Conditions: Dedifferentiated Liposarcoma
Keywords: Advanced unresectable dedifferentiated liposarcoma selinexor KCP-330 Karyopharm Phase 2 / 3 dedifferentiated liposarcoma Liposarcoma
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 342
Healthy volunteers: no

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

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

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

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

* placebo, may cross over to open-label selinexor (60mg twice-weekly)
* selinexor, will be withdrawn from further treatment and followed for survival

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

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

* Disease progression, as defined by RECIST v1.1 Response Criteria
* Clinical progression, as determined by the treating physician
* Unacceptable adverse events (AEs) or failure to tolerate study treatment
* Patient withdrawal
* Patient discontinuation due to non-compliance

Arms:
arm 1: Participants received a fixed blinding dose of 60 milligrams (mg) selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until progressive disease (PD). arm 2: Participants received a fixed blinding dose of 60 mg selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD. arm 3: Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD in double-blinded treatment period. Participants in the placebo group who had PD during the Phase 2 double-blinded treatment, will be elected to cross over to open-label selinexor. arm 4: Participants received a fixed blinding dose of placebo matched to selinexor twice-weekly on Day 1 and 3 during each 6-week (42-day) cycle until PD or development of unacceptable toxicity. Participants in the placebo group who had PD during the Phase 3 double-blinded treatment, will be elected to cross over to open-label selinexor.

Interventions: intervention 1: Selinexor intervention 2: Placebo
Intervention descriptions: intervention 1: Selinexor 60mg intervention 2: None

Protocol document:
Prot_000.pdf: 
Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020 
 
Version 9.0 
Confidential 
Page 1 
Clinical Study Protocol 
KCP-330-020 
A PHASE 2-3, MULTICENTER, RANDOMIZED, DOUBLE-
BLIND STUDY OF SELINEXOR (KPT-330) VERSUS 
PLACEBO IN PATIENTS WITH ADVANCED 
UNRESECTABLE DEDIFFERENTIATED 
LIPOSARCOMA (DDLS) 
SEAL Study: Selinexor in Advanced Liposarcoma 
Drug Development Phase: 
Phase 2-3 
Investigational Product: 
Selinexor (KPT-330) 
Indication: 
Liposarcoma 
EudraCT Number: 
2015-003594-14 
Sponsor: 
Karyopharm Therapeutics Inc. 
85 Wells Avenue  
Newton, MA USA 02459 
Protocol Date and Version: 
16 September 2015 Version 1.0 (Original) 
11 March 2016 Version 2.0 (Amendment 1; not 
implemented) 
01 November 2016 Version 3.0 (Amendment 2) 
06 July 2017 Version 4.0 (Amendment 3) 
29 September 2017 Version 5.0 (Amendment 4) 
23 August 2018 Version 6.0 (Amendment 5; not 
implemented) 
10 September 2018 Version 7.0 (Amendment 6) 
30 January 2020 Version 8.0 (Amendment 7) 
21 May 2020 Version 9.0 (Amendment 8) 
Conduct: In accordance with the ethical principles that originate from the Declaration of 
Helsinki and that are consistent with International Council for Harmonisation (ICH) 
guidelines on Good Clinical Practice (GCP) and regulatory requirements as applicable. 
 
Confidential Information: This document is the sole property of Karyopharm 
Therapeutics Inc. (Karyopharm). This document and any and all information contained 
herein has to be considered and treated as strictly confidential. This document shall be used 
only for the purpose of the disclosure herein provided. No disclosure or publication shall 
be made without the prior written consent of Karyopharm. 


Seli ne x or ( K P T- 3 3 0) 
 
Kar y o p har m T hera pe utics I nc. 
Cli nical St u d y Pr ot oc ol: K C P- 3 3 0- 0 2 0 
2 1 Ma y 2 0 2 0 
Versi o n 9. 0 
C o nfi de ntial 
Pa ge 2 
P R O T O C O L A P P R O V A L SI G N A T U R E P A G E 
S P O N S O R: K A R Y O P H A R M T H E R A P E U TI C S I N C. 
I ha ve rea d a n d u n dersta n d t he c o nte nts of t his cli nic al pr ot oc ol f or St u d y N o. K C P- 3 3 0-
0 2 0 date d 2 1 Ma y 2 0 2 0 a n d a gree t o meet all o bli g ati o ns of Kar y o p har m T hera pe utics 
I nc., as detaile d i n all a p pli ca ble re g ulati o ns a n d g ui deli n es. I n a d diti o n, I will i nf or m t he 
Pri nci pal I n vesti gat or a n d all ot her I n vesti gat ors of all rele va nt i nf or mati o n t h at bec o mes 
a vaila ble d uri n g t he c o n d uct of t his St u d y. 
 
A p pr o ve d B y: 
  
 
 
 
, P h D, M B A 
  
K ar y o p h ar m T her a pe utics I nc. 
 
  
D ate 
 
 
 
, M D 
 
K ar y o p h ar m T her a pe utics I nc. 
  
D ate 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D


Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020 
Version 9.0 
Confidential 
Page 3 
PRINCIPAL INVESTIGATOR’S AGREEMENT 
I have read and understand the contents of this clinical protocol for Study No. KCP-330-020 
dated 21 May 2020 regarding confidentiality. In addition, I will conduct the Study in 
accordance with current Good Clinical Practices (International Council for Harmonisation 
[ICH] E6) and applicable Food and Drug Administration (FDA) 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-330-020 
21 May 2020 
Version 9.0 
Confidential 
Page 4 
PROTOCOL SYNOPSIS 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase:  
Phase 2-3 
Title of Study: A Phase 2-3 Multicenter, Randomized, Double-blind Study of Selinexor 
(KPT-330) versus Placebo in Patients with Advanced Unresectable Dedifferentiated Liposarcoma 
(DDLS) 
Study Name: SEAL: Selinexor in Advanced Liposarcoma 
Protocol Number: KCP-330-020 
Indication: Dedifferentiated Liposarcoma (DDLS) 
Study Design Overview:  
This is a Phase 2-3, multicenter, randomized, double-blind, placebo-controlled study. 
Approximately 334 total patients will be randomized (57 patients in Phase 2 and approximately 
277 patients in Phase 3). Enrollment in Phase 2 has been completed. There was no break between 
Phase 2 and Phase 3 enrollment. The study overview is presented in the figure below: 
 
 
Patients in the placebo arm who have PD will have the option to cross over to open-label selinexor. 
Phase 2: 
Fifty-seven patients were randomized to selinexor or placebo in a 1:1 allocation. Randomization 
was stratified based on the following stratification factors for patients enrolled under protocol 
Versions ≤ 4: number of prior systemic therapies (1 versus ≥ 2) and prior eribulin use (prior 
eribulin versus no prior eribulin). The preplanned analysis of progression-free survival (PFS; after 
40 PFS events were observed) was performed and served as a guideline to inform the final design 
of the Phase 3 portion of the study. 
Phase 3:  
The Phase 3 accrual period began immediately after enrollment of the Phase 2 portion was 
completed and will be approximately 30 months. 
Approximately 277 patients will be randomized to selinexor (~185 patients) or placebo 
(~92 patients) in a 2:1 allocation.  
Randomization will be stratified based on (a) prior eribulin use (prior eribulin versus no prior 
eribulin), (b) prior trabectedin (Yondelis®) use (prior trabectedin versus no prior trabectedin), and 
(c) the number of prior systemic therapies excluding eribulin and trabectedin (2 versus ≥ 3).  
All radiographic responses will be determined by the central reader (see the Imaging Manual for 


Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020 
Version 9.0 
Confidential 
Page 5 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase:  
Phase 2-3 
more details). 
Patients who have progressive disease (PD) per Response Evaluation Criteria in Solid Tumors 
(RECIST) v. 1.1 (Eisenhauer 2009), will discontinue blinded study treatment and their treatment 
assignment will be unblinded. 
• 
Patients in the placebo arm who have PD will have the option to cross over to open-label 
selinexor. 
• 
Patients in the selinexor arm who have PD will only be allowed to continue on selinexor 
(as open-label treatment) if the Investigator, in consultation with the Sponsor, believes 
based on clinical judgement that the patient may derive benefit from continued treatment 
with selinexor. 
Patients who discontinue blinded study treatment at the discretion of the Investigator for reasons 
other than PD are not allowed to receive open-label selinexor. 
An interim analysis was conducted after 108 PFS events had occurred. Based on the safety and 
efficacy data, the DSMB recommendation was continuation of the study with no change to safety 
monitoring and no sample size adjustment. Approximately 34 months will be required to complete 
the primary Phase 3 PFS analysis. The primary endpoint analysis will be performed approximately 
4 months after enrollment of the last patient, once 209 PFS events are observed. Treatment 
assignment for all patients will be unblinded at the time of the primary PFS analysis and all Phase 
3 patients will be evaluable for assessment of the primary endpoint. 
Patients who are on blinded study treatment at the time of the primary PFS analysis at the end of 
Phase 3 may proceed as follows: 
• 
Patients in the placebo arm may cross over to open-label selinexor (60 mg twice weekly).  
• 
Patients in the selinexor arm will continue selinexor but as open-label treatment. 
All patients who have PD while receiving open-label selinexor will discontinue selinexor and be 
followed for survival, unless the Investigator, in consultation with the Sponsor, believes based on 
clinical judgement that the patient may derive benefit from continued treatment with selinexor. 
Objectives: 
Phase 2  
Phase 2 Primary Objective 
• 
Assess and compare progression-free survival (PFS) of patients with advanced unresectable 
DDLS treated with selinexor (60 milligrams [mg]) or placebo twice weekly. PFS is defined 
as the time from date of randomization until the first date of PD, per RECIST v. 1.1, or death 
due to any cause. 
Phase 2 Secondary Objectives  
• 
Compare time to progression (TTP) on study treatment, per RECIST v. 1.1, with TTP on 
the patient’s last prior systemic therapy. 
• 
Determine the overall response rate (ORR: Complete Response [CR] + Partial Response 
[PR]), supported by duration of response (DOR). Responses will be defined by RECIST v. 
1.1.  
• 
Assess changes at 6 weeks in tumor glucose metabolism, density, and size using 
18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed 
tomography (CT) (diagnostic). 
• 
Assess safety of each treatment arm.  
Phase 3  
Phase 3 Primary Objective 
Assess and compare PFS of patients with advanced unresectable DDLS treated with selinexor 
(60 mg) or placebo twice weekly. PFS is defined as the time from date of randomization until 


Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020 
Version 9.0 
Confidential 
Page 6 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (KPT-330) 
Developmental Phase:  
Phase 2-3 
the first date of PD, per RECIST v. 1.1, or death due to any cause. Evaluation of the 
radiographic data for the PFS primary endpoint will be based on data from a scan review by the 
independent central reader. 
Phase 3 Secondary Objectives  
• 
Assess Overall Survival (OS), measured from date of randomization until death due to any 
cause. 
• 
Compare TTP on study treatment, per RECIST v. 1.1, with TTP on the patient’s last prior 
systemic therapy. 
• 
Assess Quality of Life (QoL) and patient-reported outcomes as measured by the European 
Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life 
Questionnaire (QLQ-C30) and the EuroQoL- Group Health Questionnaire (EQ-5D-5L). 
• 
Determine the ORR, supported by DOR. Responses will be defined by RECIST v. 1.1. 
• 
Assess PFS according to the Investigator based on clinical and/or radiologic criteria.  
• 
Assess safety of each treatment arm. 
Study Population:  
This study will enroll patients ≥ 12 years of age with DDLS per World Health Organization 
(WHO) Response Criteria (Miller 1981) for Phase 2 and per RECIST v. 1.1 (Eisenhauer 2009) for 
Phase 3 who have received at least 2 but no more than 5 prior systemic therapies for the treatment 
of liposarcoma who meet all of the inclusion criteria and none of the exclusion criteria. 
Study Treatment, Dose, and Mode of Administration: 
Blinded Study Treatment (Phases 2 and 3): Selinexor at a fixed oral dose of 60 mg or matching 
placebo will be given twice weekly during Weeks 1-6 of each 6-week (42-day) cycle until PD per 
RECIST v. 1.1, intolerability, consent withdrawal, or unblinding. 
Open-label Selinexor:  
Patients on open-label selinexor will receive selinexor 60 mg twice-weekly during Weeks 1-6 of 
each six-week (42-day) cycle until PD, intolerability, or consent withdrawal.  
Duration of Treatment and Follow-up:  
Following a 21-day screening period, patients may receive study treatment until they meet the 
criteria for discontinuation of study treatment or withdraw from the study. 
Patients will be followed for survival until the end of the study, withdrawal criteria are met, or 
death. 
Statistical Methods:  
Based on the planned analysis of PFS by WHO and RECIST v. 1.1 Criteria in the Phase 2 portion 
of the study, the response criteria for the primary analysis (PFS) were changed from WHO to 
RECIST v. 1.1 in Version 4.0 of the protocol. Consequently, data from the Phase 2 portion of the 
study will be excluded from the final efficacy analysis in order to maintain statistical integrity and 
preserve overall Type I error rate. (Phase 2 safety data will be integrated with the Phase 3 safety 
data in the final safety analysis.) 
Phase 2: 
All Phase 2 analyses will be conducted among Phase 2 patients only. 
Phase 2 Primary Endpoint Analysis: 
The primary endpoint PFS for Phase 2 is defined as the time from date of randomization until the 
first date of PD, per RECIST v. 1.1, or death due to any cause.  
A preplanned preliminary analysis of PFS after 40 PFS events was conducted with an 
11 August 2017 data cut with 49 eligible patients whose treatment assignments were available. 
Patients were analyzed in the treatment arm to which they were randomized. The preliminary PFS 


Seli ne x or ( K P T -3 3 0)  
 
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y 2 0 2 0  
Versi o n 9 .0  
C o nfi de ntial  
P a ge 7  
S p o ns or:  
Kar y o p har m T hera pe utics I nc.  
I n vesti g ati o n al Pr o d uct: 
Seli ne x or ( K P T -3 3 0)  
De vel o p me nt al P h ase:  
P hase 2 -3  
a nal ysis was c o n d ucte d  b y b ot h W H O a n d R E CI S T v. 1. 1 C riteria a n d ser ve d as a g ui deli ne t o 
i nf or m t he fi nal desi g n of t he P hase 3 p orti o n of t he st u d y. 
At t he ti me of t he preli mi nar y P F S a nal ysis, t here were 4 8 e ve nts b y W H O ( 2 2  seli ne x or, 
2 6  place b o) a n d 2 8 e ve nts b y R E CI S T v. 1. 1. ( 1 0 seli ne x or, 1 8 place b o). B ot h a nal yses s h o we d 
tre n ds fa v ori n g seli ne x or o ver place b o, w hile R E CI S T v. 1. 1 res ults s h o w a m ore si g nifica nt 
effect size ( hazar d rati o [ H R ] o f 0. 8 4, 9 5 % CI [ 0. 4 7, 1. 4 9] b y W H O as c o m pare d wit h H R of 
0. 6 0, 9 5 % CI [ 0. 2 8, 1. 3 1] b y R E CI S T v. 1. 1). A La n d mar k a nal ysis base d o n R E CI S T v. 1. 1 f or 
patie nts c o nti n ui n g o n st u d y after 4 5 da ys s h o we d a m ore si g nifica nt H R of 0. 2 4 ( 9 5 % CI [ 0. 0 5, 
1. 1 5]) i n fa v or of seli ne x or.  
Of t he 5 7 patie nts i n P hase 2, 5 6 met t he eli gi bilit y criteria f or t he st u d y. T he f or mal pri mar y 
P hase 2 P F S a nal ysis will be perf or me d o n all 5 6 eli gi ble patie nts ra n d o mize d t o st u d y treat me nt 
i n P hase 2 w he n t heir treat me nt assi g n me nts are u n bli n de d. P hase 2 patie nts will be a nal yze d i n 
t he treat me nt ar m t o w hic h t he y are ra n d o mize d.  
P h ase 3:  
T he fi nal efficac y a nal ysis will be c o n d ucte d a m o n g P hase 3 patie nts o nl y.  
P hase 3 Pri mar y E n d p oi nt A nal ysis  
T he pri mar y P F S a nal ysis will be perf or me d o n t he i nte nt-t o-treat (I T T) p o p ulati o n  f or P hase 3 
patie nts  a n d o n t he per -pr ot oc ol ( P P ) p o p ulati o n as a s u p p orti ve a nal ysis.  T he stratifie d l o g -ra n k 
test will be use d t o test t he n ull h y p ot hesis t hat t he P F S distri b uti o ns are t he sa me f or b ot h 
treat me nt gr o u ps vers us  t he alter nati ve h y p ot hesis t hat t he d urati o n of P F S f or t he seli ne x or ar m 
is l o n ger t ha n t he place b o ar m usi n g a 1 -si de d test a n d al p ha = 0. 0 2 5 le vel of si g nifica nce, a dj uste d 
usi n g t he  C ui, H u n g, a n d Wa n g ( C H W) met h o d (C ui 1 9 9 9 ). 
P hase 3 Sa m ple Size a n d Statistical P o wer   
Per pr ot oc ol, t he P hase 3 sa m ple  size was re-e val uate d base d o n t he P hase 2 res ults. Sa m ple size 
calc ulati o ns were c o n d ucte d u n der t he f oll o wi n g ass u m pti o ns:  
Base d o n t hese ass u m pti o ns, a p pr o xi matel y 2 7 7  eli gi ble patie nts will be ra n d o mize d t o rec ei ve 
eit her seli ne x or ( 6 0 m g t wice wee kl y ) or place b o i n a bli n de d ma n ner t o o bser ve 2 0 9 P F S e ve nts.  
C CI
C CI


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 8 
Table 1: 
Schedule of Assessments and Study Activities: Blinded Phase 2 and Phase 3 
 
Screening 
(visits may be 
combined at site 
discretion) 
Randomized Blinded Treatment 
End of Blinded 
Treatment 
(EoBT) 
Only for patients 
NOT proceeding to 
open-label selinexor 
Visit/Call Name 
Visit 1 
Visit 2 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
EoBT Visit19 
Safety 
Follow-up 
Call20 
Survival 
Follow-
up21 
Schedule of Visit 
≤ 21 
days 
prior to 
C1 D1 
≤ 14 
days 
prior to 
C1 D1 
Days 1, 8, 
15, 22, 29, 36 
Day 3 
only22 
Days 1, 15, 
29 
Days 
10, 24,  
3822 
Days 1, 22 
Days 
10, 17, 
31, 3822 
≤ 14 days of last 
blinded dose 
30 days 
after last 
dose 
every 3 
months 
Visit window [±days] 
 
 
±1 day 
+ 1 day 
± 2 days 
+ 1 day 
± 2 days 
+ 1 day 
 
+7 days 
±14 days 
Visit number (in clinic) 
1 
2 
3-8 
Phone 
9-11 
Phone 
≥ 12 
Phone 
In Office 
Phone 
Phone 
Informed consent for blinded 
study treatment1 
X 
 
 
 
 
 
 
 
 
 
 
Informed consent for open-
label selinexor treatment1 
 
 
 
 
 
 
 
 
X 
(if applicable) 
 
 
Patient History 
 
 
 
 
Inclusion /exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Clinical Assessments 
 
Physical examination and 
vital signs (blood pressure, 
pulse, temperature)2 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Weight (indoor clothing 
without shoes) 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Height (without shoes) 
X 
 
 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
BSA3 
X 
 
 
 
X 
(D 1 only) 
 
X 
(D1 only) 
 
X 
 
 
ECOG 
X 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
12-lead ECG4 
X 
 
X5 
(D1 only) 
 
X5 
(D1 only) 
 
 
 
X 
 
 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 9 
 
Screening 
(visits may be 
combined at site 
discretion) 
Randomized Blinded Treatment 
End of Blinded 
Treatment 
(EoBT) 
Only for patients 
NOT proceeding to 
open-label selinexor 
Visit/Call Name 
Visit 1 
Visit 2 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
EoBT Visit19 
Safety 
Follow-up 
Call20 
Survival 
Follow-
up21 
Schedule of Visit 
≤ 21 
days 
prior to 
C1 D1 
≤ 14 
days 
prior to 
C1 D1 
Days 1, 8, 
15, 22, 29, 36 
Day 3 
only22 
Days 1, 15, 
29 
Days 
10, 24,  
3822 
Days 1, 22 
Days 
10, 17, 
31, 3822 
≤ 14 days of last 
blinded dose 
30 days 
after last 
dose 
every 3 
months 
Visit window [±days] 
 
 
±1 day 
+ 1 day 
± 2 days 
+ 1 day 
± 2 days 
+ 1 day 
 
+7 days 
±14 days 
Visit number (in clinic) 
1 
2 
3-8 
Phone 
9-11 
Phone 
≥ 12 
Phone 
In Office 
Phone 
Phone 
Laboratory Assessments 
 
Urinalysis4 
X 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
Hematology4 
X 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
Complete serum chemistry4 
X 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
Limited serum chemistry4 
 
 
X 
(D8, D15, D22, 
D29, D36) 
 
X 
(D15, D29) 
 
X 
(D22 only) 
 
 
 
 
Coagulation tests4 
X 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
Pregnancy test (if 
applicable)4, 23 
 
X6 
 
 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
 
 
Tumor biopsy7 
X 
 
X 
(C1 D22 only; or 
may be taken on 
C2 D1) 
 
X 
(C2 D1 only; 
if not taken 
on C1 D22) 
 
 
 
X8 
 
 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 10 
 
Screening 
(visits may be 
combined at site 
discretion) 
Randomized Blinded Treatment 
End of Blinded 
Treatment 
(EoBT) 
Only for patients 
NOT proceeding to 
open-label selinexor 
Visit/Call Name 
Visit 1 
Visit 2 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
EoBT Visit19 
Safety 
Follow-up 
Call20 
Survival 
Follow-
up21 
Schedule of Visit 
≤ 21 
days 
prior to 
C1 D1 
≤ 14 
days 
prior to 
C1 D1 
Days 1, 8, 
15, 22, 29, 36 
Day 3 
only22 
Days 1, 15, 
29 
Days 
10, 24,  
3822 
Days 1, 22 
Days 
10, 17, 
31, 3822 
≤ 14 days of last 
blinded dose 
30 days 
after last 
dose 
every 3 
months 
Visit window [±days] 
 
 
±1 day 
+ 1 day 
± 2 days 
+ 1 day 
± 2 days 
+ 1 day 
 
+7 days 
±14 days 
Visit number (in clinic) 
1 
2 
3-8 
Phone 
9-11 
Phone 
≥ 12 
Phone 
In Office 
Phone 
Phone 
Imaging 
 
Phase 2 
FDG- PET and CT9 
 
X 
 
 
X 
(D1 only; 
6 weeks post-
first dose) 
 
 
 
 
 
 
Phase 3 
CT (preferred) or MRI 
scan for tumor 
measurement10 
X 
 
 
 
X 
(D1 only; 
6 weeks post-
first dose) 
 
 
 
 
 
 
Phase 29 and Phase 310 
CT (preferred) or MRI scan 
for tumor measurement 
 
 
 
 
 
 
X 
(D1 of Cycles 
3, 4, 5, then of 
every odd # 
cycle) 
 
X 
(if ≥ 4 weeks since last 
prior scan AND 
required to document 
disease or clinical 
progression) 
 
 
Diagnosis/ assessment of 
progression/ extent of 
liposarcoma following each 
tumor scan (RECIST v. 1.1)11 
 
X 
 
 
X 
(D1 only) 
 
X 
(when tumor 
scans are 
performed) 
 
X 
(If tumor scan is 
performed) 
 
 
Treatment assignment query of 
patient and Investigator (after 
determination of PD)12 
 
 
 
 
(X) 
 
(X) 
 
(X) 
 
 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera p e utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 1  
 
Scree ni n g  
( visits m a y be 
c o m bi ne d at site 
discreti o n)  
R a n d o mize d Bli n de d Tre at me nt  
E n d of Bli n de d 
Tre at me nt 
( E o B T) 
O nl y f or p atie nts 
N O T pr ocee di n g t o 
o pe n -l a bel seli ne x or 
Visit/ C all N a me  
Visit 1  
Visit 2  
C ycle 1  
C ycle 2  
C ycle ≥ 3  
E o B T Visit 1 9 
S afet y 
F oll o w -u p 
C all 2 0  
S ur vi v al 
F oll o w -
u p 2 1 
Sc he d ule of Visit  
≤ 2 1 
d a ys 
pri or t o 
C 1  D 1  
≤ 1 4 
d a ys 
pri or t o 
C 1  D 1  
D a ys 1, 8, 
1 5, 2 2, 2 9 , 3 6  
D a y 3 
o nl y 2 2 
D a ys 1, 1 5 , 
2 9  
D a ys 
1 0, 2 4 ,  
3 8 2 2  
D a ys 1 , 2 2  
D a ys 
1 0, 1 7, 
3 1 , 3 8 2 2  
≤ 1 4 d a ys of l ast 
bli n de d d ose  
3 0 d a ys 
after l ast 
d ose  
ever y 3 
m o nt hs  
Visit wi n d o w [ ± d a ys]  
 
 
± 1 d a y  
+ 1 d a y  
± 2 d a ys  
+ 1 d a y  
± 2 d a ys  
+ 1 d a y  
 
+ 7 d a ys  
± 1 4 d a ys  
Visit n u m ber (i n cli nic)  
1  
2  
3 -8  
P h o ne  
9 -1 1  
P h o ne  
≥ 1 2  
P h o ne  
I n Office 
P h o ne  
P h o ne  
N utriti o nal c o ns ultati o n 4, 1 5 
 
 
X  
( D 1 o nl y) 
 
 
 
 
 
 
 
 
Q ualit y of Life 
q uesti o n naires 1 6 
 
X  
 
 
X  
( D 1 o nl y, 
pre d ose ) 
 
X  
( D 1 o nl y, 
pre d ose ) 
 
X  
 
 
Eli gi bilit y c o nfir mati o n b y 
S p o ns or: after scree ni n g a n d 
bef ore ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
St u d y treat me nt: i n cli nic 
d osi n g a n d dis pe nsi n g of f or 
h o me use 1 7 
 
 
X  
 
X  
 
X  
 
 
 
 
A d verse e ve nts  
T hr o u g h o ut  
 
Seri o us a d verse e ve nts  
T hr o u g h o ut  
 
C o nc o mita nt me dicati o ns  
T hr o u g h o ut  
 
 
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera p e utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 2  
 
Scree ni n g  
( visits m a y be 
c o m bi ne d at site 
discreti o n)  
R a n d o mize d Bli n de d Tre at me nt  
E n d of Bli n de d 
Tre at me nt 
( E o B T) 
O nl y f or p atie nts 
N O T pr ocee di n g t o 
o pe n -l a bel seli ne x or 
Visit/ C all N a me  
Visit 1  
Visit 2  
C ycle 1  
C ycle 2  
C ycle ≥ 3  
E o B T Visit 1 9 
S afet y 
F oll o w -u p 
C all 2 0  
S ur vi v al 
F oll o w -
u p 2 1 
Sc he d ule of Visit  
≤ 2 1 
d a ys 
pri or t o 
C 1  D 1  
≤ 1 4 
d a ys 
pri or t o 
C 1  D 1  
D a ys 1, 8, 
1 5, 2 2, 2 9 , 3 6  
D a y 3 
o nl y 2 2 
D a ys 1, 1 5 , 
2 9  
D a ys 
1 0, 2 4 ,  
3 8 2 2  
D a ys 1 , 2 2  
D a ys 
1 0, 1 7, 
3 1 , 3 8 2 2  
≤ 1 4 d a ys of l ast 
bli n de d d ose  
3 0 d a ys 
after l ast 
d ose  
ever y 3 
m o nt hs  
Visit wi n d o w [ ± d a ys]  
 
 
± 1 d a y  
+ 1 d a y  
± 2 d a ys  
+ 1 d a y  
± 2 d a ys  
+ 1 d a y  
 
+ 7 d a ys  
± 1 4 d a ys  
Visit n u m ber (i n cli nic)  
1  
2  
3 -8  
P h o ne  
9 -1 1  
P h o ne  
≥ 1 2  
P h o ne  
I n Office 
P h o ne  
P h o ne  
I n q uir y a b o ut a nti ne o plastic 
t hera p y after disc o nti n uati o n 
of bli n de d st u d y treat me nt 1 8 
 
 
 
 
 
 
 
 
X  
X  
X  
A E: a d vers e e ve nt; B S A = b o d y s urface a r ea; C T = c o m p ute d t o m o gra p h y; E C G = e lectr o car di o gra m; E C O G = Easter n C o o perati ve O nc ol o g y Gr o u p; E o S; e n d of st u d y; F D G = 
1 8F ‐fl u or o de o x y gl u c ose; h C G = h u ma n c h ori o nic g o na d otr o pi n; M RI =  ma g netic res o na nce i ma gi n g; P E T = p ositr o n e missi o n t o m o gra p h y ; P D = pr o gressi ve disease; 
 
; 
; Q o L = Q ualit y of Life; R E CI S T = Res p o nse E val u ati o n Criteria i n S oli d T u m ors; S A E: seri o us a d verse e ve nt; W H O = W orl d Healt h 
Or ga nizati o n.  
1 I nf or me d c o nse nt f or bli n de d st u d y treat me nt is re q uire d pri or t o t h e first st u d y-s pecific meas ures; n ote a ge at ti me of c o nse nt. I nf or me d c o nse nt f or o pe n-la bel seli ne x or is 
re q uire d bef ore a n y st u d y-s pecific meas ures f or o pe n-la bel seli ne x or are c on d ucte d at t h e O pe n -la bel C 1 D1 Visit. F or a d olesce nt patie nts  (per mitte d o nl y i n c o u ntries i n w hic h 
a d olesce nts h a ve bee n a p pr o ve d b y t h e nati o nal/l ocal re g ulat or y/et hical a ut h orit y ), a se parate Ass e nt F or m m ust b e si g ne d b y t h e patie nt at t he ti me of i nf or me d c o nse nt.  
2  Bl o o d press ure a n d p ulse rate s h o ul d be meas ure d after t he patie nt has b ee n i n a s u pi ne or sitti n g p ositi o n f or 5 mi n utes. Bl o o d press ure s h o ul d be assesse d o n t he sa me ar m 
t hr o u g h out t he st u d y.  P h ysical e xa mi n ati o ns will be perf or me d o n t he sc he d ule d da y, e ve n if st u d y tr eat me nt is b ei n g i nterr u pte d. 
3 B S A will be calc ulate d t o verif y t h at B S A > 1. 2 m 2 t o e ns ure t hat a n i n di vi d ual patie nt's seli ne x or d ose w o ul d n ot e xcee d 7 0 m g/ m2 t wic e wee kl y. If t h e patie nt’s wei g ht 
fl u ct u ates s u bsta ntiall y, B S A s h o ul d be re-calc ulate d at eac h treat me nt visit. B S A s h o ul d be re -calc ulate d pri or t o a n y seli ne x or/ place b o d ose c ha n ge.  
4 T he f oll o wi n g ass ess me nts ma y be perf or me d if  cli nicall y i n dicat e d  d uri n g t he st u d y: E C Gs, uri n al ysis, he mat ol o g y, c o m plete or li mite d ser u m c he mistr y, c oa g ulati o n tests , 
pre g na nc y testi n g , a n d n utriti o nal c o ns ultati o n. Cli nical la b orat or y tests will be c ollecte d a n d a nal yz e d o n t he sc he d ule d da y, e ve n if st u d y treat me nt is b ei n g i nterr u pte d (see 
Secti o n  1 0. 6. 2. 1 ).  
5 E C Gs o n Da y 1 of C ycl es 1 a n d 2 d uri n g bli n de d st u d y treat me nt are t o be perf or me d j ust pri or t o t he bl o o d sa m ple ta ke n 2 h o urs p ost d ose  (a p pr o xi matel y at t h e e x pecte d tma x  of 
plas ma s eli ne x or).  
6  F or fe males of c hil d beari n g p ote ntial  o nl y ; m ust h a ve a ne gati ve s er u m h C G pre g na nc y test at Scree ni n g wit hi n 3 da ys b ef ore t h e  first d ose  of bli n de d st u d y treat me nt . Test 
se nsiti vit y f or h C G m ust b e ≥ 2 5 mI U/ m L. 
C CI
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera p e utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 3  
7  A t u m or  bi o ps y will be c ollecte d d uri n g S cree ni n g i n or der t o perf or m c o nfir mat or y hist ol o g y at a c e ntral la b orat or y  (res ults n ot re q uire d f or ra n d o mizati o n a n d i nitiati o n of 
treat me nt) u nless a p pr o priate arc hi val material (ie, of D D L S tiss ue) is a vaila ble (see Secti o n 1 0. 4 ). If s ufficie nt material is a vaila ble fr o m t h e pretreat me nt (scree ni n g) bi o ps y 
sa m ple (arc hi val or fres h), a p orti o n of t h e sa m ple will be use d f or  
 testi n g a n d o ne a d diti o nal t u m or  bi o ps y will be c ollecte d at eit her C ycle 1 Da y 2 2 or  C ycle 2 Da y  1 f or 
 t o assess treat me nt-relate d c ha n ges usi n g i m m u n o hist oc he mic al, ge n o mic, a n d/ or pr ote o mic ass a ys (see Se cti o n 1 0. 1 1. 3 ). Bi o psies are re q uire d if feasi ble.  T he feasi bilit y of 
t h e bi o ps y pr oce d ure, i n ter ms of patie nt safet y a n d t u m or accessi bilit y, will be deter mi n e d b y t h e I n vesti gat or. N ote: T his  sec o n d bi o ps y (e g, eit her C ycle 1 Da y 2 2 or C ycle 2 
Da y 1)  s h o ul d n ot be c ollecte d fr o m a d olesce nt/ pe diatric p atie nts f or e x pl orat or y st u dies if t h ere a p pears t o be a p ote ntial f o r seri o us ris k f or t h e patie nt. 
8  T u m or  bi o ps y at t h e E o B T Visit f or pat ie nts w h o were i n t h e place b o ar m a n d are cr ossi n g o ver  t o o pe n -la bel seli ne x or o nl y. If t h e patie nt has arc hi val material (ie, of 
de differ e ntiate d li p osarc o ma tiss ue) c ollecte d  at Scree ni n g, C ycle 1 Da y 2 2, or C ycle 2 Da y 1  wit hi n 1 2 m o nt hs pri or t o  t he first d ose of o pe n -la bel seli ne x or, t h at sa m ple ma y 
s u bstit ute f or t h e bi o ps y at t h e E o B T Visit. P atie nts i n t h e seli ne x or ar m w h o c o nti n ue o n seli ne x or b ut as o pe n -la bel treat me nt are n ot re q uire d t o ha ve a n a d diti o nal t u m or 
bi o p sy at t h e E o B T Visit.  
9 P h ase 2 p atie nts : F D G -P E T a n d C T ( dia g n ostic) sca ns will be perf or me d d uri n g S cree ni n g ( wit hi n 1 4 da ys of first d ose  of bli n de d st u d y treat me nt ) a n d a p pr o xi matel y 6 wee ks 
after t h e first d ose of bli n de d st u d y tre at me nt  (ie, Da y 1 of C ycle 2) t o assess t u m or size, de nsit y, a n d S U V. N ote: If t h e F D G -P E T  sca n is c o ntrai n dicate d, t he n C T ( preferr e d) or 
M RI sca n s h o ul d be use d i nstea d, s o t h at, f or a gi ve n patie nt, t h e sa me i ma gi n g m o dalit y is mai ntai ne d t hr o u g h o ut t h e st u d y . C o pies of sca n data will be pr o vi d e d t o a ce ntral 
i ma gi n g la b f or t w o-di me nsi o nal a n d t hree -di me nsi o nal meas ure m e nts f or c orrelati o n wit h t u m or res p o nses.  A d diti o nal t u m or assess me nts usi n g C T ( preferre d) or M RI sca ns 
will be perf or me d  at a p pr o xi matel y 1 2, 1 8, a n d 2 4 wee ks aft er t h e first d ose  of bli n de d st u d y treat m e nt (ie, Da y 1 of C ycles 3, 4, a n d 5), t h e n e ver y 1 2  wee ks (ie, Da y 1 of 
o d d -n u m bere d C ycles ≥ 7) t h ereafter u ntil P D  or u n bli n di n g t o assess t u m or size ( o ne, t w o,  a n d t hree di me nsi o ns) a n d e val u ate site of disease a n d dista nt sites (a b d o me n, pel vis, 
c hest ). 
1 0 P h ase 3 p atie nts : C T ( or M RI if C T is c o ntrai n dicate d) sca ns will be perf or me d d uri n g S cree ni n g ( wit hi n 2 1  da ys of first d ose  of bli n de d st u d y treat me nt) a n d a p pr o xi mat el y 
6,  1 2, 1 8 , a n d 2 4 wee ks after t he first d ose  of bli n de d st u d y treat me nt ( ie, Da y 1 of C ycles 2, 3, 4, a n d 5), t h e n e ver y 1 2 wee ks ( ie, Da y 1 of o d d-n u m bere d C ycles ≥ 7) t h ereafter 
u ntil P D  or u n bli n di n g t o assess t u m or size ( o ne, t w o a n d t hree di me nsi o ns) a n d e val u ate site of disease a n d dista nt sites (a b d o me n, pel vis, c hest). F or a gi ve n patie nt, t he  sa me 
i ma gi n g m o dalit y s h o ul d be mai ntai ne d t hr o u g h o ut t he st u d y. P atie nts i n t h e place b o ar m w h o ha ve  cli nical pr o gressi o n m ust h a ve s u bse q ue nt ra di o gra p hic pr o gressi o n 
deter mi n e d b y t h e ce ntral rea der i n or der t o recei ve o pe n -la bel seli ne x or. C o pies of sca n dat a will be pr o vi d e d t o t h e ce ntral rea der  f or t w o-di me nsi o nal a n d t hree -di me nsi o nal 
meas ure me nts f or deter mi n ati o n of  t u m or res p o nses (see I m a gi n g M a n u al f or details). 
1 1  Assess me nt of li p osarc o ma per R E CI S T  v. 1. 1  (Eise n ha uer 2 0 0 9 ; A p pe n di x 2 ). 
1 2  After  P D  deter mi n ati o n  b ut pri or t o u n bli n di n g, rec or d i n de pe n de nt res p o nses fr o m t h e patie nt a n d t h e I n vesti gat or re gar di n g w hic h st u d y treat me nt (acti ve [seli ne x or] or 
place b o) t he y belie ve t h e patie nt recei v e d d uri n g bli n de d st u d y treat me nt.  If treat me nt assi g n me nt is u n bli n de d f or reas o ns ot h er t ha n P D (e g, if u n bli n di n g is re q uire d f or 
cli nical ma na ge me nt of a cli nicall y i m p orta nt  S A E lea di n g t o disc o nti n uati o n of st u d y treat me nt a n d k n o wle d ge of t h e recei ve d st u d y treat me nt is re q uire d f or cli nical 
ma na ge me nt a n d treat me nt of t h e S A E), q uer y s h o ul d be perf or me d pri or t o u n bli n di n g.  
1 5 T he n utriti o nal c o n s ultati o n s h o ul d occ ur o n C1 D 1 bef ore t h e first d ose of bli n de d st u d y treat me nt ( or wit hi n t h e Scree ni n g P eri o d). See Secti o n  1 0. 7. 3 . 
1 6  T he Q o L q uesti o n naires ( E O R T C Q L Q -C 3 0  a n d E ur o Q o L  E Q -5 D -5 L ) s h o ul d be c o m plete d pri or t o st u d y treat me nt a d mi nistrati o n if st u d y treat me nt is a d mi nistere d o n t he 
sa me da y t h at t h e q uesti o n naires are c o m plete d. See Secti o n  1 0. 7. 1 . 
1 7  St u d y treat me nt  d osi n g (seli ne x or or place b o) is t wice wee kl y (e g , Da ys 1, 3, 8, 1 0, etc.) d uri n g Wee ks 1 -6 of eac h 6 -wee k ( 4 2 -da y) c ycle. F or d oses o n n o n -cli nic da ys, t h e 
patie nt will be pr o vi d e d  wit h  d oses t o ta ke h o me.  
C CI
C CI
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera p e utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 4  
1 8  I nf or mati o n o n a n y a nti ne o plastic t h era pies use d after disc o nti n uati o n of bli n de d st u d y treat ment will be c ollecte d at t h e E o B T Visit ( Secti o n  9. 1. 6 ), Safet y F oll o w-u p Calls 
( Sectio n  9. 1. 7 ), a n d d uri n g S ur vi val F oll o w-u p ( Secti o n  9. 2. 6 ). 
1 9 P hase 3 patie nts i n t he seli ne x or ar m w h o c o nti n ue o n seli ne x or b ut as o pe n -la bel treat me nt m ust c o m plete t h e E o B T Visit bef ore t h eir ne xt sc he d ule d d ose. 
2 0 T he Safet y F oll o w -u p Call m ust be perf or me d f or all patie nts ( ie, wit h or wit h o ut E o B T Visit) w h o are n ot pr ocee di n g t o o pe n -la bel seli ne x or. T he p ur p ose of t his call is t o 
assess patie nt stat us, f oll o w -u p o n a n y A Es t h at wer e n ot res ol ve d at t h e E o B T Visit, a n d c ollect i nf or mati o n o n a n y a nti ne o plastic t h era pies use d si nce di sc o nti n uati o n of 
bli n de d st u d y treat me nt.  
2 1  Aft er disc o nti n uati o n of bli n de d st u d y treat me nt, a call will be ma de t o t he patie nt ( or t h e patie nt’s fa mil y) e ver y 3 m o nt hs u n til t he E o S (Secti o n  1 1. 4 ) t o i n q uire a b o ut t he 
patie nt’s li p osarc o ma stat us a n d t o o btai n a vaila ble i nf or mati o n (i ncl u di n g treat me nt t y pe, res p o nse, a n d ti me of res p o nse f o r assess me nt of  
) o n a n y a nti ne o plastic 
t h era pies use d si nce disc o nti n uati o n of bli n de d st u d y treat me nt. F or patie nts w h o pr o gress o n p ost-st u d y treat me nt a nti ne o plastic t h era p y, t h e I n vesti gat or s h o ul d e nter t he date 
of pr o gressi o n  fr o m t h e me dical rec or d i n t h e e C R F if t h at i nf or mati o n is a vaila ble t o t he I n vesti gat or. See Secti o n 1 0. 7. 4 . 
2 2 P h o ne call t o e val u ate s u p p orti ve care me dicati o ns, c o nc o mita nt me dicati o ns, a n d A Es/ S A Es , a n d t o a dj ust s u p p orti ve care as a p pr o priate.  
•  
C ycle 1: t h e tele p h o ne c o ntact wit h t h e patie nt m ust ta ke place o n Da y 3 ( + 1 da y).  
•  
C ycle 2: t h e tele p h o ne c o ntact wit h t h e patie nt will be ma de o n Da y 1 0 ( + 1  da y), Da y 2 4 ( + 1  da y) a n d Da y 3 8 ( + 1 da y), c orres p o n di n g t o Da y 3 ( + 1 da y) of e ver y 
we e k i n  C ycle 2 i n w hic h a cli nic visit d oes n ot occ ur.  
•  
C ycle ≥ 3: t h e tele p h o ne c o ntact wit h t h e patie nt will be ma de o n Da y 1 0 ( + 1  da y), Da y 1 7 ( + 1  da y), Da y 3 1 ( + 1 da y) a n d Da y 3 8 ( + 1 da y), c orres p o n di n g t o Da y 3 
( + 1  da y) of e ver y we e k i n C ycles ≥ 3 i n w h ic h a cli nic visit d oes n ot occ ur. 
2 3 F or fe male patie nts of c hil d beari n g p ote ntial o nl y; pre g na nc y testi n g (ser u m h C G or hi g h se nsiti vit y uri n e) is re q uire d pri or  t o d osi n g o n Da y 1 of C ycles ≥ 2 a n d at t he E o B T 
Visit or wit hi n 3 da ys b ef ore t h e first d ose of o pe n -la bel seli ne x or (ser u m h C G). A p ositi ve uri n e pre g na nc y test will be c o nfir me d b y a ser u m pre g na nc y test. Test se nsiti vit y f or 
h C G m ust b e ≥2 5 mI U/ m L.  
 
C CI


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 15 
Table 2: 
Schedule of Assessments and Study Activities: Open-Label Selinexor 
• 
EoBT Visit serves as baseline of Open-Label Selinexor; The EoBT Visit may occur at open-label (OL)-C1 D1 visit but 
must be ≤ 14 days of last blinded dose. OL C1 D1 must occur within 14 days of the EoBT Visit. 
• 
Patients in the selinexor arm who continue selinexor but as open-label treatment must complete the EoBT Visit before 
their next scheduled selinexor dose to maintain continuity of selinexor dosing from blinded to open-label treatment.  
• 
Physical examination assessments and laboratory assessments done at the EoBT Visit do not need to be repeated at 
OL-C1 D1. 
 
 
Open-Label Cycle 1 
(42 days/6 wks) per cycle) 
Open-Label Cycle 2 
Open-Label 
Cycle ≥ 3 
End of 
Treatment 
(EoT) Visit 
Safety Follow-
up Call15 
Survival 
Follow-up16 
Schedule of Visit 
Days 1, 8*, 15*, 
22, 29* and 36* 
Day 3 
only17 
Days 1, 15 
and 29* 
Days 10, 24 
and 3817 
Days 1 and 22 
≤ 14 days Post-
Last Dose 
30 days after 
last dose 
Every 3 months 
Visit window [±days] 
±1 day 
+ 1 day 
± 2 days 
+ 1 day 
± 2 days 
 
+7 days 
±14 days 
Visit number 
OL1-6 
Phone 
OL7-9 
Phone 
OL ≥ 10 
In Office 
Phone 
Phone 
Open-label informed consent1 
X 
(if not obtained 
at EoBT Visit) 
 
 
 
 
 
 
 
Clinical Assessments 
(if performed at EoBT, do not repeat at 
C1 D1) 
 
Physical examination and vital signs 
(blood pressure, pulse, temperature)2 
X 
 
X 
 
X 
X 
 
 
Weight (indoor clothing without shoes) 
X 
 
X 
 
X 
X 
 
 
Height (without shoes) 
 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
BSA3 
 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
ECOG 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
12-lead ECG4 
X 
(D1 only) 
 
 
 
 
X 
 
 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 16 
 
Open-Label Cycle 1 
(42 days/6 wks) per cycle) 
Open-Label Cycle 2 
Open-Label 
Cycle ≥ 3 
End of 
Treatment 
(EoT) Visit 
Safety Follow-
up Call15 
Survival 
Follow-up16 
Schedule of Visit 
Days 1, 8*, 15*, 
22, 29* and 36* 
Day 3 
only17 
Days 1, 15 
and 29* 
Days 10, 24 
and 3817 
Days 1 and 22 
≤ 14 days Post-
Last Dose 
30 days after 
last dose 
Every 3 months 
Visit window [±days] 
±1 day 
+ 1 day 
± 2 days 
+ 1 day 
± 2 days 
 
+7 days 
±14 days 
Visit number 
OL1-6 
Phone 
OL7-9 
Phone 
OL ≥ 10 
In Office 
Phone 
Phone 
Laboratory Assessments  
(if performed at EoBT, do not repeat at 
C1 D1) 
 
Urinalysis4 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
Hematology4 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
Complete serum chemistry4 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
Limited serum chemistry4 
X 
(D8, D15, D22, 
D29, D36) 
 
X 
(D15, D29) 
 
X 
(D22 only) 
 
 
 
Coagulation tests4 
X 
(D1 only) 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
Pregnancy test4, 5, 18 
 
 
X 
(D1 only) 
 
X 
(D1 only) 
X 
 
 
Tumor biopsy6 
(Only patients who cross over from placebo) 
X 
(C1 D22 only; or 
may be taken on 
C2 D1) 
 
X 
(C2 D1 only; if 
not taken on 
C1 D22) 
 
 
 
 
 
Imaging 
 
CT (preferred) or MRI scan for tumor 
measurement7 
 
 
X 
(D1 only) 
 
X 
(D1 of every odd # 
cycle) 
X 
(if ≥ 4 weeks since 
last prior scan 
AND required to 
document disease 
or clinical 
progression) 
 
 
Assessment of progression/ extent of 
liposarcoma following each tumor scan 
(RECIST v. 1.1)8 
 
 
X 
(D1 only) 
 
X 
(when tumor 
scans are 
performed) 
X 
(If tumor scan is 
performed) 
 
 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera p e utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 7  
 
O pe n -L a bel C ycle 1  
( 4 2 d a ys/ 6 w ks) per c ycle) 
O pe n -L a bel C ycle 2  
O pe n -L a bel 
C ycle ≥ 3  
E n d of 
Tre at me nt 
( E o T) Visit 
S afet y F oll o w -
u p C all 1 5  
S ur vi v al 
F oll o w -u p 1 6 
Sc he d ule of Visit  
D a ys 1, 8 *, 1 5 *,  
2 2, 2 9 * a n d 3 6 *  
D a y 3 
o nl y 1 7 
D a ys 1, 1 5 
a n d 2 9 *  
D a ys 1 0, 2 4 
a n d 3 8 1 7  
D a ys 1 a n d 2 2  
≤ 1 4 d a ys P ost -
L ast D os e  
3 0 d a ys after 
l ast d ose 
E ver y 3 m o nt hs  
Visit wi n d o w [ ± d a ys]  
± 1 d a y  
+ 1 d a y  
± 2 d a ys  
+ 1 d a y  
± 2 d a ys  
 
+ 7 d a ys  
± 1 4 d a ys  
Visit n u m ber  
O L 1 -6  
P h o ne  
O L 7 -9  
P h o ne  
O L  ≥ 1 0  
I n Office 
P h o ne  
P h o ne  
N utriti o nal c o ns ultati o n 4, 1 1 
X  
( D 1 o nl y 
 
 
 
 
 
 
 
Q ualit y of Life q uesti o n naires 1 2 
X  
(D 1 o nl y, pre d ose)  
 
X  
( D 1 o nl y, 
pre d ose  
 
X  
(D 1 o nl y, pre d ose)  
X  
 
 
Seli ne x or: i n cli nic d osi n g a n d dis pe nsi n g 
of f or h o me use1 3 
X  
 
X  
 
X  
 
 
 
A Es a n d S A Es  
T hr o u g h o ut  
 
C o nc o mita nt me dicati o ns  
T hr o u g h o ut  
 
 
I n q uir y a b o ut a nti ne o plastic t hera p y after 
disc o nti n uati o n of o pe n -la bel seli ne x or1 4 
 
 
 
 
 
X  
X  
X  
* Visits are n ot re q uired f or patie nts w h o c o nti n ue seli ne x or b ut as o pe n -la bel treat me nt. 
B S A = b o d y s urfa ce a re a; C T = c o m p ute d t o m o gra p h y; E C G = e l e ctr o car di o gra m; E C O G = Easter n C o o perati ve O nc ol o g y Gr o u p; M RI = ma g netic res o na nce i ma gi n g; P D = 
pr o gressi ve disease; 
; Q o L = Q ualit y of Life; R E CI S T = Res p o nse E val u ati o n Criteria i n S oli d T u m ors; W H O = W orl d Healt h 
Or ga nizati o n.  
1 I nf or me d c o nse nt f or o pe n-la bel seli ne x or is re q uire d bef ore a n y st u d y-s pecifi c meas ures f or o pe n-la bel seli ne x or are c on d ucte d at t he O pe n -la bel C 1 D1 Visit. F or a d olesce nt 
patie nts  (per mitte d o nl y i n c o u ntries i n w hic h a d olesce nts h a ve bee n a p pr o ve d b y t h e nati o nal/l ocal re g ulat or y/et hical a ut h orit y ), a se parate Asse nt For m m ust b e si g ne d b y t h e 
patie nt at t he ti me of i nf or me d c o nse nt.  
2 Bl o o d press ure a n d p ulse rate s h o ul d be meas ure d after t he patie nt has b ee n i n a s u pi ne or sitti n g p ositi o n f or 5 mi n utes. Bl o o d press ure s h o ul d be assesse d o n t he sa me ar m 
t hr o u g h o ut t he st u d y. P h ysical e xa mi n ati o ns will be perf or me d o n t he sc he d ule d da y, e ve n if st u d y tr eat me nt is b ei n g i nterr u pte d. 
3 . B S A will be calc ulate d t o verif y t h at B S A > 1. 2 m 2 t o e ns ure t hat a n i n di vi d ual patie nt's seli ne x or d ose w o ul d n ot e xcee d 7 0 m g/ m2 t wic e wee kl y. If t h e patie nt’s wei g ht 
fl u ct u ates s u bsta ntiall y, B S A s h o ul d be re-calc ulate d at eac h treat me nt visit. B S A s h o ul d be re -calc ulate d pri or t o a n y seli ne x or/ place b o d ose c ha n ge.  
4 T he f oll o wi n g ass ess me nts ma y be perf or me d if cli nicall y i n dicate d d uri n g t he st u d y: E C Gs, uri n a l ysis, he mat ol o g y, c o m plete or li mite d ser u m c he mistr y, c oa g ulati o n tests, 
pre g na nc y testi n g, a n d n utriti o nal c o ns ultati o n.  Cli nical la b orat or y tests will be c ollecte d a n d a nal yz e d o n t he sc he d ule d da y, e ve n if st u d y treat me nt is b ei n g i nterr u pte d (see 
Sec ti o n 1 0. 6. 2. 1 ).  
 
C CI
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera p e utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 8  
5  Fe males  of c hil d beari n g p ote ntial w h o are pr ocee di n g t o o pe n -la bel seli ne x or m ust h a ve a ne gati ve s er u m  h C G pre g na nc y test at t h e E o B T Visit ( or wit hi n 3  da ys bef ore t h e  first 
d ose of o pe n -la bel seli ne x or). Test se nsiti vit y f or h C G m ust b e ≥ 2 5 mI U/ m L.  
6 T u m or b i o ps y t o be ta ke n o nl y fr o m patie nts w h o cr oss o ver fr o m bli n de d place b o t o o pe n -la bel seli n e x or. If a bi o ps y sa m ple was o btai ne d d uri n g bli n de d treat me nt ( pre- or 
p ost -d osi n g)  wit hi n 1 2 m o nt hs pri or t o t h e first d ose of o pe n -la bel seli ne x or, o ne a d diti o nal bi o ps y will be ta ke n at eit her C ycle 1 Da y 2 2 O R C y cle 2 Da y 1 f or 
. P orti o ns of 
t his bi o ps y will be f or mali n -fi x e d a n d fr oze n -u nfi xe d as d escri b e d i n t h e L a b or at ory M a n u al . Bi o psies are re q uire d if feasi ble. T he feasi bilit y of t h e bi o ps y pr oce d ure, i n ter ms of 
patie nt safet y a n d t u m or accessi bilit y, will be deter mi n e d b y t h e I n vesti gat or. T his  sec o n d bi o ps y (e g, eit her C ycle 1 Da y 2 2 or C ycle 2 Da y 1) s h o ul d n ot be c ollecte d fr o m 
a d olesce nt/ pe diatric p atie nts f or e x pl orat or y st u dies if t h ere a p pear t o be a p ote ntial f or  seri o us ris ks f or t h e patie nt. P atie nts i n t h e seli ne x or ar m w h o c o nti n ue o n seli ne x or b ut as 
o pe n -la bel treat me nt are n ot re q uire d t o ha ve a n a d diti o nal t u m or bi o ps y o n C ycle 1 Da y 2 2 or C ycle 2 Da y 1 of o pe n-la bel treat me nt. 
7 C T ( or M RI if C T c o ntrai n dicate d) sca ns will be p erf or me d a p pr o xi matel y 6 a n d 1 2 wee ks  after t he firs t d ose  of o pe n -la bel seli ne x or (ie, Da y 1 of C ycl es 2 a n d 3 ), t he n e ver y 
1 2  wee ks ( ie, Da y 1 of o d d -n u m bere d C ycles ≥ 5 ) t h ereafter u ntil P D  t o assess t u m or size ( o ne, t w o a n d t hree di me nsi o ns) a n d e val u ate site of disease a n d dista nt sites (a b d o me n, 
pel vis, c hest). F or a gi ve n patie nt, t h e sa me  i ma gi n g m o dalit y s h o ul d be mai ntai ne d t hr o u g h o ut t he st u d y. C o pies of sca n data will be pr o vi d e d t o t he ce ntral rea der  f or t w o-
di me nsi o nal a n d t hree -di me nsi o nal meas ure me nts f or deter mi n ati o n of  t u m or res p o nses (see I m a gi n g M a n u al f or details). 
8 Assess me nt of li p osarc o ma per R E CI S T v. 1. 1 ( Eise n ha uer 2 0 0 9; A p pe n di x  2)  b y t he ce ntral rea der. 
1 1 F or patie nts i n t he place b o ar m w h o cr oss o ver t o o pe n -la bel seli ne x or, t h e n utriti o nal c o n s ultati o n s h o ul d occ ur o n C1 D 1 bef ore t he first d ose of o pe n -la bel seli ne x or. T he 
n utriti o nal c o ns ultati o n is n ot re q uire d at C 1 D1 of o pe n -la bel seli ne x or treat me nt f or patie nts i n t h e seli ne x or ar m w h o c o nti n ue o n seli ne x or b ut as o pe n -la bel treat me nt. See 
Secti o n  1 0. 7. 3 .
1 2  T he Q o L q uesti o n naires ( E O R T C Q L Q -C 3 0 a n d E ur o Q o L E Q -5 D -5 L) s h o ul d be c o m plete d pri or t o st u d y treat me nt a d mi nistrati o n if st u d y treat me nt is a d mi nistere d o n t he 
sa me da y t h at t h e q uesti o n naires are c o m plete d. See Secti o n 1 0. 7. 1 . 
1 3  Seli ne x or d osi n g is o n Da y 1 a n d 3 of Wee ks 1 -6 of eac h 6 -wee k ( 4 2 da y) c ycle. F or d oses o n n o n -cli nic d a ys, t h e patie nt will be pr o vi d e d d oses t o ta ke h o me.  
1 4 I nf or mati o n o n a n y a nti ne oplastic t h era pies use d after disc o nti n uati o n of st u d y treat me nt will be c ollecte d at t he E o T Visit ( Secti o n  9. 2. 4 ), Safet y F oll o w-u p Calls 
( Secti o n 9. 2. 5 ), a n d d uri n g S ur vi val F oll o w-u p ( Secti o n  9. 2. 6 ). 
1 5  T he Safet y F oll o w -u p Call m ust b e perf or me d f or all patie nts ( ie, wit h or wit h o ut a n E o T Visit). T he p ur p ose of t his call is  t o assess patie nt stat us, f oll o w-u p o n a n y A Es t hat 
wer e n ot res ol ve d at t he E o T Visit, a n d i nf or mati o n o n a n y  a nti ne o plastic t h era pies us e d si nce disc o nti n uati o n of o pe n -la bel seli ne x or st u d y treat me nt. 
1 6 After st u d y disc o nti n uati o n  of  o pe n -la bel seli ne x or, a call will be ma de t o t h e patie nt ( or t he patie nt’s fa mil y) e ver y 3 m o nt hs u ntil t h e E o S  ( Secti o n 1 1. 4 ) t o i n q uire a b o ut t h e 
patie nt’s li p osarc o ma stat us a n d t o o btai n a vaila ble i nf or mati o n  (i ncl u di n g treat me nt t y pe, res p o nse, a n d ti me of res p o nse f or assess me nt of  
) o n a n y  a nti ne o plastic 
t h era pies use d si nce disc o nti n uati o n of o pe n -la bel seli ne x or. F or patie nts w h o pr o gress o n p ost -st u d y treat me nt a nti ne o plastic t hera p y, t h e I n vesti gat or s h o ul d e nter t he date of 
pr o gressi o n  fr o m t h e me dical rec or d i n t he e C R F if t h at i nf or mati o n is a vaila ble t o t h e I n vesti gat or. 
1 7 P h o ne call t o e val u ate s u p p orti ve care me dicati o ns, c o nc o mita nt me dicati o ns, a n d A Es/ S A Es, a n d t o a dj ust s u p p orti ve care as a p pr o priate. 
•
C ycle 1: t h e tele p h o ne c o ntact wit h t h e patie nt m ust ta ke place o n Da y 3 ( + 1 da y).
•
C ycle 2: t h e tele p h o ne c o ntact wit h t h e patie nt will be ma de o n Da y 1 0 ( + 1  da y), Da y 2 4 ( + 1  da y) a n d Da y 3 8 ( + 1 da y), c or res p o n di n g t o Da y 3 ( + 1 da y) of e ver y
we e k i n C ycle 2 i n w hic h a cli nic visit d oes n ot occ ur.
1 8 F or fe male patie nts of c hil d beari n g p ote ntial o nl y; pre g na nc y testi n g (ser u m h C G or hi g h se nsiti vit y uri n e) is re q uire d pri or  t o d osi n g o n Da y 1 of C ycles ≥ 2 a n d at t he E o T 
Visit (ser u m h C G). A p ositi ve uri ne pre g na nc y test will be c o nfir me d b y a ser u m  pre g na nc y test. Test se nsiti vit y f or h C G m ust b e ≥ 2 5 mI U/ m L.
C CI
C CI
C CI


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 19 
Figure 1: 
Study Flow Chart  
 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 20 
Figure 2: Disposition of Patients Who Have PD Per RECIST v. 1.1 During Blinded Study Treatment and/or Who Discontinue 
Blinded Study Treatment 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
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Figure 3: 
Disposition of Patients Receiving Blinded Study Treatment at the Time of the Primary PFS Analysis at the End of Phase 3 
 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 22 
TABLE OF CONTENTS 
1. 
OVERVIEW ........................................................................................... 35 
2. 
LIPOSARCOMA .................................................................................... 36 
3. 
NUCLEAR EXPORT ............................................................................. 38 
3.1. 
Inactivation of Tumor Suppressor Proteins (TSPs) by Nuclear Export . 38 
3.2. 
Inhibition of XPO1 in Human Cancer .................................................... 38 
4. 
SELINEXOR (KPT-330) ........................................................................ 40 
4.1. 
Introduction ............................................................................................. 40 
4.2. 
Preclinical Data ....................................................................................... 40 
4.2.1. 
Pharmacology ......................................................................................... 40 
4.2.2. 
Pharmacokinetics and Toxicology .......................................................... 41 
4.3. 
Clinical Experience ................................................................................. 41 
4.3.1. 
Preliminary Efficacy with Sarcoma ........................................................ 42 
4.3.2. 
Current Study (KCP-330-020): Analysis of the PFS Results for the 
Preplanned Analysis for Phase 2 ............................................................ 42 
4.3.2.1. 
Preliminary Analysis of PFS Based on WHO Response Criteria ........... 43 
4.3.2.2. 
Preliminary Analysis of PFS Based on RECIST v. 1.1 Criteria ............. 43 
4.3.3. 
Clinical Pharmacokinetics ...................................................................... 44 
4.3.4. 
Potential Risks ........................................................................................ 44 
4.3.4.1. 
Preliminary Safety with Sarcoma ........................................................... 45 
4.3.4.2. 
Current Study (KCP-330-020): Preliminary Safety Results for the 
Preplanned Analysis for Phase 2 ............................................................ 45 
4.3.4.3. 
Reproductive Risks ................................................................................. 45 
5. 
RATIONALE FOR THE STUDY .......................................................... 46 
5.1. 
Rationale for the Doses and the Dosing Regimen .................................. 46 
5.2. 
Rationale for Change in Response Criteria from WHO Response Criteria 
to RECIST v. 1.1 for the Primary Endpoint ........................................... 46 
5.3. 
Rationale for Change in the Primary Response Population.................... 47 
6. 
STUDY OBJECTIVES .......................................................................... 48 
6.1. 
Phase 2 .................................................................................................... 48 
6.1.1. 
Phase 2 Primary Objective ...................................................................... 48 
6.1.2. 
Phase 2 Secondary Objectives ................................................................ 48 
6.1.3. 
Phase 2 Exploratory Objectives .............................................................. 48 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
Confidential 
Page 23 
6.2. 
Phase 3 .................................................................................................... 49 
6.2.1. 
Phase 3 Primary Objective ...................................................................... 49 
6.2.2. 
Phase 3 Secondary Objectives ................................................................ 49 
6.2.3. 
Phase 3 Exploratory Objectives .............................................................. 50 
7. 
STUDY DESIGN ................................................................................... 51 
7.1. 
Study Design Overview .......................................................................... 51 
7.2. 
Study Treatment Following PD and the Primary PFS Analysis and 
Follow-up After Discontinuation of Study Treatment ............................ 53 
7.2.1. 
Study Treatment After Determination of PD by the Central Reader ...... 53 
7.2.2. 
Follow-up for Patients Without PD Who Discontinue Study Treatment 53 
7.2.3. 
Study Treatment Following the Primary PFS Analysis .......................... 53 
7.2.4. 
Exception for Patients Who May Derive Benefit from Continued 
Treatment with Selinexor ....................................................................... 54 
7.3. 
Data Safety Monitoring Board ................................................................ 54 
7.4. 
Stopping Rules ........................................................................................ 55 
7.5. 
Criteria for Evaluation ............................................................................ 55 
7.5.1. 
Primary Efficacy Endpoint ..................................................................... 55 
7.5.2. 
Secondary Endpoints .............................................................................. 56 
7.5.2.1. 
Key Secondary Endpoints ....................................................................... 56 
7.5.2.2. 
Secondary Efficacy Endpoints ................................................................ 56 
7.5.3. 
QoL Endpoint (Secondary Endpoint) ..................................................... 56 
7.5.4. 
Safety Endpoints ..................................................................................... 56 
7.5.5. 
Exploratory Endpoints ............................................................................ 56 
7.6. 
Screening and Registration ..................................................................... 57 
7.6.1. 
Study Patient Number ............................................................................. 58 
7.6.2. 
Rescreening ............................................................................................. 58 
7.6.3. 
Screen Failures ........................................................................................ 58 
7.6.4. 
Replacement of Patients ......................................................................... 58 
7.7. 
Randomization to Blinded Study Treatment .......................................... 58 
7.8. 
Blinding Procedures ................................................................................ 59 
8. 
SELECTION OF PATIENTS................................................................. 60 
8.1. 
Number of Patients ................................................................................. 60 
8.2. 
Recruitment ............................................................................................. 60 


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
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Page 24 
8.3. 
Inclusion Criteria .................................................................................... 60 
8.4. 
Exclusion Criteria ................................................................................... 61 
9. 
STUDY ACTIVITIES ............................................................................ 63 
9.1. 
Description of Study Days: Blinded Treatment ...................................... 63 
9.1.1. 
Visit 1 (within 21 days prior to C1 D1); Screening Visit 1 .................... 63 
9.1.2. 
Visit 2 (within 14 days prior to C1 D1); Screening Visit 2 .................... 64 
9.1.3. 
Visits 3-8 (Cycle 1: Days 1, 8, 15, 22, 29, and 36 [±1 days]); Return to 
the Clinic ................................................................................................. 65 
9.1.3.1. 
Phone Call with Patient: Cycle 1 Day 3 Only (+ 1 day) ......................... 66 
9.1.4. 
Visits 9-11 (Cycle 2: Days 1, 15, and 29 [±2 days]); Return to the Clinic
 ................................................................................................................ 66 
9.1.4.1. 
Phone Calls with Patient: Cycle 2 Days 10, 24, and 38 (+ 1 day) .......... 67 
9.1.5. 
Visits ≥ 12 (Cycles ≥ 3: Days 1 and 22 [±2 days]); Return to the Clinic 67 
9.1.5.1. 
Phone Calls with Patient: Cycles ≥ 3 Days 10, 17, 31 and 38 (+ 1 day) 68 
9.1.6. 
End of Blinded Treatment Visit; Return to the Clinic ............................ 68 
9.1.7. 
Safety Follow-up Phone Call (30 Days [+7 days] after last dose of study 
treatment) ................................................................................................ 69 
9.1.8. 
Survival Follow-Up ................................................................................ 70 
9.2. 
Description of Study Days: Open-label Selinexor .................................. 70 
9.2.1. 
Visits OL1-6 (Cycle 1: Days 1, 8*, 15*, 22, 29*, and 36* [±1 days]); 
Return to the Clinic ................................................................................. 71 
9.2.1.1. 
Phone Call with Patient: Cycle 1 Day 3 Only (+ 1 day) ......................... 72 
9.2.2. 
Visits OL7-9 (Cycle 2: Days 1, 15, and 29* [±2 days]); Return to the 
Clinic ....................................................................................................... 72 
9.2.2.1. 
Phone Calls with Patient: Cycle 2 Days 10, 24, and 38 (+ 1 day) .......... 73 
9.2.3. 
Visits OL ≥ 10 (Cycles ≥ 3: Days 1 and 22 [±2 days]); Return to the 
Clinic ....................................................................................................... 73 
9.2.4. 
End of Treatment Visit (≤ 14 days after last dose of study treatment); 
Return to the Clinic ................................................................................. 74 
9.2.5. 
OL Safety Follow-up Phone Call (≤ 30 Days [+7 days] after last dose of 
study treatment) ...................................................................................... 75 
9.2.6. 
OL Survival Follow-Up .......................................................................... 75 
9.3. 
Unscheduled Visits ................................................................................. 75 
10. 
METHODS OF ASSESSMENT ............................................................ 76 
10.1. 
Inclusion/Exclusion Criteria ................................................................... 76 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 2 5  
1 0. 2.  
De m o gra p hic Data  .................................................................................. 7 6  
1 0. 3.  
Me dical Hist or y  ...................................................................................... 7 6  
1 0. 4.  
Li p osarc o ma Hist ol o g y  ........................................................................... 7 6  
1 0. 5.  
Efficac y Assess me nts  ............................................................................. 7 7  
1 0. 5. 1 . 
T u m or I m a gi n g  ....................................................................................... 7 7  
1 0. 5. 1. 1.  
T y pes of I ma gi n g  .................................................................................... 7 7  
1 0. 5. 1. 2.  
I ma gi n g Sc h e d ules f or P hases 2 a n d 3 ................................................... 7 8  
1 0. 5. 2.  
Dia g n osis/ Assess me nt of Pr o gressi o n/ E xte nt of Li p osarc o ma  ............ 7 8  
1 0. 6.  
Safet y Assess me nts  ................................................................................. 7 8  
1 0. 6. 1.  
Cli nical Safet y Ass ess me nts  ................................................................... 7 8  
1 0. 6. 1. 1.  
P h ysical E x a mi nati o n a n d Vital Si g ns  .................................................... 7 8  
1 0. 6. 1. 2.  
Hei g ht, W ei g ht, a n d B S A  ....................................................................... 7 9  
1 0. 6. 1. 3.  
E C O G Perf or ma n ce Stat us  ..................................................................... 7 9  
1 0. 6. 1. 4.  
Electr ocar di o gra p h y  ................................................................................ 7 9  
1 0. 6. 1. 5.  
C o nc o mita nt Me dicati o ns  ....................................................................... 7 9  
1 0. 6. 1. 6.  
A d verse E v e nts  ....................................................................................... 8 0  
1 0. 6. 2.  
La b orat or y Safet y Assess me nts  .............................................................. 8 0  
1 0. 6. 2. 1.  
Cli nical La b orat or y Tests  ....................................................................... 8 0  
1 0. 6. 2. 2.  
Pre g n a nc y T esti n g  .................................................................................. 8 1  
1 0. 7.  
Ot her Assess me nts  .................................................................................. 8 1  
1 0. 7. 1.  
Q ualit y of L if e a n d H ealt h-R elate d O utc o mes  ....................................... 8 1  
1 0. 7. 2.  
Treat me nt Assi g n me nt Q uer y  ................................................................. 8 2  
1 0. 7. 3.  
N utriti o nal C o ns ultati o n  ......................................................................... 8 2  
1 0. 7. 4.  
C ollecti o n of I nf or mati o n o n A nti ne o plastic T hera p y  ............................ 8 2  
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 2 6  
1 1.  
DI S C O N TI N U A TI O N A N D U N B LI N DI N G C RI T E RI A  .................... 8 8  
1 1. 1.  
Earl y Ter mi nati o n of t he St u d y  .............................................................. 8 8  
1 1. 2.  
Disc o nti n uati o n of St u d y Treat me nt a n d/ or Wit h dra wal of Patie nts fr o m 
t he St u d y ................................................................................................. 8 8  
1 1. 3.  
U n bl i n di n g .............................................................................................. 8 9  
1 1. 3. 1.  
U n bli n di n g of Treat me nt Assi g n me nt D uri n g Bli n de d St u d y Treat me nt
 ................................................................................................................ 8 9  
1 1. 3. 2.  
U n bli n di n g of Treat me nt Assi g n me nt f or All Patie nts at t he Pri mar y P F S 
A nal ysis at t he E n d of P hase 3  ............................................................... 8 9  
1 1. 4.  
Defi niti o n of E n d of St u d y  ..................................................................... 8 9  
1 2.  
T R E A T M E N T  ........................................................................................ 9 0  
1 2. 1.  
D osi n g a n d A d mi nistrati o n of St u d y Treat me nt  ..................................... 9 0  
1 2. 1. 1.  
La b eli n g  .................................................................................................. 9 0  
1 2. 1. 2.  
Dis pe nsi n g Directi o ns  ............................................................................. 9 0  
1 2. 1 . 3. 
D osi n g I nf or mati o n  ................................................................................. 9 0  
1 2. 1. 4.  
D osi n g I nstr u cti o ns f or t he St u d y Partici pa nts  ....................................... 9 1  
1 2. 2.  
D ose Re d ucti o n a n d S u p p orti ve Care G ui deli nes  .................................. 9 1  
1 2. 2. 1.  
D ose M o dificati o ns a n d D ose Dela y  ...................................................... 9 1  
1 2. 2. 2.  
D ose Re d ucti o n f or Decrease d Gl o mer ular Filtrati o n Rate ( G F R)  ........ 9 7  
1 2. 2. 3.  
D ose A dj ust me nt i n t he Setti n g of I nfecti o n  .......................................... 9 7  
1 2. 2. 4.  
C o n diti o ns N ot Re q uiri n g D os e Re d ucti o n  ............................................ 9 7  
1 2. 2. 4. 1.  
Misse d or V o mite d D oses  ....................................................................... 9 8  
1 2. 2. 5.  
S u p p orti ve Care a n d C o n c o mita nt Treat me nts  ....................................... 9 8  
1 2. 2. 5. 1.  
Re q uire d Pr o p h yl actic T hera p y wit h 5 -H T 3 A nta g o nists  ...................... 9 8  
1 2. 2. 5. 2.  
S u p p orti ve Care  ...................................................................................... 9 8  
1 2. 2. 5. 3.  
C o nc o mita nt Me dicati o n a n d Treat me nt  ................................................ 9 9  
1 2. 3.  
Restricti o ns a n d Preca uti o ns  ................................................................. 1 0 1  
1 2. 4.  
Pr o hi bite d Me dicati o n  .......................................................................... 1 0 1  
1 2. 5.  
St u d y Treat me nt St ora ge a n d Acc o u nt a bilit y  ....................................... 1 0 1  
1 2. 5. 1.  
Dr u g S u p pl y a n d St ora ge  ...................................................................... 1 0 1  
1 2. 5. 2.  
St u d y Treat me nt Acc o u nta bilit y  ........................................................... 1 0 2  
1 2. 5. 3.  
Dis p osal a n d Destr ucti o n  ...................................................................... 1 0 2  
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Karyopharm Therapeutics Inc. 
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21 May 2020
 
 
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12.6. 
Treatment Compliance .......................................................................... 102 
13. 
SAFETY DEFINITIONS, RECORDING, AND REPORTING .......... 103 
13.1. 
Adverse Events ..................................................................................... 103 
13.1.1. 
Definitions ............................................................................................ 103 
13.1.2. 
Recording of Adverse Events ............................................................... 103 
13.1.2.1. 
Laboratory Test Abnormalities ............................................................. 104 
13.1.2.2. 
Other Adverse Events ........................................................................... 104 
13.1.3. 
Adverse Event Severity ........................................................................ 105 
13.1.4. 
Adverse Event Causality ....................................................................... 105 
13.2. 
Serious Adverse Events ........................................................................ 105 
13.2.1. 
Recording of Serious Adverse Events .................................................. 106 
13.2.2. 
Reporting of Serious Adverse Events ................................................... 106 
13.2.3. 
Suspected Unexpected Serious Adverse Reactions .............................. 107 
13.3. 
Procedures for Handling Special Situations ......................................... 107 
13.3.1. 
Pregnancy and Breastfeeding ............................................................... 107 
13.3.2. 
Overdose, Abuse, Misuse, Medication Errors, and Occupational 
Exposure ............................................................................................... 109 
13.3.2.1. 
Overdose ............................................................................................... 109 
13.3.2.2. 
Abuse, Misuse, or Medication Error ..................................................... 109 
13.3.2.3. 
Occupational Exposure ......................................................................... 109 
14. 
STATISTICAL METHODS ................................................................. 111 
14.1. 
General Considerations ......................................................................... 111 
14.1.1. 
Determination of Sample Size .............................................................. 111 
14.1.1.1. 
Determination of Sample Size for Phase 2 ........................................... 111 
14.1.1.2. 
Determination of Sample Size for Phase 3 ........................................... 112 
14.1.2. 
Blinding and Randomization ................................................................ 113 
14.2. 
Analysis Population .............................................................................. 113 
14.2.1. 
Intent-to-Treat Population .................................................................... 113 
14.2.2. 
Per-Protocol Population ........................................................................ 113 
14.2.3. 
Safety Population .................................................................................. 113 
14.3. 
Data Analysis and Presentation ............................................................ 113 
14.3.1. 
Disposition of Patients .......................................................................... 113 
14.3.2. 
Demographic Characteristics ................................................................ 114 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 2 8  
1 4. 3. 3.  
Baseli ne C haracteristics a n d Me dical Hist or y  ...................................... 1 1 4  
1 4. 3. 4.  
Efficac y A nal ysis  .................................................................................. 1 1 4  
1 4. 3. 4. 1.  
Efficac y A nal ysis f or P h ase 2  ............................................................... 1 1 4  
1 4. 3. 4. 2.  
Efficac y A nal ysis f or P h ase 3  ............................................................... 1 1 5  
1 4. 3 . 6. 
Safet y A nal ysis  ..................................................................................... 1 1 7  
1 4. 3. 6. 1.  
A d verse E v e nts  ..................................................................................... 1 1 8  
1 4. 3. 6. 2.  
La b orat or y D ata  .................................................................................... 1 1 8  
1 4. 3. 6 . 3. 
Vital Si g ns a n d P h ysic al E x a mi nati o ns  ................................................ 1 1 9  
1 4. 3. 6. 4.  
C o nc o mita nt Me dicati o ns  ..................................................................... 1 1 9  
1 4. 3. 7.  
Pr oce d ures f or H a n dli n g Missi n g Data  ................................................. 1 1 9  
1 4. 4.  
C ha n ges i n t he C o n d uct of t he St u d y or Pla n ne d A nal ysis  .................. 1 1 9  
1 4. 5.  
Cli nical St u d y Re p orts  .......................................................................... 1 1 9  
1 5.  
D A T A C O L L E C TI O N A N D M A N A G E M E N T  .................................. 1 2 0  
1 5. 1.  
Data C o nfi de ntialit y  .............................................................................. 1 2 0  
1 5. 2.  
Site M o nit ori n g  ..................................................................................... 1 2 0  
1 5. 3.  
Data C ollecti o n  ..................................................................................... 1 2 1  
1 5. 4.  
Data base M a na ge me nt a n d Q ualit y C o ntr ol  ......................................... 1 2 1  
1 6.  
E T HI C A L A N D A D MI NI S T R A TI V E O B LI G A TI O N S  .................... 1 2 2  
1 6. 1.  
Re g ulat or y a n d Et hical C o m plia nce  ..................................................... 1 2 2  
1 6. 2.  
Res p o nsi bilities of t he I n vesti gat or a n d G o o d Cli nical Practice  .......... 1 2 2  
1 6. 3.  
I nstit uti o nal Re vie w B oar ds/I n d e pe n de nt Et hics C o m mittees ............. 1 2 2  
1 6. 4.  
I nf or me d C o nse nt ................................................................................. 1 2 2  
1 6. 5.  
Patie nt C o nfi de ntialit y a n d Discl os ure  ................................................. 1 2 3  
1 6. 5. 1.  
St u d y D oc u me ntati o n, R ec or d Kee pi n g a n d Ret e nti o n of D oc u me nts  1 2 3  
1 6. 6.  
P u blicati o n of St u d y Pr ot oc ol a n d Res ults  ........................................... 1 2 3  
1 6. 7.  
Disc o nti n uati o n of t he St u d y  ................................................................ 1 2 4  
1 6. 7. 1.  
A u dits a n d I ns p ecti o ns  .......................................................................... 1 2 4  
1 6. 8.  
Pr ot oc ol A d here n ce  .............................................................................. 1 2 4  
1 6. 9.  
A m e n d me nts t o t he Pr ot oc ol  ................................................................ 1 2 4  
1 7.  
R E F E R E N C E S  ..................................................................................... 1 2 5  
1 8.  
A P P E N DI C E S  ...................................................................................... 1 2 9  
A p pe n di x 1  W orl d H ealt h Or ga niz ati o n ( W H O) T u m or Res p o nse Criteria  ............ 1 3 0  
C CI


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
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Appendix 2    RECIST Version 1.1 ............................................................................. 132 
Appendix 3   Eastern Cooperative Oncology Group (ECOG) Performance Status Scale 
 Assessment ........................................................................................... 135 
Appendix 4    Glutathione (GSH)-, S-Adenosylmethionine (SAM)-, OR N-
 Acetylcysteine (NAC)-Containing Products (Representative List) ...... 136 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 3 0  
LI S T O F T A B L E S  
Ta ble  1:  
Sc he d ule of Assess me nts a n d St u d y Acti vities: Bli n de d P hase 2 a n d 
P hase 3  ...................................................................................................... 8  
Ta ble  2:  
Sc he d ule of Assess me nts a n d St u d y Acti vities: O p e n -La b el Seli ne x or  . 1 5  
Ta ble  3:  
Effect of X P O 1 I n hi biti o n o n O nc o ge nic a n d I nfla m mat or y Pat h wa ys  . 3 9  
Ta ble  8:  
Pre -s pecifi e d D ose/ Sc he d ule M o dificati o ns f or A d verse E ve nts Relat e d 
t o Seli ne x or/ Place b o Treat me nt .............................................................. 9 3  
Ta ble  9:  
S u p p orti ve Care a n d D os e A dj ust me nt G ui deli nes f or Selecte d A d verse 
E ve nts  ..................................................................................................... 9 4  
 
 
LI S T O F FI G U R E S  
Fi g ure  1:  
St u d y Fl o w C hart  .................................................................................... 1 9  
Fi g ure  2:  
Dis p ositi o n of Patie nts W h o Ha ve P D Per R E CI S T v. 1. 1 D uri n g 
Bli n de d St u d y Treat me nt a n d/ or W h o Disc o nti n ue Bli n de d St u d y 
Treat me nt  ................................................................................................ 2 0  
Fi g ure 3:  
Dis p ositi o n of Patie nts Recei vi n g Bli n de d St u d y Treat me nt at t he Ti me 
of t he Pri mar y P F S A nal ysis at t he E n d of P has e 3  ................................ 2 1  
 
 
C CI
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 3 1  
LI S T O F A B B R E VI A TI O N S  
A b bre vi ati o n  
Defi niti o n  
A E  
a d verse e ve nt  
A E SI  
a d verse e ve nt of s p ecial i nterest  
A L T  
ala ni ne a mi n otra nsferas e  ( S G P T) 
A M L  
ac ute m yel oi d le u ke mia  
A N C  
a bs ol ute ne utr o p hil c o u nt  
a P T T 
acti vate d partial t hr o m b o plasti n ti me  
A S T  
as partate a mi n otra nsferas e  ( S G O T) 
A U C last 
area u n d er t he c ur ve, first -last meas ure me nt 
B S A  
b o d y s urface area  
B U N  
bl o o d urea nitr o ge n  
C  
de grees Ce nti gra de  
C F R  
C o de of Fe d eral Re g ul ati o ns  
C H W  
C ui, H u n g, a n d Wa n g  
c m 
ce nti meter  
C ma x  
ma xi m u m plas ma  c o nce ntrati o n  
C M H  
C oc hra n -Ma nt el -Hae nzel  
C R  
c o m plete res p o nse  
C T  
c o m p ute d  t o m o gra p h y 
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
C P G O  
Cli nical Practice G ui deli nes i n O nc ol o g y  
D D L S  
de differe ntiate d li p osarc o ma  
D L T  
d ose li miti n g t o xicit y  
D N A  
de o x yri b o n ucleic aci d  
D O R  
d urati o n of res p o ns e  
D S M B  
Data Safet y M o nit ori n g B oar d  
E C G  
electr ocar di o gra m  
e C R F 
electr o nic case re p ort f or m  
E D C  
Electr o nic D ata Ca pt ure  
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
E O R T C  
E ur o pea n Or ga nizati o n f or Researc h a n d Treat me nt of Ca ncer  
E o S  
e n d of st u d y 
E Q -5 D -5 L  
E ur o Q o L Gr o u p Healt h Q uesti o n naire   
F %  
oral bi oa vaila bilit y  
C CI


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
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Page 32 
Abbreviation 
Definition 
°F 
degrees Fahrenheit 
FDA 
Food and Drug Administration 
FDG 
18F‐fluorodeoxyglucose 
GCP 
good clinical practice 
G-CSF 
granulocyte colony-stimulating factor 
GI 
gastrointestinal 
GMI 
growth modulation index 
GSH 
glutathione 
hCG 
human chorionic gonadotropin 
HIV 
human immunodeficiency virus 
HPV 
human papilloma virus 
HR 
hazard ratio 
hr 
hour 
5-HT3 
serotonin receptor subtype 
IEC 
independent ethics committee 
IC50 
inhibitory concentration, 50% (half maximal inhibitory concentration) 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
HPLC/MS-MS 
high performance liquid chromatography/ tandem mass spectrometry  
INR 
international normalized ratio 
IRB 
institutional review board 
ITT 
intent-to-treat 
kg 
kilogram 
LD 
longest diameter 
LDH 
lactate dehydrogenase 
LMS 
leiomyosarcoma 
m2 
square meters 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
min 
minute 
mL 
milliliter 
MLS 
myxoid/round cell liposarcoma 
MRI 
magnetic resonance imaging 
mRNA 
messenger ribonucleic acid 
MTD 
maximum tolerated dose 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 3 3  
A b bre vi ati o n  
Defi niti o n  
N A C  
N -acet yl c ystei ne  
N C C N  
Nati o nal C o m pre he nsi ve Ca ncer Net w or k  
N CI  
Nati o nal Ca ncer I nstit ute  
O R R  
o verall res p o ns e rate ( C R + P R)  
O S  
o verall s ur vi val  
O S 1 2  
o verall s ur vi val at least 1 2 m o nt hs  
P D  
pr o gressi ve dise ase  
P E T  
p ositr o n e missi o n t o m o gra p h y  
P F S  
pr o gressi o n -free s ur vi val 
P K  
p har mac o ki netic  
P P  
p er-pr ot oc ol  
P R  
partial res p o nse  
p R B  
reti n o blast o ma pr otei n 
P T  
pr ot hr o m bi n ti me  
Q L Q -C 3 0  
q ualit y of life q u esti o n naire -C 3 0  
Q o L  
q ualit y of life  
R B C  
re d bl o o d cell 
R E CI S T  
Res p o nse E val uati o n Criteria i n S oli d T u m ors  
R N A  
ri b o n ucleic aci d 
S A E  
seri o us a d verse e v e nt 
S A M  
S -a de n os yl m et hi o ni ne  
S D  
sta ble disease 
SI N E  
selecti ve i n hi bit or of n uclear e x p ort 
S O C  
s yste m or ga n class ( wit hi n A E c o nte xt) 
T -A L L  
T -cell ac ute l y m p h o c yti c le u ke mia  
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
T K  
t o xic o ki netic 
T L S  
t u m or l ysis s y n dr o me 
tma x  
ti me t o pea k plas ma c o nce ntrati o n 
T R A E  
treat me nt-relate d a d v erse e ve nt 
C CI
C CI
C CI


Selinexor (KPT-330)  
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
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Page 34 
Abbreviation 
Definition 
TSPs 
tumor suppressor proteins 
TTP 
time to progression 
ULN 
upper limit of normal 
WBC 
white blood cell 
WDLS 
well-differentiated liposarcoma 
wk 
week 
WHO 
World Health Organization 
XPO1 
exportin 1 


Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
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Page 35 
1. 
OVERVIEW 
The nuclear export of most tumor suppressor proteins (TSPs) and other growth modulators 
inactivates their anti-cancer and regulatory functions. The vast majority of TSPs are exported 
from the nucleus exclusively by exportin 1 (XPO1, also called CRM1). Selinexor (KPT-330) 
is an orally bioavailable, selective inhibitor of nuclear export (SINE) that specifically blocks 
XPO1, leading to the nuclear accumulation and re-activation of TSPs and other growth 
modulators. The reactivation of multiple TSPs through inhibition of a non-redundant, single 
protein represents a novel approach to the treatment of neoplastic diseases including those 
with multiple genomic alterations and resistance mechanisms. 
Liposarcomas are among the most frequent type of soft tissue sarcoma, accounting for 
approximately 15-20% of all soft tissue sarcomas, and are most often located in the lower 
extremities or retroperitoneum. Liposarcomas are classified into three main biologic groups: 
well-differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS), 
myxoid/round-cell liposarcoma (MLS), and pleiomorphic liposarcoma. These subtypes range 
from WDLS, which tends to be slow-growing, to DDLS and MLS, which are more 
aggressive and have greater metastatic potential. While surgery is the primary therapy for 
localized liposarcomas, there remains a need for additional therapeutic options, to treat 
advanced, recurrent, or metastatic liposarcomas. 
This Phase 2-3, randomized, double-blind, placebo-controlled study will consist of a Phase 2 
portion to compare progression-free survival (PFS) obtained with selinexor versus placebo, 
to adjust PFS assumptions and sample size for Phase 3, followed by a Phase 3 portion to 
assess whether the oral, single-agent selinexor can improve PFS (versus placebo) rates in 
patients with liposarcoma. 
 
 


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Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
Version 9.0 
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Page 36 
2. 
LIPOSARCOMA 
Soft tissue sarcomas are a group of heterogeneous malignancies with over 50 histological 
types with diverse biological behavior and often unique genetics. One of the most common 
subtypes is liposarcoma, which represents 24% of extremity sarcomas and 45% of 
retroperitoneal soft tissue sarcomas (Crago 2011). Liposarcomas are malignant mesenchymal 
tumors and are classified into three main biologic groups: (a) WDLS and DDLS, (b) MLS, 
and (c) pleiomorphic liposarcoma (Dickson 2013). 
WDLS comprise 40%–45% of all liposarcomas and is classified as a low-grade neoplasm 
that is rarely metastatic and occurs most often in the retroperitoneum and limbs. WDLS 
malignancies have a tendency to recur locally (Conyers 2011). WDLS/DDLS are considered 
to be a biphasic disease: DDLS represents progression from low-grade to high-grade 
nonlipogenic morphology within a WDLS. In contrast to WDLS, DDLS is more aggressive 
with a metastatic rate of 10%–20% and overall mortality of 50%–75% (Conyers 2011). 
Amplification of several oncogenes is associated with liposarcoma. MDM2 is the most 
frequent amplification in WDLS/DDLS (close to 100%) while CDK4 is amplified in over 
90% of cases (Dei Tos 2000, Binh 2005, Nakayama 1995). MDM2 is involved in the 
destruction of the tumor suppressor protein p53 and CDK4 enhances progression through the 
G1 cell cycle checkpoint by inactivating the tumor suppressor protein retinoblastoma (pRB). 
Thus, co-amplification of MDM2 and CDK4 proteins may result in proliferation by blocking 
cell cycle arrest and apoptosis through combined effects upon the tumor suppressor p53 and 
the cell cycle (Conyers 2011). MLS is characterized by a translocation that results in the 
FUS-CHOP gene fusion that is present in over 95% of cases (Antonescu 2001, Crozat 1993). 
Receptor tyrosine kinases, particularly signaling through the PI3K/Akt pathway, appear to be 
involved in MLS oncogenesis (Conyers 2011).  
Surgery is the primary treatment for localized liposarcoma, but approximately 40% of 
patients will eventually die from advanced disease (Gobble 2011). Advanced unresectable 
liposarcoma is relatively resistant to radiotherapy and chemotherapy, providing few options 
for these patients (Dickson 2013). Despite minimal responsiveness, most patients with 
liposarcoma currently receive anthracyclines and/or an alkylating agent. Olaratumab in 
combination with an anthracycline was granted accelerated approval in soft tissue sarcomas 
including liposarcoma based on an improvement in overall survival (OS) compared to 
doxorubicin alone. 
Additional chemotherapeutic agents have recently shown PFS or OS benefits in randomized 
studies against the alkylating agent dacarbazine. In a recent Phase 3 study (Study SAR-3007) 
in patients with liposarcoma and leiomyosarcoma (LMS), trabectedin (Yondelis®) had a 
statistically significant reduction in the risk of progressive disease (PD), with a median PFS 
of 4.2 months versus 1.5 months with dacarbazine. There was no statistically significant 
difference in OS between the two arms. In a separate Phase 3 study, 452 patients with 
advanced soft tissue sarcoma were randomized to receive eribulin or dacarbazine. Treatment 
with eribulin (Halaven®) improved OS by 7.2 months compared with dacarbazine in patients 
with advanced LMS or liposarcoma.  
Selinexor may represent a non-chemotherapy option for patients with liposarcoma. Because 
of the growth characteristics of liposarcoma, progression following selinexor or placebo in 


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the current study can be followed with the use of an anthracyline (eg, olaratumab plus 
doxorubicin), an alkylating agent, trabectedin, eribulin, or an experimental agent. Moreover, 
the study design (see Figure 1, Figure 2, and Figure 3) allows crossover from placebo to 
selinexor in order to provide patients with access to this experimental non-chemotherapeutic 
agent. 


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3. 
NUCLEAR EXPORT 
3.1. 
Inactivation of Tumor Suppressor Proteins (TSPs) by Nuclear 
Export 
Many important TSPs have been identified in cancer pathogenesis, including p53, p73, 
FOXO1 and 3a, IκB, BRCA1 and 2, APC, PP2A, and pRB (Turner 2012). TSPs mediate 
tumor suppression pathways via various functions including recognition of cellular 
(deoxyribonucleic acid [DNA]) damage, arrest of the cell cycle until repairs can be made, 
and induction of apoptosis in cells that have substantial DNA damage repair (Brown 2011).  
The tumor-suppressing and anti-cancer activity of these proteins requires their presence in 
the nucleus. Conversely, export out of the nucleus can inactivate the abilities of TSPs to 
identify DNA damage and regulate cellular processes (Xu 2010). Cancer cells exploit normal 
nuclear export to inactivate TSPs and evade normal DNA-damage controls as well as anti-
neoplastic therapy. The nuclear import (following synthesis on cytoplasmic ribosomes) and 
nuclear export of TSPs require specific shuttle proteins in order to traverse the nuclear 
envelope through the nuclear pore complexes (NPC) (Turner 2012). Although there are seven 
known nuclear export shuttle proteins (Exportins 1 – 7), exportin 1 (XPO1, also called 
CRM1) is the only known exportin protein for the vast majority of TSPs.  
3.2. 
Inhibition of XPO1 in Human Cancer 
Based on the postulated role of XPO1 in driving malignancy and chemotherapy resistance, 
XPO1 is promising as an oncologic therapeutic target (Turner 2012). XPO1 blockade causes 
the transient nuclear retention of TSPs and other growth modulators, re-establishing their 
tumor-suppressing and growth regulating effects on cancer cells and potentially reversing 
mechanisms leading to chemotherapy resistance, with clear implications for future 
combination therapies (Lain 1999, Kau 2003, Turner 2008). 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 2007). In addition, the messenger 
ribonucleic acid (mRNA) cap-binding protein eIF4E requires XPO1 in order to exit the 
nucleus with its cargo mRNA proteins. The mRNAs coding for various short half-life 
oncoproteins such as c-MYC, MDM-2 and Cyclin D have m7-guanine caps and require 
eIF4E for nuclear export. XPO1 inhibition prevents the eIF4E-mediated mRNA nuclear 
export and, therefore, the translation of these proteins, leading to their down regulation 
providing additional anti-neoplastic activity.  
Because restoration of TSP activity and reduction in oncogenic signals are relevant to 
essentially any cancer, XPO1 inhibition is expected to have activity against liposarcoma and 
many other malignancies (Table 3). 
 


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Table 3: 
Effect of XPO1 Inhibition on Oncogenic and Inflammatory Pathways 
Pathway Affected 
Effect of XPO1 Inhibition 
Reference 
p53 mutation 
p73 activation, p21 activation 
Ranganathan 2012 
p53 and/or pRB 
destabilization 
Nuclear p53 and pRB retention and 
stabilization 
Knapp 2009, Kau 
2003 
MDM2 activation 
MDM2 reduction, Nuclear p53 retention and 
activation 
Kojima 2013 and 
unpublished data 
Decreased pRB signaling 
Decreased pRB phosphorylation and increased 
nuclear pRB, p14/p16 elevation 
Fragomeni 2013 
XPO1 overexpression 
XPO1 reduction 
Walker 2013 
Bcr-Abl activation 
PP2A activation 
Walker 2013 
c-Myc amplification 
MYC protein reduction 
Schmidt 2013 
CDKN2A reduction 
p53/p73 stabilization 
Azmi 2013 
KIT activation 
KIT reduction 
Ranganathan 2012 
Bcl family overexpression 
Bcl family reduction 
Lapalombella 2012 
NF-B activation 
IB nuclear retention and activation 
Lapalombella 2012 
PIK3 or AKT activation 
FOXO1, -3, -4 activation 
Lapalombella 2012 
Survivin-cytoplasmic 
Survivin nuclear retention 
Altura 2003, Cheng 
2014 
 
 


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4. 
SELINEXOR (KPT-330) 
4.1. 
Introduction 
Several attempts to use XPO1 inhibitors as anti-cancer agents, based on the natural product 
leptomycin B, have failed due to secondary off-target effects of the drugs, which caused 
significant weight loss, diarrhea, and marked fatigue and asthenia in both animal studies and 
initial clinical studies (Mutka 2009, Newlands 1996, Roberts 1986). Modification of the 
structure of leptomycin B led to the development of parenterally administered compounds 
with improved pharmacokinetic (PK) properties and substantially improved therapeutic 
windows in preclinical studies (Mutka 2009), but clinical studies were never initiated. 
Selinexor is an oral, first in class, slowly reversible, potent SINE compound that specifically 
blocks XPO1. Selinexor restores many of the TSPs to the nucleus where they can carry out 
their normal functions. It is selectively cytotoxic for cells with genomic damage, ie, for 
tumor cells, both in vitro and in vivo. All cell types exposed to SINE compounds in vitro 
undergo G1 ± G2 cell cycle arrest, followed by a ‘genomic fidelity’ review. Cells with 
damaged genomes are induced to undergo apoptosis. Normal cells, with an intact genome, 
remain in transient, reversible cell cycle arrest until the export block is relieved. Selinexor 
and other SINE compounds are not intrinsically cytotoxic; rather, they can restore the highly 
effective tumor-suppressing pathways that lead to selective elimination of genomically 
damaged (ie, neoplastic) cells. Tumors of hematopoietic lineage are particularly susceptible 
to induction of apoptosis by XPO1 inhibition; normal hematopoietic cells and their functions 
are largely spared. Further details about the mechanism of action of selinexor are provided in 
the selinexor Investigator’s Brochure (IB). 
4.2. 
Preclinical Data  
4.2.1. 
Pharmacology 
Selinexor has shown potent pro-apoptotic activity with a median inhibitory concentration, 
50% (half maximal inhibitory concentration) (IC50) of 90 nM across a panel of 46 tumor cell 
lines representing a broad spectrum of tumor types. As noted above, selinexor had little effect 
on normal lymphocytes or other non-transformed cells, which correlated with the low 
incidence in animals of the typical adverse drug reactions seen with most anti-cancer 
therapies, such as significant myelosuppression, alopecia, mucositis and other gastrointestinal 
(GI) dysfunction. Selinexor and related SINE compounds have shown substantial efficacy, 
with dosing regimens that match those currently under investigation in humans, in a variety 
of mouse models of hematological and solid tumors. These include DLBCL, chronic 
lymphocytic leukemia, Mantle Cell Lymphoma, acute myeloid leukemia (AML), multiple 
myeloma, T-cell acute lymphocytic leukemia (T-ALL), neuroblastoma, melanoma and 
prostate, breast, lung and ovarian cancers. 
Selinexor has shown potent in vitro and in vivo anti-sarcoma activity. Selinexor induced cell 
death through apoptosis in sarcoma cell lines, with nanomolar inhibitory concentrations in 
11 of 12 lines. This cytotoxicity was associated with induction of p53 and p21 and reduction 


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in pRB expression. Furthermore, antitumor activity of selinexor was observed in two 
xenograft models of human liposarcoma (Nair 2013). Selinexor also completely suppressed 
tumor growth in human alveolar soft part sarcoma xenografts and this efficacy was 
associated with increased nuclear retention of p53 and p21 and reduced expression of 
survivin (Crochiere 2014).  
Results of a more recent study that investigated selinexor in vitro and in vivo using 17 cell 
lines and 9 sarcoma xenograft models confirm that selinexor has potent in vitro and in vivo 
activity against a wide variety of sarcoma models (Nakayama 2016). Furthermore, in 
liposarcoma cell lines with MDM2 and CDK4 amplification, selinexor induced G1-arrest and 
apoptosis irrespective of p53 expression or mutation and irrespective of pRB expression. 
Selinexor increased p53 and p21 expression at the protein but not ribonucleic acid (RNA) 
level, indicating a post-transcriptional effect.  
4.2.2. 
Pharmacokinetics and Toxicology 
The preclinical properties of selinexor were assessed in three species: mouse (CD1), rat 
(Sprague-Dawley), and monkey (cynomolgus). While PK studies were limited to male 
animals for all three species, toxicokinetic (TK) evaluations were conducted in both sexes for 
rats and monkeys as part of the selinexor toxicology studies, and no consistent sex-related 
differences were observed in either species. No accumulation was observed in any of the 
multi-dose toxicology studies with an every-other-day dosing regimen for selinexor. Overall, 
systemic exposure was generally dose-proportional in all TK studies that involved multiple 
dose levels. Higher maximum plasma concentration (Cmax) and earlier time to peak plasma 
concentration (tmax) values were observed in monkeys that were fasted versus fed prior to 
dosing. Systemic exposure (area under the curve from first to last plasma measurement, 
AUClast) to selinexor achieved with gelatin capsules was comparable to that achieved with 
oral suspension dosing, with lower Cmax and later tmax values observed with capsules. Results 
were not affected by the feeding status in monkeys. Oral bioavailability (F%) of selinexor 
was remarkably consistent among the three species with average values of 66.5%, 61.2%, 
and 67.5% in mice, rats, and monkeys, respectively.  
Nonclinical toxicology studies indicated that the major adverse drug reactions (dose limiting 
toxicities, DLTs) across all species are reduced appetite with anorexia-induced weight loss 
partially consistent with satiety induction. High calorie foods and glucocorticoids can 
mitigate weight loss in animals taking SINE XPO1 inhibitors.  
See the selinexor IB for more information. 
4.3. 
Clinical Experience 
Phase 1 and Phase 2 studies are being conducted in advanced solid tumors and hematological 
malignancies (see the selinexor IB for a summary of clinical experience). To date, more than 
2500 patients have received selinexor. Selinexor was generally well tolerated with supportive 
care given to prevent anorexia and fatigue. The aggressive use of appetite stimulants has 
reduced the severity of the anorexia and fatigue and improved the long-term tolerability of 
selinexor treatment. A maximum tolerated dose (MTD) of selinexor has been determined to 
be 65 mg/m2 twice weekly (Days 1 and 3) in Phase 1 solid tumor patients. The recommended 


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Versi o n 9. 0  
C o nfi de ntial  
P a ge 4 2  
P hase 2 d ose of seli ne x or f or use i n t his st u d y is 6 0 m g ( ~ 3 5  m g/ m 2) t wice wee kl y w hic h is 
bel o w t he M T D o bser ve d i n P hase 1 s oli d t u m or patie nts.  
C CI


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C o nfi de ntial  
P a ge 4 3  
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Versi o n 9. 0  
C o nfi de ntial  
P a ge 4 4  
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2 1  Ma y 2 0 2 0
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5. 
RATIONALE FOR THE STUDY 
Nonclinical data indicate that selinexor shows cytotoxic effects at nanomolar concentrations 
on a variety of sarcoma cell lines, whereas non-cancer cells show cytotoxic effects at much 
higher concentrations of selinexor. In murine xenograft models, three times a week oral 
treatment with selinexor inhibits the tumor growth of a variety of sarcomas including 
liposarcoma. 
Selinexor treatment resulted in SD in 30 of 52 (58%) evaluable patients with liposarcoma in 
the sarcoma Phase 1 study KCP-330-003 (Section 4.3.1). The most commonly reported 
TRAEs were nausea, fatigue, thrombocytopenia, anorexia, and hyponatremia, which were 
primarily Grade 1 or 2 (Section 4.3.4.1). Nausea and anorexia were well controlled with 
antinausea medications and appetite stimulants. These data further support the development 
of selinexor for the treatment of liposarcoma. 
5.1. 
Rationale for the Doses and the Dosing Regimen 
To date, more than 2500 patients with advanced cancers have received selinexor orally in 
clinical studies of selinexor (Phase 1, 2, and 3), and of these, 1672 adult patients in 
Karyopharm-sponsored studies were evaluated for safety as of 31 March 2018.  
Doses of 65 mg/m2 twice weekly have cleared DLT assessment and this is the MTD in the 
Phase 1 dose escalation study in advanced solid tumors, KCP-330-002. It should also be 
noted that while a dose of 70 mg/m2 cleared DLT in the AML arm of the Phase 1 study in 
patients with heavily pretreated hematological malignancies (KCP-330-001), escalating the 
dose beyond 70 mg/m2 twice weekly is prohibited in any study. 
In the present study, selinexor at a fixed oral dose of 60 mg (equivalent to ~35 mg/m2) or 
matching placebo will be given twice weekly (eg, Day 1 Monday and Day 3 Wednesday or 
Day 1 Tuesday and Day 3 Thursday or Day 1 Wednesday and Day 3 Friday) during 
Weeks 1-6 of each 6-week (42-day) cycle for a total of 12 doses per cycle.  
5.2. 
Rationale for Change in Response Criteria from WHO Response 
Criteria to RECIST v. 1.1 for the Primary Endpoint 
The Phase 2 primary PFS endpoint was evaluated using the WHO Response Criteria (as 
specified in protocol Versions ≤ 4). The WHO Response Criteria were used based on input 
from the Sponsor’s Liposarcoma Advisory Board. As RECIST Criteria have been 
traditionally used in sarcoma studies, including studies in liposarcoma, a prespecified 
analysis of PFS based on RECIST v. 1.1 was also conducted per protocol.  
The preplanned analysis of PFS based on the WHO Response Criteria was conducted and the 
results of this blinded analysis (blinded to Sponsor and sites) were provided to the Data 
Safety Monitoring Board (DSMB). 
In addition, a preliminary comparison of the PFS results by both WHO and RECIST v. 1.1 
Criteria (48 PD events by WHO and 28 PD events by RECIST v. 1.1) for all eligible patients 
whose treatment assignments were unblinded in the Phase 2 portion of the study was carried 
out to inform the selection of the most clinically relevant response criteria for the Phase 3 
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presented in Section 4.3.2. This analysis revealed that the WHO Response Criteria, which 
use a bi-dimensional evaluation of each lesion, resulted in the premature determination of 
clinically asymptomatic progression “events,” typically involving small lesions, while overall 
tumor burden was stable (as previously reported by other Investigators [Therasse 2000]). 
Based on these results, the DSMB recommended that the analysis of the primary endpoint 
should use RECIST v. 1.1 Criteria, rather than WHO Response Criteria. The lead 
Investigators for the study, as well as the Sponsor, agreed with this recommendation. 
Furthermore, the preliminary Phase 2 results using RECIST v. 1.1 Criteria were similar to 
those obtained in the Phase 1 study of selinexor in patients with sarcoma including 
liposarcoma (Gounder 2016). Based on these results and consistent with other studies in soft 
tissue sarcoma, RECIST v. 1.1 has been selected as the response criteria for the Phase 3 
primary PFS endpoint. 
5.3. 
Rationale for Change in the Primary Response Population 
Due to the change in the primary response criteria at the end of Phase 2, the primary response 
population will now consist only of Phase 3 patients who were assessed for PD throughout 
the study using RECIST v. 1.1 Criteria. A formal analysis of all 56 eligible Phase 2 patients 
will be performed separately.  


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Versi o n 9. 0  
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6.  
S T U D Y O B J E C TI V E S  
6. 1.  
P h ase 2  
6. 1. 1.  
P h ase 2 Pri m ar y O bjecti ve  
Assess a n d c o m pare P F S of patie nts wit h a d va nce d u nresect a ble D D L S treate d wit h 
seli ne x or (6 0 m g ) or place b o t wice wee kl y.  P F S is defi ne d as t he ti me fr o m date of 
ra n d o mizati o n u ntil t he first date of P D , per R es p o nse E val uati o n Criteria i n S oli d T u m ors 
( R E CI S T) v. 1. 1  (Eise n h a uer 2 0 0 9 ), or b y deat h d ue t o a n y ca us e.  
6. 1. 2.  
P h ase 2 Sec o n d ar y O bjecti ves  
•  C o m pare ti me t o pr o gressi o n (T T P ) o n st u d y treat me nt , per R E CI S T  v. 1. 1 , wit h T T P  
o n t he patie nt’s last pri or s yste mic t hera p y.  
•  Deter mi ne  t he o v erall res p o nse rate ( O R R: C R + P R), s u p p orte d b y d urati o n of 
res p o nse ( D O R). Res p o nses will be defi ne d b y R E CI S T  v. 1. 1 .  
•  Assess c ha n ges at 6 wee ks i n t u m or gl uc ose meta b oli s m, de nsit y, a n d size usi n g 
1 8F -fl u or o de o x y gl u c ose-p ositr o n e missi o n t o m o gra p h y ( F D G -P E T) a n d c o m p ute d 
t o m o gra p h y (C T ) ( dia g n ostic). 
•  Assess safet y of eac h treat me nt ar m.  
6. 1. 3.  
P h ase 2 E x pl or at or y O bjecti ves  
C CI


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2 1  Ma y 2 0 2 0
Versi o n 9. 0  
C o nfi de ntial  
P a ge 4 9  
6. 2.  
P h ase 3  
6. 2. 1.  
P h ase 3 Pri m ar y O bjecti ve  
Assess a n d c o m pare P F S of patie nts wit h a d va nce d u nresect a ble D D L S treate d wit h 
seli nex or ( 6 0 m g) or pla ce b o t wice wee kl y. P F S is defi ne d as  t he ti me fr o m date of 
ra n d o mizati o n u ntil t he first date of P D, per R E CI S T  v.  1. 1, or deat h d ue t o a n y ca use. 
E val uati o n of t he ra di o gra p hic data f or t he P F S pri mar y e n d p oi nt will be base d o n data fr o m  
a sca n re vie w b y t he i n d e pe n de nt ce ntr al rea der (see a d diti o nal  details i n Secti o n  1 0. 5. 1 ).  
6. 2. 2.  
P h ase 3 Sec o n d ar y O bjecti ves  
•  Assess O S , meas ure d fr o m date of ra n d o mizati o n u ntil deat h d ue t o a n y ca use.  
•  C o m pare T T P  o n st u d y tr eat me nt , per R E CI S T  v. 1. 1 , wit h  T T P o n  t he patie nt’s last 
pri or s yste mic t h era p y.  
•  Assess Q u alit y of Life ( Q o L) a n d patie nt -re p ort e d o utc o mes as meas ure d b y t he 
E ur o pea n Or ga niz ati o n f or Researc h a n d Treat me nt of Ca ncer ( E O R T C) Q ualit y -of -
Lif e Q uesti o n nair e ( Q L Q -C 3 0) a n d t he E ur o Q o L Gr o u p Healt h  Q uesti o n naire 
( E Q-5 D -5 L).  
•  Deter mi ne t he O R R, s u p p orte d b y D O R. Res p o ns es will be defi ne d b y 
R E CI S T  v.  1. 1 .  
C CI


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2 1  Ma y 2 0 2 0
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 5 0  
•  Assess P F S acc or di n g t o t he I n v esti gat or bas e d o n cli nical a n d/ or ra di ol o gi c criteri a.  
•  Assess safet y of eac h treat me nt ar m.  
6. 2. 3.  
P h ase 3 E x pl or a t or y O bjecti ves 
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7. 
STUDY DESIGN 
7.1. 
Study Design Overview 
This is a Phase 2-3, multicenter, randomized, double-blind, placebo-controlled study of 
patients diagnosed with advanced, unresectable liposarcoma. Approximately 334 total 
patients will be randomized to study treatment (selinexor or placebo) as described below.  
Patients must provide written informed consent AND meet all the inclusion criteria and have 
none of the exclusion criteria, before any screening tests not routinely performed may be 
conducted. The study flow chart is shown in Figure 1 and the disposition of patients is shown 
in Figure 2 and Figure 3. 
Phase 2: 
• Fifty-seven patients were randomized to selinexor (60 mg) or placebo in a 1:1 
allocation.  
• Randomization was stratified based on the following stratification factors for patients 
enrolled under protocol Versions ≤ 4: number of prior systemic therapies (1 versus ≥ 2) 
and prior eribulin use (prior eribulin versus no prior eribulin).  
The preplanned analysis of PFS was performed and served as a guideline to inform the final 
design of the Phase 3 portion of the study. See Section 4.3.2 for the preliminary efficacy 
results for Phase 2. 
 
Phase 3:  
• Approximately 277 patients will be randomized to selinexor (60 mg) or placebo in a 
2:1 allocation (~185 selinexor, ~ 92 placebo).  
• Randomization will be stratified based on (a) prior eribulin use (prior eribulin versus 
no prior eribulin), (b) prior trabectedin (Yondelis®) use (prior trabectedin versus no 
prior trabectedin), and (c) the number of prior systemic therapies excluding eribulin 
and trabectedin (2 versus ≥ 3).  
An interim analysis was conducted at 108 PFS events (see Section 14.1.1.2.1). 
The Schedule of Assessments for Blinded Phase 2/Phase 3 Treatment and Open-label 
Selinexor are provided in Table 1 and Table 2, respectively. 
Study treatment (selinexor or matching placebo) will be given twice weekly on Day 1 and 
Day 3 during Weeks 1-6 of each six-week (42-day) cycle, without interruption between 
cycles. 
All radiographic responses will be determined by the central reader (see the Imaging Manual 
for more details). 
PD per RECIST v. 1.1. will be determined by the central reader. Details for continuation of 
study treatment following PD and the primary PFS analysis and follow-up after 
discontinuation of study treatment are provided in Section 7.2.  
Treatment will continue until one or more of the following occurs: 


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2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 5 2  
•  P D , as defi ne d b y R E CI S T v. 1. 1  (see e x ce pti o n f or patie nts w h o ma y deri v e be nefit 
fr o m c o nti n ue d treat me nt wit h seli ne x or  i n Secti o n  7. 2. 4 ) 
•  Cli nical pr o gressi o n, as d eter mi ne d b y t he I n v esti gat or i n c o ns ultati o n wit h t he 
S p o ns or (m ust be d oc u me nte d b y ra di o gra p hic i m a gi n g a n d assesse d b y t h e ce ntr al 
rea der) 
•  U nacce pta ble A Es or t o xicit y t hat ca n n ot be ma na ge d b y s u p p orti ve care  
•  St u d y treat me nt is disc o nti n ue d at t he discreti o n of t he I n v esti gat or (see Secti o n  1 1. 2 ) 
•  Patie nt wit h dra ws c o nse nt  
Patie nts will be f oll o we d f or s ur vi val ( Secti o n 9. 1. 8  a n d Secti o n  9. 2. 6 ) u ntil t he e n d of t he 
st u d y, wit h dra w al criteria are m et, or death.  
Patie nts will als o recei ve best s u p p orti ve care t o ma na ge t he m ai n a d verse dr u g reacti o ns of 
seli ne x or, w hic h are na us ea, a n ore xia, a n d fati g ue. 
I n or der t o mi ni miz e na usea, u nless c o ntr ai n dicate d, all patie nts m ust recei ve ser ot o ni n 
rece pt or s u bt y p e (5 -H T 3 ) a nta g o nists ( ie, o n da nsetr o n 8 m g  or e q ui vale nt) starti n g o n D a y  1, 
bef ore t h e first d ose of bli n de d st u d y treat me nt a n d c o nti n ue d, as nee d e d, 2 -3 ti mes dail y . I n 
t h ose patie nts i n w h o m a 5-H T 3 a nta g o nist is c o ntrai n dicate d, ola nza pi ne ( 5. 0  m g at be d ti me 
or 2. 5 m g t wic e dail y) is rec o m me n de d b ase d o n I n vesti gat or e x perie nce d uri n g P hase 1 
seli ne x or st u dies. A d diti o nal o pti o ns ca n be f o u n d i n t he Nati o nal C o m pre he nsi ve Ca ncer 
Net w or k ( N C C N) Cli nic al Practice G ui d eli nes i n O nc ol o g y ( C P G O) (N C C N C P G O ) f or 
a ntie mesis a n d a n ore xia/cac h e xia ( palliati ve care).  
A p pr o xi matel y 3 4  m o nt hs will be re q uire d t o c o m plete t he pri mar y P hase 3 P F S a nal ysis. 
T he P hase  3  accr ual peri o d be g an i m me diatel y aft er e nr oll me nt of t he P hase  2 p orti o n  was 
c o m plete d a n d will be a p pr o xi matel y 3 0  m o nt hs. T he pri mar y e n d p oi nt a n al ysis will be 
perf or me d a p pr o xi matel y 4  m o nt hs after e nr oll me nt of t he last patie nt, o nce 2 0 9 P F S  e ve nts 
ha ve occ urre d, at w hic h ti me all P hase 3 patie nt s will be e val ua bl e f or assess me nt of t he 
pri mar y e n d p oi nt.  
T he I n vesti gat or ma y re m o ve a patie nt fr o m st u d y treat me nt as des cri be d i n Secti o n  1 1 . T he 
I n v esti gat or m ust deter mi ne t he pri mar y reas o n f or a patie nt’s disc o nti n uati o n of st u d y 
treat me nt a n d rec or d t his i nf or mati o n o n t he electr o nic case re p ort f or m (e C R F). Patie nts 
w h o disc o nti n ue st u d y tr eat me nt are n ot eli gi ble t o re -i nitiate treat me nt at a later dat e. 
Patie nts ma y deci de t o disc o nti n ue st u d y treat me nt f or a n y reas o n.  Patie nts w h o deci de  t o 
disc o nti n ue st u d y treat me nt s h o ul d be e nc o ura ge d t o c o nti n ue i n t he st u d y s o t hat f oll o w -u p 
i nf or mati o n o n P D  a n d s ur vi val stat us ma y b e o btai ne d.  Patie nts w h o disc o nti n ue st u d y 
treat me nt b ut c o nti n ue f oll o w-u p will be f oll o we d f or a nti -ne o plastic t h era p y i nitiati o n a n d 
 e ver y 3 m o nt hs. T h ese patie nts will be i ncl u de d i n t he I T T a n alysis if t he y are i n 
P hase  3. H o we v er, patie nts ma y wit h dra w c o nse nt a n d decli ne f urt her partici pati o n i n t he 
st u d y at a n y ti me . 
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7.2. 
Study Treatment Following PD and the Primary PFS Analysis 
and Follow-up After Discontinuation of Study Treatment 
Patients should remain on blinded study treatment until the assessment of PD by the central 
reader. 
Prior to unblinding, the patient and the Investigator will be asked which study treatment 
(active [selinexor] or placebo) they believe the patient received during blinded study 
treatment. See Section 10.7.2. 
7.2.1. 
Study Treatment After Determination of PD by the Central Reader 
Treatment assignment for patients who have PD per RECIST v. 1.1 (Eisenhauer 2009) 
determined by the central reader while receiving blinded study treatment will be unblinded. 
Note: WHO Response Criteria were used for Phase 2 patients whose treatment assignments 
were available at the time of the preplanned Phase 2 analysis. 
Patients who have PD may proceed as follows: 
• Patients in the placebo arm may cross over to open-label selinexor (60 mg twice 
weekly).  
o After their first PD on open-label selinexor, patients will discontinue study 
treatment and be followed for survival, unless the Investigator, in consultation 
with the Sponsor, believes based on clinical judgement that the patient may derive 
benefit from continued treatment with selinexor (see Section 7.2.4). 
• Patients in the selinexor arm who have PD will discontinue blinded study treatment 
and be followed for survival, unless the Investigator, in consultation with the 
Sponsor, believes based on clinical judgement that the patient may derive benefit 
from continued treatment with selinexor (see Section 7.2.4). 
7.2.2. 
Follow-up for Patients Without PD Who Discontinue Study Treatment 
Treatment assignment for patients who do NOT have PD determined by the central reader 
will not be unblinded until the primary PFS analysis at the end of Phase 3.  
Patients who do NOT have PD determined by the central reader and/or who discontinue 
blinded study treatment may proceed as follows: 
• Patients should remain on blinded study treatment until the assessment of PD from 
the central reader is obtained.  
• Patients who discontinue blinded study treatment at the discretion of the Investigator 
for reasons other than PD will be followed for survival. These patients are not 
allowed to receive open-label selinexor (see Section 11.3.1 for unblinding 
exceptions). 
7.2.3. 
Study Treatment Following the Primary PFS Analysis 
Treatment assignments for all patients will be unblinded when the required number of PFS 
events for the primary PFS analysis at the end of Phase 3 have been obtained. 


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Patients who are on blinded study treatment at the time of the primary PFS analysis at the 
end of Phase 3 may proceed as follows: 
• Patients in the placebo arm may cross over to open-label selinexor. 
• Patients in the selinexor arm will continue selinexor but as open-label treatment. 
All patients who have PD while receiving open-label selinexor will discontinue selinexor and 
be followed for survival, unless the Investigator, in consultation with the Sponsor, believes 
based on clinical judgement that the patient may derive benefit from continued treatment 
with selinexor (see Section 7.2.4). 
7.2.4. 
Exception for Patients Who May Derive Benefit from Continued Treatment 
with Selinexor 
After their first PD (determined by the central reader) on selinexor (either blinded or 
open-label) the following patients may elect to continue selinexor as open-label treatment if 
the Investigator, in consultation with the Sponsor, believes based on clinical judgement that 
the patient may derive benefit from continued treatment with selinexor: 
• Patients randomized to the selinexor arm 
• Patients randomized to the placebo arm who crossed over to open-label selinexor 
• Patients randomized to the selinexor arm who continued selinexor as open-label 
treatment at the time of the primary PFS analysis 
Once these patients have a subsequent PD, they will discontinue open-label selinexor and be 
followed for survival. 
7.3. 
Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) will be set up to review the safety of 
selinexor and to review any SAEs that occur during the study. The DSMB will develop and 
follow a data and safety monitoring plan and charter. 
The DSMB will be composed of at least two oncologists (at least one of whom specializes in 
sarcoma) and a statistician. The DSMB will be provided with all reports of AEs including 
SAEs regardless of Investigator causality assessments.  
DSMB meetings will occur on a periodic basis in accordance with the DSMB charter.  
An independent unblinded statistician conducted the preplanned Phase 2 analysis, based upon 
calculated PFS by WHO Response Criteria and provided the results of this blinded analysis 
(blinded to Sponsor and sites) to the DSMB for review. In addition, a preliminary 
comparison of the PFS results by both WHO and RECIST v. 1.1 Criteria (48 PD events by 
WHO and 28 PD events by RECIST v. 1.1) for all eligible patients whose treatment 
assignments were unblinded in the Phase 2 portion of the study was carried out to inform the 
selection of the most clinically relevant response criteria for the Phase 3 portion of the study. 
Preliminary Phase 2 results, updated as of 11 August 2017, are presented in Section 4.3.2. 
Based on these results, the DSMB recommended that the analysis of the primary endpoint 
should use RECIST v. 1.1 Criteria, rather than WHO Response Criteria. 


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An independent statistician will produce unblinded Phase 3 results for the DSMB, conduct 
the interim analysis that is planned after 105 PFS events are observed, and provide the results 
of this blinded analysis to the DSMB for review. The Phase 3 interim analysis will be based 
upon PFS calculated by RECIST v. 1.1. Criteria and analyzed for treatment futility (non-
binding) or sample size adjustment. The Sponsor (except for key team members as specified 
to monitor the conduct of the study] and the sites (eg, Investigators, staff, and patients) will 
remain blinded to the Phase 3 interim analysis results.  
The chairperson of the DSMB will be provided with SAE reports, per the DSMB charter. 
The charter of the DSMB will specify that this committee is charged with providing periodic 
reports to Karyopharm that contain recommendations that include, but are not limited to, 
(a) continuation of the study (or proposed changes to the study), and (b) termination of the 
study. The charter will also describe a procedure for adjusting sample size, if needed.  
7.4. 
Stopping Rules 
The entire study or treatment of individual patients may be stopped under defined 
circumstances as outlined in Section 11: Discontinuation Criteria.  
Adverse Event Stopping Rules: 
The stopping rules in the previous version of the protocol have been revised based on the 
current selinexor safety profile and the decisions of the DSMB to continue the study without 
modifications. Stopping rules may be adjusted in the event of either the study re-opening to 
accrual or at any time during the conduct of the study and based on new information 
regarding the AE profile of selinexor. Accrual may be suspended due to unexpected AE 
findings that have not crossed a specified rule below. 
Accrual will be temporarily suspended if, at any time, an excessive death rate, attributed to 
study treatment, as determined by the DSMB is observed. 
7.5. 
Criteria for Evaluation 
Disease assessments at the date of surgical or radiotherapy intervention may be censored in 
patients receiving such care, since these patients are receiving non-protocol specified therapy 
(ie, intervention), which may impact endpoint(s). 
7.5.1. 
Primary Efficacy Endpoint 
• Progression-free survival (PFS), defined as the time from date of randomization until 
the first date of PD, per RECIST v. 1.1, or death due to any cause. Evaluation of the 
radiologic data for the primary PFS endpoint will be based on data from a scan 
review by the independent central reader.  


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7. 5. 2.  
Sec o n d ar y E n d p oi nts  
7. 5. 2. 1.  
Ke y Sec o n d ar y E n d p oi nts  
•  O S f or n o n -i nferi orit y, d efi ne d as t he ti me fr o m ra n d o mizati o n u ntil deat h d ue t o a n y 
ca use, f or all ra n d o mize d patie nts.   
•  O S f o r s u peri orit y, defi ne d as t he ti me fr o m ra n d o mizati o n u ntil deat h d ue t o a n y ca use, 
f or all ra n d o mize d patie nts.  
7. 5. 2. 2.  
Sec o n d ar y Effic ac y E n d p oi nts  
•  T T P, defi ne d as t he ti me fr o m ra n d o mizati o n t o date of P D or deat h d u e t o disease 
pr o gressi o n, w hic he v er is earlier, p er R E CI S T v. 1. 1. Patie nts w h o re mai n 
pr o gressi o n  free ( w het her t he y wit h dre w fr o m t he st u d y or reac he d t heir m a xi m u m 
f oll o w-u p) will be ce ns ore d at t he date of t heir last disease assess me nt.  
•  O R R , defi ne d as t he pr o p orti o n of patie nts w h o ac hie ve c o m plete res p o nse ( C R) or 
partial res p o nse ( P R), per R E CI S T  v. 1. 1 .  
•  D O R, defi ne d as t he ti me fr o m first occ urre nce of C R or P R u ntil t he first date of P D 
per R E CI S T  v. 1. 1  or deat h . 
•  T u m or gl uc os e meta b olis m, de nsit y , a n d size usi n g F D G -P E T ( P has e 2 o nl y) a n d C T 
( dia g n ostic) aft er 6 wee ks of treat me nt.  
•  P F S acc or di n g t o t he I n v esti gat or, d efi ne d  as t he ti me fr o m date of ra n d o mizati o n 
u ntil  t he first date of P D, per R E CI S T v. 1. 1, or deat h  d ue t o a n y ca use  as d efi ne d b y 
t he I n v esti gat or bas e d o n cli nical a n d/ or ra di ol o gi c criteri a.  
•  Ti me t o ne xt treat me nt ( T T N T) , defi n e d as t he d urati o n of ti me fr o m ra n d o mizati o n 
t o t he date of t he ne xt a nti -ca ncer t hera p y. 
7. 5. 3.  
Q o L E n d p oi nt  ( Sec o n d ar y E n d p oi nt) 
•  Q o L as meas ur e d b y t he E O R T C Q L Q -C 3 0 t otal sc ore a n d E ur o Q o L E Q 5 D 5 L 
cate g or y s c ores a n d t otal sc ore.  
7. 5. 4.  
S afet y E n d p oi nts  
Safet y a n d t olera bilit y will be e val uate d b y A E re p orts, p h ysic al e xa mi nati o n, Easter n 
C o o perati ve O nc ol o g y Gr o u p ( E C O G) Perf or ma nce Stat us, a n d la b orat or y e val uati o n s. T he 
C T C A E, v. 4. 0 3, will be use d f or gra di n g of A Es. I n v esti gat ors will pr o vi de assess me nt of 
ca usalit y f or all A Es as eit her relate d or n ot relate d t o st u d y treat me nt. A n i n de pe n de nt 
D S M B will re vie w st u d y safet y, i ncl u di n g a n y S A Es t hat occ ur (s ee  Sec ti o n 7. 3 ). 
7. 5. 5.  
E x pl or at or y E n d p oi nts  
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7. 6.  
Scree ni n g a n d Re gistr ati o n  
T he Scree ni n g p eri o d starts o nce a p atie nt has pr o vi de d writte n i nf or me d c o nse nt t o 
partici pate i n t he st u d y a n d e n ds o n t he da y of ra n d o mizati o n. 
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Key patient eligibility (inclusion/exclusion criteria) must be confirmed by the Sponsor for all 
patients participating in the study prior to randomization. 
A Patient Enrollment Form will be sent from the site to the Karyopharm for evaluation. Upon 
confirmation of eligibility, Karyopharm will return the signed form to the site. 
7.6.1. 
Study Patient Number 
Each patient in this study will be assigned a unique patient number and will keep this number 
for the duration of the study. Patient numbers will not be reassigned or reused for any reason. 
7.6.2. 
Rescreening 
Rescreening is permitted in this study. If a patient fails any of the inclusion or exclusion 
criteria, a patient may be rescreened after a suitable period of time (the exact length is 
dependent upon the reason for the screen failure) per the documented agreement of 
Karyopharm and the Investigator. Any patient who is rescreened must be reconsented and 
will retain the same patient number. A patient may only fail screening once. 
7.6.3. 
Screen Failures 
Patients who sign an informed consent but are not randomized for any reason will be 
considered a screen failure. The reason for not being randomized will be entered on the 
eCRF. The demographic information (including screening number, informed consent date, 
and Inclusion/Exclusion pages) must also be completed for screen failure patients. No other 
data will be collected for patients who are screen failures, unless the patient experiences a 
SAE during the screening phase (see Section 13.2.2 for SAE reporting details). 
These data will also be retained in the Investigator’s study files and can be printed by the site 
in log format at the end of the study. The primary analysis for this study will be an 
intent-to-treat (ITT) analysis, therefore, screen failure data will not be analyzed. 
7.6.4. 
Replacement of Patients 
Patients who fail screening may be replaced. 
Patients who withdraw from the study after randomization will not be replaced. 
7.7. 
Randomization to Blinded Study Treatment 
In Phase 2, patients were randomized to either selinexor (60 mg) or placebo in a 1:1 ratio. 
Randomization was stratified based on the following stratification factors for patients 
enrolled under protocol Versions ≤ 4: the number of prior systemic therapies (1 versus ≥ 2) 
and prior eribulin use (prior eribulin versus no prior eribulin). 
In Phase 3, patients will be randomized to selinexor or placebo in a 2:1 ratio. Randomization 
will be stratified based on (a) prior eribulin use (prior eribulin versus no prior eribulin), (b) 
prior trabectedin (Yondelis®) use (prior trabectedin versus no prior trabectedin), and (c) the 
number of prior systemic therapies excluding eribulin and trabectedin (2 versus ≥ 3). 
Specifically, randomization will be performed within each of the following 8 strata: 
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2. ≤ 2 prior systemic therapies without prior eribulin use but with prior trabectedin use
3. ≤ 2 prior systemic therapies with prior eribulin use but without prior trabectedin use
4. ≤ 2 prior systemic therapies with both prior eribulin use and prior trabectedin use
5. ≥ 3 prior systemic therapies without prior eribulin use or prior trabectedin use
6. ≥ 3 prior systemic therapies without prior eribulin use but with prior trabectedin use
7. ≥ 3 prior systemic therapies with prior eribulin use but without prior trabectedin use
8. ≥ 3 prior systemic therapies with both prior eribulin use and prior trabectedin use
Randomization will be performed by a centralized system after confirmation of patient 
eligibility by the Sponsor (see Section 7.7). 
Study treatment will be administered in a double-blinded manner until the analysis of the 
primary PFS endpoint at the end of Phase 3, with the following exceptions: 1) patients in the 
placebo arm who have PD while they are receiving blinded study treatment may cross over to 
open-label selinexor, or 2) patients in the selinexor arm who have PD but may derive benefit 
from continued treatment with selinexor may elect to continue selinexor, but as open-label 
treatment (see Section 7.2.4). 
7.8. 
Blinding Procedures 
All study staff will be blinded to the patient treatment assignments and study treatment will 
be administered in a blinded manner during blinded study treatment. To maintain the study 
blind, it is imperative that patient treatment assignments are not shared with the patients, their 
families, or any member of the study team, either at the study site or at Karyopharm until 
unblinding is permitted (See Section 11.3). 


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8. 
SELECTION OF PATIENTS 
8.1. 
Number of Patients 
Approximately 334 patients with advanced unresectable liposarcoma meeting all the 
eligibility criteria described below will be randomized to selinexor or placebo. In Phase 2, 
57 patients were randomized to selinexor (60 mg) or placebo in a 1:1 allocation. In Phase 3, 
approximately 277 patients will be randomized to selinexor (60 mg) or placebo in a 2:1 
allocation.  
8.2. 
Recruitment 
This multicenter study will be conducted at sites in North America and Europe; patients in 
Israel and/or Asia may also be included. 
8.3. 
Inclusion Criteria 
Patients eligible for inclusion in this study must meet all of the following criteria: 
1. Written informed consent in accordance with national, local, and institutional guidelines
obtained prior to any screening procedures
2. Must be willing and able to comply with the protocol
3. Patients ≥ 12 years of age (patients <18 years of age are permitted only in countries in
which adolescents have been approved by the national/local regulatory/ethical authority).
4. Patients with a body surface area (BSA) ≥ 1.2 m2 as calculated per Dubois 1916 or
Mosteller 1987.
5. Documented histologic evidence of DDLS at any time from initial diagnosis to
randomization AND current evidence of DDLS requiring treatment (documented
evidence of disease progression from the most recent treatment):
•
Documentation of histologic evidence of DDLS requires the following:
o
This information will be provided based on prior diagnostic testing and is
required for randomization.
o
Tissue (fresh or archival) will be provided for confirmatory histology at a
central laboratory but confirmatory results are not required prior to
randomization.
o
If archival tissue > 12 months old, the quality of the sample for confirmatory
histology must be confirmed by the site histopathologist prior to
randomization.
6. Must have measurable disease according to:
•
The bidimensional WHO Response Criteria (Miller 1981) (Phase 2 patients
only)
•
RECIST v. 1.1 (Eisenhauer 2009) (Phase 3 patients only)
7. Radiologic evidence of progressive disease (PD) within 6 months prior to randomization.
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be documented after the completion of the intervening therapy, with the exception of 
patients who discontinued most recent treatment after no more than 1 dose.  
8. Must have received at least 2 but no more than 5 prior systemic therapies for the 
treatment of liposarcoma. 
9. Patients should have recovered from all major surgery, radiation or other interventions 
≥ 21 days prior to randomization. Patients must have recovered from any clinically 
significant therapy-related toxicity to ≤ Grade 1 per CTCAE v. 4.03. Minor procedures, 
such as biopsies, dental work, or placement of a port or intravenous line for infusion, are 
permitted.  
10. If patients received any previous systemic therapy, the last dose must have been ≥21 days 
prior to randomization (or ≥5 half-lives of that drug [whichever is shorter]), with all 
clinically significant therapy-related toxicities having resolved to ≤ Grade 1 CTCAE 
v. 4.03. 
11. ECOG performance status ≤1 (Oken 1982) 
12. Adequate laboratory functional values: 
• Adequate hematopoietic function:  
o Absolute neutrophil count (ANC) ≥1500/mm3  
o Platelets ≥100,000/mm3 
o Hemoglobin (Hb) ≥9 g/dL  
o Transfusions, hematopoietic growth factors, and hematinics are NOT 
permitted during screening 
• Adequate hepatic function:  
o Bilirubin ≤1.5 x upper limit of normal (ULN) (except patients with Gilbert’s 
syndrome [hereditary indirect hyperbilirubinemia] who must have a total 
bilirubin of ≤3 x ULN) 
o Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine 
aminotransferase (ALT) <3.0 x ULN (except patients with liver involvement 
of their liposarcoma who must have an AST and ALT ≤5 x ULN).  
• Adequate renal function: Serum creatinine of ≤ 1.5 mg/dL or estimated creatinine 
clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 – 
Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft 
1976).  
13. Female patients of childbearing potential must have a negative serum pregnancy test at 
Screening. Female patients of childbearing potential and fertile male patients who are 
sexually active with a female of childbearing potential must agree to use highly effective 
contraception throughout the study and for 3 months following the last dose of study 
treatment. Highly effective methods of contraception are listed in Section 13.3.1. 
8.4. 
Exclusion Criteria 
Patients meeting any of the following exclusion criteria are not eligible to enroll in this study: 
1. Patients with liposarcoma of pure WDLS, myxoid/round cell or pleomorphic tumor 
histologic subtypes. 
2. Significant cardiovascular impairment, defined as: 


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a. Cardiac failure, New York Heart Association (NYHA) Class ≥ 3 according to the 
NYHA Functional Classification 
b. Unstable angina or myocardial infarction within 3 months of enrollment 
c. Serious and potentially life-threatening arrhythmia. 
3. Patients with known central nervous system metastases.  
4. Female patients who are pregnant or nursing. 
5. Prior malignancy that required treatment or has shown evidence of recurrence (except for 
non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 
years prior to randomization. Cancer treated with curative intent > 5 years prior to 
randomization and without evidence of recurrence is allowed.  
6. Known active hepatitis B infection, as defined by seropositivity for hepatitis B surface 
antigen (HBs Ag); or known  hepatitis C infection, as defined by seropositivity for 
hepatitis C antibody, with elevated liver aminotransferases (ie, above the levels specified 
in inclusion criterion #12) or any other evidence of active hepatitis. 
7. Known human immunodeficiency virus (HIV) infection. 
8. Any medical condition, such as an uncontrolled infection or uncontrolled diabetes 
mellitus (Type 2), which in the opinion of the Investigator would make study 
involvement unreasonably hazardous 
9. Psychiatric illness that would prevent the patient from giving informed consent or being 
compliant with the study procedures 
10. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI 
disease or GI dysfunction that could interfere with absorption of study treatment 
11. Inability or unwillingness to take supportive medications such as anti-nausea and anti-
anorexia agents as recommended by the NCCN CPGO for antiemesis and 
anorexia/cachexia (palliative care). 
12. Patients who had involuntary weight loss of ≥ 10% in the 3 months prior to 
randomization. 
13. Participation in an investigational anticancer study ≤ 21 days prior to randomization. 
14. A circulating lymphocyte count of >50,000/µL (for sites in France only)


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9. 
STUDY ACTIVITIES 
The assessments to be performed during blinded study treatment and treatment with 
open-label selinexor are listed in Section 9.1 and Section 9.2, respectively. 
Additional assessments, including the following, may be performed throughout the study if 
clinically indicated: 
• 
electrocardiograms (ECGs) 
• 
urinalysis 
• 
hematology 
• 
complete or limited serum chemistry 
• 
coagulation tests 
• 
pregnancy testing 
• 
nutritional consultation 
After discontinuation of study treatment, all patients will be followed for survival 
(Section 9.1.8 and Section 9.2.6). 
9.1. 
Description of Study Days: Blinded Treatment 
Please note: screening visits may be combined at site discretion, in which case all screening 
must be completed within 14 days prior to the start of study treatment. 
9.1.1. 
Visit 1 (within 21 days prior to C1 D1); Screening Visit 1  
The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved ICF 
must be signed and dated by the patient and witnessed (as required by the IRB/IEC) prior to 
the first study-specific measures. For adolescent patients (permitted only in countries in 
which adolescents have been approved by the national/local regulatory/ethical authority), a 
separate Assent Form must be signed by the patient at the time of informed consent. 
Procedures that are part of the clinical routine evaluations during the initial diagnostic work-
up of the patient may be performed before the ICF is signed and dated (ie, procedures that are 
not specific to the conduct of the study). A copy of the ICF must be given to the patient or to 
the person signing the form on behalf of the patient. The Investigator or designee must record 
in the medical records of the patient the date when the study ICF was signed. The name and 
role of the witness should also be documented. 
The following screening assessments must be completed within 21 days prior to C1 D1 
(except as noted), as specified in Table 1: Schedule of Assessments and Study Activities.  
The screening period starts once a patient has provided written informed consent to 
participate in the study and ends on the day of randomization.  
Rescreening is permitted in this study. See Section 7.6.2. 


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The study site should not repeat procedures completed as standard of care if they are within 
the screening window, and prior to signing the ICF. The data from these procedures are part 
of the medical history and may be used for study purposes. 
The following procedures are to be performed: 
• Sign written informed consent for blinded study treatment (note age on day consent is 
signed). Adolescent patients should also sign a written Assent Form 
• Review inclusion and exclusion criteria 
• Demography (year of birth, age, gender, race, and ethnicity [Hispanic origin]) 
• Complete medical history (Section 10.3) 
• Physical examination and vital signs (blood pressure, pulse, and body temperature) 
(Section 10.6.1.1) 
• Weight, height, and BSA (Section 10.6.1.2) 
• ECOG performance status assessment (Section 10.6.1.3) 
• 12-lead ECG (Section 10.6.1.4) 
• Urinalysis (Section 10.6.2.1) 
• Hematology (Section 10.6.2.1) 
• Complete serum chemistry (Section 10.6.2.1) 
• Coagulation tests (Section 10.6.2.1) 
• Tumor biopsy to provide tissue for confirmation of liposarcoma type by histology and 
presence of DDLS; the Investigator may omit this biopsy if appropriate archival 
(ie, of DDLS tissue) material is available. See Section 10.4. 
• For Phase 3 only: Imaging to evaluate site of disease and distant sites (abdomen, pelvis, 
chest) (within 21 days prior to the first dose of blinded study treatment). CT (preferred) 
or MRI scan for tumor measurement; the same imaging modality should be maintained 
throughout the study.  
• AEs and SAEs 
• Concomitant medications 
9.1.2. 
Visit 2 (within 14 days prior to C1 D1); Screening Visit 2 
Patients will be evaluated against study inclusion and exclusion criteria and safety 
assessments. All baseline/screening CT/magnetic resonance imaging (MRI)/ PET scans, 
diagnosis and assessment of progression/extent of liposarcoma, QoL questionnaires, and 
confirmation of patient eligibility must be completed within 14 days prior to C1 D1. 
The following procedures are to be performed: 
• For Phase 2 only: Imaging to evaluate site of disease and distant sites (abdomen, pelvis, 
chest) (within 14 days prior to the first dose of blinded study treatment). FDG-PET and 
CT (diagnostic) scan for tumor density and SUV. If FDG-PET is contraindicated, CT 


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
Versi o n 9. 0  
C o nfi de ntial  
P a ge 6 5  
( preferre d) or M RI sca n s h o ul d be use d i nstea d, s o t hat, f or a gi ve n patie nt, t he sa me 
i ma gi n g m o dalit y is mai ntai ne d t hr o u g h o ut t he st u d y. 
•
Dia g n osis a n d assess me nt of pr o gressi o n/e xte nt of li p osarc o ma ( R E CI S T v. 1. 1,  
A p pe n di x 2)
•
Q o L  q u esti o n naires ( E O R T C Q L Q -C 3 0 a n d E ur o Q o L E Q -5 D -5 L) ( wit hi n 1 4  da ys
pri or t o  C 1 D 1 ) ( Secti o n 1 0. 7. 1 )
•
Ser u m h u ma n c h ori o nic g o na d otr o pi n ( h C G) pre g na nc y test (fe males of c hil d beari n g
p ote ntial o nl y, wit hi n 3 da ys b ef ore t he first d ose of bli n de d st u d y treat me nt)
( Secti o n 1 0. 6. 2. 2 )
•
Eli gi bilit y c o nfir m ati o n b y t he S p o ns or (after scree ni n g pr oce d ures a n d bef ore
ra n d o mizati o n)
•
R a n d o mizati o n
•
A Es a n d S A Es
•
C o nc o mita nt me dicati o ns
9. 1. 3.  
Visits 3 -8 ( C ycle 1: D a ys 1, 8, 1 5, 2 2, 2 9 , a n d 3 6 [ ± 1 d a ys]); Ret ur n t o t he 
Cli nic  
T here are si x cli nic visits (ie, Da ys 1, 8, 1 5, 2 2, 2 9, a n d 3 6) d uri n g t he first si x -wee k c ycle 
( C ycl e 1). 
T he f oll o wi n g  st u d y ass ess me nts will be perf or me d  d uri n g C ycle 1 , as s pecifie d i n Ta ble  1 : 
•
P h ysical e x a mi nati o n a n d vital si g ns ( bl o o d press ure, p ulse, a n d b o d y te m perat ur e)
( Da ys 1, 8, 1 5, 2 2, 2 9, a n d 3 6) ( Secti o n 1 0. 6. 1. 1 )
•
Wei g ht ( Da ys 1, 8, 1 5, 2 2, 2 9, a n d 3 6) ( Secti o n  1 0. 6. 1. 2 )
•
E C O G perf or ma nce stat us assess me nt ( Da y 1  o nl y)  ( Secti o n 1 0. 6. 1. 3 )
•
1 2 -lea d E C G ( D a y 1 o nl y, 
)
( Secti o n 1 0. 6. 1. 4 )
•
Uri nal ysis ( Da y 1  o nl y ) ( Secti o n 1 0. 6. 2. 1 )
•
He mat ol o g y ( Da y 1 o nl y)  ( Secti o n 1 0. 6. 2. 1 )
•
C o m plete ser u m c he mistr y ( Da y 1 o nl y)  ( Secti o n 1 0. 6. 2. 1 )
•
Li mite d ser u m c h e mistr y  ( Da ys 8, 1 5, 2 2, 2 9, a n d 3 6) ( Secti o n 1 0. 6. 2. 1 )
•
C oa g ulati o n tests ( Da y 1 o nl y)  ( Secti o n 1 0. 6. 2. 1 )
•
T u m or bi o ps y, o nl y if s ufficie nt materi al was a v aila ble fr o m t he scree ni n g bi o ps y
(arc hi v al or fres h) f or  
 testi n g ( Da y 2 2 o nl y; ma y b e ta ke n C ycle 2 Da y 1, see
Secti o n  9. 1. 4 ). See Secti o n 1 0. 4  a n d Secti o n  1 0. 1 1. 3  f or bi o ps y d etails. N ote: T his
sec o n d bi o ps y (e g, eit her C ycle 1 Da y 2 2 or C ycle 2 Da y 1) s h o ul d n ot be c ollecte d
C CI
C CI


Seli ne x or ( K P T -3 3 0)  
 
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 6 6  
fr o m a d olesce nt/ pe diatric patie nts f or e x pl orat or y st u dies if t here a p p ears to be a 
p ote ntial f or seri o us ris k f or t he patie nt.  
•  
•  
•  N utri ti o nal c o ns ultati o n (s h o ul d occ ur o n Da y 1 b ef ore t h e first d ose of bli n de d st u d y 
treat me nt, or wit hi n t he Scree ni n g Peri o d). See Secti o n 1 0. 7. 3 . 
•  St u d y treat me nt: i n cli nic d osi n g a n d dis pe nsi n g of f or h o me use ( Da ys 1, 8, 1 5, 2 2, 
2 9, a n d 3 6)  
•  A Es a n d S A Es (t hr o u g h o ut t he c ycle) 
•  C o nc o mita nt me dicati o ns (t hr o u g h o ut t he c ycle)  
9. 1. 3. 1.  
P h o ne C all wit h P atie nt: C ycle 1 D a y 3 O nl y ( + 1 d a y)  
A p h o ne call will be ma d e t o t he patie nt t o e val uat e s u p p orti ve care me dicati o ns, 
c o nc o mita nt me dicati o ns, a n d A Es/ S A Es, a n d t o a dj ust s u p p orti ve care as a p pr o priate.  
9. 1. 4.  
Visits 9 -1 1 ( C ycle 2: D a ys 1, 1 5 , a n d 2 9 [ ± 2 d a ys]); Ret ur n t o t he Cli nic  
T here are t hr ee cli nic visits (ie, Da ys 1, 1 5, a n d 2 9) f or C ycle 2. 
T he f oll o wi n g st u d y ass ess me nts will be perf or me d d uri n g C ycle 2, as s pecifie d  i n Ta ble  1 . 
•  P h ysical e x a mi nati o n a n d vital si g ns ( bl o o d press ure, p ulse, a n d b o d y te m perat ur e) 
( Da ys 1, 1 5, a n d 2 9) ( Secti o n 1 0. 6. 1. 1 ) 
•  Wei g ht ( Da ys 1, 1 5, a n d 2 9) ( Secti o n  1 0. 6. 1. 2 ) 
•  Hei g ht  a n d B S A  ( Da y 1 o nl y) ( Secti o n 1 0. 6. 1. 2 ) 
•  E C O G perf or ma nce stat us assess me nt ( Da y 1 o nl y)  ( Secti o n 1 0. 6. 1. 3 ) 
•  1 2 -lea d E C G ( D a y 1 o nl y, 
) 
( Secti o n 1 0. 6. 1. 4 ) 
•  Uri nal ysis ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 )  
•  He mat ol o g y ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 ) 
•  C o m plete ser u m c he mistr y ( Da y 1 o nl y) ( Secti o n 1 0. 6. 2. 1 )  
•  Li mite d ser u m c h e mistr y ( Da ys 1 5 a n d 2 9 o nl y) ( Secti o n  1 0. 6. 2. 1 ) 
•  C oa g ulati o n tests ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 )  
•  Fe male patie nts of c hil d beari n g p ot e ntial o nl y: pre g na nc y test (ser u m h C G or hi g h 
se nsiti vit y uri ne) pri or t o d osi n g o n Da y 1 o nl y. A p ositi ve uri ne pre g n a nc y test will be 
c o nfir me d b y a s er u m pre g n a nc y test. ( Secti o n  1 0. 6. 2. 2 ) 
•  T u m or bi o ps y, o nl y if s ufficie nt materi al was a v aila ble fr o m t he scree ni n g bi o ps y 
(arc hi v al or fres h) f or  
 testi n g ( Da y 1 o nl y a n d o nl y if n ot o btai ne d at C ycl e 1 
Da y 2 2, see Secti o n  9. 1. 3 ). See Secti o n  1 0. 4 , a n d Secti o n  1 0. 1 1. 3  f or bi o ps y det ails. 
N ote: T his sec o n d bi o ps y ( e g, eit her C ycl e 1 Da y 2 2 or C ycl e 2 Da y 1) s h o ul d n ot be 
C CI
C CI
C CI
C CI


Seli ne x or ( K P T -3 3 0)  
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
Versi o n 9. 0  
C o nfi de ntial  
P a ge 6 7  
c ollecte d fr o m a d olesce nt/ pe diatric patie nts f or e x pl orat or y st u dies if t here a p pears t o 
be a p ote ntial f or s eri o us ris k f or t he patie nt.  
•
I ma gi n g t o e v al uate site of disease a n d dista nt sites (a b d o me n, pel vis, c hest)
o
P hase 2: F D G -P E T a n d C T  ( dia g n ostic) s ca n a p pr o xi matel y 6 w ee ks p ost -first
d ose ( ie, Da y 1 of C ycle 2). If F D G -P E T  is c o ntr ai n dicate d, C T  ( preferre d) or
M RI sca n  s h o ul d be use d i nstea d s o t hat, f or a gi v e n patie nt, t he sa me i ma gi n g
m o dalit y is mai ntai ne d t hr o u g h o ut t he st u d y.
o
P hase 3: C T ( preferre d) or M RI s ca n f or t u m or meas ure me nt a p pr o xi matel y
6  wee ks p ost -first d ose (ie, Da y 1 of C ycl e 2); t he sa me i ma gi n g m o dalit y
s h o ul d be mai ntai ne d t hr o u g h o ut t he st u d y
•
Assess me nt of pr o gressi o n/e xte nt of li p osarc o ma b y R E CI S T v. 1. 1  ( A p pe n di x 2) 
a p pr o xi matel y 6 wee ks after t he first d ose of bli n de d st u d y tr eat me nt ( ie, Da y 1 of 
C ycle 2), base d o n 6- wee k t u m or sca n.
•
Treat me nt assi g n me nt q u er y  of patie nts a n d I n vesti gat ors ( o nl y f or patie nts wit h P D ,
q uer y pri or t o u n bli n di n g ) ( Secti o n 1 0. 7. 2 ).
•
•
Q o L  q u esti o n naires ( E O R T C Q L Q-C 3 0 a n d E ur o Q o L E Q -5 D -5 L) ( Da y 1 o nl y,
pre d ose ) (Secti o n  1 0. 7. 1 )
•
St u d y treat me nt: i n cli nic d osi n g a n d dis pe nsi n g of f or h o me use ( Da ys 1, 1 5, a n d 2 9)
•
A Es  a n d S A Es  (t hr o u g h o ut t he c ycle)
•
C o nc o mita nt me dicati o ns  (t hr o u g h o ut t he c ycle)
9. 1. 4. 1.  
P h o ne C alls wit h P atie nt: C ycle 2 D a ys 1 0, 2 4 , a n d 3 8 ( + 1 d a y)  
A p h o ne call will be ma d e t o t he patie nt t o e val uat e s u p p orti ve care me dicati o ns, 
c o nc o mita nt me dicati o ns, a n d A Es/ S A Es, a n d t o a dj ust s u p p orti ve care as a p p r o priate. 
9. 1. 5.  
Visits ≥ 1 2 ( C ycles ≥ 3: D a ys 1 a n d 2 2 [ ± 2 d a ys]); Ret ur n t o t he Cli nic  
Patie nts e nr olle d i n t his st u d y ma y c o nti n ue fr o m c ycle t o c ycl e wit h o ut i nterr u pti o n.  
T he f oll o wi n g st u d y ass ess me nts will be perf or me d for C ycles  ≥ 3, as s pecifie d i n  Ta ble  1 . 
•
P h ysical e x a mi nati o n a n d vital si g ns ( bl o o d press ure, p ulse, a n d b o d y te m perat ur e)
( Da ys 1 a n d 2 2) ( Secti o n 1 0. 6. 1. 1 )
•
Wei g ht ( Da ys 1 a n d 2 2) ( Secti o n  1 0. 6. 1. 2 )
•
Hei g ht a n d B S A ( Da y 1 o nl y) ( Secti o n 1 0. 6. 1. 2 )
•
E C O G perf or ma nce stat us assess me nt ( Da y 1 o nl y) ( Secti o n 1 0. 6. 1. 3 )
•
Uri nal ysis ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 )
•
He mat ol o g y ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 )
•
C o m plete ser u m c he mistr y ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 )
•
Li mite d ser u m c h e mistr y ( Da y 2 2 o nl y) ( Secti o n  1 0. 6. 2. 1 )
•
C oa g ulati o n tests ( Da y 1 o nl y) ( Secti o n  1 0. 6. 2. 1 )
C CI


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Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
 
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• Female patients of childbearing potential only: pregnancy test (serum hCG or high 
sensitivity urine) prior to dosing on Day 1 only. A positive urine pregnancy test will be 
confirmed by a serum pregnancy test. (Section 10.6.2.2) 
• Imaging to evaluate site of disease and distant sites (abdomen, pelvis, chest) 
o Phases 2 and 3: CT (preferred) or MRI scan for tumor measurement 
approximately12, 18, and 24 weeks after start of study treatment (ie, Day 1 of 
Cycles 3, 4, and 5), and approximately every 12 weeks thereafter (ie, Day 1 of 
odd-numbered Cycles ≥ 7); the same imaging modality should be maintained 
throughout the study 
• Assessment of progression/extent of liposarcoma by RECIST v. 1.1 (2) when tumor 
(CT/MRI) scans are performed. Assessments are to be performed approximately 12, 
18 and 24 weeks after start of study treatment (ie, Day 1 of Cycles 3, 4 and 5), and 
approximately every 12 weeks thereafter (ie, Day 1 of odd-numbered- Cycles ≥ 7), 
based on tumor scans. 
• Treatment assignment query of patients and Investigators (only for patients with PD; 
query after PD but prior to unblinding) (Section 10.7.2). 
• QoL questionnaires (EORTC QLQ-C30 and EuroQoL EQ-5D-5L) (Day 1 only, 
predose) (Section 10.7.1) 
• Study treatment: in clinic dosing and dispensing of for home use (Days 1 and 22) 
• AEs and SAEs (throughout the cycles) 
• Concomitant medications (throughout the cycles) 
9.1.5.1. 
Phone Calls with Patient: Cycles ≥ 3 Days 10, 17, 31 and 38 (+ 1 day) 
A phone call will be made to the patient to evaluate supportive care medications, 
concomitant medications, and AEs/SAEs, and to adjust supportive care as appropriate. 
9.1.6. 
End of Blinded Treatment Visit; Return to the Clinic 
At the time a patient permanently discontinues blinded study treatment or has PD prior to 
unblinding of all patients at the end of Phase 3 (ie, when the required number of PFS events 
for the primary PFS analysis are observed), a visit should be scheduled as soon as possible 
(within 14 days), at which time all of the assessments listed for the End of Blinded Treatment 
(EoBT) Visit will be performed. Study procedures will be performed ≤ 14 days after the last 
dose of study treatment, as specified in Table 1. An EoBT CRF page will be completed, 
giving the date and reason for stopping the study treatment. Patients lost to follow-up should 
be recorded as such on the appropriate eCRF.  
For patients proceeding to open-label selinexor, the EoBT Visit will serve as the baseline for 
the open-label treatment phase. After the unblinding following the PFS analyses, patients in 
the selinexor arm who are continuing on selinexor but as open-label treatment must complete 
their EoBT Visit before their next scheduled selinexor dose. 
• Informed consent for open-label selinexor (only for patients proceeding to open-label 
selinexor) and Assent Form for adolescent patients (permitted only in countries in 


Selinexor (KPT-330) 
 
Karyopharm Therapeutics Inc. 
Clinical Study Protocol: KCP-330-020 
21 May 2020
 
 
 
Version 9.0 
Confidential 
Page 69 
which adolescents have been approved by the national/local regulatory/ethical 
authority) 
• Physical examination and vital signs (blood pressure, pulse, and body temperature) 
(Section 10.6.1.1) 
• Weight, height, and BSA (Section 10.6.1.2) 
• ECOG performance status assessment (Section 10.6.1.3) 
• 12-lead ECG (Section 10.6.1.4) 
• Urinalysis (Section 10.6.2.1)  
• Hematology (Section 10.6.2.1)  
• Complete serum chemistry (Section 10.6.2.1)  
• Coagulation tests (Section 10.6.2.1)  
• Serum hCG pregnancy test (females of childbearing potential only). Females of 
childbearing potential who are proceeding to open-label selinexor must have a 
negative serum hCG pregnancy test at the EoBT Visit (or within 3 days before the 
first dose of open-label selinexor). (Section 10.6.2.2) 
• Tumor biopsy for patients who were in the placebo arm and are crossing over to 
open-label selinexor only. If the patient has archival material (ie, of DDLS tissue) 
collected at Screening, Cycle 1 Day 22, or Cycle 2 Day 1 within 12 months prior to 
the first dose of open-label selinexor, that sample may substitute for the biopsy. 
Patients in the selinexor arm who continue on selinexor but as open-label treatment 
are not required to have an additional tumor biopsy at the EoBT Visit. See 
Section 10.11.3. 
• Imaging to evaluate site of disease and distant sites (abdomen, pelvis, chest) 
o Phases 2 and 3: CT (preferred) or MRI scan for tumor measurement (if 
≥ 4 weeks since last prior scan AND required to document disease or clinical 
progression) for assessment of liposarcoma. Patients in the placebo arm who 
have clinical progression must have subsequent radiographic progression 
determined by the central reader in order to receive open-label selinexor. 
• Assessment of progression/extent of liposarcoma by RECIST v. 1.1 (2) if tumor 
(CT/MRI) scan is performed. 
• Treatment assignment query of patients and Investigators (if not performed at a 
previous visit; query after PD but prior to unblinding) (Section 10.7.2). 
• QoL questionnaires (EORTC QLQ-C30 and EuroQoL EQ-5D-5L) (Section 10.7.1) 
• AEs/SAEs 
• Concomitant medications 
• Information on any antineoplastic therapies used since discontinuation of blinded 
study treatment 
9.1.7. 
Safety Follow-up Phone Call (30 Days [+7 days] after last dose of study 
treatment) 
Only for patients NOT proceeding to open-label selinexor. 


Seli ne x or ( K P T -3 3 0)  
 
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 7 0  
At a mi ni m u m, all patie nts w h o disc o nti n ue st u d y treat me nt, i ncl u di n g t h os e w h o ref use t o  
ret ur n f or a n E o B T V isit, will be c o ntacte d f or safet y e val uati o ns d uri n g t h e 3 0 da ys 
( + 7 da ys)  f oll o wi n g t he l ast d ose of st u d y treat me nt. E ver y eff or t s h o ul d be ma de t o c o ntact 
t he patie nt ( or t he p atie nt’s fa mil y) b y tele p h o ne or b y s e n di n g a p pr o pri ate c orres p o n d e nce 
(e g, certifie d letter or e m ail).  
D uri n g t his patie nt c o nt act t he m ost i m p orta nt i nf or mati o n t o be o btai ne d i ncl u des t he 
f oll o wi n g: 
•  O verall me dical c o n diti o n of t he patie nt a n d stat us of t heir li p osarc o ma  
•  A Es, i ncl u di n g f oll o w -u p o n a n y A Es t hat were n ot res ol ve d at t he E o B T Visit  
•  C ollecti o n of i nf or mati o n (i ncl u di n g tr eat me nt t y p e, res p o nse, a n d ti me of res p o nse 
f or assess me nt of  
) o n a n y a nti ne o plastic t hera pies use d after disc o nti n uati o n of 
bli n de d st u d y treat me nt. F or patie nts w h o pr o gress o n p ost-st u d y treat me nt 
a nti ne o plastic t hera p y, t h e I n vesti ga t or s h o ul d e nt er t he date of pr o gressi o n fr o m t he 
me dical rec or d  i n t he e C R F if t hat i nf or mati o n is a vaila ble t o t he I n v esti gat or. 
9. 1. 8.  
S ur vi v al F oll o w -U p  
O nl y f or patie nts N O T pr ocee di n g t o o pe n -l a bel seli ne x or. 
After disc o nti n uati o n of bli n de d st u d y treat me nt , a call will be ma de t o t he patie nt ( or t he 
patie nt’s fa mil y) e v er y 3  m o nt hs t o i n q uire a b o ut t he pat ie nt’s li p osarc o m a stat us, well-bei n g, 
a n d i nf or mati o n o n a n y a nti ne o plastic t hera pies us e d si nce disc o nti n uati o n of st u d y tr eat me nt 
(f or ass ess me nt of 
). If t he patie nt has die d, t he patie nt’s date of deat h will be c ollecte d, 
t o get her wit h t he reas o n f or deat h, if p ossi ble.  
Patie nts l ost t o f oll o w  u p s h o ul d be rec or de d as s u c h o n t he e C R F -. F or patie nts w h o are l ost 
t o f oll o w-u p, t he I n vesti gat or s h o u l d s h o w " d u e dili ge nce" b y d oc u me nti n g i n t he s o urce 
d oc u me nts ste ps ta ke n t o c o ntact t he patie nt, e g, d ates of tele p h o n e calls, re gistere d letters, 
etc. (see Secti o n  1 1. 2 ). 
9. 2.  
Descri pti o n of St u d y D a ys:  O pe n -l a bel Seli ne x or 
Ple ase n ote:  
•  E o B T V isit ser ves as bas eli ne of O pe n-La bel Seli ne x or; T he E o B T V isit ma y o cc ur 
o n t he da y of t he patie nt’s first o pe n -la bel d ose (O L -C 1 D 1 V isit) b ut m ust be 
≤ 1 4  da ys of last bli n de d d ose.  O L C 1 D 1 m ust occ ur wit hi n 1 4 da ys of t he E o B T 
Visit.  
•  P atie nts  i n t he seli ne x or ar m w h o  c o nti n ue seli ne x or b ut as o pe n-la bel treat me nt m ust 
c o m plete t he E o B T Visit bef ore t h eir ne xt sc he d ule d seli ne x or d ose t o mai ntai n 
c o nti n uit y of seli ne x or d osi n g fr o m bli n de d t o o p e n -la bel treat me nt.  
•  P h ysical e x a m i nati o n assess me nts a n d la b or at or y assess me nts d o ne at t he E o B T V isit 
d o n ot nee d t o be re p eate d at O L  C 1 D 1.   
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Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 7 1  
9. 2. 1.  
Visit s O L 1 -6 ( C y cle 1: D a ys 1, 8 *, 1 5 *, 2 2, 2 9 * , a n d 3 6 * [ ± 1 d a ys]); Ret ur n t o 
t he Cli nic 
T here are si x cli nic visits (ie, Da ys 1, 8 *, 1 5 *, 2 2, 2 9 *, a n d 3 6 *) d uri n g t he first si x -wee k 
c ycle ( C ycl e 1).  
* Visits ( ie, Da ys 8 *, 1 5 *, 2 9 *, a n d 3 6 *) are n ot re q uire d f or patie nts w h o c o nti n ue seli ne x or 
b ut as o pe n -la bel treat me nt. 
T he f oll o wi n g st u d y ass ess me nts will be perf or me d d uri n g C ycle 1, as s pecifie d i n  Ta ble  2 .  
•  P h ysical e x a mi nati o n a n d vital si g ns ( bl o o d press ure, p ulse, a n d b o d y te m perat ur e) 
( Da ys 8 *, 1 5 *, 2 2, 2 9 *, a n d 3 6 *) Secti o n  1 0. 6. 1. 1 ) 
•  Wei g ht ( Da ys  8 *, 1 5 *, 2 2, 2 9 *, a n d 3 6 *) ( Secti o n  1 0. 6. 1. 2 ) 
•  Li mite d ser u m c h e mistr y ( Da ys 8 *, 1 5 *, 2 2, 2 9 * a n d 3 6 *) ( Secti o n  1 0. 6. 2. 1 )  
•  T u m or  bi o ps y, o nl y f or p atie nts w h o cr oss o ver fr o m bli n de d place b o t o o p e n -la bel 
seli ne x or a n d ha ve s ufficie nt material a vaila ble fr o m a bi o ps y sa m ple o btai ne d d uri n g 
bli n d e d st u d y treat me nt ( pre - or p ost -d osi n g)  wit hi n 1 2 m o nt hs pri or t o t he first d ose 
of o pe n -la b el seli ne x or (Da y 2 2 o nl y) . N ote: If t he b i o ps y is n ot perf or me d o n 
C ycle  1 Da y 2 2, it ma y b e perf or me d o n C ycle 2 Da y 1  (see Secti o n 9. 2. 2 ). Patie nts 
i n t he seli ne x or ar m w h o c o nti n ue o n seli ne x or b ut as o pe n-la bel treat me nt are n ot 
re q uire d t o ha v e a n a d diti o nal t u m or bi o ps y o n C ycle 1 Da y 2 2 of o pe n-la bel 
treat me nt. See Secti o n  1 0. 1 1. 3  f or bi o ps y d etails. 
•  
•  
•  N utri ti o nal c o ns ultati o n (s h o ul d occ ur o n Da y 1 b ef ore t h e first d ose of o pe n-la bel 
seli ne x or) f or patie nts i n t he place b o ar m w h o cr oss o ver t o o pe n-la bel seli ne x or. T he 
n utriti o nal c o ns ul tati o n is n ot re q uire d at C 1 D1 of o pe n -la bel seli ne x or treat me nt f or 
patie nts i n t he seli ne x or ar m w h o c o nti n ue o n seli n e x or b ut as o pe n -la bel treat me nt. 
See Secti o n  1 0. 7. 3 . 
•  Seli ne x or : i n cli nic d osi n g a n d dis p e nsi n g of f or h o me use 
•  A Es  a n d S A Es  (t hr o u g h o ut t he c ycle) 
•  C o nc o mita nt me dicati o ns  (t hr o u g h o ut t he c ycle) 
T he f oll o wi n g O L 1 Visit ( C 1 D 1) assess me nts will be perf or me d o nl y if t he y were n ot 
perf or me d at t he E o B T V isit: 
•  I nf or me d c o nse nt f or o p e n-la bel s eli ne x or a n d Asse nt F or m f or a d oles ce nt patie nts  
(per mitte d o nl y i n c o u ntries i n w hic h a d olesce nts ha ve bee n a p pr o ve d b y t he 
nati o nal/l ocal re g ulat or y/ et hical a ut h orit y ) m ust be si g ne d o n or b ef ore t he O L 1 Visit 
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before any study-specific procedures for treatment with open-label selinexor are 
conducted at the OL1 Visit (Day 1 only) 
• Physical examination and vital signs (blood pressure, pulse, and body temperature) 
(Day 1) Section 10.6.1.1) 
• Weight (Day 1) (Section 10.6.1.2) 
• ECOG performance status assessment (Day 1 only) (Section 10.6.1.3) 
• 12-lead ECG (Day 1 only) (Section 10.6.1.4) 
• Urinalysis (Day 1 only) (Section 10.6.2.1) 
• Hematology (Day 1 only) (Section 10.6.2.1)  
• Complete serum chemistry (Day 1 only) (Section 10.6.2.1)  
• Coagulation tests (Day 1 only) (Section 10.6.2.1) 
• QoL questionnaires (EORTC QLQ-C30 and EuroQoL EQ-5D-5L); Day 1 only, 
predose) (Section 10.7.1) 
9.2.1.1. 
Phone Call with Patient: Cycle 1 Day 3 Only (+ 1 day) 
A phone call will be made to the patient to evaluate supportive care medications, 
concomitant medications, and AEs/SAEs, and to adjust supportive care as appropriate.  
9.2.2. 
Visits OL7-9 (Cycle 2: Days 1, 15, and 29* [±2 days]); Return to the Clinic 
There are three clinic visits (Days 1, 15, and 29*) for Cycle 2. 
*Visit (ie, Day 29*) is not required for patients who continue selinexor but as open-label 
treatment. 
The following study assessments will be performed during Cycle 2, as specified in Table 2. 
• Physical examination and vital signs (blood pressure, pulse, and body temperature) 
(Days 1, 15, and 29*) (Section 10.6.1.1) 
• Weight (Days 1, 15, and 29*) (Section 10.6.1.2) 
• Height and BSA (Day 1 only) (Section 10.6.1.2) 
• ECOG performance status assessment (Day 1 only) (Section 10.6.1.3) 
• Urinalysis (Day 1 only) (Section 10.6.2.1)  
• Hematology (Day 1 only) (Section 10.6.2.1)  
• Complete serum chemistry (Day 1 only) (Section 10.6.2.1)  
• Limited serum chemistry (Days 15 and 29 only) (Section 10.6.2.1)  
• Coagulation tests (Day 1 only) (Section 10.6.2.1)  
• Female patients of childbearing potential only: pregnancy test (serum hCG or high 
sensitivity urine) prior to dosing on Day 1 only. A positive urine pregnancy test will be 
confirmed by a serum pregnancy test. (Section 10.6.2.2) 
• Tumor biopsy only for patients who cross over from blinded placebo to open-label 
selinexor and have sufficient material available from a biopsy sample obtained during 
blinded study treatment (pre- or post-dosing) within 12 months prior to the first dose 


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of open-label selinexor (Day 1 only and only if not taken at Cycle 1 Day 22, see 
Section 9.2.1). Patients in the selinexor arm who continue on selinexor but as 
open-label treatment are not required to have an additional tumor biopsy on Cycle 2 
Day 1 of open-label treatment. See Section 10.11.3 for biopsy details. 
• Imaging to evaluate site of disease and distant sites (abdomen, pelvis, chest) 
o CT (preferred) or MRI scan for tumor measurement approximately 6 weeks 
post-first dose (ie, Day 1 of Cycle 2) to evaluate site of disease and distant 
sites (abdomen, pelvis, chest) 
• Assessment of progression/extent of liposarcoma by RECIST v. 1.1 (2) 
approximately 6 weeks after the first dose of open-label selinexor (ie, Day 1 of 
Cycle 2), based on 6-week tumor scan. 
• QoL questionnaires (EORTC QLQ-C30 and EuroQoL EQ-5D-5L) (Day 1 only, 
predose) (Section 10.7.1) 
• Selinexor: in clinic dosing and dispensing of for home use (Days 1, 15, and 29) 
• AEs and SAEs (throughout the cycle) 
• Concomitant medications (throughout the cycle) 
9.2.2.1. 
Phone Calls with Patient: Cycle 2 Days 10, 24, and 38 (+ 1 day) 
A phone call will be made to the patient to evaluate supportive care medications, 
concomitant medications, and AEs/SAEs, and to adjust supportive care as appropriate.  
9.2.3. 
Visits OL ≥ 10 (Cycles ≥ 3: Days 1 and 22 [±2 days]); Return to the Clinic 
Patients enrolled in this study may continue from cycle to cycle without interruption. 
The following study assessments will be performed for Cycles ≥ 3, as specified in Table 2: 
• Physical examination and vital signs (blood pressure, pulse, and body temperature) 
(Days 1 and 22) (Section 10.6.1.1) 
• Weight (Days 1 and 22) (Section 10.6.1.2) 
• Height and BSA (Day 1 only) (Section 10.6.1.2) 
• ECOG performance status assessment (Day 1 only) (Section 10.6.1.3) 
• Urinalysis (Day 1 only) (Section 10.6.2.1)  
• Hematology (Day 1 only) (Section 10.6.2.1)  
• Complete serum chemistry (Day 1 only) (Section 10.6.2.1)  
• Limited serum chemistry (Day 22 only) (Section 10.6.2.1)  
• Coagulation tests (Day 1 only) (Section 10.6.2.1)  
• Female patients of childbearing potential only: pregnancy test (serum hCG or high 
sensitivity urine) prior to dosing on Day 1 only. A positive urine pregnancy test will 
be confirmed by a serum pregnancy test. (Section 10.6.2.2) 
• Imaging to evaluate site of disease and distant sites (abdomen, pelvis, chest) 
o CT (preferred) or MRI scan for tumor measurement approximately 12 weeks 
after start of open-label selinexor (ie, Day 1 of Cycle 3), and approximately 


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every 12 weeks thereafter (ie, Day 1 of odd-numbered Cycles ≥ 5) to evaluate 
site of disease and distant sites (abdomen, pelvis, chest); the same imaging 
modality should be maintained throughout the study 
• Assessment of progression/extent of liposarcoma by RECIST v. 1.1 (2) when tumor 
(CT/MRI) scans are performed. Assessments are to be performed approximately 
12 weeks after start of open-label selinexor (ie, Day 1 of Cycle 3), and approximately 
every 12 weeks thereafter (ie, Day 1 of odd-numbered Cycles ≥ 5), based on tumor 
scans.  
• QoL questionnaires (EORTC QLQ-C30 and EuroQoL EQ-5D-5L) (Day 1 only, 
predose) (Section 10.7.1) 
• Selinexor: in clinic dosing and dispensing of for home use (Days 1 and 22) 
• AEs and SAEs (throughout the cycles) 
• Concomitant medications (throughout the cycles) 
9.2.4. 
End of Treatment Visit (≤ 14 days after last dose of study treatment); Return 
to the Clinic 
At the time a patient permanently discontinues selinexor a visit should be scheduled as soon 
as possible (within 14 days), at which time all of the assessments listed for the End of 
Treatment (EoT) Visit will be performed. Study procedures will be performed ≤ 14 days after 
the last dose of selinexor as specified in Table 2. An EoT CRF page will be completed, 
giving the date and reason for stopping the selinexor. Patients lost to follow-up should be 
recorded as such on the appropriate eCRF. 
• Physical examination and vital signs (blood pressure, pulse, and body temperature) 
(Section 10.6.1.1) 
• Weight, height, and BSA (Section 10.6.1.2) 
• ECOG performance status assessment (Section 10.6.1.3) 
• 12-lead ECG (Section 10.6.1.4) 
• Urinalysis (Section 10.6.2.1)  
• Hematology (Section 10.6.2.1)  
• Complete serum chemistry (Section 10.6.2.1)  
• Coagulation tests (Section 10.6.2.1)  
• Serum hCG pregnancy test (females of childbearing potential only). 
(Section 10.6.2.2) 
• Imaging to evaluate site of disease and distant sites (abdomen, pelvis, chest) 
o CT (preferred) or MRI scan for tumor measurement (if ≥4 weeks since last 
prior scan AND required to document disease or clinical progression) for 
assessment of liposarcoma. 
• Assessment of progression/extent of liposarcoma by RECIST v. 1.1 (2) if tumor 
(CT/MRI) scan is performed. 
• QoL questionnaires (EORTC QLQ-C30 and EuroQoL EQ-5D-5L) (Section 10.7.1) 
• AEs and SAEs 


Seli ne x or ( K P T -3 3 0)  
 
Kar y o p har m T hera pe utics I nc.  
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C o nfi de ntial  
P a ge 7 5  
•  C o nc o mita nt me dicati o ns  
•  I nf or mati o n o n a n y a nti n e o plastic t hera pies us e d si nce disc o nti n uati o n of o pe n -la bel 
seli ne x or 
9. 2. 5.  
O L S afet y F oll o w -u p P h o ne C all ( ≤ 3 0 D a ys [ +7 d a ys] after l ast d ose of st u d y 
tre at me nt)  
At a mi ni m u m, all patie nts w h o disc o nti n ue st u d y treat me nt, i ncl u di n g t h os e w h o ref use t o  
ret ur n f or a n E o T Visit, will be c o ntacte d f or safet y e v al uati o ns d uri n g t h e 3 0 da ys ( + 7 da ys) 
f oll o wi n g t he last d ose of st u d y treat me nt. E ver y eff ort s h o ul d be ma de t o c o ntact t he patie nt  
( or t he patie nt’s fa mil y) b y tele p h o n e or b y se n di n g a p pr o priate c orres p o n de nce ( e g, certifie d 
letter or e mail).  
D uri n g t his patie nt c o nt act t he m ost i m p orta nt i nf or mati o n t o be o btai ne d i ncl u des t he 
f oll o wi n g: 
•  O verall me dical c o n diti o n of t he patie nt a n d stat us of t heir li p osarc o ma  
•  A Es, i ncl u di n g f oll o w -u p o n a n y A Es t hat were n ot res ol ve d at t he E o T Visit  
•  C ollecti o n of i nf or mati o n (i ncl u di n g tr eat me nt t y p e, res p o nse, a n d ti me of 
res p o nse f or assess me nt of  
) o n a n y a nti ne o plastic t hera pies use d after 
disc o nti n uati o n of o pe n -la bel seli ne x or. F or patie nts w h o pr o gress o n p ost-st u d y 
treat me nt a nti ne o plastic t hera p y, t he I n vesti gat or s h o ul d e nter the date of 
pr o gressi o n  fr o m t he me dical rec or d i n t he e C R F if t hat i nf or mati o n is a vaila ble 
t o t he I n v esti gat or.  
9. 2. 6.  
O L  S ur vi v al F oll o w -U p  
After disc o nti n uati o n  of treat me nt wit h o pe n -l a bel seli ne x or, a call will be ma de t o t he 
patie nt ( or t he patie nt’s fa mil y) e v er y 3 m o nt hs t o i n q uire a b o ut t he pati e nt’s li p osarc o ma 
stat us, well-bei n g, a n d i nf or mati o n o n a n y  a nti ne o plastic t hera pies us e d si n ce disc o nti n uati o n 
of st u d y tr eat me nt (f or assess me nt of  
). If t he patie nt has die d, t he pati e nt’s date of 
dea t h will be c ollecte d, t o get h er wit h t he reas o n f or deat h, if p ossi ble.  
Patie nts l ost t o f oll o w -u p s h o ul d be rec or de d as s u c h o n t he e C R F. F or pati e nts w h o are l ost 
t o f oll o w-u p, t he I n vesti gat or s h o ul d s h o w " d u e dili ge nce" b y d oc u me nti n g i n t he s o urce 
d oc u me nts ste ps ta ke n t o c o ntact t he patie nt, e g, d ates of tele p h o n e calls, re gistere d letters, 
etc. (see Secti o n 1 1. 2 ). 
9. 3.  
U nsc he d ule d Visits  
U nsc he d ule d visits ma y be c o n d ucte d at a n y ti me d uri n g t he bli n de d or o pe n -la bel p orti o ns 
of t he st u d y at t he discreti o n of t he I n vesti gat or. A d diti o nal testi n g (e g, bl o o d testi n g or 
i ma gi n g sca ns) ma y be p erf or me d t o e ns ure p atie nt safet y.  
If u nsc he d ule d i ma gi n g s ca ns are perf or me d, t he y will be e val uate d as descri be d i n 
Secti o n  1 0. 5. 1. 1 . If P D is c o nfir me d bas e d o n a n u nsc he d ule d i ma gi n g sca n, t he o pti o ns f or 
st u d y treat me nt descri b e d i n Secti o n 7. 2. 1  will a p pl y. 
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2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 7 6  
1 0.  
M E T H O D S O F A S S E S S M E N T  
1 0. 1.  
I ncl usi o n/ E xcl usi o n Criteri a 
T he patie nt m ust mee t t he all of t he i ncl usi o n criteria ( Secti o n 8. 3 ) a n d n o n e of t he e x cl usi o n 
criteria ( Secti o n  8. 4 ). 
Ke y patie nt eli gi bilit y (i n cl usi o n/e x cl usi o n criteria) will be c o nfir me d b y t h e S p o ns or f or all 
patie nts partici pati n g i n t he st u d y pri or t o ra n d o mi zati o n ( Secti o n  7. 6 ). 
See Secti o n  7. 7  f or ra n d o mizati o n details. 
1 0. 2.  
De m o gr a p hic D at a  
P atient de m o g rap hics  (i ncl u di n g dat e of birt h, se x, race, et h nicit y, a ge at ti me of c o nse nt, a n d 
t u m or t y pe) will be c ollecte d at st u d y e ntr y.  
1 0. 3.  
Me dic al Hist or y  
A c o m plete me dic al hist or y will be o btai ne d fr o m eac h p atie nt.  Me dical hist or y will i ncl u de  
baseli ne li p osarc o ma s y m pt o ms as well as a detaile d hist or y of pri or pr oce d ures a n d pri or 
ca ncer t hera pies (ie, c he m ot hera p y, h or m o nal t hera p y, i m m u n ot hera p y, bi ot hera p y, 
ra di ot hera p y, a n d s ur ger y) i ncl u di n g start a n d st o p dates, best res p o ns e, P D  d uri n g or aft er 
t hera p y, as w ell as disc o nti n uati o ns d ue t o i nt olera bilit y or t o xicit y.  
A detaile d hist or y of disease -s pecific dia g n ostic a n d pr o g n ostic testi n g a n d test res ults (s uc h 
as p he n ot y pic a n d c yt o ge netic pr ofiles) will als o b e c ollecte d.   
1 0. 4.  
Li p os arc o m a H ist ol o g y 
F or all patie nts, t u m or tiss ue will be a nal yz e d b y a ce ntral la b orat or y f or c o nfir mat or y 
hist ol o g y ( ie, t o c haract eriz e t u m or hist ol o g y a n d c o nfir m t he prese n ce of D D L S); t he res ults 
of t he ce ntr al hist ol o gic assess me nt are n ot r e q uire d f or ra n d o m izati o n a n d i nitiati o n of 
treat me nt. A t u m or bi o ps y will be c ollecte d d uri n g scree ni n g u nless a p pr o priate arc hi v al 
material is a vaila ble. At t he I n vesti gat or’s discreti o n, a p pr o priate arc hi v al material ma y 
s u bstit ute f or t he bi o ps y d uri n g scree ni n g. A p pr o priate arc hi val materi al i ncl u des D D L S 
tiss ue c ollecte d as part of cli nical sta n dar d of care wit hi n 1 2 m o nt hs pri or t o t he first d ose of 
bli n de d st u d y treat me nt or >  1 2 m o nt hs if t he q ualit y of t he s a m ple f or c o nfir mat or y 
hist ol o g y is c o nfir me d b y t he site hist o pat h ol o gist bef ore ra n d o mizati o n.  
It s ufficie nt tiss ue is a vaila ble, a p orti o n of t he sa m ple will be use d f or  
 testi n g (see 
Secti o n  1 0. 1 1. 3 ). 
If a pretreat me nt (scree ni n g) t u m or bi o ps y sa m ple (arc hi v al or fres h) was o btai ne d f or  
 
 
. P orti o ns of t his bi o ps y will be f or mali n-fi x e d a n d fr oze n-u nfi x e d as 
descri be d i n t he L a b or at ory M a n u al . Bi o psies are re q uire d if feasi ble. T h e feasi bilit y of t he 
bi o ps y pr oce d ure, i n ter ms of patie nt safet y a n d t u m or accessi bilit y, will b e deter mi ne d b y 
t he I n v esti gat or. N ote: T his sec o n d bi o ps y (e g, eit her C ycle 1 Da y 2 2 or C ycl e 2 Da y 1) 
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Versi o n 9. 0  
C o nfi de ntial  
P a ge 7 7  
s h o ul d n ot be c ollecte d fr o m a d olesce nt/ pe diatric patie nts f or e x pl orat or y st u dies if t here 
a p pears t o b e a p ote ntial f or seri o us ris k f or t he patie nt.  
Bi o psies s h o ul d be perf or me d per I nstit uti o nal G ui deli nes a n d ma y be eit her a c ore nee dle 
bi o ps y or a n o p e n bi o ps y.  
Please see t he L a b or at or y M a n u al  f or a d diti o nal details o n c ollecti o n, ha n dli n g, a n d s hi p pi n g 
of bi o ps y tiss ue.  
1 0. 5.  
Effic ac y Assess me nts  
1 0. 5. 1.  
T u m o r I m a gi n g  
1 0. 5. 1. 1.  T y pes of I m a gi n g  
T w o f or ms of i ma gi n g will be use d  t o i ma ge t u m ors t o e val uate site of disease a n d dista nt 
sites (a b d o me n, pel vis, c hest): 
•  
1 8F ‐fl u or o de o x y gl uc os e p ositr o n e missi o n t o m ogra p h y/ c o m p ute d t o m o gra p h y 
(F D G -P E T a n d C T ) will be use d t o c o m bi ne t he hi g h a n at o mical detail of C T wit h  
t he assess me nt of t u m or gl uc ose m eta b olic acti vit y pr o vi de d b y  F D G -P E T i ma gi n g  
(f or P hase 2 o nl y  a n d o nl y f o r scree ni n g a n d t he first p ost-d ose sca n ). If F D G -P E T is 
c o ntrai n dicate d f or a gi v e n patie nt, t he n a C T  sca n, w hic h is t he preferre d m o dalit y, 
s h o ul d be use d i nstea d. If C T is als o c o ntrai n dicate d, t he n a n M RI  sca n s h o ul d be 
use d. Please n ote t hat, f or a gi ve n patie nt, t he s a me i ma gi n g m o dalit y s h o ul d be 
mai ntai ne d  t hr o u g h o ut t h e st u d y, w here a p pr o pri ate. T he sc h e d ule f or F D G -P E T a n d 
C T  ( dia g n ostic) is gi ve n i n Secti o n 1 0. 5. 1. 2 . 
•  C T i ma gi n g is  c o nsi dere d t o be  t he preferre d m o d alit y  f or t h e cli nical ima gi n g of 
sarc o ma a n d will be use d f or t his stu d y  ( P hase 2 st arti n g wit h t he s ec o n d p ost -d ose 
sca n a n d P hase 3  st arti n g wit h scree ni n g). If C T is c o ntrai n dicate d f or a gi v e n patie nt, 
t he n M RI s h o ul d be us e d i nstea d. Please n ote t hat, f or a gi ve n patie nt, t he sa me 
i ma gi n g m o dalit y s h o ul d be mai ntai ne d t hr o u g h o ut t he st u d y, w here a p pr o priate. T he 
sc he d ule f or C T (preferre d) or M RI  is gi ve n i n Secti o n 1 0. 5. 1. 2 . 
All sca ns , i ncl u di n g u nsc he d ule d sca ns, m ust be tr a ns mitte d as s o o n as p ossi ble t o t he ce ntral 
rea der. Sca ns will be ce ntrall y ass esse d b y a n i n de pe n de nt re vie wer, as f oll o ws, f or: 
•  Si n gle -di me nsi o nal (l o n gest cr oss -secti o nal di me nsi o n) meas ure me nts (res p o nse per 
R E CI S T  v. 1. 1 ) 
•  T w o -di me nsi o nal ( pr o d u ct of l o n gest dia meter a n d greatest per pe n dic ular dia meter) 
meas ure me nts (res p o nse per W H O Res p o nse Criteria ) 
•  
•  T u m or de nsit y a n d S U V deter mi nati o ns f or ass ess me nt of t u m or res p o nse defi ne d as 
≥ 1 0 % re d ucti o n i n t u m or s u m of l o n gest dia meters or >  1 5 % re d ucti o n i n t u m or 
de nsit y or >  3 0 %  re d ucti o n i n S U V ( F D G-P E T a n d C T sca ns f or P hase 2 o nl y ) 
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Additional details will be provided in the Imaging Manual. 
10.5.1.2. Imaging Schedules for Phases 2 and 3 
Blinded Study Treatment 
Phase 2 
• FDG-PET and CT (diagnostic) at screening and approximately 6 weeks after the 
first dose of blinded study treatment (ie, Day 1 of Cycle 2).  
• CT (preferred) or MRI scan will be performed at approximately 12, 18, and 
24 weeks after the first dose of blinded study treatment (ie, Day 1 of Cycles 3, 4, 
and 5), then every 12 weeks (ie, Day 1 of odd-numbered Cycles ≥ 7) thereafter 
until PD or unblinding. 
Phase 3 
• CT (preferred) or MRI will be performed at Screening and approximately 6, 12, 
18, and 24 weeks after the first dose of blinded study treatment (ie, Day 1 of 
Cycles 2, 3, 4, and 5), then every 12 weeks (ie, Day 1 odd-numbered Cycles ≥ 7) 
thereafter until PD or unblinding. 
Open-label Selinexor 
• CT (preferred) or MRI at approximately 6 and 12 weeks after the first dose of 
open-label selinexor (ie, Day 1 of Open-label Cycles 2 and 3), then every 12 weeks 
(ie, Day 1 of odd-numbered Cycles ≥ 5) thereafter until PD. 
10.5.2. 
Diagnosis/ Assessment of Progression/ Extent of Liposarcoma 
Assessment of liposarcoma per RECIST v. 1.1 will be performed following each tumor scan. 
10.6. 
Safety Assessments 
Safety evaluations will be conducted as described below. Refer to Table 1, Table 2, and 
Section 9 for the timing of all safety assessments. 
10.6.1. 
Clinical Safety Assessments 
10.6.1.1. Physical Examination and Vital Signs 
The physical examination will be performed according to the standards at each institution. 
Physical examination, including vital signs, will be performed on the scheduled day, even if 
study treatment is being interrupted. Physical examinations should include general 
appearance, dermatological, head, eyes, ears, nose, throat, respiratory, cardiovascular, 
abdominal, lymph nodes, musculoskeletal, and neurological examinations. 


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All vital signs will include: 
•
Body temperature (oC or oF)
•
Systolic and diastolic blood pressure and pulse rate should be measured after the
patient has been in a supine or sitting position for 5 minutes. Blood pressure should
be assessed on the same arm throughout the study.
Information about the physical examination must be present in the source documentation at 
the study site. The result of the physical examination prior to the start of study treatment 
must be included in the Relevant Medical History/Current Medical Conditions eCRF. 
Clinically relevant findings made after the start of study treatment, which meet the definition 
of an AE, must be recorded on the AE eCRF. 
10.6.1.2. Height, Weight, and BSA 
Height (without shoes) in centimeters (cm) and weight (indoor clothing without shoes) in 
kilograms (kg) will be measured. BSA will be calculated by the Dubois (Dubois 1916) or 
Mosteller (Mosteller 1987) method to verify that BSA > 1.2 m2 to ensure that an individual 
patient's selinexor dose would not exceed 70 mg/m2 twice weekly. If the patient’s weight 
fluctuates substantially, BSA should be re-calculated at each treatment visit. BSA should be 
re-calculated prior to any selinexor/placebo dose change. 
10.6.1.3. ECOG Performance Status 
ECOG performance status assessments (Oken 1982) will be performed during the study to 
assess how the disease affects the daily living abilities of the patients (Appendix 3). 
10.6.1.4. Electrocardiography 
Standard 12-lead ECGs will be performed. The ECGs performed on Day 1 of Cycles 1 and 2 
during blinded study treatment are to be performed just prior to the blood sample taken 
2 hours postdose (approximately at the expected tmax of plasma selinexor). ECGs may also be 
performed as clinically indicated during the study. 
Patients must rest for at least 5 minutes prior to any 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 time the ECG was performed and the 
following parameters will be recorded in the eCRF: heart rate, PR interval, QT interval, QRS 
interval, and QT corrected using either Bazett’s or Fredericia’s formula. 
10.6.1.5. Concomitant Medications 
Concomitant medications will be documented for each patient at each scheduled visit. A 
detailed history of medications will be documented for each patient at screening and C1 D1. 
Subsequently, at each study visit, patients will be asked whether they have taken any 
medication other than the study treatment 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 in the eCRF.  
Necessary supportive care such as appetite stimulants, anti-emetics and anti-diarrheal 
medication, etc., will be allowed (see Section 12.2.5).  


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10.6.1.6. Adverse Events 
Information regarding AEs and SAEs will be collected. See Section 13.1.2. 
10.6.2. 
Laboratory Safety Assessments 
10.6.2.1. Clinical Laboratory Tests 
The following clinical laboratory tests will be performed by the sites’ local laboratories. In 
addition, laboratory tests will be collected and analyzed on the scheduled day, even if study 
treatment is being interrupted. More frequent assessments may be performed if clinically 
indicated, or at the Investigator’s discretion and these should be recorded on the Unscheduled 
Visit eCRFs: 
• Hematology (blood sample: ethylenediaminetetraacetic acid) will include 
hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, 
mean corpuscular hemoglobin concentration, white blood cell (WBC) count, WBC 
differential, RBC count, lymphocytes, monocytes, neutrophils, band neutrophils, 
eosinophils, basophils, platelets. WBC differential may be automated or manual as 
per institutional standards. Reticulocytes may be done only when clinically indicated. 
• Serum Chemistry (blood sample: serum) 
- 
Complete Serum Chemistry will include sodium, potassium, chloride, 
bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, calcium, phosphate, 
magnesium, ALT, AST, alkaline phosphatase, total bilirubin, lactate 
dehydrogenase (LDH), total protein, albumin, creatinine kinase, uric acid. 
- 
Limited Serum Chemistry will include sodium, potassium, chloride, bicarbonate, 
BUN, creatinine, glucose, ALT, AST, alkaline phosphatase, total bilirubin, and 
LDH.  
- 
If the total bilirubin concentration is increased above 1.5 times the upper normal 
limit, total bilirubin should be differentiated into the direct and indirect reacting 
bilirubin. 
• Coagulation tests will include prothrombin time (PT), international normalization 
ratio (INR), and activated partial thromboplastin time (aPTT). 
• Urinalysis will include appearance, color, urine bilirubin, glucose, hemoglobin, 
ketones, pH, protein, specific gravity, and urobilinogen. Microscopy will only be 
performed if clinically indicated. 
Blood chemistry will be analyzed at each study center by a certified laboratory. The 
Investigator or designee will review the laboratory report after receipt of the results and 
assess the clinical significance of all abnormal values. Results must be reviewed prior to 
dosing and appropriate action taken for any clinically significant abnormal values.  
At any time during the study, abnormal laboratory values which are clinically relevant 
(eg, require dose modification and/or interruption of study treatment, lead to clinical 
symptoms or signs or require therapeutic intervention), whether specifically requested in the 
protocol or not, must be documented in the eCRF. If any abnormal laboratory value or test 
result constitutes an AE, then these must be recorded on the AE eCRF. Values will be 
documented on the laboratory report until stabilized, or the laboratory value returns to a 


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clinically acceptable range (regardless of relationship to study treatment) or baseline. Any 
laboratory value that remains abnormal at the EoBT Visit (early discontinuation patients) or 
EoT Visit (open-label patients) and that is considered clinically significant will be followed 
according to accepted medical standards for up to 30 days or until resolution of the 
abnormality or return to baseline. 
Toxicity will be assessed using the NCI CTCAE, v. 4.03. 
Karyopharm must be provided with a copy of the laboratory certification and normal ranges 
for each parameter measured. In addition, if at any time a patient has laboratory parameters 
obtained from a different outside laboratory, Karyopharm must be provided with a copy of 
the certification and normal ranges for that laboratory. 
10.6.2.2. Pregnancy Testing 
Pregnancy testing will be performed for females of childbearing potential only. A negative 
serum hCG pregnancy test must be obtained at Screening within 3 days before the first dose 
of blinded study treatment. For females of childbearing potential who are proceeding to 
open-label selinexor a negative serum hCG pregnancy test must be obtained at the EoBT 
Visit (or within 3 days before the first dose of open-label selinexor). Test sensitivity for hCG 
must be ≥ 25 mIU/mL.  
Pregnancy testing (serum hCG or high sensitivity urine) is also required for females of 
childbearing potential prior to dosing on Day 1 of Cycles ≥ 2 during both blinded and open-
label treatment and at the EoT Visit (serum hCG). A positive urine pregnancy test will be 
confirmed by a serum pregnancy test. 
Pregnancy testing may be performed if clinically indicated during the study. 
10.7. 
Other Assessments 
10.7.1. 
Quality of Life and Health-Related Outcomes 
QoL questionnaires should be completed prior to study treatment administration on the days 
when QoL questionnaire is completed. 
EORTC QLQ-C30: The QLQ-C30 is a validated, patient self-administered instrument for 
assessing the health-related QoL of cancer patients participating in international clinical 
studies. It is a questionnaire containing both multi-item and single scales, including five 
functional scales (physical, role, emotional, social and cognitive), three symptom scales 
(fatigue, nausea & vomiting and pain) and a global health status/QoL scale and six single 
items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). 
EuroQoL EQ-5D-5L: The EQ-5D-5L is a validated, patient self-administered instrument 
used for multiple health conditions and treatments, to provide a simple descriptive profile and 
a single index value of health status. 


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10.7.2. 
Treatment Assignment Query 
Prior to unblinding, the patient and the Investigator will be asked which study treatment 
(active [selinexor] or placebo) they believe the patient received during blinded study 
treatment. 
Specifically: 
• After PD but prior to unblinding, the patient and the Investigator will be asked which 
study treatment (active [selinexor] or placebo) they believe the patient received 
during blinded study treatment and their responses will be recorded. 
• If blinded study treatment is discontinued without PD, query should be performed at 
the time that blinded study treatment is discontinued and prior to unblinding. See 
Section 11.3. 
• If unblinding is required for clinical management of a clinically important SAE 
leading to discontinuation of study treatment and knowledge of the received study 
treatment is required for clinical management and treatment of the SAE, query should 
be performed prior to unblinding. 
10.7.3. 
Nutritional Consultation 
It is strongly recommended that the Investigator, or his/her designee, provide patients with a 
nutritional consultation to discuss any food recommendations and strategies for managing 
potential nausea and appetite changes experienced with selinexor. This consultation does not 
need to be performed by a nutritionist. 
During blinded study treatment, the nutritional consultation should occur on C1 D1 before 
the first dose of blinded study treatment (or within the Screening Period). 
During treatment with open-label selinexor, the nutritional consultation should occur on 
C1 D1 before the first dose of open-label selinexor for patients in the placebo arm who cross 
over to open-label selinexor. The nutritional consultation is not required at C1 D1 of 
open-label selinexor treatment for patients in the selinexor arm who continue on selinexor 
but as open-label treatment. 
The nutritional consultation may be also performed at any time during the study, as 
necessary. 
10.7.4. 
Collection of Information on Antineoplastic Therapy 
Information on any antineoplastic therapies used after discontinuation of study treatment will 
be collected at the EoBT Visit (Section 9.1.6), the EoT Visit (Section 9.2.4), Safety 
Follow-up Calls (Section 9.1.7 and Section 9.2.5), and during Survival Follow-up 
(Section 9.1.8 and Section 9.2.6). 
For patients who progress on post-study treatment antineoplastic therapy, the Investigator 
should enter the date of progression from the medical record in the eCRF if that information 
is available to the Investigator. 


Seli ne x or ( K P T -3 3 0)  
 
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1 1.  
DI S C O N TI N U A TI O N A N D U N B LI N DI N G C RI T E RI A  
1 1. 1.  
E arl y T er mi n ati o n  of t he St u d y  
T he st u d y ma y b e ter mi n ate d  at t he s ole discreti o n of t he S p o ns or f or a n y reas o n, i ncl u di n g 
me dical or et hical reas o ns affecti n g t he c o nti n ue d perf or ma n ce of t he st u d y, or diffic ulties i n 
t he recr uit me nt of patie nts. If t his occ urs, t he S p o ns or will n otif y IE Cs, I R Bs, I n v esti gat ors, 
a n d re g ulat or y a ut h orities.  
1 1. 2.  
D isc o nti n u ati o n of  St u d y Tre at me nt a n d/ or Wit h dr a w al of 
P atie nts fr o m t he St u d y  
T he I n vesti gat or ma y re m o ve a patie nt fr o m st u d y treat me nt f or a n y of t he f oll o wi n g reas o ns: 
•  P D  as defi ne d b y t he ce ntral rea d er b y R E CI S T v. 1. 1  (see e x ce pti o n f or patie nts w h o 
ma y d eri ve be n efit fr o m c o nti n ue d treat me nt  wit h seli ne x or  i n Secti o n  7. 2. 4 ) 
•  Cli nical pr o gressi o n as d eter mi ne d b y t he I n v esti gat or i n c o ns ultati o n wit h t he 
S p o ns or ( m ust be d oc u me nte d b y ra di o gra p hic i m a gi n g a n d assesse d b y t h e ce ntr al 
rea der) 
•  U nacce pta ble A Es or t o xicit y t hat ca n n ot be ma na ge d b y s u p p orti ve care  
•  Si g nifica nt  de viati o ns fr o m i ncl usi o n/e xcl usi o n  criteria  
•  Mis use of st u d y treat me nt (e g, d eli berate o ver d osi n g b y patie nt)  
•  Misse d / u nsc he d ule d / off -sc h e d ule / i nc o m plete / i nc orrect assess me nts t hat res ult i n 
patie nts bei n g p ut at ris k  
•  A n y ot her me dicall y a p pr o priate reas o n or si g nifi ca nt pr ot oc ol v i olati o n, i n t he 
o pi ni o n of t he I n v esti gat or.  
T he I n vesti gat or m ust  re m o ve a patie nt fr o m st u d y treat me nt f or a n y of t he f oll o wi n g 
reas o ns: 
•  Patie nt wit h dra ws c o nse nt t o c o nti n ue st u d y treat me nt  
•  Pre g n a nc y  
•  Use of ra diati o n t o treat t he patie nt’s li p osarc o m a (see Secti o n  1 2. 2. 5. 3 ) 
Patie nts ma y disc o nti n ue st u d y treat me nt f or a n y reas o n.  Patie nts w h o deci de  t o disc o nti n ue 
st u d y treat me nt s h o ul d be e nc o ura ge d t o c onti n ue i n  t he st u d y s o t hat f oll o w-u p i nf or mati o n 
o n P D  a n d s ur vi val stat us ma y b e o btai ne d.  Patie nts w h o disc o nti n ue st u d y treat me nt b ut 
c o nti n ue f oll o w -u p  will be f oll o we d f or a nti -ne o pl astic t hera p y i nitiati o n a n d 
 e ver y 
3  m o nt hs . T hese patie nts will be i ncl u de d i n t he I T T a nal ysis  if t he y are i n P hase 3.  
P atie nts ma y wit h dra w c o nse nt a n d decli ne f u rt her partici pati o n i n t he st u d y at a n y ti me. 
Patie nts w h o wit h dra w c o nse nt m ust be wit h dra w n fr o m t he st u d y.  
A n y p atie nt w h o d oes n ot wit h dra w fr o m t he st u d y b ut w h o st o ps atte n di n g st u d y visits a n d 
d oes n ot res p o n d t o t hree d oc u me nte d c o ntact atte m pts wi ll be c o nsi dere d l ost t o f oll o w-u p.  
T he I n vesti gat or m ust deter mi ne t he pri mar y reas o n f or a patie nt’s disc o nti n uati o n of st u d y 
treat me nt/ wit h dra w al fr o m t he st u d y a n d rec or d t his i nf or mati o n o n t he e C R F. 
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11.3. 
Unblinding 
11.3.1. 
Unblinding of Treatment Assignment During Blinded Study Treatment 
Patients who have PD per RECIST v. 1.1 will discontinue blinded study treatment and their 
treatment assignment will be unblinded. Unblinding will take place within 14 days of the last 
blinded dose and may occur on or before the patient’s EoBT Visit (Section 9.1.6). Only the 
patient, the Investigator at the study site, and key Sponsor team members as specified to 
monitor the conduct of the study will be unblinded to the treatment assignment. 
Treatment assignments for patients who discontinue blinded study treatment without 
determination of PD by the central reader (including patients who discontinue blinded study 
treatment for reasons other than PD) will not be unblinded until the primary PFS analysis at 
the end of Phase 3 and these patients are not allowed to receive open-label selinexor.  
• Exception: Treatment assignment may be unblinded in the event of a clinically 
important SAE only if unblinding is required for clinical management of a clinically 
important SAE leading to discontinuation of study treatment and knowledge of the 
received study treatment is required for clinical management and treatment of the 
SAE. If the patient is on the placebo arm and PD has not been documented, the 
patient will not be eligible to receive open-label selinexor. 
11.3.2. 
Unblinding of Treatment Assignment for All Patients at the Primary PFS 
Analysis at the End of Phase 3 
Once the required number of PFS events for the primary PFS analysis at the end of Phase 3 
are observed, unblinding of treatment assignment for all patients will take place and the 
primary PFS analysis will be conducted. Patients who did not have PD at the time of 
unblinding will 1) continue selinexor but as open-label treatment if they were in the selinexor 
arm, or 2) have the option to cross over to open-label selinexor if they were in the placebo 
arm. 
11.4. 
Definition of End of Study 
End of Study (EoS) will be upon completion of the follow-up period for the last patient 
treated in the study. Completion of follow-up for the last patient will occur when the last 
patient in the study has expired, has been followed for 24 months after enrollment, has been 
lost to follow-up, or has withdrawn consent, whichever occurs first. 
 
 


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12. 
TREATMENT 
Selinexor (KPT-330) immediate release tablets for oral administration and matching placebo 
will be supplied in blister packs. Selinexor tablets will be provided in a coated tablet strength 
of 20 mg. 
12.1. 
Dosing and Administration of Study Treatment 
12.1.1. 
Labeling 
Medication labels for each blister pack of selinexor and matching placebo tablets will be in 
the local language and comply with the legal requirements of each country. They will include 
storage conditions for the drug and the randomization number but no information about the 
patient. 
12.1.2. 
Dispensing Directions 
The Investigator or responsible site personnel must instruct the patient or caregiver to take 
the study treatment as per protocol. Study treatment will be dispensed to the patient by 
authorized site personnel only. Dispensing instruction will be provided in the 
Pharmacy Manual. 
12.1.3. 
Dosing Information 
Selinexor tablets should be taken orally with at least 120 mL (4 ounces) of water. Selinexor 
can be taken with or without food. For additional details on drug formulation, preparation, 
and administration, please refer to the Pharmacy Manual and the selinexor IB. 
In order to avoid contact with skin, tablets must be swallowed whole and should not be 
crushed. 
Blinded Study Treatment (Phases 2 and 3):  
Selinexor and matching placebo will be administered as fixed blinded oral doses of three 
20 mg tablets given twice weekly (eg, Day 1 Monday and Day 3 Wednesday or Day 1 
Tuesday and Day 3 Thursday or Day 1 Wednesday and Day 3 Friday) on Weeks 1-6 of each 
6-week (42-day) cycle until PD, intolerability, consent withdrawal, or unblinding. Patients 
with a BSA < 1.2 m2 as calculated per Dubois 1916 or Mosteller 1987 will be excluded from 
the study. Selinexor will be administered as a flat-fixed dose, and not by body weight or 
BSA. 
Open-Label Selinexor:  
Patients on open-label selinexor will receive selinexor 60 mg twice-weekly during Weeks 1-6 
of each 6-week (42-day) cycle.  
The following 4 groups of patients may receive open-label selinexor: 
(a) Patients in the placebo arm who have PD per RECIST v. 1.1 during blinded study 
treatment who elect to cross over to open-label selinexor 


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(b) Patients in the selinexor arm who have PD per RECIST v. 1.1 during blinded study 
treatment who may derive benefit from continued treatment with selinexor (see 
Section 7.2.4). 
(c) Patients in the placebo arm who are receiving blinded study treatment at the time of 
the primary PFS analysis at the end of Phase 3 who elect to continue to cross over to 
open-label selinexor 
(d) Patients in the selinexor arm who are receiving blinded study treatment at the time of 
the primary PFS analysis at the end of Phase 3 who elect to continue selinexor but as 
open-label treatment 
C1D1 of treatment with open-label selinexor for all 4 groups of patients listed above must 
occur within 14 days of the patient’s EoBT Visit. For patients in the selinexor arm during 
blinded study treatment who continue selinexor but as open-label treatment there will be no 
break in the patient’s twice-weekly dosing schedule. These patients must complete the EoBT 
Visit before their next scheduled selinexor dose to maintain continuity of selinexor dosing 
from blinded to open-label treatment. 
12.1.4. 
Dosing Instructions for the Study Participants 
Study treatment will be provided for twice weekly dosing during Weeks 1-6 for all cycles. 
Patients will be provided adequate doses to take home to complete dosing until the next 
scheduled clinic visit. Patients will be asked to bring remaining study medicine, if any, when 
returning to the clinic for any scheduled or unscheduled visit.  
The Investigator should promote compliance by instructing the patient to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the patient’s 
safety and the validity of the study. The patient should be instructed to contact the 
Investigator if he/she is unable for any reason to take the study treatment. 
Supportive treatment for the management of known toxicities will be provided as needed. 
All dosages prescribed and dispensed to the patient and all dose changes during the study 
must be recorded on the eCRF. Compliance to study treatment will be recorded by study 
personnel after discussion with the patient and completion of drug accountability. Medication 
compliance will be monitored by the Investigator or a delegate and recorded in source 
documents. The date will be recorded as per the study treatment schedule. The Investigator or 
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 of explanations for deviations. The Investigator or 
designee will try to ensure complete compliance with the dosing schedule by providing 
timely instructions to the patients and re-education when necessary.  
12.2. 
Dose Reduction and Supportive Care Guidelines 
12.2.1. 
Dose Modifications and Dose Delay 
For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are 
permitted in order to allow the patient to continue the study treatment. The criteria for dose 
modifications for toxicities considered related to the study treatment, as well as 


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recommended supportive care, are outlined below and in Section 12.2. All interruptions or 
changes to study treatment administration must be recorded on the eCRF. 
A dose reduction should be considered if the patient missed 2 consecutive doses or 
3 nonconsecutive doses in a cycle due to an AE(s). The missed doses may be the result of a 
combination of AEs during the cycle (eg, Day 1 doses of Weeks 1 and 2 missed due to 
nausea, Day 1 dose of Week 3 missed due to fatigue). Following a dose reduction, dose 
re-escalation is allowed only after consultation with the Sponsor Medical Monitor. 
Patients who require extended dose interruptions without disease progression (eg, 
unacceptable toxicities) will remain on study and continue with tumor scans per schedule of 
assessments as specified in Table 1 and Table 2. 
Patients who withdraw from the study for a study-related AE or an abnormal laboratory value 
must be followed as described in Section 13.1.2. Based on observations from the Phase 1 
studies in patients with advanced hematological and solid tumors, selinexor shows a 
reasonably wide therapeutic range with activities from ~10 mg/m2 to ≥ 60 mg/m2. Based on 
observations in over 1000 patients treated with selinexor alone or in combination with other 
agents, fatigue, anorexia and weight loss associated with selinexor are highly variable and 
patient-specific. Therefore, in order to optimize specific antitumor activity and the patient’s 
tolerability, we will allow for dose or schedule modifications as described in Section 12.2 
below and in Table 9 (pre-specified dose/schedule modifications for AEs related to study 
treatment and supportive care/dose adjustment guidelines, respectively. Patients should also 
be treated aggressively with supportive care to reduce toxicities. If more than one different 
type of toxicity occurs concurrently, the most severe grade will determine the modification. 
For all ≥ Grade 3 hematological or Grade 3 non-hematological AEs that are NOT treatment 
related, after consultation with the Medical Monitor and at the discretion of the Investigator, 
dosing may be maintained provided that the patient can continue to take the agent by mouth.  
For all Grade 4 non-hematologic toxicities, protocol-specified study treatment 
(selinexor/placebo) must be suspended and the Sponsor Medical Monitor consulted regarding 
options for continuation (ie requirements for resuming study treatment or permanent 
discontinuation). 


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Table 8: 
Pre-specified Dose/Schedule Modifications for Adverse Events Related to 
Selinexor/Placebo Treatment 
Dose Level1 
Dose/Schedule Modifications of Selinexor/Placebo2 
Total mg 
Selinexor/Placebo 
Per Week 
Selinexor/Placebo Dose/Schedule 
Dose level 0  
(starting dose) 
120 mg 
60 mg selinexor/placebo 
 (3 tablets) twice weekly (Day 1, Day 3) 
Dose level -1 
100 mg 
100 mg selinexor/placebo on Day 1 
OR 
divided as 60 mg selinexor/placebo on Day 1 and 
40 mg selinexor/placebo on Day 3 
Dose level -2 
80 mg 
80 mg selinexor/placebo on Day 1  
OR  
40 mg selinexor/placebo on Days 1 and 3 
Dose level -3 
60 mg 
60 mg selinexor/placebo on Day 1 
 OR 
divided as 40 mg selinexor/placebo on Day 1 and 
20 mg selinexor/placebo on Day 3 
Dose level -4 
40 mg 
40 mg selinexor/placebo on Day 1  
OR  
20 mg selinexor/placebo on Days 1 and 3 
1For some AEs, dose interruption rather than reduction is recommended. See Table 9 for specific 
recommendations. 
2All placebo doses will contain 0 mg of selinexor. 
 
 


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Table 9: 
Supportive Care and Dose Adjustment Guidelines for Selected Adverse 
Events 
Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Fatigue  
Grade 1  
Maintain dose. Rule out other causes. If found to be anemic and 
symptomatic, consider transfusing even with hemoglobin >8 g/dL 
(anemia Grade <3). 
Patients with significant fatigue after several doses of selinexor may 
have an antitumor response. Consider an unscheduled assessment of 
tumor response as part of the patient’s evaluation.  
Grade 2 lasting ≤7 days 
As per NCCN guidelines, consider stimulants such as methylphenidate 
5mg QD in the morning only. 
Grade 2 lasting >7 days or 
Grade ≥3 
Rule out other causes. If found to be anemic and symptomatic, consider 
transfusions for hemoglobin >8 g/dL (Grade <3); transfusions usually 
indicated for Hb <8 g/dL (Grade ≥3). Interrupt selinexor dosing until 
resolved to Grade 1 or baseline.  
For first occurrence, restart selinexor at current dose.  
For  second occurrence, reduce selinexor by 1 dose level. 
Patients with significant fatigue after several doses of selinexor may 
have an antitumor response. Consider an unscheduled assessment of 
tumor response as part of the patient’s evaluation. 
As per NCCN guidelines, consider stimulants such as methylphenidate 
5mg QD in the morning only. 
Anorexia or Weight loss 
Grade 1 anorexia  
Maintain dose. Rule out other causes. Consider nutritional consultation 
and use nutritional supplements (eg, Ensure®, Boost®). 
For persistent symptoms, initiate appetite stimulants, such as olanzapine 
(2.5 to 5 mg PO every morning) or megesterol acetate (400 mg QD), as 
per NCCN guidelines. 
Grade 1 weight loss 
Grade 2 anorexia 
Initiate appetite stimulants, such as olanzapine (2.5 to 5 mg PO every 
morning) or megesterol acetate (400 mg QD), as per NCCN guidelines. 
Grade 2 weight loss 
Grade 3 anorexia,  
or Grade 3 weight loss 
Interrupt selinexor dosing until improved to Grade 1 or baseline and 
weight stabilizes. Reduce selinexor by 1 dose level. 
Rule out other causes. Consider nutritional consultation and use 
nutritional supplements (eg, Ensure®, Boost®)  
Initiate appetite stimulants as above, 


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


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


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Tumor lysis syndrome 
If TLS risk factors are identified, provide prophylactic IV hydration and regular monitoring of hydration 
(especially when increasing the dose of selinexor), renal function, urine output, and clinical laboratory 
measures of interest for TLS (eg, phosphorus, potassium, calcium, LDH, uric acid). Consider administration 
of hypouricemic agents to reduce the risk of TLS. 
Hold selinexor in patient with hyperkalemia (≥7.0 mmol/L) and/or symptoms of hyperkalemia, an increase in 
uric acid, or other changes in biochemical blood parameters suggestive of TLS. Start IV hydration, and 
consider hypouricemic agent until levels return to normal. Selinexor can be reintroduced at the normal or 
reduced dose. 
Other selinexor-related adverse events 
Grade 1 or 2 
Rule out other causes. Maintain dose. Start treatment and/or standard 
supportive care per institutional guidelines. 
Grade 3 or 4 
Rule out other causes. Interrupt selinexor until recovers to Grade 2 or 
baseline and reduce selinexor by 1 dose level. 
Isolated values of Grade ≥3 alkaline phosphatase do NOT require dose 
interruption. Determination of liver versus bone etiology should be 
made, and evaluation of gamma-glutamyl transferase, 5'-nucleotidase, or 
other liver enzymes should be performed. 
IV: intravenous; NCCN: National Comprehensive Cancer Network; QD: once daily; PO: oral; SC: 
subcutaneous: TLS: tumor lysis syndrome. 
aFor all Grade ≥3 hematologic or non-hematologic AEs that are NOT selinexor related, after consultation 
with the Medical Monitor and at the discretion of the Investigator, selinexor dosing may be maintained. 
bFor all selinexor-related AE’s, if the below prescribed dose reductions/interruptions result in a stabilization 
of 4 weeks, a re-escalation may be considered after approval from the Medical Monitor. 
All dose modifications should be based on the worst preceding toxicity. 
Note: When toxicities due to selinexor have returned to baseline levels or the patient has stabilized, the dose 
of selinexor may be re-escalated in consultation with the Medical Monitor. 
12.2.2. 
Dose Reduction for Decreased Glomerular Filtration Rate (GFR) 
Selinexor is not significantly eliminated by the kidney. Therefore, no dose alteration of 
selinexor/placebo is required in patients with renal dysfunction. 
12.2.3. 
Dose Adjustment in the Setting of Infection 
Patients with active uncontrolled or suspected infections should have treatment interrupted 
until the patient is clinically stable. When ready to resume dosing, treatment may continue at 
the original dose. Missed doses will not be replaced. Patients may continue antibiotics for 
prolonged periods while re-initiating their treatment at the discretion of the Investigator.  
12.2.4. 
Conditions Not Requiring Dose Reduction 
The following conditions are exceptions to the guidelines. Dosing does not need to be 
interrupted in the following cases: 
• Alopecia of any grade 
• Electrolyte or serum analyte (eg, urate) abnormalities that is reversible with standard 
interventions 
• Isolated values of Grade ≥ 3 alkaline phosphatase. Determination of liver versus bone 
etiology should be made, and evaluation of gamma-glutamyl transferase, 
5' nucleotidase, or other liver enzymes should be performed. 


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12.2.4.1. Missed or Vomited Doses 
Missed and Delayed Doses 
A maximum of 2 doses may be given per week.  
If a dose was missed, the schedule of that week should be altered to accommodate two doses 
in that week with at least 36 hr between two consecutive doses.  
If a dose must be skipped (eg, due to recommendation of Investigator), the next dose will 
be taken as per schedule. Doses should not be administered less than 36 hr apart and all 
missed and delayed doses should be documented. 
Vomited Doses 
If a dose is vomited within one hour of ingestion, it will be replaced. If vomiting occurs more 
than one hour after dosing, it will still be considered a complete dose. 
If a patient missed a full week of dosing for non-study treatment related events (eg, a 
required medical procedure or an unanticipated personal emergency), the days missed will 
not be replaced. For example, if patient missed dosing from Cycle 2 Day 7 to Cycle 2 
Day 14, then the patient will re-start dosing on Cycle 2 Day 15. 
12.2.5. 
Supportive Care and Concomitant Treatments 
12.2.5.1. Required Prophylactic Therapy with 5-HT3 Antagonists 
In order to minimize nausea, unless contraindicated, all patients should receive 5-HT3 
antagonists (8 mg or equivalent) starting before the first dose of blinded study treatment and 
continued 2-3 times daily thereafter, as needed. Alternative treatment may be provided if the 
patient does not tolerate 5-HT3 antagonists. 
12.2.5.2. Supportive Care 
General Supportive Care Recommendations 
Supportive measures for optimal medical care should be provided during participation in this 
clinical study. Based on clinical observations 1672 adult patients in Karyopharm-sponsored 
studies as of 31 March 2018, the main adverse drug reactions are primarily related to 
anorexia with poor caloric and fluid intake, fatigue, and nausea. Thrombocytopenia also 
occurs, although it is rarely associated with bleeding. Besides the required 5-HT3 
prophylaxis (Section 12.2.5.1), supportive care including anti-nausea / anti-emetic therapy, 
acid suppression (proton pump inhibitors and/or H2-blockers) and other treatments may be 
administered as described below: 


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a. Appetite stimulants: megesterol acetate at a dose of 80-400 mg daily.  
b. Centrally acting agents, such as olanzapine (5.0 mg at bedtime or 2.5 mg twice daily). 
Additional options, including D2 antagonists, can be found in the NCCN CPGO for 
antiemesis and anorexia/cachexia (palliative care). 
c. 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. 
Supportive Care and Dose Adjustment Recommendations for Specific 
Selinexor-Related Adverse Events 
Please see detailed recommendations in Table 9: Supportive Care and Dose Adjustment 
Guidelines.  
12.2.5.3. Concomitant Medication and Treatment 
Concomitant medication includes any prescription or over-the-counter preparation, including 
vitamins and supplements. 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.  
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. 
Contraception Requirements 
For females of childbearing potential, a negative serum hCG pregnancy test must be obtained 
at Screening within 3 days before the first dose of blinded study treatment. For females of 
childbearing potential who are proceeding to open-label selinexor, a negative serum hCG 
pregnancy test must be obtained at the EoBT Visit (or within 3 days before the first dose of 
open-label selinexor). 
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.  
Female patients should not breastfeed a baby while on this study. It is important that patients 
understand the need to use birth control while on this study.  
Female patients of childbearing potential and fertile male patients who are sexually active 
with a female of childbearing potential must use highly effective methods of contraception 
throughout the study and for 3 months following the last dose of study treatment. 
Highly effective methods of contraception are listed in Section 13.3.1.  
Use of Blood Products 
During treatment, patients may receive RBC or platelet transfusions, if clinically indicated, 
per institutional guidelines. Patients who require repeated transfusion support should be 
discussed with the PI, Sponsor, and Medical Monitor. 


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Appropriate anti-coagulation is allowed during the study (eg, low molecular weight heparin, 
direct factor Xa inhibitors, etc.). Warfarin is allowed during the study provided patients are 
monitored for INR twice a week during the first two cycles of therapy, then weekly to 
biweekly thereafter.  
Patients may receive supportive care with erythropoietin, darbepoetin, granulocyte-colony 
stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF), 
pegylated growth factors, and platelet stimulatory factors, in accordance with clinical 
practice or institutional guidelines, prior to entry and throughout the study.  
Glucocorticoid Therapy 
Glucocorticoids ≤ 20 mg oral prednisone (or equivalent) per day are permitted at baseline 
and during the study for non-malignant conditions (ie, asthma, irritable bowel disease, etc.), 
as needed, but patients should preferably have been on a stable dose for at least two weeks 
before study entry. 
Radiation Treatment 
If clinically indicated, palliative radiation therapy to non-target lesions is permitted but study 
treatment should be interrupted for two days before the start of palliative radiation therapy 
and 2 days after palliative radiation therapy. Treatment shall not be discontinued solely due 
to palliative radiation. (Radiation may be needed to treat the patient’s liposarcoma and would 
require discontinuation of study treatment.) 


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12.3. 
Restrictions and Precautions 
Fasting: 
Patients should maintain an adequate diet. 
Diet: 
There are no dietary restrictions in this study. Patients should maintain 
adequate caloric and fluid intake. 
Medications: 
• Acetaminophen There are not any restrictions on the use of acetaminophen or 
acetaminophen-containing products in combination with study treatment, EXCEPT 
on days on study treatment dosing, when acetaminophen must not exceed a total daily 
dose of 1 gram. 
• Patients should not take any products containing glutathione (GSH), 
S-adenosylmethionine (SAM), or N-acetylcysteine (NAC) during their participation 
in this study as these products may enhance the metabolism of selinexor. Please see 
Appendix 4 for a list of representative products. Patients must report all prescription 
and non-prescription medicines to the Investigator during this study. 
12.4. 
Prohibited Medication 
Acetaminophen must not exceed a total daily dose of 1 gram on days on dosing. On days 
when dose is not taken, there are no restrictions on the use of acetaminophen or 
acetaminophen-containing products 
Patients should not take any products containing GSH, SAM, or NAC during their 
participation in this study as these products may enhance the metabolism of selinexor. Please 
see Appendix 4 for a list of representative products. Patients must report all prescription and 
non-prescription medicines to the Investigator during this study. 
Concurrent therapy with any other approved or investigative anticancer therapeutic is not 
allowed.  
Use of any immunosuppressive agents during the study must be approved by the Medical 
Monitor prior to use.  
Other investigational agents should not be used in conjunction with study treatment but are 
allowed during Survival Follow-up. 
12.5. 
Study Treatment Storage and Accountability 
12.5.1. 
Drug Supply and Storage 
Study treatments must be received by designated personnel at the study site, handled and 
stored safely and properly, and kept in a secured location to which only the Investigator and 
designated site personnel have access. Upon receipt, the study treatment should be stored 
according to the instructions specified on the drug labels and in the selinexor IB. 
The investigational drugs (selinexor and matching placebo) will be supplied by Karyopharm. 


Seli ne x or ( K P T -3 3 0)  
 
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 0 2  
1 2. 5. 2.  
St u d y T re at me nt Acc o u nt a bilit y  
T he I n vesti gat or or desi g nee m ust mai ntai n a n acc urate rec or d of t he s hi p me nt a n d 
dis pe nsi n g of st u d y treat me nt i n a dr u g acc o u nta bilit y l o g. Dr u g acc o u nta bilit y will be n ote d 
b y t he m o ni t or d uri n g site visits a n d at t he c o m pleti o n of t he st u d y. Patie nts will be as ke d t o 
ret ur n all u n use d st u d y tr eat me nt a n d pac ka gi n g o n a re g ular basis, at t he e n d of t he st u d y or 
at t he ti me of st u d y tr eat me nt disc o nti n uati o n.  
At st u d y cl ose -o ut, a n d, as a p pr o priate d uri n g t h e c o urse of t he st u d y, t he I n vesti gat or will 
ret ur n all use d a n d u n us e d st u d y treat me nt, pac k a gi n g, dr u g la bels, a n d a c o p y of t h e 
c o m plete d dr u g acc o u nta bilit y l o g t o t he m o nit or.  
1 2. 5. 3.  
Dis p os al a n d Destr ucti o n  
T he st u d y tr eat me nt s u p pl y ca n be destr o ye d at t he i n vesti gati ve site or t hir d part y, as 
a p pr o priate. D oc u me ntati o n of destr ucti o n is re q uire d if n ot u n derta ke n b y a Kar y o p h ar m 
t hir d part y facilit y. 
1 2. 6.  
Tre at me nt C o m pli a nce  
C o m plia nce will be assesse d b y t h e I n vesti gat or a n d/ or st u d y pers o n nel at eac h p atie nt visit 
a n d i nf or mati o n pr o vi de d b y t he p atie nt a n d/ or care gi v er will be ca pt ure d i n t he s o urce 
d oc u me ntati o n. T his i nf or mati o n m ust be ca pt ure d i n t he s o urce d oc u m e nt at eac h p atie nt 
visit. T he res pecti ve d ose f or i n vesti gati o nal dr u g a n d a n y c h a n ges i n d osi n g m ust be 
ca pt ure d i n t he e C R F. A d diti o nall y, t h e e x act ti me a n d date of d osi n g will be ca pt ur e d o n t he 
da ys of  
 sa m pli n g  
 
C CI


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13. 
 SAFETY DEFINITIONS, RECORDING, AND REPORTING 
13.1. 
Adverse Events 
13.1.1. 
Definitions 
• Adverse event (AE): Any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with 
the use of study treatment, whether or not considered related to the study 
treatment.  
• Treatment-emergent adverse event (TEAE): Any event that was not present prior 
to the initiation of study treatment or any event already present that worsens in 
either intensity or frequency following exposure to study treatment.  
• Adverse event of special interest (AESI): Any AE (serious or nonserious) that is of 
scientific and medical concern specific to the study treatment, for which ongoing 
monitoring and rapid communication by the Investigator to the Sponsor is 
appropriate.  
• Serious adverse event (SAE): Any untoward medical occurrence that, at any dose, 
results in death; is life threatening (ie, an event in which the patient was at risk of 
death at the time of the event; it does not refer to an event that hypothetically 
might have caused death if it were more severe); requires inpatient hospitalization 
or prolongation of existing hospitalization; results in persistent or significant 
disability/incapacity; or is a congenital anomaly/birth defect. (See Section 13.2.2 
for additional information about SAE reporting.) 
13.1.2. 
Recording of Adverse Events 
All AEs that begin or worsen after the patient has provided informed consent will be 
recorded on the Adverse Events eCRF, regardless of whether dosing with study drug has 
commenced. AE monitoring should be continued for at least 30 days following the last dose 
of study treatment (ie, through 30 days following last dose or until resolution or through the 
end of the study for events considered related to study treatment by the Investigator). AEs 
(including laboratory abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. When a 
clear diagnosis cannot be identified, each sign or symptom should be recorded as a separate 
AE. 
The Investigator should ask the patient non-leading questions to determine if AEs occur 
during the study. AEs may also be recorded when they are volunteered by the patient, or 
through physical examination, laboratory tests, or other clinical assessments. 
An AE should be followed until its resolution or until it is judged to be permanent, and 
assessment should be made at each visit (or more frequently, if necessary) of any changes in 


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severity of the event, the suspected relationship to the study treatment, the interventions 
required to treat the event, and the outcome. 
13.1.2.1. Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (ie, are considered to be 
clinically significant, induce clinical signs or symptoms, require concomitant therapy, or 
require changes in study treatment) should be recorded on the Adverse Events eCRF. 
Whenever possible, a diagnosis, rather than a symptom should be provided (eg, anemia 
instead of low hemoglobin). Laboratory abnormalities that meet the criteria for an AE should 
be followed until they have returned to baseline (at screening) or an adequate explanation of 
the abnormality is identified. When an abnormal laboratory or test result corresponds to a 
sign/symptom of an already reported AE, it is not necessary to separately record the 
laboratory/test result as an additional event. 
A laboratory abnormality that does not meet the definition of an AE should not be reported as 
an AE. A Grade 3 or 4 event (severe per NCI CTCAE v. 4.03) does not automatically 
indicate an SAE unless it meets the definition of serious as defined in Section 13.1.1 and/or 
as per Investigator’s discretion. A laboratory abnormality that results in a dose being 
interrupted or modified would, by definition, be an AE and must be recorded as such in the 
eCRFs. 
13.1.2.2. Other Adverse Events 
13.1.2.2.1. Tumor Lysis Syndrome  
As of May 2018, 8 TLS cases have been reported: 4 patients in Karyopharm-sponsored 
studies, 2 patients in Investigator-sponsored studies, and 2 patients in the expanded access 
program (compassionate use). Of the 8 patients, 5 had MM reported as their underlying 
cancer and 3 had hematological malignancies (including AML and acute lymphoblastic 
leukemia). The event onset latency ranged from 3 to 8 days (median 4 days). The total 
selinexor dose prior to event onset ranged from 40 mg to 320 mg (median 160 mg). The 
outcome was reported as recovered in 4 patients, not recovered in 2 patients, and the outcome 
was not reported in 2 patient. The Investigators assessed 7 of the events as related to 
selinexor. Of the 8 cases summarized above, there were 3 cases with Grade 5 TEAEs 
reported. The cause of death in each of these cases was reported as: respiratory failure 
secondary to advanced MM (Grade 5), sepsis (Grade 5), and respiratory failure, 
chemotherapy-induced cardiomyopathy and acute lymphoid leukemia (Grade 5). No fatal 
outcomes due to TLS have been reported in any studies with selinexor, or in the ongoing 
expanded access program. Although the incidence of TLS is low (~0.3%), the causal 
relationship between selinexor treatment and TLS cannot be completely excluded. Early 
recognition of signs and symptoms in patients at risk for TLS, including identification of 
abnormal clinical and laboratory values, is key and Investigators must ensure that patients 
being treated with selinexor maintain adequate caloric and fluid intake. Close monitoring and 
management of patients with hematological malignancies for potential signs and symptoms 
of TLS are most relevant. See Table 9 for supportive care and Table 8 for selinexor dose 
modification guidance.  


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13.1.3. 
Adverse Event Severity 
The severity of the AE will be graded by the Investigator according to the NCI CTCAE 
Grading Scale, v. 4.03 (the NCI CTCAE files can be accessed online at the following URL: 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html). 
If NCI CTCAE grading does not exist for an AE, the severity will be characterized as “mild,” 
“moderate,” “severe,” or “life-threatening (corresponding to Grades 1 to 4) according to the 
following definitions: 
• Grade 1 (Mild) events are usually transient and do not interfere with the patient’s 
daily activities. 
• Grade 2 (Moderate) events introduce a low level of inconvenience or concern to 
the patient and may interfere with daily activities. 
• Grade 3 (Severe) events interrupt the patient’s usual daily activities. 
• Grade 4 events are Life-threatening. 
The term “severe” is used to describe the intensity of an AE; the event itself could be of 
relatively minor clinical significance (eg, ‘severe’ headache). This is not the same as a 
“serious” AE. 
13.1.4. 
Adverse Event Causality 
The Investigator will make a judgment regarding the relationship of the AE to study 
treatment, as defined below. 
• Not related: 
These events will lack a temporal relationship of the event to 
the study treatment, making a causal relationship not 
reasonably possible. Exposure to other drugs, therapeutic 
interventions, or underlying conditions may provide a 
sufficient explanation for the event. 
• Related: 
There is a temporal relationship of the event to the study 
treatment making a definitive relationship, and the event is 
more likely explained by exposure to the study treatment than 
by any other drugs, therapeutic interventions, or underlying 
conditions. 
13.2. 
Serious Adverse Events 
See Section 13.1.1  for the definition of an SAE. Please note that SAEs that occur at any time 
between the signing of the ICF up to the first dose of study treatment must be reported (in 
addition to SAEs that occur after the first dose of study treatment).  
Important medical events that may not result in death, are not life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention 
to prevent 1 of the outcomes listed in this definition. Examples of such events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 


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dyscrasias or convulsions that do not result in in-patient hospitalization, or the development 
of drug dependency or drug abuse. 
Events that Do Not Meet the Definition of an SAE 
Elective hospitalizations to administer, or to simplify study treatment or study procedures 
(i.e., an overnight stay to facilitate 24-hour urine capture) or other medical procedures are not 
considered SAEs. However, a hospitalization meeting the regulatory definition for ‘serious’ 
is any inpatient hospital admission that includes a minimum of an overnight stay in a health 
care facility. An emergency room visit is not considered a hospitalization unless it results in 
an official admission to the hospital (eg, undesirable effects of any administered treatment) 
must be documented as an SAE. 
Progression of the malignancy (including fatal outcomes) should NOT be reported as an SAE 
during the study or within the safety reporting period (see Section 13.2.2). Sudden and 
unexplained death should be reported as an SAE. If there is any uncertainty about a finding 
being due solely to progression of malignancy, the finding should be reported as an AE or 
SAE, as appropriate, Section 13.1.1).  
13.2.1. 
Recording of Serious Adverse Events 
It is the responsibility of the Investigator to record and document all SAEs occurring from 
the signing of the ICF until at least 30 days after the patient has stopped study treatment. All 
SAEs must be reported on the designated sponsor SAE Report Form in addition to being 
recorded in the eCRF. The original SAE report form must be retained in the Investigator’s 
site file. 
All applicable sections of the form must be completed in order to provide a clinically 
thorough report. The Investigator must assess and record the relationship of each SAE to 
study treatment and complete the SAE Report Form (in English). 
See ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting, Attachment 1) for key data elements that are required for expedited reporting. 
13.2.2. 
Reporting of Serious Adverse Events 
Every SAE, regardless of the causal relationship to the study treatment, occurring after the 
patient has signed informed consent, until at least 30 days after the patient has stopped study 
treatment, must be reported to the Karyopharm Pharmacovigilance Department within 
24 hours of learning of its occurrence. The investigational site personnel must use the SAE 
Report Form provided by Karyopharm for reporting any SAE to the Karyopharm 
Pharmacovigilance Department. 
Upon completion, the SAE Report Form must be immediately emailed or faxed to: 
Pharmacovigilance Department 
Karyopharm Therapeutics Inc. 
Email: pharmacovigilance@karyopharm.com 
Fax: 
+1-617-334-7617 (USA) 
+49-89-9218-5650 (Germany) 


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Any SAE observed after the 30-day follow-up period should only be reported to Karyopharm 
if the Investigator suspects that the SAE has a causal relationship to study treatment. 
Recurrent episodes, complications, or progression of the initial SAE must be reported as 
follow-up to the original episode within 24 hours of the Investigator receiving the follow-up 
information.  
An SAE should be followed until its resolution or until it is judged to be permanent, and 
assessment should be made at each visit (or more frequently, if necessary) of any changes in 
severity of the event, the suspected relationship to the study treatment, the interventions 
required to treat the event, and the outcome. 
13.2.3. 
Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are SAEs that are unexpected and 
judged by the Investigator or Karyopharm to be related to the study treatment administered. 
SUSARs will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with the FDA’s “Safety Reporting Requirements for 
Investigational New Drugs and Bioanalytical/Bioequivalence Studies” or as per national 
regulatory requirements in participating countries. 
In addition, Karyopharm will communicate all cases of cerebellar toxicity, Grade 3 or higher, 
to regulatory authorities, central ethics committees (eg, IRBs), and Investigators, in the 
format of an expedited Safety Report, within 7 days of awareness of the event.  
If required by local regulations, the Investigator is responsible for notifying his/her IRB or 
local ethics committee of all SAEs. 
13.3. 
Procedures for Handling Special Situations 
13.3.1. 
Pregnancy and Breastfeeding 
Note: Pregnancy per se is not considered to be an AE; however, it is discussed here because 
of the importance of reporting pregnancies that occur during studies and because a medical 
occurrence observed in the mother or fetus/newborn would be classified as an AE. 
During both blinded and open-label treatment, female patients of childbearing potential and 
fertile male patients will be informed as to the potential risk of conception while participating 
in this study and will be advised that they must use highly effective contraception listed 
below (ie, results in a low failure rate when used consistently and correctly) during the 
dosing period and for a period of at least 3 months after the end of treatment. 
Highly effective methods include: 
• 
combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation:  
o oral 
o intravaginal 
o transdermal 
• 
progestogen-only hormonal contraception associated with inhibition of ovulation:  


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o oral 
o injectable 
o implantable 
• 
intrauterine device 
• 
intrauterine hormone-releasing system 
• 
bilateral tubal occlusion 
• 
vasectomized partner 
• 
sexual abstinence 
During both blinded and open-label treatment a pregnancy test will be performed on each 
premenopausal female patient of childbearing potential prior to the first dose of study drug, 
on Day 1 of Cycles ≥2 while on treatment, and again at treatment discontinuation during the 
End-of-Treatment visit. A negative pregnancy test must be documented prior to 
administration of study drug. 
If a patient is confirmed pregnant during the study, study drug administration must be 
discontinued immediately. The Investigator must immediately notify the sponsor medical 
monitor of this event and record the Pregnancy on the Pregnancy Form. The initial 
information regarding a pregnancy must be forwarded to Karyopharm Pharmacovigilance by 
email or fax within 24 hours of first knowledge of its occurrence. A pregnancy report form is 
provided by Karyopharm. 
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. 
Pregnancies must be reported to Karyopharm, regardless of whether the patient received 
selinexor or other study drugs, regardless of whether the patient withdraws from the study or 
the study is completed, for 3 months after the patient receives his/her last dose of study 
treatment. Patients should be instructed to inform the Investigator regarding any pregnancies. 
Any SAE that occurs during pregnancy must be recorded on the SAE report form (eg, 
maternal serious complications, therapeutic abortion, ectopic pregnancy, stillbirth, neonatal 
death, congenital anomaly, birth defect) and reported within 24 hours in accordance with the 
procedure for reporting SAEs. 
A pregnancy in a female partner of a male patient must be reported to Karyopharm within 
24 hours of learning of its occurrence. Pregnancies in female partners should only be 
followed if the male patient is being treated with a selinexor-containing regimen. Consent to 
report information regarding these pregnancy outcomes should be obtained from the female 
partner. 
It is not known whether selinexor passes into the breast milk. Mothers should not breastfeed 
while being treated with selinexor-containing regimen. 


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13.3.2. 
Overdose, Abuse, Misuse, Medication Errors, and Occupational Exposure 
All incidences of overdose, abuse, misuse, medication errors, and occupational exposure are 
required to be reported to Karyopharm Pharmacovigilance on an SAE report form, emailed to 
pharmacovigilance@karyopharm.com, regardless of whether or not there is an associated AE 
or SAE. 
13.3.2.1. Overdose 
An overdose is a deliberate or accidental administration of any study treatment to a study 
patient, at a dose greater than that which was assigned to that patient per the study protocol. 
If an overdose occurs, the Investigator and Karyopharm should be notified immediately, and 
the patient should be observed closely for AEs. Resulting symptoms should be treated, as 
appropriate, and the incident of overdose and related AEs and/or treatment should be 
documented in the patient’s medical record and in the eCRF. Overdose is to be reported on 
an SAE report form to Karyopharm Pharmacovigilance regardless of whether or not an AE or 
SAE has occurred due to the overdose. If the overdose is associated with an SAE, the SAE 
report form must be submitted to Karyopharm Pharmacovigilance within 24 hours of 
awareness. If there is no AE or SAE, the report must be submitted within 24 hours of 
awareness. 
As selinexor is metabolized by GSH conjugation, it is possible, but not demonstrated, that 
hepatic GSH depletion might occur in case of extreme overdose. Therefore, in overdose 
cases, if patients develop liver function test abnormalities, supportive measures such as SAM 
or other drugs that can replace GSH might be considered as part of the overall management 
plan. 
13.3.2.2. Abuse, Misuse, or Medication Error 
Abuse is the persistent or sporadic, intentional excessive use of the study treatment which is 
accompanied by harmful physical or psychological effects.  
A medication error is any preventable incident that may cause or lead to inappropriate study 
treatment use or patient harm while the study treatment is in the control of the health care 
professionals or patients. Such incident may be due to health care professional practice, 
product labeling, packaging and preparation, procedures for administration, and systems, 
including the following: prescribing, order communication, nomenclature, compounding, 
dispensing, distribution, administration, education, monitoring, and use. 
All occurrences of abuse, misuse, or medication error with any study treatment are to be 
reported on an SAE report form to Karyopharm Pharmacovigilance regardless of whether or 
not an AE or SAE has occurred due to the abuse, misuse, or medication error. If the abuse, 
misuse, or medication error is associated with an SAE, the SAE report form must be 
submitted to Karyopharm Pharmacovigilance within 24 hours of awareness. If there is no AE 
or SAE, the report must be submitted within 24 hours of awareness. 
13.3.2.3. Occupational Exposure 
Occupational exposure is the exposure to a study treatment as a result of one’s professional 
or non-professional occupation.  


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All occurrences of occupational exposure with any study treatment are to be reported on an 
SAE report form to Karyopharm Pharmacovigilance regardless of whether or not an AE or 
SAE has occurred due to the occupational exposure. If the occupational exposure is 
associated with an SAE, the SAE report form must be submitted to Karyopharm 
Pharmacovigilance within 24 hours of awareness. If there is no AE or SAE, the report must 
be submitted within 24 hours of awareness. 
  


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14. 
STATISTICAL METHODS 
A statistical analysis plan (SAP) will be finalized prior to database lock. Any deviation from 
the statistical plan will be described in the final report. 
14.1. 
General Considerations 
This is a multicenter randomized double-blind Phase 2-3 study of the SINE selinexor given 
orally in patients with advanced unresectable liposarcoma.  
Enrollment in Phase 2 has been completed and the preplanned analysis of PFS (after 40 PFS 
events were observed) was performed. Details are provided in Section 14.1.1.1. 
There was no break between Phase 2 and Phase 3 enrollment. 
In Phase 3, patients will be randomized in a 2:1 fashion to receive selinexor (60 mg) or 
placebo. Randomization details are provided in Section 7.7.  
Patients in the placebo arm who have PD while they are receiving blinded study treatment 
will be allowed to cross over to open-label selinexor (see Section 7.2.1).  
Patients who are on blinded study treatment at the time of the primary PFS analysis at the 
end of Phase 3 may proceed as follows: 
• 
Patients in the placebo arm may cross over to open-label selinexor. 
• 
Patients in the selinexor arm will continue selinexor but as open-label treatment. 
Tabulations will be produced for appropriate demographic, baseline, efficacy, and safety 
parameters. For categorical variables, summary tabulations of the number and percentage of 
patients within each category (with a category for missing data) of the parameter will be 
presented, as well as two-sided 95% CIs, unless otherwise stated. For continuous variables, 
the number of patients, mean, median, standard deviation, minimum, and maximum values 
will be presented. Time-to-event data will be summarized with Kaplan-Meier methodology 
using 25th, 50th (median), and 75th percentiles with associated 2-sided 95% CIs as well as 
percentage of censored observations.  
14.1.1. 
Determination of Sample Size 
14.1.1.1. Determination of Sample Size for Phase 2 
Enrollment in Phase 2 has been completed.  
Fifty-seven patients were randomized to selinexor or placebo in a 1:1 allocation. 
Randomization details are provided in Section 7.7.  
The preplanned analysis of PFS (after 40 PFS events were observed) was performed and 
served as a guideline to inform the final design of the Phase 3 portion of the study. 
A summary of the preliminary efficacy results for Phase 2 is provided in Section 4.3.2. 


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Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 1 2  
1 4. 1. 1. 2.  Deter mi n ati o n of S a m ple Size f or P h ase 3  
Per pr ot oc ol, t he  P hase 3 sa m ple  siz e was re-e val u ate d base d o n t he P has e 2 res ults . Sa m ple 
siz e calc ulati o ns were c o n d ucte d u n der t he f oll o wi n g ass u m pti o ns: 
Base d o n t h ese ass u m pti o ns, a p pr o xi matel y 2 7 7  eli gi ble patie nts will be r a n d o mize d 2: 1 t o 
recei v e eit her s eli ne x or ( 6 0 m g t wice wee kl y ) or place b o, res pecti vel y i n a bli n ded ma n ner t o 
o bs er ve 2 0 9 P F S e v e nts . Sa m ple siz e ma y be re-esti mate d base d o n t he i nteri m a nal ysis (see  
Secti o n  1 4. 1. 1. 2. 1 ). 
1 4. 1. 1. 2. 1.  P h ase 3 I nteri m A n al ysis After 1 0 5 P F S E ve nts 
T he i nteri m a nal ysis was c o n d ucte d at 1 0 8 P F S e v e nts a n d t he res ults were re vie we d b y t h e 
D S M B o n Se pte m ber 2 5, 2 0 1 9 . T he p ur p ose of t his i nteri m a nal ysis was f or sa m ple siz e re -
esti mati o n wit h a n  earl y st o p pi n g b o u n dar y f or efficac y.  
A n e xter nal, u n bli n de d statisticia n calc ulate d a n d prese nte d t o D S M B m e m bers  
C CI
C CI
C CI


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Based on the safety and efficacy data, the DSMB recommendation was continuation of the 
study with no change to safety monitoring and no sample size adjustment.   
All sample size calculations were conducted using EAST Version 6.4 or higher (East 2016). 
14.1.2. 
Blinding and Randomization 
Study treatment will be administered in a blinded manner. Randomization will be performed 
across study sites within the stratification factors, in order to maintain the required 
1:1 (selinexor:placebo in Phase 2) or 2:1 (selinexor:placebo in Phase 3) randomization. 
Randomization will be performed by a centralized system after confirmation of patient 
eligibility by the Sponsor (see Section 7.6 and Section 7.7). 
14.2. 
Analysis Population 
14.2.1. 
Intent-to-Treat Population 
The intent-to-treat (ITT) population will consist of all patients who are randomized to study 
treatment in Phase 3. This population will be used for primary analyses of efficacy. Patients 
will be analyzed in the treatment arm to which they were randomized. 
14.2.2. 
Per-Protocol Population 
The per-protocol (PP) population will consist of all patients in the ITT population who have 
no major protocol violations, including mis-randomizations, that would compromise the 
assessment of efficacy; this would include receipt of sufficient study treatment 
(80% compliance or more). Major violations will be determined independently of knowledge 
of response to study treatment. This population will be used for supportive inferences 
concerning efficacy. Patients will be analyzed according to the treatment actually received. 
14.2.3. 
Safety Population 
The safety population will consist of all patients who have received any amount of study 
treatment. Patients will be analyzed according to the treatment actually received. 
14.3. 
Data Analysis and Presentation 
Summary tabulations will be provided for disposition, 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.  
14.3.1. 
Disposition of Patients 
A tabulation of patient disposition will be presented including the number in each analysis 
population, the number in each analysis population, the number censored at each of the PFS 
and OS analyses, the number lost to follow-up, the number that withdrew, and reason(s) for 
withdrawal. 
A by-patient listing of patient disposition information including the reason for study 
withdrawal, where applicable, will be presented. 


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14.3.2. 
Demographic Characteristics 
Demographic characteristics will be summarized by treatment arm, as well as overall, and 
will include gender, race, ethnicity (Hispanic origin), and age at time of consent. For gender, 
race, and Hispanic or Latino 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 arm and the total sample. No formal hypothesis testing of 
treatment differences will be performed. 
14.3.3. 
Baseline Characteristics and Medical History 
Baseline characteristics include ECOG performance status, duration from initial diagnosis, 
response to previous therapy, types of prior therapy, and number of prior therapies. Baseline 
data will be summarized for each treatment group using summary statistics; no formal 
hypothesis testing of treatment differences will be performed. 
Medical history and physical examination results at baseline will be tabulated by treatment. 
14.3.4. 
Efficacy Analysis 
Disease assessments at the date of surgical or radiotherapy intervention may be censored in 
patients receiving such care, since these patients are receiving non-protocol specified therapy 
(ie, intervention), which may impact endpoint(s).  
Based on the preplanned analysis of PFS by WHO and RECIST v. 1.1 Criteria in the Phase 2 
portion of the study, the response criteria for the primary analysis (PFS) were changed from 
WHO to RECIST v. 1.1 Criteria in Version 4.0 of the protocol. Consequently, data from the 
Phase 2 portion of the study will be excluded from the final efficacy analysis in order to 
maintain statistical integrity and preserve overall Type I error rate. 
14.3.4.1. Efficacy Analysis for Phase 2 
All Phase 2 analyses will be conducted among Phase 2 patients only. 
Phase 2 Primary Endpoint Analysis: 
The preplanned analysis of PFS after 40 PFS events was conducted with an 11 August 2017 
data cut with 49 eligible patients whose treatment assignments were available. Patients were 
analyzed in the treatment arm to which they were randomized. The preplanned PFS analysis 
was conducted by both WHO and RECIST v. 1.1 Criteria and served as a guideline to inform 
the final design of the Phase 3 portion of the study. See Section 4.3.2 for a summary of the 
preliminary data.  
The primary endpoint PFS for Phase 2 is defined as the time from date of randomization 
until the first date of PD, per RECIST v. 1.1, or death due to any cause. Evaluation of the 
radiographic data for the PFS primary endpoint will be based on data from a scan review 
by the independent central reader. 
The formal primary Phase 2 PFS analysis will be performed on all 56 eligible patients 
randomized to study treatment in Phase 2 when their treatment assignments are unblinded. 
Patients will be analyzed in the treatment arm to which they are randomized.  


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P F S data will be s u m mariz e d wit h Ka pla n -Meier met h o d ol o g y usi n g 2 5t h, 5 0t h ( me dia n), 
a n d 7 5t h perce ntiles wit h ass ociate d 2 -si de d 9 5 % CIs , as w ell as perce nta ge of ce ns ore d 
o bser vati o ns. T he stratifi e d l o g -ra n k test will be use d t o c o m pare t h e P F S distri b uti o ns 
bet wee n tr eat me nt ar ms.  
P hase 2 Sec o n dar y E n d p oi nt A nal ysis  
Sec o n dar y effic ac y varia bles will i ncl u de t he f oll o wi n g, acc or di n g t o t he d efi niti o ns 
descri be d i n t he o bje cti ves a n d st u d y e n d p oi nts:  
•  T T P  o n st u d y treat me nt c o m pare d wit h T T P o n t he patie nt’s last pri or s yste mic 
t hera p y 
•  O R R  
•  D O R  
•  T u m or gl uc os e meta b olis m, de nsit y, a n d size usi n g F D G -P E T a n d C T ( dia g n ostic) 
after 6 wee ks of treat me nt.  
Sec o n dar y ti me -t o-e ve nt e n d p oi nts will be a nal yze d usi n g t he stratifie d l o g -ra n k test as 
descri be d a b o ve.  
P has e 2 Sa m ple Siz e Calc ulati o n a n d Statistical P o wer:  
E nr oll me nt i n P hase 2 has bee n c o m plete d.  Details are pr o vi de d i n Secti o n  1 4. 1. 1. 1 . 
1 4. 3. 4. 2.  Effic ac y A n al y sis f or P h ase 3 
T he fi nal efficac y a nal ysis will be c o n d ucte d a m o n g P hase 3 p atie nts o nl y.  
Stratifie d l o g -ra n k tests will be use d t o c o m pare t he distri b uti o ns of ti me-t o-e ve nt e n d p oi nt s 
( P F S, O S, D O R, T T P) bet wee n t he t w o ar ms usi n g a 1-si de d test a n d al p h a = 0. 0 2 5 le vel of 
si g nifica n ce, a n d t o esti mate e ve nt free rate at vari o us ti me p oi nts ( e g, 1- ye ar rat e, 2 -year 
rate, etc.) al o n g wit h 9 5 % CIs . Stratificati o n fact ors f or t he stratifie d l o g-ra n k test are t h ose 
t hat were us e d f or ra n d o mizati o n. T he C ui,  H u n g, a n d Wa n g ( C H W) met h o d (C ui  1 9 9 9 ) will 
be use d t o acc o u nt f or i nt eri m testi n g a n d p ossi ble sa m ple -siz e re-esti mati o n t o preser ve t h e 
o verall T y pe I err or rat e.  
1 4. 3. 4. 2. 1.  P h ase 3 Pri m ar y E n d p oi nt A n al ysis  
T he pri mar y P F S a n al ysis wil l be perf or me d o n t h e I T T p o p ulati o n f or P hase 3 patie nts i n  
a n d o n t he P P p o p ulati o n as a s u p p orti ve a n al ysis. T he stratifie d l o g -ra n k test will be use d 
t o test t he n ull h y p ot h esis t hat t he P F S distri b uti o ns are t he sa m e f or b ot h treat me nt gr o u ps 
vers us  the alter nati ve h y p ot hesis t hat t he d urati o n of P F S f or t he seli ne x or ar m is l o n ger  
t ha n t he place b o ar m usi n g a 1-si de d test a n d al p h a = 0. 0 2 5 le vel of si g nifica nce, a dj uste d 
usi n g t he C H W met h o d .  
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Multivariable Cox proportional hazards model will be used to assess PFS, adjusted for 
stratification factor and other prognostic covariates. Model assumptions will be examined, 
and in the presence of non-proportional predictors, stratification or including a 
time-dependent variable of the non-proportional predictors will be considered as 
appropriate. 
14.3.4.2.2. Phase 3 Secondary Key and Efficacy Endpoint Analysis 
Secondary Key Endpoint Analysis 
Key secondary variables will include the following, assessed in hierarchical fashion in the 
order presented (to preserve the overall Type I error for the study), according to the 
definitions described in the objectives and study endpoints:  
• OS for non-inferiority 
• OS for superiority 
OS endpoints will be analyzed using the stratified log-rank test as described above. In 
sensitivity analysis for OS, the 2-stage estimation method will be implemented to assess the 
impact of cross-over on the effect of selinexor on OS (Latimer 2017, Latimer 2018). 
Secondary Efficacy Endpoint Analysis 
The comparison of TTP in the current study to TTP on the most recent prior therapy will be 
performed as time-to-event using a stratified log-rank test stratified by patient IDs to 
account for correlation within patient and adjusted for treatment arm. Note that TTP for the 
current study may represent censored results, therefore, to minimize the impact of 
censoring, this analysis may require maturation of the TTP data beyond the required time at 
which the number of events for the primary PFS analysis at the end of Phase 3 have 
occurred. 
Comparison of ORR between the two treatment arms will be performed using the 
Cochran-Mantel-Haenszel (CMH) χ2 or exact test as appropriate, stratified by the 
randomization stratification factors. For OS, an additional descriptive comparison of the 
median OS from the randomized selinexor arm will be made to historical OS to the extent 
feasible, to assist in providing the proper context for the ITT analysis of selinexor versus 
placebo. 
DOR and PFS according to the Investigator will be analyzed using the stratified log rank 
test as described above. 
QoL Analysis 
The QoL endpoint as assessed by the EORTC QLQ-C30 and EuroQoL EQ-5D-5L 
questionnaires will be analyzed as a total score, using a linear mixed effects model with 
fixed effect of treatment arm, randomization stratification factors, and the baseline value 
for the parameter in the model as a covariate, as well as random effect of subjects and 
repeated measures over time points. For EORTC QLQ-C30 the transformed score will be 
used, calculated according to the EORTC QLQ-C30 Scoring Manual. For the EuroQoL 
EQ-5D-5L questionnaire, the overall health score will be used. 


Seli ne x or ( K P T -3 3 0)  
 
Kar y o p har m T hera pe utics I nc.  
Cli nical St u d y Pr ot oc ol: K C P -3 3 0 -0 2 0  
2 1  Ma y  2 0 2 0
 
 
 
Versi o n 9. 0  
C o nfi de ntial  
P a ge 1 1 7  
1 4. 3. 4. 2. 3.  P h ase 3 E x pl or at or y E n d p oi nt A n al ysis  
1 4. 3. 6.  
S afet y A n al ysis  
Safet y a nal yses will be perf or me d o n t h e Safet y P o p ulati o n , w hic h i ncl u des all patie nts w h o 
recei v e at least o ne d os e of st u d y tr eat me nt . Patie nts will be a nal yze d acc or di n g t o t he 
treat me nt act u all y recei ve d. 
P hase 2 safet y d ata will be i nte grate d wit h t he P hase 3 safet y dat a i n t he fi n al safet y a n al ysis.  
T he safet y a n d t olera bilit y of s eli ne x or will be e val uate d b y m ea ns of dr u g -relate d A E 
re p orts, p h ysical e x a mi nati o ns, a n d la b orat or y s afet y e val uati o ns. C T C A E, v. 4. 0 3 will be 
use d f or gra di n g of A Es. I n v esti gat ors will pr o vi de t heir assess me nt as eit her r el ate d or n ot 
relate d t o st u d y treat me nt.  
T E A Es, S A Es, A Es of at least Gra d e 3 i n se verit y, relate d A Es, a n d A Es le a di n g t o 
wit h dra wal of tr eat me nt will be s u m marize d b y tr eat me nt gr o u p a n d i n t he o verall safet y 
p o p ulati o n. T E A Es will be t h ose t hat start or w orse n o n or after t he first d a y of st u d y 
treat me nt, t hr o u g h 3 0 da ys after last d ose; r elate d A Es will be t h ose wit h a n I n v esti gat or 
deter mi nati o n of rel ate d t o treat me nt. La b orat or y d ata will be a nal yz e d b y s u m mar y 
statistics o ver ti me, as well as b y shift ta bles b ase d o n C T C A E v. 4. 0 3 gra des of se verit y.  
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14.3.6.1. Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and 
displayed in tables and listings using MedDRA system organ class (SOC) and Preferred 
Term. 
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 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 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 causal relationship between the occurrence of an AE and the study treatment will be 
judged by the Investigator as either related or not related to study treatment. In the event a 
patient experiences repeat episodes of the same AE, then the event with the highest severity 
and/or strongest causal relationship to treatment will be used for purposes of tabulations.  
SAEs will also 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: patient deaths; serious AEs; and AEs leading to withdrawal. 
14.3.6.2. Laboratory Data 
Clinical laboratory values will be expressed using conventional SI units. 
For each treatment arm, the actual value and change from baseline (Day 1, prior to the first 
administration of study treatment) to each on study evaluation will be summarized for each 
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 criteria (eg, those 
measures that have a corresponding CTCAE grade classification). Labs with CTCAE grades 
greater than or equal to 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 
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14.3.6.3. Vital Signs and Physical Examinations 
The actual value and change from baseline (Day 1, prior to the first administration of study 
treatment) to each on study evaluation will be summarized for vital signs. 
By-patient listings of vital sign measurements will be presented in data listings. 
Abnormal physical examination results at screening, and abnormal physical examination 
results (AEs) during the study, will be summarized. All physical examination findings will be 
presented in by-patient data listings. 
14.3.6.4. Concomitant Medications 
The use of concomitant medications will be included in by-patient data listings. 
14.3.7. 
Procedures for Handling Missing Data 
No imputation of missing efficacy data is planned for the primary analysis of efficacy 
endpoints. For patient reported QoL measurements, missing data will be handled as described 
in the EORTC-QLQ-C30 and EuroQoL EQ-5D-5L Scoring Manuals. Additional sensitivity 
analyses will be done using the Jump to Reference (J2R) and last observation carried forward 
imputation approaches.  
For time to event analyses, patients who have no efficacy evaluations will be considered as 
censored at time 0. For OS, patients will be censored on the date they were last known to be 
alive regardless of disease status.  
For AEs, missing dates will not be imputed; however, if partial dates are available, they will 
be used to assess if the AE occurred during the treatment period. Missing severities of AEs 
will not be imputed and will be considered missing in any tabulations of AE severity. If an 
AE is missing a response to the question regarding relationship to treatment, the event will be 
considered to be related. 
14.4. 
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. 
14.5. 
Clinical Study Reports 
A primary clinical study report (CSR) may be written based on all available patients’ data 
following completion of the primary PFS analysis. The final CSR will be reported when all 
patients have completed the follow-up period, withdrawn consent, lost to follow-up, or have 
died. 
  


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15. 
DATA COLLECTION AND MANAGEMENT 
15.1. 
Data Confidentiality 
Information about study patients will be kept confidential and managed under the applicable 
laws and regulations. Those regulations require a signed patient authorization informing the 
patient of the following: 
• What protected health information (PHI) will be collected from patients in this study  
• Who will have access to that information and why  
• Who will use or disclose that information  
• The rights of a research patient to revoke their authorization for use of their PHI.  
In the event that a patient revokes authorization to collect or use PHI, the Investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization. For patients that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect follow-up safety information (eg has the 
patient experienced any new or worsened AEs) at the end of their scheduled study period. 
The data collection system for this study uses built-in security features to encrypt all data for 
transmission in both directions, preventing unauthorized access to confidential participant 
information. Access to the system will be controlled by a sequence of individually assigned 
user identification codes and passwords, made available only to authorized personnel who 
have completed prerequisite training. 
15.2. 
Site Monitoring 
Before study initiation, at a site initiation visit or at an Investigator’s meeting, Karyopharm 
personnel (or designated contract research organization) will review the protocol and CRFs 
with the Investigators and their staff. During the study, the monitor will visit the site 
regularly to check the completeness of patient records, accuracy of entries on the CRFs, 
adherence to the protocol and to Good Clinical Practice (GCP), progress of enrollment, and 
to ensure that study treatment is being stored, dispensed, and accounted for according to 
specifications. Key study personnel must be available to assist the monitor during these 
visits. 
The Investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. All 
information recorded on CRFs must be traceable to source documents in the patient's file. 
The Investigator must also keep the original signed ICF (a signed copy is given to the 
patient). 
The Investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the CRF entries. Karyopharm monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion 
criteria and documentation of SAEs. Additional checks of the consistency of the source data 
with the CRFs are performed according to the study-specific monitoring plan. 


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15.3. 
Data Collection 
This study will utilize Electronic Data Capture (EDC), the designated clinical site staff will 
enter the data required by the protocol into the eCRF. The eCRFs have been built using fully 
validated secure web-enabled software that conforms to 21 CFR Part 11 requirements. 
Clinical site staff will not be given access to the EDC system until they have been trained. 
Automatic validation programs check for data discrepancies in the eCRFs and allow 
modification or verification of the entered data by the Investigator staff. 
The Investigator is responsible for assuring that the data entered into the eCRF is complete 
and accurate, and that entry and updates are performed in a timely manner. 
Concomitant treatments and prior medications entered into the database will be coded using 
the WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical 
classification system. Medical history/current medical conditions and AEs will be coded 
using the MedDRA terminology. 
15.4. 
Database Management and Quality Control 
Karyopharm personnel (or designated contract research organization) will review the eCRF 
data entered by investigational staff for completeness and accuracy. Electronic data queries 
stating the nature of the problem and requesting clarification will be created for discrepancies 
and missing values and sent to the investigational site via the EDC system. Designated 
Investigator site staff are required to respond promptly to queries and to make any necessary 
changes to the data. 
At the conclusion of the study, after discrepancies and missing values have been completed 
and the data have been verified to be complete and accurate, the database will be declared 
locked.  
For EDC studies, after database lock, the Investigator will receive a CD-ROM or paper 
copies of the patient data for archiving at the investigational site. 


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16. 
ETHICAL AND ADMINISTRATIVE OBLIGATIONS 
16.1. 
Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
the International Council for Harmonisation (ICH) Harmonized Tripartite Guidelines for 
Good Clinical Practice, with applicable local regulations (including European Directive 
2001/20/EC and US Code of Federal Regulations (CFR) Title 21), and with the ethical 
principles that originate from the Declaration of Helsinki. 
16.2. 
Responsibilities of the Investigator and Good Clinical Practice 
16.3. 
Institutional Review Boards/Independent Ethics Committees 
The protocol and the proposed ICF(s) must be reviewed and approved by a properly 
constituted IRB/IEC 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 procedures found in this protocol and to 
give access to all relevant data and records to Karyopharm monitors, auditors, designated 
agents of Karyopharm, IRBs/IECs and regulatory authorities as required. 
16.4. 
Informed Consent 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent. 
In addition to the signing of informed consent by their parents, adolescent patients (permitted 
only in countries in which adolescents have been approved by the national/local 
regulatory/ethical authority) should sign written Assent Forms (witnessed, where required by 
law or regulation). 
Informed consent for blinded study treatment must be obtained before conducting any 
study-specific procedures (ie, all of the procedures described in the protocol). Informed 
consent for open-label selinexor must be obtained before any study-specific measures for 
open-label selinexor are conducted at the Open-label C1 D1 Visit. The process of obtaining 
informed consent should be documented in the patient source documents. The date when a 
patient’s Informed Consent was actually obtained will be captured in their CRFs. 
Karyopharm will provide to Investigators, in a separate document, proposed ICFs that are 
considered appropriate for this study and comply with the ICH GCP guideline and regulatory 
requirements. Any changes to the ICFs suggested by the Investigator must be agreed to by 
Karyopharm before submission to the IRB/IEC, and a copy of the approved version(s) must 
be provided to the Karyopharm after IRB/IEC approval. 
Females of childbearing potential should be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirements for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study. 


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16.5. 
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. Signed ICFs and patient enrollment logs 
must be kept strictly confidential to enable patient identification at the site. 
16.5.1. 
Study Documentation, Record Keeping and Retention of Documents  
Each participating site will maintain appropriate medical and research records for this study, 
in compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional 
requirements for the protection of confidentiality of patients. As part of participating in a 
Karyopharm-sponsored study, each site will permit authorized representatives of 
Karyopharm 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 study necessary for the reconstruction and evaluation of the study. 
Examples of these original documents and data records include, but are not limited to, 
hospital records, clinical and office charts, laboratory notes, memoranda, patients’ diaries or 
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 
patient files and records kept at the pharmacy, at the laboratories, and medico-technical 
departments involved in the clinical study. 
Data collection is the responsibility of the clinical study staff at the site, under the 
supervision of the site Investigator. The study eCRF is the primary data collection instrument 
for the study. The Investigator should ensure the accuracy, completeness, legibility, and 
timeliness of the data reported in the eCRFs and all other required reports. Data reported on 
the eCRF that 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. An audit trail will be maintained by the eCRF 
system. 
The Investigator/institution should maintain the study 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 study unless Karyopharm 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. 
16.6. 
Publication of Study Protocol and Results 
Karyopharm assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 


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finalization of the study report the results of this study will be either submitted for 
publication and/or posted in a publicly accessible database of clinical study results.,  
16.7. 
Discontinuation of the Study 
Karyopharm reserves the right to discontinue this study under the conditions specified in the 
clinical study agreement.  
16.7.1. 
Audits and Inspections 
Source data/documents must be available to inspections by Karyopharm or designee or 
Health Authorities. 
16.8. 
Protocol Adherence 
Investigators ascertain they will apply due diligence to avoid protocol deviations. All 
significant protocol deviations will be recorded and reported in the CSR. 
16.9. 
Amendments to the Protocol 
Any change or addition to the protocol can only be made in a written protocol amendment 
that must be approved by Karyopharm, Health Authorities where required, and the IRB/IEC. 
Only amendments that are required for patient safety may be implemented prior to IRB/IEC 
approval. Notwithstanding the need for approval of formal protocol amendments, the 
Investigator is expected to take any immediate action required for the safety of any patient 
included in this study, even if this action represents a deviation from the protocol. In such 
cases, Karyopharm should be notified of this action and the IRB/IEC at the study site should 
be informed according to local regulations (eg, UK requires the notification of urgent safety 
measures within 3 days) but not later than 10 working days. 
 
 


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17. 
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Tissue Sarcoma. J Clin Oncol 2016; 34, 3166-3174. 
23. Gray LJ, Bjelogrlic P, Appleyard VC, et al. Selective induction of apoptosis by 
leptomycin B in keratinocytes expressing HPV oncogenes. Int. J. Cancer 
2007(Jun):120(11):2317-2324. 
24. Kau TR, Silver PA. Nuclear transport as a target for cell growth. Drug Discov Today. 
2003 Jan 15; 8(2):78-85. 
25. Knapp AA, McManus PM, Bockstall K, Moroianu J. Identification of the nuclear 
localization and export signals of high risk HPV16 E7 oncoprotein. Virology. 2009 Jan:5; 
383(1):60-68. 
26. Kojima K, Kornblau SM, Ruvolo V, et al. Prognostic impact and targeting of CRM1 in 
acute myeloid leukemia. Blood. 2013;121(20):4166–4174. 
27. Lain S, Xirodimas D, Lane DP. Accumulating active p53 in the nucleus by inhibition of 
nuclear export: a novel strategy to promote the p53 tumor suppressor function. Exp Cell 
Res. 1999;253(2):315-324. 
28. Lapalombella R, Sun Q, Williams K, et al. Selective inhibitors of nuclear export show 
that CRM1/XPO1 is a target in chronic lymphocytic leukemia. Blood. 
2012;120(23):4621–4634.  


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29. Latimer NR, Abrams KR, Lambert PC, et al. Adjusting for treatment switching in 
randomized controlled trials – a simulation study and a simplified two-stage method. Stat 
Methods Med Res. 2017;26(2):724–51. 
30. Latimer NR, Abrams KR, Lambert PC, Morden JP, Crowther MJ. Assessing methods for 
dealing with treatment switching in clinical trials: a follow-up simulation study. Stat 
Methods Med Res. 2018;27(3):765–84. 
31. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. 
Cancer. 1981 Jan 1;47(1):207-14. 
32. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 
1987;317:1098. 
33. Mutka SC, Yang WQ, Dong SD, et al. Identification of nuclear export inhibitors with 
potent anticancer activity in vivo. Cancer Res. 2009; 69(2):510-517. 
34. Nair JS, Tap W, Vasudeva SD, et al. KPT-330, a selective small molecule inhibitor of 
nuclear export, is active in bone and soft tissue sarcoma. Cancer Res. 2013 
Apr;73(8 Suppl):5210. 
35. Nakayama R, Zhang YX, Czaplinski JT, et al. Preclinical activity of selinexor, an 
inhibitor of XPO1, in sarcoma. Oncotarget. 2016; 7:16581-16592. 
36. Nakayama T, Toguchida J, Wadayama B, et al. MDM2 gene amplification in bone and 
soft-tissue tumors: Association with tumor progression in differentiated adipose-tissue 
tumors. Int J Cancer. 1995 Oct 20;64(5):342-6. 
37. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in 
Oncology (NCCN Guidelines®): Fatigue, Palliative Care, and Antiemesis. Available on 
line at http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. 
38. Newlands ES, Rustin GJ, Brampton MH. Phase I trial of elactocin. Br J Cancer. 1996; 
74(4):648-649. 
39. 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. 
40. Penel N, Demetri GD, Blay JY, et al. Growth modulation index as metric of clinical 
benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as 
a salvage therapy. Ann Oncol. 2013; 24:537-542. 
41. Ranganathan P, Yu X, Na C, et al. Preclinical activity of a novel CRM1 inhibitor in acute 
myeloid leukemia. Blood. 2012;120(9):1765–1773. 
42. Roberts BJ, Hamelehle KL, Sebolt JS, Leopold WR. In vivo and in vitro anticancer 
activity of the structurally novel and highly potent antibiotic CI-940 and its hydroxy 
analog (PD 114,721). Cancer Chemother Pharmacol. 1986;16(2):95-101. 
43. Schmidt J, Braggio E, Kortuem KM, et al. Genome-wide studies in multiple myeloma 
identify XPO1/CRM1 as a critical target validated using the selective nuclear export 
inhibitor KPT-276. Leukemia. 2013 Dec;27(12):2357-65. 


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44. Therasse PP, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response 
to treatment in solid tumors. European Organization for Research and Treatment of 
Cancer, National Cancer Institute of the United States, National Cancer Institute of 
Canada. J Natl Cancer Inst. 2000; 92:205-16. 
45. Turner JG, Sullivan DM. CRM1-mediated nuclear export of proteins and drug resistance 
in cancer. Curr Med Chem. 2008;15(26):2648-55. 
46. Turner JG, Dawson J, Sullivan DM. Nuclear export of proteins and drug resistance in 
cancer. Biochem Pharmacol. 2012;83(8):1021-1032. 
47. Van der Watt PJ, Maske CP, Hendricks DT, et al. The Karyopherin proteins, CRM1 and 
Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell 
survival and proliferation. Int J Cancer. 2009 Apr 15;124(8):1829-40. 
48. Walker CJ, Oaks JJ, Santhanam R, et al. Preclinical and clinical efficacy of XPO1/CRM1 
inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias. Blood. 2013; 
22(17):3034–3044.  
49. Xu D, Farmer A, Chook YM. Recognition of nuclear targeting signals by Karyopherin-
beta proteins. Curr Opin Struct Biol. 2010;20(6):782-790. 
 
 


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18. 
APPENDICES  
 


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APPENDIX 1 World Health Organization (WHO) Tumor Response 
Criteria 
(Adapted from Miller AB, et al., Reporting results of cancer treatment. Cancer. 1981;47:207 
214.) 
Characteristic 
Criteria 
Tumor Burden 
No maximal number of lesions specified.  
No limitations specified per organ site 
Measurability of 
lesions at 
baseline  
1. Measurable, bidimensional (product of LD and greatest perpendicular 
diameter)a  
2. Nonmeasurable/evaluable (eg, lymphangitic pulmonary metastases, 
abdominal masses)  
Objective 
response  
 
1. Measurable disease (change in sum of products of LDs and greatest 
perpendicular diameters, no maximum number of lesions specified)  
CR: disappearance of all known disease, confirmed at ≥ 4 wk  
PR: ≥ 50% decrease from baseline, confirmed at ≥ 4 wk.  
• 
Bidimensional: single lesion, greater than or equal to 50% 
decrease in tumor area (multiplication of longest diameter by the 
greatest perpendicular diameter); multiple lesions, a 50% 
decrease in the sum of the products of the perpendicular 
diameters of the multiple lesions.  
• 
Unidimensional: greater than or equal to 50% decrease in linear 
tumor measurement. 
• 
No new lesions or progression of any lesions. 
PD: ≥ 25% increase of one or more lesions, or appearance new lesions  
NC (SD): neither PR or PD criteria met  
2. Nonmeasurable disease  
CR: disappearance of all unknown disease, confirmed at ≥ 4 wk  
PR: estimated decrease of 50%, confirmed at ≥ 4 wk  
PD: ≥ 25% in existent lesions of appearance of new lesions  
NC (SD): neither PR or PD criteria met 
3. Bone Metastases 
CR: Complete disappearance of all lesions on x-ray or scan for at least 
four weeks.  
PR: Partial decrease in size of lytic lesions, recalcification of lytic 
lesions, or decreased density of blastic lesions for at least four 
weeks. 
PD: Increase in size of existent lesions or appearance of new lesions. 
NC (SD): Because of the slow response of bone lesions, the designation 
of no change should not be applied until ≥ 8weeks have passed from 
start of therapy. 
Occurrence of bone compression or fracture and its healing should not be 
used as the sole indicator for evaluation of therapy. 


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Characteristic 
Criteria 
Overall response  
1. Best response recorded in measurable disease  
2. NC in nonmeasurable lesions will reduce a CR in measurable lesions to 
an overall PR  
3. NC in nonmeasurable lesions will not reduce a PR in measurable lesions  
Duration of 
response 
1. CR: From date CR criteria first met to date PD first noted. 
2. Overall Response: From date of treatment start to date PD first noted. 
3. In patients who only achieve a PR, only the period of overall response 
should be recorded  
LD = longest diameter; CR = complete response; PR = partial response; PD = progressive disease; NC = no 
change; SD = stable disease.  
aLesions that can be measured only unidimensionally are considered measurable (eg, mediastinal adenopathy, 
malignant hepatomegaly). 
 


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APPENDIX 2 RECIST Version 1.1  
(Modified from Eisenhauer 2009) 
All patients will have their BEST RESPONSE on study classified as outlined below: 
Complete Response (CR) 
Disappearance of all target lesions. Any pathological lymph nodes (whether target or 
non-target) must have reduction in the short axis to < 10mm. 
Partial Response (PR) 
At least a 30% decrease in the sum of diameters of target lesions, taking as reference the 
baseline sum diameters. 
Stable Disease (SD) 
Steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD. 
Progressive Disease (PD) 
At least a 20% increase in the sum of diameters of measured lesions taking as references the 
smallest sum of diameters recorded since the treatment started. In addition to the relative 
increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 
Appearance of one or more new lesions will also constitute PD.  
Response Duration 
Response duration will be measured from the time measurement criteria for CR/PR 
(whichever is first recorded) are first met until the first date that recurrent or PD is 
objectively documented, taking as reference the smallest measurements recorded since the 
treatment started. 
Stable Disease Duration 
Stable disease duration will be measured from the time of start of therapy until the criteria for 
progression are met, taking as reference the smallest measurements recorded since the 
treatment started. 


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Evaluation of Best Overall Response – Patient with Target (+/- non-target) disease 
Target lesions 
Non-Target lesions 
New Lesions 
Overall response 
CR 
CR 
No 
CR 
CR 
Non-CR-Non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD/or not all 
evaluated 
No 
PR 
SD 
Non-PD/or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
Evaluation of Best Overall Response – Patient with Non-Target Disease 
Non-Target lesions 
New Lesions 
Overall response 
CR 
No 
CR 
Non-CR-Non-PD 
No 
Non-CR/Non-PD1 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
 
Note: Patients with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of PD at that time should be reported as “symptomatic 
deterioration”. Every effort should be made to document the objective progression even after 
discontinuation of treatment. 


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Method of Measurement 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up.  
Clinical Lesions 
Clinical lesions will only be considered measurable when they are superficial (eg, skin 
nodules, palpable lymph nodes). For the case of skin lesions, documentation by color 
photography including a ruler to estimate the size of the lesion is recommended.  
Chest X-ray 
Lesions on chest X-ray are acceptable as measurable lesions when they are clearly defined 
and surrounded by aerated lung. However, CT is preferable.  
CT (preferred) or MRI  
CT (preferred) and MRI imaging might be the best currently available and reproducible 
methods to measure target lesions selected for response assessment. Conventional CT and 
MRI should be performed with cuts of 10 mm or less in slice thickness contiguously. Spiral 
CT should be performed using a 5 mm contiguous reconstruction algorithm. This applies to 
the chest, abdomen and pelvis. Head & neck and extremities usually require specific 
protocols. 
Ultrasound 
When the primary endpoint of the study is objective response evaluation, ultrasound (US) 
should not be used to measure tumour lesions that are clinically not easily accessible. It is a 
possible alternative to clinical measurements for superficial palpable nodes, subcutaneous 
lesions and thyroid nodules. Ultrasound might also be useful to confirm the complete 
disappearance of superficial lesions usually assessed by clinical examination. 
Cytology, Histology 
These techniques can be used to differentiate between PR and CR in rare cases (for example, 
residual lesions in tumour types such as germ cell tumours, where known residual benign 
tumours can remain). The cytological confirmation of the neoplastic origin of any effusion 
that appears or worsens during treatment when the measurable tumour has met criteria for 
response or stable disease is mandatory to differentiate between response or stable disease 
(an effusion may be an adverse drug reaction of the treatment) and/or PD. 
 


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APPENDIX 3 Eastern Cooperative Oncology Group (ECOG) 
Performance Status Scale Assessment 
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 
(eg, 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. 
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 
 
 


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APPENDIX 4 Glutathione (GSH)-, S-Adenosylmethionine (SAM)-, OR N-
Acetylcysteine (NAC)-Containing Products 
(Representative List)  
 
Glutathione 
N-acetylcysteine (NAC) 
S-adenosylmethionine (SAM) 
Product Name 
Ingredient 
Product Name Ingredient 
Product Name 
Ingredient 
Glutathione 
glutathione 
Antidote for 
acetaminophen 
overdose 
acetylcysteine  
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 
 
 
 
 
 

SAP_001.pdf: 
KCP-330-020/SEAL 
Statistical Analysis Plan 
Karyopharm Therapeutics, Inc. 
 
 
2.0 
 
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CONFIDENTIAL 
1 
 
STATISTICAL ANALYSIS PLAN 
 
Protocol KCP-330-020 
 
A PHASE 2-3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND 
STUDY OF SELINEXOR (KPT-330) VERSUS 
PLACEBO IN PATIENTS WITH ADVANCED 
UNRESECTABLE DEDIFFERENTIATED 
LIPOSARCOMA (DDLS) 
 
 
 
 
 
 
 
 
 
 
 
This statistical analysis plan contains confidential information and is the proprietary property 
of Karyopharm Therapeutics, Inc. It may not be copied or made available for review by an 
unauthorized person or firm without the prior written authorization of Karyopharm 
Therapeutics, Inc. 
 
 
Protocol Version: 
9.0 
 
Version: 
2.0  
 
Date: 
20 September 2020 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
2  
S T A TI S TI C A L A N A L Y SI S P L A N SI G N A T U R E P A G E  
 
See l ast p a ge f or si g n at ures.  
 
T he u n dersi g ne d h as de v el o pe d t his statistical a nal ysis pla n ( S A P):  
 
 
 
T he u n dersi g ne d h a ve re vie we d t his S A P a n d a p pr o ve it i n its e ntiret y:   
 
 
 
 
 
 
 
 
 
 
 
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
3  
D O C U M E N T HI S T O R Y  
 
Versi o n  
D ate  
A ut h or(s)  
Brief S u m m a r y of C h a n ges  
1. 0  
1 5 A u g 2 0 1 9  
 
 
Ori gi nal  
2. 0  
2 0 Se p  2 0 2 0  
 
 
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patie nts i n t he P hase 3 p orti o n of t he 
st u d y base d o n pr ot oc ol v ersi o n 8 . 0 
date d 3 0  J a n uar y 2 0 2 0. 
Ti me -t o-pr o gressi o n ( T T P) was 
c ha n ge d fr o m a ke y s ec o n dar y 
e n d p oi nt t o a sec o n dar y efficac y 
e n d p oi nt . I n s e nsiti vit y a nal ysis f or 
O S, t he t w o -sta ge esti mati o n met h o d 
will be i m ple me nte d t o assess t he 
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seli ne x or o n O S base d o n pr ot oc ol 
versi o n 9. 0 date d 2 1 Ma y 2 0 2 0.  
 
 
 
P P D
P P D
P P D


KCP-330-020/SEAL 
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TABLE OF CONTENTS 
Section 
Page 
1. 
OVERVIEW AND INVESTIGATIONAL PLAN ...................................................... 12 
1.1. 
STUDY DESIGN................................................................................................. 12 
1.2. 
OBJECTIVES ...................................................................................................... 13 
1.2.1. 
Phase 2 Objectives .............................................................................. 13 
1.2.1.1. Phase 2 Primary Objective .................................................. 13 
1.2.1.2. Phase 2 Secondary Objectives............................................. 14 
1.2.1.3. Phase 2 Exploratory Objectives .......................................... 14 
1.2.2. 
Phase 3 Objectives .............................................................................. 15 
1.2.2.1. Phase 3 Primary Objective .................................................. 15 
1.2.2.2. Phase 3 Secondary Objectives............................................. 15 
1.2.2.3. Phase 3 Exploratory Objectives .......................................... 15 
1.3. 
DETERMINATION OF SAMPLE SIZE ............................................................ 16 
1.3.1. 
Determination of Sample Size for Phase 2........................................ 16 
1.3.2. 
Determination of Sample Size for Phase 3........................................ 16 
1.4. 
STUDY PLAN ..................................................................................................... 17 
1.5. 
INTERIM ANALYSIS ........................................................................................ 18 
1.6. 
DATABASE LOCK ............................................................................................ 19 
1.7. 
MODIFICATIONS TO THE STATISTICAL SECTION OF THE 
PROTOCOL ........................................................................................................ 19 
1.8. 
STATISTICAL MODIFICATIONS MADE IN THE STATISTICAL 
ANALYSIS PLAN .............................................................................................. 19 
2. 
GENERAL STATISTICAL METHODS AND DATA HANDLING ....................... 21 
2.1. 
GENERAL ANALYSIS METHODS .................................................................. 21 
2.2. 
MISSING DATA HANDLING IN DATA PRESENTATION ........................... 21 
2.2.1. 
Handling of Computation of Treatment Duration if 
Study Treatment End of Treatment Date is Missing....................... 21 
2.2.2. 
Handling of Missing/Partial Dates for Adverse Events or 
Concomitant Medications .................................................................. 21 
2.2.3. 
Handling of Missing or Partial Birth Date for 
Calculation of Age ............................................................................... 22 
2.2.4. 
Handling of AEs When Date and Time of First Dose of 
Study Treatment Are Missing ........................................................... 22 


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Page 
2.2.5. 
Handling of Missing Assessment of Relationship of AEs 
to Study Treatment ............................................................................. 22 
2.2.6. 
Handling of Missing Severity of AEs ................................................ 22 
2.2.7. 
Handling of Missing Data in Patient-Reported QoL 
Measurements ..................................................................................... 22 
2.3. 
STUDY TREATMENT DOSING DATE ........................................................... 22 
2.4. 
OBSERVATION PERIOD .................................................................................. 23 
2.5. 
STUDY DAY CALCULATION ......................................................................... 23 
2.6. 
BASELINE MEASUREMENT ........................................................................... 24 
2.7. 
VISIT WINDOWS............................................................................................... 24 
2.8. 
SUBGROUPS ...................................................................................................... 25 
2.9. 
POOLING OF CENTERS FOR STATISTICAL ANALYSES .......................... 25 
2.10. COMPUTING AND CODING STANDARDS................................................... 25 
3. 
PATIENT INFORMATION ......................................................................................... 27 
3.1. 
DISPOSITION OF PATIENTS AND ANALYSIS POPULATIONS ................ 27 
3.1.1. 
Efficacy Populations ........................................................................... 27 
3.1.2. 
Safety Populations............................................................................... 28 
3.1.3. 
Additional Analysis Populations ....................................................... 28 
3.2. 
DEMOGRAPHICS, MEDICAL HISTORY, AND BASELINE 
CHARACTERISTICS ......................................................................................... 28 
3.2.1. 
Demographic Data .............................................................................. 28 
3.2.2. 
Prior Antineoplastic Therapy ............................................................ 29 
3.2.2.1. Prior Antineoplastic Therapy- Medication ....................... 29 
3.2.2.2. Prior Antineoplastic Therapy- Radiation .......................... 29 
3.2.2.3. Prior Antineoplastic Therapy- Surgery ............................. 29 
3.2.3. 
Medical History ................................................................................... 29 
3.2.4. 
Disease History .................................................................................... 30 
3.2.5. 
Baseline Characteristics ..................................................................... 30 
3.3. 
PRIOR AND CONCOMITANT MEDICATIONS AND 
PROCEDURES.................................................................................................... 30 
3.3.1. 
Prior and Concomitant Medications and Procedures ..................... 30 
3.4. 
EXTENT OF STUDY TREATMENT EXPOSURE AND 
COMPLIANCE.................................................................................................... 31 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
6  
Secti o n  
Pa ge  
3. 4. 1.  
E xte nt of St u d y Tre at me nt E x p os ure  ............................................... 3 1  
3. 4. 2.  
Tre at me nt C o m pli a nce  ....................................................................... 3 2  
4.  
E F FI C A C Y  ..................................................................................................................... 3 3  
4. 1.  
P RI M A R Y E F FI C A C Y E N D P OI N T S  ................................................................ 3 3  
4. 1. 1.  
Pr o g ressi o n -Free S ur vi v al ( P F S)  ....................................................... 3 3  
4. 2.  
S E C O N D A R Y E F FI C A C Y E N D P OI N T S  ......................................................... 3 5  
4. 2. 1.  
Ke y Sec o n d ar y Effic ac y E n d p oi nts  ................................................... 3 5  
4. 2. 1. 1.  O ver all S ur vi v al ( O S)  .......................................................... 3 6  
4. 2. 2.  
Ot her Sec o n d ar y Effic ac y E n d p oi nts  ................................................ 3 6  
4. 2. 2. 1.  Ti me t o Pr o gressi o n ( T T P)  .................................................. 3 6  
4. 2. 2. 2.  Q L Q -C 3 0  .............................................................................. 3 7  
4. 2. 2. 3.  E Q -5 D -5 L .............................................................................. 3 8  
4. 2. 2. 4.  O R R  ....................................................................................... 3 9  
4. 2. 2. 5.  Ti me t o Ne xt T re at me nt ( T T N T) ........................................ 3 9  
4. 3.  
E X P L O R A T O R Y E N D P OI N T S  ......................................................................... 3 9  
4. 4.  
M U L TI P L E C O M P A RI S O N S/ M U L TI P LI CI T Y  ............................................... 4 1  
5.  
S A F E T Y  .......................................................................................................................... 4 3  
5. 1.  
A D V E R S E E V E N T S  ........................................................................................... 4 3  
5. 1. 1.  
Defi nit i o ns of Tre at me nt-E mer g e nt A d vers e E ve nts 
( T E A Es), Seri o us A d verse E ve nts ( S A Es), a n d 
Tre at me nt -E mer ge nt T re at me nt -Rel ate d A d verse 
E ve nts ( T R A Es) ................................................................................... 4 4  
5. 1. 1. 1.  Tre at me nt -E mer ge nt A d verse E ve nt ( T E A E) ................... 4 4  
5. 1. 1. 2.  Seri o us A d verse E ve nt ( S A E)  ............................................. 4 4  
C CI


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Section 
Page 
5.1.1.3. Treatment-emergent Treatment-Related 
Adverse Events (TRAEs) ..................................................... 44 
5.1.1.4. Adverse Event of Clinical Interest (AECI) ........................ 45 
5.1.2. 
Analysis Methods ................................................................................ 45 
5.1.3. 
Analysis of TEAE ................................................................................ 45 
5.1.4. 
Analysis of SAE ................................................................................... 46 
5.1.5. 
Analysis of AECI ................................................................................. 46 
5.2. 
DEATH ................................................................................................................ 47 
5.3. 
LABORATORY SAFETY VARIABLES ........................................................... 47 
5.3.1. 
Definitions ............................................................................................ 47 
5.3.2. 
Analysis of Laboratory Variables ..................................................... 48 
5.4. 
VITAL SIGNS, ECOG, AND PHYSICAL EXAMINATION 
VARIABLES ....................................................................................................... 48 
5.5. 
ELECTROCARADIOGRAM (ECG) .................................................................. 49 
6. 
REFERENCES ............................................................................................................... 50 
7. 
APPENDICES ................................................................................................................ 51 
7.1. 
Appendix I: World Health Organization (WHO) Tumor Response 
Criteria ................................................................................................................. 51 
7.2. 
Appendix II: RECIST Version 1.1....................................................................... 53 
 
 
 


KCP-330-020/SEAL 
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TABLES INCLUDED IN THE TEXT 
 
Page 
Table 2-1  
Visit Windows for Clinical Laboratory Tests for Patients in Blinded 
Treatment ........................................................................................................................ 24 
Table 2-2  
Visit Windows for Clinical Laboratory Tests for Patients Who Enter Open-
Label Treatment .............................................................................................................. 25 
Table 4-1  
PFS Outcome and Censoring Definitions ........................................................................ 34 
Table 4-2  
Scoring the QLQ-C30 version 3.0 ................................................................................... 38 
Table 5-1  
AECI Categories.............................................................................................................. 47 
 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
9  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S  
A b bre vi ati o n  
Defi niti o n  
A E  
ad verse e ve nt 
A L T  
ala ni ne tra nsa mi nase ( S G P T) 
A S T  
as partate tra nsa mi nase ( S G O T)  
A T C  
A nat o mic T hera pe utic Class  
B S A  
b o d y s urface area  
C H W  
C ui, H u n g , a n d Wa n g 
C M H  
C oc hra n -Ma ntel -Hae nszel  
CI  
co nfi de nce inter val  
C R  
co m plete res p o nse 
C 1 D 1  
C ycle 1 Da y 1  
c m 
ce nti meter 
C P  
c o n diti o nal p o wer 
C S R  
cli nical st u d y re p ort 
C T  
c o m p ute d t o m o gra p h y  
C T C A E  
C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts  
D D L S  
de differe ntiate d li p osarc o ma  
D O R  
d urati o n of res p o nse 
D S M B  
Data Safet y M o nit ori n g B oar d  
E C G  
E lectr ocar di o gra m 
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
e C R F 
Electr o nic case re p ort for m  
E o B T  
E n d of Bli n de d Treat me nt  
E o S  
E n d of St u d y  
E o T  
E n d of Treat me nt  
E O R T C  
E ur o pea n Or ga nizati o n f or Researc h a n d Treat me nt of Ca ncer  
E Q -5 D -5 L  
E ur o Q o L Gr o u p Healt h Q uesti o n naire  
F D G  
1 8F -fl u or o de o x y gl uc ose 
H R  
hazar d rati o  
I C R 
I n de pe n de nt Ce ntralize d Re vie w 
I T T 
inte nt -t o-treat 
k g  
kil o gra m  
K M  
Ka pla n -Meier  
C CI


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 0  
A b bre vi ati o n  
Defi niti o n  
L L N  
l o wer li mit of n or mal 
m 2 
s q uare meters 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
m g  
m illi gra m 
mi n  
mi n ute  
m L  
Milliliter  
M L S  
M y x oi d/r o u n d cell li p osarc o ma  
M RI  
Ma g neti c res o na nce i ma gi n g 
N CI  
Nati o nal Ca ncer I nstit ute  
O R R  
o verall res p o nse rate 
O S  
o verall sur vi val  
O S 1 2  
o verall s ur vi val at least 1 2 m o nt hs 
P D  
p r o gressi o n of d isease 
P E T  
p ositr o n e missi o n t o m o gra p h y  
P F S  
p r o gressi o n-free sur vi val  
P P  
p er-p r ot oc ol 
P R  
p artial res p o nse 
P T  
p referre d ter m 
Q L Q -C 3 0  
q ualit y of life q uesti o n naire -C 3 0  
Q o L  
q ualit y of life 
R E CI S T  
Res p o nse E val uati o n Criteria i n S oli d T u m ors  
S A E  
seri o us ad verse eve nt  
S A P  
statistical anal ysis p la n 
S D  
sta ble d isease 
S D 1 2  
sta ble disease at 1 2 wee ks  
SI N E  
selecti ve i n hi bit or of n uclear e x p ort 
S O C  
syste m o r ga n class 
St d De v  
sta n dar d de viati o n 
S U V  
sta n dar dize d u pta ke val ue 
C CI
C CI
C CI
C CI
C CI


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 1  
A b bre vi ati o n  
Defi niti o n  
T E A E  
treat me nt-e mer ge nt ad verse eve nt  
T R A E  
treat me nt-relate d a d verse e ve nt 
T T P  
ti me t o pr o gressi o n 
U L N  
u p per li mit of n or mal  
W B C  
w hite bl o o d cell  
W k  
wee k  
W H O  
W orl d Healt h Or ga nizati o n  
X P O 1  
ex p orti n 1  
 
 
 
 
 
 
 
 
 
 
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1. 
 OVERVIEW AND INVESTIGATIONAL PLAN 
1.1. 
STUDY DESIGN 
This is a Phase 2-3, multicenter, randomized, double-blind, placebo-controlled study. 
Approximately 334 total patients were planned to be enrolled. At the conclusion of enrollment, 
three hundred and forty-two (342) patients have been randomized (57 patients in Phase 2 and 
285 patients in Phase 3).  
 
The study overview is presented in the figure below. 
 
 
 
Patients in the placebo arm who have PD will have the option to cross over to open-label 
selinexor. 
 
Phase 2: 
Fifty-seven patients were randomized to selinexor or placebo in a 1:1 allocation. Randomization 
was stratified based on the following stratification factors for patients enrolled under protocol 
Versions ≤ 4: number of prior systemic therapies (1 versus ≥ 2) and prior eribulin use (prior 
eribulin versus no prior eribulin). The preplanned analysis of progression-free survival (PFS; 
(after 40 PFS events were observed) was performed and served as a guideline to inform the final 
design of the Phase 3 portion of the study. 
Phase 3:  
Two hundred and eighty-five (285) patients have been randomized to selinexor or placebo in a 
2:1 allocation.  
Randomization was based on  
• Prior eribulin use (prior eribulin versus no prior eribulin) 
• Prior trabectedin (Yondelis®) use (prior trabectedin versus no prior trabectedin) 
• The number of prior systemic therapies excluding eribulin and trabectedin (≤2 versus 
≥ 3).  
 


KCP-330-020/SEAL 
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20 September 2020 
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All radiographic responses will be determined by the Independent Centralized Review (see the 
Imaging Manual for more details). Patients who have progressive disease (PD) per Response 
Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 (Eisenhauer 2009) per central review, will 
discontinue blinded study treatment and their treatment assignment will be unblinded. 
• Patients in the placebo arm who have PD will have the option to cross over to open-label 
selinexor. 
• Patients in the selinexor arm who have PD will only be allowed to continue on selinexor 
(as open-label treatment) if the Investigator, in consultation with the Sponsor, believes 
based on clinical judgement that the patient may derive benefit from continued treatment 
with selinexor. 
 
Patients who discontinue blinded study treatment at the discretion of the Investigator for reasons 
other than centrally confirmed PD are not allowed to receive open-label selinexor.  
 
An interim analysis was conducted after 108 PFS events were observed. The interim analysis 
was designed to allow early stopping for efficacy, futility (non-binding), or sample size re-
estimation (up to a maximum of 50% increase in sample size).  Based on interim analysis 
results, DSMB recommended the study to continue.  
 
Approximately 34 months will be required to complete the primary Phase 3 PFS analysis. The 
primary endpoint analysis will be performed approximately 4 months after enrollment of the last 
patient, once 209 PFS events are observed. Treatment assignment for all patients will be 
unblinded at the time of the primary PFS analysis and all Phase 3 patients will be evaluable for 
assessment of the primary endpoint. 
Patients who are on blinded study treatment at the time of the primary PFS analysis at the end of 
Phase 3 may proceed as follows: 
• Patients in the placebo arm may cross over to open-label selinexor (60 mg twice 
weekly).  
• Patients in the selinexor arm will continue selinexor but as open-label treatment. 
All patients who have PD while receiving open-label selinexor will discontinue selinexor and be 
followed for survival, unless the Investigator, in consultation with the Sponsor, believes based 
on clinical judgement that the patient may derive benefit from continued treatment with 
selinexor. 
1.2. 
OBJECTIVES 
1.2.1. 
Phase 2 Objectives 
1.2.1.1. 
Phase 2 Primary Objective 
• Assess and compare progression-free survival (PFS) of patients with advanced 
unresectable DDLS treated with selinexor (60 milligrams [mg]) or placebo twice 
weekly. PFS is defined as the time from date of randomization until the first date of PD, 
per RECIST v. 1.1 (Eisenhauer 2009), or death due to any cause. 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 4  
1. 2. 1. 2.  
P h ase 2 Sec o n d ar y O bjecti ves  
•  C o m pare ti me t o pr o gressi o n ( T T P) o n st u d y treat me nt, per R E CI S T  v.  1. 1, wit h T T P o n 
t he patie nt’s last pri or s yste mic thera p y.  
•  Deter mi ne t he o v erall res p o nse rate ( O R R: C o m plete Res p o nse [ C R] + Partial Res p o nse 
[ P R]), s u p p orte d b y d urati o n of res p o nse ( D O R). Res p o nses will be defi ne d b y 
R E CI S T  v. 1. 1.  
•  Assess c ha n ges at 6 wee ks i n t u m or gl uc ose meta b olis m, de nsit y, a n d siz e usi n g 
1 8F -fl u or o de o x y gl u c ose-p ositr o n e missi o n t o m o gra p h y ( F D G -P E T) a n d c o m p ute d 
t o m o gra p h y ( C T) ( dia g n ostic). 
•  Assess safet y of eac h treat me nt ar m.   
1. 2. 1. 3.  
P h ase 2 E x pl or at or y O bjecti ves  
C CI


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 5  
1. 2. 2.  
P h ase 3 O bjecti v es 
1. 2. 2. 1.  
P h ase 3 Pri m ar y O bjecti ve  
Assess a n d c o m pare P F S of patie nts wit h a d va nce d u nresect a ble D D L S t reate d wit h seli ne x or 
( 6 0 m g) or place b o t wice wee kl y. P F S is defi ne d as ti me fr o m date of ra n d o mizati o n u ntil t he 
first date of pr o gressi o n per R E CI S T v. 1. 1, or deat h d ue t o a n y ca use. E val uati o n of t he 
ra di o gra p hic d ata f or t he P F S pri mar y e n d p oi nt will be base d o n data fr o m a sca n re vie w b y  
In d e pe n de nt C e ntr alize d  R e vie w (I C R). 
1. 2. 2. 2.  
P h ase 3 Sec o n d ar y O bjecti ves  
•  Assess o verall s ur vi val ( O S ), meas ure d fr o m date of ra n d o mizati o n u ntil deat h d ue t o 
a n y ca use.  
•  C o m pare  T T P o n st u d y tr eat me nt, per R E CI S T v. 1. 1, wit h  T T P o n t he patie nt’s last pri or 
s yste mic t hera p y. 
•  Assess Q ualit y of Life ( Q o L) a n d patie nt -re p ort e d o utc o mes as meas ure d b y t he 
E ur o pea n Or ga niz ati o n f or Researc h a n d Treat me nt of Ca ncer ( E O R T C) Q ualit y -of -Life 
Q uesti o n na ire ( Q L Q-C 3 0) a n d t he E ur o Q o L Gr o u p Healt h Q uesti o n na ire ( E Q-5 D -5 L).  
•  Deter mi ne t he O R R, s u p p orte d b y D O R. Res p o ns es will be defi ne d b y R E CI S T v. 1. 1.  
•  Assess P F S acc or di n g t o t he I n v esti gat or bas e d o n cli nical a n d/ or ra di ol o gi c criteri a.  
•  Assess safet y of eac h treat me nt ar m.  
1. 2. 2. 3.  
P h ase 3 E x pl or at o r y O bjecti ves  
C CI
C CI


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 6  
1. 3.  
D E T E R MI N A TI O N O F S A M P L E SI Z E  
1. 3. 1.  
Deter mi n ati o n of S a m ple Size f or P h ase 2  
Fift y -se v e n patie nts were ra n d o mize d t o seli ne x or or place b o i n a 1: 1 all ocati o n. Ra n d o mizati o n 
details are pr o vi d e d i n Secti o n 7. 7  of t he Pr ot oc ol . 
T he pre pla n n e d a n al ysis of P F S was perf or me d a n d ser ve d as g ui d eli ne t o i nf or m t he fi nal 
desi g n of t h e P hase 3 p orti o n of t he st u d y.   
1. 3. 2.  
Deter mi n ati o n of S a m ple Size f or P h ase 3  
Per pr ot oc ol, t he P hase 3 sa m ple siz e was re -e val u ate d base d o n t he P has e 2 res ults. Sa m ple siz e 
calc ulati o ns were c o n d u cte d u n der t he f oll o wi n g ass u m pti o ns:  
C CI
C CI


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 7  
Base d o n t h ese ass u m pti o ns, a p pr o xi matel y 2 7 7  eli gi ble patie nts will be ra n d o mize d 2: 1 t o 
recei v e eit her s eli ne x or ( 6 0 m g t wice wee kl y) or place b o, res pecti vel y i n a bli n de d ma n ner t o 
o bser ve 2 0 9 P F S e v e nts. S a m ple siz e ma y be a dj uste d  base d o n t he i nteri m a nal ys is res ults (see 
Secti o n 1 4. 1. 1. 2. 1  of t he Pr ot oc ol ). 
1. 4.  
S T U D Y P L A N  
F or eac h patie nt t hat si g ns t he i nf or me d c o nse nt, t he st u d y c o nsists of:  
•  Scree ni n g/ baseli ne visit: occ urs wit hi n 2 1 da ys pri or t o recei vi n g t he 1 st d os e of st u d y 
treat me nt 
•  Bli n de d t reat me nt: e x pecte d t o be u p t o 1 2 m o nt hs, b ut t here is n o ma xi m u m treat me nt 
d urati o n.  Patie nts will be treate d u ntil diseas e pr o gressi o n , deat h, t o xicit y t hat ca n n ot be 
ma na ge d b y sta n dar d c are, or wit h dra wal  fr o m st u d y, w hic h e ver occ urs first 
•  ( O pti o nal) O pe n-la bel seli ne x or treat me nt: patie nt i n t he place b o ar m ma y cr oss o ver t o 
o pe n -la bel seli ne x or. Patie nts i n t he seli ne x or ar m w h o ha ve P D will disc o nti n ue bli n de d 
st u d y treat me nt a n d be f oll o we d f or s ur vi val, u nless t he I n v esti gat or, i n c o ns ultati o n 
wit h t he S p o ns or, belie ves base d o n cli nical j u d ge me nt t hat t he patie nt ma y deri ve 
be nefits fr o m c o nti n ue d treat me nt wit h seli ne x or (see Pr ot oc ol Secti o n 7. 2. 4)  
•  F oll o w -u p peri o d: after l ast d o se of seli ne x or or place b o  b li n de d treat me nt/ o pe n-la bel 
seli ne x or treat me nt, patie nts will be c o ntacte d a p pr o xi matel y e ver y 3 m o nt hs f or 
d ura bilit y of res p o nse a n d s ur vi val f oll o w -u p  
E n d of St u d y ( E o S) will be u p o n c o m pleti o n of t he f oll o w -u p peri o d f or t h e last patie nt treate d 
i n t he st u d y. C o m pleti o n of f oll o w-u p f or t h e last patie nt will occ ur w he n t he last patie nt i n t he 
st u d y has e x pire d, has b ee n f oll o we d f or 2 4 m o nt hs after e nr oll me nt, has bee n l ost t o f oll o w -u p, 
or has wit h dra w n c o nse nt, w hic he ver o cc urs first.  
C CI
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Please refer to protocol schedule of assessment and study activities for patients NOT proceeding 
to open-label selinexor and patients proceeding to open-label selinexor respectively. 
1.5. 
INTERIM ANALYSIS 
An interim analysis is scheduled to be conducted after 105 PFS events (50% of the events) or 3 
months before enrollment is expected to complete, whichever occurs first.  DSMB will review 
interim analysis results and consider the following recommendations: 
• Stop trial early for efficacy 
• Continue trial as planned 
• Adjust sample size 
• Stop trial early for futility (non-binding) 
The boundary p value for the stratified log-rank test used at the time of interim PFS analysis will 
depend on when the interim analysis actually takes place. The early-stopping boundary for 
efficacy is calculated using the Lan DeMets (Lan and DeMets, 1983) alpha spending function 
with the O’Brien-Fleming type of boundary. If the null hypothesis for the primary PFS endpoint 
is rejected at the interim analysis, it will remain being rejected and will not be re-tested at any 
subsequent point. 
If efficacy stopping boundary is not reached at the interim analysis, the unblinded sample size 
re-estimation will be conducted. It is based on the method of conditional power (CP), defined as 
the probability to detect a statistically significant difference for the primary PFS endpoint at the 
end of study given the current data observed at this interim analysis, assuming this interim trend 
continues. The CP will be calculated for the primary PFS endpoint using East software with 
CHW method (Cui et al., 1999).  
The hazard ratio (HR) and associated Z statistic will be obtained for PFS between selinexor vs. 
placebo arms based on the observed data at the interim analysis, then the CP will be calculated 
using East. The calculated CP will be assigned to one of the 3 zones:  
1. favorable (CP ≥90%) 
2. promising (30% ≤ CP <90%) 
3. unfavorable (CP< 30%) 
The original planned total sample size of 222 patients (209 PFS events) will be increased to 
achieve the targeted power of 90%, up to a maximum of 333 patients when the conditional 
power is in the promising zone. If the CP is <30%, the trial may be stopped for futility (non-
binding). Otherwise, if the CP is ≥90% the trial continues as planned.  
Overall type I error for the final PFS analysis is maintained using the CHW method (Cui et al, 
1999) if the unblinded sample size re-estimation is conducted.  
The interim analysis has occurred with a data cut date of July 31, 2019 and 108 PFS events. 
Based on interim analysis results, the DSMB recommended the study to continue without 
sample size adjustment. 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
1 9  
1. 6.  
D A T A B A S E L O C K  
A p pr o xi matel y  4  m o nt hs after e nr oll me nt of t he las t patie nt, o nce t he tar gete d 2 0 9 P F S e ve nts 
are o bser ve d , dat a base i nteri m l oc k will be  c o n d ucte d.  T he pri mar y P F S a n al yses will be 
perf or me d  i n cl u di n g a nal ys es of efficac y a n d safet y dat a . A cli nical st u d y re p ort ( C S R) will be 
pre pare d aft er t he pri mar y P F S a n al ys es.   
T he fi nal a n al ysis will be perf or me d at t he e n d of t he st u d y after all pa tie nts ha ve c o m plete d t h e 
f oll o w-u p peri o d  w it h data base fi nal l oc k. 
 
1. 7.  
M O DI FI C A TI O N S T O T H E S T A TI S TI C A L S E C TI O N O F T H E 
P R O T O C O L  
T he c urre nt S A P is base d o n Pr ot oc ol v 9 . 0 date d 2 1  Ma y  2 0 2 0 .  
T he f oll o wi n g e n d p oi nts will n ot be a nal yze d  as t he c orres p o n di n g data are n ot a vaila ble.  All 
e n d p oi nts c orres p o n d t o  P hase 2 a n d P hase 3 E x pl orat or y O bjecti ves e x ce pt 1 e n d p oi nt fr o m 
P hase 2 Sec o n dar y O bjecti ve as n ote d bel o w.  
•  Assess c ha n ges at 6 wee ks i n t u m or gl uc ose meta b olis m, de nsit y, a n d size usi n g 
1 8F -fl u or o de o x ygl u c ose -p ositr o n e missi o n t o m o gra p h y ( F D G -P E T) a n d c o m p ute d 
t o m o gra p h y ( C T) ( dia g n ostic) ( P hase 2 Sec o n d ar y O bjecti ve). 
•  
•  
•  
•  
•  
T he P ha se 3 Per-Pr ot o c ol P o p ulati o n ( P h 3 -P P) defi niti o n  was m o difie d . Please refer S A P 
secti o n 3. 1. 1 f or t he defi niti o n.  
 
1. 8.  
S T A TI S TI C A L M O DI FI C A TI O N S M A D E I N T H E 
S T A TI S TI C A L A N A L Y SI S P L A N  
C h a n ges t o Versi o n 1. 0  
C ha n ges t hr o u g h o ut t he d oc u me nt i ncl u de mi n or e dit orial c ha n ges.  
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KCP-330-020/SEAL 
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• Increase the number of enrolled patients in the Phase 3 portion of the study based on 
protocol version 8.0 dated 30 January 2020. 
• Time-to-progression (TTP) was changed from a key secondary endpoint to a secondary 
efficacy endpoint. In sensitivity analysis for OS, the two-stage estimation method will be 
implemented to assess the impact of cross-over on the effect of selinexor on OS based on 
protocol version 9.0 dated 21 May 2020. 
• Add more details to the TEAE definition 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
2 1  
2.  
G E N E R A L S T A TI S TI C A L M E T H O D S  A N D D A T A H A N D LI N G  
T his statistical a nal ysis pla n ( S A P) o utli ne s t he met h o ds t o be use d i n t he a nal ysis of cli nical  
data i n or der t o a ns wer t h e st u d y o bjecti ves. P o p ulati o ns f or a nal ysis, data ha n dli n g r ules, a n d 
statistical met h o ds are pr o vi de d. T his S A P d oes n ot i ncl u de e n d p oi nts a n d met h o ds t o be use d i n 
t he a nal ysis of 
; t hese will be i ncl u de d i n a se parate 
pla n . 
2. 1.  
G E N E R A L A N A L Y SI S M E T H O D S  
T his is a m ultice nter ra n d o mize d d o u ble -bli n d P hase 2 -3 st u d y . All s u m mar y statistics will be 
c o m p ute d a n d dis pla ye d a m o n g t he c orres p o n di n g a nal ysis p o p ulati o n, a n d b y eac h sc h e d ule d 
assess me nt  ti me p oi nt w he ne ver a p plica ble. S u m mar y st atistics f or c o nti n u o us varia bles will 
mi ni mall y i ncl u de n, m e dia n,  mea n, sta n dar d de viati o n, mi ni m u m, a n d ma xi m u m. F or 
cate g orical varia bl es, fre q ue ncies a n d p erce nta ges will be prese nte d. F or ti me -t o-e ve nt 
varia bles, t he K a pla n -M eier met h o d will be use d f or descri pti ve s u m maries. Gra p hical dis pla ys 
will be pr o vi de d as a p pr o priate.  
Data fr o m p h ase 2 a n d p hase 3 will be pres e nte d se parat el y.  
2. 2.  
MI S SI N G D A T A H A N D LI N G I N D A T A P R E S E N T A TI O N  
I n ge neral, missi n g baseli nes will n ot be i m p ute d. T he f oll o wi n g a p pr oac hes are defa ult met h o ds 
f or missi n g data h a n dli n g i n s u m mar y ta bles. 
•  Cate g orical data at baseli ne will be s u m marize d usi n g c o u nts ( n) a n d perce nta ges ( %). 
De n o mi nat or will be t he a nal ysis p o p ulati o n s pe cifie d f or t he s u m mar y, u nl ess ot her wise 
s pecifie d. Missi n g d ata ma y b e pres e nte d as a s e parate cate g or y.  
•  C o nti n u o us data: s u m maries will be base d o n o bs er ve d dat a o nl y.  
2. 2. 1.  
H a n dli n g of C o m p ut ati o n of T re at me nt D ur ati o n if S t u d y Tre at me nt  E n d of 
T re at me nt D ate is M issi n g 
F or t he calc ulati o n of tr eat me nt d urati o n, t he date of t he last d ose of st u d y treat me nt is e q ual t o 
t he date of last st u d y treat me nt d osi n g re p ort e d o n st u d y treat me nt d osi n g f or m. If all t he d osi n g 
dates are missi n g, t he n t h e d urati o n is missi n g.  
T he last  d ose i nta ke  s h o ul d be clearl y i de ntifie d o n t he eC R F d osi n g p a ge a n d s h o ul d n ot be 
a p pr o xi mate d b y t he last ret ur ne d p ac ka ge date.  
2. 2. 2.  
H a n dli n g of M issi n g/P arti al D ates f or A d vers e E ve nts or C o nc o mit a nt 
M e dic ati o ns  
I n ge neral, t he i m p utati o n s h o ul d be c o nser vati ve s uc h t hat o nset dates s h o ul d be i m p ute d t o be 
as earl y as p ossi ble a n d res ol uti o n dates will be i m p ute d t o be as late as p ossi ble.  I m p ute 
res ol uti o n date first a n d t he n i m p ute o nset date usi n g i m p ute d res ol uti o n date. H o we ver, f or 
cate g orizati o n p ur p ose, if t he partial A E o nset dat e i nf or mati o n d oes n ot i n dicate w het h er t he 
A E starte d pri or t o treat me nt or after t h e treat me nt -e mer ge nt a d verse e ve nt ( T E A E) peri o d, t he 
A E will be classifie d as treat me nt -e mer ge nt.  Ha n dli n g of missi n g or partial dates f or A E or 
c o nc o mita nt me dicati o ns will c o nsi der t he start date of seli ne x or f or patie nts w h o cr oss o ver 
fr o m place b o t o o p e n -la b el seli ne x or. 
C CI


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These data imputations are for categorization purpose or calculation of AE duration, and will 
not be used in listings. In data listings, an ongoing flag will be identified from the eCRF AE 
page. 
Refer to Karyopharm Biostatistics and Statistical Programming Rule Book v2.0 for details on 
imputation methods. 
2.2.3. 
Handling of Missing or Partial Birth Date for Calculation of Age 
Refer to Karyopharm Biostatistics and Statistical Programming Rule Book v2.0 for details on 
imputation methods. 
2.2.4. 
Handling of AEs When Date and Time of First Dose of Study Treatment Are 
Missing 
When the date and time of the first dose of study treatment are missing, all AEs that occurred on 
or after signing the informed consent should be considered as TEAEs. The exposure duration 
should be kept as missing. 
2.2.5. 
Handling of Missing Assessment of Relationship of AEs to Study Treatment 
If the assessment of the relationship to study treatment is missing, then the relationship to study 
treatment in the frequency tables is considered as possibly related. 
2.2.6. 
Handling of Missing Severity of AEs 
If the severity is missing for one of the treatment-emergent occurrences of an AE, the maximal 
severity on the remaining occurrences will be considered. If the severity is missing for all the 
occurrences, a “missing” category will be added in the summary table. 
2.2.7. 
Handling of Missing Data in Patient-Reported QoL Measurements 
For patient-reported QoL measurements, missing data will be handled as described in the 
EORTC-QLQ-C30 and EQ-5D-5L scoring manuals. 
2.3. 
STUDY TREATMENT DOSING DATE 
Study treatment dosing date is the date on which a patient actually received study treatment 
(selinexor or placebo, partial or complete). 
For blinded treatment, 
• Except for few patients who were randomized to selinexor in blinded treatment and 
entered open-label phase, the date of first study treatment is defined as the earliest date 
of non-zero dose of either selinexor or placebo. The date of last study treatment is 
defined as the latest date of non-zero dose of either selinexor or placebo before end of 
blinded treatment.  
• For patients who were randomized to selinexor in blinded treatment and entered open-
label phase, the date of first study treatment is defined as the earliest date of non-zero 
dose of selinexor, the date of last study treatment is defined as the latest date of non-zero 
dose of selinexor, regardless of blinded or open-label phase. 
For open-label treatment, the date of first study treatment is defined as the earliest date of non-
zero dose of open-label selinexor. The date of last study treatment is defined as the latest date of 


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non-zero dose of open-label selinexor. This definition only applies to patients who were 
randomized to placebo in blinded treatment and entered open-label phase. 
2.4. 
OBSERVATION PERIOD 
For the patients who do not enter open-label selinexor, the observation period will be divided by 
the following: 
• The pre-treatment period is defined as the time since the signed informed consent date 
up to the time before the date of first blinded study treatment. 
• The blinded treatment period is defined as the time from the date of first blinded study 
treatment up to the date of last blinded study treatment + 30 days inclusive, or the day 
before initiation of a new anti-neoplastic treatment, whichever occurs first. 
• The post-treatment period is defined as the time beyond the blinded treatment period. 
For the patients who were randomized to placebo in blinded phase and entered open-label 
selinexor, the observation period will be divided by the following: 
• The pre-treatment period is defined as the time since the signed informed consent date 
up to the time before the date of first blinded study treatment. 
• The blinded treatment period is defined as the time from the date of first blinded study 
treatment up to the date of last blinded study treatment + 30 days inclusive, or the date of 
first open-label study treatment exclusive, whichever occurs first. 
• The open-label treatment period is defined as the time since the date of first open-label 
study treatment to the date of last open-label study treatment + 30 days inclusive, (or the 
day before initiation of a new anti-neoplastic treatment, whichever occurs first). 
• The post-treatment period is defined as the time beyond the open-label treatment period. 
For the few patients who were randomized to selinexor in blinded phase and entered open-label 
selinexor, the observation period will be divided by the following: 
• The pre-treatment period is defined as the time since the signed informed consent date 
up to the time before the date of first study treatment. 
• The blinded treatment period is defined as the time from the date of first study treatment 
up to the date of last study treatment + 30 days inclusive, or the day before initiation of a 
new anti-neoplastic treatment, whichever occurs first. Please note that open-label 
selinexor is not considered a new anti-neoplastic treatment here. 
• The post-treatment period is defined as the time beyond the blinded treatment period. 
 
Please refer to Section 2.3 for the definitions of dates of first and last study treatment. 
2.5. 
STUDY DAY CALCULATION 
Based on the study protocol, study Day 1 is the first study treatment dosing date in blinded 
treatment period. The day before Day 1 is considered Day -1, there is no Day 0. 
The study day in open-label selinexor will also be calculated using the start date of open-label 
selinexor treatment as reference point. For example, the first dose date of open-label selinexor 
will be referred as open-label Day 1 or OL Day 1.  


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A patient is considered as treated in a cycle if the patient received any non-zero dose of either 
selinexor or placebo in that cycle. 
Study day for a given assessment is defined as  
• the assessment date – the date of first study treatment + 1 if the assessment date is on or 
after Day 1, or  
• the assessment date – the date of first study treatment if the assessment date is before 
Day 1. 
2.6. 
BASELINE MEASUREMENT 
For blinded treatment period, the baseline value is defined as the latest value prior to the first 
dose of blinded study treatment. In the case an assessment performed on the same date as the 
first dosing date, but it is impossible to determine the evaluation time relative to the time of 
taking the first dose, the evaluation time will be assumed to be following the protocol-defined 
schedule. 
For patients who proceed to open-label period, the baseline value for assessments in open-label 
treatment period will be the latest value prior to the date of first open-label study treatment. 
2.7. 
VISIT WINDOWS 
For safety data that are summarized/plotted by time points, non-missing assessments from all 
scheduled and unscheduled visits will be mapped to an appropriate analysis visit using a 
windowing scheme. Analysis visit windows are defined in Table 2-1 to Table 2-2. If there are 2 
or more assessments mapped to the same analysis visit for a patient, the assessment that is 
closest to the target visit day will be used for analysis. If there are 2 or more assessments 
mapped to the same analysis visit with the same distance from the target visit day, then select 
the latest one for the analysis. 
Table 2-1  
Visit Windows for Clinical Laboratory Tests for Patients in Blinded 
Treatment 
Analysis Visit Name 
Target Visit Day 
Study Day Range in Window 
Baseline 
Day 1 
Prior to or on Day 1 
Day 43 
Day 43 
Day 2 to 64 
Day 85 
Day 85 
Day 65 to 106 
Day 127 
Day 127 
Day 107 to 148 
Day 169 
Day 169 
Day 149 to 190 
… 
 
 
(every 42 days) 
 
 
NOTE: Day 1 is the start date of blinded treatment period. The visit window is Target Date 
– 20 days to Target Date + 21 days for post-baseline visits, except Day 43 analysis visit. 


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Analysis visit and visit window may change for certain parameters depending on the data 
availability. 
 
Table 2-2  
Visit Windows for Clinical Laboratory Tests for Patients Who Enter Open-
Label Treatment 
Analysis Visit Name 
Target Visit Day 
Study Day Range in Window 
OL Baseline 
OL Day 1 
Prior to or on OL Day 1 
OL Day 43 
OL Day 43 
OL Day 2 to 64 
OL Day 85 
OL Day 85 
OL Day 65 to 106 
OL Day 127 
OL Day 127 
OL Day 107 to 148 
OL Day 169 
OL Day 169 
OL Day 149 to 190 
… 
 
 
(every 42 days) 
 
 
NOTE: Day 1 is the start date of open-label treatment period. The visit window is Target 
Date – 20 days to Target Date + 21 days for post-baseline visits, except OL Day 43 analysis 
visit. Analysis visit and visit window may change for certain parameters depending on the 
data availability. 
 
2.8. 
SUBGROUPS 
The following subgroup analyses on selected efficacy endpoints will be conducted for Phase 3 
part: 
• Prior eribulin use (prior eribulin vs. no prior eribulin). 
• Prior trabectedin use (prior trabectedin vs. no prior trabectedin). 
• Number of prior systemic therapies excluding eribulin and trabectedin (≤ 2 vs. ≥ 3). 
 
2.9. 
POOLING OF CENTERS FOR STATISTICAL ANALYSES 
All participating centers in the study will be pooled together for analysis. 
2.10. 
COMPUTING AND CODING STANDARDS 
Activities will be performed using the following tools: 
 
Table, listing, and figure production 
 
SAS Version 9.4 or higher 


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Coding 
 
 AEs 
 
MedDRA Version 23.0 or higher 
 Medical Histories 
 
MedDRA Version 23.0 or higher 
 Prior and Concomitant Medications 
 
WHO DDE Version September 2019 or 
higher 
Grading 
 
 AEs 
 
CTCAE Version 4.03  
 Labs 
 
CTCAE Version 4.03 


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3. 
PATIENT INFORMATION 
3.1. 
DISPOSITION OF PATIENTS AND ANALYSIS POPULATIONS 
Patient disposition will be summarized in each of the following categories: 
• Patients who were randomized: 
o Patients who were randomized but did not receive any dose of study treatment 
(partial or complete) 
o Patients who were randomized and received at least one dose of study treatment 
(partial or complete) 
• End of blinded treatment: 
o Patients who were still on blinded treatment 
o Patients who discontinued blinded treatment and primary reason for treatment 
discontinuation 
• Patients who proceeded to open-label period (this applies to blinded placebo arm only) 
• Survival follow-up status post end of blinded treatment for patients who did not proceed 
to open-label period:  
o Patients in survival follow-up 
o Patients who have completed survival follow-up  
o Patients who died during survival follow-up 
o Patients who discontinued from the study without starting or completing survival 
follow-up. 
• End of study for patients who did not proceed to open-label period 
o Patients who withdrew from study and primary reason for study withdrawal 
A separate disposition summary will be presented for patients who entered open-label period 
including end of open-label treatment status, survival follow-up status post end of open-label 
treatment, and end of study status. This applies only to patients randomized to the placebo arm 
in the blinded phase eho entered open-label. 
For few patients who were randomized to selinexor in blinded phase and entered open-label 
selinexor, their end-of-treatment status, date, and reason will be used for end of blinded 
treatment summary.  
 
3.1.1. 
Efficacy Populations 
The following populations are defined: 
• The Phase 3 Intent-to-Treat Population (Ph3-ITT) will consist of all patients 
randomized to study treatment in Phase 3, regardless of whether or not they received 
study treatment. This population will be used for primary analyses of efficacy. Patients 


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will be analyzed in the treatment arm to which they are randomized and strata 
assignment at the time of randomization. 
• The Phase 3 Per-Protocol Population (Ph3-PP) will consist of all ITT patients who 
have received at least 1 dose of study treatment, have no major protocol violations 
expected to affect assessment of efficacy, and have ≥70% compliance to study treatment 
(see Section 3.4.2 for definition on study treatment compliance). Patients who progress 
or die are included regardless of duration of time on study treatment. This population 
will be used for supportive analyses of efficacy. Patients will be analyzed in the 
treatment arm to which they were randomized. 
3.1.2. 
Safety Populations 
For evaluation of safety, the following safety populations are defined: 
• The Phase 3 Safety Population (Ph3-SAF) will consist of all patients in Phase 3 who 
have received at least one dose of blinded study treatment. 
• The Phase 2 Safety Population (Ph2-SAF) will consist of all patients in Phase 2 who 
have received at least one dose of blinded study treatment. 
Patients in safety populations will be analyzed according to the actual treatment received. 
3.1.3. 
Additional Analysis Populations 
• The Phase 3 Open-Label Population (Ph3-OL) will consist of all patients in Phase 3 
who were randomized to placebo in blinded phase, entered open-label period and have 
received at least one dose of open-label selinexor. 
• The Phase 2 Intent-to-Treat Population (Ph2-ITT) will consist of all patients 
randomized to study treatment in Phase 2, regardless of whether or not they received 
study treatment. Patients will be analyzed in the treatment arm to which they were 
randomized and strata assignment at the time of randomization. 
• The Phase 2 Open-Label Population (Ph2-OL) will consist of all patients in Phase 2 
who were randomized to placebo in blinded phase, entered open-label period and have 
received at least one dose of open-label selinexor. 
3.2. 
DEMOGRAPHICS, MEDICAL HISTORY, AND BASELINE 
CHARACTERISTICS 
Demographics, medical history and baseline characteristics will generally be summarized 
among the Ph3-ITT, Ph3-SAF, Ph3-OL, Ph2-ITT, Ph2-SAF, and Ph2-OL populations, unless 
otherwise specified. No formal hypothesis testing will be performed. P-values on demographic, 
medical history and baseline characteristic data will not be calculated. 
In general, the baseline value is defined as latest value prior to the first dose of blinded study 
treatment. 
3.2.1. 
Demographic Data 
Demographic data will be summarized by treatment arm, as well as overall, and will include sex 
(female, male), race, ethnicity, country, and age at time of consent.  


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3.2.2. 
Prior Antineoplastic Therapy 
3.2.2.1. 
Prior Antineoplastic Therapy- Medication 
Prior antineoplastic medications will be summarized by treatment arm, as well as overall, and 
will include the following variables: 
• Number of prior antineoplastic regimen (summarized as a continuous variable and as a 
categorical variable) 
• Number of unique prior antineoplastic medications 
• Whether patient had prior exposure to eribulin 
• Whether patient had prior exposure to trabectedin 
• Best response to most recent antineoplastic regimen 
• Duration of most recent antineoplastic regimen 
• Days since discontinuation of most recent antineoplastic medication to randomization 
date, which will be calculated as randomization date – stop date of most recent 
antineoplastic medication + 1 
3.2.2.2. 
Prior Antineoplastic Therapy- Radiation 
Prior radiation therapy will be summarized by treatment arm, as well as overall, and will include 
the following variables: 
• Number of patients who received any prior radiation therapy  
• Number of prior radiation therapies (summarized as a continuous variable and as a 
categorical variable, with cut-off of 1 and > 1 prior radiation therapy) 
• Best response to most recent radiation therapy 
3.2.2.3. 
Prior Antineoplastic Therapy- Surgery 
Prior antineoplastic surgery will be summarized by treatment arm, as well as overall, and will 
include the following variables: 
• Number of patients who received any prior antineoplastic surgery 
• Number of prior antineoplastic surgeries (summarized as a continuous variable and as a 
categorical variable, with cut-off of 1 and > 1 prior surgery therapy) 
3.2.3. 
Medical History 
Medical history will be summarized by system organ class (SOC) and preferred term (PT) using 
the number and percentage of patients who have at least one occurrence of a SOC and PT. The 
summary will be sorted by alphabetic order in SOC, and further by decreasing frequency of PT 
within each SOC. When more than one PT has the same frequency, the order of presentation 
will be alphabetical in PTs. 
A separate summary will be provided for ongoing medical history conditions. 


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3.2.4. 
Disease History 
Disease history data will be summarized by treatment arm, as well as overall, and will include 
the following variables: 
• Time since first initial diagnosis to randomization date 
• Time since most recent progression to randomization date 
• Stage of current liposarcoma diagnosis  
3.2.5. 
Baseline Characteristics 
Baseline characteristics data will be summarized by treatment arm, as well as overall, and will 
include the following variables: 
• Baseline height (cm)/ weight (kg)/ body surface area (m2)/ BMI (kg/m2) 
• Baseline ECOG performance status 
• Number of unique ongoing medical history (Preferred Terms) per patient 
• Number of unique ongoing medications (Anatomical Therapeutic Class [ATC] Level 4 
and preferred name) per patient 
3.3. 
PRIOR AND CONCOMITANT MEDICATIONS AND 
PROCEDURES 
Concomitant medications consist of 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). Concomitant medications include any 
medications used to treat symptoms, concomitant diseases such as diabetes, hypertension, etc., 
AEs and intercurrent illnesses that are medically necessary as part of standard care. All 
concomitant medication(s) must be reported on 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. Concomitant medication 
will generally be summarized among ITT and safety populations, unless otherwise specified. 
All medications will be coded using the World Health Organization Drug Dictionary Enhanced 
(WHO DDE). 
3.3.1. 
Prior and Concomitant Medications and Procedures 
Prior medications are any treatments received by the patient prior to the first dose of blinded 
study treatment. Prior medications can be discontinued before first dose of study treatment or 
can be ongoing during treatment period. 
For Ph3-ITT, Ph3-SAF, Ph2-ITT, and Ph2-SAF populations, summaries will be presented 
among medications concomitant to blinded treatment period i.e., any treatments received by the 
patient concomitantly during the blinded treatment period from first dose of blinded study 
treatment to last dose of blinded study treatment + 30 days inclusive, or if applicable, the date of 
first open-label study treatment exclusive, whichever occurs first. Please refer to Section 2.4 for 
definitions of blinded treatment period for patients who did or did not proceed to open-label 
period respectively. 


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For Ph2-OL and Ph3-OL populations, summaries will be presented among medications 
concomitantly to open-label treatment period, i.e., any treatments received by the patient 
concomitantly during the open-label treatment period from first dose of open-label study 
treatment to last dose of open-label study treatment + 30 days. 
Concomitant medications will be summarized according to the WHO DDE by the ATC level 2 
(therapeutic level), level 4 (generic level) and preferred name. A patient taking the same drug 
multiple times will only be counted once. 
Note that a medication can be classified as both a prior medication and a concomitant 
medication.  
3.4. 
EXTENT OF STUDY TREATMENT EXPOSURE AND 
COMPLIANCE 
Extent of study treatment exposure and compliance will be summarized among the Ph3-ITT, 
Ph3-SAF, Ph3-OL, Ph2-ITT, Ph2-SAF, and Ph2-OL populations, unless otherwise specified. 
3.4.1. 
Extent of Study Treatment Exposure 
For Ph3-ITT, Ph3-SAF, Ph2-ITT, and Ph2-SAF populations, summary on exposure will be 
presented using the following variables: 
• Duration of exposure during blinded treatment (summarized as a continuous variable and 
as a categorical variable), which is defined as the date of last blinded treatment – date of 
first blinded treatment + 1 
• Total dose received during blinded treatment 
• Average dose received per week during blinded treatment, which is defined as total dose 
received during blinded treatment divided by duration of exposure during blinded 
treatment, presented in mg/week. 
• Number and percentage of patients with dose modification including dose reduction and 
interruption during blinded treatment  
o Number and percentage of patients with dose reduction 
o Number and percentage of patients with drug interruption 
• Number and percentage of patients in which blinded treatment was discontinued 
For Ph3-OL and Ph2-OL populations, summary on exposure will be presented using the 
following variables: 
• Duration of exposure during open-label treatment (summarized as a continuous variable 
and as a categorical variable), which is defined as the date of last open-label treatment – 
date of first open-label treatment + 1 
• Total dose received during open-label treatment 
• Average dose received per week during open-label treatment, which is defined as total 
dose received during open-label treatment divided by duration of exposure during open-
label treatment, presented in mg/week. 
• Number and percentage of patients with dose modification including dose reduction and 
interruption during open-label treatment  


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o Number and percentage of patients with dose reduction during open-label treatment 
o Number and percentage of patients with drug interruption during open-label treatment 
• Number and percentage of patients with open-label treatment discontinued 
 
3.4.2. 
Treatment Compliance 
Study treatment compliance will be summarized descriptively as a quantitative variable, 
calculated as 
number of study treatment doses taken
number of  study treatment doses prescribed × 100%. 
Note that the number of scheduled study treatment doses (selinexor or placebo) does not include 
doses missed due to treatment interruption or other reasons not related to patient choice. Patients 
with study treatment compliance < 70% will be excluded from the PP population. 
Study treatment compliance will be calculated for blinded treatment period and if applicable, 
open-label treatment period separately. The number and percentage of patients with blinded 
study treatment compliance ≥70% will be provided among Ph3-ITT, Ph3-SAF, Ph2-ITT, and 
Ph2-SAF populations.  The number and percentage of patients with open-label study treatment 
compliance ≥70% will be provided among Ph3-OL and Ph2-OL populations. 


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4. 
EFFICACY 
Patient response will be assessed centrally by ICR, according to RECIST v.1.1 (Eisenhauer 
2009). Unless otherwise specified, response assessment refers to assessment determined by ICR. 
The primary efficacy analyses will be conducted using the ITT population, unless otherwise 
specified. Efficacy analyses using the PP population will be considered as supportive. 
If the interim analysis of unblinded sample size re-estimation is conducted, CHW method will 
be applied to the primary analysis of the PFS endpoint, with details in Section 1.5. 
4.1. 
PRIMARY EFFICACY ENDPOINTS 
4.1.1. 
Progression-Free Survival (PFS) 
Progression-free survival (PFS), defined as the time from date of randomization until ICR-
determined PD per RECIST v.1.1, or death due to any cause, whichever occurs first.  
The primary analysis of PFS will be performed by treatment arm (selinexor versus placebo) 
using the Ph3-ITT population. The analysis will be repeated for the Ph3-PP population as a 
supportive analysis.  
Duration is calculated as end date – start date +1. For instance, if a PFS event occurs, then PFS 
time (in days) is defined as event date – date of randomization +1. If a censoring event occurs, 
then PFS time is defined as the censoring date – date of randomization +1. 
Please refer to Table 4-1 for details on PFS outcome status (PFS event vs. censored) and 
censoring definitions.  
 
 


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Table 4-1  
PFS Outcome and Censoring Definitions 
# 
Situation 
Date of event or censoring 
Outcome 
1 
No baseline disease assessment 
Randomization 
Censored 
2 
No adequate post-baseline disease status 
assessment unless death occurs prior to 
first post-baseline assessment 
Randomization 
Censored 
3 
ICR-determined PD without a gap of 2 or 
more consecutively missed scheduled 
disease assessment before PD. 
Date of PD 
PFS 
Event 
4 
Death before ICR-determined PD and 
without a gap of 2 or more consecutively 
missed scheduled disease assessment 
before death. 
Date of death 
PFS 
Event 
5 
No ICR-determined PD or death on or 
before  
• Database cut 
• Withdrawal of informed consent 
• Lost to follow-up  
• Date of discontinuation from 
blinded treatment + 30 days  
• A gap of 2 or more consecutively 
missed scheduled disease 
assessment 
• Start of new antineoplastic 
therapy*, whichever occurs first 
Date of last adequate disease 
assessment prior to the events 
listed in the left column 
Censored 
*For the purpose of calculating PFS for blinded treatment, start of open-label selinexor will be considered as 
initiating a new antineoplastic therapy. 
The number and percentage of patients who had a PFS event will be reported. Median PFS with 
95% confidence interval (CI) will be summarized using the Kaplan-Meier (KM) method for 
each treatment arm. The KM curves for PFS will be provided by treatment arm. 
A stratified log-rank test will be used to compare the PFS between treatment arms (selinexor 
versus placebo) for the primary efficacy assessment. The strata will be those used for stratified 
randomization (i.e., prior eribulin use, prior trabectedin use, number of prior systemic therapies 
excluding eribulin and trabectedin).  


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Hazard ratios and its 95% CI will be estimated by a stratified Cox proportional hazards model, 
with Efron’s method of tie handling, with treatment as the factor. The strata will be those used 
for stratified randomization.  A non-stratified log-rank test and a Cox proportional hazards 
model will be used as sensitivity analyses. 
For exploratory purposes, PFS in Ph3-ITT population will also be analyzed:  
• In subgroups based on the stratification factors as randomized 
• In a sensitivity analysis similar to the primary PFS analysis but where initiation of new 
antineoplastic therapy is considered as a PFS event 
• In a sensitivity analysis similar to the primary PFS analysis but where clinical 
progression is considered as a PFS event. Clinical progression is defined as the event 
where a patient discontinues blinded treatment with reason being either disease 
progression or clinical progression but is not classified as PD by ICR. 
• Based on response assessment per investigator 
4.2. 
SECONDARY EFFICACY ENDPOINTS 
The secondary efficacy endpoints will be summarized by randomized treatment arm (selinexor 
vs. placebo), unless otherwise specified.  
For time-to-event endpoints, a stratified log-rank test and stratified Cox proportional hazards 
model analysis will be conducted to assess the effect of selinexor. The strata will be those used 
for stratified randomization. Median event times with 95% CIs will be estimated based on the 
KM method for each treatment arm. The KM curves will be provided. The number and 
percentage of patients with the corresponding events (e.g., death) will be provided. If nominal p-
values are computed for those secondary efficacy analyses, they should be interpreted with 
caution due to potential issues of multiplicity. 
For dichotomous endpoints, treatment differences will be tested using the Cochran-Mantel-
Haenszel (CMH) test, stratified by the randomization stratification factors. The number and 
percentage of patients will also be summarized by treatment arm. 
4.2.1. 
Key Secondary Efficacy Endpoints 
The following 2 overall survival (OS) endpoints are defined as key secondary endpoints: OS 
defined as time since randomization until death due to any cause. Patients who are alive will 
have their OS follow-up time censored at the latest date for which the patient was known to be 
alive 
• OS for non-inferiority in Ph3-ITT population with a non-inferiority margin of HR=1.15.  
• OS for superiority in Ph3-ITT population. 
Statistical significance of key secondary endpoints will not be claimed until the primary analysis 
of PFS has reached significance. The key secondary endpoints will be tested using the 
hierarchical testing procedure to maintain the overall type I error at a 1-sided 0.025 level of 
significance. More details on the strategy to address multiplicity issues are provided in Section 
4.4. 
The testing sequence will be:  


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• OS for non-inferiority in Ph3-ITT population with a non-inferiority margin of HR=1.15.  
• OS for superiority in Ph3-ITT population. 
4.2.1.1. 
Overall Survival (OS) 
OS is defined as time since randomization until death due to any cause. If death event did not 
occur during the follow-up period, the patient is censored at the date of discontinuation from the 
study, or date of last participating visit (e.g., a telephone contact with patient status being alive) 
on or before database cut-off date, whichever occurs first.  
The OS analyses will be conducted among the Ph3-ITT, Ph3-PP, and Ph2-ITT populations. 
In sensitivity analysis for OS, the two-stage estimation method will be implemented to assess 
the impact of cross-over on the effect of selinexor on OS. 
For exploratory purposes, OS will be analyzed among Ph3-ITT and Ph2-ITT populations 
respectively:  
• Among the subset of Ph3-ITT population removing patients with the blinded phase 
treatment unblinded without ICR-confirmed PD 
• In a sensitivity analysis in which patients will be censored at the start date of first new 
antineoplastic therapy including open-label selinexor. 
• Among the subset of Ph3-ITT and Ph2-ITT populations, respectively, who did not enter 
open-label period. 
• Assessing the proportion of patients whose OS ≥ 12 months (OS12). Patients who were 
censored before 12 months is considered not meeting the criteria of having OS ≥ 12 
months. Treatment differences between the selinexor and placebo arms will be tested 
using the Cochran-Mantel-Haenszel (CMH) test, stratified by the randomization 
stratification factors. The number and percentage of patients will also be summarized by 
treatment arm.  
4.2.2. 
Other Secondary Efficacy Endpoints 
4.2.2.1. 
Time to Progression (TTP) 
Time to progression (TTP) is defined as the time from date of randomization until ICR-
determined PD per RECIST v.1.1, or death due to disease progression, whichever occurs first. 
TTP outcome and censoring definitions are similar to the outcome and censoring definitions for 
PFS in Table 4-1, with the only exception that only death due to disease progression will be 
considered a TTP event. Death due to reasons other than disease progression will be a new 
censoring event under situation #5. 
TTP on patient’s last prior systemic therapy is defined as time since start of last prior systemic 
therapy to date of disease progression. For patients without a disease progression date, their TTP 
will be censored on the discontinuation date of last prior systemic therapy.  
The comparison of TTP on study treatment to TTP on last prior therapy will be performed using 
a stratified Cox proportional hazards regression model stratifying on patient IDs to account for 
correlation within patient. This analysis will be conducted respectively among Ph3-ITT and 
Ph2-ITT patients randomized to selinexor. 


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For exploratory purpose, TTP will be summarized among Ph3-ITT patients randomized to 
placebo arm, Ph3-OL population, Ph2-ITT patients randomized to placebo arm, and Ph2-OL 
population respectively. For open-label selinexor, TTP is measured as time since the start of 
open-label treatment until ICR-determined PD per RECIST v.1.1, or death due to disease 
progression, whichever occurs first. Median TTP time with 95% CIs will be presented using the 
KM method. 
4.2.2.2. 
QLQ-C30 
QLQ-C30 contains 30 questions and includes five functional scales (Physical, Role, Emotional, 
Social, and Cognitive Functioning), three symptom scales (Fatigue, Nausea/Vomiting and Pain) 
and a Global Health Status/QoL scale, and six single-item symptom items (dyspnoea, insomnia, 
appetite loss, constipation, diarrhoea and financial difficulties). The principle for scoring these 
scales is the same: 1. Calculate the mean of the items that contribute to the scale; this is the raw 
score. 2. Use a linear transformation to standardise the raw score, so that scores range from 0 to 
100.  
For functional scales and the global heath status/QoL, a higher score represents a better level of 
functioning (better health status); for symptom scales/items, a higher score represents a higher 
level of symptomatology/problems (worse health status). 
The missing data will be handled based on EORTC QLQ-C30 scoring manual (Fayers et al., 
2001). The raw score (mean of the items that contribute to the scale) will only be calculated if at 
least half of the items (i.e., 3 of 6 items, or 3 of 5 items) from the domain have been answered. 
As a result, none of the single-item measures will be imputed. 
The actual value and change from baseline before initiating a new antineoplastic treatment will 
be summarized using descriptive statistics over time for each of the five functional scales, three 
symptom scales and six items, and the global health status/QoL scale.  
QLQ-C30 analyses will be summarized by treatment arm among Ph3-ITT, Ph3-PP, and Ph2-
ITT populations.  For exploratory purpose, QLQ-C30 will also be summarized in Ph3-OL and 
Ph2-OL populations, in which changes from baseline will be calculated using baseline values 
for the open-label period, i.e., last assessment on or before the start of open-label treatment. 


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Table 4-2  
Scoring the QLQ-C30 version 3.0 
 
4.2.2.3. 
EQ-5D-5L 
The EQ-5D-5L is a validated quality of life questionnaire developed by the EuroQol group in 
order to provide a simple, generic utility measure for characterizing current health states of 
patients. It consists of 2 parts, the descriptive system and the visual analogue scale (VAS). 
EQ-5D-5L descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels (no problems, slight 
problems, moderate problems, severe problems and extreme problems). EQ-5D-5L health states, 
defined by the EQ-5D-5L descriptive system, will be converted into a single index value 
according to the U.S. population (van Hout et al, 2012). The VAS records the respondent’s self-
rated health status on a vertical visual analogue scale. The VAS ‘thermometer’ has 100 (best 
imaginable health state) at the top and 0 (worst imaginable health state) at the bottom.  
The actual value and change from baseline before initiating a new antineoplastic therapy will be 
summarized using descriptive statistics over time for EQ-5D-5L health states and VAS. 
EQ-5D-5L analyses will be summarized by treatment arm among Ph3-ITT, Ph3-PP, and Ph2-
ITT populations.  For exploratory purpose, EQ-5D-5L will also be summarized in Ph3-OL and 


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
 
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
3 9  
P h 2 -O L p o p ulati o ns, i n w hic h c ha n ges fr o m bas eli ne will be calc ulate d usi n g bas eli ne val ues 
f or t he o pe n-l a bel peri o d, i.e., last assess me nt o n or bef ore t he start of o p e n-la bel treat me nt. 
4. 2. 2. 4.  
O R R  
O R R is defi ne d as t he pr o p orti o n of patie nts w h o a c hie ve an  I C R-deter mi ne d best o verall 
res p o nse of P R or C R per R E CI S T v. 1. 1, bef ore I C R-c o nfir me d P D or i nitiati n g a n e w 
a nti ne o plastic t hera p y. O pe n -la bel seli ne x or is c o nsi dere d a n e w a nti ne o pl astic t hera p y f or t he 
p ur p ose of ass essi n g O R R f or bli n de d st u d y treat me nt.  
T he n u m ber a n d p erce nta ge of patie nts a c hie vi n g P R or C R will be s u m marize d b y treat me nt 
ar m a m o n g P h 3 -I T T a n d P h 2-I T T p o p ul ati o ns res pecti vel y.  
4. 2. 2. 5.  
Ti me t o Ne xt T re at me nt ( T T N T)  
T T N T is defi ne d as ti me si nce ra n d o mizati o n u ntil t he first ne w a nti ne o plastic t hera p y or deat h 
d ue t o a n y ca us e, w hic he ver occ urs first. F or patie nts wit h o ut a n e ve nt, t heir f oll o w -u p ti me will 
be ce ns or e d at t he d ate of disc o nti n uati o n fr o m t he st u d y, or dat e of last partici pati n g visit (e. g., 
a tele p h o ne c o ntact wit h patie nt stat us bei n g ali ve) o n or bef ore dat a base c ut -off date, w hic he ver 
occ urs first.  
T T N T o n patie nt’s last pri or s yste mic t hera p y is defi ne d as ti me si nce start of last pri or s yst e mic 
t hera p y t o start of bli n de d st u d y treat me nt or deat h d ue t o a n y caus e, w hic he ver occ urs first. F or 
patie nts w h o were ra n d o mize d b ut ne ver recei ve d st u d y treat me nt, a n d di d n ot die bef ore 
disc o nti n uati o n fr o m st u d y, t heir f oll o w -u p ti me will be ce ns ore d at t he date of disc o nti n uati o n 
fr o m t he st u d y, or date of last partici pati n g visit (e. g., a t ele p h o ne c o ntact wit h patie nt stat us 
bei n g ali ve) o n or bef ore data base c ut -off d ate, w hic he ver occ urs first.  
T he a nal ysis c o m pari n g T T N T o n st u d y tr eat me nt vs. o n last pri or s yste mi c t hera p y will be 
c o n d ucte d a m o n g p atie nts  i n t he P h 3 -I T T p o p ulati o n ra n d o mize d t o seli ne x or a n d place b o  ar ms 
se parat el y. T o acc o u nt f or wit hi n -pers o n c orrelati o n, a stratifie d C o x pr o p orti o nal hazar ds 
m o del a nal ysis will be c o n d ucte d stratif yi n g o n patie nt I Ds. K M m e dia n T T N T ti mes wit h 9 5 % 
CIs, a n d K M c ur ves will be pr o vi de d.  
 
4. 3.  
E X P L O R A T O R Y E N D P OI N T S  
C CI


K C P -3 3 0 -0 2 0/ S E A L  
St atistic al A n alysis Pl a n  
K ary o p h ar m T her a pe utics, I nc.  
 
 
2. 0  
2 0  Se pte m ber 2 0 2 0  
C O N FI D E N TI A L  
4 0  
C CI


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4.4. 
MULTIPLE COMPARISONS/MULTIPLICITY 
The overall type I error for the primary endpoint and each key secondary endpoint is strictly 
controlled at 0.025 (one-sided).  
The graphical multiple testing procedure in Bretz et al (2009) will be used to test the primary 
and key secondary endpoints. It is a Bonferroni-based closed test procedure, so it strongly 
controls the family-wise error rate across the endpoints. See the figure below for the alpha 
reallocation for the primary and key secondary endpoints.  
Figure 4-1: Graphical illustration of the propagation of endpoint-specific alpha 
 
 
 
 


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To account for the interim analysis with options to stop for futility (non-binding) or efficacy, 
type I error is adjusted using the Lan DeMets (Lan and DeMets, 1983) alpha spending function 
with the O’Brien-Fleming type of boundary. If the interim analysis is conducted for the 
unblinded sample size re-estimation, the overall type I error for the final analysis of the primary 
efficacy PFS endpoint will be maintained using the CHW method (Cui et al, 1999) (see Section 
1.5). 
Statistical significance of key secondary endpoints will not be claimed until the primary 
endpoint of PFS have reached significance. The key secondary endpoints will be tested using 
the hierarchical testing procedure as shown in Figure 4-1 to maintain the overall type I error. 
 


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5. 
SAFETY 
Safety analyses will be reported by the actual treatment arm patients received and overall, 
among the Ph3-SAF and Ph2-SAF populations respectively. Unless otherwise specified, only 
data from the blinded treatment period will be presented. Please refer to Section 2.4 on 
definitions of observation periods. 
For patients in the Ph3-OL and Ph2-OL populations respectively, selected safety data from the 
open-label period will be presented in separate summaries.  
Safety analyses will be based on the reported AEs and other safety information, such as 12-lead 
electrocardiogram (ECG), vital signs, physical examination, ECOG performance status, clinical 
laboratory assessments including hematology and serum chemistry. 
General rules 
All safety analyses will be performed using the following common rules: 
• Safety data in patients who do not belong to the safety population (e.g., enrolled but did 
not receive any dose of study treatment, partial or complete) will be listed separately. 
• The baseline value is the last available value before first dose of study treatment. Please 
refer to Section 2.6 for details. 
• The analyses of the safety variables will be essentially descriptive with no systematic 
testing planned.  
5.1. 
ADVERSE EVENTS 
An AE is defined as any untoward medical occurrence in a 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 treatment, whether or not related to the 
study treatment. 
All AEs (including serious adverse events [SAEs]) will be coded to a preferred term (PT) and 
associated primary system organ class (SOC) using the MedDRA. 
The severity of all AEs will be graded according to the NCI CTCAE Grading Scale, v. 4.03. An 
AE with a CTCAE grade of 3 or higher is considered a severe AE. The severity of the AE is 
different from the seriousness of the AE. For AEs not covered by CTCAE, the severity will be 
characterized as “mild,” “moderate,” “severe”, “life-threatening” (corresponding to Grades 1 to 
4) according to the following definitions: 
• Mild events are usually transient and do not interfere with the patient’s daily activities.  
• Moderate events introduce a low level of inconvenience or concern to the patient and 
may interfere with daily activities.  
• Severe events interrupt the patient’s usual daily activities. 
• Life-threatening. 
 


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5.1.1. 
Definitions of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse 
Events (SAEs), and Treatment-Emergent Treatment-Related Adverse Events 
(TRAEs) 
5.1.1.1. 
Treatment-Emergent Adverse Event (TEAE) 
For AE summaries for blinded treatment period, treatment-emergent adverse events (TEAEs) 
are defined as any event that developed or worsened or became serious during the blinded 
treatment period, i.e., from the date of first blinded study treatment up to the date of last blinded 
study treatment + 30 days inclusive (or the day before initiation of a new anti-neoplastic 
treatment, whichever occurs first), or if applicable, the date of first open-label study treatment 
exclusive, whichever occurs first. Please refer to Section 2.4 on definitions on observation 
periods. Additionally, TEAEs also include any event that developed post the blinded treatment 
period but was assessed by the Investigator as related to study treatment. Please note for few 
patients who were randomized to selinexor in blinded phase and entered open-label selinexor, 
their blinded study treatment period ends on the date of last non-zero dose of open-label 
selinexor + 30 days inclusive. To these patients, open-label selinexor is not considered a new 
anti-neoplastic therapy. 
For AE summaries for the open-label period, TEAEs are defined as any event that developed or 
worsened or became serious during the open-label treatment period, i.e., from the date of first 
open-label study treatment up to the date of last open-label study treatment + 30 days inclusive 
(or the day before initiation of a new anti-neoplastic treatment, whichever occurs first). 
Additionally, TEAEs also include any event that developed post the open-label treatment period 
but was assessed by the Investigator as related to open-label selinexor. This definition applies to 
Ph3-OL and Ph2-OL populations only. 
5.1.1.2. 
Serious Adverse Event (SAE) 
An SAE is any untoward medical occurrence, at any dose, that: 
• Results in death 
• Is life-threatening (i.e., an event in which the patient was at risk of death at the time of 
the event; it does not refer to an event that hypothetically might have caused death if it 
were more severe) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Results in a congenital anomaly/birth defect 
SAE needs to be clearly documented on the AE form. SAEs that occur at any time between the 
signing of the ICF up to the first dose of study treatment, must be reported (in addition to SAEs 
that occur after the first dose of study treatment). 
5.1.1.3. 
Treatment-emergent Treatment-Related Adverse Events (TRAEs) 
A TRAE is any TEAE that is assessed by the Investigator as related to study treatment.   
For summaries on TRAEs for the open-label period, a TRAE is any TEAE that is assessed by 
the Investigator as related to open-label selinexor. 


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5.1.1.4. 
Adverse Event of Clinical Interest (AECI) 
Any AE (serious or non-serious) that is of scientific and medical concern specific to the study 
treatment, for which ongoing monitoring and rapid communication by the Investigator to the 
Sponsor is appropriate.  
 
5.1.2. 
Analysis Methods 
The primary focus of AE reporting will be on TEAEs. 
If an AE date/time of onset (occurrence or worsening) is incomplete, an imputation algorithm 
will be used to determine the AE as treatment-emergent. The algorithm for imputing date/time 
of onset will be conservative and will classify an AE as treatment-emergent unless there is 
definitive information to determine it is not treatment emergent. Details on classification of AEs 
with missing or partial onset dates are provided in Section 2.2.2. 
AE summaries will include number (n) and percentage (%) of patients who have experienced an 
AE. The denominator for computation of percentages is the number of patients in the 
corresponding treatment arm. Multiple occurrences of the same event in the same patient will be 
counted only once in the tables. 
Unless otherwise specified, sorting order will follow the alphabetic order in SOC, and further by 
decreasing frequency of PTs within each SOC. When more than one PT has same number of 
events, the order of presentation will be alphabetical in PTs.  
Based on the entries on the eCRF AE page, an AE is considered related to study treatment if the 
entry for “Relationship to study treatment” is “Related” or “Possibly Related”. 
5.1.3. 
Analysis of TEAE 
An TEAE overview summary table will be provided, which will include the number of patients 
with at least one of the adverse events:  
• TEAEs  
• Grade 3/4 TEAEs  
• Serious TEAEs  
• TEAEs leading to dose modifications of study treatment 
− TEAEs leading to dose reduction of study treatment 
− TEAEs leading to dose interruption of study treatment 
• TEAEs leading to study treatment discontinuation 
• TEAEs leading to death  
• TRAE 
• Serious TRAEs  
• TRAEs leading to dose modifications of study treatment 


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− TRAEs leading to dose reduction of study treatment 
− TRAEs leading to dose interruption of study treatment 
• TRAEs leading to study treatment discontinuation 
• TRAEs leading to death  
TEAEs will be summarized by primary SOC and PT and will include the following categories:  
• All TEAEs  
• All TEAEs, by maximum grade  
• Grade 3 or higher TEAEs  
• TEAEs leading to dose modifications of study treatment 
The most commonly reported (at least 10% of all patients) TEAEs will be presented by PT only 
and will include the following categories:  
• The most commonly reported TEAEs  
• The most commonly reported TRAEs, a lower cut-off (e.g., 5% or 2% depending on 
TRAE frequency) will be used. 
5.1.4. 
Analysis of SAE 
Treatment-emergent SAEs will be summarized by primary SOC and PT and will include the 
following categories:  
• All treatment-emergent SAEs  
• All treatment-emergent treatment-related SAEs 
• Treatment-emergent SAEs leading to dose modifications of study treatment 
• Treatment-emergent SAEs leading to study treatment discontinuation 
• All treatment-emergent SAEs leading to death 
All SAE will be provided in a data listing.  
5.1.5. 
Analysis of AECI 
Standard MedDRA Query (SMQ), Customized MedDRA Query (CMQ), or specific Preferred 
Terms will be utilized for AECI analysis. Analyses of treatment-emergent AECI will be 
performed separately for each pre-specified AECI category. Overview summary of all AECI 
will be summarized similarly as in Section 5.1.3. 
The following AECI will be summarized by PT: 
• All TEAEs 
• Serious TEAEs 
The list of AECI categories are provided in Table 5-1. The search strategy of preferred terms for 
each category will be provided in a separate document. 


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Table 5-1  
AECI Categories 
Group Category 
AECI Category 
Hematologic events 
Neutropenia 
Thrombocytopenia 
Eye disorders events 
Blurred Vision 
Cataract 
Gastrointestinal events 
Nausea 
Vomiting 
Decreased Appetite  
Weight Decreased  
Infection 
 
 
Pneumonia 
Sepsis 
Metabolism and nutrition disorders 
Hyponatremia 
Nervous system disorders 
Neurological Toxicity 
5.2. 
 DEATH 
The following summaries on death events will be provided: 
• An overview of all death events that occurred during the blinded/open-label treatment 
period, and primary cause of death 
• TEAEs leading to death (death as an outcome on the AE report page as reported by the 
Investigator), by primary SOC and PT 
• TRAEs leading to death, by primary SOC and PT 
• Listing of all TEAEs leading to death 
• Listing of all death events 
5.3. 
LABORATORY SAFETY VARIABLES 
5.3.1. 
Definitions 
Clinical laboratory data consists of blood analysis, including hematology and serum chemistry. 
Clinical laboratory values in conventional units will be converted using the international system 
of units (SI).  
The laboratory parameters will be classified as follows: 
• Hematology (blood sample: ethylenediaminetetraacetic acid) will include hemoglobin, , 
white blood cell (WBC) count, lymphocytes, neutrophils, platelets. WBC differential 


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may be automated or manual as per institutional standards. Reticulocytes may be done 
only when clinically indicated. 
• Serum Chemistry (blood sample: serum) 
o Complete Serum Chemistry will include sodium, potassium, chloride, 
bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, calcium, phosphate, 
magnesium, ALT, AST, alkaline phosphatase, total bilirubin, lactate 
dehydrogenase (LDH), total protein, albumin, creatinine kinase, uric acid. 
o Limited Serum Chemistry will include sodium, potassium, chloride, bicarbonate, 
BUN, creatinine, glucose, ALT, AST, alkaline phosphatase, total bilirubin, and 
LDH.  
o If the total bilirubin concentration is increased above 1.5 times the upper normal 
limit, total bilirubin should be differentiated into the direct and indirect reacting 
bilirubin. 
5.3.2. 
Analysis of Laboratory Variables 
Whenever applicable, severity of selected clinical laboratory measures will be determined based 
on the CTCAE criteria. Laboratory values with CTCAE Grade ≥ 3 will be presented in a data 
listing. The worst toxicity grade in hematology and chemistry will be summarized by toxicity 
grade. Shift tables that present changes from baseline to worst on-study relative to CTCAE 
classification ranges will be presented. These shift tables will include results from unscheduled 
visits. 
For selected key laboratory parameters, box plots on measurements over time as well as 
by-patient plots for patient-level measurements over time may be presented. 
A listing of cases where ALT or AST > 3x upper limit of normal (ULN) with simultaneous total 
bilirubin > 2x ULN will be presented. 
Thresholds/Range analyses for selected laboratory parameters will be conducted. The number 
and percentage of patients classified into each category based on worst values will be presented. 
5.4. 
VITAL SIGNS, ECOG, AND PHYSICAL EXAMINATION 
VARIABLES 
The physical examination (PE) will be performed according to the standards at each institution. 
Physical examination, including vital signs, will be performed on the scheduled day, even if 
study treatment is being interrupted. Physical examinations should include general appearance, 
dermatological, head, eyes, ears, nose, throat, respiratory, cardiovascular, abdominal, lymph 
nodes, musculoskeletal, and neurological examinations. 
Vital signs include height (without shoes) in centimeters (cm), weight (indoor clothing without 
shoes) in kilograms (kg), body surface area (BSA), systolic and diastolic blood pressure (SBP 
and DBP), pulse measurements, and body temperature (oC). BSA will be calculated by the 
Dubois (Dubois 1916) method.  
An ECOG score assessment with grades 0-5 will be performed during screening, day 1 of each 
cycle, and EoBT and/or EoT visits.  


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The actual value and change from baseline to each on-study evaluation will be summarized for 
vital signs including pulse, temperature, systolic blood pressure, diastolic blood pressure, BSA 
and weight. Shift tables that present changes from baseline to highest on-study and lowest on-
study for systolic blood pressure and diastolic blood pressure will be presented. Shift tables that 
present changes from baseline to worst on-study and last on-study ECOG performance status 
values will also be produced.  
Abnormal vital signs results will be summarized in the threshold/range analyses. 
Abnormal PE findings will be provided in a data listing. 
5.5. 
ELECTROCARADIOGRAM (ECG) 
Standard 12-lead ECGs will be performed. The ECGs performed on Day 1 of Cycles 1 and 2 
during blinded study treatment are to be performed just prior to the blood sample taken 2 hours 
postdose (approximately at the expected tmax of plasma selinexor). ECGs may also be performed 
as clinically indicated during the study. 
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 following will be assessed: heart rate, PR 
interval, QT interval, QRS interval, and QT corrected Bazett’s or Fredericia’s formula. 
Changes from baseline to highest on-study post baseline measurement for PR interval, QRS 
interval, and QT corrected will be summarized using shift tables. For heart rate, changes from 
baseline to lowest and highest on-study post baseline measurement will be presented.  
Abnormal ECG results will be summarized in the threshold/range analyses.  
 
 
 


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6. 
REFERENCES 
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective 
multiple test procedures. Statistics in medicine. 2009;28(4):586-604. 
Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, Chen LL, 
Podoloff DA, Benjamin RS. Correlation of computed tomography and positron emission 
tomography in patients with metastatic gastrointestinal stromal tumor treated at a single 
institution with imatinib mesylate: proposal of new computed tomography response criteria. 
J Clin Oncol. 2007 May 1;25(13):1753-9. 
Cui L, Hung HMJ, and Wang, SJ. (1999), Modification of Sample Size in Group Sequential 
Trials. Biometrics 1999;55:853–857. 
DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight 
be known. Arch Intern Medicine. 1916;17:863-871. 
East (2016) Software for design and monitoring of group sequential and adaptive trials; 6.4. 
Cytel, Inc., MA. www.cytel.com. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
Revised RECIST guideline (Version 1.1). Eur J Cancer. 2009:45:228-247 
EORTC QLQ-C30 Scoring Manual (3rd edition). Fayers PM, Aaronson NK, Bjordal K, 
Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. 
Brussels: EORTC, 2001. ISBN: 2-9300 64-22-6 
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. 
Van Hout B, Janssen MF, Feng YS, et al. Interim scoring for the EQ-5D-5L: mapping the EQ-
5D-5L to EQ-5D-3L value sets. Value in Health. 2012;15(5):708-15. 
Lan K, DeMets D. Discrete sequential boundaries for clinical trials. Biometrika. 1983;70:659-
63. 
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. 
Cancer. 1981 Jan 1;47(1):207-14 
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. 
Xin Yan & Xiao-Gang Su (2010) Stratified Wilson and Newcombe Confidence Intervals for 
Multiple Binomial Proportions, Statistics in Biopharmaceutical Research, 2:3, 329-335, 
DOI: 10.1198/sbr.2009.0049 
Latimer NR, Abrams KR, Lambert PC, Crowther MJ, Wailoo AJ, Morden JP, Akehurst RL, 
Campbell MJ. Adjusting for treatment switching in randomized controlled trials – a simulation 
study and a simplified two-stage method. Stat Methods Med Res. 2017;26(2):724–51 
Latimer NR, Abrams KR, Lambert PC, Morden JP, Crowther MJ. Assessing methods for 
dealing with treatment switching in clinical trials: a follow-up simulation study. Stat 
Methods Med Res. 2018;27(3):765–84. 


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7. 
APPENDICES 
7.1. 
Appendix I: World Health Organization (WHO) Tumor Response 
Criteria 
Table 7-1 World Health Organization (WHO) Tumor Response Criteria 
(Adapted from Miller AB, et al., Reporting results of cancer treatment. Cancer. 
1981;47:207-214.) 
Characteristic 
Criteria 
Tumor Burden 
No maximal number of lesions specified.  
No limitations specified per organ site 
Measurability of 
lesions at 
baseline  
1. Measurable, bidimensional (product of LD and greatest perpendicular 
diameter)a  
2. Nonmeasurable/evaluable (e.g., lymphangitic pulmonary metastases, 
abdominal masses)  
Objective 
response  
 
1. Measurable disease (change in sum of products of LDs and greatest 
perpendicular diameters, no maximum number of lesions specified)  
CR: disappearance of all known disease, confirmed at ≥ 4 wk  
PR: ≥ 50% decrease from baseline, confirmed at ≥ 4 wk.  
• 
Bidimensional: single lesion, greater than or equal to 50% 
decrease in tumor area (multiplication of longest diameter by the 
greatest perpendicular diameter); multiple lesions, a 50% 
decrease in the sum of the products of the perpendicular 
diameters of the multiple lesions.  
• 
Unidimensional: greater than or equal to 50% decrease in linear 
tumor measurement. 
• 
No new lesions or progression of any lesions. 
PD: ≥ 25% increase of one or more lesions, or appearance new lesions  
NC (SD): neither PR or PD criteria met  
2. Nonmeasurable disease  
CR: disappearance of all unknown disease, confirmed at ≥ 4 wk  
PR: estimated decrease of 50%, confirmed at ≥ 4 wk  
PD: ≥ 25% in existent lesions of appearance of new lesions  
NC (SD): neither PR or PD criteria met 
3. Bone Metastases 
CR: Complete disappearance of all lesions on x-ray or scan for at least 
four weeks.  
PR: Partial decrease in size of lytic lesions, recalcification of lytic 
lesions, or decreased density of blastic lesions for at least four 
weeks. 
PD: Increase in size of existent lesions or appearance of new lesions. 


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Characteristic 
Criteria 
NC (SD): Because of the slow response of bone lesions, the designation 
of no change should not be applied until ≥ 8weeks have passed from 
start of therapy. 
Occurrence of bone compression or fracture and its healing should not be 
used as the sole indicator for evaluation of therapy. 
Overall response  
1. Best response recorded in measurable disease  
2. NC in nonmeasurable lesions will reduce a CR in measurable lesions to 
an overall PR  
3. NC in nonmeasurable lesions will not reduce a PR in measurable lesions  
Duration of 
response 
1. CR: From date CR criteria first met to date PD first noted. 
2. Overall Response: From date of treatment start to date PD first noted. 
3. In patients who only achieve a PR, only the period of overall response 
should be recorded  
LD = longest diameter; CR = complete response; PR = partial response; PD = progressive disease; NC = no 
change; SD = stable disease.  
aLesions that can be measured only unidimensionally are considered measurable (e.g., mediastinal adenopathy, 
malignant hepatomegaly). 
 
 


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7.2. 
Appendix II: RECIST Version 1.1 
(Modified from Eisenhauer 2009) 
All patients will have their BEST RESPONSE on study classified as outlined below: 
Complete Response (CR) 
Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) 
must have reduction in the short axis to < 10mm. 
Partial Response (PR) 
At least a 30% decrease in the sum of diameters of target lesions, taking as reference the 
baseline sum diameters. 
Stable Disease (SD) 
Steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD. 
Progressive Disease (PD) 
At least a 20% increase in the sum of diameters of measured lesions taking as references the 
smallest sum of diameters recorded since the treatment started. In addition to the relative 
increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 
Appearance of one or more new lesions will also constitute PD.  
Response Duration 
Response duration will be measured from the time measurement criteria for CR/PR (whichever 
is first recorded) are first met until the first date that recurrent or PD is objectively documented, 
taking as reference the smallest measurements recorded since the treatment started. 
Stable Disease Duration 
Stable disease duration will be measured from the time of start of therapy until the criteria for 
progression are met, taking as reference the smallest measurements recorded since the treatment 
started. 
 
 
Table 7-2-1 Evaluation of Best Overall Response – Patient with Target (+/- non-target) 
Disease 
Target lesions 
Non-Target lesions 
New Lesions 
Overall response 
CR 
CR 
No 
CR 
CR 
Non-CR-Non-PD 
No 
PR 
CR 
NE 
No 
PR 


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Target lesions 
Non-Target lesions 
New Lesions 
Overall response 
PR 
Non-PD/or not all 
evaluated 
No 
PR 
SD 
Non-PD/or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
Table 7-2-2 Evaluation of Best Overall Response – Patient with Non-Target Disease Only 
Non-Target lesions 
New Lesions 
Overall response 
CR 
No 
CR 
Non-CR-Non-PD 
No 
Non-CR/Non-PD1 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of PD at that time should be reported as “symptomatic 
deterioration”. Every effort should be made to document the objective progression even after 
discontinuation of treatment. 
Method of Measurement 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up.  
Clinical Lesions 
Clinical lesions will only be considered measurable when they are superficial (e.g. skin nodules, 
palpable lymph nodes). For the case of skin lesions, documentation by color photography 
including a ruler to estimate the size of the lesion is recommended.  
Chest X-ray 


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Lesions on chest X-ray are acceptable as measurable lesions when they are clearly defined and 
surrounded by aerated lung. However, CT is preferable.  
CT (preferred) or MRI  
CT (preferred) and MRI imaging might be the best currently available and reproducible methods 
to measure target lesions selected for response assessment. Conventional CT and MRI should be 
performed with cuts of 10 mm or less in slice thickness contiguously. Spiral CT should be 
performed using a 5 mm contiguous reconstruction algorithm. This applies to the chest, 
abdomen and pelvis. Head & neck and extremities usually require specific protocols. 
Ultrasound 
When the primary endpoint of the study is objective response evaluation, ultrasound (US) 
should not be used to measure tumour lesions that are clinically not easily accessible. It is a 
possible alternative to clinical measurements for superficial palpable nodes, subcutaneous 
lesions and thyroid nodules. Ultrasound might also be useful to confirm the complete 
disappearance of superficial lesions usually assessed by clinical examination. 
Cytology, Histology 
These techniques can be used to differentiate between PR and CR in rare cases (for example, 
residual lesions in tumour types such as germ cell tumours, where known residual benign 
tumours can remain). The cytological confirmation of the neoplastic origin of any effusion that 
appears or worsens during treatment when the measurable tumour has met criteria for response 
or stable disease is mandatory to differentiate between response or stable disease (an effusion 
may be an adverse drug reaction of the treatment) and/or progressive disease. 
 
 
 
 


D oc u me nt A p pr o vals
A p pr o ve d Date: 2 8 Se p 2 0 2 0
A p pr o val Tas k
Ver dict:  A p pr o ve
I a p pr o ve t his d oc u me nt
2 7- Se p- 2 0 2 0 1 4: 0 6: 1 7 G M T + 0 0 0 0
A p pr o val Tas k
Ver dict:  A p pr o ve
I a p pr o ve t his d oc u me nt
2 8- Se p- 2 0 2 0 0 1: 0 6: 3 5 G M T + 0 0 0 0
A p pr o val Tas k
Ver dict:  A p pr o ve
I a p pr o ve t his d oc u me nt
2 8- Se p- 2 0 2 0 1 1: 4 6: 5 7 G M T + 0 0 0 0
A p pr o val Tas k
Ver dict:  A p pr o ve
I a p pr o ve t his d oc u me nt
2 8- Se p- 2 0 2 0 1 2: 5 3: 2 6 G M T + 0 0 0 0
A p pr o val Tas k
Ver dict:  A p pr o ve
I a p pr o ve t his d oc u me nt
2 8- Se p- 2 0 2 0 1 5: 3 6: 3 9 G M T + 0 0 0 0
P P D
P P D
P P D
P P D
P P D