A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose Dexamethasone (Sd) in Patients With Multiple Myeloma Previously Treated With Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and an Anti-CD38 Monoclonal Antibody (mAb) Daratumumab, and Refractory to Prior Treatment With Glucocorticoids, an Immunomodulatory Agent, a Proteasome Inhibitor, and an the Anti-CD38 mAb Daratumumab
Phase: PHASE2
Conditions: Multiple Myeloma
Sponsor: Karyopharm Therapeutics Inc

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 1 
Clinical Study Protocol 
KCP-330-012 
A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus 
Low-Dose Dexamethasone (Sd) in Patients with Multiple Myeloma Previously 
Treated with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and 
Daratumumab, and Refractory to Prior Treatment with Glucocorticoids, an 
Immunomodulatory Agent, a Proteasome Inhibitor, and the anti-CD38 mAb 
Daratumumab 
Study Name:  STORM (Selinexor Treatment of Refractory Myeloma)  
Drug Development Phase: 
Phase 2b 
Investigational Product: 
Selinexor (KPT-330) 
Indication: 
Multiple myeloma (MM) previously treated with 
lenalidomide, pomalidomide, bortezomib, carfilzomib, 
and daratumumab, and refractory to prior treatment with 
glucocorticoids, an immunomodulatory agent (IMiD), a 
proteasome inhibitor (PI), and the anti-CD38 mAb 
daratumumab  
EudraCT Number: 
2016-003094-18 
Sponsor: 
Karyopharm Therapeutics Inc. 
85 Wells Avenue 
Newton, MA 02459 USA 
Tel. + (617) 658-0600 
Protocol Date and Version: 
24 December 2014, Version 1.0 
05 February 2015, Version 2.0 
25 September 2015, Version 3.0 
11 August 2016, Version 4.0- ROW (Rest of World) 
06 February 2017, Version 4.1 US (Country-specific) 
28 April 2017, Version 5.0 
13 December 2017, Version 6.0 
CONDUCT 
In accordance with the ethical principles that originate from the Declaration of Helsinki and that 
are consistent with International Conference on 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. 

PPD
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Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 3 
PRINCIPAL INVESTIGATOR’S AGREEMENT 
I have read and understand the contents of this clinical protocol for Study No. KCP-330-012 
dated 13 December 2017 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 Practices, ICH E6, and applicable FDA regulatory requirements: 
Name of Principal Investigator: 
Principal Investigator’s Signature: 
 
Principal Investigator’s Name: 
 
Institution: 
 
Date: 
 
 
 
 
 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 4 
PROTOCOL SYNOPSIS 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase: 
Phase 2b 
Title of Study:   
A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose 
Dexamethasone (Sd) in Patients with Multiple Myeloma Previously Treated with 
Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and Daratumumab, and 
Refractory to Prior Treatment with Glucocorticoids, an Immunomodulatory Agent, a 
Proteasome Inhibitor, and the anti-CD38 mAb Daratumumab 
Protocol Number: KCP-330-012: STORM (Selinexor Treatment of Refractory Myeloma) 
Indication: Multiple myeloma previously treated with lenalidomide, pomalidomide, 
bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with 
glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the 
anti-CD38 mAb daratumumab (penta-refractory MM) 
Objectives: 
Primary: 
Evaluate the efficacy (overall response rate [ORR]) for treatment with selinexor 80 mg 
plus low-dose dexamethasone (20 mg) (Sd) twice weekly (four-week cycles) in patients 
with MM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, 
and daratumumab, and refractory to prior treatment with glucocorticoids, an 
immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb 
daratumumab (herein referred to as penta-refractory MM). 
ORR will include patients who experience partial response (PR), very good partial 
response (VGPR), complete response (CR), or stringent complete response (sCR), based 
on International Myeloma Working Group (IMWG) response criteria (Kumar 2016) for 
patients with penta-refractory MM in Part 2 (Expansion). 
Secondary: 
The following endpoints will be analyzed separately for (a) Part 1 patients with quad-
refractory MM (i.e., previously treated with lenalidomide, pomalidomide, bortezomib, 
carfilzomib, but not an anti-CD38 mab), (b) Part 1 patients with penta-refractory MM, and 
(c) Part 2 (expansion) patients with penta-refractory MM. Additionally, analyses of safety 
and tolerability will be performed on the overall population of patients from Parts 1 and 2 
who received at least one dose of study treatment. 
x Duration of response (DOR = Duration from first observation of at least PR to time 
of disease progression, or deaths due to disease progression, whichever occurs first.  
DOR will be censored for death due to any causes other than disease progression. 
x Clinical Benefit Rate (CBR = sCR + CR + VGPR + PR + minimal response [MR]), 
and duration of clinical benefit (Duration from first observation of at least MR to 
time of disease progression or death due to disease progression, whichever occurs 
first. Duration of clinical benefit will be censored for death due to any causes other 
than disease progression) 

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CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 6 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase: 
Phase 2b 
eventually relapse with their disease becoming drug-resistant. With over 12,600 deaths 
from MM anticipated in 2016 in the US alone, there is an unmet medical need for therapies 
in patients with relapsed and/or refractory (RR) MM that has progressed on available 
treatments.  
Selinexor is an orally bioavailable, selective inhibitor of nuclear export (SINE) compound 
that specifically blocks exportin 1 (XPO1). Selinexor and other SINE compounds have 
demonstrated anti-MM activity in preclinical studies.  In the Phase-1 study, selinexor alone 
(all doses) showed an ORR of 5%, and with low-dose dexamethasone (Sd; all doses) the 
ORR was 32%.   Therefore, the Sd regimen was carried forward into this ongoing Phase 2 
study.   
Rationale for Expansion (protocol version 4.0) 
For Part 1 of this study, 78 patients with measurable RR MM have been evaluated 
(79 patients were enrolled, but 1 patient did not have measurable MM at baseline): 
48 patients with quad-refractory MM (IMIDs and PIs) and 30 patients with penta-
refractory MM (quad + anti-CD38 refractory). Patients were initially dosed with 6 doses of 
Sd per cycle, and this was increased to 8 doses of Sd per cycle. The ORR adjudicated by a 
four-physician Independent Review Committee (IRC) across all patients was 21% and the 
clinical benefit rate (CBR) is 33%. Similar ORR were seen in the patients with “penta” and 
“quad” MM, with higher CBR in patients who received 8 vs. 6 doses/cycle consistent with 
improved disease control with continuous dosing. The median duration of response (DOR) 
was ~5 months, with 9 patients continuing on study. There was a trend towards higher 
ORR in the 8-dose per cycle Sd regimen, with little difference in tolerability. Furthermore, 
there was a trend to increased time on study in patients with baseline hemoglobin (Hb) 
≥ 8.5 gm/dL. Therefore, based on the current unmet medical need for patients with RR 
MM and these preliminary clinical results, this study is now being expanded to evaluate 
the efficacy and safety of twice-weekly Sd in patients with penta-refractory MM.  
Methodology: 
This is a Phase 2b, single-arm, open-label, multicenter study of Sd, dosed twice weekly 
each week in four-week cycles, in patients with penta-refractory MM (Parts 1 and 2) or 
quad-refractory MM (Part 1 only).  
The population for the primary efficacy analysis will contain only patients with penta-
refractory MM enrolled in Part 2. Response results for patients with quad-refractory MM 
and patients with penta-refractory MM enrolled in Part 1 will be analyzed separately. 
Safety analyses will be performed on the overall population of patients who received at 
least one dose of study drug, presented overall and by study part, and separately for Part 1 
penta-refractory and quad-refractory patient populations. 
Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be 
managed by standard care, or withdrawal, whichever occurs first. 
Inclusion/Exclusion Criteria: 
Inclusion: 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 7 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase: 
Phase 2b 
Patients must meet all of the following inclusion criteria to be eligible to enroll in this 
study: 
1. Written informed consent in accordance with federal, local, and institutional 
guidelines. 
2. Age ≥ 18 years at the time of signing informed consent. 
3. Measurable MM based on IMWG guidelines as defined by at least one of the 
following: 
a. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA 
myeloma, by quantitative IgA 
b. Urinary M-protein excretion ≥ 200 mg/24 hours  
c. FLC ≥ 100 mg/L, provided that the FLC ratio is abnormal.  
d. If serum protein electrophoresis is felt to be unreliable for routine M-protein 
measurement, then quantitative Ig levels by nephelometry is acceptable. 
4. Patients must have previously received ≥ 3 anti-MM regimens including: an alkylating 
agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and a 
glucocorticoid. There is no upper limit on the number of prior therapies provided that 
all other inclusion/exclusion criteria are met. 
5. MM refractory to previous treatment with one or more glucocorticoids, parenteral PI 
(i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), 
and daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression 
during therapy or progression within 60 days after completion of therapy. 
6. Multiple myeloma that is refractory to the patient’s most recent anti-MM regimen. 
(Documented severe intolerance to the patient’s last therapy is allowed upon approval 
by the Medical Monitor.) 
7. Any clinically significant non-hematological toxicities (except for peripheral 
neuropathy as described in exclusion criterion #17) that patients experienced from 
treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 
Day 1. 
8. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x 
upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have 
a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.  
9. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine 
clearance of ≥ 20 mL/min, calculated using the formula of Cockroft and Gault.  
10. 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. Male patients must use an effective barrier 
method of contraception if sexually active with a female of child-bearing potential.  
For both male and female patients, effective methods of contraception must be used 
throughout the study and for three months following the last dose of study treatment. 
11. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2. 
12. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion 
Criterion #20 for transfusion washout periods for RBCs and platelets):  
a. Total WBC count > 1,000/mm3 
b. ANC ≥ 1000/mm3 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 8 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase: 
Phase 2b 
c. Platelet count ≥ 75,000/mm3 (patients in whom < 50% of bone marrow nucleated 
cells are plasma cells) or ≥ 50,000/mm3 (patients in whom ≥ 50% of bone marrow 
nucleated cells are plasma cells.  [Platelet transfusions < 1 week prior to Cycle 1 
Day 1 are prohibited (see below).] 
13. Hemoglobin level ≥ 8.5 g/dL. In certain cases, patients with stable baseline 
hemoglobin level > 8.0 may be included following approval by the Medical Monitor. 
[Red blood cell transfusions < 2 weeks prior to Cycle 1 Day 1 are prohibited (see 
below).] 
14. Confirmation of patient eligibility for specific key criteria for study participation with 
the Medical Monitor. 
Exclusion Criteria: 
1. Active smoldering MM. 
2. Active plasma cell leukemia. 
3. Documented systemic amyloid light chain amyloidosis. 
4. Active central nervous system (CNS) MM. 
5. Pregnancy or breastfeeding. 
6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks 
prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1. 
7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 
Day 1  
8. Life expectancy of < 4 months. 
9. Major surgery within four weeks prior to Cycle 1 Day 1. 
10. Active, unstable cardiovascular function: 
a. Symptomatic ischemia, or  
b. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with 
ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree 
atrioventricular (AV) block or asymptomatic left anterior fascicular block/right 
bundle branch block (LAFB/RBBB) will not be excluded), or 
c. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, 
or 
d. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1. 
11. Active, uncontrolled hypertension. 
12. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals 
within one week prior to first dose. 
13. Known HIV seropositive. 
14. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or 
HBsAg (HBV surface antigen). 
15. 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 enrollment. Cancer treated with curative intent > 5 years previously 
and without evidence of recurrence will be allowed. 
16. Active GI dysfunction interfering with the ability to swallow tablets, or any GI 
dysfunction that could interfere with absorption of study treatment. 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 9 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase: 
Phase 2b 
17. Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 21 days 
prior to Cycle 1 Day 1. 
18. Serious, active psychiatric or medical conditions which, in the opinion of the 
Investigator, could interfere with treatment. 
19. Participation in an investigational anti-cancer study within 21 days prior to Cycle 1 
Day 1. 
20. Receipt of transfusions as follows: 
a. Platelet infusion within 1 week prior to Cycle 1 Day 1. 
b. RBC transfusion within 2 weeks prior to Cycle 1 Day 1. 
21. Receipt of the following blood growth factors within 2 weeks prior to Cycle 1 Day 1: 
Granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony 
stimulating factor (GM-CSF), erythropoietin (EPO), or megakaryocyte growth factor. 
22. Known intolerance to or contraindication for glucocorticoid therapy at Cycle 1 Day 1. 
23. Prior exposure to a SINE compound, including selinexor. 
24. Unable or unwilling to comply with protocol requirements, including providing a 
24-hour urine samples at the required study time points. 
Documentation Requirements  
For enrollment consideration, patients may be eligible if they have documented evidence of 
previous treatment for MM that substantiates disease status as follows: 
x Refractory to a glucocorticoid 
x Refractory to lenalidomide and/or pomalidomide (only 1 required) and evidence of 
prior treatment* with both lenalidomide and pomalidomide 
x Refractory to bortezomib and/or carfilzomib (only 1 required) and evidence of prior 
treatment* with both bortezomib and carfilzomib 
x Refractory to daratumumab 
* Prior treatment is defined as either refractory, treatment with ≥ 2 cycles, or documented 
severe intolerance. 
Documented evidence will include at least one of the following:  
1. Medical records that support start and stop dates (month/year) of prior treatment (both 
dose and schedule), best response on prior treatment and, if applicable, date of 
progression (including both dose and schedule at the time of progression). 
2. Myeloma marker values (SPEP, UPEP, Immunoglobulin, FLC) at the time of prior 
treatment start, stop and time of progression (accompanied by #1). 
3. Formal, signed physician letter by Investigator (on hospital/clinic letterhead), to be 
included in the patient’s medical and research record, indicating start/stop dates of 
prior treatment (both dose and schedule), best response on treatment and, if applicable, 
date of progression (including both dose and schedule at the time of progression). 
4. Formal, signed physician letter from referring physician (on hospital/clinic letterhead), 
to be included in the patient’s medical and research record, that includes prior 
treatment history indicating start/stop dates of prior treatment (both dose and 
schedule), best response on prior treatment and, if applicable, date of progression 
(including both dose and schedule at the time of progression). 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
13 December 2017, Version 6.0 
Confidential 
Page 10 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase: 
Phase 2b 
Test Product, Dose and Mode of Administration: 
Selinexor will be given at an oral fixed milligram (mg) dose of 80 mg twice weekly each 
week for four-week cycles (total of 8 selinexor doses per cycle).  
Dexamethasone 20 mg will be given with each dose of selinexor. If a patient develops 
partial intolerance to glucocorticoids (as determined by the Investigator) during the study, 
a minimum dose of dexamethasone 10 mg is permitted. If any patient is not able to tolerate 
this dose, then a potential discontinuation or further decrease in dosage would be allowed 
after a discussion with the Medical Monitor on a case by case basis. 
In select cases (e.g., for patients showing SD, MR or PR and tolerating treatment 
particularly well), the selinexor dose may be increased by 20 mg (i.e., to 100 mg twice 
weekly) after consultation with the Medical Monitor. The dose level for an individual 
patient may be escalated based on efficacy considerations after completing a minimum of 
2 cycles of study therapy. However, in no case may the dose for a given patient exceed 
70 mg/m2.   
Concomitant Medications: 
To minimize nausea, unless contraindicated, all patients should receive 5-
hydroxytryptamine (5-HT3) antagonists (e.g., ondansetron 8 mg or equivalent) starting on 
Day 1 before the first dose of selinexor and continued 2-3 times daily, as needed. 
Alternative anti-emetic agents should be used if the patient does not tolerate 5-HT3 
antagonists. Additional anti-nausea and anti-anorexia agents may be given as needed (per 
National Comprehensive Cancer Network® [NCCN] Clinical Practice Guidelines® for 
Antiemesis and NCCN Clinical Practice Guidelines® for Palliative Care). Patients will also 
receive therapy as needed to mitigate selinexor side effects, as part of best supportive care.  
Blood product transfusions, antimicrobials, and (as appropriate) growth factors including 
granulocyte colony-stimulating factors for neutropenia, erythropoietins for anemia, and/or 
platelet-stimulating factors for thrombocytopenia are also permitted. 
Patients may continue their baseline medication(s). Medications to treat concomitant 
diseases such as diabetes, hypertension, etc., are allowed. Patients will also receive 
concomitant medications that are medically necessary as standard care to treat symptoms, 
AEs and intercurrent illnesses. Patients may receive red blood cell or platelet transfusions, 
or blood growth factors, if clinically indicated, per institutional guidelines.  
Concurrent therapy with any other approved or investigational anti-cancer therapy is not 
allowed. Other investigational agents should not be used during the study. 
Study Numbers: 
Approximately 210 patients will be enrolled overall, including 79 patients (with quad-
refractory MM and penta-refractory MM) in Part 1 and ~130 patients (with penta-
refractory MM only) in Part 2 (to achieve the target population size of N = 122 for the 
primary efficacy analysis). 
Study Duration: 
The enrollment period for this study is expected to be approximately 24 months. There is 
no maximum treatment duration for the study or pre-defined number of treatment cycles 

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Selinexor (KPT-330) 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 14 
Table 1: 
Schedule of Assessments and Study Activities  
Activity/Assessment  
Screenin
g 
Cycle 1 
Cycle 2 
Cycles ≥ 3 
End-of-
Treatment 
(EoT) Visit 
Safety 
Follow-up 
Call 
Durability 
of Response 
and Survival 
Follow-up15 
Day -21 
to Day -1 
Day 1 Day 314 Day 8 Day 15 
Day 1 
Day 15 
Day 1 
≤ 14 Days 
Post Last 
Dose 
30 Days 
Post-Last 
Dose 
Every 3 mo. 
-1 day +1 day ± 1 day ± 1 day ± 2 days ± 2 days 
± 2 days 
+ 7 days 
± 14 days 
Informed consent1 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history2 
X 
X 
 
 
 
 
 
 
 
 
 
Patient height  
X 
 
 
 
 
 
 
 
 
 
 
Patient weight 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 
Body Surface Area (BSA)3 
X 
 
 
 
 
 
 
 
 
 
 
Physical examination, full 
including vital signs4  
X 
 
 
 
 
 
 
 
X 
 
 
Physical examination, symptom-
directed, including vital signs4 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
ECOG5 
X 
 
 
 
X 
 
X 
X 
 
 
Echocardiogram or MUGA6 
X 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
X 
 
 
Ophthalmic exam7 
X 
 
 
 
 
 
 
X 
 
 
Clinical Labs 
Urinalysis5 
X 
 
 
 
 
 
 
X 
 
 
CBC with differential5 
X 
 
 
X 
X 
X 
X 
X 
 
 
TSH5 
X 
 
 
 
 
 
 
X 
 
 
Complete serum chemistry5 
X 
 
 
 
X 
 
X 
X 
 
 
Limited serum chemistry 
 
 
 
X 
X 
 
X 
 
 
 
 
Coagulation tests5 
X 
 
 
 
 
 
 
X 
 
 

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Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 18
TABLE OF CONTENTS
PROTOCOL APPROVAL SIGNATURE PAGE ....................................................... 2 
PRINCIPAL INVESTIGATOR’S AGREEMENT ..................................................... 3 
PROTOCOL SYNOPSIS ............................................................................................ 4 
TABLE OF CONTENTS........................................................................................... 18 
LIST OF TABLES..................................................................................................... 24 
LIST OF ABBREVIATIONS.................................................................................... 25 
1. 
OVERVIEW........................................................................................... 31 
2. 
MULTIPLE MYELOMA....................................................................... 32 
3. 
NUCLEAR EXPORT............................................................................. 33 
3.1. 
Inhibition of XPO1 in Human Cancer.................................................... 33 
4. 
SELINEXOR (KPT-330)........................................................................ 34 
4.1. 
Introduction............................................................................................. 34 
4.2. 
Preclinical Data....................................................................................... 35 
4.2.1. 
Selinexor plus Dexamethasone Combination Studies ............................ 35 
4.3. 
Clinical Experience................................................................................. 36 
4.3.1. 
Preliminary Results for Patients with MM, Study KCP-330-001, as of 
13 December 2016.................................................................................. 36 
4.3.1.1. 
Preliminary Efficacy Results for Patients with MM, Study KCP-330-
001 .......................................................................................................... 36 
4.3.1.2. 
Preliminary Safety Results for Patients with MM, Study KCP-330-00136 
4.3.1.3. 
Preliminary Efficacy (Response) Results for Patients with MM, Study 
KCP-330-012.......................................................................................... 37 
4.3.1.4. 
Preliminary Safety Results for Patients with MM, Study KCP-330-01237 
4.3.1.5. 
Summary................................................................................................. 38 
4.4. 
Potential Risks ........................................................................................ 38 
4.4.1. 
Reproductive Risks................................................................................. 39 
5. 
RATIONALE FOR THE STUDY.......................................................... 39 
5.1. 
Rationale for Selinexor Dose Schedule .................................................. 39 
6. 
STUDY OBJECTIVES .......................................................................... 40 
6.1. 
Primary Objectives ................................................................................. 40 
6.2. 
Secondary Objectives ............................................................................. 40 

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Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 23
APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG)
PERFORMANCE STATUS CRITERIA ............................................... 88 
APPENDIX 2. INTERNATIONAL STAGING SYSTEM FOR MULTIPLE
MYELOMA............................................................................................ 89 
APPENDIX 3. INTERNATIONAL MYELOMA WORKING GROUP 
RESPONSE CRITERIA, MYELOMA .................................................. 90 
APPENDIX 4. SELINEXOR FORMULATION AND ADMINISTRATION ...... 94 
APPENDIX 5. LENS OPACITIES CLASSIFICATION SYSTEM ...................... 96 
APPENDIX 6. GLUTATHIONE (GSH)-, S-ADENOSYLMETHIONINE (SAM)-,
OR N-ACETYLCYSTEINE (NAC)-CONTAINING PRODUCTS 
(REPRESENTATIVE LIST).................................................................. 97 
APPENDIX 7. SUMMARY OF CHANGES ......................................................... 98 

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 24
LIST OF TABLES
Table 1: 
Schedule of Assessments and Study Activities ...................................... 14 
Table 2: 
Effect of XPO1 Inhibition on Oncogenic and Inflammatory Pathways . 34 
Table 3: 
Response by Doses per Cycle and Prior Therapy Status as of 01 Dec 
2016 ........................................................................................................ 37 
Table 4: 
Multiple Myeloma Disease-specific Assessments.................................. 50 
Table 5: 
Pre-specified Dose/Schedule Modifications for Adverse Events Related 
to Study Drug.......................................................................................... 59 
Table 6: 
Supportive Care and Dose Adjustment Guidelines ................................ 59 
Table 7: 
Classification of Adverse Events by Causality....................................... 70 
Table 8: 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Criteria.................................................................................................... 88 
Table 9: 
International Staging System for Multiple Myeloma ............................. 89 
Table 10: International Myeloma Working Group Response Criteria (Kumar 
2016)....................................................................................................... 90 
Table 11: Lens Opacities Classification System..................................................... 96 
Table 12: Glutathione (GSH)-, S-Adenosylmethionine (SAM)-, OR N-
Acetylcysteine (NAC)-Containing Products (Representative List)........ 97 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 25 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
5-HT3 
5-hydroxytryptamine 
ACS 
acute cerebellar syndrome 
AE 
adverse event 
ALT 
alanine transaminase (SGPT) 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ASCT 
autologous stem cell transplantation 
AST 
aspartate transaminase (SGOT) 
AUClast 
area under the curve, first-last measurement 
AUC(0-∞) 
area under the curve, time zero to last 
AV 
arterioventricular 
bid 
twice daily 
BMSC 
bone marrow stroma cells 
BP 
blood pressure 
BSA 
body surface area 
BSC 
best supportive care 
BUN 
blood urea nitrogen 
qC 
degrees Centigrade 
CBC 
complete blood count 
CBR 
clinical benefit rate 
CD 
cluster of differentiation 
anti-CD38 mAb 
monoclonal antibodies against CD38 antigen expressed by leukocytes  
CD-ROM 
compact disc, read-only-memory 
CFR 
Code of Federal Regulations 
CHF 
congestive heart failure 
CI 
confidence interval 
CLL 
chronic lymphocytic leukemia 
Cm 
centimeter 
Cmax 
maximum serum concentration 
CML 
chronic myeloid leukemia 
CNS 
central nervous system 
CR 
complete response 
CRA 
clinical research associate 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 26 
Abbreviation 
Definition 
CRF 
case report form 
CRM1 
chromosomal region maintenance protein 1 
CSF 
cerebrospinal fluid 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
cyclo 
cyclophosphamide 
DCR 
disease control rate  
Dex 
dexamethasone 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose limiting toxicity 
DM 
diabetes mellitus 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
Dox 
doxorubicin 
DSMC 
Data Safety Monitoring Committee 
DT 
dexamethasone + thalidomide 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eDC 
electronic data capture 
ECOG 
Eastern Cooperative Oncology Group 
EDTA 
ethylenediaminetetraacetic acid 
F% 
oral bioavailability 
qF 
degrees Fahrenheit 
FACT-G 
Functional Assessment of Cancer Therapy (general version) 
FACT-MM 
Functional Assessment of Cancer Therapy - Multiple Myeloma 
FDA 
Food and Drug Administration 
FFPE 
formalin fixed paraffin embedded 
FISH 
fluorescent in situ hybridization 
FLC 
free light chain (kappa/lamba ratio) 
FLT3 
fms-like tyrosine kinase 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte-colony stimulating factor 
GGT 
gamma-glutamyl transferase 
GI 
gastrointestinal 
GM-CSF 
granulocyte macrophage-colony stimulating factor 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 27 
Abbreviation 
Definition 
GRP 
growth regulatory protein 
GSH 
glutathione 
Hb 
hemoglobin 
HBsAg 
hepatitis B virus surface antigen 
HBV 
hepatitis B virus 
hCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HPLC/MS-MS 
high performance liquid chromatography/tandem mass spectrometry 
hr 
hour 
IC50 
inhibitory concentration, 50% (half maximal inhibitory concentration) 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IFNα 
interferon alpha 
IFNγ 
interferon gamma 
IgA 
immunoglobulin A 
IgVH 
immunoglobulin heavy chain variable region 
IL-1α 
interleukin 1 alpha 
IL-6 
interleukin 6 
IL-8 
interleukin 8 
IL-10 
interleukin 10 
IMiD 
immunomodulatory drug 
IMWG 
International Myeloma Working Group 
INR 
international normalization ratio 
IRC 
Independent Review Committee 
ISS 
International Staging System 
ITT 
intent-to-treat 
IV 
intravenous 
kg 
kilogram 
KM 
Kaplan-Meier 
LAFB 
left anterior fascicular block 
LDH 
lactate dehydrogenase 
LMW 
low molecular weight 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 28 
Abbreviation 
Definition 
LOCSIII 
Lens Opacities Classification System 
m2 
square meters 
MAb 
monoclonal antibody 
MCP1 
monocyte chemo-attractant protein-1 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MHRA 
Medicines and Healthcare Products Regulatory Agency 
MI 
myocardial infarction 
min 
minute 
miRNA 
microRNA 
mL 
milliliter 
mITT 
modified intent-to-treat 
MM 
multiple myeloma 
mmHg 
millimeters of mercury 
MTD 
maximum tolerated dose 
MR 
minimal response 
mRNA 
messenger ribonucleic acid 
MUGA 
multiple gated acquisition 
5'NT 
5'-nucleotidase 
NAC 
N-acetylcysteine 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NES 
nuclear export sequences 
NHL 
non-Hodgkin’s lymphoma 
NK1R 
neurokinin 1 receptor 
NPC 
nuclear pore complex 
NPM1 
nucleophosmin 
NYHA 
New York Heart Association 
OPG 
osteoprotegerin 
ORR 
overall response rate  
OS 
overall survival 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PDn 
pharmacodynamic 
PE 
physical examination 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 29 
Abbreviation 
Definition 
PFS 
progression free survival 
PI 
proteasome inhibitor (within drug treatment context) 
PI 
principal investigator (within clinical context) 
PK 
pharmacokinetic 
po 
by mouth 
PP 
per protocol 
PPI 
proton pump inhibitor 
PR 
partial response 
prn 
as needed 
PT 
prothrombin time 
qAM 
every morning 
qd 
once daily 
qhs 
at bedtime 
qid 
four times daily 
QoL 
quality of life 
qRT-PCR 
quantitative real time polymerase chain reaction 
RBBB 
right bundle branch block 
RBC 
red blood cell 
RNA 
ribonucleic acid 
RP2D 
recommended Phase 2 dose 
RPPA 
reverse phase protein array 
RR 
resistant/refractory 
RT 
Richter’s transformation 
SAE 
serious adverse event 
SAM 
S-adenosylmethionine 
sCR 
stringent complete response 
Sd 
selinexor 80 mg plus dexamethasone 20 mg (“low-dose” 
dexamethasone) 
SD  
stable disease 
SIADH 
Syndrome of Inappropriate Antidiuretic Hormone Secretion 
SINE 
selective inhibitor of nuclear export 
SOC  
standard of care (within treatment context) 
SOC  
system organ class (within adverse event context) 
SOP 
standard operating procedure 
SPEP 
serum protein electrophoresis 

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Abbreviation 
Definition 
TEAE 
treatment-emergent adverse event 
TRAE 
treatment-related adverse event 
tid 
three times daily 
TK 
toxicokinetic 
Tmax 
time to maximum serum concentration 
TNFα 
tumor necrosis factor alpha 
TOI 
trial outcomes index 
TSH 
thyroid stimulating hormone 
TSP 
tumor suppressor protein 
TTP 
time to progression 
TUNEL 
terminal deoxyribonucleotidyl transferase-dUTP nick end labeling 
ULN 
upper limit of normal 
UPEP 
urine protein electrophoresis 
VEGFα 
vascular endothelial growth factor alpha 
VGPR 
very good partial response 
WBC 
white blood cell 
XPO1 
exportin 1 

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1. 
OVERVIEW 
Multiple myeloma (MM) is the second most common hematological malignancy (after 
non-Hodgkin’s lymphoma), representing 1% of all cancers and 2% of all cancer deaths. 
Despite the increased effectiveness of first-line agents, the majority of patients will 
eventually relapse and become resistant to all classes of available anti-MM therapies. With 
over 30,000 new cases and approximately 12,600 deaths from MM anticipated in 2016 in the 
USA alone (ACS 2016), there remains a need for novel therapies for the treatment of 
refractory MM that can improve the overall survival rate.  
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and 
inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor 
proteins (TSPs). XPO1 protein levels are significantly elevated in MM, leading to the nuclear 
exclusion of TSPs, the glucocorticoid receptor (GR), and enhanced translation of certain 
oncogene mRNAs (Tai 2014). Transient retention of TSPs in the nucleus at high levels via 
XPO1 blockade activates their cell cycle checkpoint and genome surveying actions. This 
leads to the death of nearly all types of malignant cells, whereas normal cells undergo 
transient cell cycle arrest and recovery when the export block is released. XPO1 also exports 
the GR, leading to attenuation of its transcriptional activity. In the presence of 
glucocorticoids, XPO1 blockade leads to nuclear accumulation and activation of the GR. In 
addition, XPO1 inhibition leads to the nuclear entrapment of cap-binding protein 
(eIF4E)-dependent oncogene mRNAs, thus preventing their translation into proteins in the 
cytoplasm. In this way, SINEs lead to reduction in key oncoproteins such as c-Myc, Cyclin 
D, hDM2 and others. The reactivation of multiple TSP pathways as well as glucocorticoid 
signaling, along with reduced translation of key oncoproteins through inhibition of a non-
redundant, single protein, i.e., XPO1, represents a novel approach to the treatment of 
neoplastic diseases including those with multiple genomic alterations and resistance 
mechanisms. 
Single-agent Phase 1 studies with oral selinexor have been conducted in advanced 
hematological malignancies including MM, acute myeloid leukemia (AML), non-Hodgkin’s 
leukemia (NHL) and chronic lymphocytic leukemia (CLL) (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, DLBCL, Richter’s transformation, glioblastoma, gynecological malignancies, 
and dedifferentiated liposarcoma (DDLS). More than 2,000 patients with objectively 
progressing tumors at study entry have received selinexor as of 31 March 2017.  
The most frequently reported side effects of selinexor seen in clinical studies to date are 
anorexia, fatigue, nausea, vomiting, and thrombocytopenia. These adverse events (AEs) may 
be mitigated or eliminated with standard supportive care. In addition, their prevalence and 
intensity typically decline after 4-8 weeks of treatment. Selinexor treatment is not associated 
with significant major organ toxicity. Moreover, clinically-relevant cumulative toxicities 
have not been observed during long term treatment, with more than 28 patients receiving 
single-agent selinexor for over 1 year and 6 patients for over 2 years. Please see the current 
Selinexor Investigator’s Brochure (IB) for more information. 

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Selinexor has shown single-agent, durable, anti-cancer activity in patients with multiple RR 
hematologic and solid tumor malignancies, including MM, at doses of ≥6 mg/m2 body 
surface area (BSA) in initial Phase 1 dose-escalation studies. In addition, results from a small 
number of patients suggests that selinexor in combination with dexamethasone 20 mg has 
increased efficacy in RR MM patients relative to selinexor alone (Chen 2014, Data on file).
In the current study, patients will receive low-dose dexamethasone (20 mg) to both improve 
the tolerability of selinexor and provide additional efficacy benefit as selinexor has been 
shown to activate glucocorticoid signaling through its receptor. Dexamethasone has been 
shown in previous studies to be an effective prophylactic treatment for the common AEs of 
selinexor described above. While untreated MM is exquisitely sensitive to glucocorticoids, 
this benefit wanes over time with treatment, which usually includes glucocorticoids in 
combination therapy. Patients with MM which has relapsed after multiple treatments are
unlikely to respond to glucocorticoid treatment alone, but dexamethasone should provide 
symptomatic relief of selinexor-associated toxicity. In addition, dexamethasone may provide 
synergistic efficacy in combination with selinexor, which can reactivate glucocorticoid 
receptor (GCR) signaling. The current study will evaluate selinexor combined with 
dexamethasone for the treatment of MM in patients whose disease is refractory to previous 
treatment with a glucocorticoid, proteasome inhibitor (PI), an immunomodulatory agent 
(IMiD), and the anti-CD38 monoclonal antibody (anti-CD38 mAb) daratumumab.
2.
MULTIPLE MYELOMA 
Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation 
of monoclonal plasma cells in the bone marrow, the presence of monoclonal 
immunoglobulin, or M protein in the serum or urine, bone disease, kidney disease, and 
immunodeficiency. It is more common in elderly patients (median age at diagnosis is 
65-70 years; only 2% of patients are younger than 40 years) (Raab 2009).
MM is the second most common hematological malignancy (after non-Hodgkin’s 
lymphoma), representing 1% of all cancers and 2% of all cancer deaths. With current 
therapy, median survival is 5.2 years after diagnosis (Kumar 2014).
Although the cause of MM is unknown, a number of mutated genes have been found with 
significant frequency in patients with MM. These include mutations in NRAS, KRAS, TP53 
and BRAF, which are well known oncogenic drivers for other cancers (Lohr 2014) and 
mutations in many genes associated with NFκB activation (Keats 2007). Also, certain risk 
factors make patients more susceptible to the disease. MM is more common in individuals 
over the age of 65, in males, and in those with family members affected by MM. Fifty 
percent (50%) of patients with MM harbor mutations in the immunoglobulin heavy-chain 
locus on chromosome 14q32, partial or complete loss of chromosome 13, and partial loss of 
chromosome 17 (Raab 2009; Kyle 2004).
The diagnosis of MM is based on the key characteristics of the disease, occupation of the 
bone marrow cavity, the presence of space occupying bone lesions, and the production of 
paraprotein (Raab 2009; IMWG 2003). The staging of MM is based on β2-microglobulin 
level, which is directly correlated to renal function, tumor mass, and albumin level 
(Greipp 2005). The stages are summarized in Appendix 2.

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The treatment of MM has improved in the last 20 years due to the use of high-dose 
chemotherapy (i.e., alkylating agents) and autologous stem cell transplantation, the 
introduction of immunomodulatory agents, such as thalidomide, lenalidomide, and 
pomalidomide, and the proteasome inhibitors, bortezomib and carfilzomib. However, despite 
the increased effectiveness of these agents, most patients develop highly resistant MM and 
succumb to the disease. With over 12,500 deaths from MM expected in the USA in 2016 
(ACS 2016), there remains a high unmet medical need to develop anti-MM agents with novel 
mechanisms.  
3. 
NUCLEAR EXPORT 
3.1. 
Inhibition of XPO1 in Human Cancer 
Many important tumor suppressing proteins (TSPs) have been identified in cancer 
pathogenesis, including but not limited to TP53, FOXO3a, IκB, BRCA1, APC, PP2A, and 
Rb (Turner 2012; Senapedis 2014; Tan 2014; Yang 2014). TSPs mediate tumor suppression 
pathways via various functions including recognition of cellular damage, arrest of the cell 
cycle until repairs can be made, and induction of apoptosis in cells that are beyond repair 
(Brown 2011). Similarly, glucocorticoid binding to, and nuclear localization of, the GCR is 
required for its signaling.  
The tumor suppression and anti-cancer activity of these TSPs and the GCR requires their 
presence in the nucleus. Conversely, export to the cytoplasm by nuclear export shuttle 
protein XPO1 can inactivate their abilities to regulate cellular processes (Xu 2010) and 
cancer cells exploit these functions to successfully evade normal DNA-damage controls as 
well as anti-neoplastic therapy. XPO1 is the only known nuclear export protein for the vast 
majority of TSPs and the GCR. Of note, XPO1 has been identified as a selective survival 
gene in MM by unbiased high-throughput short interfering ribonucleic acid (siRNA) 
screening (Tiedemann 2012) and is commonly overexpressed in MM (Tai 2014).  
XPO1 blockade causes transient nuclear retention of TSPs, the GCR, and other growth 
modulators, re-establishing their tumor suppressing and growth regulating effects on cancer 
cells and potentially reversing mechanisms leading to chemotherapy resistance (which holds 
possible future implications for combination therapies) (Lain 1999).  
Certain growth-promoting (including oncogene) messenger RNAs (mRNAs) require 
specialized nuclear export via a “cap-binding complex” in order to exit the nucleus into the 
cytoplasm where they are translated into proteins (Culjkovic 2013; Koehler 2007). Several 
key MM genes including c-Myc, Cyclin D1, hDM2 and others utilize this complex via 
binding to the protein eIF4E in order to exit the nucleus and undergo efficient translation into 
protein. The cap-binding complex protein eIF4E is exported out of the nucleus into the 
cytoplasm exclusively by XPO1. As these proteins tend to have very short half-lives, 
constant translation is required to maintain their cellular levels. Inhibition of XPO1-mediated 
nuclear export leads to reduced translation of these growth-promoting proteins, and 
subsequently significant drops in their levels. 
In normal cells, XPO1 inhibition transiently arrests the cell cycle without cytotoxicity 
followed by recovery after the inhibitor is removed (Lain 1999; van der Watt 2009; Gray 

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2007). Several attempts to develop this class of anti-cancer drug have failed due to off-target 
effects of the drugs which led to significant weight loss, diarrhea, and marked fatigue and 
asthenia in the early clinical trials (Mutka 2009; Newlands 1996; Roberts 1986).
It is now well recognized that forced nuclear retention of TSPs can counteract a multitude of 
oncogenic, growth stimulatory (and inflammatory) pathways that perpetuate the neoplastic 
phenotype. Similarly, nuclear retention of the GR in the presence of glucocorticoids could 
restore its activity. Finally, inhibition of eIF4E/XPO1-mediated mRNA export of 
oncoproteins lead to reductions in their levels. Because restoration of TSP ± GR activity and 
reduction in oncogenic signals are relevant to essentially any cancer, XPO1 inhibition is 
expected to have activity against MM and many other malignancies (Table 2).
Table 2:
Effect of XPO1 Inhibition on Oncogenic and Inflammatory Pathways
Pathway Affected
Effect of XPO1 Inhibition
Reference
XPO1 overexpression
XPO1 reduction
Walker 2013
Glucocorticoid Receptor (GR) 
Inactivation (nuclear export)
Nuclear GR retention (in presence of 
glucocorticoids) and reactivation
Chen 2014
p53 mutation
p73 activation, p21 activation
Ranganathan 2012
hDM2 (MDM2) activation
Nuclear p53 retention and activation, hDM2 
protein reduction
Kojima 2013
c-Myc amplification
MYC protein reduction
Schmidt 2013
Cyclin D1 overexpression
Cyclin D1 reduction
Gao 2014
NPM1 mutation
Restoration of nuclear NPM1
Falini 2007
CEBPA down-regulation
Nuclear retention and activation
Ranganathan 2012
CDKN2A reduction
p53/p73 stabilization
Azmi 2013
Rb reduction
Rb hypophosphorylation, p14/p16 elevation
Fragomeni 2013
FLT3 activation
FLT3 reduction
Ranganathan 2012
c-KIT activation
c-KIT reduction
Ranganathan 2012
NF-NB activation
INB nuclear retention and activation
Lapalombella 2012
PIK3 or AKT activation
FOXO1, -3, -4 activation
Lapalombella 2012
Survivin – cytoplasmic
Survivin nuclear retention
Altura 2003
Bcr-Abl activation
PP2A activation
Walker 2013
4.
SELINEXOR (KPT-330)
4.1.
Introduction
Selinexor is an oral, first-in-class, slowly reversible, potent selective inhibitor of nuclear 
export (SINE) compound that specifically blocks exportin 1 (XPO1). XPO1 is responsible 
for the unidirectional export of ~220 different cargo proteins from the nucleus to the 
cytoplasm (Xu et al., 2010). The anti-neoplastic activity of SINE compounds is mediated 

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through at least three distinct pathways involving tumor suppressor proteins (TSPs), 
oncoproteins, and the glucocorticoid receptor. First, SINE compounds induce nuclear 
localization and functional activation of multiple TSPs, leading to rapid apoptosis of multiple 
myeloma (MM) (Tai et al., 2014) and other malignant cells. By forcing the nuclear 
localization and activation of TSPs, all cell types exposed to SINE compounds undergo G1 ± 
G2 cell cycle arrest, followed by a ‘genomic fidelity’ review. Cells with genomic damage (ie, 
malignant cells) are induced to undergo apoptosis both in vitro and in vivo. Normal cells, 
with an intact genome, remain in transient, reversible cell cycle arrest until the XPO1 block 
is relieved. A second anti-neoplastic effect of SINE compounds is mediated through the 
mRNA cap-binding protein eIF4E, which is also an XPO1 cargo. Amongst other functions, 
eIF4E is responsible for the efficient nuclear export and delivery of several growth-
promoting (oncoprotein) mRNAs to cytoplasmic ribosomal for translation. By forcing the 
nuclear retention of the eIF43 bound to XPO1, SINE compounds reduce the cytoplasmic 
ribosomal synthesis of oncoprotein mRNAs including c-Myc, hDM2, Cyclin D1 and Bcl-
XL. Finally, SINE compounds also lead to restoration of anti-myeloma glucocorticoid 
receptor (GR) signaling in the presence of glucocorticoids; selinexor and other SINE 
compounds do not appear to exacerbate the hyperglycemic effects of glucocorticoids.  Thus, 
by inhibiting the key nuclear/cytoplasmic control protein XPO1, SINE compounds exhibit 
broad and deep anti-cancer activities. 
4.2. 
Preclinical Data 
In this section, a brief summary of preclinical data is provided. Additional information is 
presented in the current Selinexor/KPT-330 Investigator’s Brochure. 
In vitro experiments with continuous (~72 hour) exposure to selinexor demonstrated potent 
pro-apoptotic activity across a broad panel of tumor-derived cell lines and patient samples in 
culture, including multidrug-resistant cancers. Moreover, selinexor demonstrated cytotoxicity 
in MM and CLL cells in the absence or presence of bone marrow stroma cells (BMSC).  
Pharmacokinetic (PK) studies were conducted in mice, rats and monkeys. Selinexor showed 
dose proportional exposure with no accumulation. Please see the current 
Selinexor/KPT-330 Investigator’s Brochure for more information. 
Several studies were conducted to evaluate the effect of SINE compounds on MM in vivo. In 
MM1.S xenograft tumors, treatment with the SINE compound KPT-276 showed a marked 
decreased in tumor volume (40%) whereas tumor volume increased by 36% with placebo 
(Schmidt 2013). KPT-276 was also active in the Vk*MYC mouse model of MM, which has a 
positive predictive value of 67% for the activity of single-agent compounds in clinical trials 
(Schmidt 2013; Chesi 2012).  
4.2.1. 
Selinexor plus Dexamethasone Combination Studies 
In vitro studies showed selinexor and dexamethasone in combination were found to have a 
synergistic effect on reducing MM1.S human MM cell viability relative to either drug alone 
(Chen 2014). Increased GR nuclear localization and concomitantly activated GCR-mediated 
transcription in the presence of glucocorticoids were at least partly responsible for the 
synergistic cytotoxicity of this combination. (Gao 2014). 

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Enhanced activity of the selinexor plus dexamethasone combination was also observed in 
two xenograft models of human MM. The addition of dexamethasone to selinexor enhanced 
activity (86%) relative to selinexor alone. 
In summary, the combination of selinexor and dexamethasone is synergistic in vitro and 
in vivo in MM cell cytotoxicity assays through increased nuclear localization of GCR and 
amplified GCR transcriptional activity. Taken together, these studies demonstrate that SINE 
compounds are active anti-MM compounds that cause decreased cell viability, increased 
apoptosis, and cell cycle arrest in vitro and potent inhibition of MM tumor growth in vivo,
and that the addition of dexamethasone can augment these effects.
4.3.
Clinical Experience
As part of a Phase 1 clinical study of selinexor in patients with advanced hematological 
malignancies (KCP-330-001), 68 patients with MM that was relapsed and/or refractory to all 
available classes of approved therapies and was progressing on study entry received selinexor 
on a twice-weekly dose schedule. Preliminary results, as of 13 December 2016, are 
summarized below.
4.3.1.
Preliminary Results for Patients with MM, Study KCP-330-001, as of 
13 December 2016
4.3.1.1.
Preliminary Efficacy Results for Patients with MM, Study KCP-330-001
Selinexor plus Dexamethasone 
As of 13 December 2016, the best responses among the 22 evaluable patients who received 
selinexor plus dexamethasone (Sd) were: 1 CR (5%), 5 PRs (23%), 3 MRs (14%), 8 SDs 
(36%), and 5 PDs (23%). The ORR was 27% and the CBR was 41%. Several patients 
remained on study for >9 months and one patient remained on study for >1 year.
Single-agent Selinexor 
Selinexor showed modest efficacy as a single-agent with 4% of patients achieving an 
objective response (≥PR in 2 of 46 patients) and 26% showing clinical benefit (≥MR in 12 
of 46 patients). Overall, these preliminary Phase 1 results suggest that selinexor ± 
dexamethasone has clear anti-MM activity in heavily pretreated patients. 
4.3.1.2.
Preliminary Safety Results for Patients with MM, Study KCP-330-001
Adverse events in patients receiving single-agent selinexor were generally low-grade, 
consistent with events observed in patients with other hematological malignancies and 
responsive to standard supportive care. Preliminary Results for Patients with MM, Study 
KCP-330-012, as of 01 December 2016
Preliminary efficacy and safety results from the first 79 patients were presented at the 2016 
American Society of Hematology annual meeting and are summarized below (Vogl et al., 
2016).

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4.3.1.3.
Preliminary Efficacy (Response) Results for Patients with MM, Study KCP-
330-012
Response rates in patients with MM previously treated with lenalidomide, pomalidomide, 
bortezomib, carfilzomib, and refractory to one proteasome inhibitor (PI), one 
immunomodulatory drug (Imid) and glucocorticoids (“quad” refractory) and in patients with
MM refractory to the “quad” agents as well as to an anti-CD38 Ab (“penta” refactory) were 
adjudicated by an Independent Review Committee (IRC) and are presented in Table 3. for 
the first portion of the study overall, for 8 vs. 6 doses per 28-day cycle and “penta” vs. 
“quad” MM (Vogl et al., 2016). One patient did not have measurable myeloma at baseline 
and is not included in the efficacy analyses. The ORR across all patients is 21% and the 
clinical benefit rate (CBR) is 33%. Similar ORR were seen in the patients with “penta” and 
“quad” MM, with higher CBR in patients who received 8 vs. 6 doses/cycle consistent with 
improved disease control with continuous dosing.  The additional 122 patients with “penta” 
MM to be added will receive 8 doses / cycle based on these analyses.
Table 3:
Response by Doses per Cycle and Prior Therapy Status as of 01 Dec 2016
Category
Na
ORR 
(%)
CBR 
(%)
VGPR 
(%)
PR   
(%)
MR 
(%)
SD   
(%)
PD  
(%)
NE (%)
Overall
78
16
(21%)
26
(33%)
4
(5%)
12
(15%)
10
(13%)
27
(35%)
9
(12%)
16
(21%)
8 doses/cycle
27
6
(22%)
11
(41%)
1
(4%)
5
(19%)
5
(19%)
6
(22%)
5  
(19%)
5
(19%)
6 doses/cycle
51
10
(20%)
15
(29%)
3
(6%)
7
(14%)
5
(10%)
21
(41%)
4
(8%)
11
(22%)
Pentab
30
6
(20%)
12
(40%)
2
(7%)
4
(13%)
6
(20%)
6
(20%)
5  
(17%)
7
(23%)
Quadc
48
10
(21%)
14
(29%)
2
(4%)
8
(17%)
4
(8%)
21
(44%)
4
(8%)
9
(19%)
CBR=Clinical Benefit Rate (sCR+PR+MR), MR=Minor Response, NE=Non-Evaluable, ORR=Overall 
Response Rate (sCR+PR), PD=Progressive Disease, PR=Partial Response, SD=Stable Disease, VGPR=Very 
Good Partial Response
a one patient not included, did not have measurable myeloma at baseline
b the majority of these patients (19 of 30) received 8 doses per cycle
c the majority of these patients (40 of 48) received 6 doses per cycle
4.3.1.4.
Preliminary Safety Results for Patients with MM, Study KCP-330-012
Common treatment-related adverse events (TRAEs) based on a preliminary analysis of safety 
and tolerability (N=92; safety data cut off 31 March 2017):
x
Hematological: thrombocytopenia (overall: 64%, Grades 3/4: 51%), neutropenia 
(overall: 26%, Grades≥ 3 19%), and anemia (overall: 39%, Grade 3/4: 22%). 
There was one case of febrile neutropenia (1%) and one case of clinically 
significant bleeding related to thrombocytopenia (1%). 

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x Non-hematological: nausea (overall: 68%, Grade 3: 8%), fatigue (overall: 64%, 
Grade 3: 14%) anorexia (overall: 51%, Grade 3: 2%), vomiting (overall 41%, 
Grade 3: 2%), hyponatremia (overall 33%, Grade 3: 18%), diarrhea (overall 40%, 
Grade 3: 4%), and weight loss (overall: 33%, Grade 3: 1%).  
These results are generally consistent with the overall TEAE results reported for all selinexor 
studies in patients with hematological malignancies (see the Selinexor/KPT-330 IB). 
4.3.1.5. 
Summary 
Based on the promising preliminary efficacy results described above and on the considered 
feedback from MM experts that the population of patients with penta-refractory MM 
represents a current and growing high unmet medical need where there are no approved 
agents and there is no established standard of care, Karyopharm is expanding the number of 
patients with penta-refractory  MM enrolled in this single-arm study to a total of 
~160 patients with penta-refractory MM to receive Sd twice weekly for every week of each 
four-week cycle (8 doses/cycle). 
4.4. 
Potential Risks 
Selinexor is currently in clinical development and has not been approved by the FDA for 
commercial use. Over 2,000 patients have received selinexor (as of 31 March 2017), however 
the entire safety profile is not known at this time. Measures will be taken to ensure the safety 
of the patients participating in this trial, including the use of stringent inclusion and exclusion 
criteria and close monitoring.  
If toxicities are encountered, adjustments will be made to the study treatment as detailed in 
the sections that follow. All AEs and serious adverse events (SAEs) will be recorded during 
the trial and for up to 30 days after the last dose of study treatment or until the initiation of 
another anti-cancer therapy, whichever occurs first. 
In ongoing clinical studies with selinexor, the most common AEs possibly related to 
selinexor are anorexia, fatigue, nausea, vomiting, diarrhea, and thrombocytopenia. Virtually 
all of these side effects can be managed effectively with dose modification and/or supportive 
care initiated prior to first dosing. Overall, the most frequently observed laboratory 
abnormalities include thrombocytopenia, hyponatremia, and a decrease in red blood cells. 
The majority of these have been mild to moderate. Please refer to the current 
Selinexor/KPT-330 Investigator’s Brochure for more information.  
Acute cerebellar syndrome (ACS) was reported at high doses in one adult (85 mg/m2) and 
two pediatric (70 mg/m2) patients in two phase 1 studies.  The maximum doses in adults 
(70 mg/m2) and children (55 mg/m2) have been established largely based on these events.  An 
adult patient, heavily pre-treated for recurrent pancreatic cancer, developed ACS following 
3 doses of selinexor at 85 mg/m2 twice weekly. The patient experienced abnormal speech, 
loss of coordination, and was unable to walk. Selinexor was discontinued and the patient’s 
symptoms resolved to near baseline by ~6 weeks.  A five-year old with refractory AML 
developed ACS following 4 doses of selinexor (70 mg/m2) followed by 5 days of fludarabine 
and cytarabine (without intrathrecal therapy). The patient was empirically treated with 
intravenous immunoglobulin for 5 days, improved significantly over the next 3 weeks, and 

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CCI

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 40
45 mg/m2 (~80 mg) plus dexamethasone 20 mg, both dosed twice weekly, experienced 
durable response without clinically relevant cumulative toxicities. (See Section 4.3.)
Patients in the present study will receive selinexor 80 mg (45 mg/m2 BSA) plus 
dexamethasone 20 mg, both dosed twice weekly, for each week of four-week cycles.
Dexamethasone 20 mg will be given with each dose of selinexor. For patients with partial 
intolerance to glucocorticoids (as determined by the Investigator) a minimum dose of 
dexamethasone 10 mg with each dose of selinexor is permitted. If any patient is not able to 
tolerate this dose, then a potential discontinuation or further decrease in dosage would be 
allowed after a discussion with the Medical Monitor on a case by case basis.
In select cases (e.g., for patients showing SD or PR and tolerating treatment particularly 
well), the selinexor dose may be increased by 20 mg to 100 mg, based on efficacy and safety 
considerations, after a minimum of two cycles of study therapy. However, in no case may the 
dose for any patient exceed 70 mg/m2. Prior to any potential dose increase, the BSA for the 
patient should be calculated. Patients with BSA < 1.4 m2 may not have their dose increased, 
as this would result in a dose > 70 mg/m2 selinexor.
6.
STUDY OBJECTIVES
6.1.
Primary Objectives
Evaluate the efficacy (overall response rate [ORR]) for treatment with selinexor 80 mg plus 
low-dose dexamethasone (20 mg) (Sd) twice weekly (four-week cycles) in patients with MM 
previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, and 
daratumumab; and refractory to prior treatment with glucocorticoids, an immunomodulatory 
agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb daratumumab (herein 
referred to as “penta-refractory” MM).
ORR will include patients who experience partial response (PR), very good partial response 
(VGPR), complete response (CR), or stringent complete response (sCR), based on 
International Myeloma Working Group (IMWG) response criteria (Kumar 2016) for patients 
with penta-refractory MM in Part 2 (expansion phase).
6.2.
Secondary Objectives
The following endpoints will be analyzed separately for (a) Part 1 patients with quad-
refractory MM, (b) Part 1 patients with penta-refractory MM, and (c) Part 2 (expansion) 
patients with penta-refractory MM. Additionally, analyses of safety and tolerability will be 
performed on the overall population of patients from Parts 1 and 2 who received at least one
dose of study treatment.
x
Duration of response (DOR = Duration from first observation of at least PR to 
time of disease progression, or death due to disease progression, whichever occurs 
first. DOR will be censored for death due to any causes other than disease 
progression)

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CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 42 
 Lytic lesions as assessed by skeletal survey (or similar bone imaging) 
7. 
STUDY DESIGN 
7.1. 
Overview 
This is a Phase 2b, single-arm, open-label, multicenter study of Sd (selinexor 80 mg plus 
dexamethasone 20 mg), both dosed twice weekly, four weeks of each four-week cycle, in 
patients with MM previously treated with lenalidomide, pomalidomide, bortezomib, 
carfilzomib, and daratumumab, and refractory to prior treatment with glucocorticoids, an 
immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the anti-CD38 mAb 
daratumumab. (Note: Refractory is defined as ≤ 25% response to therapy, progression during 
the previously described therapies, or progression within 60 days after completion of 
therapy.) 
This study consists of two parts and will enroll approximately 210 patients overall. Part 1 
(protocol V1.0-3.0) enrolled patients with both quad-refractory MM and penta-refractory 
MM. Part 2 (protocol V≥4.0) will enroll patients with penta-refractory MM only, but 
continue all patients enrolled in Part 1.  
The population for the primary efficacy analysis will contain only patients with penta-
refractory MM enrolled in Part 2. Efficacy results for patients with quad-refractory MM and 
patients with penta-refractory MM enrolled in Part 1 will be analyzed separately. Safety 
analyses will be performed on the overall population of patients who received any amount of 
study treatment, presented overall and by study part, and separately for Part 1 penta-
refractory MM patients and quad-refractory MM patients. 
Patients will receive selinexor 80 mg (45 mg/m2 BSA) plus dexamethasone 20 mg (Sd), both 
dosed twice weekly, for each week of four-week cycles. Patients will receive treatment until 
PD, death, toxicity that cannot be managed by standard care, or withdrawal, whichever 
occurs first.  
Patients will also receive best supportive care to mitigate selinexor side effects, including 
blood product transfusions, antimicrobials, and (as appropriate) growth factors including 
granulocyte colony-stimulating factors for neutropenia, erythropoietins for anemia, and/or 
platelet-stimulating factors for thrombocytopenia. 
In select cases (e.g., for patients showing SD or PR and tolerating treatment particularly 
well), the selinexor dose may be increased by 20 mg after consultation with the Medical 
Monitor. The dose level for an individual patient may be escalated based on efficacy 
considerations only after a minimum of 2 cycles of study therapy. However, in no case may 
the dose for any patient exceed 70 mg/m2. Prior to any potential dose increase, the body 
surface area (BSA) for the patient will be calculated and an individual patient’s dose may not 
be increased if it would result in a dose > 70 mg/m2. 
In Part 2, MM-specific assessments (i.e., SPEP, UPEP, serum/urine immunofixation, 
quantitative Ig levels, serum FLC, and bone marrow aspirate) must be confirmed by a central 
laboratory to confirm CR or sCR, and select VGPR, per IMWG. Additional information is 
provided in the Study Manual. 

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 43
The Investigator may remove a patient from study treatment using criteria described in
Section 10.2. Patients may decide to discontinue study treatment for any reason. Patients who 
elect to discontinue study treatment should be encouraged to continue in the study so that 
follow-up information on disease progression, other antineoplastic therapy, symptoms and 
survival status may be obtained. However, patients may elect to withdraw consent and 
decline further participation in the trial at any time.
The Investigator must determine the primary reason for a patient’s discontinuation of study 
treatment and record this information on the electronic case report form (eCRF). Patients 
who are prematurely withdrawn from study treatment are not eligible to re-initiate study 
treatment on this protocol at a later date.
7.2.
Data Safety Monitoring Board
An independent Data Safety Monitoring Board (DSMB) will review the safety of study 
treatment and any SAEs that occur during the study. Details on how the DSMB will review 
safety and response data are provided in the DSMB Charter.
The DSMB will be comprised of a minimum of two oncologists (at least one of whom 
specializes in hematologic oncology) and a statistician. Following their initial meeting, 
DSMB meetings will occur on a periodic basis in accordance with their charter. 
7.3.
Independent Review Committee
An Independent Review Committee (IRC), will review disease assessment data to 
independently assess disease response. The IRC will review data that will be used for the 
analysis of the primary endpoint. The IRC’s assessments of disease response and time to 
progression (TTP) 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 disease assessments) will be described in the 
IRC Charter.
7.4.
Stopping Rules
The entire study or treatment of individual patients may be stopped under defined 
circumstances as outlined in Section 10.
7.5.
Study Endpoints
Study objectives and endpoints are provided in Section 6.
7.6.
Blinding and Randomization
Not applicable; this is an open-label, single-arm, multicenter study. 
7.7.
End of Study
The End of Study (EoS) will occur when all patients have completed the one-year Follow-up
Period (i.e., when the last patient has expired, been followed for 12 months after last dose of 
study drug, been lost to follow-up, or has withdrawn consent, whichever occurs first).

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 44
8.
SELECTION OF PATIENTS
8.1.
Number of Patients
Approximately 210 patients will be enrolled overall, including ~160 patients with 
penta-refractory MM (Part 1 [~30] and Part 2 [~130]) and ~50 patients with quad-refractory
MM (Part 1 only). See Section 7.1.
8.2.
Recruitment
This study will be conducted at multiple sites in the United States and Europe.
8.3.
Documentation Requirements 
For enrollment consideration, patients may be eligible if they have documented evidence of
previous treatment for MM that substantiates disease status as follows:
x
Refractory to a glucocorticoid
x
Refractory to lenalidomide and/or pomalidomide (only 1 required) and evidence 
of prior treatment* with both lenalidomide and pomalidomide
x
Refractory to bortezomib and/or carfilzomib (only 1 required) and evidence of 
prior treatment* with both bortezomib and carfilzomib
x
Refractory to daratumumab
* Prior treatment is defined as either refractory, treatment with ≥ 2 cycles, or documented 
severe intolerance.
Documented evidence will include at least one of the following:
1. Medical records that support start and stop dates (month/year) of prior treatment (both 
dose and schedule), best response on prior treatment and, if applicable, date of 
progression (including both dose and schedule at the time of progression).
2. Myeloma marker values (SPEP, UPEP, Immunoglobulin, FLC) at the time of prior 
treatment start, stop and time of progression (accompanied by #1).
3. Formal, signed physician letter by Investigator (on hospital/clinic letterhead), to be 
included in the patient’s medical and research record, indicating start/stop dates of 
prior treatment (both dose and schedule), best response on treatment and, if
applicable, date of progression (including both dose and schedule at the time of 
progression).
4. Formal, signed physician letter from referring physician (on hospital/clinic 
letterhead), to be included in the patient’s medical and research record, that includes 
prior treatment history indicating start/stop dates of prior treatment (both dose and 
schedule), best response on prior treatment and, if applicable, date of progression 
(including both dose and schedule at the time of progression).

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 45 
8.4. 
Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible to enroll in this study: 
1. Written informed consent in accordance with federal, local, and institutional 
guidelines. 
2. Age ≥ 18 years at the time of signing informed consent. 
3. Measurable MM based on IMWG guidelines as defined by at least one of the 
following: 
a. Serum M-protein ≥ 0.5 g/dL by serum electrophoresis (SPEP) or, for IgA 
myeloma, by quantitative IgA 
b. Urinary M-protein excretion ≥ 200 mg/24 hours  
c. FLC ≥ 100 mg/L, provided that the FLC ratio is abnormal.  
d. If serum protein electrophoresis is felt to be unreliable for routine M-protein 
measurement, then quantitative Ig levels by nephelometry is acceptable. 
4. Patients must have previously received ≥ 3 anti-MM regimens including: an 
alkylating agent, lenalidomide, pomalidomide, bortezomib, carfilzomib, 
daratumumab, and a glucocorticoid. There is no upper limit on the number of prior 
therapies provided that all other inclusion/exclusion criteria are met. 
5. MM refractory to previous treatment with one or more glucocorticoids, parenteral PI 
(i.e., bortezomib and/or carfilzomib), IMiD (i.e., lenalidomide and/or pomalidomide), 
and daratumumab. Refractory is defined as ≤ 25% response to therapy, or progression 
during therapy or progression within 60 days after completion of therapy. 
6. Multiple myeloma that is refractory to the patient’s most recent anti-MM regimen. 
(Documented severe intolerance to the patient’s last therapy is allowed upon approval 
by the Medical Monitor.) 
7. Any clinically significant non-hematological toxicities (except for peripheral 
neuropathy as described in exclusion criterion #17) that patients experienced from 
treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 
Day 1. 
8. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x 
upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have 
a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.  
9. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine 
clearance of ≥ 20 mL/min, calculated using the formula of Cockroft and Gault.  
10. 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. Male patients must use an 
effective barrier method of contraception if sexually active with a female of 
child-bearing potential.  For both male and female patients, effective methods of 
contraception must be used throughout the study and for three months following the 
last dose of study treatment. 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 46 
11. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2. 
12. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See 
Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):  
a. Total WBC count > 1,000/mm3 
b. ANC ≥ 1000/mm3 
c. Platelet count ≥ 75,000/mm3 (patients in whom <50% of bone marrow nucleated 
cells are plasma cells) or ≥ 50,000/mm3 (patients in whom ≥ 50% of bone marrow 
nucleated cells are plasma cells. (Platelet transfusions < 1 week prior to Cycle 1 
Day 1 are prohibited [see below].)  
13. Hemoglobin level ≥ 8.5 g/dL. In certain cases, patients with stable baseline 
hemoglobin level > 8.0 may be included following approval by the Medical Monitor. 
(Red blood cell transfusions < 2 weeks prior to Cycle 1 Day 1 are prohibited [see 
below].) 
14. Confirmation of patient eligibility for specific key criteria for study participation with 
the Medical Monitor. 
8.5. 
Exclusion Criteria 
1. Active smoldering MM. 
2. Active plasma cell leukemia. 
3. Documented systemic amyloid light chain amyloidosis. 
4. Active central nervous system (CNS) MM. 
5. Pregnancy or breastfeeding. 
6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 
weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 
Day 1. 
7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 
Day 1  
8. Life expectancy of < 4 months. 
9. Major surgery within four weeks prior to Cycle 1 Day 1. 
10. Active, unstable cardiovascular function: 
a. Symptomatic ischemia, or  
b. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with 
ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree 
atrioventricular (AV) block or asymptomatic left anterior fascicular block/right 
bundle branch block (LAFB/RBBB) will not be excluded), or 
c. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 
3, or 
d. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1. 
11. Active, uncontrolled hypertension. 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 47 
12. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or 
antifungals within one week prior to first dose. 
13. Known HIV seropositive. 
14. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA 
or HBsAg (HBV surface antigen). 
15. 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 enrollment. Cancer treated with curative intent > 5 
years previously and without evidence of recurrence will be allowed. 
16. Active GI dysfunction interfering with the ability to swallow tablets, or any GI 
dysfunction that could interfere with absorption of study treatment. 
17. Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 21 days 
prior to Cycle 1 Day 1. 
18. Serious, active psychiatric or medical conditions which, in the opinion of the 
Investigator, could interfere with treatment. 
19. Participation in an investigational anti-cancer study within 21 days prior to Cycle 1 
Day 1. 
20. Receipt of transfusions as follows: 
a. Platelet infusion within 1 week prior to Cycle 1 Day 1. 
b. RBC transfusion within 2 weeks prior to Cycle 1 Day 1. 
21. Receipt of the following blood growth factors within 2 weeks prior to Cycle 1 Day 1: 
Granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony 
stimulating factor (GM-CSF), erythropoietin (EPO), or megakaryocyte growth factor. 
22. Known intolerance to or contraindications for glucocorticoid therapy at Cycle 1 Day 
1. 
23. Prior exposure to a SINE compound, including selinexor. 
24. Unable or unwilling to comply with protocol requirements, including providing a 24-
hour urine samples at the required study time points. 
8.6. 
Screen Failures 
Patients who sign an informed consent form and do not receive study treatment for any 
reason are defined as screen failures. For all screen failures, the Investigator will enter the 
screening number, patient initials; and reason(s) for screen failure onto electronic case report 
forms (eCRFs). Screen failures will be replaced. Screen failures may be re-screened. 
8.7. 
Study Patient Numbers 
Each patient will be assigned a unique study number and will keep this number for the 
duration of the study. Patient numbers will not be reassigned or reused for any reason. 

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 48
Patients will be identified to the Sponsor only by their assigned number, initials, date of birth, 
and sex. The Investigator must maintain a patient identification master log.
8.8.
Study Patient Number
Each patient will be assigned a unique study 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 Karyopharm only by their assigned number, initials, year of
birth (as allowed by national and local regulatory authorities), and sex. The Investigator must 
maintain a patient identification master log.
9.
METHODS OF ASSESSMENT AND ENDPOINTS
9.1.
Standard Study Assessments
All assessments should be performed as outlined in Table 1.
9.1.1.
Demographic Data
During Screening, patient demographic data will be collected. These data include year of
birth, age, gender, race, and ethnicity.
9.1.2.
Medical History
A complete medical history will be obtained from each patient. Medical history includes 
historic MM assessment values (Day -30 and Day -60), baseline symptoms as well as a 
detailed history of prior procedures for MM and other prior cancer therapies (i.e., transplant, 
chemotherapy, hormonal therapy, immunotherapy, biotherapy, radiotherapy, and surgery)
including start and stop dates, best response, disease progression dates (during or after 
therapy), as well as discontinuations due to intolerability or toxicity. Smoking history will be 
recorded. Data should be reviewed by the Investigator prior to dosing on Cycle 1 Day 1.
9.1.3.
Concomitant Medications
Concomitant medications will be documented for each patient at each scheduled visit. A 
detailed history of medications will be documented in the eCRF. Subsequently, at each study 
visit, patients will be asked whether they have taken any medication other than the study 
medication (from Screening through the end of the study). All concomitant medications 
including dietary supplements, over-the-counter medications, and oral herbal preparations, as 
well as changes in medication, will be recorded on the eCRFs. 
Supportive care (such as appetite stimulants, anti-emetics, and anti-diarrheals, etc.) is 
encouraged (see Section 11.4.2).
9.1.4.
Physical Examination 
Full physical examinations (PE) during Screening and the EoT Visit will be performed. All 
other PEs during the study should be symptom-directed PEs. Significant findings that were 
present prior to the signing of informed consent must be included on the medical history page 
on the patient’s CRF. Significant new findings, including the presence of plasmacytomas, 

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 49
that begin or worsen after informed consent must be recorded on the Adverse Event or 
Plasmacytoma page of the patient’s CRF.
PEs, unless otherwise noted, will include the following:
x
Height (without shoes) in centimeters (cm) measured during Screening only 
x
Body weight (indoor clothing without shoes) in kilograms (kg) 
x
Body temperature 
x
Systolic and diastolic BP and pulse rate measured at each visit after the patient 
has been in a supine or sitting position for 5 minutes. BP should be assessed on 
the same arm at each visit.
Information about the PE must be present in the source documentation at the study site. 
Clinically relevant findings made after the start of selinexor plus dexamethasone dosing, 
which meet the definition of an AE, must be recorded on the AE eCRF.
9.1.5.
ECOG Score
An ECOG Score Assessment (see Appendix 1) will be performed during Screening, Day 1 of 
each cycle, and the EoT visit.
9.2.
Multiple Myeloma Disease Specific Assessments
Patient response will be assessed by the procedures summarized in Table 4 and graded 
according to the IMWG response criteria summarized in Table 10 (Appendix 3). Per IMWG, 
quantitative Ig levels by nephelometry may be used in place of SPEP for routine M-protein 
measurements 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. All MM assessments outlined in this protocol are required to be performed at 
each study visit, prior to dosing. If MM assessments are collected at unscheduled times, those 
results must be documented in the eCRF as unscheduled visits. This includes SPEP, UPEP, 
serum FLC, β2 microglobulin, quantitative Ig, and serum/urine protein immunofixation. 
Results of pre-screening MM assessments at Day -30 (window: Screening – 2 weeks) and 
Day -60 (±15 days) will also be provided.
SPEP with serum protein immunofixation, quantitative Ig, serum FLC, and 24-hour UPEP, 
with immunofixation, must be collected at each required time point. An aliquot of the blood 
and urine samples should be retained.  If the local laboratory results indicate a CR or sCR, 
sequential MM disease assessment samples, per IMWG, will be collected. The sequential 
samples will be split – one aliquot of each sample will be sent to the local lab while the other 
aliquots, along with the initial assessment aliquots, will be sent to the central laboratory to 
confirm CR or sCR. If the results do not indicate CR or sCR, then the aliquots may be 
destroyed. Refer to the Study Manual for details.
All disease assessments (SPEP, UPEP, FLC, quantitative Ig, and serum/urine protein 
immunofixation) should be performed regardless of the diagnosis that is being followed (e.g., 
24 hour UPEP collection must be collected at each time point outlined in the protocol even if 
the patient is being followed by SPEP, Ig or FLC). 

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Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 52
9.4.
Safety Assessments
Safety evaluations will be conducted at each visit and will include the procedures 
summarized below. 
9.4.1.
12-Lead ECG
A standard 12-lead ECG will be performed as indicated in Table 1. Patients must rest for at 
least 5 minutes prior to the ECG recording. The Investigator will interpret the ECG using one 
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 (QTc) using Bazett’s formula or calculated by the Fridericia correction 
formula (Bazett 1920, Fridericia 1920). If Bazett correction is entered by the site, the 
Fridericia corrected QTc interval (QTcF) will be derived using the formula: QT/(RR^[1/3]), 
where RR = 60/heart rate.
9.4.2.
Ophthalmic Exam
A full ophthalmic examination will be performed prior to the patient's first dose of selinexor. 
Prior to dilation, best corrected visual acuity (Snellen’s Equivalent based on either Snellen 
chart or ETDRS chart), slit lamp examination including tonometry, following dilation, and 
fundoscopy. If a cataract is seen during the examination, the cataract will be graded as 
follows:
x
Lens Opacities Classification System III (LOCS III) – Patients who enrolled in 
this study under the original Protocol or Protocol Amendments 1 or 2 and had 
detectable cataracts graded according to the LOCS III will continue to have their 
cataracts graded according to LOCS III and will not switch to the new AOA 
Grade 1-4 cataract scale.   For new patients or patients in whom no cataracts have 
been detected to date, if cataracts are detected, they will be graded according to 
the Grade 1-4 scale.
x
American Optometric Association (AOA) Cataract Grading System – Starting 
with Protocol Amendment 3, new patients will be evaluated using the AOA 
grading system until they complete the study. This system is modified from the 
Optometric Clinical Practice Guideline: Care of the Adult Patient with Cataract, 
which is available on the AOA website (www.aoa.org)(See Appendix 5.)
9.4.3.
Clinical Laboratory Assessments
The following clinical laboratory tests should be performed as indicated in Table 1.
x
Hematology (blood sample: ethylenediaminetetraacetic acid [EDTA]) tests 
including hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular 
hemoglobin, mean corpuscular hemoglobin concentration, white blood cell 
(WBC) count, WBC differential, red blood cell count, lymphocytes, monocytes, 
neutrophils, eosinophils, basophils, and platelets. WBC differential may be 
automated or manual as per institutional standards.

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CCI

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 56
10.
DISCONTINUATION CRITERIA
10.1.
Early Discontinuation 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. 
The DSMB will inform the sponsor if a safety signal is detected (see Section 7.2). The 
sponsor, in conjunction with appropriate regulatory authorities, would then decide if the trial 
should be modified or terminated. If this occurs, the sponsor will notify IRB/REB/ECs and 
investigators.
10.2.
Early Discontinuation of Individual Patients
The Investigator may remove a patient from study treatment at his/her discretion for any of 
the following reasons:
x
Disease progression defined according to IMWG for progression of MM, 
including confirmatory analysis to document progression. Disease progression 
must be confirmed by the IRC prior to discontinuation of the study treatment
x
Unacceptable AE(s) or failure to tolerate the study treatment
x
Patient decides to discontinue study therapy
x
Any medically appropriate reason or significant protocol violation, in the opinion 
of the Investigator
Reasons for discontinuation must be clearly documented in the source and in the study CRFs, 
including reasons for patient withdrawal and Investigator decision to discontinue the patient.
Patients may discontinue study treatment for any reason. Patients who elect to discontinue 
study treatment should be encouraged to continue in the study so that follow-up information 
on disease progression and survival status may be obtained. However, patients may elect to 
withdraw consent and decline further participation in the trial.
11.
TREATMENT
Selinexor study medication will be in the form of a coated, immediate-release tablet for oral 
administration. Selinexor tablets will be supplied as single-strength (20 mg) tablets in wallet-
size blister packs. Dexamethasone 20 mg will be given with each dose of selinexor. 
Additional information is provided in Section 11.1.3.
11.1.
Dosing and Administration
11.1.1.
Dose Modifications
All dosing modifications should be discussed with the study Medical Monitor prior to 
implementing the dosing change.

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Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 58
11.1.4.
Dose Modifications for Patients with VGPR
In an effort to improve long-term disease control and tolerability, this protocol allows for 
dose reductions in patients with very good anti-tumor activity of selinexor. Thus, for patients 
who achieve ≥ VGPR for ≥ 6 months and who, in the opinion of the Investigator may benefit 
from dose reduction(s), the following modifications may be considered: (a) The dose of 
dexamethasone may be reduced by 40% or (b) the dose of selinexor may be reduced by 
20 mg or (c) the frequency of selinexor may be reduced to once weekly, after consultation 
with the Medical Monitor. In general, dexamethasone should always be given on the day(s) 
of selinexor dosing. Patients whose doses are reduced under this schema should have 
appropriate MM markers monitored at least every two weeks (e.g., with FLC) so that dose 
may be re-escalated to their initial dose if evidence of progression occurs. These monitoring 
studies may be done at local laboratories. 
11.1.5.
Dose Reduction Guidelines for Toxicity
Toxicity will be graded according to CTCAE v.4.03 criteria; the therapy modifications 
described below are applied according to this severity grading.
If more than one type of toxicity occurs concurrently, the most severe grade will determine 
the modification.
Re-escalation of the study drug is allowed as outlined in the sections that apply for the 
specific toxicity. If drug-related toxicity requires a treatment delay of more than 28 days, the 
patient is taken off protocol treatment.
Each dose modification or treatment delay must be documented in the eCRF, including the 
respective reason.
Based on observations from the ongoing Phase 1 studies in patients with advanced 
hematological and solid tumors, selinexor shows a reasonably wide therapeutic range, with 
activities from ~6 mg/m2 to ≥60 mg/m2. Therefore, in order to optimize specific anti-tumor 
activity and the patient’s tolerability, dose reductions and/or schedule modifications will be 
allowed as described in Table 5 and Table 6. Patients should also be treated aggressively with 
supportive care to reduce toxicities.
For all Grade ≥3 hematological or non-hematological AEs that are NOT selinexor related, 
after consultation with the Medical Monitor and at the discretion of the Investigator, 
selinexor dosing may be maintained, provided that the patient can continue to take the agent 
by mouth. 

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 59
Table 5:
Pre-specified Dose/Schedule Modifications for Adverse Events Related to 
Study Drug 
Dose 
Level
Selinexor Dosing
1
100 mg BIW (total dose of 200 mg per week) 
Starting 
Dose
0
80 mg BIW (total of 160 mg per week)
Dose 
Reductions
-1
60 mg BIW (120 mg total per week)
-2
100 mg total per week: 100 mg one day OR divided as 60 mg and 40 mg on separate 
days
-3
80 mg total per week: 80 mg one day OR divided as 40 mg per day on 2 days
-4
60 mg total per week: 60 mg one day OR divided as 40 mg one day and 20 mg on 
another day 
-5
40 mg total per week: 40 mg one day OR divided as 20 mg per day on separate days
Abbreviation: BIW = twice weekly
Table 6:
Supportive Care and Dose Adjustment Guidelines 
Please note the following recommendations:
x
After consultation with the Medical Monitor and at the discretion of the 
Investigator, selinexor dosing may be maintained for all hematological or non-
hematological AEs that are NOT related to selinexor.
x
For all selinexor-related AEs, if the prescribed dose reductions/interruptions in
Table 8 result in a stabilization of ≥ 4 weeks, a re-escalation may be considered 
after approval from the Medical Monitor.
Toxicity and Intensity
Selinexor Dose Modification
Fatigue (common)
Grade 1 or
Grade 2 lasting ≤ 7 days
Maintain dose. Rule out other causes of fatigue, particularly dehydration and 
anemia.  If found to be anemic, consider transfusing for hemoglobin < 8 g/dL. 
Institute supportive care medications per institutional guidelines and NCCN 
CPGO.
Patients with significant fatigue after several doses of selinexor may have an 
ongoing anti-tumor response.  If fatigue is significant, consider assessment of 
tumor response as part of the patient’s evaluation.
Grade 2 lasting > 7 days or
Grade 3
Rule out other causes of fatigue, particularly dehydration and anemia.  If found 
to be anemic, consider transfusing for hemoglobin < 8 g/dL. Institute 
supportive care medications per institutional guidelines and NCCN CPGO.
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 when resuming 
selinexor. (Table 5). 
Patients with significant fatigue after several doses of selinexor may have an 
ongoing anti-tumor response.  If fatigue is significant, consider assessment of 
tumor response as part of the patient’s evaluation.

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 60
Toxicity and Intensity
Selinexor Dose Modification
Anorexia or Weight Loss
Grade 1 anorexia 
Grade 1 weight loss
Grade 2 anorexia
Maintain dose. Rule out other causes and consider a repeat nutritional 
consultation and nutritional supplements (e.g., Ensure ®, Boost®, etc.).
Institute supportive care medications per institutional guidelines and NCCN 
CPGO.
Grade 2 weight loss
Grade ≥ 3 anorexia or 
weight loss
Rule out other causes and consider a repeat nutritional consultation and 
nutritional supplements (e.g., Ensure ®, Boost®, etc.). Institute supportive 
care medications per institutional guidelines and NCCN CPGO.
Interrupt dosing with selinexor until improves to Grade 1 or baseline and 
weight stabilizes, then reduce selinexor by 1 dose level when resuming 
selinexor (Table 5). 
Consult Medical Monitor to discuss persistent or ≥second occurrence of 
weight loss after stabilization.
Nausea, Acute (common)
Grade 1 or 2
(If intolerable or persistent 
Grade 2 not responsive to 
supportive care, follow 
guidelines for Grade 3 
below)
Maintain dose. Rule out other causes of nausea. Implement additional 
anti-nausea medications to supplement the protocol-required 5-HT3 
antagonists using institutional guidelines and NCCN CPGO.  
Grade 3
Rule out other causes of nausea. Implement additional anti-nausea medications 
to supplement the protocol-required 5-HT3 antagonists using institutional 
guidelines and NCCN CPGO.  
Interrupt selinexor dosing until resolved to Grade ≤ 2 or baseline and restart 
selinexor at 1 dose level lower (Table 5).
Hyponatremia (common)
Grade 1 (sodium levels 
< Normal to 130 mmol/L)
Maintain dose. Rule out other causes including drug (e.g., 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. 
Consider addition of salt tablets to patient’s diet.
Grade 3 with sodium 
levels 120 to <130 mmol/L 
without symptoms 
Correct for hyperglycemia as outlined under Grade 1. Treat hyponatremia per 
institutional guidelines. If (corrected) sodium is Grade ≤ 3 and continues to be 
asymptomatic, then patient may continue current dosing provided that 
intravenous saline and/or salt tablets (1-3 times daily) are provided.
If Grade 3 is persistent or worsens or does not respond to treatment, hold 
selinexor until resolved to Grade 1 or baseline and reduce selinexor by 1 dose 
level.
Grade 3 with sodium 
levels 120 to <130 mmol/L 
with symptoms or Grade 4 
(<120 mmol/L)
Correct for hyperglycemia as outlined under Grade 1. Treat hyponatremia per 
institutional guidelines. Delay/hold selinexor until resolved to Grade 1 or 
baseline then reduce selinexor dose by 1 level (Table 5).

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CCI

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 66
11.4.2.
Supportive Care
Supportive measures for optimal medical care should be provided during participation in this 
clinical trial. Based on clinical observations for 2103 adult patients evaluable for safety as of 
the 31 March 2017 safety data cutoff point, the main side effects associated with selinexor 
are primarily related to anorexia with poor caloric and fluid intake, fatigue, and nausea. 
Thrombocytopenia also occurs, although it is rarely associated with bleeding. In addition to 
dexamethasone included in the standard treatment plan, and required 5-HT3 prophylaxis 
(Section 11.4.1), supportive care including anti-nausea/anti-emetic therapy, acid suppression 
(proton pump inhibitors [PPI] and/or H2-blockers) and other treatments may be administered 
as described below:
x
Appetite stimulants: megesterol acetate at a dose of 80-400 mg daily. 
x
Centrally acting agents: per National Comprehensive Cancer Network® [NCCN] 
Clinical Practice Guidelines® for antiemesis and anorexia/cachexia [palliative 
care])
x
Neurokinin 1 receptor antagonist (NK1R antagonist): aprepitant or equivalent 
should be considered and will be covered for selected patients who have severe 
nausea and vomiting.
11.4.3.
lnfection
Appropriate broad-spectrum intravenous antibiotics and antifungal agents should be started 
immediately in patients who develop fever or other signs of systemic infection. Selinexor 
should be suspended in any patient with Grade 4 infection or clinical sepsis (in the absence of 
documented infection) until the condition is stabilized. Selinexor can then be re-started at the 
same dose.
11.4.3.1.
Other Glucocorticoid Side Effects
The management of common glucocorticoid side effects is well documented. Aggressive use 
of proton-pump inhibitors (PPIs), anti-hypertensives 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.
11.4.4.
Concomitant Medication and Treatment
Concomitant medication is defined as any prescription or over-the-counter preparation, 
including vitamins, dietary supplements, over-the-counter medications, and oral herbal 
preparations. 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. 

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 67
11.4.4.1.
Permitted Concomitant Medication 
Patients will receive concomitant medications to treat symptoms, AEs, and intercurrent 
illnesses that are medically necessary as standard care. Medications to treat concomitant 
diseases like diabetes, hypertension, etc., are allowed.
11.4.5.
Restricted Medications 
Medications:
Although acetaminophen (paracetamol) use in combination with selinexor 
was restricted in previous selinexor studies based on theoretical interactions 
with glutathione (GSH), ongoing clinical safety evaluations on the use of 
these drugs together have not shown any significant clinical or laboratory 
abnormalities with doses of acetaminophen up to 1 gram and selinexor up to 
55 mg/m2 (approximately 80-100 mg). Therefore, there are no longer any 
restrictions on the use of acetaminophen or acetaminophen-containing 
products in combination with selinexor, EXCEPT on days of selinexor 
dosing, when acetaminophen must not exceed a total daily dose of 1 gram.
Diet:
There are no dietary restrictions on this study. Patients should maintain 
adequate caloric and fluid intake.
11.4.6.
Prohibited Medications
Concurrent 
therapies: 
Concurrent therapy with any non-study anticancer therapeutic is not 
allowed. Other investigational agents should not be used during the study. 
Use of any immunosuppressive agents during the study must be confirmed 
by the Medical Monitor. 
.
Medications: 
Patients should not take glutathione (GSH)-, S-adenosylmethionine (SAM)-,
or N-acetylcysteine (NAC)-containing products during this study as these 
products may enhance the metabolism of selinexor. Please see Appendix 6
for a list of representative products. Patients must report all prescription and 
non-prescription medicines to their physicians during this study.
11.4.7.
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 must agree to use 2 methods of 
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. 
Highly effective methods include: 
1. Hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, 
injectables, and implants) 
2. Intrauterine device or intrauterine system

Selinexor (KPT-330)
Karyopharm Therapeutics Inc.
Clinical Study Protocol: KCP-330-012
13 December 2017, Version 6.0
Confidential
Page 68
3. Vasectomy or tubal ligation
Effective methods include: 
1. Barrier methods of contraception (e.g., male condom, female condom, cervical cap, 
diaphragm, and contraceptive sponge)
Of particular note,
x
No barrier method by itself achieves a highly effective standard of contraception
x
The proper use of diaphragm or cervical cap includes use of spermicide and is 
considered 1 barrier method.
x
The cervical cap and contraceptive sponge are less effective in parous women.
x
The use of spermicide alone is not considered a suitable barrier method for 
contraception.
x
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.
x
Male and female condoms should not be used together as they can tear or become 
damaged.
Alternatively, the following fulfill the contraception requirements:
1. A sexual partner who is permanently surgically sterilized or post-menopausal.
2. 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 4.4.1 for additional safety information related to pregnancy.
11.4.8.
Radiation Treatment
If clinically indicated, palliative radiation therapy to non-target lesions is permitted but study 
drug should be held for ≥ 1 day before the start of palliative radiation therapy and ≥ 1 day 
following each dose of palliative radiation therapy. Treatment with selinexor shall not be 
discontinued solely due to palliative radiation. 
11.5.
Treatment Compliance
The Investigator or other study staff will supervise study drug treatment given in the clinic
and instruct the patient on study medication self-administration.

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Patients will be asked to bring their study medication container with them at each visit and 
compliance with protocol-defined study drug intake will be checked by pill count.  
Compliance to study medication will be recorded by study personnel after discussion with 
the patient and drug accountability. Compliance to study medication will be assessed by the 
Investigator or delegate and recorded in source documents. The date will be recorded as per 
study drug schedule. The Investigator or the designee will account for the number of tablets 
dispensed against those returned by the patient. Any deviations and missed doses will be 
recorded in the eCRF and drug accountability logs for verification with the reasons.  
The Investigator or designee will try to ensure complete compliance with the dosing schedule 
by providing timely instructions to the patients. In case of non-compliance, the patients will 
be instructed again. 
12. 
ADVERSE EVENTS 
An AE is defined as any undesired medical occurrence in a patient or clinical investigation 
patient receiving a pharmaceutical product regardless of a causal relationship with this 
treatment. An AE can therefore be any unfavorable sign and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporarily associated with the use of a 
study drug, whether or not related to the study drug. 
Any treatment-emergent abnormal laboratory result or test result (e.g., PE, ECG, Echo, 
vitals, etc.), which is clinically significant, (i.e., meets one or more of the conditions listed 
below), should be recorded as a single diagnosis on the AE page in the eCRF:  
1. Accompanied by clinical symptoms  
2. Leading to a change in study medication (e.g., dose modification, interruption or 
permanent discontinuation)  
3. Requiring a change in concomitant therapy (e.g., addition of, interruption of, 
discontinuation of, or any other change in a concomitant medication, therapy or 
treatment) 
It is the responsibility of the Investigator to document all AEs that occur during the study. 
AE information will be elicited by asking the patient a non-leading question, for example, 
“Have you experienced any new or changed symptoms since we last asked/since your last 
visit?” AEs should be reported on the appropriate page of the eCRF. 
AEs should be reported for their actual grade and duration. 
The term “severe” is used to describe the intensity of an AE; the event itself could be of 
relatively minor clinical significance (e.g., ‘severe’ headache). This is not the same as 
“serious.”  Seriousness of AEs is based on the outcome of an AE and usually associated with 
events that pose a threat to a patient’s life or functioning. 
The severity of the AE will be graded according to the CTCAE Grading Scale (see the 
CTCAE web page at http://ctep.cancer.gov for details). For AEs not covered by CTCAE, the 
severity will be characterized as “mild,” “moderate,” or “severe” according to the following 
definitions: 

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x
Mild events are usually transient and do not interfere with the patient’s daily 
activities.
x
Moderate events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities.
x
Severe events interrupt the patient’s usual daily activities.
The Investigator will make a judgment regarding the AE’s relationship to study drug, as
outlined below in Table 7.
Table 7:
Classification of Adverse Events by Causality
Not related
The lack of a temporal relationship of the event to study treatment makes a 
causal relationship not reasonably possible, or by any other drugs, 
therapeutic interventions or underlying conditions that provide a sufficient 
explanation.
Related
The temporal relationship of the event to study treatment makes 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.
12.1.
Serious Adverse Events
A serious adverse event (SAE) is any untoward medical occurrence that occurs at any dose 
(including after the ICF is signed and prior to dosing) that:
x
Results in death
x
Is life-threatening (patient is at immediate risk of death from the event as it 
occurred)
x
Requires in-patient hospitalization (formal admission to a hospital for medical 
reasons) or prolongation of existing hospitalization
x
Results in persistent or significant disability/incapacity
x
Results in a congenital anomaly/birth defect
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 may jeopardize the patient and may require medical or surgical intervention 
to prevent one 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.
Hospitalizations for elective surgery or other medical procedures that are not related to a 
treatment-emergent AE are not considered SAEs.

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Progression of the malignancy (including fatal outcomes) should not be reported as an SAE 
during the study or within the safety reporting period (see below). Sudden and unexplained 
death should be reported as an SAE.
12.1.1.
AE and SAE Follow-up
All AEs occurring during the study are to be followed up in accordance with good medical 
practice until they are resolved, stabilized or judged no longer clinically significant or, if a 
chronic condition, until fully characterized. Any AEs that are considered drug-related must 
be followed until resolution or until stabilization. 
12.1.2.
Post-Study Adverse Events and Serious Adverse Events
All unresolved AEs should be followed by the Investigator until the events are resolved, the 
patient is lost to follow-up, or the AE is otherwise explained. At the last scheduled visit, the 
Investigator should instruct each patient to report any subsequent event(s) that the patient, or 
the patient’s personal physician, believes might reasonably be related to participation in this 
study.
Prior to the conclusion of the study at the site, the Investigator should notify the Karyopharm 
Pharmacovigilance Department (see Section 12.1.3.1) of any death or AE occurring at any 
time after a patient has discontinued or terminated study participation that may reasonably be 
related to this study. 
After study conclusion, the Investigator should notify Karyopharm Therapeutics Inc., or its 
designee, of any death or AE he or she is aware of occurring at any time after a patient has 
discontinued or terminated study participation that may reasonably be related to this study. 
Karyopharm Therapeutics Inc. should also be notified if the Investigator should become 
aware of the development of cancer or of a congenital anomaly in a subsequently conceived 
offspring of a patient that has participated in this study.
12.1.3.
Serious Adverse Event Reporting
12.1.3.1.
Reporting Requirements
ALL SAEs occurring in any patient, must be reported to the Karyopharm Pharmacovigilance 
Department within 24 hours of first knowledge of the event by the principal investigator or 
assigned site personnel. The following information will be requested from the investigational 
site:
x
Protocol number
x
Site and/or investigator number
x
Patient number
x
Demographic data
x
Brief description of the event
x
Onset date and time
x
Resolution date and time, if the event resolved

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Clinical Study Protocol: KCP-330-012
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x
Current status, if event not yet resolved
x
Any concomitant treatment and medication
x
Investigator’s assessment of the SAE’s relationship to investigational product 
x
Outcome of the event, if available
This information will be captured in the SAE report form and/or the study specific safety 
database and will be forwarded to:
x
Pharmacovigilance Department
x
Karyopharm Therapeutics Inc.
x
Email: pharmacovigilance@karyopharm.com
x
North American sites, Fax to US:+1-617-334-7617
European sites, Fax to Germany: +49-89-9218-5650
Suspected unexpected serious adverse reactions 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.
All investigators participating in ongoing clinical studies with the study medication will 
receive copies of these reports for prompt submission to their Institutional Review Board 
(IRB) or Ethics committee (EC), as applicable. Reporting of SAEs by the Investigator to the 
IRB or EC will be done in accordance with the standard operating procedures and policies of 
the IRB/EC. Adequate documentation must be maintained showing that the IRB/EC was 
properly notified.
In addition, Karyopharm Therapeutics Inc. will communicate all cases of cerebellar toxicities 
of Grade 3 or higher to the regulatory authority, IRBs and investigators, in the format of an 
expedited Safety Report within 7 days of awareness of the event.
12.2.
Overdose
An overdose is defined as a deliberate or accidental administration of study medication to a 
study patient at a dose above that which is assigned to that individual patient according to the 
study protocol. In the event of drug overdose, the Investigator and Karyopharm Medical 
Monitor should be notified immediately and the patient observed closely for AEs. The patient 
should be treated symptomatically as appropriate, and the incident of overdose and related 
AEs and/or treatment documented in the patient's medical record. In addition to documenting 
the overdose in the patient's records, the overdose must be reported to Karyopharm 
Pharmacovigilance on an SAE report form.  Any AE or SAE observed as a consequence of 
the overdose will be handled as described in Section 12.2, as appropriate.
As selinexor is metabolized by GSH conjugation, it is conceivable that hepatic GSH 
depletion can occur in case of overdose. Therefore, in patients who develop liver function 
test abnormalities, supportive measures such as SAM 400 mg orally 1-4 times a day, or other 
drugs that can replace GSH, should be considered.

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Medication errors, and uses of the study medication outside what is foreseen in the protocol, 
including misuse and abuse of the product must also be reported to Karyopharm 
Pharmacovigilance on an SAE report form. 
12.3. 
Pregnancies 
Pregnancy per se is not considered an AE unless there is cause to believe that the 
investigational drug may have interfered with the effectiveness of a contraceptive 
medication. 
Each pregnancy in a patient or partner of a patient on selinexor must be reported to the 
Sponsor within 24 hours of learning of its occurrence. The pregnancy should be followed up 
to determine outcome, including spontaneous or voluntary termination, details of the birth, 
and the presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications. Follow-up and documentation must occur even if the patient 
withdraws from the study or the study is completed. 
The avoidance of fathering a child is recommended for 3 months following the 
discontinuation of selinexor therapy. No information is currently available regarding the 
effects of selinexor on fertility, gestation or subsequent child development. 
Any pregnancy within 3 months post-study should be reported to the study investigator and 
the sponsor’s designee. 
13. 
STATISTICAL METHODS 
13.1. 
General Considerations 
13.1.1. 
Statistical and Analytical Plans 
This is a Phase 2b, single-arm, open-label, multicenter study of selinexor 80 mg with 
dexamethasone 20 mg (Sd), both given orally twice weekly for each week of four-week 
cycles, to patients with MM previously treated with lenalidomide, pomalidomide, 
bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with 
glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and the 
anti-CD38 mAb daratumumab.  
This study consists of two parts and will enroll approximately 210 patients overall. Part 1 
(protocol V1-3) enrolled patients with both penta-refractory MM and quad-refractory MM. 
Part 2 (protocol V≥4.0) will enroll patients with penta-refractory MM only, but continue all 
patients enrolled in Part 1.    
The population for the primary efficacy analysis will contain only patients with penta-
refractory MM enrolled in Part 2. Efficacy results for patients with quad-refractory MM and 
patients with penta-refractory MM enrolled in Part 1 will be analyzed separately. Safety 
analyses will be performed on the overall population of patients who received any amount of 
study treatment, presented overall and by study part, and separately for Part 1 penta-
refractory MM patients and quad-refractory MM patients. 

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13.2.1.4. Sub-group Efficacy Analyses 
The subgroup comparisons of interest will be evaluated per the Statistical Analysis Plan 
(SAP) (version 1.0). 
13.3. 
Data Analysis and Presentation 
Summary tabulations will be presented separately for each study part and by penta-refractory 
MM patients and quad-refractory MM patients in Part 1 for disposition as noted above, and 
for demographic, baseline, efficacy and safety data as noted in the following sections. All 
data collected on the eCRF will be provided in by-patient data listings. 
13.3.1. 
Demographic Characteristics 
Demographic characteristics will be summarized for the mITT, PP, and Safety populations 
and will include gender, race, ethnicity (Hispanic origin), and age at time of consent. For 
gender, race, and Hispanic origin, the summary statistics will be the number and percentage 
of patients within each category. The categories for race will be those recorded in the 
database. For age at time of consent, the mean, median, minimum, maximum, and standard 
deviation will be provided for each group and the total sample. 
13.3.2. 
Baseline Characteristics and Medical History 
Baseline characteristics include: performance status, duration from initial diagnosis, response 
to previous therapy, types of prior therapy, and height/weight. Baseline data will be tabulated 
using summary statistics for the mITT, PP, and Safety populations; no formal hypothesis 
testing will be performed. 
Medical history and physical examination results at baseline will be tabulated for the same 
analysis populations. 
13.3.3. 
Primary Endpoint 
The primary statistical analysis of efficacy will be performed on ORR (achievement of PR, 
VGPR, CR or sCR) for the mITT population. For the primary analysis of superiority to the 
minimal threshold ORR, analysis will be performed using a two-sided 95% confidence 
interval, calculated for the rate of ORR, and statistical significance will be declared if the 
lower bound of this interval is greater than 10%. 
13.3.4. 
Secondary Endpoints 
The following secondary efficacy endpoints will be analyzed separately for mITT and PP 
populations.  
x Duration of response (DOR = Duration from first observation of at least PR to 
time of disease progression [PD] or death due to disease progression, whichever 
occurs first. DOR will be censored for death due to any causes other than disease 
progression. 
x Clinical Benefit Rate (CBR = sCR + CR + VGPR + PR + minimal response 
[MR]), and duration of clinical benefit (Duration from first observation of at least 

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Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
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MR to time of disease progression or death due to disease progression, whichever 
occurs first. Duration of clinical benefit will be censored for death due to any 
causes other than disease progression) 
x Disease Control Rate (DCR = CBR + stable disease [SD; for a minimum of 12 
weeks])  
x Progression Free Survival (PFS = Duration from start of study treatment to PD or 
death [regardless of cause], whichever comes first)  
x Time to Progression (TTP = Duration from start of study treatment to time of 
disease progression) obtained with selinexor plus dexamethasone vs. TTP on most 
recent prior therapy 
x Time to Next Treatment (TTNT = Duration from start of study treatment to start 
of next anti-MM treatment or death due to disease progression, whichever occurs 
first)  
x Overall Survival (OS = Duration from start of study treatment to death)  
x Quality of Life (QoL) using the Functional Assessment of Cancer Therapy - 
Multiple Myeloma (FACT-MM) 
Time-to-event endpoints (including duration of response, PFS, TTP, and OS) will be 
assessed using Kaplan-Meier (KM) methods, including an estimate of the median, as well as 
the 25th and 75th percentiles, along with two-sided 95% CIs. Duration of CBR will be 
regarded as descriptive adjuncts to the analyses of response rates. Clinical benefit (CBR) and 
disease control (DCR) rates will be statistically evaluated using two-sided 95% confidence 
intervals. 
QoL will be assessed using the Functional Assessment of Cancer Therapy-Multiple Myeloma 
(FACT-MM). This instrument combines the General version of the FACT (FACT-G) with a 
MM-specific subscale (14 items). The subscales for the FACT-G are Physical Well-Being (7 
items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional 
Well-Being (7 items). The trial outcomes index (TOI; total of 41 items) will be the primary 
measurement of interest, comprised of the Physical and Functional subscales plus the MM-
specific subscale. Each item is rated on a 5-point Likert scale, ranging from 0 (“Not at all”) 
to 4 (“Very much”), therefore the TOI has a score ranging from 0 to 120. The QoL 
assessment will be performed at Baseline (prior to first dose of study treatment), Day 1 of 
each cycle on or after the second, and at the Final visit. The QoL analysis will be based on 
changes in the total TOI score from Baseline using paired T-tests. A secondary analysis of 
QoL will be performed in a similar manner using the total of all subscales. All 5 individual 
subscale total scores will be summarized over time using descriptive statistics. 
Additionally, the following analyses of safety and tolerability secondary endpoints will be 
performed on the overall population of patients who received any amount of study treatment, 
presented overall and by study part. 
x Safety and tolerability using National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE), v 4.03. 
x Describe the PK properties of selinexor in this patient population (Part 1 only). 

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Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 79 
Analyses of AEs will be performed for those events that are considered treatment-emergent, 
where treatment-emergent is defined as any AE with onset, or worsening of a pre-existing 
condition, on or after the first dose of study treatment through 30 days following the last dose 
of study treatment, or any event considered drug-related by the Investigator through the end 
of the study. AEs with partial dates will be assessed using the available date information to 
determine if treatment-emergent; AEs with completely missing dates will be assumed to be 
treatment-emergent. No formal hypothesis-testing of AE incidence rates will be performed. 
AEs will be summarized by patient incidence rates, therefore, in any tabulation, a patient 
contributes only once to the count for a given AE (preferred term). The number and 
percentage of patients with any treatment-emergent adverse events (TEAE) will be 
summarized for each treatment group, classified by SOC and preferred term. The number and 
percentage of patients with TEAEs assessed by the Investigator as at least possibly related to 
treatment will also be tabulated. The number and percentage of patients with any Grade ≥ 3 
TEAE will be tabulated in the same manner.  
The Investigator will judge the causal relationship between the occurrence of an AE and the 
study drug as not related, unlikely related, possibly related, or related. In the event a patient 
repeatedly experiences 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.  
All reported SAEs will be tabulated. 
All AEs (treatment-emergent and post-treatment) will be listed in by-patient data listings, 
classified by treatment, patient and day on study. In addition, separate by-patient listings will 
be provided for the following: deaths; SAEs; and AEs leading to withdrawal. 
13.3.7.2. Laboratory Data 
Clinical laboratory values will be expressed using conventional units International System of 
Units (SI) units. The actual value and change from baseline (Day 1, prior to the first 
administration of study drug) to each on-study evaluation will be summarized for each 
clinical laboratory parameter, including hematology, clinical chemistry, coagulation and 
urinalysis. In the event of repeat values, the last non-missing value per study day/time 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 lab measures will be determined using CTCAE v.4.03 criteria (e.g., 
those measures that have a corresponding CTCAE grade classification). Labs with CTCAE 
Grades ≥ 3 will be presented in a data listing. Shift tables that present changes from Baseline 
to worst on-study and Baseline to last on-study values relative to CTCAE classification 
ranges will be produced. 
13.3.7.3. Vital Signs, Physical Examinations, and ECOG Performance Status 
The actual value and change from baseline (Day 1) to each on-study evaluation will be 
summarized for vital signs.  Shift tables that present changes from baseline to worst on-study 
and last on-study ECOG performance status values will be produced.  By-patient listings of 
all vital sign measurements and ECOG performance status scores will be presented in data 
listings. 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 80 
Physical examination results at Screening, and physical examination results changes during 
the study, will be summarized. All physical examination findings will be presented in by-
patient data listings. 
13.3.7.4. Electrocardiogram Results 
Electrocardiogram results will be summarized descriptively, including heart rate and PR, 
QRS, QT, and QTc intervals (calculated by the Fridericia correction formula) intervals. If 
Bazett correction is entered by the site, the Fridericia corrected QTc interval (QTcF) will be 
derived using the formula: QT/(RR^[1/3]), where RR = 60/heart rate. Actual values and 
changes from baseline will be reported for each study visit. 
Electrocardiogram data for each patient will be provided in a data listing. 
13.3.7.5. Ophthalmic Examinations 
Ophthalmic examination findings will be summarized descriptively by visit. All ophthalmic 
examination findings will be presented in the data listings. 
13.3.7.6. Concomitant Medications 
The use of concomitant medications will be included in by-patient data listings. 
13.3.8. 
Procedures for Handling Missing Data 
The procedures for handling missing data will be performed per the SAP (version 1.0). 
13.4. 
Changes in the Conduct of the Study or Planned Analysis 
All deviations from the original statistical analysis plan will be documented and provided in 
the final clinical study report.  
14. 
REGULATORY, ETHICAL AND LEGAL OBLIGATIONS  
14.1. 
Regulatory and Ethical Compliance  
This clinical study was designed, and shall be implemented and reported in accordance with, 
the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (including European Directive 2001/20/EC and US Code of Federal Regulations 
Title 21), Division 5 of the Health Canada Food and Drug Regulations - Drugs For Clinical 
Trials Involving Human Subjects, and with the ethical principles laid down in the Declaration 
of Helsinki. 
14.2. 
Institutional Review Boards/Ethics Committees 
The protocol and the proposed informed consent form (ICF) must be reviewed and approved 
by a properly constituted Institutional Review Board/Independent Ethics 
Committee/Research Ethics Board (IRB/IEC/REB) before study start. 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 these documents and all of the instructions and 

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CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 82 
14.7. 
Patient Confidentiality and Disclosure 
The Investigator must ensure anonymity of the patients; patients must not be identified by 
names in any documents submitted to Karyopharm or their designees. Signed informed 
consent forms and patient enrollment log must be kept strictly confidential to enable patient 
identification at the site. 
14.8. 
Collection, Auditing Study Documentation, and Data Storage 
14.8.1. 
Study Documentation, Record Keeping and Retention of Documents 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional 
requirements for the protection of confidentiality of patients. Each site will permit authorized 
representatives of the sponsor and regulatory agencies to examine (and when required by 
applicable law, to copy) clinical records for the purposes of quality assurance reviews, audits 
and evaluation of the study safety and progress. 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. 
Examples of these original documents and data records include, but are not limited to, 
hospital records, clinical and office charts, laboratory notes, memoranda, evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies 
or transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, and subject files and records 
kept at the pharmacy, at the laboratories, and medico-technical departments involved in the 
clinical trial. 
Data collection is the responsibility of the clinical trial 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 should ensure the accuracy, completeness, and timeliness of the data 
reported in the eCRFs and all other required reports. Data reported on the eCRFs, which are 
derived from source documents, should be consistent with the source documents or the 
discrepancies should be explained. All data requested on the eCRF must be recorded. Any 
missing data must be explained. For electronic CRFs an audit trail will be maintained by the 
system.  
The Investigator/institution should maintain the trial documents as specified in Essential 
Documents for the Conduct of a Clinical Trial (ICH 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. 
Essential documents (written and electronic) should be retained for a period of not less than 
fifteen (15) years from the completion of the Clinical Trial unless 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. 

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CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 84 
15. 
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multiple myeloma. Leukemia 2006;20(9):1467-73. 
12. Falini B, Nicoletti I, Martelli MF, Mecucci C. Acute myeloid leukemia carrying 
cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features. 
Blood. 2007;1;109(3):874-85. 
13. Fragomeni RAS, Chung HW, Landesman Y, et al. CRM1 and BRAF inhibition synergize 
and induce tumor regression in BRAF-mutant melanoma. Mol Cancer Ther. 
2013;12(7):1171-9. 
14. Fridericia L. Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei 
Herzkranken. [The duration of systole in the electrocardiogram of normal subjects and of 
patients with heart disease.]. Acta Medica Scandinavica. 1920;53:469-86. 

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15. Gao J, Azmi AS, Aboukameel A, Kauffman M, Shacham S, Abou-Samra AB, 
Mohammad RM. Nuclear retention of Fbw7 by specific inhibitors of nuclear export leads 
to Notch1 degradation in pancreatic cancer. Oncotarget. 2014 15;5(11):3444-54.  
16. Gray LJ, Bjelogrlic P, Appleyard VC, et al. Selective induction of apoptosis by 
leptomycin B in keratinocytes expressing HPV oncogenes. Int J Cancer. 
2007:120(11):2317-2324. 
17. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple 
myeloma. J Clin Oncol. 2005;23:3412-3420. 
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gammopathies, multiple myeloma and related disorders: a report of the International 
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NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007 Aug;12(2):131-44. 
20. Koehler A, Hurt E. Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Cell 
Biol. 2007;8:761-73. 
21. Kojima K, Kornblau SM, Ruvolo V, et al. Prognostic impact and targeting of CRM1 in 
acute myeloid leukemia. Blood. 2013;121(20):4166–4174.  
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23. Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group 
consensus criteria for response and minimal residual disease assessment in multiple 
myeloma. Lancet Oncol. 2016;17:e328-46. 
24. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860-1873. 
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32. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in 
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49. Turner JG, Dawson J, Emmons MF, Cubitt CL, Kauffman M, Shacham S, Hazlehurst 
LA, Sullivan DM. CRM1 Inhibition Sensitizes Drug Resistant Human Myeloma Cells to 
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inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias. Blood. 
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Phosphorylated MAPK and Apoptosis in Human Melanoma Cells. PLoS One. 2014 Jul 
24;9(7):e102983. 

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APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP 
(ECOG) PERFORMANCE STATUS CRITERIA 
Table 8: 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Criteria 
Source: Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-655) 
 
 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity. Fully active, able to carry on all pre-disease performance without 
restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory 
and able to carry out work of a light or sedentary nature (e.g., light housework, office 
work). 
2 
In bed < 50% of the time. Ambulatory and capable of all self-care, but unable to carry 
out any work activities. Up and about more than 50% of waking hours. 
3 
In bed > 50% of the time. Capable of only limited self-care, confined to bed or chair 
more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined 
to bed or chair. 
5 
Dead. 

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APPENDIX 2. INTERNATIONAL STAGING SYSTEM FOR 
MULTIPLE MYELOMA 
Table 9: 
International Staging System for Multiple Myeloma 
 Source: Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420 
 
 
Stage 
Characteristics 
Stage I 
β2-microglobulin <3.5 mg/L, albumin ≥3.5 g/dL 
Stage II 
β2-microglobulin <3.5 mg/L and albumin <3.5 g/dL, or β2-
microglobulin 3.5-5.5 mg/L irrespective of the serum albumin 
Stage III 
β2-microglobulin ≥5.5 mg/L 

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APPENDIX 3. INTERNATIONAL MYELOMA WORKING GROUP 
RESPONSE CRITERIA, MYELOMA 
Table 10: 
International Myeloma Working Group Response Criteria (Kumar 2016) 
Standard IMWG Response Criteria1,2,3 
Response Subcategory 
Response Criteria 
Complete response (CR) 
Negative immunofixation of serum and urine, disappearance of any 
soft tissue plasmacytomas (SPDs), and < 5% plasma cells in bone 
marrow aspirates 
Stringent complete response 
(sCR)  
CR as defined above plus normal FLC ratio4 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 
cells5 
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 
M-protein 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.  
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.6  
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.6 
Stable disease (SD) 
Not recommended for use as an indicator of response; stability of 
disease is best described by providing the TTP estimates. Not meeting 
criteria for CR, VGPR, PR, MR, or PD. 
Progressive disease (PD)7,8 
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; 

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Standard IMWG Response Criteria1,2,3 
Response Subcategory 
Response Criteria 
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 SPD6 of 
> 1 lesion, or ≥ 50% increase in the longest diameter of a previous 
lesion > 1 cm in short axis; 
≥ 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 
TTP 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 SPD6 of the measurable 
lesion; 
Hypercalcaemia (> 11 mg/dL); 
Decrease in haemoglobin 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 
disease-free survival) 
Any 1 or more of the following criteria: 
Reappearance of serum or urine M-protein immunofixation or 
electrophoresis; 
Development of ≥ 5% plasma cells in the bone marrow; 
Appearance of any other sign of progression (i.e,. new 
plasmacytoma, lytic bone lesion, or hypercalcaemia see above) 

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Standard IMWG Response Criteria1,2,3 
Response Subcategory 
Response Criteria 
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 cell 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; 
Appearance of any other sign of progression (i.e., 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; TTP = time to progression; VGPR = 
very good partial response. 
Source: Kumar, 2016 
 
1 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 (e.g., 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. 
2 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; 
Kumar, 2016). 
3 Derived from international uniform response criteria for MM (Durie 2011). MR definition and clarifications 
derived from Rajkumar (Rajkumar 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. 
4 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). 
5 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. 

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6 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. 
7 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. 
8 In the case where a value is felt to be a spurious result per Investigator discretion (e.g., a possible laboratory 
error), that value will not be considered when determining the lowest value.  
 
Questions regarding interpretation of these criteria may be addressed by consulting the, “Practical 
considerations for application of IMWG consensus criteria,” section of the guidelines (page e340, Kumar 2016). 

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APPENDIX 4. SELINEXOR FORMULATION AND 
ADMINISTRATION 
Description of Selinexor (KPT-330) 
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor specifically 
blocks nuclear export by binding to the nuclear export protein XPO1. 
The chemical name is: (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-
(pyrazin-2-yl)acrylohydrazide 
The molecular formula is: C17H11F6N7O.  
The molecular weight is: 443.31 
Form 
Selinexor will be supplied and administered as 20 mg, coated, immediate-release tablets.  
Storage and Stability 
Selinexor tablets (20 mg) will be supplied in plastic film blisters with an aluminum foil 
lidding packaged in a secondary paper wallet with childproofing. Selinexor should be stored 
in a locked and secured area with access restricted to the site staff pharmacist or designee(s), 
with temperature at or below 30˚C (86˚F). Room temperature storage is recommended, 
refrigerated is suitable. Tablets should not be stored frozen. 
Selinexor tablets are currently in on-going stability studies. The expiry will be based on 
concurrent stability studies and extended during the course of the study as further stability 
data becomes available. 
Handling 
Qualified personnel, familiar with procedures that minimize undue exposure to themselves 
and the environment, should undertake the preparation, handling, and safe disposal of the 
chemotherapeutic agent in a self-contained and protective environment. 
Availability 
Selinexor is an investigational agent and will be supplied free-of-charge from Karyopharm 
Therapeutics Inc. 
Preparation 
No special preparation required. 
NOTE: Tablets of selinexor should not be crushed because of increased risk of dermatologic 
toxicity if powder comes in contact with skin. 
Administration 
Selinexor will be provided as tablets for oral administration. Selinexor is to be taken within 
30 minutes of solid food consumption together with at least 120 mL (4 ounces) of fluids 
(water, milk, etc.). 
Patients in the present study will receive selinexor 80 mg (45 mg/m2 BSA) plus 
dexamethasone (20 mg), both twice weekly, during Weeks 1-4 of each four-week cycle. 

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Accountability 
The Investigator, or a responsible party designated by the Investigator, must maintain a 
careful record of the inventory and disposition of the agent (investigational or free of charge) 
using the NCI Drug Accountability Record or another comparable drug accountability form. 
(see the Cancer Therapy Evaluation Program [CTEP] website at 
http://ctep.cancer.gov/protocolDevelopment for the “Policy and Guidelines for Accountability 
and Storage of Investigational Agents” or to obtain a copy of the drug accountability form). 
Destruction and Return 
At the end of the study, unused supplies of selinexor should be destroyed according to 
institutional policies. Destruction will be documented in the Drug Accountability Record 
Form. 

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APPENDIX 5. LENS OPACITIES CLASSIFICATION SYSTEM 
For patients enrolled under protocol version 3.0, if a cataract is seen during the slit lamp 
examination to document lens clarity, the cataract will be graded according to the grading 
system shown below. 
Table 11: 
Lens Opacities Classification System 
Grading of Cataracts* 
Cataract Type 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Nuclear 
Yellowing and sclerosis of the 
lens nucleus 
Mild 
Moderate 
Pronounced 
Severe 
Cortical 
Measured as aggregate percentage 
of the intrapupillary space 
occupied by the opacity 
Obscures 10% 
of 
intrapupillary 
space 
Obscures 
10% -50% of 
intra-pupillary 
space 
Obscures 
50% -90% of 
intra-pupillary 
space 
Obscures >90% 
of 
intrapupillary 
space 
Posterior subcapsular 
Measured as the aggregate 
percentage of the posterior 
capsular area occupied by the 
opacity 
Obscures 10% 
of the area of 
the posterior 
capsule 
Obscures 30% 
of the area of 
the posterior 
capsule 
Obscures 50% 
of the area of 
the posterior 
capsule 
Obscures >50% 
of the area of 
the posterior 
capsule 
*Designation of cataract severity that falls between grade levels can be made by addition of a + sign (e.g., 
1+, 2+). Grading of cataracts is usually done when pupil is dilated. 
Source: Optometric Clinical Practice Guideline:  Care of the Adult Patient with Cataracts (CPG8). American Optometric 
Association at www.aoa.org. 
 

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APPENDIX 6. GLUTATHIONE (GSH)-, S-ADENOSYLMETHIONINE 
(SAM)-, OR N-ACETYLCYSTEINE (NAC)-
CONTAINING PRODUCTS (REPRESENTATIVE LIST) 
Table 12: 
Glutathione (GSH)-, S-Adenosylmethionine (SAM)-, OR N-Acetylcysteine 
(NAC)-Containing Products (Representative List) 
Glutathione (GSH) 
N-acetylcysteine (NAC) 
S-adenosylmethionine (SAM) 
Product Name 
Ingredient 
Product Name Ingredient 
Product Name 
Ingredient 
Glutathione 
glutathione 
Antidote for 
acetaminophen 
overdose 
acetylecysteine  SAM-e 
Complete 
S-adenosyl-
methionine 
L-Glutathione 
L-glutathione 
Cerefolin NAC: 
medical food 
for age-related 
memory loss 
L-methylfolate 
vitamin B12 
N-acetyl 
cysteine 
SAMe 
S-adenosyl-L-
methionine 
Glutathione 
reduced 
glutathione 
NAC 
N-acetyl 
cysteine 
Double Strength 
SAMe 400 
S-adenosyl-
methionine 
Reduced 
glutathione with 
alpha lipoic acid 
Setria L-
glutathione 
N-A-C Sustain 
N-acetyl L-
cysteine 
 
 
Glutathione, 
Cysteine & C 
glutathione 
L-cysteine 
vitamin C 
Best NAC 
Detox 
Regulators 
N-acetyl 
cysteine 
 
 
(Mega-) 
Liposomal 
Glutathione 
glutathione 
 
  
 
 
Lypospheric 
GSH 
glutathione 
 
 
 
 
Ivory Caps Skin 
Enhancement 
Formula 
glutathione 
 
 
 
 
 

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Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 100 
Amendment 2  
Amendment Rationale 
The primary purposes for this amendment were to: 
1. Revise the study target patient population from “quad-refractory” to “dual-refractory” 
as shown in the following modified inclusion criteria: 
From: Patients must have “MM refractory to lenalidomide, pomalidomide, 
bortezomib, and carfilzomib.” 
To: “Patients must have been previously exposed to lenalidomide, pomalidomide, 
bortezomib, and carfilzomib” and have “MM double refractory to previous treatment 
with both the PI and IMiD drug classes”  
2. Change the study treatment (selinexor plus dexamethasone) dose schedule from 
“twice weekly for three weeks of every four-week cycle” to “twice weekly for every 
week of each four-week cycle.” 
The revised protocol Version 3.0, dated 25 September 2015 will be submitted by the 
Principal Investigator(s) 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 key changes that were made to protocol Version 2.0, including rationales for 
these changes, is provided below. 
Changes to the Protocol 
Administrative Changes 
x Revisions were made to harmonize procedures and assessments with those in clinical 
protocol KCP-330-017 (STOMP): A Phase 1b/2 Study of Selinexor (KPT-330) in 
Combination with Backbone Treatments for Resistant/Refractory Multiple Myeloma. 
x Internal changes were made to improve clarity and eliminate inconsistencies across 
sections (Modified sections:  Global) 
x Updated the version number and date of protocol from Version 2.0 dated 05 February 
2015 to Version 3.0 dated 25 September 2015 (Modified sections: Global) 
Specific Content Changes 
Title 
From: A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) plus Low-
Dose Dexamethasone in Patients with Multiple Myeloma Quad-refractory to Previous 
Therapies 
To: A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) plus 
Dexamethasone in Patients with Multiple Myeloma Double-refractory to Previous 
Therapies 
Indication 
From: Multiple myeloma quad-refractory to prior treatment with bortezomib, 
carfilzomib, lenalidomide, and pomalidomide 

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Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 104 
x Table 12.2 (Dose Adjustment Guidelines for Selinexor) – removed dose adjustment 
guidelines for dexamethasone 
Section 13 Adverse Events 
x Table 13.1 (Classification of Adverse Events by Causality) – Added a fourth option 
of “unlikely related” (to treatment with study drug) 
Section 15.11 Reporting and Publication of Study Documentation 
x Revised to include options for reporting study results in more than one CSR 
 
 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 105 
Amendment 3 
Protocol Version 4  
Amendment Rationale 
The primary purposes for this amendment were to: 
1. Expand the population of patients with penta-refractory MM by enrolling 
approximately 130 additional patients. The overall study population is now ~210 
patients. 
2. Revise the study design to make the expansion population (Part 2) the mITT 
population for the primary efficacy analysis (using ORR); ORR for patients enrolled 
in Part 1 became a secondary analysis. 
The revised protocol Version 4.0, dated 11 August 2016 will be submitted by the Principal 
Investigator(s) 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 key changes that were made to protocol Version 3.0, including rationales for 
these changes, is provided below. 
Changes to the Protocol 
Administrative Changes 
x Revisions were made to simplify the protocol, including the elimination of repetitive 
references to schedules. (Modified sections: Global; Section 9 [in previous versions] 
was removed in its entirety) 
x Added the abbreviation “Sd” to denote selinexor plus low-dose dexamethasone (i.e., 
selinexor [80 mg] plus dexamethasone [20 mg]) 
x Internal changes were made to improve clarity and eliminate inconsistencies across 
sections (Modified sections:  Global) 
x Updated the version number and date of protocol (Modified sections: Global) 
Specific Content Changes 
Title 
From: A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) plus 
Dexamethasone in Patients with Multiple Myeloma Double-refractory to Previous 
Therapies 
To: A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose 
Dexamethasone (Sd) in Patients with Multiple Myeloma Previously Treated with 
Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and an anti-CD38 Monoclonal 
Antibody (mAb) and Refractory to Prior Treatment with Glucocorticoids, an 
Immunomodulatory Agent, a Proteasome Inhibitor and an anti-CD38 mAb 

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CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 107 
 Adjusted inclusion criterion #13 (now #12), requiring adequate platelet count of ≥ 
50,000/mm3 (patients in whom ≥ 50% of bone marrow nucleated cells are plasma 
cells) at baseline. 
 Added inclusion criteria #13, regarding baseline hemoglobin level ≥ 8.5 g/dL. 
 Deleted exclusion criteria #3, MM that does not express either M-protein of FLC is 
no longer excluded.  
 Added exclusion criteria #20 and #21, also to require adequate hematopoietic 
function at baseline. 
 Added exclusion criterion #22, to ensure that patients can tolerate dexamethasone. 
 Added exclusion criterion #23, a standard item in protocols. 
Documentation Requirements (also in Section 8.3) 
 A formal statement was added to describe what documentation is needed to establish 
that patients are refractory to prior treatments. 
Study Numbers (also in Section 13.1.2) 
 Revised estimated enrollment for N=122 (for power analysis), and ~130 for 
enrollment. 
Study Duration: 
 Revised enrollment period from 15 months to 24 months. 
Statistical Methods (also in Section 13) 
 Re-stated the statistical assumptions underlying the revised primary endpoint. 
Table 1 (Schedule of Assessments) 
 Added FLC on C1D15 and C2D15 
 Added emphasis that MM-specific lab assessments (i.e., SPEP, UPEP, FLC and 
quantitative Ig) must be performed at the time of PD to evaluate response. This is an 
essential requirement of the IMWG and was included in previous versions of this 
protocol, but its visibility is being increased in this version to support investigatory 
site staff. 
 Reduced size of footnotes and added cross-referencing to protocol sections 
List of Abbreviations:  
 Deleted abbreviations that were not in use and added several new abbreviations 
Protocol, Main Body 
Sections 7.2, 7.3 and 9.9.1 
 Establish an IRC to perform the central read of response data (for the efficacy 
analysis) that had been previously included under the Data Safety Monitoring 
Committee (DSMC) in previous versions of this protocol. The DSMC, now referred 
to as Data Safety Monitoring Board (DSMB) will retain its role of reviewing all study 

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CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 110 
Amendment 3.1 
Protocol Version 4.1 
Amendment Rationale 
The primary purpose for this amendment was to remove isatuximab as an allowable anti-
CD38 agent for inclusion in the study. Per the FDA, it is not appropriate to include patients 
who have received isatuximab as the anti-CD38 agent for inclusion in the study because it is 
not approved at this time. 
The revised protocol Version 4.1 (US-specific amendment), dated 06 February 2017 will be 
submitted by the Principal Investigator(s) 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 key changes that were made to protocol Version 4.0, including rationales for 
these changes, is provided below. 
Changes to the Protocol 
Administrative Changes (Modified Sections: Global) 
x Updated the version number and date of protocol  
x Updated the number of patients who have received selinexor to the number based on 
the most recent Investigator’s Brochure (14 November 2016)  
x Replaced “minor” with “minimal” in regard to response  
x Removed the qualifier “modified” from IMWG response criteria because the response 
criteria were updated to that based on Kumar 2016 
x Internal changes to improve clarity  
Specific Content Changes 
Title (Modified Sections: Global) 
From: A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-
Dose Dexamethasone (Sd) in Patients with Multiple Myeloma Previously Treated with 
Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and an anti-CD38 Monoclonal 
Antibody (mAb) and Refractory to Prior Treatment with Glucocorticoids, an 
Immunomodulatory Agent, a Proteasome Inhibitor and an anti-CD38 mAb 
To: A Phase 2b, Open-Label, Single-Arm Study of Selinexor (KPT-330) Plus Low-Dose 
Dexamethasone (Sd) in Patients with Multiple Myeloma Previously Treated with 
Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib, and Daratumumab, and 
Refractory to Prior Treatment with Glucocorticoids, an Immunomodulatory Agent, a 
Proteasome Inhibitor, and the anti-CD38 mAb Daratumumab 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 111 
Indication (Modified Sections: Global) 
From: Multiple myeloma (MM) previously treated with lenalidomide, pomalidomide, 
bortezomib, carfilzomib, and an anti-CD38 monoclonal antibody (mAb) (i.e., 
daratumumab or isatuximab) and refractory to prior treatment with glucocorticoids, an 
immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 mAb 
To: Multiple myeloma (MM) previously treated with lenalidomide, pomalidomide, 
bortezomib, carfilzomib, and daratumumab, and refractory to prior treatment with 
glucocorticoids, an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and 
the anti-CD38 mAb daratumumab 
Protocol Approval Signature Page 
 Replaced Michael Kauffman, MD, PhD, Acting Chief Medical Officer, with 
Humphrey Gardner, M.D., Senior Vice President, Clinical Development, as a 
signatory. 
Inclusion/Exclusion Criteria (also in Sections 8.4 and 8.5) 
 Modified inclusion criteria #3d to remove turbidometry as an acceptable method to 
measure quantitative Ig levels. 
 Modified inclusion criteria #4 and #5 to remove isatuximab due to FDA request 
 Corrected inclusion criteria #7 to refer to exclusion criteria #17 
 Corrected inclusion criteria #12 to refer to exclusion criteria #20 
 Changed inclusion criteria #12a to total WBC count > 1,000/mm3 to update criteria 
for this patient population. 
 Corrected exclusion criteria #17 to add ≥ before Grade 2 painful neuropathy 
 Modified exclusion criteria #22 to add or contraindication for before glucocorticoids 
to further clarify the medical intent of the original language. 
 Added a new exclusion criterion immediately after exclusion criteria #22 and moved 
the previous #23 to #24. The addition of exclusion criteria #23, prior exposure to a 
SINE compound, including selinexor, provides consistency across Karyopharm 
protocols. 
IMWG Response Criteria (also in Sections 6.1, 9.3, and Appendix 3) 
 Updated the IMWG response criteria for myeloma to align with the most recent 
IMWG criteria (Kumar, Lancet. 2016;17:328-346). The definition for MR was 
changed from “minor” to “minimal” response to align with the IMWG Consensus 
Criteria. 
Documentation Requirements (also in Section 8.3) 
 Removed the requirement to show a patient was refractory to isatuximab to align with 
feedback on isatuximab from FDA.  
Table 1 (Schedule of Assessments and also in Section 9.7.2.4) 

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CCI
CCI

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 113 
discretion of the Investigator, selinexor dosing may be maintained for all 
hematological or non-hematological AEs that are NOT related to selinexor. For all 
selinexor-related AEs, if the prescribed dose reductions/interruptions in Table 8 result 
in a stabilization of ≥ 4 weeks, a re-escalation may be considered after approval from 
the Medical Monitor. 
 Updated text throughout table to reflect the most recent supportive care information 
available. 
Section 11.2 and Appendix 4 
 Modified text to state that selinexor tablets (20 mg) will be supplied in polyvinyl 
chloride/polychlorotrifluoroethylene/polyvinyl chloride (PVC/PCTFE/PVC) film 
blisters (or equivalent) with an aluminum foil lidding in a secondary paper wallet 
with childproofing to reflect current information. 
Section 11.4.6 
 Removed text to align with the selinexor Investigator’s Brochure: Alcohol:
 
Ethanol should be avoided on selinexor dosing days as it may compete for 
GSH-mediated metabolism 
Section 12.1.1 
 Revised text to align with Table 9. 
Section 15:  
 Added references to the list that were inadvertently removed from previous versions 
of the protocol. 
 Added Durie 2006, Kumar 2016, and Rajkumar 2011 to the list of references 
 Removed Kyle 2009 and Palumbo 2014 from the list of references 
Appendix 7:  
Some of the detailed information in the Protocol Version 4 ROW SOC was not included in 
the Protocol Version 4 SOC for the US because the Protocol Version 4 ROW SOC was 
revised after Protocol Version 4 for the US was published. 
 

Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 114 
Amendment 4 
Protocol Version 5.0 
Amendment Rationale 
The primary purpose for this amendment was to address comments received from Regulatory 
Authorities. 
The revised protocol Version 5.0 dated 28 April 2017 will be submitted by the Principal 
Investigator(s) 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 key changes that were made to protocol Version 4.1, including rationales for 
these changes, is provided below. 
Changes to the Protocol 
Administrative Changes 
x Updated the version number and date of protocol (Modified sections: Global) 
x Updated the number of patients who have received selinexor to the number based on 
the most recent Investigator’s Brochure (31 March 2017) (Modified sections: Global) 
x Internal changes to improve clarity (Modified sections:  Global) 
Specific Content Changes 
Protocol Approval Signature Page 
 Replaced Humphrey Gardner, M.D., Senior Vice President, Clinical Development, 
with Michael Kauffman, MD, PhD, Acting Chief Medical Officer, as a signatory. 
Synopsis 
 Added the following text to the Background and Study Rationale to align with the most 
recent IB, “across all patients was 21% and the clinical benefit rate (CBR) is 33%. 
Similar ORR were seen in the patients with “penta” and “quad” MM, with higher CBR 
in patients who received 8 vs. 6 doses/cycle consistent with improved disease control 
with continuous dosing.” 
 Added the following text, “If any patient is not able to tolerate this dose, then a potential 
discontinuation or further decrease in dosage would be allowed after a discussion with 
the Medical Monitor on a case by case basis,” to allow for adjustments to the dosing of 
dexamethasone. 
Inclusion/Exclusion Criteria (also in Synopsis and Sections 8.4 and 8.5) 
 Modified inclusion criteria #10 to clarify that female patients of childbearing 
potential must agree to use 2 methods of contraception (including 1 highly effective 
and 1 effective method of contraception). 
 Modified inclusion criteria #13 to remove “on Cycle 1 Day 1” for hemoglobin level ≥ 
8.5 g/dL. 

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Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 117 
 Modified text to simplify the description of the blister packaging. 
Section 11.4.7 
 Revised Prevention of Pregnancy language to Contraception Requirements to clarify 
that female patients of childbearing potential must agree to use 2 methods of 
contraception (including 1 highly effective and 1 effective method of contraception). 
Section 12.1.3.1 
 Added the Karyopharm German PV fax number for European sites. 
 Revise text to modify reporting suspected unexpected serious adverse reactions 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 order to ensure safety information is reported to authorities 
in all countries participating in the study. 
Section 14.11 
 Clarified the publication language to include the following text, “Publication will be 
in a relevant peer- reviewed journal, with authorship status and ranking designated 
according to the acknowledged contributions of participating investigators, 
institutions and the Sponsor.” 
Section 15 
 Added Vogl 2016 to the list of references 
Appendix 7:  
 Revised Changes to the Protocol for Protocol Version 4.1 to accurately capture 
changes made to that version of the protocol. 
 
 

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Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-012 
 
 
 
13 December 2017, Version 6.0 
Confidential 
Page 120 
Appendix 7:  
 Added Summary of Changes for Protocol Version 6.0 to describe changes made to 
version 5.0.