PD, will have an End of Vd Treatment Visit and a C1D1 Visit for 
SVdX or SdX Treatment (Table 3). At the discretion of the Investigator, these visits may be combined. After the C1D1 Visit for 
SVdX or SdX Treatment, SVdX and SdX patients will follow the schedule in Table 2. 
SVdX (Table 6) and SdX (Table 7) patients will undergo MM evaluations every 5 weeks. 
Table 3: 
Unique Visits Required for Crossover to SVdX or SdX: Separate OR Combined Visits 
Separate Visits 
Combined Visitsa 
End of Vd Treatment Visit 
(within 14 days after IRC PD 
confirmationb) 
 
Separate C1D1 Visit for SVdX or SdX 
Treatmentc 
(>5 days and ≤14 days after IRC PD 
confirmation)b 
End of Vd Treatment Visit and C1D1 Visit 
for SVdX or SdX Treatment Combined 
(>5 days and ≤14 days after IRC PD 
confirmation)b 
Informed consent for SVdX or SdX 
treatmentd 
 
Informed consent for SVdX or SdX treatmentd 
All assessments for EoT Visit in 
Table 2, including MM disease 
assessments (SPEP, UPEP, serum 
protein and urine protein 
immunofixation, quantitative Ig, serum 
FLC, and clinical plasmacytoma 
assessment) 
MM disease assessments (SPEP, UPEP, 
serum protein and urine protein 
immunofixation, quantitative Ig, serum FLC, 
and clinical plasmacytoma assessment)  
All assessments for EoT Visit in Table 2, 
including MM disease assessments (SPEP, 
UPEP, serum protein and urine protein 
immunofixation, quantitative Ig, serum FLC, 
and clinical plasmacytoma assessment)  
 
BSA 
Vital signs 
Nutritional consultation 
BSA 
Vital signs 
Nutritional consultation 
Abbreviations: BSA = body surface area; EoT = end of treatment; FLC = free light chain; Ig = immunoglobulin; IRC = Independent Review Committee; MM = multiple 
myeloma; PD = progressive disease; SdX = selinexor plus low-dose dexamethasone treatment after crossover; SPEP = serum protein electrophoresis; SVd = selinexor 
plus bortezomib plus low-dose dexamethasone; SVdX = SVd treatment after crossover; UPEP = urine protein electrophoresis; Vd = bortezomib plus 
lowdose- dexamethasone. 
a The End of Vd Treatment Visit and the C1D1 Visit for SVdX or SdX treatment may be combined at the discretion of the Investigator. 
b PD confirmation date is the date the IRC informs the site that PD has been confirmed. 
c If the C1D1 Visit for SVdX/SdX Treatment is a separate visit from the End of Vd Treatment Visit, the clinical and laboratory assessments performed at the End 
of Vd Treatment Visit do not need to be repeated and the symptom-directed physical examination listed for C1D1 in Table 2 does not need to be performed. 
However, MM disease assessments and the nutritional consultation must be performed on C1D1. 
d Informed consent for SVdX/SdX treatment must be signed before conducting any study-specific procedures for SVdX/SdX. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 29 
Version 4.0 
3.1. 
Schedules of Visits for In-clinic Dosing and MM Evaluations 
Table 4: 
SVd Arm: Schedule of Visits for In-clinic Dosing and MM Evaluations 
Cycles 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
1 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
M* 
 
 
 
 
 
 
3 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
M* 
 
 
 
 
 
 
6 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
7 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
≥8 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: X = Visit for in-clinic dosing and MM disease assessment; C = Visit for in-clinic dosing only; M = Visit for MM disease assessments only; MM = multiple 
myeloma; SVd = selinexor plus bortezomib plus low-dose dexamethasone. 
*Note: On C2D29 and C5D29, selinexor and dexamethasone dosing should be performed in the clinic during MM disease assessment visits. 
 
Table 5: 
Vd Arm: Schedule of Visits for In-clinic Dosing and MM Evaluations 
Cycles 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
1 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8 
X 
 
 
C 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
10 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
M 
 
 
 
 
 
 
≥11 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: X = Visit for in-clinic dosing and MM disease assessment; C = Visit for in-clinic dosing only; M = Visit for MM disease assessments only; MM = multiple 
myeloma; Vd = bortezomib plus low-dose dexamethasone. 

Investigational Product (KPT-330) 
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Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 30 
Version 4.0 
Table 6: 
SVdX Treatment: Schedule of Visits for In-clinic Dosing and MM Evaluations 
Cycles 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
≥1 
X 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: X = Visit for in-clinic dosing and MM disease assessment; C = Visit for in-clinic dosing only; MM = multiple myeloma; SVd = selinexor plus bortezomib plus 
low-dose dexamethasone; SVdX = SVd treatment after crossover. 
Note: SVdX will follow the dose schedule for SVd (Table 8). 
Table 7: 
SdX Treatment: Schedule of Visits for In-clinic Dosing and MM Evaluations 
Cycles 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
≥1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: X = Visit for in-clinic dosing and MM disease assessment; MM = multiple myeloma; SdX = selinexor plus low-dose dexamethasone treatment after crossover. 
Note: SdX will follow the dose schedule in Table 11. 

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3.2. 
Dose Schedules 
Table 8: 
SVd Arm/SVdX Treatment Dose Schedule; 5-Week (35-Day) Cycle 
SVd/ 
SVdXa 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29
30 
31 
32 
33 
34 
35 
SVd/SVdX Dose Schedule 
Selb 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Bortc 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Rest period 
Dexd 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
Selinexor Dose Escalation for Cycles ≥3: 
Only Considered for Patients in the SVd Arm or on SVdX Treatment Who Meet the Following 3 Criteria: 1) Do Not Achieve At Least a PR Within the 
First 2 Cycles, 2) Are Tolerating SVd or SVdX Well at Dose Level 0, and 3) Do Not Have Any AEs Related to Study Treatment Grade >2 (NCI 
CTCAE v. 4.03) at the Time of Dose Escalation 
Sele 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
Bortc 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Rest period 
Dexd 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
Abbreviations: AE = adverse event; BIW = twice weekly; Bort = bortezomib; BSA = body surface area; CTCAE = Common Terminology Criteria for Adverse Events; D = day; 
Dex = dexamethasone; eCRF = electronic case report form; MM = multiple myeloma; NCI = National Cancer Institute; PR = partial response: QW = once weekly; SC = 
subcutaneous; Sel = selinexor; SVd = selinexor plus bortezomib plus low-dose dexamethasone. 
a If the patient’s weight fluctuates substantially from baseline (ie, >20%) during treatment, BSA should be recalculated. 
b Selinexor will be given as a fixed oral 100 mg dose QW. In no case may the selinexor dose exceed 70 mg/m2 per dose for any patient. 
c Bortezomib will be given at a dose of 1.3 mg/m2 SC QW during Weeks 1 through 4, followed by a 13-day rest period. 
d Dexamethasone will be given as an oral 20 mg dose BIW (ie, a total of 40 mg weekly). For patients who develop partial intolerance to glucocorticoids during 
the study (as determined by the Investigator), a dose reduction to a minimum dose of 10 to 12 mg dexamethasone BIW (ie, a total of 20 to 24 mg weekly) is 
permitted after a clear documentation of intolerance. Any dose reductions should be documented in the patient’s research record and the eCRF. 
e Selinexor may be given as a fixed oral 60 mg dose BIW during Weeks 1 through 5 of Cycles ≥3. 

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Table 9: 
Dose Schedule for Vd Arm Cycles 1 through 8; 3-Week (21-day) Cycle 
Vd 
Week 1 
Week 2 
Week 3 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Borta 
X 
 
 
X 
 
 
 
X 
 
 
X 
Rest period 
Dexb 
X 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
Abbreviations: BIW = twice weekly; Bort = bortezomib; Dex = dexamethasone; eCRF = electronic case report form; SC = subcutaneous; Sel = selinexor; QIW = 4 times per 
week; Vd = bortezomib plus low-dose dexamethasone. 
a Bortezomib will be given at a dose of 1.3 mg/m2 SC BIW during Weeks 1 and 2 of each cycle, followed by a 10-day rest period. If the patient’s weight 
fluctuates substantially from baseline (ie, >20%) during treatment, BSA should be recalculated.  
b Dexamethasone will be given as an oral 20 mg dose QIW (ie, a total of 80 mg weekly) during Weeks 1 and 2 of each cycle. For patients who develop partial 
intolerance to glucocorticoids during the study (as determined by the Investigator), a dose reduction to a minimum dose of 10 to 12 mg dexamethasone BIW 
(ie, a total of 20 to 24 mg weekly) is permitted after a clear documentation of intolerance. Any dose reductions should be documented in the patient’s research 
record and the eCRF. 
Table 10: 
Dose Schedule for Vd Arm Cycles ≥9; 5-Week (35-day) Cycle 
Vd 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
Borta 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Rest period 
Dexb 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
Abbreviations: BIW = twice weekly; Bort = bortezomib; D = day; Dex = dexamethasone; eCRF = electronic case report form; QW = once weekly; SC = subcutaneous; 
Sel = selinexor; Vd = bortezomib plus low-dose dexamethasone. 
a Bortezomib will be given at a dose of 1.3 mg/m2 SC QW during Weeks 1 through 4, followed by a 13-day rest period. If the patient’s weight fluctuates 
substantially from baseline (ie, >20%) during treatment, BSA should be recalculated. 
b Dexamethasone will be given as an oral 20 mg dose BIW (ie, a total of 40 mg weekly) during Weeks 1 through 5. For patients who develop partial intolerance 
to glucocorticoids during the study (as determined by the Investigator), a dose reduction to a minimum dose of 10 to 12 mg dexamethasone BIW (ie, a total of 
20 to 24 mg weekly) is permitted after a clear documentation of intolerance. Any dose reductions should be documented in the patient’s research record and the 
eCRF. 
 

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Table 11: 
Dose Schedule for SdX Patients; 5-Week (35-Day) Cycle 
Sda 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Day 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21
1 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
33 
34 
35 
Sd Dose Schedule 
Selb 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Dexc 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
X X 
 
 
 
 
 
Selinexor Dose Escalation for Cycles ≥3: 
Only Considered for Patients Who Meet the Following 3 Criteria: 1) Do Not Achieve At Least a PR Within the First 2 Cycles on Sd, and 2) Are 
Tolerating Sd Well at Dose Level 0, and 3) Do Not Have Any AEs Related to Study Treatment Grade >2 (NCI CTCAE v. 4.03) at the Time of Dose 
Escalation 
Seld 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
Dexc 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
Abbreviations: AE = adverse event; BIW = twice weekly; BSA = body surface area; CTCAE = Common Terminology Criteria for Adverse Events; D = day; 
Dex = dexamethasone; eCRF = electronic case report form; MM = multiple myeloma; NCI = National Cancer Institute; PR = partial response: QW = once weekly; 
SC = subcutaneous; Sel = selinexor; Sd = selinexor plus low-dose dexamethasone. 
a If the patient’s weight fluctuates substantially from baseline (ie, >20%) during treatment, BSA should be recalculated. 
b Selinexor will be given as a fixed oral 100 mg dose QW. In no case may the selinexor dose exceed 70 mg/m2 per dose for any patient. 
c Dexamethasone will be given as an oral 20 mg dose BIW (ie, a total of 40 mg weekly). For patients who develop partial intolerance to glucocorticoids during 
the study (as determined by the Investigator), a dose reduction to a minimum dose of 10 to 12 mg dexamethasone BIW (ie, a total of 20 to 24 mg weekly) is 
permitted after a clear documentation of intolerance. Any dose reductions should be documented in the patient’s research record and the eCRF. 
d Selinexor may be given as a fixed oral 60 mg dose BIW during Weeks 1 through 5 of Cycles ≥3. 
 
 

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Figure 1: 
Study KCP-330-023 Overview 
 
Abbreviations: IA = interim analysis; IRC = Independent Review Committee; ITT = intent-to-treat; PD = progressive disease; PFS = progression-free survival; SdX = selinexor 
plus low-dose dexamethasone treatment after crossover; SVd = selinexor plus bortezomib plus low-dose dexamethasone; SVdX = SVd treatment after crossover; Vd = bortezomib 
plus low-dose dexamethasone.

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4. 
INTRODUCTION 
4.1. 
Multiple Myeloma 
4.1.1. 
Disease Background 
Multiple myeloma (MM) is the second most common hematological malignancy (after 
non-Hodgkin’s lymphoma [NHL]), representing 1% of all cancers and 2% of all cancer deaths. 
With over 30,000 new cases and approximately 12,700 deaths from MM anticipated in 2018 in 
the United States of America (USA) (ACS 2018) and about twice as many in Europe, there is an 
unmet medical need for therapies in patients with relapsed or refractory multiple myeloma 
(RRMM) that has progressed on available agents. 
4.1.2. 
MM Treatment 
The treatment of MM has improved over the last 20 years and overall survival (OS) has 
increased considerably with the approval of non-chemotherapeutic agents including 
immunomodulatory drugs, such as thalidomide, lenalidomide, and pomalidomide, and the 
proteasome inhibitors (PIs) bortezomib, carfilzomib, and oral ixazomib (which was approved 
more recently). These agents have served as “backbone” therapies for patients with MM, are 
often used in combination (eg, lenalidomide with bortezomib), and are typically combined with 
“low-dose” dexamethasone (ie, ≤40 mg/week). Additional drug classes, including histone 
deacetylase inhibitors such as panabinostat, along with anti-CD38 (daratumumab) and anti-CS1 
(elotuzumab) monoclonal antibodies (mAbs), have recently been approved and are all 
contributing to prolonged survival in MM. Despite this progress, essentially all patients will 
develop refractory MM and succumb to the disease. 
The prognosis remains poor for patients with RRMM who have already received at least 1 prior 
anti-MM regimen. For these patients, the median progression-free survival (PFS) is 6.2 to 
9.4 months with bortezomib (Richardson 2007, Dimopoulos 2016) and median OS is 
approximately 29.8 months (Richardson 2007). 
Second-line combination therapies have a significant burden of toxicity with extended sequelae, 
representing significant unmet medical need. Peripheral neuropathy, in particular, has an 
extended long-term burden for patients. 
4.2. 
Selinexor 
A summary of the relevant background information for selinexor, including the mechanism of 
action, nonclinical and clinical studies, and potential risks is presented below. Please refer to the 
Selinexor Investigator’s Brochure (IB) for more detailed information. 
4.2.1. 
Selinexor Mechanism of Action 
Selinexor is an oral, first-in-class, slowly reversible, potent selective inhibitor of nuclear export 
(SINE) compound that specifically blocks exportin 1 (XPO1). Selinexor binds covalently to 
cysteine 528 in the cargo binding pocket of XPO1 and shuts down its nuclear export activity 
(Neggers 2016, Neggers 2015, Hing 2016). This results in marked nuclear accumulation of TSPs 

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and their functional reactivation as well as abrupt reduction of eIF4E transcriptionally-dependent 
proto oncogene proteins. Activation of TSPs and downregulation of proto-oncogenes block the 
cell division cycle and induce apoptosis across a range of solid and hematologic tumor cells in 
vitro and in vivo, while sparing normal cells. 
4.2.2. 
Selinexor Pharmacodynamics and Dosing Frequency 
Nonclinical studies have demonstrated that SINE compound binding to XPO1 results in a rapid 
and sustained loss of XPO1 protein expression and nuclear export function with a reciprocal 
induction of XPO1 mRNA (Ranganathan 2012, Tai 2014, Zhang 2013). Furthermore, by 
determining the time course and dose dependence of XPO1 target binding by selinexor, it has 
been demonstrated that selinexor target occupancy correlates with inhibition of XPO1 function 
(Crochiere 2016). These studies demonstrated that significant XPO1 inhibition is sustained for 
up to 72 hours following a single dose of selinexor, with the level of XPO1 mRNA induction and 
the duration of XPO1 inhibition varying with the dose. This long pharmacodynamic (PDn) 
half-life for selinexor supports once weekly (QW) to twice weekly (BIW) dosing for doses in the 
range of 60 to 100 mg. 
The PDn of the selinexor effect on XPO1 mRNA in leukocytes from adult and pediatric patients 
in solid tumor and hematological cancer studies has been evaluated. XPO1 mRNA expression is 
significantly induced by 2 hours post-selinexor dose and reaches a plateau of approximately 4- to 
6-fold, which is sustained for at least 48 hours (Abdul Razak 2016, Alexander 2016). Predose 
XPO1 mRNA expression is maintained at a level comparable to the fold induction achieved 
following the first dose, indicating that the maximal XPO1 inhibition in leukocytes following the 
first dose is maintained throughout the dosing schedule. 
4.2.3. 
Selinexor Pharmacokinetics 
The pharmacokinetics (PK) of selinexor has been investigated in 3 completed Phase 1 studies in 
patients with hematological and solid tumor malignancies as described. Overall, PK parameters 
were similar in all 3 Phase 1 studies including patients with advanced hematologic malignancies 
(Study KCP-330-001), advanced solid tumors (Study KCP-330-002), and advanced soft tissue or 
bone sarcomas (Study KCP-330-003). 
Selinexor is orally bioavailable in patients with hematological and solid tumor malignancies. The 
absorption is moderately rapid with a median time to peak plasma concentration (tmax) of 2 to 
4 hours. In dose escalation studies in patients with hematological and solid tumor malignancies 
(KCP-330-001 and KCP-330-002), selinexor exhibited linear PK, and dose-proportional 
exposure (area under the concentration versus time curve [AUC] and maximum plasma 
concentration [Cmax]). At the therapeutic dose of 80 mg (~45 mg/m2), the mean Cmax was 
680 ng/mL (1.5 μM) and AUC0-∞was 5386 ng•hr/mL. Moreover, the consistent tmax and 
elimination (terminal) half-life ( t½) across the range of doses evaluated (3 to 85 mg/m2) suggest 
overall dose-independent absorption and clearance. 
PK analyses support the use of fixed, rather than body surface area (BSA)-based, dosing for 
selinexor. Pooled analyses of data from Studies KCP-330-001, -002, and -003, indicated that 
BSA-adjusted dosing of selinexor did not reduce interpatient variability. Additionally, the impact 
of body weight- or BSA-normalized dosing regimens were evaluated in a population PK 
analysis. The population PK analysis confirmed the original observation that plasma selinexor 

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exposure was generally not affected by BSA within each dose category (low dose of <30 mg/m2; 
mid-dose of 30 to 55 mg/m2, and a high dose of >55 mg/m2), with the exception of the lowest 
end of the low-dose category. These results suggest that there is limited value to adjusting patient 
dose by BSA or weight and therefore support fixed-dose administration.  
4.2.4. 
Selinexor Metabolism/Drug-drug Interactions 
Metabolism data suggest that clinically relevant inhibition of the major CYP450s by selinexor is 
unlikely in the clinical setting and no induction of CYP450 activity has been observed. In human 
plasma, the primary route of metabolism is via glucuronidation and subsequent hepatobiliary 
elimination. Given the route of metabolism and elimination of selinexor, the rapid onset of target 
inhibition, and the long PDn half-life, selinexor PDn are not expected to be impacted by 
co-administration of other drugs.  
Selinexor is not expected to alter exposures of other drugs. Across clinical studies of selinexor in 
>2500 patients with advanced cancers treated with selinexor alone or in combination to date, no 
significant drug-drug interactions have been reported. In population PK analyses, the exposures 
to selinexor were not altered in the presence of any of the major human CYP modifiers, 
including CYP3A4 inhibitors or inducers. Patients also received comedications which are 
inhibitors of CYP2C9/19 (eg, fluconazole), CYP2D6 (eg, bupropion, paroxetine, terbinafine), 
and CYP1A2 (eg, ciprofloxacin). No overt differences in PK leading to adverse events (AEs) 
were observed for selinexor and no major changes in the AE profile of these (or other 
concomitant) drugs were reported. Selinexor does not accumulate over time, thus further 
minimizing its potential for drug-drug interactions. 
Additional PK analysis will be conducted to evaluate the impact of coadministration of 
anticancer agents, including bortezomib, on the selinexor population PK model. 
4.2.5. 
Selinexor Nonclinical Combination with Dexamethasone and Proteasome 
Inhibitors 
In nonclinical models, the combination of SINE compounds with dexamethasone demonstrates 
synergistic anti-myeloma effects. This synergism emanates from at least 2 effects of the drug 
combination. The first is the induction of total of glucocorticoid receptor (GR) protein levels and 
the second is through the direct suppression of the mTOR pathway by the drug combination 
(Argueta 2018). 
Nonclinical studies in vitro and in vivo have shown that selinexor strongly synergizes with PIs 
such as bortezomib (Turner 2013, Turner 2016, Tai 2014, Wu 2016) and carfilzomib (Kandarpa 
2013, Rosebeck 2016) leading to inhibition of cell proliferation and induction of MM cell death. 
The mechanism for the synergy includes (a) nuclear IκB retention and inhibition of NF-κB 
transcriptional activity (Kashyap 2016, Turner 2016), (b) enhanced nuclear localization and 
activation of TSP levels (Turner 2013, Wu 2016) and (c) induction of autophagy (Kandarpa 
2013, Rosebeck 2016). Moreover, as demonstrated by Turner (Turner 2016), in models of 
bortezomib resistant disease (refractory patient MM cells; rodent PI inhibitor resistant xenograft 
models), combining selinexor and bortezomib induced synergistic apoptotic cell death, tumor 
growth inhibition, and increased survival. 
Importantly, bone marrow mononuclear cells isolated from patients with myeloma refractory to 
PIs are sensitized by selinexor to bortezomib and carfilzomib ex vivo, as shown by increased 

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induction of apoptosis by the combination with no increased effect on normal non-myeloma cells 
(Turner 2016). These findings mirror the clinical findings that combination treatment of 
selinexor and PIs can result in durable responses in patients with MM, including those whose 
disease is refractory to PIs. 
4.2.6. 
Overall Clinical Experience with Selinexor 
To date, more than 2500 patients with hematologic or solid tumors have received selinexor in 
clinical studies (including Karyopharm-sponsored studies and Investigator-sponsored studies) in 
>10 disease indications, the majority of patients were treated with selinexor as a single agent but 
>300 patients received selinexor in combination with a diverse array of other anticancer agents. 
Single-agent Phase 1 studies with oral selinexor have been conducted in advanced hematological 
malignancies including MM, acute myeloid leukemia (AML), NHL, and chronic lymphocytic 
leukemia (KCP-330-001); in solid tumors (KCP-330-002); and in soft tissue and bone sarcomas 
(KCP-330-003). Broad antitumor activity has been observed in all of these studies. In addition, 
Phase 2 studies are ongoing in MM, AML, diffuse large B-cell lymphoma, glioblastoma, 
gynecological malignancies, and dedifferentiated liposarcoma (Phase 2 and 3). 
In Studies (KCP-330-001 and KCP-330-012) alone, 227 patients with MM have been exposed to 
selinexor ± dexamethasone:  
•
Results of the Phase 1 Study KCP-330-001 indicate that selinexor ± low-dose
dexamethasone (20 mg QW) has clear anti-MM activity in heavily pretreated patients.
•
In Part 2 of the ongoing pivotal Phase 2 Study KCP-330-012 (STORM), treatment
with selinexor 80 mg with dexamethasone 20 mg (Sd), both orally twice per week,
resulted in an ORR of 25.4% and a CBR (patients with ≥MR) of 39.3% in patients
entering the study with rapidly progressive disease refractory to currently available 
MM therapies with known clinical benefit (ie, penta-exposed, triple class-refractory 
MM). Median duration of response was 4.4 months. The median OS in the patients 
with any response (≥MR; n=39) was significantly longer than those with a best 
response of PD/NE (p<0.0001), and was even longer in patients with a best response 
of SD (39.3% of patients) compared with patients who had PD/NE. Despite the 
highly aggressive nature of the MM in the patients, the Sd regimen was able to halt 
MM disease progression (SD or better) in ~80% of the patients entering the study 
(Study KCP-330-012 CSR).
Selinexor is also being studied in combination with PIs (ie, bortezomib and carfilzomib): 
•
Preliminary results of Study KCP-330-017 (STOMP; NCT02343042) in patients with
relapsed and/or refractory MM have shown that adding selinexor to subcutaneous
(SC) bortezomib and oral dexamethasone (SVd regimen) resulted in improved
response rates (Section 4.2.6.1).
•
Final results of a Phase 1 investigator-sponsored study (IST; NCT02199665)
evaluating the combination of selinexor with carfilzomib and low-dose
dexamethasone in patients with RRMM demonstrate encouraging activity
(Jakubowiak 2016). The ORR for 19 patients with heavily pretreated MM was 63%.

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4.2.6.1. 
Study KCP-330-017 (STOMP) 
Study KCP-330-017 (STOMP) is an ongoing Phase 1b/2 study of selinexor in combination with 
multiple backbone therapies for the treatment of relapsed and/or refractory MM. The study is 
designed to independently assess the efficacy and safety of multiple regimens (with selinexor 
dose escalations within each arm), including selinexor and low-dose dexamethasone plus either 
bortezomib (SVd), pomalidomide (SPd), or lenalidomide. 
As of the data cut off of 05 June 2018, 40 patients treated with SVd were evaluable for response. 
Best responses based on interim unaudited data are provided in Table 12.  
Preliminary results include the following (Bahlis 2017): 
• The high ORR rate of 83% in patients with PI-relapsed or PI-naïve MM treated with 
≤3 prior therapies treated with SVd and the PFS of 17.8 months in patients with 
PI-relapsed or PI-naïve MM treated with SVd support this BOSTON study evaluating 
SVd vs. Vd. 
• The ORR of 84% in patients with PI-relapsed or naïve MM treated with SVd is higher 
than the expected ORR ≤65% with Vd alone. 
• The ORR of 43% in patients with PI-refractory MM treated with SVd supports the 
nonclinical findings that selinexor resensitizes and overcomes resistance to PIs 
(Section 4.2.5). 
• An ORR of 83% in PI-relapsed or naïve patients with ≤3 prior treatments (ie, the 
“BOSTON” Phase 3 population). 
• Responses on SVd were rapid and typically occurred within 1 cycle of treatment, often 
improving over time. 
Table 12: 
KCP-330-017 Best Responses in Evaluable SVd Patients as of 05 June 2018 
Categorya 
Nb 
ORR 
(%) 
CBR 
(%) 
sCR 
(%) 
CR 
(%) 
VGPR 
(%) 
PR 
(%) 
MR 
(%) 
SD 
(%) 
PD 
(%) 
PI-Relapsed or Naïve 
19 
16  
(84%) 
18 
(95%) 
1 
(5%) 
3 
(16%) 
3 
(16%) 
9 
(47%) 
2 
(11%) 
1 
(5%) 
-- 
PI-Refractory 
21 
9 
(43%) 
14 
(67%) 
-- 
1 
(5%) 
4 
(19%) 
4 
(19%) 
5 
(24%) 
6 
(29%) 
1 
(5%) 
PI-Relapsed or Naïve, ≤3 
Prior Treatments (BOSTONc) 
18 
15 
(83%) 
16 
(89%) 
1 
(6%) 
3 
(17%) 
4 
(22%) 
7 
(39%) 
1 
(6%) 
2 
(11%) 
-- 
Abbreviations: CBR + clinical benefit rate (ORR+MR); CR + complete response; IMWG = International Myeloma 
Working Group; M = minor response; ORR = overall Response Rate (sCR+CR+VGPR+PR); PD = progressive 
disease; PR = partial response; sCR = stringent complete response; SD = stable disease; VGPR = very good partial 
response. 
a Responses as of 05 June 2018 based on interim unaudited data. Responses were adjudicated according to the 
IMWG criteria. 
b Two patients not evaluable for response: 1 death unrelated to myeloma and 1 withdrawal of consent before disease 
follow-up. 
c BOSTON: patient population eligible for the ongoing Phase 3 Randomized BOSTON Study of SVd versus Vd. 

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The maximum tolerated dose (MTD) was not reached and prolonged tolerability and efficacy 
were observed in the SVd cohort.  
The most common treatment-related AEs in the SVd Arm were nausea, anorexia, fatigue, and 
diarrhea, all mainly Grades 1-2, and thrombocytopenia with minimal bleeding. Peripheral 
neuropathy (all cases unrelated to selinexor) was limited to 6 patients (Grade 1: 4 patients, 
Grade 2: 2 patients) of which 5 had prior bortezomib exposure. This incidence rate is consistent 
with the published data cited in the literature (discussed below) for QW bortezomib dosing. 
Based on the results from the dose escalation phase, the recommended Phase 2 dose (RP2D) is a 
5-week cycle with selinexor 100 mg QW continuous, bortezomib 1.3 mg/m2 SC QW for 
Weeks 1 through 4, and dexamethasone 20 mg on Days 1 and 2 BIW continuous. An expansion 
phase at the RP2D is currently ongoing with preliminary tolerability and efficacy results 
consistent with above findings. 
Of note, the QW recommended regimen of SVd in STOMP uses 40% less bortezomib and 25% 
less dexamethasone compared with standard BIW (for 2 of every 3 weeks) Vd regimens, and 
consequently is expected to have significantly less peripheral neuropathy and other significant 
AEs than standard Vd, as well as to be more convenient for patients than standard Vd and the 
majority of Vd combinations, which require BIW clinic visits for SC (or intravenous [IV]) 
administration of bortezomib (Richardson 2007, Dimopoulos 2016,  Palumbo 2016, Bringhen 
2010).  
These preliminary results appear to confirm the nonclinical data supporting the additive or 
synergistic effects of selinexor in combination with PIs (Section 4.2.5), with good tolerability, 
and support this BOSTON study of SVd versus Vd. 
4.2.7. 
Potential Risks of Selinexor 
At the time of the most recent Selinexor IB update, clinical experience with selinexor had been 
evaluated in 1672 patients (as of the 31 March 2018 safety data analysis).  
In ongoing clinical studies, the most commonly reported TEAEs have been low-grade and 
reversible, including nausea, fatigue, anorexia, vomiting, and diarrhea; thrombocytopenia and 
anemia, which can be higher grade, have been also reported primarily in patients with 
hematologic malignancies. 
In a previous study, 1 patient, heavily pretreated for recurrent pancreatic cancer, developed acute 
cerebellar syndrome following 3 doses of selinexor at 85 mg/m2 (approximately 145 mg) BSA 
BIW. The patient experienced abnormal speech and loss of coordination, and was unable to 
walk. This patient recovered to near baseline with both speech and mobility over ~6 weeks. No 
other adult patients have reported similar symptoms to date. 
Eight tumor lysis syndrome (TLS) cases have been reported, including 5 patients with MM, 
1 patient with AML, and 2 patients with acute lymphoblastic leukemia; as of the date of this 
amendment), including 4 patients in company-sponsored studies, 2 patients in Investigator-
sponsored studies, and 2 patients in the expanded access program (compassionate use). Further 
details about these patients are provided in Section 12.1.2.3.1. 

Investigational Product (KPT-330) 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
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Version 4.0 
4.2.7.1. 
Reproductive Risks for Selinexor 
Macroscopic and microscopic changes in reproductive organs were noted during rat and monkey 
toxicology studies, most of which partially or fully resolved during the recovery period. The 
long-term effects of these changes on reproductive potential are unknown. Secondary 
developmental effects due to reduced maternal body weights were also noted during a study on 
rat embryo/fetal development. 
It is unknown whether similar effects may occur in humans. As it is unknown whether selinexor 
might have reproductive toxicity in humans, patients must agree to use effective contraception 
(see Contraception Requirements, Section 10.8.1) during the study and for 3 months following 
the last dose of study treatment. 
4.3. 
Bortezomib and Dexamethasone (Vd) 
Bortezomib, a modified dipeptidyl boronic acid, is a reversible inhibitor of the mammalian 
proteasome, demonstrating rapid inhibition of 20S proteasome activity in peripheral blood 
following drug administration (Velcade® Prescribing Information). Bortezomib systemic 
exposure is equivalent following either SC or IV administration; plasma concentrations show 
multi-exponential decline with a rapid initial phase followed by a prolonged terminal phase and 
extensive peripheral tissue distribution. Peak PDn activity is achieved within 5 to 30 minutes 
postdose and declines slowly over the dosing interval with 22 to 48% inhibition of 20S activity 
observed at 48 hours postdose (Moreau 2012, Reece 2011). Bortezomib is cytotoxic to a variety 
of cancer cell types and causes a delay in tumor growth in nonclinical tumor models, including 
MM. 
In the USA, Canada, and Europe, bortezomib (a first-in-class PI) is approved for the treatment of 
both newly diagnosed and relapsed MM. In RRMM, bortezomib is given with low-dose 
dexamethasone as a standard treatment worldwide. SC administration of bortezomib showed 
comparable efficacy to IV administration with lower rates of all AEs, in particular high-grade 
peripheral neuropathy (Richardson 2003, Richardson 2005, Moreau 2011). SC BIW bortezomib 
with low-dose dexamethasone (Vd) represents a standard, approved therapy for early relapsed 
MM despite recent approvals of new MM therapies.  
The safety and efficacy profiles of Vd have been extensively documented in multiple 
randomized, controlled studies. Furthermore, the well-established dose and combinability of the 
Vd control arm have supported its use in multiple recent (NCT02136134 and NCT01568866) 
and ongoing (NCT01734928 and NCT02755597) pivotal myeloma studies. 
Please refer to the full prescribing information for bortezomib (different local/regional trade 
names may be used) for the most current clinical experience and safety and reproductive risk 
information. 
4.4. 
Study and Dose Rationale 
4.4.1. 
Study Rationale 
This Phase 3 study of SVd versus Vd in patients with RRMM, who have received 1 to 3 prior 
anti-MM regimens, is based on preliminary supportive safety and efficacy data from patients 
with relapsed MM treated with SVd in the Phase 1b/2 Study KCP-330-017 (STOMP) 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 42 
Version 4.0 
demonstrating that SVd has very high levels of anti-myeloma activity, even in patients with 
PI-refractory disease, and a relatively low incidence of AEs (Section 4.2.6.1). 
This SVd regimen could serve a current and rapidly growing unmet medical need in patients 
with RRMM, providing for increased response rates and durability of response over Vd, with 
improved tolerability with respect to peripheral neuropathy-associated untoward effects of 
bortezomib. 
Crossover of patients on the control arm (Vd Arm), which is a commonly used backbone therapy 
for patients with RRMM throughout the world (Section 4.3), to SVdX following Independent 
Review Committee (IRC)-confirmed progressive disease (PD) will allow for direct assessment of 
selinexor’s ability to restore sensitivity in PI-resistant MM (Section 4.2.5). Crossover from the 
Vd Arm to SdX will be allowed, following IRC-confirmed PD, as compassionate use for patients 
who are not able to tolerate continued treatment with bortezomib (Section 6.2). 
4.4.2. 
Dose Rationale 
The rationale for the proposed dosing regimen used in this BOSTON study is based on the 
totality of clinical safety, efficacy, PK, and PDn data from Company- and Investigator-sponsored 
studies of selinexor and is supported by nonclinical pharmacology data for selinexor and other 
SINE compounds. The QW regimen of oral selinexor (100 mg), SC bortezomib (1.3 mg/m2), and 
oral dexamethasone (20 mg), which is the RP2D in Study KCP-330-017 (STOMP), enables 
sustained concomitant inhibition of nuclear export and proteasome activity while limiting 
treatment-emergent adverse events (TEAEs) such as fatigue, thrombocytopenia, and peripheral 
neuropathy. The high rate of response, good safety and tolerability profile, and reduced treatment 
burden on patients observed with this dose regimen in Study KCP-330-017 (STOMP) support its 
prospective investigation in the BOSTON study. 
This dose regimen is supported by the following findings: 
• Selinexor synergistically sensitized MM cells to the cytotoxic effects of PIs in vitro, in 
vivo and ex vivo while not affecting peripheral blood or non-myeloma bone marrow 
mononuclear cells (Section 4.2.5). 
• Data from patients enrolled in Study KCP-330-017 (STOMP) demonstrate that the 
combination of QW bortezomib with selinexor and low-dose dexamethasone has very 
high levels of anti-myeloma activity with relatively low AE rates, even in patients with 
PI-refractory disease (Section 4.2.6.1). 
• The use of QW bortezomib is associated with relatively low levels of peripheral 
neuropathy even with extended dosing and reduced treatment burden on patients with 
only 1 clinic visit per week (Section 4.2.6.1). Moreover, when used in combination in 
clinical studies, QW bortezomib shows similar activity and superior tolerability to BIW 
combination regimens (Section 4.4.2.1). 
• As QW dosing of selinexor and bortezomib aligns the long PDn half-lives of both agents 
(Section 4.2.2 and Section 4.3 at their respective targets and limits effects on maturation 
of immune cell subsets, QW dosing is associated with low level cytopenias. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 43 
Version 4.0 
4.4.2.1. 
Bortezomib QW Dose Rationale 
The QW dose schedule provides for a considerable reduction (~40%) in overall bortezomib dose 
versus the control arm (Vd Arm) that, in addition to the relatively low dose of selinexor, may be 
associated with better tolerability (eg, reduced peripheral neuropathy) compared with current 
second-line Vd and Vd-based combination regimens.  
Varying the dose regimen of bortezomib from QW to BIW was explored in 3 patients in the 
Study KCP-330-017 (STOMP). Following DLT clearance in 4 patients at the dose level of 
selinexor 80 mg QW and bortezomib 1.3 mg/m2 QW, 3 patients were treated with selinexor 
80 mg QW and bortezomib 1.3 mg/m2 BIW. All patients had MM that was refractory to a PI 
therapy. Responses were early and occurred within 1 month of treatment initiation. Response 
rates and duration on study were similar between these 2 dose groups (bortezomib QW 
[1 VGPR, 1 PR, 1 minimal response (MR), 1 PD] versus bortezomib BIW [2 PRs, 1 MR, 1 PD]) 
and also in comparison with the ORR for all SVd treated patients. However, all patients on BIW 
bortezomib were dose reduced to QW bortezomib following Cycle 1 due to increased fatigue or 
cytopenias. 
Other clinical studies have also compared bortezomib combinations that utilize QW versus BIW 
bortezomib doses and have shown similar response rates between the 2 arms with improved 
tolerability in the QW dose group (Bringhen 2010, Mateos 2014, Reeder 2010). 
Based on these results, the efficacy and tolerability of the SVd regimen using QW bortezomib 
has been demonstrated to be optimal. Furthermore, the expected response rate of Vd regimen in 
patients with 1-3 prior therapies is approximately 60% (Palumbo 2016). Results from the 
ongoing Study KCP-330-017 (STOMP) for SVd in PI-relapsed or naive MM are promising with 
an ORR of 84%. 

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CCI

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 47 
Version 4.0 
6.
INVESTIGATIONAL PLAN
6.1. 
Overall Study Design and Plan
This Phase 3, 2-arm, randomized, active comparator-controlled, open-label, multicenter study 
will compare the efficacy and HR-QoL and assess the safety of selinexor plus bortezomib 
(Velcade® or generic equivalent) plus low-dose dexamethasone (SVd) versus bortezomib 
plus low-dose dexamethasone (Vd) in adult patients with RRMM who have received 1 to 3 
prior anti-MM regimens. 
The study overview is presented in Figure 1. 
Approximately 364 patients will be randomized from up to 120 global investigative sites. 
Patients will be randomized to 1 of 2 treatment arms (SVd or Vd) in a 1:1 allocation, as follows: 
•
SVd Arm (~182 patients): selinexor + bortezomib (QW) + dexamethasone
•
Vd Arm (~182 patients): bortezomib (BIW)+ dexamethasone
Randomization (Section 8.2) will be stratified based on: 
•
Prior PI therapies (Yes or No)
•
Number of prior anti-MM regimens (1 versus >1)
•
R-ISS stage at study entry, based on screening results (R-ISS Stage III versus R-ISS
Stage I or II) (Palumbo 2015). If data for chromosomal abnormalities (CA) and serum
lactate dehydrogenase (LDH) required for R-ISS staging are not available, patients
will be assigned to the R-ISS category corresponding to their ISS stage.
It is planned to randomize patients within individual countries in a 1:1 allocation to SVd:Vd. 
The number of patients enrolled may be adjusted based on the results of the interim analysis (IA) 
for sample size re-estimation (first IA). 
Patients in the Vd Arm who have PD that is confirmed by the IRC will be allowed to cross over 
to a regimen that includes selinexor: 1) SVd treatment (SVdX) for patients who are able to 
tolerate continued bortezomib, or 2) SdX for patients who have significant tolerability issues 
with bortezomib, following the process described in Section 6.2. Patients who cross over will be 
referred to as SVdX patients or SdX patients, respectively (Section 6.2). 
The Schedule of Assessments is provided in Table 2. Patients will have in-clinic visits for dosing 
of study treatment during MM evaluations (Table 13) and telephone contacts (Section 11.7.3). 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 48 
Version 4.0 
Table 13: 
In-clinic Dosing and MM Evaluations 
Assessmentsa 
MM Evaluation Visits 
In-clinic Dosing Visits 
Weight, ECOG, HR-QoL, and pregnancy 
test (serum hCG or urine) 
 
Day 1 of each cycleb 
CBC with differential and serum chemistry 
X 
C1D8 only 
SPEP, UPEP, quantitative Ig level, serum 
FLC, clinical plasmacytoma assessment (if 
clinically indicated) 
X 
 
Skeletal survey 
Frequency determined by the Investigator 
Bone marrow aspirate and biopsy 
At the time of response to confirm CR or sCR 
Administration of study treatment 
 
X 
Symptom-directed physical examinations 
If clinically indicated 
Vital signs, AE and concomitant 
medication recording, and SAE reporting 
X 
X 
Ophthalmic exam and 12-lead ECG 
If clinically indicated 
Abbreviations: AE = adverse event; BSA = body surface area; CXDX = Cycle X Day X; CBC = complete blood 
count; D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FLC = free light 
chain; hCG = human chorionic gonadotropin; HR-QoL = health-related quality of life; Ig = immunoglobulin; SAE 
= serious adverse event; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis.  
a See Table 2 for details on assessments/schedule. 
b BSA should be recalculated if weight fluctuates substantially from baseline (ie, >20%) during treatment. 
The Schedule of Visits for In-clinic Dosing and MM Evaluations is provided in Table 4 for the 
SVd Arm, in Table 5 for the Vd Arm, in Table 6 for SVdX patients, and in Table 7 for SdX 
patients. Patients randomized to the SVd and Vd Arms will undergo MM evaluations every 
3 weeks from baseline MM evaluations on C1D1 (regardless of dose interruptions) through the 
first day of Week 37 (ie, 12 MM evaluations after C1D1) to identify patients who progress 
quickly, then every 5 weeks for the remainder of the study regardless of cycle length. This will 
result in comparable PFS data from both arms. SVdX/SdX patients will undergo MM evaluations 
every 5 weeks. 
Dose schedules are provided in Section 3.2. 
Dose modifications for selinexor to manage tolerability will be allowed (see Section 10.4). 
Information on dose modifications for the other agents is provided in Section 10.4.3 
(bortezomib) and Section 10.4.4 (dexamethasone). 
Study treatment (SVd, Vd, SVdX, or SdX) may continue until PD is confirmed by the IRC, 
Investigator or patient decision to discontinue study treatment, pregnancy, unacceptable AEs or 
toxicity that cannot be managed by supportive care, withdrawal of consent, death, or Sponsor 
decision to terminate the study. 
If PD is suspected but the IRC does not confirm PD, patients will either remain on study 
treatment until PD is confirmed by the IRC or discontinue study treatment, complete the End of 
Treatment (EoT) Visit, and be followed for survival. An exception is allowed for patients in the 
Vd Arm who terminate bortezomib treatment prior to IRC-confirmed PD if the termination is 

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due to significant toxicities such as peripheral neuropathy and all treatment measures addressing 
these toxicities are exhausted and documented prior to bortezomib termination. Early termination 
of bortezomib should be discussed and approved by the Sponsor Medical Monitor in order to 
allow crossover to SdX after progression is confirmed by the IRC.  
After IRC-confirmed PD: 
• Patients in the SVd Arm will complete the EoT Visit and be followed for survival. 
• Patients in the Vd Arm may: 
− cross over (Section 6.2) to SVdX (returning to Cycle 1) after completing the End 
of Vd Treatment Visit if they are able to tolerate continued bortezomib treatment, 
− cross over (Section 6.2) to SdX (returning to Cycle 1) after completing the End of 
Vd Treatment Visit if they are unable to tolerate continued bortezomib treatment, 
or 
− discontinue study treatment, complete the EoT Visit, and be followed for survival. 
• SVdX patients will discontinue study treatment, complete the EoT Visit, and be 
followed for survival. 
• SdX patients will discontinue study treatment, complete the EoT Visit, and be 
followed for survival.  
6.2. 
Crossover 
Crossover from the Vd Arm to a treatment that includes selinexor (ie, SVdX or SdX) will be 
allowed at the point of IRC-confirmed objective disease progression per the IMWG criteria for 
patients in the Vd Arm. 
The following process will be used in order to prevent premature crossover:  
1. Investigators will assess PD according to the IMWG criteria including repeat testing if 
PD is based on serum and/or urine M-protein, quantitative immunoglobulins for IgA/IgD, 
or serum free light chain (FLC). PD may also be based on new or enlarging 
plasmacytoma(s) or bone lesion(s) or on other symptoms and signs of clinical progression 
that meet the IMWG criteria. 
2. All cases of PD must be confirmed by the IRC prior to crossover. 
3. Crossover will not be permitted based purely on Investigator-assessed progression that 
does not meet any IMWG criteria for PD and cannot be verified by IRC (eg, deteriorating 
performance status). 
4. Crossover will not be permitted if dosing of bortezomib is terminated before PD is 
confirmed by the IRC, unless termination of bortezomib is due to significant toxicities 
such as peripheral neuropathy, and all treatment measures addressing these toxicities are 
exhausted and documented prior to bortezomib termination. Early termination of 
bortezomib should be discussed and approved by the Sponsor Medical Monitor in order 
to allow crossover to SdX after progression is confirmed by the IRC. 

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5. Investigator-assessed presumptive PD events that are not confirmed by the IRC will have 
their PFS censored at the time of treatment discontinuation. 
Patients in the Vd Arm who are able to tolerate continued bortezomib treatment will be allowed 
to cross over to SVdX treatment. 
Patients in the Vd Arm who have significant tolerability issues with bortezomib (ie, are unable to 
tolerate any continued bortezomib treatment, eg, due to Grade >2 peripheral neuropathy 
or Grade ≥2 peripheral neuropathy with pain) will be allowed to cross over to SdX treatment. 
Patients who do not elect to cross over to SVdX or SdX from the Vd Arm will discontinue 
treatment, proceed to the EoT Visit, and be followed for survival. 
6.3. 
Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) will be set up for the study to review 
safety data for this study. The DSMB is made up of a group of individuals with pertinent 
expertise that reviews, on a predetermined schedule, safety data from this clinical study. It is the 
DSMB's responsibility to weigh risks and benefits throughout the study's duration. The DSMB 
will provide oversight and safety monitoring of the study in compliance with applicable 
regulations, legislation and associated guidance materials for the nature of the study.  
As appropriate, the DSMB will provide recommendations to the Sponsor regarding continuation, 
modification, or discontinuation of the study based on its assessment of the reviewed safety data. 
This DSMB will be composed of 4 voting members (3 oncologists and an independent 
statistician) who will review safety data from the study. The DSMB membership, functioning, 
and procedures are described in the DSMB charter. 
6.4. 
Independent Review Committee 
An IRC will be formed to review MM disease assessment data for this study, to independently 
assess disease response and time of PD. PD based on site generated MM disease assessment data 
must be confirmed by the IRC prior to discontinuing treatment from either arm (unless medically 
contraindicated). PD as a result of plasmacytoma(s) or bone lesion(s) will be reviewed by the 
IRC and results will be compared with baseline assessments. IRC confirmation of PD is required 
for all patients and, for those patients in the Vd Arm, confirmation is required prior to initiation 
of SVdX/SdX treatment in the crossover (Section 6.2). The IRC will review data (generated by 
the local and central laboratory) that will be used for the final analysis of the primary endpoint. 
The IRC’s assessments of PFS will be used as the basis for the evaluation of the primary 
endpoint. The IRC membership, functioning, and procedures (including resolution of any 
disagreements with Investigators regarding MM disease assessments) are described in the IRC 
charter. 

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7. 
STUDY POPULATION SELECTION 
7.1. 
Study Population 
This study will enroll patients ≥18 years of age with RRMM who have received 1 to 3 prior 
anti-MM regimens and who meet all of the inclusion criteria and none of the exclusion criteria. 
Inclusion/exclusion criteria will be assessed during Screening. 
7.2. 
Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible to enroll in this study: 
1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined 
by at least 1 of the following: 
a. Serum M-protein ≥0.5 g/dL (>5 g/L) by serum protein electrophoresis (SPEP) or for 
immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or 
b. Urinary M-protein excretion at least 200 mg/24 hours; or  
c. Serum FLC ≥100 mg/L, provided that the serum FLC ratio is abnormal (normal FLC 
ratio: 0.26 to 1.65). 
2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. 
Induction therapy followed by stem cell transplant and consolidation/maintenance 
therapy will be considered as 1 anti-MM regimen. 
3. Documented evidence of progressive MM (based on the Investigator's determination 
according to the IMWG response criteria) on or after their most recent regimen. 
4. Prior treatment with bortezomib or other PI is allowed, provided all of the following 
criteria are met:  
− Best response achieved with prior bortezomib at any time was ≥ PR and with the 
last PI therapy (alone or in combination) was ≥ PR, AND  
− Participant did not discontinue bortezomib due to Grade ≥3 related toxicity, AND 
− Must have had at least a 6-month PI-treatment-free interval prior to C1D1 of 
study treatment. 
5. Must have an ECOG Status score of 0, 1, or 2. 
6. Written informed consent in accordance with federal, local, and institutional guidelines. 
7. Age ≥18 years. 
8. Resolution of any clinically significant non-hematological toxicities (if any) from 
previous treatments to Grade ≤1 by C1D1. Patients with chronic, stable Grade 2 
non-hematological toxicities may be included following approval from the Medical 
Monitor. 
9. Adequate hepatic function within 28 days prior to C1D1: 
a. Total bilirubin <1.5 × upper limit of normal (ULN) (except patients with Gilbert’s 
syndrome who must have a total bilirubin of <3 × ULN), and 

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b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to 
<2 × ULN. 
10. Adequate renal function within 28 days prior to C1D1 (estimated creatinine clearance 
[CrCl] of ≥20 mL/min, calculated using the formula of Cockroft and Gault): 
(140-Age) × Mass (kg)/(72 × creatinine mg/dL) 
Multiply by 0.85 if the patient is female, or if CrCl is ≥20 mL/min as measured by 
24-hour urine collection. 
11. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell 
(WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL 
and platelet count ≥75,000/mm3 (patients for whom < 50% of bone marrow nucleated 
cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow 
nucleated cells are plasma cells). 
a. Patients receiving hematopoietic growth factor support, including erythropoietin, 
darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte 
macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, 
eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between 
growth factor support and the Screening assessments, but they may receive growth 
factor support during the study. 
b. Patients must have: 
− At least a 2-week interval from the last red blood cell (RBC) transfusion prior to 
the Screening hemoglobin assessment, and  
− At least a 1-week interval from the last platelet transfusion prior to the Screening 
platelet assessment. 
However, patients may receive RBC and/or platelet transfusions as clinically indicated 
per institutional guidelines during the study.  
12. Female patients of childbearing potential must have a negative serum pregnancy test at 
Screening. Female patients of childbearing potential and fertile male patients who are 
sexually active with a female of childbearing potential must use highly effective methods 
of contraception throughout the study and for 3 months following the last dose of study 
treatment. Highly effective methods of contraception are listed in Section 10.8.1. 
7.3. 
Exclusion Criteria 
Patients meeting any of the following exclusion criteria are not eligible to enroll in this study: 
1. Prior exposure to a SINE compound, including selinexor. 
2. Prior malignancy that required treatment or has shown evidence of recurrence (except for 
non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 
5 years prior to randomization. Cancer treated with curative intent for >5 years previously 
and without evidence of recurrence will be allowed. 

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3. Has any concurrent medical condition or disease (eg, uncontrolled active hypertension, 
uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with 
study procedures. 
4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals 
within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled 
infection within 1 week prior to C1D1 are acceptable.  
5. Active plasma cell leukemia. 
6. Documented systemic light chain amyloidosis. 
7. MM involving the central nervous system. 
8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin 
changes (POEMS) syndrome. 
9. Spinal cord compression. 
10. Greater than Grade 2 peripheral neuropathy or Grade ≥2 peripheral neuropathy with pain 
at baseline, regardless of whether or not the patient is currently receiving medication. 
11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids. 
12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including 
investigational therapies) ≤2 weeks prior to C1D1. Localized radiation to a single site at 
least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are 
permitted. Patients on long-term glucocorticoids during Screening do not require a 
washout period but must be able to tolerate the specified dexamethasone dose in this 
study. 
13. Prior autologous stem cell transplantation <1 month or allogeneic stem cell 
transplantation <4 months prior to C1D1. 
14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1. 
15. Pregnant or breastfeeding females. 
16. BSA <1.4 m2 at baseline, calculated by the Dubois (Dubois 1916) or Mosteller (Mosteller 
1987) method. 
17. Life expectancy of <4 months. 
18. Major surgery within 4 weeks prior to C1D1. 
19. Active, unstable cardiovascular function: 
a. Symptomatic ischemia, or  
b. Uncontrolled clinically significant conduction abnormalities (eg, patients with 
ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree 
atrioventricular block or asymptomatic left anterior fascicular block/right bundle 
branch block will not be excluded), or 
c. Congestive heart failure of New York Heart Association Class ≥3 or known left 
ventricular ejection fraction <40%, or 
d. Myocardial infarction within 3 months prior to C1D1. 

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20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity. 
21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus 
ribonucleic acid (RNA) or hepatitis B virus surface antigen. 
22. Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow 
tablets, or any active gastrointestinal dysfunction that could interfere with absorption of 
study treatment. 
23. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion 
of the Investigator, could interfere with treatment, compliance, or the ability to give 
informed consent.  
24. Contraindication to any of the required concomitant drugs or supportive treatments. 
25. Patients unwilling or unable to comply with the protocol, including providing 24-hour 
urine samples for urine protein electrophoresis at the required time points. 

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8. 
REGISTRATION AND RANDOMIZATION 
8.1. 
Screening and Registration 
The Screening period will start once a patient has provided written informed consent to 
participate in the study and ends on the day of study entry (C1D1). 
Patient enrollment information will be provided by the site to Karyopharm for evaluation and 
approval. Upon confirmation of key eligibility criteria, Karyopharm will approve enrollment of 
the patient. After approval by Karyopharm, the patient may be randomized. See Section 8.2 for 
randomization procedures. 
8.1.1. 
Study Patient Number 
Each patient will be assigned a unique patient number and will keep this number for the duration 
of the study. Patient numbers will not be reassigned or reused for any reason. Patients will be 
identified to the Sponsor by their assigned number, date of birth, and sex. The Investigator must 
maintain a patient master log. 
8.1.2. 
Rescreening 
Rescreening is permitted in this study. If a patient fails any of the inclusion or exclusion criteria, 
a patient may be rescreened after a suitable period of time (the exact length is dependent upon 
the reason for the screen failure) per the documented agreement of Karyopharm and the 
Investigator. Any patient who is rescreened must be reconsented and will retain the same patient 
number. A patient may only fail screening once. 
8.1.3. 
Screen Failures 
A Screen Failure is defined as any patient who signs the informed consent form (ICF) but who is 
not randomized into the study. The reason for not randomizing the patient will be entered in the 
electronic case report form (eCRF). The demographic information, informed consent, and 
inclusion/exclusion pages must also be completed for screen failure patients. No other data will 
be entered into the clinical database for patients who are screen failures, unless the patient 
experiences a serious adverse event (SAE) during the Screening period. 
8.1.4. 
Replacement of Patients 
Patients who withdraw from the study without completing at least 1 cycle due to reasons that are 
unrelated to study treatment and/or disease state may be replaced. 
8.2. 
Randomization to Study Treatment 
An Interactive Response Technology system will be used to perform treatment randomization. 
Patients will be randomized to a treatment arm in a block of randomization codes that have been 
assigned to the patient’s country and stratum.  
Randomization will be performed prior to dosing.  
Randomization will be stratified based on the following stratification factors and will maintain 
the 1:1 allocation between treatment arms (SVd, Vd) within each of the stratification categories: 

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• Prior PI therapies (Yes or No) 
• Number of prior anti-MM regimens (1 versus >1) 
• R-ISS stage based on screening results (R-ISS Stage III versus R-ISS Stage I or II) 
(Palumbo 2015) (Table 14). If data for CA and serum LDH required for R-ISS 
staging are not available, patients will be assigned to the R-ISS category 
corresponding to their ISS stage. 
It is planned to randomize patients within individual countries in a 1:1 allocation to SVd:Vd. 
Table 14: 
Revised International Staging System for Multiple Myeloma 
Prognostic Factor 
Criteria 
ISS Stage 
Stage I 
β2-microglobulin < 3.5 mg/L, serum albumin ≥3.5 g/dL 
Stage II 
Not ISS Stage I or III 
Stage III 
β2-microglobulin ≥5.5 mg/L 
CA by iFISH 
High Risk 
Presence of del(17p), and/or translocation t(4;14), and/or 
translocation t(14;16) 
Standard Risk 
No high-risk CA 
LDH 
Normal 
Serum LDH < the upper limit of normal 
High 
Serum LDH > the upper limit of normal 
R-ISS Stage 
I 
ISS Stage I and standard-risk CA by iFISH and normal LDH 
II 
Not R-ISS Stage I or III 
III 
ISS Stage III and either high-risk CA by iFISH or high LDH 
Abbreviations: CA = chromosomal abnormalities; iFISH = interphase fluorescent in situ hybridization; 
ISS = International Staging System; LDH = lactate dehydrogenase; R-ISS = Revised International Staging System. 
Source: (Palumbo 2015). 
8.3. 
Blinding Procedures 
Not applicable, this is an open-label study. 

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9. 
DISCONTINUATION CRITERIA 
9.1. 
Early Termination of the Study 
The study may be discontinued at the sole discretion of the Sponsor for any reason, including 
medical or ethical reasons affecting the continued performance of the study, or difficulties in the 
recruitment of patients. If this occurs, the Sponsor will notify ethics committees (eg, Institutional 
Review Boards [IRBs]), Investigators, and regulatory authorities. 
The Sponsor will ensure that any patients receiving study treatment at the time of early 
termination of the study will be given the opportunity to continue study treatment under a 
separate treatment protocol (eg, maintenance or extension protocol). The patients will be 
followed for safety and antitumor responses by the clinical site Investigators as defined in the 
new treatment protocol.  
9.2. 
Discontinuation of Study Treatment and/or Withdrawal of Patients 
from the Study 
The Investigator may remove a patient from study treatment after consultation with the Sponsor 
for any of the following reasons: 
• Unacceptable AEs or toxicity that cannot be managed by supportive care (this must 
be linked in the study database to the AE or toxicity event to support discontinuation) 
• Any medically appropriate reason or significant protocol violation, in the opinion of 
the Investigator 
The Investigator must remove a patient from study treatment for any of the following reasons: 
• IRC-confirmed PD. Patients in the Vd Arm who have IRC-confirmed PD and are able 
to tolerate continued bortezomib treatment may cross over to SVdX and continue 
treatment until the they have IRC-confirmed PD during SVdX treatment if they meet 
the criteria in Section 6.2. Patients in the Vd Arm who have IRC-confirmed PD and 
who have significant tolerability issues with bortezomib may cross over to SdX 
treatment and continue treatment until the they have IRC-confirmed PD during SdX 
treatment if they meet the criteria in Section 6.2.  
• Patient elects to discontinue study treatment 
• Pregnancy 
Patients may discontinue study treatment for any reason. Patients who choose to discontinue 
study treatment should be encouraged to continue in the study so that follow-up information on 
PD and survival status may be obtained. 
Patients who do not have IRC-confirmed PD while receiving study treatment but are 
discontinued from study treatment for other reasons will be followed for survival. 
Patients may elect to withdraw consent and decline further participation in the study at any time. 
Patients who withdraw consent must be withdrawn from the study. 
The reason for the patient’s discontinuation of study treatment/withdrawal from the study must 
be recorded in the eCRF. The reason for discontinuation must be clearly documented in the study 

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database and include supporting data (ie, discontinuation for PD must be accompanied by data 
points in the database to support PD; additionally, if the reason for discontinuation is physician 
decision, ample justification must be provided and linked to PD values, AEs, etc.). 
Any patient who does not withdraw from the study but who stops attending study visits and does 
not respond to 3 documented contact attempts will be considered lost to follow-up. 
All patients will be followed until the end of the study (Section 9.3) or until they withdraw 
consent, are withdrawn from the study by the Investigator, have died, or have been lost to 
follow-up, whichever occurs first. 
9.3. 
End of Study Definition 
End of study (Last Patient, Last Visit) will be upon completion of the Survival Follow-up period 
for the last patient treated in the study. Completion of follow-up for the last patient will occur 
when the last patient in the study has been followed for up to 5 years after their last dose of 
SVd/Vd/SVdX/SdX treatment, has withdrawn consent, has been withdrawn from the study by 
the Investigator, has died, or has been lost to follow-up, whichever occurs first. 

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10. 
STUDY TREATMENTS 
10.1. 
Treatments Administered 
10.1.1. 
Study Treatments 
Selinexor will be provided as film-coated, immediate-release tablets for oral administration in 
blister packs. Selinexor tablets will contain selinexor 20 mg of the Active Pharmaceutical 
Ingredient (API). Refer to the Study Manual for selinexor storage. 
Bortezomib (for SC injection) and dexamethasone (oral tablets) to be used in combination with 
selinexor in this study will be obtained by the investigational sites, unless otherwise specified in 
the contractual agreement. Bortezomib and dexamethasone should be stored as described on their 
respective product labels. 
Study treatments must be dispensed only by a pharmacist or appropriately qualified staff. Study 
treatments are to be dispensed only to patients enrolled in this study. 
10.2. 
Dose Schedules and Administration 
10.2.1. 
Labeling 
All labels will include conditions for storage, lot number, and other information required by the 
Food and Drug Administration (FDA), International Council for Harmonisation (ICH), and/or 
Annex 13, and all local regulations for investigational medications. 
10.2.2. 
Dispensing Directions 
Dispensing instructions for selinexor will be provided in the Study Manual. 
10.2.3. 
Dosing Information 
10.2.3.1. Dosing Sequence and Timing 
In general, where possible, each study treatment (ie, selinexor, bortezomib, dexamethasone) 
should be given at least 1 to 2 hours apart. However, on C2D15 (the day of PK sampling for 
patients in the PK subset of the SVd Arm), selinexor should be dosed within 15 minutes prior to 
bortezomib (Section 11.4). 
Dexamethasone should be administered at least 1 hour before selinexor (SVd Arm) and 
bortezomib. 
10.2.3.2. Selinexor 
For details of selinexor formulation, preparation, and administration, please refer to the Study 
Manual. 
Selinexor tablets should be taken orally with at least 120 mL (4 ounces) of water at 
approximately the same time each day. It can be taken with or without food. Selinexor tablets 
should be swallowed whole (not crushed) to prevent an increased risk of dermatologic toxicity if 
the powder comes in contact with skin. 

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For doses of selinexor that are to be taken on non-clinic days, the patient will be provided with 
selinexor by the site pharmacy and selinexor may be self-administered by the patient on an 
outpatient basis. 
10.2.3.3. Bortezomib 
For details of bortezomib formulation, preparation, and administration, please refer to the full 
prescribing information for bortezomib (different local/regional trade names may be used). 
Bortezomib will only be administered by qualified site personnel during clinic visits in 
accordance with the prescribing information for bortezomib (in the appropriate local language). 
10.2.3.4. Dexamethasone 
For details of dexamethasone formulation, preparation, and administration, please refer to the 
full prescribing information for dexamethasone as it is locally available. 
For doses of dexamethasone that are to be taken on non-clinic days, the patient will be provided 
with dexamethasone and its schedule of administration by the site pharmacy. Dexamethasone 
may be self-administered by the patient on an outpatient basis. 
10.2.4. 
Dose Schedules for Evaluation 
See Section 10.4 for dose modifications. 
10.2.4.1. SVd Arm 
The dose schedule for the SVd Arm (5-week [35-day] cycle) is provided in Table 8. 
• Selinexor will be given as a fixed oral 100 mg dose on Days 1, 8, 15, 22, and 29 of 
each 35-day cycle. 
• Bortezomib will be given at a dose of 1.3 mg/m2 SC on Days 1, 8, 15, and 22 of each 
35-day cycle. 
• Dexamethasone will be given as an oral 20 mg dose on Days 1, 2, 8, 9, 15, 16, 22, 23, 
29, and 30 of each 35-day cycle. 
In no case may the selinexor dose exceed 70 mg/m2 per dose for any patient (see 
Section 11.5.1.1). 
10.2.4.2. Vd Arm 
The dose schedule for Cycles 1 through 8 (3-week [21-day] cycle) for the Vd Arm is provided 
in Table 9. 
• Bortezomib will be given at a dose of 1.3 mg/m2 SC on Days 1, 4, 8, and 11 of each 
21-day cycle for the first 8 cycles. 
• Dexamethasone will be given as an oral 20-mg dose on Days 1, 2, 4, 5, 8, 9, 11, and 
12 of each 21-day cycle for the first 8 cycles. 
The dose schedule for Cycles ≥9 (5-week [35-day] cycle) for the Vd Arm is provided in 
Table 10. 

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• Bortezomib will be given at a dose of 1.3 mg/m2 SC on Days 1, 8, 15, and 22 of each 
35-day cycle. 
• Dexamethasone will be given as an oral 20 mg dose on Days 1, 2, 8, 9, 15, 16, 22, 23, 
29, and 30 of each 35-day cycle. 
10.2.4.3. SVdX Patients 
SVdX patients will return to Cycle 1 for SVd treatment (Table 8) and undergo MM evaluations 
every 5 weeks. SVdX patients will follow the dose schedule for the SVd Arm (Section 10.2.4.1). 
10.2.4.4. SdX Patients 
SdX patients will return to Cycle 1 for Sd treatment (Table 11) and undergo MM evaluations 
every 5 weeks.  
• Selinexor will be given as a fixed oral 100 mg dose on Days 1, 8, 15, 22, and 29 of 
each 35-day cycle. 
• Dexamethasone will be given as an oral 20 mg dose on Days 1, 2, 8, 9, 15, 16, 22, 23, 
29, and 30 of each 35-day cycle. 
10.2.5. 
Selinexor Dose Escalation 
A selinexor dose escalation may be considered for patients being treated with a 
selinexor-containing regimen (ie, SVd Arm, SVdX treatment, or SdX treatment) who meet the 
following 3 criteria: 1) do not achieve at least a PR within the first 2 cycles, 2) are tolerating SVd 
well at dose level 0, and 3) do not have any AEs related to study treatment Grade >2 (National 
Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v. 4.03) at 
the time of dose escalation. The dose schedule for Cycles ≥3 for patients who have a selinexor 
dose escalation is provided in Table 8. 
• For Cycles ≥3, selinexor may be increased to a fixed oral 60 mg dose BIW during 
Weeks 1 through 5. For patients who dose escalate, selinexor will be given as a 60 mg 
dose on Days 1, 3, 8, 10, 15, 17, 22, 24, 29, and 31 of each 35-day cycle. 
Dexamethasone (20 mg) will be given on the same days as selinexor. 
10.2.6. 
Duration of Treatment and Follow-up 
Study treatment (SVd, Vd, SVdX, or SdX) may continue until PD is confirmed by the IRC, 
Investigator or patient decision to discontinue study treatment, pregnancy, unacceptable AEs or 
toxicity that cannot be managed by supportive care, withdrawal of consent, death, or Sponsor 
decision to terminate the study. 
10.3. 
Supportive Care for All Patients 
10.3.1. 
Required 5-HT3 Antagonists 
In order to minimize nausea, all patients should receive 5-hydroxytryptamine (5-HT3) 
antagonists (8 mg or equivalent) unless contraindicated, starting on C1D1 before the first dose of 

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study treatment and continued 2 to 3 times daily thereafter, as needed. Alternative treatment may 
be provided if the patient does not tolerate 5-HT3 antagonists.  
10.3.2. 
Recommended Supportive Care 
Supportive measures for optimal medical care should be provided to all patients in both arms 
during participation in this study. In addition to the required prophylactic therapy with 5-HT3 
antagonists (Section 10.3.1), supportive care per institutional guidelines and/or the National 
Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (NCCN) 
should be used as clinically indicated at the discretion of the Investigator. 
Supportive care guidelines for managing AEs are provided in Table 16. 
10.3.3. 
Infection 
No prophylactic antimicrobial agent is recommended for most patients initiating therapy with 
selinexor. Patients with a history of recurrent infections or those at high risk for specific 
infections may continue their prophylactic antimicrobial regimens without modification when 
initiating selinexor therapy. 
In patients who develop fever or other signs of systemic infection, an appropriate antimicrobial 
should be initiated immediately. Selinexor should be suspended in any patient with a Grade 4 
infection or sepsis (even in the absence of documented infection) until the patient’s clinical 
condition is stabilized. Selinexor can then be restarted at the previous dose once the patient’s 
clinical status has stabilized, even in the setting of continued IV (and/or oral) antimicrobial 
agents. Selinexor is not known to have any drug interactions with standard antimicrobials. Please 
also see Table 16. 
10.3.4. 
Glucocorticoid Side Effects 
The management of common glucocorticoid side effects is well documented. Aggressive use of 
proton-pump inhibitors, anti-hypertensives, glucose-lowering drugs, and other agents is strongly 
encouraged in order to maintain the use of dexamethasone in combination with selinexor in this 
study. 
Patients with documented osteopenia or osteoporosis should continue to take dexamethasone 
with selinexor as indicated in the study. Standard precautions such as use of bisphosphonates 
should be instituted unless contraindicated. 
10.3.5. 
Overdose 
As selinexor is metabolized by glutathione (GSH) conjugation, it is possible, but not 
demonstrated, that hepatic GSH depletion might occur in case of extreme overdose. Therefore, in 
patients who develop liver function test abnormalities, supportive measures such as SAM or 
other drugs that can replace GSH might be considered as part of the overall management plan. 
10.4. 
Dose Modifications 
All dose modifications will be captured in the eCRF. 

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10.4.1. 
Selinexor Dose Reduction Guidelines 
Selinexor, a specific XPO1 inhibitor, alters a variety of tumor suppressors, cell cycle regulators, 
oncoproteins, and transcriptional factors. Given this complex mechanism, the relationship 
between dose and antitumor activity, as well as tolerability, is expected to be highly dependent 
on both tumoral and patient factors. Consistent with this, based on observations from the ongoing 
studies in patients with advanced hematological and solid tumors, selinexor shows a wide 
therapeutic range with antitumor activity from 12 to 120 mg. Therefore, in order to optimize the 
antitumor activity and tolerability, dose reductions and/or schedule modifications will be allowed 
as outlined below and in Table 15 and Table 16. For some AEs, dose interruption rather than 
reduction is recommended. See Table 16 for specific recommendations. 
While drug-related major organ toxicities are not prominent, thrombocytopenia and a number of 
constitutional side effects can limit dosing with selinexor. Therefore, patients should also be 
treated with supportive care to reduce toxicities (see Section 10.3). In addition, it should be noted 
that the constitutional side effects often attenuate over the first 4 to 6 weeks of dosing. Finally, 
some patients with rapid tumor responses experience significant fatigue, nausea, malaise, and/or 
asthenia after 1 or more doses of selinexor. This effect has not been associated with typical 
markers of TLS, but if suspected, assessment of tumor response is strongly recommended in 
order to better inform treatment recommendations. 
The NCI CTCAE v. 4.03 will be used for grading the severity of AEs; the study treatment 
modifications described below are applied according to this severity grading. Toxicity will be 
documented as described in Section 12.1.3. If more than 1 type of toxicity occurs concurrently, 
the most severe grade will determine the modification. 
Each dose modification or treatment delay, as well as the reason, must be documented (Table 15 
and Table 16). 
Table 15 summarizes the starting dose for selinexor (100 mg), the allowed escalation (60 mg 
BIW), and the preferred dose modifications (80 to 40 mg) for AEs listed in Table 16. 
 
Table 15: 
Pre-specified Dose Modifications for AEs Related to Selinexor 
Selinexor Dose Level 
Total Weekly Selinexor Dose 
Selinexor Dose Schedule 
Dose Level +1a 
120 mg 
60 mg BIW (ie, 120 mg QW not allowed) 
Dose Level 0 
(Starting Level) 
100 mg 
100 mg QW 
Dose Level -1 
80 mg 
80 mg QW 
Dose Level -2 
60 mg 
60 mg QW 
Dose Level -3 
40 mg 
40 mg QW 
Abbreviations: AEs = adverse events; BIW = twice weekly; CTCAE = Common Terminology Criteria for Adverse 
Events; NCI = National Cancer Institute; QW = once weekly. 
a Dose level +1 may be considered for patients who meet the following 3 criteria: 1) do not achieve at least a PR 
after the first 2 cycles of SVd, and 2) are tolerating SVd well at dose level 0, and 3) do not have any AEs related to 
study treatment Grade >2 NCI CTCAE v. 4.03 at the time of dose escalation. 

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Table 16: 
Supportive Care and Selinexor Dose Adjustment Guidelines for AEs Related 
to Selinexor 
Toxicity and Intensity 
Supportive Care and Selinexor Dose Adjustment Guidelines 
Fatiguea, b 
Grade 1  
Maintain dose. Rule out other causes. If found to be anemic and 
symptomatic, consider transfusing even with hemoglobin >8 g/dL (anemia 
Grade <3). 
Patients with significant fatigue after several doses of selinexor may have 
an antitumor response. Consider an unscheduled assessment of tumor 
response as part of the patient’s evaluation.  
Grade 2 lasting ≤7 days 
As per NCCN guidelines, consider stimulants such as methylphenidate 
5 mg QD in the morning only. 
Grade 2 lasting >7 days or 
Grade ≥3 
Rule out other causes. If found to be anemic and symptomatic, consider 
transfusions for hemoglobin >8 g/dL (Grade <3); transfusions usually 
indicated for Hb <8 g/dL (Grade ≥3). Interrupt selinexor dosing until 
resolved to Grade 1 or baseline.  
For first occurrence, restart selinexor at current dose.  
For  second occurrence, reduce selinexor by 1 dose level. 
Patients with significant fatigue after several doses of selinexor may have 
an antitumor response. Consider an unscheduled assessment of tumor 
response as part of the patient’s evaluation. 
As per NCCN guidelines, consider stimulants such as methylphenidate 
5 mg QD in the morning only. 
Anorexia or Weight loss 
Grade 1 anorexia  
Maintain dose. Rule out other causes. Consider nutritional consultation and 
use nutritional supplements (eg, Ensure®, Boost®). 
For persistent symptoms, initiate appetite stimulants, such as olanzapine 
(2.5 to 5 mg PO every morning) or megesterol acetate (400 mg QD), as per 
NCCN guidelines. 
Grade 1 weight loss 
Grade 2 anorexia 
Initiate appetite stimulants, such as olanzapine (2.5 to 5 mg PO every 
morning) or megesterol acetate (400 mg QD), as per NCCN guidelines. 
Grade 2 weight loss 
Grade 3 anorexia,  
or Grade 3 weight loss 
Interrupt selinexor dosing until improved to Grade 1 or baseline and weight 
stabilizes. Reduce selinexor by 1 dose level. 
Rule out other causes. Consider nutritional consultation and use nutritional 
supplements (eg, Ensure®, Boost®). 
Initiate appetite stimulants as above. 

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Toxicity and Intensity 
Supportive Care and Selinexor Dose Adjustment Guidelines 
Nausea, Acute  
Grade 1 or 2 
 
Maintain dose. Rule out other causes. Use standard additional anti-nausea 
medications to supplement the protocol-required 5-HT3 antagonists. 
If persistent, use additional anti-nausea medications to supplement the 
protocol-required 5-HT3 antagonist(s). Olanzapine 2.5 to 5 mg PO every 
morning, as per NCCN guidelines, can mitigate nausea and anorexia. 
Grade 3 
Rule out other causes. Use additional anti-nausea medications to 
supplement the protocol-required 5-HT3 antagonist(s). Olanzapine 2.5 to 
5 mg PO every morning, as per NCCN guidelines, can mitigate nausea and 
anorexia. 
Interrupt selinexor dosing until resolved to Grade ≤2 or baseline and reduce 
selinexor by 1 dose level.  
Patients with significant nausea/vomiting after several doses of selinexor 
may have an antitumor response. Consider an unscheduled assessment of 
tumor response as part of the patient’s evaluation. 
Hyponatremia  
Grade 1 (sodium levels < Normal 
to 130 mmol/L)  
Maintain dose. Rule out other causes including drug (eg, diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150 mg/dL).  
Treat hyponatremia per institutional guidelines including dietary review. 
Provide supplemental oral and/or intravenous fluids if dehydration is 
present. Consider addition of salt tablets to patient’s diet. 
Grade 3 with sodium levels 
<130-120 mmol/L without 
symptoms  
Rule out other causes including drug (eg, diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150 mg/dL).  
If (corrected) sodium is Grade ≤3 and continues to be asymptomatic, then 
patient may continue current dosing without interruption provided that IV 
saline and/or salt tablets are provided and patient is followed closely.  
If Grade 3 is persistent or worsens or does not respond to treatment, 
interrupt selinexor dosing until resolved to Grade 1 or baseline and reduce 
selinexor by 1 dose level. 
Grade 3 with sodium levels 
<130-120 mmol/L with symptoms 
or Grade 4 (<120 mmol/L) 
Rule out other causes including drug (eg, diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150 mg/dL).  
Interrupt selinexor dosing until resolved to Grade 1 or baseline and without 
symptoms. Reduce selinexor by 1 dose level. 
Diarrhea  
Grade 1 
Maintain dose. Rule out other causes including drug effects. Treat per 
institutional guidelines with anti-diarrheals, such as loperamide. 
Grade 2 
Rule out other causes including drug effects. Treat per institutional 
guidelines with anti-diarrheals. Interrupt selinexor dosing until resolved to 
Grade 1 or baseline.  
For first occurrence, restart selinexor at current dose.  
For  second occurrence, reduce selinexor by 1 dose level. 
Grade 3 or 4  
Interrupt selinexor dosing until resolved to Grade 1 or baseline and patient 
is clinically stable. Reduce selinexor dose by 1 dose level. 

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Toxicity and Intensity 
Supportive Care and Selinexor Dose Adjustment Guidelines 
Thrombocytopenia 
Grade 1 or 2 
Maintain dose. Rule out other causes including drug effects. 
Grade 3 without bleeding 
Rule out other causes including drug effects.  
For first occurrence: skip 1 dose and reduce selinexor by 1 dose level. 
If recurrent, unless contraindicated, initiate treatment with moderate to high 
doses of thrombopoietin stimulating agents such as romiplostim 5 to 
10 µg/kg SC weekly (preferred) or eltrombopag 100 to 150 mg QD. 
In cases where there is significant disease involvement in the bone marrow 
or pre-existing compromised marrow function (eg, due to prior marrow-
toxic therapy), or if there is thrombocytopenia Grade 2 to 4 at baseline, the 
Investigator in consultation with the Medical Monitor may decide to 
continue selinexor dosing without dose reductions and/or interruptions as 
specified above, provided that platelet counts and bleeding symptoms/signs 
are closely monitored. Thrombopoietin stimulating agents are 
recommended. 
Grade 4 without bleeding 
Rule out other causes including drug effects.  
Interrupt selinexor until patient recovers to Grade 2 or baseline. Selinexor 
dosing may be reduced by 1 dose level (it is recommended to have only 
1 dose modification per cycle) 
If recurrent, unless contraindicated, initiate treatment with moderate to high 
doses of thrombopoietin stimulating agents as above.  
In cases where there is significant disease involvement in the bone marrow 
or pre-existing compromised marrow function (eg, due to prior marrow-
toxic therapy), the Investigator in consultation with the Medical Monitor 
may decide to continue selinexor dosing without dose reductions and/or 
interruptions as specified above, provided that platelet counts and bleeding 
symptoms/signs are closely monitored. 
Grade ≥3 with bleeding 
 
Interrupt selinexor dosing and check platelet counts weekly until the 
bleeding has stopped, patient is clinically stable, and the platelets have 
recovered to Grade 2 or baseline. When resuming selinexor, reduce by 
1 dose level. 
If recurrent, unless contraindicated, initiate treatment with moderate to high 
doses of thrombopoietin stimulating agents as above. 
Neutropenia 
Grade 3 or 4 neutropenia (afebrile) 
OR 
Febrile neutropenia 
Institute colony stimulating factors and prophylactic antibiotics as 
clinically indicated per institutional guidelines. 
Interrupt selinexor and check neutrophils at least weekly until recovers to 
Grade 2 or baseline and without fever (if febrile) and the patient is 
clinically stable. Reinitiate selinexor therapy and colony stimulating factors 
per institutional guidelines. 
If recurrent, continue colony stimulating factors, interrupt selinexor until 
neutrophil counts improve to Grade ≤2 or baseline levels, and reduce dose 
of selinexor 1 dose level. 
Anemia 
Treat per institutional guidelines including blood transfusions and/or erythropoietins. Consider transfusing for 
symptoms with hemoglobin >8 g/dL (Grade <3) or for any Grade 3 (hemoglobin <8 g/dL). If possible, maintain 
selinexor dose as long as patient is clinically stable, but if a dose reduction or interruption is desired, consult with 
the Medical Monitor. 

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Toxicity and Intensity 
Supportive Care and Selinexor Dose Adjustment Guidelines 
Tumor lysis syndrome 
If TLS risk factors are identified, provide prophylactic IV hydration and regular monitoring of hydration 
(especially when increasing the dose of selinexor), renal function, urine output, and clinical laboratory measures 
of interest for TLS (eg, phosphorus, potassium, calcium, LDH, uric acid). Consider administration of 
hypouricemic agents to reduce the risk of TLS. 
Interrupt selinexor in patient with hyperkalemia (≥7.0 mmol/L) and/or symptoms of hyperkalemia, an increase in 
uric acid, or other changes in biochemical blood parameters suggestive of TLS. Start IV hydration and consider 
hypouricemic agent until levels return to normal. Selinexor can be reintroduced at the normal or reduced dose. 
Other selinexor-related adverse events 
Grade 1 or 2 
Rule out other causes. Maintain dose. Start treatment and/or standard 
supportive care per institutional guidelines. 
Grade 3 or 4 
Rule out other causes. Interrupt selinexor until recovers to Grade 2 or 
baseline and reduce selinexor by 1 dose level. 
Isolated values of Grade ≥3 alkaline phosphatase do NOT require dose 
interruption. Determination of liver versus bone etiology should be made, 
and evaluation of gamma-glutamyl transferase, 5'-nucleotidase, or other 
liver enzymes should be performed. 
Abbreviations: IV = intravenous; LDH = lactate dehydrogenase; NCCN = National Comprehensive Cancer 
Network; QD = once daily; PO = oral; SC = subcutaneous: TLS = tumor lysis syndrome. 
a For all Grade ≥3 hematologic or non-hematologic AEs that are NOT selinexor related, after consultation with the 
Medical Monitor and at the discretion of the Investigator, selinexor dosing may be maintained. 
b For all selinexor-related AE’s, if the below prescribed dose reductions/interruptions result in a stabilization of 
≥4 weeks, a re-escalation may be considered after approval from the Medical Monitor. 
All dose modifications should be based on the worst preceding toxicity. 
Note: When toxicities due to selinexor have returned to baseline levels or the patient has stabilized, the dose of 
selinexor may be re-escalated in consultation with the Medical Monitor. 
 
Additional recommendations for supportive care to help manage selinexor-related AEs are 
provided in Section 10.3.2. 
The possibility of overlapping toxicities with bortezomib and/or dexamethasone should be 
considered and it is strongly recommended that the Investigator dose reduces or interrupts 1 drug 
at a time (see Section 10.4.2). 
10.4.1.1. Selinexor Dose Adjustment in the Setting of Infection 
Patients with active uncontrolled or suspected infections should have treatment withheld until the 
infection has clinically resolved and/or the patient is clinically stable. When ready to resume 
dosing, treatment may continue at the original dose. Missed doses will not be replaced. Patients 
may continue on antibiotics for prolonged periods while re-initiating their treatment at the 
discretion of the Investigator.  
10.4.1.2. Conditions Not Requiring Selinexor Dose Reduction 
The following conditions are exceptions to the dose-modification guidelines. Selinexor does not 
need to be interrupted in the following cases: 
• Alopecia of any grade 
• Electrolyte or serum analyte (eg, urate) abnormalities that are reversible with standard 
interventions 

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• Isolated values of Grade ≥3 alkaline phosphatase. Determination of liver versus bone 
etiology should be made, and evaluation of gamma-glutamyl transferase, 
5'-nucleotidase, or other liver enzymes should be performed. 
10.4.2. 
Dose Modifications for Overlapping Toxicities 
Thrombocytopenia and neutropenia are potential overlapping toxicities for selinexor with 
bortezomib. If a patient experiences drug-induced thrombocytopenia and/or neutropenia while 
receiving the combination under investigation in this study, the Investigator should attempt to 
determine which drug may be responsible and treat appropriately, including dose modifications, 
as necessary. If, during the management of an AE for an individual patient receiving both 
selinexor and bortezomib, the Investigator suspects that bortezomib may be the cause of that 
event, the Investigator should discuss the case with the Medical Monitor. If the cause cannot be 
attributed to a single drug, it is strongly recommended that the Investigator dose reduces or 
interrupts 1 drug at a time. Please refer to Table 16 for AEs presumed to be related to selinexor. 
The manufacturers of bortezomib have provided dose adjustment guidelines for managing 
Grade 3 to 4 thrombocytopenia and neutropenia that occur during treatment with bortezomib in 
the prescribing information. 
10.4.3. 
Bortezomib Dose Modifications 
In the event of bortezomib-related peripheral neuropathy (Grade 1 with pain or Grade 2 
[moderate symptoms; limiting instrumental activities of daily living]), during treatment with 
1.3 mg/m2 bortezomib BIW, change treatment schedule to 1.3 mg/m2 bortezomib QW. 
For all other bortezomib-related events, the bortezomib dose may be adjusted during treatment 
according to the guidelines in the prescribing information for bortezomib (different 
local/regional trade names may be used). 
10.4.4. 
Dexamethasone Dose Modifications 
The dose of dexamethasone should preferably remain constant throughout the study. 
However, for patients with partial intolerance to dexamethasone, a dose reduction to a minimum 
dose of 10 to 12 mg dexamethasone BIW (ie, a total minimum dose of 20 to 24 mg weekly) is 
permitted after a clear documentation of intolerance. Any dose reductions should be documented 
in the patient’s research record and the eCRF. 
10.5. 
Missed or Vomited Doses 
10.5.1. 
Missed Doses of Study Treatments (Selinexor, Bortezomib, and Dexamethasone) 
Missed doses of study treatments should be managed as follows:  
For doses missed for protocol- or study-related reasons (eg, due to recommendation of the 
Investigator, such as due to an AE): 
• Missed dose of bortezomib for patients in the Vd Arm Only: If a bortezomib dose 
was missed, the schedule of that week should be altered to accommodate 2 doses in 
that week with at least 72 hours between 2 consecutive doses of bortezomib. 

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• Missed dose of any study treatment for all patients: If a dose of any study 
treatment must be missed, the next dose will be taken as per schedule. All missed and 
delayed doses should be documented. 
For doses missed for reasons not related to the protocol/study (eg, a required medical 
procedure or an unanticipated personal emergency): 
• If a patient missed a full 1- or 2-week period of study treatment dosing for events that 
are not related to the protocol or the study the days missed will be replaced. For 
example, if a patient missed C2D7 to C2D14, then the patient will start the next 
dosing on C2D7 following the break. Similarly, if a patient misses C3D1 to C3D15, 
then the patient will start the next dosing on C3D1. 
The schedule of MM evaluations will be maintained regardless of drug holidays or drug 
interruptions (Section 11.3.1). 
10.5.2. 
Vomited Doses of Selinexor 
If a dose of selinexor is vomited within 1 hour of ingestion, it will be replaced. If vomiting 
occurs more than 1 hour after dosing, it will be considered a complete dose. 
10.6. 
Sponsor-supplied Study Treatment Accountability 
The Investigator or designee must maintain an accurate record of receipt of shipment and 
dispensing of Sponsor-supplied study treatment in a drug accountability log. Accountability for 
Sponsor-supplied study treatment will be documented throughout the study and reconciled. 
Patients will be asked to return all unused Sponsor-supplied study treatment and packaging on a 
regular basis, at the end of the study or at the time of discontinuation of selinexor. All unused 
Sponsor-supplied study treatment must be destroyed with accompanied documentation. 
10.7. 
Compliance 
The Investigator or other study staff will either directly administer or supervise study treatment 
given in the clinic and instruct the patient on study treatment self-administration, as appropriate. 
Patients will be asked to bring their Sponsor-supplied study treatment containers with them at 
each visit, and compliance with Sponsor-supplied protocol-defined study treatment intake at 
home will be checked by tablet count. 
Compliance to oral Sponsor-supplied study treatment taken at home will be assessed by the 
Investigator and/or study personnel at each visit and recorded in source documents after 
discussion with the patient and after performing Sponsor-supplied study treatment 
accountability. 
The Investigator will account for the number of Sponsor-supplied tablets dispensed against those 
returned by the patient. Any deviations and missed doses will be recorded in the eCRF and drug 
accountability logs along with the reasons for subsequent verification. 

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10.8. 
Contraception Requirements and Concomitant Medications 
10.8.1. 
Contraception Requirements 
Patients should not become pregnant or father a child while on this study because the study 
treatments in this study can affect an unborn baby. Women should not breastfeed a baby while 
on this study. It is important that patients understand the need to use birth control while on this 
study.  
Female patients of childbearing potential and fertile male patients must agree to use highly 
effective contraception listed below (ie, results in a low failure rate when used consistently and 
correctly) during the dosing period and for a period of at least 3 months after the end of 
treatment. 
Highly effective methods include: 
• combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device 
• intrauterine hormone-releasing system 
• bilateral tubal occlusion 
• vasectomized partner 
• sexual abstinence 
Please see Section 4.2.7.1 for additional safety information related to pregnancy.  
10.8.2. 
Non-study-related Concomitant Medication and Treatment 
Concomitant medications include any prescription or over-the-counter preparation, including 
vitamins, dietary supplements, over-the-counter medications, and oral herbal preparations taken 
during the study. Patients may continue their baseline medication(s). All concomitant 
medication(s) must be reported in the eCRF. Any diagnostic, therapeutic, or surgical procedure 
performed during the study period should be recorded, including the dates, description of the 
procedure(s), and any clinical findings, if applicable.  

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10.8.2.1. Permitted Concomitant Medication 
Patients will receive concomitant medications to treat symptoms, AEs, and intercurrent illnesses 
that are medically necessary as part of standard care. Medications to treat concomitant diseases 
like diabetes, hypertension, etc. are allowed.  
10.8.2.2. Use of Blood Products 
During treatment, patients may receive RBC or platelet transfusions, if clinically indicated, per 
institutional guidelines. Patients who require repeated transfusion support should be discussed 
with the Sponsor. 
Appropriate anti-coagulation is allowed during the study (eg, low molecular weight heparin, 
direct factor Xa inhibitors, etc.). Warfarin is allowed during the study provided patients are 
monitored for INR twice a week during the first 2 cycles of study treatment, then weekly to 
biweekly thereafter. 
Patients may receive supportive care with erythropoietin, darbepoetin, G-CSF or GM-CSF, 
pegylated growth factors, and platelet stimulatory factors, in accordance with clinical practice or 
institutional guidelines throughout the study. 
The use of blood products, transfusions, etc. will be documented in the eCRF. 
10.8.2.3. Radiation Treatment 
If clinically indicated, palliative radiation therapy to non-target lesions is permitted but study 
treatment should be held for ≥1 day before the start of palliative radiation therapy and ≥1 day 
following each dose of palliative radiation therapy. Study treatment shall not be discontinued 
solely due to palliative radiation. 
10.8.3. 
Restrictions for Study Treatment 
10.8.3.1. Restrictions for Selinexor 
Medications: There are no restrictions on the use of acetaminophen or acetaminophen-
containing products in combination with selinexor, EXCEPT on days of selinexor 
dosing, when acetaminophen use must not exceed a total daily dose of 1 g. 
Patients should not take GSH-, S-adenosylmethionine (SAM)-, or 
N-acetylcysteine-containing products during their participation in this study as 
these products may enhance the metabolism of selinexor. However, they are 
permitted if the patient has elevated liver function tests. 
Diet: 
There are no dietary restrictions on this study. Patients on selinexor should 
maintain adequate caloric and fluid intake. 
10.8.3.2. Restrictions for Bortezomib and Dexamethasone 
Refer to the full prescribing information for bortezomib (different local/regional trade names 
may be used) for the most current information for restrictions. 

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10.8.4. 
Prohibited Medications 
Concurrent therapy with any approved or investigative anticancer therapeutic outside of those 
included in this study is not allowed. Use of any immunosuppressive agents during the study 
must be confirmed by the Sponsor. Refer to the full prescribing information for bortezomib 
(different local/regional trade names may be used) for the most current information on prohibited 
concurrent medications. 

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11. 
ASSESSMENTS 
Procedures that are performed as part of standard of care should not be repeated if they are 
within the Screening window and are done prior to signing the ICF. 
11.1. 
Informed Consent 
Assessments may not be performed until the patient provides written informed consent (see 
Section 14.6). 
SVdX/SdX patients will be required to sign a separate ICF for treatment with SVd/Sd. 
11.2. 
Demographic and Baseline Characteristics Assessments 
11.2.1. 
Demographics 
Patient demographics (including date of birth, sex, race, ethnicity, and age at the time of consent) 
will be collected. 
11.2.2. 
Medical History 
A complete medical history will be obtained from each patient. Medical history will include 
baseline symptoms as well as a detailed history of prior procedures for the patient’s MM and 
other prior cancer therapies (ie, chemotherapy, hormonal therapy, immunotherapy, biotherapy, 
radiotherapy, and surgery), including start and end dates, best response, PD during or after 
therapy, as well as discontinuations due to intolerability or toxicity. Smoking history will be 
recorded. A detailed history of disease-specific diagnostic and prognostic testing and test results 
(such as phenotypic and cytogenetic profiles) will also be collected. Evaluate the risk of TLS 
based on a clinical evaluation of comorbidity (such as presence of renal impairment or cardiac 
insufficiency). 
Data from standard-of-care procedures will be part of the patient's medical history and may be 
used for study purposes. 
11.3. 
Efficacy Assessments 
Efficacy evaluations will be performed as described below. Refer to Table 2, Table 4, Table 5, 
Table 6, and Table 7 for the timing of all efficacy assessments. 
11.3.1. 
Multiple Myeloma Disease Assessments 
Patient response will be assessed by the procedures described in the following subsections and 
graded according to the IMWG response criteria summarized in Table 17 (Kumar 2016). Per 
IMWG, quantitative Ig levels by nephelometry may be used in place of SPEP for routine 
M-protein measurement for patients with IgA or IgD myeloma. Also, per IMWG, response may 
be confirmed if the patient fails to provide 24-hour urine sample collection after screening 
activities occur. However, all MM disease assessments outlined below are required to be 
performed at the study visits specified in Table 2, Table 4, Table 5, Table 6, and Table 7 and the 
Investigator should make all attempts to collect all MM disease assessments at each time point as 
outlined in this protocol. 

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Patients randomized to the SVd and Vd Arms will undergo MM evaluations every 3 weeks from 
baseline MM evaluations on C1D1 (regardless of drug holidays or drug interruptions) through 
the first day of Week 37 (ie, 12 MM evaluations after C1D1) to identify patients who progress 
quickly, then every 5 weeks for the remainder of the study regardless of cycle length (see Table 4 
and Table 5). This will result in comparable PFS data from both arms. SVdX patients (Table 6) 
and SdX patients (Table 7) will undergo MM evaluations every 5 weeks. If additional MM 
disease assessments (ie, SPEP, urine protein electrophoresis [UPEP], serum FLC, quantitative Ig, 
serum/urine protein immunofixation, and clinical plasmacytoma assessment) are performed at 
unscheduled times, those results must be documented in the eCRF as unscheduled visits.  
Samples on C1D1 must be collected either on Day -1 or predose on C1D1 for baseline values. 
All MM disease assessments should be performed regardless of the diagnosis that is being 
followed (ie, 24-hour urine collection for UPEP must be performed at each time point outlined in 
the protocol even if the patient is being followed by SPEP). 
Two consecutive assessments are needed to confirm response (Table 17). For patients who 
achieve CR or sCR, confirmatory samples for SPEP with serum protein immunofixation, 
quantitative Ig, and serum FLC must be collected in duplicate at the time of response and the 
duplicate samples must be provided to the central laboratory. A confirmatory 24-hour urine 
sample must also be collected, and an aliquot will be provided to the central laboratory for UPEP 
with urine protein immunofixation. Refer to the Study Manual for details. 
For the purposes of Risk-Based Monitoring activities, sites may be requested/required to provide 
de-identified laboratory results (MM disease assessments) via the electronic data capture system. 
Further instructions will be provided in the Study Manual. 
Table 17: 
International Myeloma Working Group Response Criteria, Myeloma 
(Kumar, 2016) 
IMWG Response Criteriaa, b, c 
Response Subcategory 
Response Criteria 
Complete response (CR) 
Negative immunofixation of serum and urine, disappearance of any 
soft tissue plasmacytomas, and <5% plasma cells in bone marrow 
aspirates 
Stringent complete response 
(sCR)  
CR as defined above plus normal FLC ratiod and absence of clonal 
cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio 
≤4:1 or ≥1:2 for κ and λ patients, respectively, after counting 
≥100 plasma cellse 
Very good partial response 
(VGPR)  
Serum and urine M-protein detectable by immunofixation but not on 
electrophoresis or ≥90% reduction in serum M-protein plus urine 
Mprotein- level <100 mg per 24 hr 
Partial response (PR)  
≥50% reduction of serum M-protein plus reduction in 24-hr urinary 
M-protein by ≥90% or to <200 mg/24 hr.  

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IMWG Response Criteriaa, b, c 
Response Subcategory 
Response Criteria 
If the serum and urine M-protein are not measurable, a ≥50% 
decrease in the difference between involved and uninvolved FLC 
levels is required in place of the M-protein criteria. 
If serum and urine M-protein and serum FLC assay are not 
measurable, ≥50% reduction in plasma cells is required in place of 
M-protein, provided baseline bone marrow plasma cell percentage 
was ≥30%. 
In addition to the above criteria, if present at baseline, a ≥50% 
reduction in the size (SPD) of soft tissue plasmacytomas is also 
required.f  
Minimal response (MR)  
≥25% but <49% reduction of serum M-protein and reduction in 24-hr 
urine M-protein by 50–89%. 
In addition to the above criteria, if present at baseline, a ≥50% 
reduction in the size (SPD) of soft tissue plasmacytomas is also 
required.f 
Stable disease (SD) 
Not recommended for use as an indicator of response; stability of 
disease is best described by providing the time-to-progression 
estimates. Not meeting criteria for CR, VGPR, PR, MR, or PD. 
Progressive disease (PD)g, h 
Any 1 or more of the following criteria: 
Increase of 25% from lowest confirmed response value in 1 or 
more of the following criteria: 
Serum M-protein with absolute increase of ≥0.5 g/dL; 
Serum M-protein increase ≥1 g/dL if the lowest M-component 
was ≥5 g/dL; 
Urine M-protein (absolute increase must be ≥200 mg/24 hr);  
In patients without measurable serum and urine M-protein levels: 
the difference between involved and uninvolved FLC levels 
(absolute increase must be >10 mg/dL); 
In patients without measurable serum and urine M-protein levels 
and without measurable involved FLC levels: bone marrow 
plasma cell percentage irrespective of baseline status (absolute 
increase must be ≥10%); 
Appearance of a new lesion(s), ≥50% increase from nadir in SPDf of 
>1 lesion, or ≥50% increase in the longest diameter of a previous 
lesion >1 cm in short axis; 

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IMWG Response Criteriaa, b, c 
Response Subcategory 
Response Criteria 
≥50% increase in circulating plasma cells (minimum of 200 cells per 
μL) if this is the only measure of disease 
Clinical relapse 
Clinical relapse requires 1 or more of the following criteria: 
Direct indicators of increasing disease and/or end organ 
dysfunction (CRAB features) related to the underlying clonal 
plasma-cell proliferative disorder. It is not used in calculation of 
time-to-progression or PFS but is listed as something that can be 
reported optionally or for use in clinical practice; 
Development of new soft tissue plasmacytomas or bone lesions 
(osteoporotic fractures do not constitute progression); 
Definite increase in the size of existing plasmacytomas or bone 
lesions. A definite increase is defined as a 50% (and ≥1 cm) 
increase as measured serially by the SPDf of the measurable 
lesion; 
Hypercalcaemia (>11 mg/dL); 
Decrease in hemoglobin of ≥2 g/dL not related to therapy or 
other non-myeloma-related conditions; 
Rise in serum creatinine by 2 mg/dL or more from the start of the 
therapy and attributable to myeloma; 
Hyperviscosity related to serum paraprotein 
Relapse from CR (to be used 
only if the endpoint is 
diseasefree- survival) 
Any 1 or more of the following criteria: 
Reappearance of serum or urine M-protein by immunofixation or 
electrophoresis; 
Development of ≥5% plasma cells in the bone marrow; 
Appearance of any other sign of progression (ie, new 
plasmacytoma, lytic bone lesion, or hypercalcaemia see above) 
Relapse from MRD negative 
(to be used only if the endpoint 
is disease-free survival) 
Any 1 or more of the following criteria: 
Loss of MRD negative state (evidence of clonal plasma cells on 
NGF or NGS, or positive imaging study for recurrence of 
myeloma); 
Reappearance of serum or urine M-protein by immunofixation or 
electrophoresis; 
Development of ≥5% clonal plasma cells in the bone marrow; 

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IMWG Response Criteriaa, b, c 
Response Subcategory 
Response Criteria 
Appearance of any other sign of progression (ie, new 
plasmacytoma, lytic bone lesion, or hypercalcaemia) 
Abbreviations: ASCT = autologous stem-cell transplantation; CR = complete response; CRAB features = calcium elevation, 
renal failure, anemia, lytic bone lesions; CT = computed tomography; DOR = duration of response; FDG = 
fluorodeoxyglucose; FLC = free light chain; hr = hour; Ig = immunoglobulin; IMWG = International Myeloma Working 
Group; MM = multiple myeloma; MR = minimal response; MRD = minimal residual disease; MRI = magnetic resonance 
imaging; NGF = next-generation flow; NGS = next-generation sequencing; PD = progressive disease; PET = positron 
emission tomography; PFS = progression-free survival; PR = partial response; sCR = stringent complete response; SD = 
stable disease; SPD = sum of the products of the maximal perpendicular diameters of measured lesions; VGPR = very good 
partial response. 
Source: Kumar, 2016 (Kumar 2016). 
a All response categories require 2 consecutive assessments made any time before starting any new therapy; for 
MRD there is no need for 2 consecutive assessments, but information on MRD after each treatment stage is 
recommended (eg, after induction, high-dose therapy/ASCT, consolidation, maintenance). MRD tests should be 
initiated only at the time of suspected CR. All categories of response and MRD require no known evidence of 
progressive or new bone lesions if radiographic studies were performed. However, radiographic studies are not 
required to satisfy these response requirements except for the requirement of FDG PET if imaging MRD-negative 
status is reported. 
b Per IMWG, quantitative Ig levels by nephelometry may be used in place of SPEP for routine M-protein 
measurement for patients with IgA or IgD myeloma. Also, per IMWG, response may be confirmed if the patient 
fails to provide 24-hour urine sample collection after screening activities occur. See “Practical considerations for 
application of IMWG consensus criteria” section of the guidelines (page e340 in Kumar [Kumar 2016]). 
c Derived from international uniform response criteria for MM (Durie 2006). MR definition and clarifications 
derived from Rajkumar (Rajkumar 2011Rajkumar 2011Rajkumar 2011). When the only method to measure 
disease is by serum FLC levels: CR can be defined as a normal FLC ratio of 0.26 to 1.65 in addition to the CR 
criteria listed previously. VGPR in such patients requires a ≥90% decrease in the difference between involved and 
uninvolved FLC levels. All response categories require 2 consecutive assessments made at any time before the 
institution of any new therapy; all categories also require no known evidence of progressive or new bone lesions or 
extramedullary plasmacytomas if radiographic studies were performed. Radiographic studies are not required to 
satisfy these response requirements. Bone marrow assessments do not need to be confirmed. Each category, except 
for SD, will be considered unconfirmed until the confirmatory test is performed. The date of the initial test is 
considered as the date of response for evaluation of time dependent outcomes such as DOR. 
d All recommendations regarding clinical uses relating to serum FLC levels or FLC ratio are based on results 
obtained with the validated Freelite test (Binding Site, Birmingham, United Kingdom). 
e Presence/absence of clonal cells on immunohistochemistry is based upon the κ/λ/L ratio. An abnormal κ/λ ratio by 
immunohistochemistry requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence 
of an abnormal clone is κ/λ of >4:1 or <1:2. 
f Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT 
scans where applicable. For patients with only skin involvement, skin lesions should be measured with a ruler. 
Measurement of tumor size will be determined by the SPD. 
g Positive immunofixation alone in a patient previously classified as achieving a CR will not be considered 
progression. For purposes of calculating time-to-progression and PFS, patients who have achieved a CR and are 
MRD-negative should be evaluated using criteria listed for PD. Criteria for relapse from a CR or relapse from 
MRD should be used only when calculating disease-free survival. 
h In the case where a value is felt to be a spurious result per Investigator discretion (eg, a possible laboratory error), 
that value will not be considered when determining the lowest value. 

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Questions regarding interpretation of the IMWG criteria (Table 17) may be addressed by 
consulting the, “Practical considerations for application of IMWG consensus criteria,” section of 
the guidelines (page e340 in Kumar (Kumar 2016). 
11.3.1.1. SPEP 
SPEP with monoclonal protein band (M-spike) quantification and serum protein immunofixation 
will be performed to assess response. 
11.3.1.2. UPEP 
UPEP (24-hour urine) with M-spike quantification and urine protein immunofixation will be 
performed to assess response. UPEP must be determined from a urine sample collected for 
24 hours – no other method is acceptable.  
UPEP must be performed at each time point outlined in the protocol even if the patient is being 
followed by SPEP. 
11.3.1.3. Quantitative Immunoglobulin Levels 
If SPEP is felt to be unreliable for routine M-protein measurement (eg, patients with IgA or IgD 
myeloma), then quantitative Ig levels by nephelometry is acceptable. However, this must be 
explicitly reported, and even though nephelometry can be used for the patient to assess response, 
SPEP and nephelometric values cannot be used interchangeably (Durie 2006).  
11.3.1.4. Serum FLC 
Serum FLC will be performed to assess response. 
For patients whose disease is only measurable by serum FLC: 
• CR requires negative serum and urine immunofixation plus a normal serum FLC ratio 
of 0.26 to 1.65 on 2 consecutive assessments. Laboratories may use their own 
reference ranges. 
• VGPR requires >90% decrease in the difference between involved and uninvolved 
serum FLC levels on 2 consecutive assessments. 
11.3.1.5. β2 microglobulin 
β2 microglobulin will be performed for MM staging (Table 14) and will not be used to assess 
response. 
11.3.1.6. LDH 
Serum LDH will be performed for MM staging (Table 14). 
11.3.1.7. Skeletal Survey 
A baseline skeletal survey will be performed using X-rays and/or other clinically appropriate 
imaging modalities (eg, magnetic resonance imaging ([MRI], whole body computed tomography 
[CT], or positron emission tomography [PET]/CT) as determined by the Investigator. 

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The skeletal survey should include a lateral radiograph of the skull, anterioposterior and lateral 
views of the spine, and anterioposterior views of the pelvis, ribs, femora, and humeri. 
If lytic bone lesions or plasmacytomas are observed at baseline, their number and size should be 
recorded in the eCRF. Bone lesions and/or plasmacytomas detected by imaging at baseline 
should be reassessed during the study, at a frequency determined by the Investigator, using the 
same imaging modality that was used at baseline to document response.  
• For patients without soft tissue plasmacytomas (ie, bone lesions only), skeletal survey 
by X-rays or low-dose CT should be performed. Contrast is not required. 
• For patients with soft tissue plasmacytomas, skeletal survey by X-rays or low-dose 
CT should be performed (contrast not required) and in addition MRI or CT or 
PET/CT, usually requiring contrast enhancement, should be performed. 
Skeletal imaging does not need to be repeated in Cycle 1. 
Skeletal survey results will be read by the local laboratory. Refer to the Study Manual for details.  
11.3.1.8. Clinical Plasmacytoma Assessment 
If plasmacytomas are detected at baseline by physical examination/palpation, they should be 
counted and measured per IMWG guidelines and recorded, and then reassessed as clinically 
indicated during the symptom-directed physical examinations. 
11.3.1.9. Bone Marrow Aspirate 
A bone marrow aspirate will be collected at Screening and a portion will be provided to the 
central laboratory for karyotyping and fluorescence in situ hybridization (FISH) analysis to 
confirm diagnosis and classify cytogenetic MM subtypes for R-ISS staging.  
Another portion of the Screening bone marrow aspirate will be used to isolate plasma, non-tumor 
CD138- and tumor CD138+ cell fractions for future PDn testing (see Section 11.4.2.1). 
Evaluation of cytogenetic alterations will include deletion of 17p [del(17p)], a translocation of 
chromosome [t(4;14)], a translocation of chromosome 14 and chromosome 16 [t(14;16)], and 
chromosome 1q21 amplification. 
A bone marrow aspirate is required at the time of response for the MRD test for patients in either 
arm who achieve CR or sCR, unless after consultation with the Medical Monitor the collection 
and/or processing of the sample is not considered to be feasible.  
A portion of the bone marrow aspirate collected at the time of response will be provided to the 
central laboratory. Refer to the Study Manual for details. 
MRD will be assessed by fluorescence activated cell sorting (FACS) of bone marrow aspirates. 
MRD results will be quantitative: MRD positive = number of malignant clones per 
100,000 leukocytes >0; MRD negative = number of malignant clones per 100,000 leukocytes 
= 0.  
Bone marrow aspiration may also be performed, as clinically indicated, to assess progression. 

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11.3.1.10. Bone Marrow Core (Trephine) Biopsy 
At the time of response, a bone marrow core (trephine) biopsy is required to confirm CR and 
sCR.  
A tissue block collected at the time of response for patients in either arm who achieve CR or sCR 
will be provided to the central laboratory. Refer to the Study Manual for details. 
A bone marrow core (trephine) biopsy may also be performed, as clinically indicated, to assess 
progression. 
11.4. 
Pharmacokinetic and Pharmacodynamic Procedures 
11.4.1. 
Pharmacokinetic Endpoints 
PK sampling will only be performed at selected investigational sites that can accommodate 
patients for up to 4 hours. 
• PK sampling for bortezomib will be performed for up to 25 patients in the Vd Arm. 
• PK sampling for bortezomib and selinexor will be performed for up to 25 patients in 
the SVd Arm. 
Blood draws for PK analysis will be performed in accordance with Table 18. For the SVd Arm, 
selinexor should be dosed within 15 minutes prior to bortezomib on C2D15. 
Details of PK sample collection and processing can be found in the Study Manual. 
Plasma samples will be analyzed via validated methods for plasma bortezomib and selinexor 
concentrations. 
PK endpoints may include, but are not limited to, estimations of Cmax, AUC, and tmax. 
Table 18: 
Collection Time Points for Bortezomib and Selinexor PK 
Time Points for PK Sample Collection 
Vd Arm 
(bortezomib 
PK) 
SVd Arm 
(bortezomib and 
selinexor PK) 
C2D11 
C2D15a 
Predose (before dosing of bortezomib in the Vd 
Arm and before dosing of selinexor and 
bortezomib in the SVd Arm) 
X 
X 
30 min (± 5 min) post-bortezomib dose 
X 
X 
1 hr (± 10 min) post-bortezomib dose 
X 
X 
2 hr (± 10 min) post-bortezomib dose 
X 
X 
4 hr (± 10 min) post-bortezomib dose (if 
feasible) 
X 
X 
Abbreviations: hr = hours; min = minutes; PK = pharmacokinetics; SVd = selinexor plus bortezomib 
plus low-dose dexamethasone; Vd = bortezomib plus low-dose dexamethasone. 
a Selinexor should be dosed within 15 minutes prior to bortezomib on C2D15. 

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11.4.2. 
Pharmacodynamic Studies 
11.4.2.1. Bone Marrow Aspirates for PDn 
Bone marrow aspirate will be collected at Screening to isolate plasma, non-tumor CD138- and 
tumor CD138+ cell fractions for subsequent PDn studies. Studies may include transcriptomic, 
genomic and/or proteomic analyses to identify predictive biomarkers of selinexor response and 
to characterize the knowledge of selinexor’s mechanism of action. In addition, tumor cells will 
be used to assess the presence of the high risk mutations including del(17p), t(14;16) and t(4;14) 
translocations and chromosome 1q21 amplification. Cytogenetic analysis by karyotyping and 
FISH will be performed at a central laboratory to identify specific chromosomal translocations at 
sites known to show rearrangements in MM. 
Aspirate samples containing patient DNA may be used for pharmacogenetic research to do the 
following:  
• study the causes of human diseases  
• help understand how different individuals respond to drugs  
• obtain information to help develop new methods to diagnose and treat diseases 
The samples may be stored up to 15 years, depending on the laws of country where the study is 
conducted. The samples will be labeled with a code rather than with patient name or any other 
detail that could be used to identify the patient. These samples will be stored under the control of 
the Sponsor. 
Details of PDn sample collection and processing can be found in the Study Manual. 
11.5. 
Safety Assessments 
Safety evaluations will be performed as described below. Refer to Table 2 for the timing of all 
safety assessments. 
11.5.1. 
Clinical Safety Assessments 
11.5.1.1. Weight, Height, and BSA 
Height (without shoes) in centimeters and weight (indoor clothing without shoes) in kilograms 
will be measured. BSA will be calculated by the Dubois (Dubois 1916) or Mosteller (Mosteller 
1987) method to determine the volume of bortezomib to be administered and to ensure that an 
individual patient's selinexor dose does not exceed 70 mg/m2. In no case may the selinexor dose 
exceed 70 mg/m2 per dose for any patient. If the patient’s weight fluctuates substantially from 
baseline (ie, >20%) during treatment, BSA should be recalculated. 
11.5.1.2. Physical Examination, Vital Signs, and ECOG Performance Status 
Complete physical examinations should include general appearance, skin, neck, eyes, ears, nose, 
throat, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological examinations.  
Symptom-directed physical examinations should include body systems as appropriate, including 
the presence/absence or change in size of plasmacytomas identified at Screening. These 
examinations will be performed according to the standards at each institution.  

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Information about the physical examinations must be present in the source documentation at the 
study site. Clinically relevant findings made after the start of study dosing, which meet the 
definition of an AE, must be recorded in the AE eCRF. 
Vital signs include systolic and diastolic blood pressure (BP), pulse measurements, and body 
temperature (°C or °F). Vital signs should be assessed predose on the scheduled visit day, if 
possible. BP and pulse rate should be measured after the patient has been in a supine or sitting 
position for 5 minutes. BP should be assessed on the same arm throughout the study. Note: If the 
visit for MM disease assessments occurs on the same day as the in-clinic dosing visit, vital signs 
should only be performed once. 
ECOG performance status assessments (Oken 1982) will be performed during the study to assess 
how the disease affects the daily living abilities of the patients. 
11.5.1.3. Electrocardiography 
A standard 12-lead ECG will be performed. Patients must rest for at least 5 minutes prior to the 
ECG recording. The Investigator will interpret the ECG using 1 of the following categories: 
normal, abnormal but not clinically significant, or abnormal and clinically significant. The date 
and time the ECG was performed and the following parameters will be recorded in the eCRF: 
heart rate, PR interval, QT interval, QRS interval, and QT corrected using Fridericia's formula 
(Fridericia 1920). 
11.5.1.4. Ophthalmic Examination 
An ophthalmic examination by an optometrist or ophthalmologist is required prior to the first 
dose of study treatment and should be repeated if clinically indicated during the study (eg, 
monitoring of pre-existing cataracts, visual disturbances). 
Any patient reporting de-novo or worsening of visual symptoms should immediately be referred 
for further examination. All visual symptoms must be documented in the eCRF. 
The ophthalmic examination is to include the following:  
• Prior to dilation: 
− best corrected visual acuity  
− slit lamp examination (for cataracts or other abnormalities) 
− tonometry 
• Following dilation:  
− fundoscopy 
− slit lamp examination to document lens clarity 
If a cataract/lens opacity is seen during the examination, the cataract/lens opacity will be graded 
according to the American Optometric Association (AOA) Cataract Grading System, which is 
available on the AOA website (www.aoa.org). 

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11.5.1.5. Concomitant Medications 
Concomitant medications will be documented for each patient. A detailed history of medications 
will be documented. At each study visit, patients will be asked whether they have taken any 
medication other than the study treatment. All concomitant medications including dietary 
supplements, over-the-counter medications, and oral herbal preparations, as well as changes in 
medication, will be recorded in the eCRFs. 
Necessary supportive care, such as appetite stimulants, anti-emetics, anti-diarrheals, etc. is 
allowed (see Table 16 and Section 10.3). 
11.5.1.6. Adverse Events 
Information regarding AEs and SAEs will be collected. See Section 12. 
11.5.2. 
Laboratory Safety Assessments 
11.5.2.1. Clinical Laboratory Tests 
Table 19 presents the clinical laboratory tests that will be performed during the study. 
Table 19:  
Clinical Laboratory Tests 
Complete Blood Count with Differential (Blood sample: whole blood + EDTA) 
Hemoglobin 
Hematocrit 
Mean corpuscular 
volume 
Mean corpuscular 
hemoglobin 
Mean corpuscular 
hemoglobin 
concentration 
WBC count 
WBC differentiala 
RBC count 
Lymphocytes 
Monocytes 
Neutrophils 
Eosinophils 
Basophils 
Platelets 
 
Complete Serum Chemistry (Blood sample: serum) 
Sodium 
Potassium 
Chloride 
Bicarbonate 
Urea or blood urea 
nitrogenb 
Creatinine 
Glucose 
Calcium 
Phosphate 
Magnesium 
ALT 
AST 
Alkaline Phosphatase 
Total bilirubin 
 
Total protein 
Albumin 
Creatine kinase 
Urate 
 
Coagulation 
Prothrombin time 
International 
normalized ratio 
Activated 
thromboplastin time 
 
 
Urinalysisc 
Appearance 
Color 
Glucose 
Hemoglobin 
Ketones 
pH 
Protein 
Specific gravity 
 
 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; EDTA = 
ethylenediaminetetraacetic acid; RBC = red blood cell; ULN = upper limit of normal; WBC = white blood cell.  
a WBC differential may be automated or manual as per institutional standards. Reticulocytes may be done only 
when clinically indicated. 
b Urea (mg/dL) = Blood urea nitrogen (mg/dL) × 2.14. 
c Microscopy will only be performed if clinically indicated. 

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CCI

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 86 
Version 4.0 
12. 
SAFETY DEFINITIONS, RECORDING, AND REPORTING 
Note: For urgent medical issues in which the study’s Medical Monitor should be contacted, 
please refer to the Study Manual for complete contact information. 
12.1. 
Adverse Events 
12.1.1. 
Definitions 
• Adverse event (AE): Any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease temporally associated with the use of 
study treatment, whether or not considered related to the study treatment.  
• Treatment-emergent adverse event (TEAE): Any event that was not present prior to 
the initiation of study treatment or any event already present that worsens in either 
intensity or frequency following exposure to study treatment.  
• Adverse event of special interest (AESI): Any AE (serious or nonserious) that is of 
scientific and medical concern specific to the study treatment, for which ongoing 
monitoring and rapid communication by the Investigator to the Sponsor is 
appropriate.  
• Serious adverse event (SAE): Any untoward medical occurrence that, at any dose, 
results in death; is life threatening (ie, an event in which the patient was at risk of 
death at the time of the event; it does not refer to an event that hypothetically might 
have caused death if it were more severe); requires inpatient hospitalization or 
prolongation of existing hospitalization; results in persistent or significant 
disability/incapacity; or is a congenital anomaly/birth defect. (See Section 12.2.3 for 
additional information about SAE reporting.)  
12.1.2. 
Recording of Adverse Events 
All AEs that begin or worsen after the patient has provided informed consent will be recorded on 
the Adverse Events eCRF, regardless of whether dosing with study drug has commenced. For 
events that are considered by the Investigator to be related to the study drug, the monitoring of 
the AE should be continued through the end of the study, for at least 30 days following the last 
dose of study drug, or until resolution.  
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
When a clear diagnosis cannot be identified, each sign or symptom should be recorded as a 
separate AE. 
The Investigator should ask the patient non-leading questions to determine if any AEs have 
occurred during the study, since the last study visit. Adverse events may also be recorded when 
they are volunteered by the patient, or through physical examination, laboratory tests, or other 
clinical assessments. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 87 
Version 4.0 
An AE should be followed until its resolution or until it is judged to be permanent, and 
assessment should be made at each visit (or more frequently, if necessary) of any changes in 
severity of the event, the suspected relationship to the study treatment, the interventions required 
to treat the event, and the outcome. 
12.1.2.1. Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (ie, are considered to be 
clinically significant, induce clinical signs or symptoms, require concomitant therapy, or require 
changes in study treatment), should be recorded on the Adverse Events eCRF. Whenever 
possible, a diagnosis, rather than a symptom should be provided (eg, anemia instead of low 
hemoglobin).  
Laboratory abnormalities that meet the criteria for an AE should be followed until they have 
returned to baseline levels (as measured during the Screening visit) or an adequate explanation of 
the abnormality is identified. When an abnormal laboratory or test result corresponds to a 
sign/symptom of an already reported AE, it is not necessary to separately record the 
laboratory/test result as an additional event. 
A laboratory abnormality that does not meet the definition of an AE should not be reported as an 
AE. A Grade 3 or 4 event (considered to be severe per NCI CTCAE, v. 4.03) does not 
automatically indicate an SAE unless it meets the definition of serious as defined in 
Section 12.1.1 and/or as per the opinion of the Investigator. A laboratory abnormality that results 
in a dose being held or modified would, by definition, be an AE and must be recorded as such in 
the eCRFs. 
12.1.2.2. Adverse Events of Special Interest  
AESIs for selinexor include cataracts and acute cerebellar syndrome. All cases of cerebellar 
toxicity, Grade 3 or higher must be reported (see Section 12.2.3). 
12.1.2.3. Other Adverse Events  
12.1.2.3.1. Tumor Lysis Syndrome  
As of the date of this protocol, there have been 8 reports of TLS: 4 patients in Karyopharm-
sponsored studies, 2 patients in Investigator-sponsored studies, and 2 patients in the expanded 
access program (compassionate use). Of the 8 patients, 5 had MM reported as their underlying 
cancer and 3 had hematological malignancies (including 1 AML and 2 acute lymphoblastic 
leukemia). The event onset latency ranged from 3 to 8 days (median 4 days). The total selinexor 
dose prior to event onset ranged from 40 to 320 mg (median 160 mg). The outcome was reported 
as recovered in 4 patients and not recovered in 2 patients; the outcome was not reported in 
2 patients. The Investigators assessed 7 of the events as being related to selinexor. Of the 8 cases 
summarized above, there were 3 cases in which the patient died as a result of a TEAE. The cause 
of death in each of these cases was reported as: respiratory failure secondary to advanced MM, 
sepsis, and respiratory failure, chemotherapy induced cardiomyopathy and acute lymphoblastic 
leukemia. No fatal outcomes due to TLS have been reported in any studies with selinexor, or in 
the ongoing EAP. Although the incidence of TLS is low (~0.3%), the causal relationship 
between selinexor treatment and TLS cannot be completely excluded. Early recognition of signs 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 88 
Version 4.0 
and symptoms in patients at risk for TLS, including identification of abnormal clinical and 
laboratory values, is key and Investigators must ensure that patients being treated with selinexor 
maintain adequate caloric and fluid intake. Close monitoring and management of patients with 
hematological malignancies, including MM, for potential signs and symptoms of TLS are most 
relevant. See Section 10.3 for supportive care and Table 16 for selinexor dose modification 
guidance.  
12.1.3. 
Adverse Event Severity 
The term “severe” is used to describe the intensity of an AE; the event itself could be of 
relatively minor clinical significance (eg, ‘severe’ headache). This is not the same as a “serious” 
AE. 
The severity of the AE will be graded by the Investigator according to the NCI CTCAE Grading 
Scale, v. 4.03 (the NCI CTCAE files can be accessed online at the following URL: 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html). 
If there is not a specific NCI CTCAE grading for an AE, the severity will be characterized as 
mild, moderate, severe, or life-threatening, according to the following definitions: 
•
Grade 1 (mild) events are usually transient and do not interfere with the patient’s
daily activities.
•
Grade 2 (moderate) events introduce a low level of inconvenience or concern to the
patient and may interfere with daily activities.
•
Grade 3 (severe) events interrupt the patient’s usual daily activities.
•
Grade 4 events are those that are considered to be life-threatening.
12.1.4. 
Adverse Event Causality 
The Investigator will make a judgment regarding the relationship of the AE to study treatment, as 
defined below. 
•
Not related: These events will lack a temporal relationship of the event to the study
treatment, making a causal relationship not reasonably possible. 
Exposure to other drugs, therapeutic interventions, or underlying 
conditions may provide a sufficient explanation for the event. 
•
Related:
There is a temporal relationship of the event to the study treatment 
making a definitive relationship, and the event is more likely explained 
by exposure to the study treatment than by any other drugs, therapeutic 
interventions, or underlying conditions. 
12.2. 
Serious Adverse Events 
See Section 12.1.1 for the definition of an SAE. Please note that SAEs that occur at any time 
between the signing of the ICF up to the first dose of study treatment, must be reported (in 
addition to SAEs that occur after the first dose of study treatment). 
Important medical events that may not result in death, are not life-threatening, or do not require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 89 
Version 4.0 
may jeopardize the patient and may require medical or surgical intervention to prevent 1 of the 
outcomes listed in this definition. Examples of such events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in in-patient hospitalization, or the development of drug dependency or drug 
abuse. 
12.2.1. 
Events that Do Not Meet the Definition of a Serious Adverse Event 
Elective hospitalizations to administer, or to simplify study treatment or study procedures (ie, an 
overnight stay to facilitate 24-hour urine collection) or other medical procedures are not 
considered SAEs. A ‘serious’ hospitalization is defined as any inpatient hospital admission that 
includes a minimum of an overnight stay in a health care facility. An emergency room visit is not 
considered a hospitalization unless it results in an official admission as an inpatient to the 
hospital (eg, undesirable effects of any administered treatment) and must be documented as an 
SAE. 
Progression of the malignancy/disease (including fatal outcomes) should NOT be reported as an 
SAE during the study or within the safety reporting period (see Section 12.2.3). Sudden or 
unexplained death should be reported as an SAE. If there is any uncertainty about a finding being 
due solely to progression of malignancy/disease, the finding should be reported as an AE or 
SAE, as appropriate.  
12.2.2. 
Recording of Serious Adverse Events 
It is the responsibility of the Investigator to record and document all SAEs occurring from the 
time when the ICF is signed until at least 30 days after the patient has stopped study treatment. 
All SAEs must be reported on the designated Sponsor’s SAE Report Form in addition to being 
recorded in the eCRF. The original SAE report form must be retained in the Investigator’s site 
file. 
All applicable sections of the SAE Report Form must be completed in order to provide a 
clinically thorough report. The Investigator must assess and record the relationship of each SAE 
to study treatment and complete the form in English. 
See ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting, Attachment 1) for key data elements that are required for expedited reporting. 
12.2.3. 
Reporting of Serious Adverse Events 
Every SAE, regardless of the causal relationship to the study treatment, occurring after the 
patient has signed informed consent, until at least 30 days after the patient has stopped study 
treatment, must be reported to the Karyopharm Pharmacovigilance Department within 24 hours 
of learning of its occurrence. The investigational site personnel must use the SAE Report Form 
provided by Karyopharm for reporting any SAE to the Karyopharm Pharmacovigilance 
Department. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 90 
Version 4.0 
Upon completion, the SAE Report Form must be immediately emailed or faxed to: 
Pharmacovigilance Department 
Karyopharm Therapeutics Inc. 
Email: pharmacovigilance@karyopharm.com 
Fax: 
+1-617-334-7617 (USA) 
+49-89-9218-5650 (Germany) 
Any SAE observed after the 30-day follow-up period should only be reported to Karyopharm if 
the Investigator suspects that the SAE has a causal relationship to the study treatment. Recurrent 
episodes, complications, or progression of the initial SAE must be reported, as follow-up to the 
original episode, within 24 hours of the Investigator receiving the follow-up information.  
An SAE should be followed until its resolution or until it is judged to be permanent. An 
assessment should be made at each study visit (or more frequently, if necessary) of any changes 
in severity of the event, the suspected relationship to the study treatment, the interventions 
required to treat the event, and the outcome of the event. 
12.2.4. 
Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are SAEs that are unexpected and 
judged by the Investigator or Karyopharm to be related to the study treatment administered. All 
SUSARs will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with the FDA’s “Safety Reporting Requirements for Investigational 
New Drugs and Bioanalytical/Bioequivalence Studies” or as per national regulatory requirements 
in participating countries. 
In addition, Karyopharm will communicate all cases of cerebellar toxicity, Grade 3 or higher, to 
regulatory authorities, central ethics committees (eg, IRBs), and Investigators, in the format of an 
expedited Safety Report, within 7 days of awareness of the event.  
If required by local regulations, the Investigator is responsible for notifying his/her IRB or local 
ethics committee of all SAEs. 
12.3. 
Procedures for Handling Special Situations 
12.3.1. 
Pregnancy and Breastfeeding 
Note: Pregnancy per se is not considered to be an AE; however, it is discussed here because of 
the importance of reporting pregnancies that occur during studies and because a medical 
occurrence observed in the mother or fetus/newborn would be classified as an AE. 
Female patients of childbearing potential and fertile male patients will be informed as to the 
potential risk of conception while participating in this study and will be advised that they must 
use highly effective contraception listed in Section 10.8.1 (ie, results in a low failure rate when 
used consistently and correctly) during the dosing period and for a period of at least 3 months 
after the end of treatment. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 91 
Version 4.0 
A pregnancy test will be performed on each premenopausal female patient of childbearing 
potential prior to the first dose of study drug, on Day 1 of Cycles ≥2 while on treatment, and 
again at treatment discontinuation during the End-of-Treatment visit. A negative pregnancy test 
must be documented prior to administration of study drug. 
If a patient is confirmed pregnant during the study, study drug administration must be 
discontinued immediately. The Investigator must immediately notify the Sponsor’s Medical 
Monitor of the event and record the pregnancy on the Pregnancy Form (provided by 
Karyopharm). The initial information regarding a pregnancy must be forwarded to Karyopharm’s 
Pharmacovigilance by email or fax within 24 hours of first knowledge of its occurrence.  
The pregnancy should be followed up to determine the outcome, including spontaneous or 
voluntary termination, details of the birth, and any birth defects, congenital abnormalities, or 
maternal and/or newborn complications.  
All pregnancies occurring within 3 months after the patient’s last dose of study drug must be 
reported to Karyopharm, regardless of whether the patient received selinexor or other study 
drugs, withdraws from the study, or the study is completed. Patients should be instructed to 
inform the Investigator regarding any pregnancies.  
Any SAE that occurs during pregnancy must be recorded on the SAE report form (eg, maternal 
serious complications, therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, 
congenital anomaly, or birth defect) and reported within 24 hours in accordance with the 
procedure for reporting SAEs (described in Section 12.2.3). 
A pregnancy in a female partner of a male patient must be reported to Karyopharm within 
24 hours of learning of its occurrence. Pregnancies in female partners should only be followed if 
the male patient is being treated with a selinexor-containing regimen. Consent to report 
information regarding these pregnancy outcomes should be obtained from the female partner. 
It is not known whether selinexor passes into the breast milk. Mothers should not breastfeed 
while being treated with selinexor-containing regimen.  
12.3.2. 
Overdose, Abuse, Misuse, Medication Errors, and Occupational Exposure 
All incidences of overdose, abuse, misuse, medication errors, and occupational exposure are 
required to be reported to Karyopharm Pharmacovigilance on an SAE report form and emailed to 
pharmacovigilance@karyopharm.com, regardless of whether or not there is an associated AE or 
SAE. 
12.3.2.1. Overdose 
An overdose is a deliberate or accidental administration of any study treatment to a study patient, 
at a dose greater than that which was assigned to that patient per the study protocol. If an 
overdose occurs, the Investigator and Karyopharm should be notified immediately, and the 
patient should be observed closely for AEs. Resulting symptoms should be treated, as 
appropriate, and the incident of overdose and related AEs and/or treatment should be 
documented in the patient’s medical record and in the eCRF. Information regarding the overdose 
is to be recorded on an SAE report form and sent to Karyopharm Pharmacovigilance regardless 
of whether or not an AE or SAE has occurred due to the overdose. If the overdose is associated 
with an SAE, the SAE report form must be submitted to Karyopharm Pharmacovigilance within 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 92 
Version 4.0 
24 hours of awareness. If there is no AE or SAE, the report must be submitted within 24 hours of 
awareness. 
As selinexor is metabolized by GSH conjugation, it is possible, but not demonstrated, that 
hepatic GSH depletion might occur in case of extreme overdose. Therefore, in overdose cases, if 
patients develop liver function test abnormalities, supportive measures such as SAM or other 
drugs that can replace GSH might be considered as part of the overall management plan. 
12.3.2.2. Abuse, Misuse, or Medication Error 
Abuse is the persistent or sporadic, intentional excessive use of the study treatment which is 
accompanied by harmful physical or psychological effects.  
A medication error is any preventable incident that may cause or lead to inappropriate study 
treatment use or patient harm while the study treatment is in the control of the health care 
professionals or patients. Such incident may be due to health care professional practice, product 
labeling, packaging and preparation, procedures for administration, and systems, including the 
following: prescribing, order communication, nomenclature, compounding, dispensing, 
distribution, administration, education, monitoring, and use. 
All occurrences of abuse, misuse, or medication error with any study treatment are to be 
recorded on an SAE report form and sent to Karyopharm Pharmacovigilance, regardless of 
whether or not an AE or SAE has occurred due to the abuse, misuse, or medication error. If the 
abuse, misuse, or medication error is associated with an SAE, the SAE report form must be 
submitted to Karyopharm Pharmacovigilance within 24 hours of awareness. If there is no AE or 
SAE, the report must be submitted within 24 hours of awareness. 
12.3.2.3. Occupational Exposure 
Occupational exposure is the exposure to a study treatment as a result of one’s professional or 
non-professional occupation. For this protocol, please follow the instructions for preparation and 
administration of selinexor, bortezomib, and dexamethasone. 
All occurrences of occupational exposure with any study treatment are to be recorded on an SAE 
report form and sent to Karyopharm Pharmacovigilance, regardless of whether or not an AE or 
SAE has occurred due to the occupational exposure. If the occupational exposure is associated 
with an SAE, the SAE report form must be submitted to Karyopharm Pharmacovigilance within 
24 hours of awareness. If there is no AE or SAE, the report must be submitted within 24 hours of 
awareness. 

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CCI

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 96 
Version 4.0 
stratification level, the number who discontinue treatment and reason(s) for treatment 
discontinuation, the number that withdrew from the study and reason(s) for study withdrawal, the 
number on treatment at the date of data cut-off, Durability of Response, and Survival Follow-up 
phase status. 
13.4.3. 
Demographic Characteristics 
Demographic characteristics will be summarized by treatment arm (SVd, Vd, SVdX, and SdX) 
and overall, and will include sex, race, ethnicity (Hispanic origin), and age at time of consent. 
For sex, race, ethnicity, the summary statistics will be the number and percentage of patients 
within each category. For age at time of consent, the mean, standard deviation, median, 
minimum, and maximum will be provided for each arm and the total sample. No formal 
hypothesis testing of treatment arm differences will be performed. 
13.4.4. 
Baseline Characteristics and Medical History 
Baseline characteristics include height, weight, BSA, ECOG performance status, and smoking 
history. If the Dubois (Dubois 1916) method for calculating BSA is entered by the site, BSA 
using the Mosteller (Mosteller 1987) method will be derived using the formula:  
BSA = Square Root ([Height(cm)×Weight(kg)]/3600). 
A complete medical history (Section 11.2.2) will be obtained from each patient.  
Medical history will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) 
system organ class (SOC) and preferred term. Baseline data will be summarized for each 
treatment arm using summary statistics; no formal hypothesis testing of treatment arm 
differences will be performed. Baseline symptoms will be listed only. 
13.5. 
Efficacy Analysis 
13.5.1. 
Primary Analysis for PFS 
The PFS primary endpoint is defined as time from date of randomization until the first date of 
PD, per IMWG response criteria, or death due to any cause, whichever occurs first. PD for the 
primary PFS endpoint will be assessed centrally by the IRC (see Section 6.4). Clinical 
deterioration in the absence of objective M-protein increase is not considered PD. Patients who 
end study treatment due to clinical deterioration without an objective M-protein increase meeting 
the IMWG definition of PD will be censored for the PFS analysis. Unless specified otherwise, 
relapse from CR by positive immunofixation or trace amount (defined as less than 0.5 g/dL) of 
M-protein is not considered to be PD. 
The primary analysis of PFS will be performed on the ITT population. The analysis will be 
repeated for the PP population as a supportive analysis. 
PFS data will be summarized with KM methodology using 25th, 50th (median), and 75th 
percentiles with associated 2-sided 95% CIs, as well as percentage of censored observations and 
proportion of events. Patients who remain progression-free (whether they withdraw from the 
study or reach their maximum follow-up) will be censored at the date of their last disease 
assessment. A stratified log-rank test will be used to compare the PFS distributions between 
treatment arms for the primary efficacy assessment; the strata will be those used for stratified 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 97 
Version 4.0 
randomization. Hazard ratios will be estimated by a stratified Cox proportional hazards model 
with treatment as the only factor, the strata will be those used for stratified randomization. A 
non-stratified log-rank test and a Cox proportional hazards model will be used as sensitivity 
analyses. 
Additional sensitivity analyses will be performed on the ITT population for the PFS primary 
endpoint as outlined below: 
• Sensitivity Analysis #1: Events are defined as documented progression as verified by 
the IRC or death when the patient is closely followed, whichever occurs first. Patients 
are censored at the date of last disease assessment if no progression is confirmed by 
the IRC, treatment is discontinued for any reason, new anticancer treatment is started, 
or death or progression occurs after 2 or more missed visits. 
• Sensitivity Analysis #2: Similar to the primary PFS endpoint analysis but where 
treatment discontinuation for any reason is counted as an event. 
• Sensitivity Analysis #3: Similar to the primary PFS endpoint analysis but where the 
initiation of non-study antineoplastic therapy is counted as an event. 
• Sensitivity Analysis #4: Similar to the primary PFS endpoint analysis but where 
clinical progression is counted as an event in addition to IRC-confirmed PD. Clinical 
progression is defined as the event when a patient discontinues the treatment with 
reason of PD but is not classified as PD by IRC. 
• Sensitivity Analysis #5: Similar to the primary PFS endpoint analysis but where the 
timing of IRC-confirmed PD at an unscheduled visit is changed to the next scheduled 
visit.  
• Comparison of PFS endpoint by treatment based on Investigator’s assessment. 
13.5.2. 
Analyses of the Key Secondary Endpoints 
The following 3 endpoints, which are defined as key secondary endpoints, will be tested at the 
time of the second PFS IA according to the test sequence below: 
1. ORR, defined as any response ≥PR (ie, PR, VGPR, CR, or sCR) based on the IRC’s 
response outcome assessments, according to the IMWG response criteria 
2. Incidence of any Grade ≥2 peripheral neuropathy events  
3. Response rates for responses ≥VGPR based on the IRC’s assessment 
The hierarchical testing procedure will be used to maintain the overall Type I error of these 
3 tests at a 1-sided 0.025 level of significance. 
Statistical significance of the key secondary endpoints will not be claimed until the primary 
endpoint of PFS has reached significance. 
13.5.2.1. Overall Response Rate 
The secondary efficacy endpoint of ORR is defined as the proportion of patients who achieve a 
confirmed PR or better (ie, PR, VGPR, CR, or sCR) based on the IRC’s response outcome 
assessments, according to the IMWG response criteria, before IRC-confirmed PD or initiating a 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 98 
Version 4.0 
new MM treatment. All changes in MM disease assessments will be based on baseline MM 
disease assessments. ORR will be assessed on the ITT population at the time of the second PFS 
IA. The analysis will be repeated for the PP population as a supportive analysis. 
Comparison of ORR between the 2 treatment arms will be performed using the Cochran Mantel 
Haenszel (CMH) test stratified by the randomization stratification factors. The Breslow-Day test 
will be used to evaluate the homogeneity of odds ratios across the strata associated with this 
endpoint. Patients missing post-C1D1 MM disease assessments will be imputed as non-
responders. 
A sensitivity analysis for ORR will be conducted on ITT patients where patients who have not 
had the opportunity to complete at least 2 post-C1D1 MM evaluations will be considered 
non-responders. 
13.5.2.2. Incidence of Any Grade ≥2 Peripheral Neuropathy Events  
The analysis for this safety endpoint is provided Section 13.7.1.1. 
13.5.2.3. Response Rate for Responses ≥VGPR Based on the IRC’s Assessment 
The response rate for responses ≥ VGPR will be assessed on the ITT population at the time of 
the second PFS IA. The analysis will be performed in a similar manner to the secondary efficacy 
endpoint of ORR using the CMH test. The unadjusted number and percentage of patients will be 
summarized by treatment arm (SVd versus Vd) along with associated 95% CIs and the Breslow-
Day test will be performed to assess homogeneity of odds ratios across the strata. Only responses 
≥VGPR that occurred before IRC-confirmed PD or initiating a new MM treatment will be 
included in the analysis. 
13.5.3. 
Analyses of the Non-Key Secondary Effiacy Endpoints 
Brief summaries of the analyses for the non-key secondary efficacy endpoints are provided 
below. Additional details may be found in the SAP. These non-key secondary efficacy endpoints 
will be summarized by treatment arm for the ITT population, unless otherwise stated below or in 
the SAP.  
• Overall survival: The analysis of OS will be performed by treatment arm (SVd versus 
Vd) based on the stratified log-rank test. The strata will be those used for stratified 
randomization. Median OS time with 95% CI will be estimated based on the KM 
method for each treatment arm. A sensitivity analysis will be performed for OS, in 
which patients will be censored at the date of first dose of the new anti-MM 
treatment. 
• Response ≥CR, ≥sCR, or MRD negative (for patients who achieve CR or sCR): The 
number and percentage of patients with response ≥CR or response ≥sCR at any time 
prior to IRC-confirmed PD or initiating a new MM treatment will be summarized. 
The number and percentage of patients with MRD negative status at the time of 
response will be presented by treatment arm among those patients who achieve CR or 
sCR. 

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Investigational Product (KPT-330) 
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Clinical Study Protocol: KCP-330-023 
 
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13.7.1. 
Analysis of the Key Secondary Safety Endpoint 
13.7.1.1. Peripheral Neuropathy Events 
The analysis of the peripheral neuropathy events will be performed at the time of the second PFS 
IA. Statistical significance of peripheral neuropathy endpoint will not be claimed until PFS has 
reached significance. 
Treatment differences for the incidence of any Grade ≥2 peripheral neuropathy events (the key 
secondary safety endpoint) will be tested using the Cochran-Mantel-Haenszel (CMH) test, 
stratified by the randomization stratification factors. The treatment difference will be assessed 
using the safety population. The number and percentage of patients will also be summarized by 
treatment arm (SVd versus Vd) along with the odds ratio and associated 95% CIs and the 
Breslow-Day test will be performed to assess homogeneity of odds ratios across the strata. A 
sensitivity analysis for the incidence of any Grade ≥2 peripheral neuropathy events will be 
conducted on the safety population where all Grade ≥2 peripheral neuropathy events that occur 
for Vd patients regardless of cross-over status will be included in the sensitivity analysis.  
Similar analysis using the CMH test and the Breslow-Day test as described in Section 13.5.2 will 
be repeated to assess the incidence of any Grade peripheral neuropathy events on the safety 
population, as well as for Grades 2, 3, and 4 separately.  
All peripheral neuropathy events may also be provided in a data listing. 
13.7.2. 
Analyses of the Non-Key Secondary Safety Endpoints 
13.7.2.1. Study Treatment Exposure 
The following study treatment exposure data will be summarized: duration of exposure, number 
of cycles completed, percent compliance, dose intensity (defined as total study treatment 
received divided by duration of exposure, presented in mg/week and mg/day), number of missed 
doses, number of dose interruptions, duration of dose interruption, number of dose reductions, 
and number of dose escalations. Additional definition and analysis details may be found in the 
SAP.  
13.7.2.2. Adverse Events 
AEs will be coded using the MedDRA and displayed in tables and listings using MedDRA SOC 
and preferred term. The incidence rates of treatment-emergent AEs (TEAEs; separated by 
relationship to study treatment as assessed by the Investigator and maximum severity), SAEs, 
AEs of at least Grade 3 in severity using NCI CTCAE v. 4.03, treatment-related treatment-
emergent SAEs, AEs leading to withdrawal of study treatment, and AEs leading to death will be 
summarized. TEAEs will be AEs that start or worsen on or after the first day dose of study 
treatment, through 30 days after the last dose, or any event considered treatment-related by the 
Investigator through the end of the study; related AEs will be AEs with an Investigator 
determination of related to treatment.  
AEs with partial dates will be assessed using the available date information to determine if 
treatment-emergent using rules outlined in the SAP. AEs with completely missing dates will be 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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assumed to be treatment-emergent. No formal hypothesis-testing of AE incidence rates will be 
performed. 
The causal relationship between the occurrence of an AE and the study treatment will be judged 
by the Investigator as not related or related (see Section 12.1.4). In the event a patient 
experiences repeat episodes of the same AE, then the event with the highest severity and/or 
strongest causal relationship to treatment will be used for purposes of tabulations. 
13.7.2.3. Clinical Laboratory Data 
Clinical laboratory values will be expressed using conventional International System of Units 
(SI) units. 
For each treatment arm, the actual value and change from baseline (Day 1, prior to the first 
administration of study treatment) to each on-study evaluation will be summarized for each 
quantitative clinical laboratory parameter, including, but not limited to, hematology, clinical 
chemistry, coagulation, and urinalysis. In the event of repeat values, the last non-missing value 
per study day will be used. In the event that Day 1 data are unavailable for a given 
patient/parameter, the screening value will substitute as the baseline value. 
Severity of select clinical laboratory measures will be determined using NCI CTCAE criteria (eg, 
those measures that have a corresponding NCI CTCAE grade classification). Laboratory test 
results with NCI CTCAE Grades ≥3 will be presented in a by-patient data listing. Shift tables 
that present changes from baseline to worst on-study values and from baseline to last on-study 
values relative to NCI CTCAE classification ranges will be produced. 
All laboratory data will be provided in by-patient data listings. 
13.7.2.4. Vital Signs and Physical Examinations 
The actual value and change from baseline (Day 1, prior to the first administration of study 
treatment) to each on-study evaluation will be summarized for vital signs including pulse rate, 
temperature, systolic BP, diastolic BP, weight, and BSA. Shift tables that present changes from 
baseline to worst on-study and last on-study ECOG performance status values will be produced.  
Vital sign measurements and all physical examination findings will be presented in by-patient 
data listings. 
13.7.2.5. Electrocardiogram 
ECG results will be summarized descriptively, including heart rate and PR, QRS, QT, and QTc 
intervals (calculated by the Fridericia correction formula (Fridericia 1920); intervals. Actual 
values and changes from baseline will be reported for each study visit.  ECG data for each patient 
will be provided in a by-patient data listing. 
13.7.2.6. Ophthalmological Examinations 
Ophthalmological examination findings will be summarized descriptively by visit and presented 
in by-patient data listings. 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
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14. 
ADMINISTRATIVE MATTERS 
14.1. 
Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH Harmonised Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local 
regulations (including European Directive 2001/20/EC and United States Code of Federal 
Regulations Title 21), and with the ethical principles laid down in the Declaration of Helsinki. 
14.2. 
Ethics Committees 
The protocol, the proposed ICF, and any other relevant records must be reviewed and approved 
by a properly constituted ethics committee (eg, IRB) before study start. 
14.3. 
Regulatory Authority Approval 
Before implementing this study, the protocol must be approved by relevant, competent 
regulatory authorities. 
14.4. 
Protocol Adherence 
Prior to study start, the Investigator is required to sign a protocol signature page confirming 
his/her agreement to conduct the study in accordance with the instructions and procedures found 
in this protocol. Investigators attest they will apply due diligence to avoid protocol deviations. 
All data points listed in this protocol and in the eCRFs are considered required. Any deviations 
from the protocol are to be recorded in the eCRF. All significant protocol deviations will be 
recorded and reported in the CSR. 
14.5. 
Amendments to the Protocol 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be provided by the Sponsor and approved by regulatory authorities where required, and the 
ethics committee (eg, IRB). Only amendments that are required for patient safety may be 
implemented prior to ethics committee (eg, IRB) approval. Notwithstanding the need for 
approval of formal protocol amendments, the Investigator is expected to take any immediate 
action required for the safety of any patient included in this study, even if this action represents a 
deviation from the protocol. In such cases, the Sponsor should be notified of this action, and the 
ethics committee (eg, IRB) at the study site should be informed according to local regulations but 
not later than 10 working days.  
14.6. 
Informed Consent 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law, ethics committee [eg, IRB], or regulation), ethics committee (eg, IRB)-approved 
informed consent.  
Informed consent must be obtained before conducting any study-specific procedures. Note age 
on date consent is signed. Procedures that are part of the clinical routine evaluations during the 
initial diagnostic work-up of the patient may be performed before the ICF is signed and dated (ie, 
procedures that are not specific to the conduct of the study). 

Investigational Product (KPT-330) 
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Clinical Study Protocol: KCP-330-023 
17 August 2018 
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Informed consent must also be obtained for SVdX/SdX patients before conducting any study-
specific procedures for SVdX/SdX treatment. 
The process of obtaining informed consent should be documented in the patient source 
documents. A copy of the ICF must be given to the patient or to the person signing the form on 
behalf of the patient. The Investigator or designee must record the date when the study ICF was 
signed in the medical records of the patient. The name and role of the witness, if required, should 
also be documented. 
The Sponsor will provide to Investigators, in a separate document, a proposed ICF that is 
appropriate for this study and complies with the ICH GCP guideline and regulatory 
requirements. Any changes to this ICF suggested by the Investigator must be agreed to by 
Karyopharm before submission to the ethics committee (eg, IRB). If an ethics committee 
requests substantive changes to the ICF as part of their review, those revisions must also be 
submitted to Karyopharm for consideration prior to re-submission back to the IRB. A copy of the 
approved version must be provided to Karyopharm after ethics committee (eg, IRB) approval. 
14.7. 
Patient Confidentiality and Disclosure 
The Investigator must ensure anonymity of all patients; patients must not be identified by names 
in any documents submitted to Sponsor or its representative. Signed ICFs and patient enrollment 
logs must be kept strictly confidential. 
14.8. 
Study Documentation, Data Collection and Storage, and Study 
Monitoring and Auditing Procedures 
14.8.1. 
Study Documentation, Record Keeping, and Retention of Documents 
Each participating site will maintain appropriate medical and research records for this study, in 
compliance with Section 4.9 of ICH GCP E6, and regulatory and institutional requirements. Each 
site will permit authorized representatives of the Sponsor and regulatory agencies to examine 
(and when required by applicable law, to copy) anonymized clinical records for the purposes of 
quality assurance reviews, audits, and evaluation of the study safety and progress. 
Source data include all information, original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction and evaluation of the study. 
Data collection is the responsibility of the clinical study staff at the site under the supervision of 
the site Investigator. The study eCRF is the primary data collection instrument for the study. The 
Investigator is responsible for the accuracy, completeness, and timeliness of the data reported in 
the eCRFs and all other required reports. Data reported in the eCRFs, which are derived from 
source documents, should be consistent with the source documents or the discrepancies should 
be explained. All data requested in the eCRF must be recorded. Any missing data must be 
explained. For eCRFs an audit trail will be maintained by the system. 
The Investigator/institution should maintain study documents as specified in Essential 
Documents for the Conduct of a Clinical Trial (ICH GCP E6 Section 8) and as required by 
applicable regulations and/or guidelines. The Investigator/institution should take measures to 
prevent accidental or premature destruction of these documents. 

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Clinical Study Protocol: KCP-330-023 
 
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Essential documents (written and electronic) should be retained for a period of not less than 
15 years from the completion of the clinical study unless the Sponsor provides written 
permission to dispose of them or, requires their retention for an additional period of time because 
of applicable laws, regulations, and/or guidelines. 
14.8.2. 
Study Monitoring and Auditing Procedures 
A representative of Karyopharm will determine the adequacy of the facilities to perform the 
study in accordance with the protocol. These evaluations may occur before, at any time during, 
and/or after the study has been completed. 
This study will be monitored in accordance with the ICH GCP E6 Section 5.18.4. The site 
monitor will perform visits to the study site at regular intervals. 
In addition to the routine monitoring procedures, the Sponsor or its representative may conduct 
an audit and/or the regulatory authority may conduct an inspection (during the study or after its 
completion) to evaluate compliance with the protocol and the principles of GCP and ensure the 
validity and integrity of the study data. 
During the study, when necessary, the Sponsor or its representatives, as well as regulatory 
authorities, must be permitted to review all study-related documents and other materials at the 
study site, including the Investigator Site File, study drug(s), and patients’ original medical 
records/files.  
The Investigator agrees that representatives of the Sponsor and regulatory authorities will have 
direct access, both during and after the course of this study, to audit and review all study-relevant 
medical records.  
In the event that major compliance or regulatory concerns arise, the Sponsor may conduct an 
audit without prior notice. 
14.9. 
Disclosure of Information 
All information provided to the Investigator by the Sponsor, or its representative, will be kept 
strictly confidential. No disclosure shall be made except in accordance with a right of publication 
granted to the Investigator in the Clinical Trial Agreement. 
No information about this study or its progress will be provided to anyone not involved in the 
study other than to the Sponsor, or its authorized representatives, or in confidence to the ethics 
committee (eg, IRB), or similar committee, except if required by law.  
14.10. 
Discontinuation of the Study 
It is agreed that, for reasonable cause, either the Investigator or the Sponsor may terminate the 
Investigator’s participation in this study after submission of a written notice. The Sponsor may 
terminate the study at any time upon immediate notice for any reason including the Sponsor’s 
belief that termination of the study is necessary for patient safety.  

Investigational Product (KPT-330) 
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Clinical Study Protocol: KCP-330-023 
 
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14.11. 
Study Report and Publication Policy 
Karyopharm assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as www.clinicaltrials.gov. In addition, upon study completion and 
analysis of the resulting clinical data, the study will be: 
• Reported to appropriate, competent regulatory authorities in full compliance with ICH 
E3: Structure and Content of Clinical Study Reports. A separate primary CSR may be 
prepared to summarize the results of the primary PFS analysis, followed by a final CSR 
after completion of the follow-up for all patients. 
• Submitted for publication and/or posted in a publicly accessible database of clinical study 
results. 

Investigational Product (KPT-330) 
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Clinical Study Protocol: KCP-330-023 
 
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15. 
LIST OF REFERENCES 
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Clinical Study Protocol: KCP-330-023 
 
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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 110 
Version 4.0 
27. NCT02136134. Addition of daratumumab to combination of bortezomib and 
dexamethasone in participants with relapsed or refractory multiple myeloma –sponsored 
by Janssen Research & Development, LLC. Available from: 
https://clinicaltrials.gov/ct2/show/NCT02136134. 
28. NCT02199665. Selinexor, carfilzomib, and dexamethasone in treating patients with 
relapsed or refractory multiple myeloma (SINE) –sponsored by the University of 
Chicago. Available from: https://clinicaltrials.gov/ct2/show/NCT02199665. 
29. NCT02343042. Selinexor and backbone treatments of multiple myeloma patients 
(STOMP) –sponsored by Karyopharm. Available from: 
https://clinicaltrials.gov/ct2/show/NCT02343042. 
30. NCT02755597. A study evaluating venetoclax (ABT-199) in multiple myeloma subjects 
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31. Neggers JE, Vanstreels E, Baloglu E, et al. Heterozygous mutation of cysteine528 in 
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32. Neggers JE, Vercruysse T, Jacquemyn M, Vanstreels E, Baloglu E, Shacham S, et al. 
Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by 
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Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 111 
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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
17 August 2018 
Confidential 
Page 112 
Version 4.0 
APPENDIX 1. PROTOCOL AMENDENT: RATIONALES AND 
SUMMARY OF CHANGES 
Amendment 3, Version 4.0 
Summary of Changes 
This primary reason for amending this protocol is to: 
•
Change ORR from a primary endpoint to a key secondary endpoint to address
concerns expressed by the Agencies regarding including ORR as a primary endpoint
(ie, an analysis of ORR could jeopardize the integrity of the study for the ultimate
assessment of PFS).
The revised protocol Version 4.0 dated 17 August 2018 will be submitted to all applicable 
Institutional Review Boards (IRBs), Independent Ethics Committees (IECs), or Research Ethics 
Boards (REBs), and by Karyopharm Therapeutics Inc. to all applicable Regulatory Authorities. 
A summary of the key changes that were made to Version 3.0 of the protocol, including the 
rationale for these changes, in Version 4.0 is provided in the table below. Global changes or 
modification of large amounts of text are not described in detail, rather, a general description of 
the change is provided. When appropriate, exact changes to the text are provided. In these 
instances, red font indicates text that was deleted. Text that was added is provided in blue font. 
Changes that were primarily editorial or administrative in nature or were made for readability 
and clarity are not detailed in the table. 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 114 
Version 4.0 
Section(s) 
Description of Change 
Rationale for the Change 
Section 4.2.5: Selinexor 
Nonclinical Combination with 
Dexamethasone and Proteasome 
Inhibitors 
Section 4.2.6: Overall Clinical 
Experience with Selinexor 
Section 4.2.6.1: Study KCP-330-
017 (STOMP) 
Section 4.2.7: Potential Risks of 
Selinexor 
Section 15: List of References 
Section 14.5: Amendments to the 
Protocol 
Revised the term “Health Authorities” to “regulatory 
authorities 
Administrative 
Section 14.8:Study 
Documentation, Data Collection 
and Storage, and Study 
Monitoring and Auditing 
Procedures 
Section 14.8.2: Study Monitoring 
and Auditing Procedures 
 
Clarified study monitoring guidelines, combined the study 
monitoring subsection (14.12 in v3.0) with the auditing 
procedure subsection (Section 14.8.2) and revised the 
titles of Section 14.8 and Section 14.8.2. 
 
Administrative 
Section 15: List of References 
Added a missing reference 
Administrative 
Section 3: Study Schematics and 
Schedule of Assessments and 
Dosing for Study KCP-330-023 
(Table 3: Unique Visits Required 
for Crossover to SVdX or Sdx) 
Revised the definition of  “IRC-confirmed PD” in Table 3 
and renamed the term as “IRC PD confirmation.” 
Revised footnote b: 
The IRC-confirmed PD date is the date of the first of the 2 
consecutive assessments that meet the response criteria for 
PD, not the date PD confirmation date is the date that the 
IRC informs the site that PD has been confirmed. 
To clarify the start date of the 14-day window 
for the End of Vd Treatment Visits and C1D1 
Visits for SVdX or SdX. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 115 
Version 4.0 
Section(s) 
Description of Change 
Rationale for the Change 
Section 3.1 Schedules of Visits 
for In-clinic Dosing and MM 
Evaluations (Table 4: SVd Arm: 
Schedule of Visits for In-clinic 
Dosing and MM Evaluations) 
Section 6.1: Overall Study Design 
and Plan 
Revised Note in Table 4: 
*Note: On C2D29 and C5D29, selinexor and 
dexamethasone dosing should be performed in the clinic 
PD during MM disease assessment visits. 
Revised sentence in Section 6.1: 
The Schedule of Assessments is provided in Table 2. 
Patients will have in-clinic visits for dosing of study 
treatment during MM evaluations (Table 13) and 
telephone contacts (Section 11.7.3). 
To clarify that selinexor and dexamethasone 
dosing will occur in the clinic during MM 
disease assessment visits. 
Section 1:List of Abbreviations 
and Definitions of Terms 
Section 4.2.7: Potential Risks of 
Selinexor 
Section 10.4.1: Selinexor Dose 
Reduction Guidelines (Table 16: 
Supportive Care and Selinexor 
Dose Adjustment Guidelines for 
AEs Related to Selinexor) 
Section 11.2.2: Medical History 
Section 12.1.2.3: Other Adverse 
Events 
Section 12.1.2.3.1: Tumor Lysis 
Syndrome (new subsection) 
Added a description of the 8 tumor lysis syndrome (TLS) 
cases reported as of May 2018. The major change was the 
addition of Section 12.1.2.3.1. 
Section 12.1.2.3.1. Tumor Lysis Syndrome  
As of the date of this amendment, there have been 8 
reports of TLS: 4 patients in Karyopharm-sponsored 
studies, 2 patients in Investigator-sponsored studies, and 2 
patients in the expanded access program (compassionate 
use). Of the 8 patients, 5 had MM reported as their 
underlying cancer and 3 had hematological malignancies 
(including AML and acute lymphoblastic leukemia). The 
event onset latency ranged from 3 to 8 days (median 4 
days). The total selinexor dose prior to event onset ranged 
from 40 to 320 mg (median 160 mg). The outcome was 
reported as recovered in 4 patients and not recovered in 2 
patients;  the outcome was not reported in 2 patients. The 
Investigators assessed 7 of the events as being related to 
selinexor. Of the 8 cases summarized above, there were 3 
cases in which the patient died as a result of a TEAE. The 
cause of death in each of these cases was reported as: 
respiratory failure secondary to advanced MM, sepsis, and 
respiratory failure, chemotherapy induced cardiomyopathy 
and AML. No fatal outcomes due to TLS have been 
reported in any studies with selinexor, or in the ongoing 
To update safety information for selinexor 
related to TLS. 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 117 
Version 4.0 
Section(s) 
Description of Change 
Rationale for the Change 
Section 13.2.1.1: Interim 
Analysis of PFS for Sample Size 
Re-estimation 
Section 13.2.1.2: Interim 
Analysis of PFS for Futility or 
Superiority 
Section 13.5.1.2: Primary 
Analysis for ORR (in v3) was 
deleted 
Section 13.5.2.1: Overall 
Response Rate (new) 
Section 14.11: Study Report and 
Publication Policy 
 
• 
To compare the ORR (≥ PR) based on the IRC’s 
response outcome assessments (Section 6.4), in 
patients randomized to the SVd Arm versus the 
Vd Arm 
Section 5.1.2 Secondary Objectives  
• 
To compare the ORR (≥ PR) based on the IRC’s 
response outcome assessments (Section 6.4), in 
patients randomized to the SVd Arm versus the Vd 
Arm 
• 
To compare the incidence of any Grade ≥2 
peripheral neuropathy events (total Grade ≥2 and 
separately for Grades 2, 3, and 4) in patients 
randomized to the SVd Arm versus patients 
randomized to the Vd Arm 
• 
…… 
Section 5.2.1 Primary Endpoints 
• 
PFS, defined as time from date of randomization 
until the first date of PD, per IMWG response 
criteria, or death due to any cause, whichever 
occurs first. For the purposes of PFS 
determination, PD will be determined by the IRC. 
• 
ORR, defined as any response ≥ PR based on the 
IRC’s response outcome assessments, according 
to the IMWG response criteria. All changes in 
MM disease assessments will be based on 
baseline MM disease assessments from C1D1 of 
study treatment. 
Section 5.2.2.1 Key Secondary Efficacy Endpoints 
• 
ORR, defined as any response ≥ PR (ie, PR, VGPR, 
CR, or sCR) based on the IRC’s response outcome 
assessments, according to the IMWG response criteria. 
All changes in MM disease assessments will be based 
on baseline MM disease assessments. 
events have occurred, regardless of 
association with accrual status. 
5) The definition of ORR was revised to align 
with the statistical analysis plan (SAP). 

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CCI

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
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Description of Change 
Rationale for the Change 
• 
R-ISS stage at original MM diagnosis study entry, 
based on screening results (R-ISS Stage III versus 
R-ISS Stage I or II) (Palumbo 2015). If data for 
chromosomal abnormalities (CA) and serum lactate 
dehydrogenase (LDH) required for R-ISS staging are 
not available, patients will be assigned to the R-ISS 
category corresponding to their ISS stage. 
… 
Related changes were made in Section 6.1. 
Section 6.1: Overall Study Design 
and Plan 
Section 6.2: Crossover 
Added an exception to the requirement that patients will 
either remain on study treatment until PD is confirmed by 
the IRC or discontinue study treatment, complete the EoT 
Visit, and be followed for survival. The exception only 
applies to patients in the Vd Arm who must terminate 
bortezomib prior to IRCconfirmed PD due to significant 
toxicities. 
Section 6.2 Crossover 
… 
The following process will be used in order to prevent 
premature crossover:  
1. Investigators will assess PD according to the 
IMWG criteria including repeat testing if PD is 
based on serum and/or urine M-protein, 
quantitative immunoglobulins for IgA/IgD, or 
serum free light chain (FLC). PD may also be 
based on new or enlarging plasmacytoma(s) or 
bone lesion(s) or on other symptoms and signs of 
clinical progression that meet the IMWG criteria. 
2. All cases of PD must be confirmed by the IRC 
prior to crossover. 
To give patients in the Vd Arm who must 
terminate bortezomib prior to IRC-confirmed 
PD due to significant toxicities an opportunity 
to receive selinexor. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
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Rationale for the Change 
3. Crossover will not be permitted based purely on 
Investigator-assessed progression that does not 
meet any IMWG criteria for PD and cannot be 
verified by IRC (eg, deteriorating performance 
status). 
4. Crossover will not be permitted if dosing of 
bortezomib is terminated before PD is confirmed 
by the IRC, unless termination of bortezomib is 
due to significant toxicities such as peripheral 
neuropathy, and all treatment measures addressing 
these toxicities are exhausted and documented 
prior to bortezomib termination. Early termination 
of bortezomib should be discussed and approved 
by the Sponsor Medical Monitor in order to allow 
crossover to SdX after progression is confirmed 
by the IRC. 
5. Investigator-assessed presumptive PD events that 
are not confirmed by the IRC will have their PFS 
censored at the time of treatment discontinuation. 
--- 
Related changes were made to the other sections noted. 
Section 6.3: Data Safety 
Monitoring Board 
Added a more detailed description of the Data Safety 
Monitoring Board (DSMB). 
Section 6.3 Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) 
will be set up for the study to review safety data for this 
study. The DSMB will review safety data at intervals 
outlined in the DSMB charter. The DSMB is made up of a 
group of individuals with pertinent expertise that reviews, 
on a predetermined schedule, safety data from this clinical 
study. It is the DSMB's responsibility to weigh risks and 
benefits throughout the study's duration. The DSMB will 
provide oversight and safety monitoring of the study in 
To align with the DSMB charter 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 125 
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Section(s) 
Description of Change 
Rationale for the Change 
compliance with applicable regulations, legislation and 
associated guidance materials for the nature of the study.  
As appropriate, Tthe DSMB will provide 
recommendations to the Sponsor regarding continuation, 
modification, or discontinuation of the study based on the 
safety results its assessment of the reviewed safety data. 
This DSMB will be composed of 4 voting members (3 
oncologists and an independent statistician) a Chairperson 
and 3 voting members who will review safety data from 
the study. The DSMB membership, functioning, and 
procedures are described in the DSMB charter. 
Section 3: Study Schematics and 
Schedule of Assessments and 
Dosing for Study KCP-330-023 
(Table 2: Schedule of 
Assessments for Study KCP-330-
023, footnote p) 
Section 7.2: Inclusion Criteria 
Section 10.8.1: Contraception 
Requirements 
Section 12.3.1: Pregnancy and 
Breastfeeding 
Revised inclusion criterion #12, contraception 
requirements, and guidance for pregnancy and 
breastfeeding. 
Section 7.2 Inclusion Criteria 
… 
12. Female patients of childbearing potential must agree to 
use 2 methods of contraception (including 1 highly 
effective and 1 effective method of contraception) and 
have a negative serum pregnancy test at Screening. 
Female patients of childbearing potential and fertile 
Mmale patients who are sexually active with a female 
of childbearing potential must use an highly effective 
barrier methods of contraception if sexually active with 
a female of childbearing potential. For both male and 
female patients, effective methods of contraception 
must be used throughout the study and for 3 months 
following the last dose of study treatment. Highly 
effective methods of contraception are listed in 
Section 10.8.1. 
Section 10.8.1 Contraception Requirements 
Patients should not become pregnant or father a child 
while on this study because the study treatments in this 
To align with the highly effective methods 
and pregnancy/breastfeeding guidance 
described in the new safety language template 
provided by the Karyopharm 
Pharmacovigilance Department 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Description of Change 
Rationale for the Change 
study can affect an unborn baby. Women should not 
breastfeed a baby while on this study. It is important that 
patients understand the need to use birth control while on 
this study.  
Female patients of childbearing potential and fertile male 
patients must agree to use 2 methods of highly effective 
contraception (1 highly effective and 1 effective) and have 
a negative serum pregnancy test at Screening, and male 
patients must use an effective barrier method of 
contraception if sexually active with a female of 
childbearing potential listed below (ie, results in a low 
failure rate when used consistently and correctly) during 
the dosing period and for a period of at least 3 months 
after the end of treatment. 
Highly effective methods include: 
• Hormonal contraceptives (e.g., combined oral 
contraceptives, patch, vaginal ring, injectables, and 
implants)  
• combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition 
of ovulation: 
o oral 
o intravaginal 
o transdermal 
• progestogen-only hormonal contraception 
associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• Iintrauterine device or  
• intrauterine hormone-releasing system 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Rationale for the Change 
• Vasectomy or tubal ligation 
• bilateral tubal occlusion 
• vasectomized partner 
• sexual abstinence 
Effective methods include:  
• Barrier methods of contraception (e.g., male condom, 
female condom, cervical cap, diaphragm, and 
contraceptive sponge) 
Of particular note, 
o No barrier method by itself achieves a highly effective 
standard of contraception 
o The proper use of diaphragm or cervical cap includes 
use of spermicide and is considered 1 barrier method. 
o The cervical cap and contraceptive sponge are less 
effective in parous women. 
o The use of spermicide alone is not considered a suitable 
barrier method for contraception. 
o A combination of male condom with either cap, 
diaphragm or sponge with spermicide (double barrier 
methods) are also considered acceptable (i.e., effective), 
but not highly effective, birth control methods. 
o Male and female condoms should not be used together as 
they can tear or become damaged. 
Alternatively, the following fulfill the contraception 
requirements: 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Rationale for the Change 
• A sexual partner who is permanently surgically sterilized 
or post-menopausal. 
• Total (true) abstinence (when this is in line with the 
preferred and usual lifestyle of the patient) is an 
acceptable method of contraception. Note: Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, and 
post-ovulation methods) and withdrawal are not 
acceptable methods of contraception. 
The methods of acceptable contraception must be explained to 
both male and female potential patients. In order to be eligible 
for the study, patients must agree to use the methods of birth 
control described above throughout the study and for 3 months 
following the last dose of study treatment at the time of consent 
for the study. 
Please see Section 4.2.7.1 for additional safety 
information related to pregnancy. 
Section 12.3.1 Pregnancy and Breastfeeding 
Note: Pregnancy per se is not considered to be an AE; 
however, it is discussed here because of the importance of 
reporting pregnancies that occur during studies and 
because a medical occurrence observed in the mother or 
fetus/newborn would be classified as an AE.  
To ensure patient safety, a pregnancy occurring while the 
patient is on study treatment must be reported to 
Karyopharm Pharmacovigilance by email or fax within 24 
hours of first knowledge of its occurrence. A pregnancy 
report form is provided by Karyopharm. 
Female patients of childbearing potential and fertile male 
patients will be informed as to the potential risk of 
conception while participating in this study and will be 
advised that they must use highly effective contraception 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Description of Change 
Rationale for the Change 
listed in Section 10.8.1 (ie, results in a low failure rate 
when used consistently and correctly) during the dosing 
period and for a period of at least 3 months after the end 
of treatment. 
A pregnancy test will be performed on each 
premenopausal female patient of childbearing potential 
prior to the first dose of study drug, on Day 1 of Cycles ≥2 
while on treatment, and again at treatment discontinuation 
during the End-of-Treatment visit. A negative pregnancy 
test must be documented prior to administration of study 
drug. 
If a patient is confirmed pregnant during the study, study 
drug administration must be discontinued immediately. 
The Investigator must immediately notify the Sponsor’s 
Medical Monitor of the event and record the pregnancy on 
the Pregnancy Form (provided by Karyopharm). The 
initial information regarding a pregnancy must be 
forwarded to Karyopharm’s Pharmacovigilance by email 
or fax within 24 hours of first knowledge of its 
occurrence.  
The pregnancy should be followed up to determine the 
outcome, including spontaneous or voluntary termination, 
details of the birth, and any birth defects, congenital 
abnormalities, or maternal and/or newborn complications.  
Pregnancies must be reported to Karyopharm, regardless 
of whether the patient withdraws from the study or the 
study is completed, for 3 months after the patient receives 
his/her last dose of study treatment. Patients should be 
instructed to inform the Investigator regarding any 
pregnancies. 
All pregnancies occurring within 3 months after the 
patient’s last dose of study drug must be reported to 
Karyopharm, regardless of whether the patient received 
selinexor or other study drugs, withdraws from the study, 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Rationale for the Change 
or the study is completed. Patients should be instructed to 
inform the Investigator regarding any pregnancies.  
Any SAE that occurs during pregnancy must be recorded 
on the SAE report form (eg, maternal serious 
complications, therapeutic abortion, ectopic pregnancy, 
stillbirth, neonatal death, congenital anomaly, or birth 
defect) and reported within 24 hours in accordance with 
the procedure for reporting SAEs (described in Section 
12.2.3). 
A pregnancy in a female partner of a male patient must be 
reported to Karyopharm within 24 hours of learning of its 
occurrence. Pregnancies in female partners should only be 
followed if the male patient is being treated with a 
selinexor-containing regimen. Consent to report 
information regarding these pregnancy outcomes should 
be obtained from the female partner. 
It is not known whether selinexor passes into the breast 
milk. Mothers should not breastfeed while being treated 
with selinexor-containing regimen. 
 
Section 10.2.3.2: Selinexor 
Clarified the wording for how selinexor should be 
administered and removed the need to take selinexor with 
food. 
Selinexor tablets should be taken with food, or within 
30 minutes after the patient has eaten, together orally with 
at least 120 mL (4 ounces) of fluids water at 
approximately the same time each day. It can be taken 
with or without food. Selinexor tablets should be 
swallowed whole (not crushed) to prevent an increased 
risk of dermatologic toxicity if the powder comes in 
contact with skin. 
To align with the guidance in the current 
Selinexor Investigator’s Brochure (IB) 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Description of Change 
Rationale for the Change 
Section 10.5.1: Missed Doses of 
Study Treatments (Selinexor, 
Bortezomib, and Dexamethasone) 
Revised the guidance for doses of study treatment that 
must be missed due to protocol- or study-related reasons 
to: 
1) Provide 72 hours between 2 consecutive doses of 
bortezomib 
2) Remove the requirement for 36 hours between doses 
Section 10.5.1 Missed Doses of Study Treatments 
(Selinexor, Bortezomib, and Dexamethasone) 
Missed doses of all study treatments should be managed 
as follows:  
For doses missed for protocol- or study-related reasons 
(eg, due to recommendation of the Investigator, such as 
due to an AE): 
• If a dose was missed, the schedule of that week 
should be altered to accommodate 2 doses in that 
week with at least 36 hours between 2 consecutive 
doses. 
• If a dose must be skipped (e.g., due to 
recommendation of the Investigator), the next dose 
will be taken as per schedule. Doses should not be 
administered less than 36 hours apart, and all 
missed and delayed doses should be documented. 
• Missed dose of bortezomib for patients in the Vd 
Arm Only: If a bortezomib dose was missed, the 
schedule of that week should be altered to 
accommodate 2 doses in that week with at least 72 
hours between 2 consecutive doses of bortezomib. 
• Missed dose of any study treatment for all 
patients: If a dose of any study treatment must be 
missed, the next dose will be taken as per schedule. 
All missed and delayed doses should be 
documented. 
1) To provide 72 hours between 2 consecutive 
doses of bortezomib in a week for patients in 
the Vd Arm as required in the Velcade® 
Prescribing Information 
2) To clarify that the next dose for study 
treatments missed due to protocol- or study-
related reasons should be taken per schedule 
and to remove the requirement for 36 hours 
between doses 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Description of Change 
Rationale for the Change 
For doses missed for reasons not related to the 
protocol/study (eg, a required medical procedure or an 
unanticipated personal emergency): 
• If a patient missed a full 1- or 2-week period of 
study treatment dosing for events that are not 
related (e.g., a required medical procedure or an 
unanticipated personal emergency), to the protocol 
or the study the days missed will be replaced. For 
example, if a patient missed C2D7 to C2D14, then 
the patient will start the next dosing on C2D7 
following the break. Similarly, if a patient misses 
C3D1 to C3D15, then the patient will start the next 
dosing on C3D1. 
The schedule of MM evaluations will be maintained 
regardless of drug holidays or drug interruptions (Section 
11.3.1). 
Section 10.3.3: Infection 
Section 10.4.1: Selinexor Dose 
Reduction Guidelines (Table 16: 
Supportive Care and Selinexor 
Dose Adjustment Guidelines for 
AEs Related to Selinexor) 
Section 10.4.1.1: Selinexor Dose 
Adjustment in the Setting of 
Infection 
Updated the supportive care instructions for consistency 
with current clinical practice. 
To align with the guidance in the current 
Selinexor IB 
Section 10.8.3.1: Restrictions for 
Selinexor 
Deleted the restriction for alcohol use on study treatment 
dosing days. 
To align with the guidance in the current 
Selinexor IB 
Section 3: Study Schematics and 
Schedule of Assessments and 
Dosing for Study KCP-330-023 
(Table 2: Schedule of 
Added text in a new subsection (Section 11.4.2.1) to 
indicate that a portion of the bone marrow aspirate will be 
collected to isolate plasma, non-tumor CD138- and tumor 
CD138+ cell fractions for subsequent PDn studies.  
Section 11.4.2.1 
Bone Marrow Aspirates for PDn 
To obtain samples to be used in analyses to 
identify predictive biomarkers of selinexor 
response, characterize the knowledge of 
selinexor’s mechanism of action, and/or 
assess the presence of the high risk mutations. 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
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Description of Change 
Rationale for the Change 
Assessments for Study KCP-330-
023, footnote v) 
Section 11.3.1.9: Bone Marrow 
Aspirate 
Section 11.4.2 Pharmacodynamic 
Studies (new) 
Section 11.4.2.1: Bone Marrow 
Aspirates for PDn (new) 
Bone marrow aspirate will be collected at Screening to 
isolate plasma, non-tumor CD138- and tumor CD138+ 
cell fractions for subsequent PDn studies. Studies may 
include transcriptomic, genomic and/or proteomic 
analyses to identify predictive biomarkers of selinexor 
response and to characterize the knowledge of selinexor’s 
mechanism of action. In addition, tumor cells will be used 
to assess the presence of the high risk mutations including 
del(17p), t(14;16) and t(4;14) translocations and 
chromosome 1q21 amplification. Cytogenetic analysis by 
karyotyping and FISH will be performed at a central 
laboratory to identify specific chromosomal translocations 
at sites known to show rearrangements in MM. 
Aspirate samples containing patient DNA may be used for 
pharmacogenetic research to do the following:  
• study the causes of human diseases  
• help understand how different individuals respond 
to drugs  
• obtain information to help develop new methods to 
diagnose and treat diseases 
The samples may be stored up to 15 years, depending on 
the laws of country where the study is conducted. The 
samples will be labeled with a code rather than with 
patient name or any other detail that could be used to 
identify the patient. These samples will be stored under 
the control of the Sponsor. 
Details of PDn sample collection and processing can be 
found in the Study Manual. 
Related changes were made to the other sections noted. 
Section 3: Study Schematics and 
Schedule of Assessments and 
Dosing for Study KCP-330-023 
Removed the North American restriction for PK sampling.  To provide flexibility for PK sampling to be 
performed at selected sites outside of North 
America 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
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Version 4.0 
Section(s) 
Description of Change 
Rationale for the Change 
(Table 2: Schedule of 
Assessments for Study KCP-330-
023, PK row and footnote q) 
Section 11.4.1: Pharmacokinetic 
Endpoints 
Section 1:List of Abbreviations 
and Definitions of Terms 
Section 11.5.1.4: Ophthalmic 
Examination 
Added the specific grading system (ie, the American 
Optometric Association) for cataract/lens opacity.  
 
Section 11.5.1.4 Ophthalmic Examination  
… 
If a cataract/lens opacity is seen during the examination, 
the cataract/lens opacity will be graded according to a 
Grade 1 to 4 system the American Optometric Association 
(AOA) Cataract Grading System, which is available on 
the AOA website (www.aoa.org). 
 
To provide the specific grading system (ie, the 
American Optometric Association)  that will 
be used to assess cataract/lens opacity 
Section 12.1.2: Recording of 
Adverse Events 
Section 12.1.2.1 Laboratory Test 
Abnormalities 
Section 12.1.3: Adverse Event 
Severity 
Section 12.2.2: Recording of 
Serious Adverse Events 
 
Made minor wording changes to the guidance in these 
sections for clarity. 
 
To align with the new safety language 
template provided by the Karyopharm 
Pharmacovigilance Department 
Section 12.2: Serious Adverse 
Event 
Section 12.2.1: Events that Do 
Not Meet the Definition of a 
Serious Adverse Event 
Added a new subsection (Section 12.2.1) with text 
clarifying the definition of events that do not meet the 
definition of an SAE.  
Section 12.2.1 Events that Do Not Meet the Definition 
of a Serious Adverse Event 
To align with the definition of SAEs 
described in the new safety language template 
provided by the Karyopharm 
Pharmacovigilance Department 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
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Description of Change 
Rationale for the Change 
Hospitalizations for elective surgery or other medical 
procedures that are not due to an AE are not considered 
SAEs. A hospitalization meeting the regulatory definition 
for ‘serious’ is any inpatient hospital admission that 
includes a minimum of an overnight stay in a health care 
facility. An emergency room visit is not considered a 
hospitalization unless it results in an official admission to 
the hospital. Elective hospitalizations to administer, or to 
simplify study treatment or study procedures (ie, an 
overnight stay to facilitate 24-hour urine collection) or 
other medical procedures are not considered SAEs. A 
‘serious’ hospitalization is defined as any inpatient 
hospital admission that includes a minimum of an 
overnight stay in a health care facility. An emergency 
room visit is not considered a hospitalization unless it 
results in an official admission as an inpatient to the 
hospital (eg, undesirable effects of any administered 
treatment) and  must be documented as an SAE. 
Progression of the malignancy/disease (including fatal 
outcomes) should NOT be reported as an SAE during the 
study or within the safety reporting period (see Section 
12.2.2 12.2.3). Sudden or unexplained death should be 
reported as an SAE. If there is any uncertainty about a 
finding being due solely to progression of 
malignancy/disease, the finding should be reported as an 
AE or SAE, as appropriate. 
Section 12.3.2: Overdose, Abuse, 
Misuse, Medication Errors, and 
Occupational Exposure 
Section 12.3.2.1: Overdose 
Section 12.3.2.2: Abuse, Misuse, 
or Medication Error 
Changed the reporting mechanism for reporting overdose, 
abuse, misuse, medication errors, and occupational 
exposure from fax to email. 
Revised the timing for reporting of overdose, abuse, 
misuse, medication errors, and occupational exposure for 
events that are not AEs or SAEs from “as soon as 
possible” to “within 24 hours of awareness.” 
To align with the guidance described in the 
new safety language template provided by the 
Karyopharm Pharmacovigilance Department 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 138 
Version 4.0 
Section(s) 
Description of Change 
Rationale for the Change 
Section 13.7.2.7 Concomitant Medications 
Concomitant medications will be coded using the World 
Health Organization Drug Dictionary and will be 
summarized by Anatomic Therapeutic Chemical 
Classification System 3 level 2 (therapeutic level), level 4 
(generic level), and standard preferred names. Both prior 
and concomitant medications will be included in by-
patient data listings. 
 
 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 139 
Version 4.0 
Amendment 2, Version 3.0 
Amendment Rationale 
The primary purpose for this amendment is to incorporate changes the statistical analysis 
sections to address comments from the FDA received on 04 April 2017.  
Other changes include: 
• Additional pregnancy testing and a clarification to contraception requirements to 
align with the recommendations of the Clinical Trial Facilitation Group 
• Details for continuation of study treatment for patients if the study is terminated early 
to comply with ICH GCP E6 
The revised protocol Version 3.0 dated 06 April 2017 will be submitted by the Principal 
Investigator(s) to all applicable Institutional Review Boards, Independent Ethics Committees, or 
Research Ethics Boards, and by Karyopharm Therapeutics Inc. to all applicable regulatory 
authorities. 
A summary of the changes that were made to Version 2.0 of the protocol in Version 3.0 is 
provided below. 
Changes to the protocol 
Administrative 
• Updated the version number and date to Version 3.0 and 06 April 2017 throughout to 
reflect the changes made in this version (Modified sections: Global). 
• Revised “> Grade X” to “Grade > X” and “≥ Grade X” to “Grade ≥ X” (Modified 
sections: Global). 
• Revised the first signatory to the Chief Executive Officer and Acting Chief Medical 
Officer (Modified section: Signature Page).  
• Made minor editorial changes to the supportive care table (Modified section: 
Table 15). 
Randomization 
• Added details for the Interactive Response Technology system that will be used to 
perform treatment randomization to address the FDA request to include a 
randomization method in the protocol (Modified section: 8.2). 
Early Termination of the Study 
• Added details for continuation of study treatment for patients if the study is 
terminated early to comply with ICH GCP E6 (Modified section: Section 9.1).  
Contraception Requirements 
• Clarified that double-barrier contraception methods are considered effective but not 
highly effective to align with the recommendations of the Clinical Trial Facilitation 
Group. Revised text: “A combination of male condom with either cap, diaphragm or 
sponge with spermicide (double barrier methods) are also considered acceptable (ie, 

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CCI

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 141 
Version 4.0 
Changed the Hochberg procedure for testing the secondary endpoints to a hierarchical testing 
procedure to address the FDA recommendation to use a hierarchical testing procedure for the 
secondary endpoints. Per the FDA, the Hochberg procedure is not an assumption-free method. 
Although it provides adequate overall alpha-control for independent and for certain types of 
positively correlated endpoints, its properties for other types of dependent endpoints are not fully 
known (Modified sections: Sections 13.5.2 and 15). 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 142 
Version 4.0 
Amendment 1, Version 2.0 
Amendment Rationale 
The primary purpose for this amendment is to incorporate changes to address comments from the 
FDA received on 05 January 2017. The majority of these changes, as detailed below, were made 
to the efficacy analysis and the background and administrative sections. 
The revised protocol Version 2.0 dated 22 February 2017 will be submitted by the Principal 
Investigator(s) to all applicable Institutional Review Boards, Independent Ethics Committees, or 
Research Ethics Boards, and by Karyopharm Therapeutics Inc. to all applicable regulatory 
authorities. 
A summary of the changes that were made to Version 1.0 of the protocol in Version 2.0 is provided 
below. 
Changes to the protocol 
Administrative 
• Updated the version number and date to Version 2.0 and 22 February 2017 
throughout to reflect the changes made in this version (Modified sections: Global). 
• Removed Section 1 (Sponsor Information) because the information was redundant 
and renumbered the sections globally (Modified sections: Global). 
• Internal changes to improve clarity and eliminate inconsistencies between sections 
(Modified sections: Global). 
• Revised color of active links ie, (numbers for sections and table/figure links) to blue 
font to align with new medical writing practices (Modified sections: Global). 
• Revised the first signatory to the Senior Vice President of Clinical development 
(Modified section: Signature Page). 
• Removed details for the statistical analyses from the Synopsis (Modified section: 
Synopsis). 
• Updated the list of abbreviations and added the definition of Study Manual to 
improve clarity (Modified section: Table 1). 
• Corrected footnote #7 in Table 2 to provide C10D29 as an example of an in-clinic 
dosing visit on which the window for MM disease assessments may be extended 
(Modified section: Table 2). 
• Clarified that the End of Vd Treatment Visit and the C1D1 Visit for SVdX or SdX 
Treatment may be combined at the discretion of the Investigator. Also clarified that 
the IRC-confirmed PD date is the date of the first of the 2 consecutive assessments 
that meet the response criteria for PD, not the date that the IRC informs the site that 
PD has been confirmed (Modified section: Table 3).  
• Removed Figure 2, which contained redundant information for MM disease 
assessments and the dosing scheme (Modified sections: Section 6.1 and Figure 2). 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 143 
Version 4.0 
• Expanded the introduction section to include additional justification for the proposed 
dosing regimen to address the FDA request to add adequate justification of the 
proposed dosing regimen in the protocol, including PK, PDn, nonclinical, efficacy, 
and safety data (Modified sections: Sections 4.2.5, 4.2.6.1, and 4.3; New Sections: 
4.2.2, 4.2.3, 4.2.4, 4.4.2, and 4.4.2.1). 
• Updated clinical study data for clinical experience with selinexor (Modified sections: 
Sections 4.2.6 and 4.2.6.1). 
• Removed the use of a Patient Enrollment Form to reflect the electronic enrollment 
process that is being used for this study (Modified section: Section 8.1). 
• Minor wording changes to improve clarity related to dosing information for 
bortezomib and dexamethasone (Modified sections: Sections 10.2.3.3, 10.2.3.4, 
10.4.3, 10.8.3.2, and 10.8.4). 
• Added a separate subsection (Section 10.2.6) for duration of treatment and follow-up 
(Modified section: Section 10.2). 
• Corrected footnote #1 in Table 14 to indicate that patients who are tolerating SVd 
well may be dose escalated to correct a typographical error (Modified section: 
Table 14).  
• Removed the following sentence, which is not accurate from the missed doses 
section: “In this fashion, laboratory and radiographic assessments remain appropriate 
for timing of the administration of anticancer therapy” (Modified section: 
Section 10.5.1). 
• Added note regarding contact information for urgent medical issues (Modified 
section: Section 12). 
• Moved section for Procedures for Handling Missing Data from the Safety Analysis 
section to the appropriate location in the Data Analysis and Presentation section 
(Modified sections: Sections 13.4.1 and 13.7).  
• Revised references to Endnote format to align with new medical writing practices. 
(Modified section: Section 15).  
Study Design 
• Added crossover to treatment with selinexor and dexamethasone (SdX) as an option 
for patients in the Vd Arm after PD is confirmed by the IRC if they have significant 
tolerability issues with bortezomib (eg, Grade >2 peripheral neuropathy or Grade ≥2 
peripheral neuropathy with pain). This change was made to provide access to 
selinexor treatment for patients randomized to the Vd Arm who are unable to tolerate 
continued treatment with bortezomib after PD is confirmed (Modified sections: 
Synopsis, Sections 4.4.1, 5.1.2, 5.1.3, 5.2.2.1, 5.2.3, 6.1, 6.2, 6.4, 9.2, 9.3, 10.2.4, 
11.1, 11.3.1, 11.7.3, 11.7.4, 13.3.5, 13.4, 13.4.3, 14.6, and Tables 2 and 3, and Figure 
1; New sections: Sections 13.3.3 and 13.3.4 and Tables 7 and 11. 

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Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 145 
Version 4.0 
• Revised exclusion #12 to clarify that patients treated with an investigational 
anticancer therapy within 2 weeks prior to C1D1 are specifically excluded from the 
study (Modified section: Section 7.3). 
Schedule of Assessments 
• Clarified that symptom-directed physical examinations will only be performed if 
clinically indicated to address questions regarding invoicing symptom-directed 
physical examinations that came up during preparation of the site contracts (Modified 
sections: Tables 2 and 12). 
• Clarified that clinical plasmacytoma assessments are to be performed if clinically 
indicated at MM Disease Assessment Visits and at Durability of Response and 
Survival Follow-up Visits. Also corrected the window for detection of 
plasmacytomas at baseline by physical examination/palpation from “within 45 days” 
to “within 28 days” prior to C1D1 in footnote #21 of Table 2 (Modified sections: 
Section 11.3.1.8 and Tables 2 and 12). 
• Clarified that a skeletal survey is required at the EoT Visit (Modified section: 
Table 2). 
Study Treatment Administration 
• Removed the requirement for dose escalation for patients in the SVd Arm who do not 
achieve at least a PR within the first 2 cycles, are tolerating SVd well, and do not 
have any AEs related to study treatment Grade >2 at the time of dose escalation. Dose 
escalation is no longer be required for these patients, however, a dose escalation may 
still be considered. This change was made to provide a greater margin of safety by 
making a determination for escalation of the selinexor dose based on the medical 
status of each individual patient. Also clarified that dose escalation is an option for all 
selinexor-containing regimens (Modified sections: Synopsis, Section 10.2.4.1, and 
Tables 8, 11, and 14; New section: Section 10.2.5). 
Multiple Myeloma Disease Assessments 
• Added a requirement for baseline bone marrow aspirate at Screening for all because 
the expectation in the field is that a baseline bone marrow aspirate is necessary to 
obtain accurate 17p status prior to starting a new therapy, Also, clarified that a portion 
of the bone marrow aspirate collected at Screening will be provided to the central 
laboratory for karyotyping and fluorescence in situ hybridization (FISH) analysis to 
confirm diagnosis and classify cytogenetic MM subtypes for R-ISS staging. 
(Modified sections: Section 11.3.1.9 and Table 2).  
• Removed turbidometry as an acceptable method for measuring quantitative Ig levels 
because, unlike nephelometry, turbidometry cannot be used to assess response. Also 
clarified that nephelometry may be used in place of SPEP for routine M-protein 
measurement for patients with IgD myeloma in addition to patients with IgA 
myeloma (Modified sections: Sections 11.3.1 and 11.3.1.3). 

Investigational Product (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-023 
 
17 August 2018 
Confidential 
Page 146 
Version 4.0 
PK Assessments 
• Added PK assessments for bortezomib and selinexor in a subset of patients 
randomized to each arm (ie, the Vd Arm and the SVd Arm) in order to explore 
exposure-response relationships and drug-drug interactions between bortezomib and 
selinexor, and to evaluate any differences in PK related to age, race, sex, BMI, 
baseline disease state, or other demographic characteristics (Modified sections: 
Section 10.2.3.1 and Table 2; New Sections 5.1.4, 5.2.4, 11.4, and 13.6). 
Clinical Safety Assessments 
• Clarified that BSA should be recalculated if the patient’s weight fluctuates 
substantially from baseline (ie, >20%) during treatment (including Vd, SVd, SVdX, 
and SdX) (Modified sections: Global). 
Analysis Populations 
• Revised the definition of the per-protocol (PP) population from all ITT patients who 
have received “any amount” to “at least 1 dose “of study treatment to clarify that the 
population does not include patients who have not received study treatment 
(Modified sections: Synopsis and Section 13.3.2). 
Efficacy Analysis 
• Added justification for the sample size calculation assumptions. This change was 
made to address the FDA request to provide justification for the assumptions for the 
sample size calculation (Modified sections: Sections 13.2.1 and 13.2.2). 
• Specified that an independent third party (the DSMB) will conduct and review the 
sample size re-estimation and that an interim analysis charter will be created to 
outline the operational procedures associated with both PFS IAs. This change was 
made to address the FDA recommendation that the conduct/review of the sample size 
re-estimation be conducted by an independent third party (Modified section: 
Section 13.2.3.1). 
• Clarified timing and details for the second IA (Modified section: Section 13.2.3.2). 
• Added a sensitivity analysis using the Breslow-Day test to evaluate the homogeneity 
of odds ratios across the strata associated with the ORR endpoint and the two 
secondary efficacy endpoint analyses which are analyzed using the Cochran-Mantel-
Haenszel test. This change was made to address the FDA request to include a 
sensitivity analysis to evaluate the robustness of secondary efficacy endpoints 
analysis results. (Modified sections: Sections 13.5.1 and 13.5.2). 
• Added sensitivity analyses for the primary efficacy endpoint and the key secondary 
efficacy endpoints to address the FDA request to provide sensitivity analyses to 
evaluate the robustness of efficacy results in the protocol, which includes different 
censoring rules for the analyses of time-to-event endpoints. The sensitivity analyses, 
based on the guidance “Clinical Trial Endpoints for the Approval of Cancer Drugs 
and Biologics” will consider the events in which patients have taken other anticancer 
therapy, missed assessments, or been lost-to-follow-up (Modified sections: 
Sections 13.5.1.1, 13.5.1.2, and 13.5.2). 

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