Clinical trial NCT03095612
Conditions: Non-small Cell Lung Cancer
Sponsor: University of Texas Southwestern Medical Center
Start date: 2018-03-22; Completion date: 2023-03-03
Enrollment: 41 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is being done to evaluate the safety of the investigational study drug, selinexor when given with docetaxel to patients who have been previously treated for advanced KRAS mutant lung cancer.

Detailed description:
This is a phase 1/2 single-arm, non-blinded, multi-institutional study. Selinexor will be administered once weekly starting one week before chemotherapy initiation (to permit pharmacodynamic assessment of selinexor alone and in combination with chemotherapy).This study will compare safety and outcomes with historical controls (docetaxel monotherapy).

Arms: arm 1: For the selinexor monotherapy cohort, 6 patients each will be treated in two dosing cohorts (weekly and biweekly). Selinexor once weekly oral (40mg, 60mg, 80mg) OR Selinexor twice weekly oral (60mg, 40mg, 60mg weekly).

Selinexor will be administered once weekly starting one week before chemotherapy initiation in combination with docetaxel. Docetaxel will be given once every 3 weeks. Treatment will be administered in 21-day cycles. Selinexor dose escalation: 60, 80, 40 mg once weekly. Docetaxel 75 mg/m2 IV, 60 every 3 weeks.
Interventions: intervention 1: Selinexor intervention 2: Docetaxel
Intervention descriptions: intervention 1: Selinexor once weekly oral or twice weekly oral intervention 2: Docetaxel once every 3 weeks (75 mg/m2 IV)

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
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CONFIDENTIAL 
This material is the property of the UTSW Simmons Comprehensive Cancer Center.  
Do not disclose or use except as authorized in writing by the study sponsor. 
Template Updated: 2/2017; 11/2017; 11/2018; 11/2020 
 
Cover Page 
 
Title: An investigator-sponsored, phase 1/2 trial of the oral 
XPO1 inhibitor selinexor (KPT-330) monotherapy and in 
combination with docetaxel for previously treated, 
advanced KRAS mutant non-small cell lung cancer 
(NSCLC) 
 
NCT: NCT03095612 
 
Document Date: August 05, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
STU032017-003 Gerber FormA-ResearchProtocol-Amd5.0-08.05.22 Mod_34 08-08-22 (5) 
 
 
CONFIDENTIAL 
This material is the property of the UTSW Simmons Comprehensive Cancer Center.  
Do not disclose or use except as authorized in writing by the study sponsor. 
Template Updated: 2/2017; 11/2017; 11/2018; 11/2020 
 
IST-USA-000000116600 
An investigator-sponsored, phase 1/2 trial of the oral XPO1 inhibitor selinexor (KPT-330) 
monotherapy and in combination with docetaxel for previously treated, advanced KRAS mutant 
non-small cell lung cancer (NSCLC) 
 
Principal Investigator:  
David Gerber, MD 
 
 
 
 
Harold C. Simmons Comprehensive Cancer Center 
 
 
 
 
Division of Hematology/Oncology 
 
 
 
 
University of Texas Southwestern Medical Center 
 
 
 
 
5323 Harry Hines Boulevard, Mail Code 8852 
 
 
 
 
Dallas, TX 75390 
 
 
 
 
214-648-4180  
 
 
 
 
214-648-1955 
 
 
 
 
david.gerber@utsouthwestern.edu 
 
Biostatistician: 
 
Song Zhang, PhD 
 
 
 
 
University of Texas Southwestern Medical Center 
 
 
 
 
5323 Harry Hines Boulevard, Mail Code 8852 
 
 
 
 
Dallas, TX 75390 
 
 
 
 
214/648-3235  
 
 
 
 
 
 
 
Song.zhang@utsouthwestern.edu 
 
Study Drug/Treatment: 
Selinexor (KPT-330), Docetaxel 
 
IND/IDE Number: 
 
135814 
 
IND/IDE Holder Name:  
UT Southwestern Medical Center 
 
Funding Source:  
Karyopharm Therapeutics, Inc. 
 
NCT Number: 
NCT03095612 
 
Initial version: 
Version 1.0 dated 10 February 2017 
Amended: 
 
Version 2.0 dated 11 November 2017 
 
 
Version 3.0 dated 26 November 2018 
 
 
Version 4.0 dated 06 November 2020 
 
 
Version 5.0 dated 05 August 2022 
 
UT Southwestern Medical Center (UTSW) 
Harold C. Simmons Comprehensive Cancer Center 
Attn: Clinical Research Office 
5323 Harry Hines Blvd. MC 9179 
Dallas, Texas 75390-9179 
 


 
 
 
 
STU032017-003 Gerber FormA-ResearchProtocol-Amd5.0-08.05.22 Mod_34 08-08-22 (5) 
 
 
CONFIDENTIAL 
This material is the property of the UTSW Simmons Comprehensive Cancer Center.  
Do not disclose or use except as authorized in writing by the study sponsor. 
Template Updated: 2/2017; 11/2017; 11/2018; 11/2020 
 
 
Signature Page 
 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, including 
all statements regarding confidentiality, and according to local legal and regulatory requirements and 
applicable U.S. federal regulations and ICH guidelines. 
 
Amendment/Version # 5 dated 05 August 2022 
IST-USA-000000116600 
An investigator-sponsored, phase 1/2 trial of the oral XPO1 inhibitor selinexor (KPT-330) 
monotherapy and in combination with docetaxel for previously treated, advanced KRAS mutant 
non-small cell lung cancer (NSCLC) 
 
 
Principal Investigator (PI) Name: _____________________________ 
 
 
 
PI Signature: _____________________________ 
 
 
 
Date: ____________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


STU 032017-003– SCCC-04517- Version 5.0  
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Clinical Study Protocol: IST-USA-000000116600 
 
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TABLE OF CONTENTS 
List of Abbreviations and Definitions of Terms ..............................................................7 
Study Design and Schema ...............................................................................................10 
Study Summary ................................................................................................................12 
1.0 .......................................................................................... BACKGROUND AND RATIONALE
..........................................................................................................................................111 
1.1 
Disease Background .........................................................................................111 
1.2 
Study Agent(s)/Therapy(ies) Background and Associated Known Toxicities ...15 
1.3 
Clinical Experience .............................................................................................17 
1.4 
Efficacy ...............................................................................................................18 
1.5 
Safety…………………………………………………………………………..18 
1.6 
Rationale .............................................................................................................19 
1.7 
Correlative Studies ..............................................................................................21 
2.0................................................................................................... STUDY OBJECTIVES
............................................................................................................................................21 
2.1 
Primary Objectives .............................................................................................21 
2.2 
Secondary Objectives .........................................................................................21 
2.3 
Exploratory Objectives .......................................................................................21 
2.4 
Endpoints ............................................................................................................21 
3.0.............................................................................................. PATIENT ELIGIBILITY
............................................................................................................................................22 
3.1 
Inclusion Criteria ................................................................................................22 
3.2 
Exclusion Criteria ...............................................................................................23 
4.0..................................................................................................... TREATMENT PLAN
............................................................................................................................................22 


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4.1 
Treatment Dosage and Administration .......................................................................... 22 
4.2 
Concomitant Medications .............................................................................................. 22 
4.3 
Toxicities and Dosing Delays/Dose Modifications ......................................................... 24 
4.4 
Dose Adjustments .......................................................................................................... 24 
4.5 
Dose Limiting Toxicities ................................................................................................. 24 
4.6 
Safety Cohort Review .................................................................................................... 25 
4.7 
Dose reduction and supportive care guidelines ............................................................ 26 
4.8 
Supporitve care and concomitant therapy ..................................................................... 33 
4.9 
Other modalities of procedures ..................................................................................... 34 
 
5.0................................................................................................ STUDY PROCEDURES
............................................................................................................................................36 
5.1 
Screening/Baseline Procedures .................................................................................... 37 
5.2 
Procedures During Treatment ....................................................................................... 37 
5.3 
End of Treatment visit…………………………………………………………………………39 
5.4 
Follow-up Procedures .................................................................................................... 39 
5.5 
Schedule of Study Activities and Assessments ............................................................. 41 
5.6 
Removal of Subjects from Study ................................................................................... 47 
6.0     MEASUREMENT OF EFFECT ..........................................................................47 
6.1 
Antitumor Effect ............................................................... Error! Bookmark not defined. 
6.2 
Definitions ...................................................................................................................... 47 
6.3 
Disease Parameters ...................................................................................................... 48 
6.4 
Methods for evaluation of measurable disease ............................................................. 49 
6.5 
Response Criteria .......................................................................................................... 49 
6.6 
Duration of Response .................................................................................................... 50 
6.7 
Progression Free Survival .............................................................................................. 51 
6.8 
Safety/Tolerability ......................................................................................................... 51 


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7.0...................................................................................................... ADVERSE EVENTS
............................................................................................................................................51 
7.1 
Experimental Therapy.................................................................................................... 51 
7.2 
Adverse Event Monitoring ............................................................................................. 52 
7.3 
Definitions………………………………………………………………………………………53 
7.4 
UPIRSOs……………………………………………………………………………………….53   
7.5 
Steps to Determine If an Adverse Event Requires Expedited Reporting ...................... 54 
7.6 
Reporting SAEs and UPIRSOS to SCCC DSMC .......................................................... 55 
7.7 
Unblinding Procedures .................................................................................................. 58 
7.8 
Stopping Rules .............................................................................................................. 58 
8.0..................................................................... DRUG/TREATMENT INFORMATION
............................................................................................................................................58 
8.1 
Study Drugs ................................................................................................................... 58 
8.2 
Placebo or Control ......................................................................................................... 59 
8.3 
Labeling ......................................................................................................................... 59 
8.4 
Dosing Information ......................................................................................................... 59 
8.5 
Dosing Instructions for patients ..................................................................................... 59 
9.0...................................................................... CORRELATIVES/SPECIAL STUDIES
............................................................................................................................................59 
9.1 
Sample Collection, storage and shipping .................................................................... 589 
9.2 
Pharmacodynamic assessments ................................... Error! Bookmark not defined.9 


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10.0........................................................................ STATISTICAL CONSIDERATIONS
............................................................................................................................................60 
10.1 
Study Design/Study Endpoints .................................................................................... 590 
10.2 
Sample Size and Accrual ............................................................................................ 591 
10.3 
Data Analyses Plans...................................................... Error! Bookmark not defined.1 
 
10.4 
Efficacy Analysis ............................................................................................................ 61 
10.5 
Pharmacodynamics variables ........................................................................................ 61 
10.6 
Safety Analysis .............................................................................................................. 61 
10.7 
Laboratory Data ............................................................................................................. 61 
10.8 
Vital signs and Physical Examination ............................................................................ 61 
 
11.0............................................................................................ STUDY MANAGEMENT
............................................................................................................................................61 
11.1 
Conflict of Interest .......................................................... Error! Bookmark not defined.1 
11.2 
Institutional Review Board (IRB) Approval and Consent ............................................. 611 
11.3 
Required Documentation ............................................................................................... 61 
11.4 
Registration Procedures ................................................................................................ 62 
11.5 
Patient Updates ............................................................................................................. 63 
11.6 
Data Management and Monitoring/Auditing .................................................................. 63 
11.7 
Adherence to the Protocol ............................................................................................. 64 
11.8 
Amendments to the Protocol ......................................................................................... 66 
11.9 
Record Retention ........................................................................................................... 66 
11.10 Obligations of Investigators ........................................................................................... 66 
12.0.............................................................................................................. REFERENCES
............................................................................................................................................67 
13.0............................................................................................................... APPENDICES
............................................................................................................................................68 
 


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LIST OF IN-TEXT TABLES 
Table 1 Schedule of Study Activities and Assessments . Error! Bookmark not defined. 
Table 2 Dosing Schedule ................................................................................................25 
Table 3 Pre-specified dosing levels of selinexor and docetaxel .....................................25 
 
Table 4 
 
Table 5 Dose escalation rules for defining MTD............................................................50 
Table 6 Supportive Care and Dose Adjustment Guidelines ...........................................53 
      Table 7     Dose adjustment for docetaxel-related hematological toxicity……………….59 
      Table 8     Dose adjustment for docetaxel-related non-hematological toxicity………......59 
 Table 9 Clinical Laboratory Tests ..................................................................................66 
Table 10 Classification of Adverse Events by Causality ..................................................71 
 
LIST OF IN-TEXT FIGURES 
Figure 1-3  Preclinical activity  .................................................................................... 40-41 
 
LIST OF APPENDICES 
Appendix 1 Eastern Cooperative Oncology Group Performance Status Criteria ...........94 
Appendix 2 Selinexor Formulation and Administration .................................................95 
Appendix 3    RECISTcriteria……………………………………………………………97 
 
 
 
 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
AE 
adverse event 
ALT 
ALK 
alanine transaminase (SGPT) 
anaplastic lymphoma kinase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
AV 
aspartate transaminase (SGOT) 
Atrio-ventricular 
BIW 
twice weekly 


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Abbreviation 
Definition 
BP 
blood pressure 
BSA 
body surface area 
BUN 
blood urea nitrogen 
C 
degrees Celsius 
CBC 
complete blood count 
CHF 
congestive heart failure 
CLL 
chronic lymphocytic leukemia 
cm 
centimeter 
CNS 
central nervous system 
CR 
complete remission 
CrCl 
creatinine clearance 
CRF 
case report form 
CRM1 
chromosomal region maintenance protein 1 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
DCR 
disease control rate (CR, PR, SD ≥ 4 weeks) 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose limiting toxicity 
EC 
Ethics committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDTA 
EGFR 
EU 
ethylenediaminetetraacetic acid 
epidermal growth factor receptor 
European Union 
F 
degrees Fahrenheit 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte-colony stimulating factor 
GGT 
gamma-glutamyl transferase 
GI 
gastrointestinal 
GM-CSF 
granulocyte macrophage-colony stimulating factor 
GSH 
glutathione 
Hb 
hemoglobin 
HBsAg 
hepatitis B virus surface antigen 


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Abbreviation 
Definition 
HBV 
hepatitis B virus 
hCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
hr 
hour 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IL 
interleukin  
IMWG 
International Myeloma Working Group 
INR 
international normalization ratio 
IR 
intermediate risk 
IRB 
Institutional Review Board 
IV 
intravenous 
kg 
kilogram 
LAFB 
left anterior fascicular block 
LDH 
lactic dehydrogenase 
m2 
square meters 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
MI 
myocardial infarction 
min 
minute 
mL 
MM 
mm 
Milliliter 
Multiple Myeloma 
Millimeter 
mmHg 
millimeters of mercury 
MTD 
maximum tolerated dose 
MR 
minor response 
NAC 
N-acetylcysteine 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NES 
nuclear export sequences 
NHL 
non-Hodgkin’s lymphoma 
NK1R 
neurokinin 1 receptor 
NPM1 
NSCLC 
Nucleophosmin 
Non-small cell lung cancer 


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Abbreviation 
Definition 
NYHA 
New York Heart Association 
ORR 
overall response rate (sCR + CR + VGPR + PR) 
OS 
overall survival 
PD 
progressive disease 
PDn 
pharmacodynamic 
PE 
physical examination 
PFS 
progression free survival 
PK 
pharmacokinetic 
PP 
per protocol 
PPI 
proton pump inhibitor 
PR 
partial response 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
qd 
once daily 
QW 
once weekly 
RBBB 
right bundle branch block 
RBC 
red blood cell 
RNA 
ribonucleic acid 
RP2D 
RR 
recommended Phase 2 dose 
relapsed/refractory 
SAE 
serious adverse event 
SAM 
S-adenosylmethionine 
SC 
subcutaneous 
sCR 
stringent complete response 
SD  
stable disease; standard deviation 
SINE 
selective inhibitor of nuclear export 
SOC  
standard of care; system organ class 
Tmax 
time to maximum serum concentration 
TSP 
tumor suppressor protein 
ULN 
upper limit of normal 
US 
United States 
VGPR 
very good partial response 
WBC 
wt 
white blood cell 
wild type 
XPO1 
exportin 1 
Study Design and Schema: 


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This is a phase 1/2 single-arm, non-blinded, multi-institutional study. In the combination cohorts, 
selinexor will be administered once weekly starting one week before chemotherapy initiation (to 
permit pharmacodynamic assessment of selinexor alone and in combination with chemotherapy), 
chemotherapy),in combination with docetaxel.  Docetaxel will be given once every 3 weeks. 
Treatment will be administered in 21-day cycles. Dose limiting toxicities (DLTs) will be 
assessed based on the first cycle (7-day lead-in plus 21-day cycle = 28 days) toxicity using the 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [NCI 
CTCAE] version 4.03. A standard 3 + 3 dose escalation paradigm will be used.   
 
In the docetaxel plus selinexor cohort, depending on cohort expansion requirements, a total of 
9-24 patients will be accrued to the dose-escalation phase 1 pilot trial, with a minimum of 6 
patients treated at the MTD.  A total of 35 patients will be enrolled to this expansion cohort, for a 
total of 31-46 patients. For the selinexor monotherapy cohort, 6 patients each will be treated in 
two dosing cohorts (weekly and biweekly). Based on the totality of clinical data, one regimen 
will be selected for the expansion cohort, enrolling an additional  22 patients for a total of 28 
patients. Thus, the total enrollment to the selinexor monotherapy cohort will be 6 + 6 + 22 = 34 
patients. The expected total enrollment for the overall study is 31-46 + 34 = 65-80 patients. 
Because the trial population will be drawn from a multi-institution base, it is anticipated that 
accrual will be completed over 36 months. 
In the docetaxel plus selinexor expansion cohort, enrollment of 35 patients will provide 90% power 
to detect an improvement in the primary endpoint of radiographic response rate from 10% 
(historical control) to 35%, with a two-sided alpha of 0.05.  The sample size estimate is based on 
the exact one-sample binomial test for proportions. 
Subjects will be enrolled into the study after informed consent is signed and all 
inclusion/exclusion criteria have been verified. At that time, the dose level and subject 
identification number will be assigned, followed by randomization to any of the available 
treatment arms for which the subject is eligible.  
 
 
 
 
 
 
 
 
 
 
 
 
 
‘3x3’ Dose escalation (cycle = 21 days) 
Selinexor once weekly oral administration 
(cohorts 60mg, 80mg, 100mg…)* 
Docetaxel once every 3 weeks (75 
mg/m2 IV) 
  
*cohort escalation until MTD is 
established 
CR, PR, 
SD 
Disease 
Progression 
Patient registration 
Dose expansion at MTD  
(after dose escalation) 
 
Selinexor once weekly oral administration  
Docetaxel once every 3 weeks (75 mg/m2 IV) 
Monotherapy arm  
(after MTD expansion) 
 
Selinexor once weekly oral 
(40mg, 60mg, 80mg) 
OR 
Selinexor twice weekly oral 
(60mg, 40mg, 60mg weekly) 
 
 
Disease Evaluation by CT/MRI 
(end of every 2 cycles; every 4 cycles 
after 12 months on study) 


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STUDY SUMMARY 
Title 
An investigator-sponsored, phase 1/2 trial of the oral XPO1 
inhibitor selinexor (KPT-330) monotherapy and in combination 
with docetaxel for previously treated, advanced KRAS mutant non-
small cell lung cancer (NSCLC) 
Short Title 
Phase 1/2 Trial of Selinexor (KPT-330) Monotherapy and With Docetaxel 
for KRAS mutant NSCLC) 
Protocol Number 
IST-USA-000000116600 
Phase 
1/2 
Methodology 
. 
Open label 
Study Duration 
48 months 
Study Center(s) 
Multi-Center clinical trial with UT Southwestern Medical Center as lead 
center and 4 sub-sites 
Objectives 
Primary Objective: 
To determine the safety and the MTD and RP2D of 
selinexor administered with the standard dose of docetaxel 
in patients with advanced KRAS mutant NSCLC (docetaxel 
+ selinexor cohort). 
Secondary Objective: 
To evaluate the efficacy of selinexor monotherapy and in 
combination with docetaxel in patients with advanced KRAS 
mutant NSCLC   
 
Number of Subjects 
65-80 
Diagnosis and Main 
Inclusion Criteria 
Mutant Non-small cell lung cancer (NSCLC) 
Study Product(s), Dose, 
Route, Regimen 
Selinexor monotherapy and in combination with docetaxel 
Reference therapy 
Docetaxel 


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Statistical Methodology 
General considerations: UT Southwestern will be the coordinating 
center for this study and will be responsible for registering patients 
and for maintaining a complete database of the study information. 
Analysis of Clinical Endpoints: The design of this Phase 1-2 trial is 
described earlier, as is the definition of MTD and the rules for dose 
escalation. Safety and efficacy will be assessed using the CTCAE 
and RECIST criteria as above. 
Estimated accrual time: Review of patient accrual onto recent studies 
suggests that the study should be completed in 48 months. 
Justification for sample size:  
Combination—docetaxel plus selinexor:  We anticipate enrolling 9-
24 patients in the dose escalation component as follows:  number 
dose levels=3-4; number patients per dose level=3-6.  In the 
expansion cohort, enrollment of 35 patients will provide 90% power 
to detect an improvement in the primary endpoint of radiographic 
response rate from 10% (historical control) to 35%, with a two-sided 
alpha of 0.05.  The sample size estimate is based on the exact one-
sample binomial test for proportions. 
Single-agent selinexor:  Initially two separate dose/schedule 
regimens will be evaluated:  60 mg PO twice weekly (N=6) and 80 
mg PO once weekly (N=6). Based on the totality of clinical data 
from these 12 patients, one of these regimens will be selected to 
complete an expansion cohort of 28 total patients. The 6 patients 
from the selected regimen will be included in the expansion 
cohort, so 22 additional patients will be required, for a total 6 + 6 + 
22 = 34 patients. 
 
 
 


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1.0 
BACKGROUND AND RATIONALE 
1.1 
Disease Background  
KRAS mutant lung cancer remains a challenging and resistant disease. In non-small cell lung 
cancer (NSCLC), KRAS mutations convey a poor prognosis, insensitivity to adjuvant 
chemotherapy, and resistance to epidermal growth factor receptor (EGFR) inhibitors. Representing 
approximately 30% of adenocarcinomas, KRAS mutant NSCLC, in contrast to tumors harboring 
EGFR mutations or anaplastic lymphoma kinase (ALK) rearrangements, lacks a specific therapy. 
Development of RAS inhibitors has been hindered by the strong affinity of the GTP substrate to 
RAS, which prevents effective binding of pharmacologic agents. There has been some suggestion 
that targeting downstream mediators of KRAS signal transduction might be an effective alternative 
to direct targeting. In the Biomarker-Integrated Approaches of Targeted Therapy for Lung cancer 
Elimination (BATTLE) trial, the RAF inhibitor sorafenib demonstrated >50% disease control rate 
in KRAS mutant NSCLC.2  However, despite promising results in a phase 2 trial, the strategy of 
MEK targeting in KRAS mutant NSCLC did not demonstrate efficacy in a confirmatory phase 3 
trial.  Specifically, the combination of docetaxel and selumetinib did not improve progression-free 
survival compared to docetaxel alone. 
More recently, direct KRASG12C inhibitors (eg, AMG 510) have demonstrated efficacy in this 
subset, which represents approximately one-third of KRAS mutations in NSCLC. As of May 
2020, these agents remain in clinical development. 
Lung cancer remains the leading cause of cancer-related deaths worldwide with an estimated 
incidence of 1.6 million cases resulting in 1.4 million deaths annually. Non-small-cell lung 
cancer (NSCLC) represents 80-85% of cases, and adenocarcinoma is the most common 
histology. The majority of NSCLC patients present with advanced or metastatic disease that is 
not amenable to surgical resection.  For these patients, platinum-based combination 
chemotherapy has reached a therapeutic plateau with a median overall survival (OS) of 7.4 to 9.9 
months.    KRAS mutations are the most commonly identified driver mutation in NSCLC, 
occurring in 25 percent of adenocarcinomas. The presence of oncogenic KRAS alterations has 
been proposed to portend poor response to conventional treatment and poor clinical outcomes.  
To date, pharmacologic attempts at inhibiting KRAS directly have proven unsuccessful, with the 
exception of direct KRAS G12C inhibitors limited to that subset of cases. Further, the mechanistic 
networks active in KRAS mutant lung cancers are subject to substantial diversity, proving the 
identification of an appropriate therapeutic surrogate target challenging. Therefore, novel concepts 
are needed to improve treatment and outcomes in KRAS mutant NSCLC.  
Pre-clinical studies performed at UT Southwestern have demonstrated sensitivity of KRAS mutant 
NSCLC cell lines to the novel group of selective inhibitor of nuclear export (SINE) compounds. 
In a multi-genomic, data-driven approach obtained by analysis of 106 cell lines, nuclear transport 
machinery was identified as an obligatory function required for cell survival. By application of 
selinexor (KPT-330), tumor cell growth was halted and apoptotic cell death was induced at 
bioavailable concentrations (0.5 – 10 μM). Specificity to nuclear export machinery (XPO1 cargo 
transport) was identified via temporary modification of target expression.  Accumulation of IκB 


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05 August 2022 
 
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in the nucleus and resulting dysregulation of crucial survival pathways via NFκB as the responsible 
mechanism of cell death induction was identified. Resistance mechanisms through over-activation 
of FSTL5/Hippo pathway by co-occurring mutations in FSTL5 were elucidated. Compared to 
KRAS mutant cell lines, treatment of KRAS wild-type cell lines resulted in significantly lower 
induction of cancer cell death.  
As of March 2020, Selinexor had been received by over 3,720 patients in over 12 Karyopharm-
sponsored trials, over 30 investigator-sponsored clinical studies, and through an expanded access 
program. Preliminary findings from ongoing studies show that selinexor induces durable anti-
tumor responses across a broad range of hematologic and solid malignancies. Preliminary safety 
information available for 1,175 patients indicated that selinexor is generally well tolerated with 
the most frequent selinexor-related treatment-emergent adverse events including low-grade nausea 
(62%), fatigue (55%), anorexia (50%), thrombocytopenia (43%), and vomiting (38%) that were 
manageable with standard supportive care.  
The combination of selinexor with docetaxel is proposed for the following reasons:  (1) among the 
two FDA approved cytotoxic agents for advanced NSCLC progressing after platinum doublet 
therapy (docetaxel, pemetrexed), it is the most feasible in this indication, as pemetrexed is 
increasingly used as a component of first-line and/or maintenance therapy; (2) the activity of 
docetaxel monotherapy has been extensively characterized in advanced NSCLC, including KRAS 
mutant cases; (3) preclinical data combining selinexor with taxane-based therapy suggests strong 
synergy (combinations with paclitaxel in breast and ovarian cancer mouse models); (4) the 
widespread use of docetaxel as a backbone for combination therapy in NSCLC (including KRAS 
mutant cases) offers a straightforward developmental path to subsequent clinical development  
Although selinexor has not previously been combined with docetaxel in human clinical trials, it 
has been administered with the related drug paclitaxel.  Specifically, the safety and efficacy of 
paclitaxel 80 mg/m2 IV Days 1 and 8 every 3 weeks combined with selinexor 60 mg PO twice 
weekly was explored in an investigator-sponsored trial. It was found to be safe and well tolerated 
in the 9 patients who have been dosed to date, and the cohort is currently being expanded. 
Selinexor monotherapy is being studied in a cohort of patients for the following reasons: (1) 
preclinical data demonstrate single-agent activity of selinexor in KRAS mutant lung 
adenocarcinoma models; (2) some patients with KRAS mutant NSCLC treated with docetaxel 
plus selinexor appear to have experienced clinical benefit (eg, improved pain, diminished size of 
cutaneous metastasis, decreased LDH and alkaline phosphatase) during the 7-day lead-in period 
of selinexor monotherapy. 
1.2 
Study Agent(s)/Therapy(ies) Background and Associated Known Toxicities 
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates 
Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor proteins (TSPs). 
Transient retention of TSPs in the nucleus at high levels via XPO1 blockade activates their cell 
cycle checkpoint and genome surveying actions. This leads to the death of nearly all types of 
malignant cells, whereas normal cells undergo transient cell cycle arrest and recovery when the 
export block is released. The reactivation of multiple tumor suppressor pathways and inhibition of 
translation of key pro-survival proteins 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. More information about the mechanism of action, 


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pharmacology, and pre-clinical studies of selinexor is available in the Selinexor/KPT-330 
Investigator’s Brochure (IB). 
In July 2019, the FDA granted accelerated approval to selinexor (Xpovio) for use in combination 
with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma 
who have received ≥4 prior therapies and whose disease is refractory to ≥2 proteasome inhibitors, 
≥2 immunomodulatory agents, and a CD38-targeted monoclonal antibody. The approval was 
based on a 25% response rate in a subgroup of patients in the pivotal phase IIb STORM study. 
Beyond multiple myeloma, selinexor has been studied in several hematologic malignancies and 
solid tumors. Phase 1 studies with oral selinexor have been being conducted in advanced 
hematological malignancies including non-Hodgkin's lymphoma (NHL), chronic lymphocytic 
leukemia (CLL), multiple myeloma (MM), and acute myeloid leukemia (AML) (KCP-330-001), 
in solid tumors and in soft tissue and bone sarcomas (KCP-330-002 and -003). In addition, Phase 
2 studies have been conducted in glioblastoma, gynecological malignancies, squamous cell 
carcinoma, prostate cancer, acute myeloid leukemia (AML), diffuse large B-cell lymphoma 
(DLBCL), and Richter’s transformation. More than 1,900 patients with objectively progressing 
tumors at study entry have received selinexor as of 01 November 2016 (refer to latest IB for more 
details).   
Overall, in clinical studies selinexor has been relatively well tolerated, with the most frequently 
reported selinexor-related treatment-emergent adverse events (TEAEs) being generally low-grade 
nausea (62%), fatigue (55%), anorexia (50%), thrombocytopenia (43%), and vomiting (38%), that 
were manageable with standard supportive care. 
Selinexor treatment is not associated with significant major organ toxicity. Moreover, clinically-
relevant cumulative toxicities have not been observed during long-term treatment, with more than 
28 patients receiving single-agent selinexor for over 1 year and 6 patients for over 2 years. These 
results suggest that selinexor may be administered long term with acceptable tolerability, and offer 
promise when used in combination with a wide range of other anti-cancer therapies.  
Selinexor has shown single-agent, durable, anti-cancer activity in patients with multiple RR 
hematologic and solid tumor malignancies. Additional information about clinical studies of 
selinexor is available in the Selinexor/KPT-330 IB. 
Over 3,100 patients have received selinexor in clinical studies (including Karyopharm sponsored 
trials and ISTs), most with single-agent selinexor. Based on this experience, selinexor has been 
relatively well tolerated, with the most frequently reported treatment-emergent adverse events 
(TEAEs) in Karyopharm-sponsored trials being nausea (65%), fatigue (58%), thrombocytopenia 
(52%), anorexia (51%), anemia (42%), and vomiting (38%). These events are generally low-grade, 
reversible, and manageable with standard supportive care and dose modification (Section 5.4,  and 
Section 6.4 “Clinical Safety Results,” IB v9.0).  
Karyopharm plans to continue the development of selinexor to treat a wide variety of malignancies, 
including diseases that are not currently mentioned in the IB. 
Preliminary findings from ongoing clinical studies have shown that selinexor induces durable anti-
tumor responses across a broad range of relapsed/refractory (RR) hematologic and solid tumor 
cancers, which is consistent with its proposed mechanism of action, namely, induction of TSPs 
and reduction in oncoprotein levels in malignant cells. In general, these effects appear to be 


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Selinexor (KPT-330)/docetaxel 
 
Clinical Study Protocol: IST-USA-000000116600 
 
05 August 2022 
 
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independent of tumor type or prior treatment(s). More information about preliminary results from 
ongoing clinical studies is available in the current Selinexor/KPT-330 IB. 
Selinexor is currently US FDA approved for the treatment of multiple myeloma and remains in 
clinical development for multiple other indications. Clinical experience with Selinexor has been 
evaluated to date in >2,000 and >1,000 patients enrolled in Company-sponsored and investigator-
sponsored trials (IST), respectively, with the longest duration of >2 years without clinically 
significant toxicities. Use of Selinexor has been generally safe and well tolerated, and no major 
organ and/or systemic toxicities were observed to date.  
A brief summary of preclinical data is provided below. More detailed information is available in 
the Selinexor/KPT-330 IB. 
Pre-clinical studies with SINE compounds (not limited to KPT-330) on MM in vivo predict 
favorable efficacy and safety responses in the treatment of hematological malignancies and other 
types of cancer in humans. Selinexor and dexamethasone in combination were found to have a 
synergistic effect on MM1.S human MM cell viability relative to either drug alone. Enhanced 
activity of selinexor plus dexamethasone was also observed in two MM1.S xenograft models of 
human MM, which may predict enhanced efficacy of selinexor with dexamethasone in MM 
patients who are refractory to dexamethasone alone.  
In animal models, the combination of selinexor and dexamethasone is synergistic for in vitro and 
in vivo MM cell cytotoxicity. Selinexor has also shown additive or synergistic activity when 
combined with other MM drugs, including proteasome inhibitors;3-5, topoisomerase II inhibitors,4 
and lenalidomide (unpublished data). These studies suggest that selinexor has anti-MM activity 
that can cause decreased cancer cell viability, increased apoptosis, and increased cell cycle arrest 
in vitro and lead to potent inhibition of MM tumor growth in vivo, and that the addition of 
dexamethasone can augment these effects.  
More information is provided in the Selinexor/KPT-330 IB. 
Preclinical Data in KRAS mutant NSCLC is described in “Study Rationale” (Section 1.4) below.  
1.3 
Clinical Experience 
1.3.1 Pharmacokinetics and Pharmacodynamics 
Oral selinexor pharmacokinetics (PK) are predictable, approximately dose-proportional, and 
exhibit moderate- to moderately-high inter-patient variability across a wide dose range of doses 
in male and female patients with advanced hematological malignancies or solid tumors.  
Additional details are available in the Selinexor/KPT-330 Investigator’s Brochure. 
Clinical pharmacodynamics (PDn) of selinexor have been studied in patients with advanced 
neoplasms.  Following selinexor treatment, XPO1 mRNA was induced in peripheral white blood 
cells (WBC) from patients following XPO1 inhibition.  Peak XPO1 mRNA induction was 
observed at 4-8 hours post dose and levels remained elevated for 24 48 hours; there was no 
difference in extent or kinetics of XPO1 induction in peripheral WBC when evaluated by cancer 
subtype.  XPO1 MRNA induction was maximal during Cycle 1 and waned in later cycles due in 
large part to persistent elevation of XPO1 mRNA expression at baseline.  The half-life for decline 


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Selinexor (KPT-330)/docetaxel 
 
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15 
of XPO1 mRNA exceeded that of selinexor half-life suggesting a prolonged PDn effect likely due 
to the covalent inhibition of XPO1 and the relatively long half-life of the XPO1 protein. 
1.4 
Efficacy 
Preliminary findings from ongoing clinical studies, notably studies KCP-330-001 and -002, have 
shown that selinexor induces durable anti-tumor responses across a broad range of 
relapsed/refractory (RR) hematologic and solid-tumor cancers, which is consistent with its 
proposed mechanism of action, namely, induction of TSPs and reduction in oncoprotein levels in 
malignant cells. Broad anti-tumor activity has also been preliminarily observed in additional 
ongoing clinical studies with selinexor in patients with hematologic or solid tumors (clinical 
studies KCP-330-003 to -010 and -013). In general, these effects appear to be independent of tumor 
type or prior treatment(s). Responses across a variety of hematologic malignancies have generally 
been more rapid, deeper, and more durable compared to those in solid tumors.  Please refer to the 
Selinexor/KPT-330 IB for more information.  
1.5 
Safety  
Over 3,100 patients have received selinexor in clinical studies (including Karyopharm sponsored 
trials and ISTs), most with single-agent selinexor. Based on this experience, selinexor has been 
relatively well tolerated, with the most frequently reported treatment-emergent adverse events 
(TEAEs) in Karyopharm-sponsored trials being nausea (65%), fatigue (58%), thrombocytopenia 
(52%), anorexia (51%), anemia (42%), and vomiting (38%). These events are generally low-grade, 
reversible, and manageable with standard supportive care and dose modification (Section 5.4,  and 
Section 6.4 “Clinical Safety Results,” IB v9.0).  
Karyopharm plans to continue the development of selinexor to treat a wide variety of malignancies, 
including diseases that are not currently mentioned in the IB. 
Preliminary findings from ongoing clinical studies have shown that selinexor induces durable anti-
tumor responses across a broad range of relapsed/refractory (RR) hematologic and solid tumor 
cancers, which is consistent with its proposed mechanism of action, namely, induction of TSPs 
and reduction in oncoprotein levels in malignant cells. In general, these effects appear to be 
independent of tumor type or prior treatment(s). More information about preliminary results from 
ongoing clinical studies is available in the current Selinexor/KPT-330 IB. 
Selinexor is currently US FDA approved for the treatment of multiple myeloma and remains in 
clinical development for multiple other indications. Clinical experience with Selinexor has been 
evaluated to date in >2,000 and >1,000 patients enrolled in Company-sponsored and investigator-
sponsored trials (IST), respectively, with the longest duration of >2 years without clinically 
significant toxicities. Use of Selinexor has been generally safe and well tolerated, and no major 
organ and/or systemic toxicities were observed to date.  
 
1.5.1 Reproductive Risks 
No mutagenic potential was observed in nonclinical studies that included a GLP bacterial reverse 
mutation assay (Ames Test), in a chromosomal abnormality screen, or in a micronucleus assay. 


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Selinexor (KPT-330)/docetaxel 
 
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There have been no adequate and well-controlled studies of selinexor in pregnant women. In non-
clinical toxicology studies, macroscopic and microscopic changes in reproductive organs were 
noted during rat and monkey toxicology studies, most of which partially or fully resolved during 
the recovery period. The long-term effects of these changes on reproductive potential are unknown. 
Secondary developmental effects due to reduced maternal body weights were also noted during a 
study on rat embryo/fetal development. It is unknown whether similar effect may occur in humans. 
Please refer to the Selinexor/KPT-330 IB for additional information. As it is unknown whether 
selinexor might have reproductive toxicity in humans, patients must agree to use effective 
contraception (see Section 5.3.3.3) during the study and for 3 months after the end of treatment. 
 
1.6 
Rationale 
 
Lung cancer remains the leading cause of cancer-related deaths worldwide with an estimated 
incidence of 1.6 million cases resulting in 1.4 million deaths in annually.  Non-small-cell lung 
cancer (NSCLC) represents 80-85% of cases, and adenocarcinoma is the most common histology.6 
The majority of NSCLC patients present with advanced or metastatic disease that is not amenable 
to surgical resection.  KRAS mutations are the most commonly identified driver mutation in non-
small cell lung cancer, occurring in 25 percent of adenocarcinomas.7 The presence of oncogenic 
KRAS alterations has been proposed to portend poor response to conventional treatment and poor 
clinical outcomes. Platinum-based combination chemotherapy has reached a therapeutic plateau 
with a median overall survival (OS) of 7.4 to 9.9 months.   
To date, pharmacologic attempts at inhibiting KRAS directly have proven unsuccessful. Further, 
the mechanistic networks active in KRAS mutant lung cancers are subject to significant diversity, 
proving the identification of an appropriate therapeutic surrogate target challenging. Therefore, 
novel concepts are needed to improve treatment in KRAS mutant non-small cell lung cancer.  
Recently, pre-clinical data derived in the laboratory of Dr. Michael White at UT Southwestern 
have demonstrated sensitivity of KRAS mutant NSCLC cell lines to the novel group of selective 
inhibitors of nuclear export (SINE) (Figures 1-3). In a multi-genomic, data-driven approach 
obtained by analysis of 106 cell lines, we identified the nuclear transport machinery as an 
obligatory function required for cell survival. By application of selinexor (KPT-330), tumor cell 
growth was halted and apoptotic cell death was induced at bioavailable concentrations (0.5 – 10 
µM). Specificity to the nuclear export machinery (XPO1 cargo transport) was identified via 
temporary modification of target expression, identify accumulation of IκB in the nucleus and 
resulting dysregulation of crucial survival pathways via NFκB as the responsible mechanism of 
cell death induction and were also able to identify resistance mechanisms through over-activation 
of FSTL5/Hippo pathway by co-occuring mutations in FSTL5. Treatment of KRAS wild-type 
cell lines resulted in significantly lower induction of cancer cell death.  


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Selinexor (KPT-330)/docetaxel 
 
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Figure 1.  Differential cell viability following XPO1 depletion in KRAS mutant versus KRAS wt cell lines.8 
 
 
Figure 2.  In vivo selective sensitivity of KRAS mutant NSCLC cells (red, KRAS mutant; blue, KRAS wt) to chemical inhibition 
of the nuclear transport receptor XPO1.  (a) Tumor volume fold change of KRAS mutant and KRAS wt xenografts upon XPO1 
inhibition. *P<0.05; **P<0.01. (b) Representative lung MR image of KRAS G12D mutant mouse shown before and after 
treatment for each cohort.  Post-treatment H&E-stained left lung lobe is shown.8 
 
 
Figure 3.  In vitro selective sensitivity of KRAS mutant NSCLC cells (red, KRAS mutant; blue, KRAS wt) to chemical inhibition 
of the nuclear transport receptor XPO1.  (a) dose response curves following 72-hr exposure to KPT-330; (b) Induction of caspase 
3/7 activity in KRAS mutant lines by KPT-185; (c) accumulation of cleaved PARP in KRAS mutant lines following exposure to 
KPT-185.8 
 
The combination of selinexor with docetaxel is proposed for the following reasons:  (1) among the 
two FDA approved cytotoxic agents for second-line treatment of advanced NSCLC (docetaxel, 
pemetrexed), it is the most feasible in this indication, as pemetrexed is increasingly used as a 


STU 032017-003– SCCC-04517- Version 5.0  
Selinexor (KPT-330)/docetaxel 
 
Clinical Study Protocol: IST-USA-000000116600 
 
05 August 2022 
 
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18 
component of first-line or maintenance therapy; (2) the activity of docetaxel monotherapy has been 
extensively characterized in advanced NSCLC, including KRAS mutant cases; (3) preclinical data 
combining selinexor with taxane-based therapy suggests strong synergy (combinations with 
paclitaxel in breast and ovarian cancer); (4) the widespread use of docetaxel as a backbone for 
combination therapy in NSCLC (including KRAS mutant cases) offers a straightforward 
developmental path to regulatory approval. Although selinexor has not previously been combined 
with docetaxel in human clinical trials, it has been administered with the related drug paclitaxel.  
Specifically, the safety and efficacy of paclitaxel 80 mg/m2 IV Days 1 and 8 every 3 weeks 
combined with selinexor 60 mg PO twice weekly was explored in an investigator-sponsored trial. 
It was found to be safe and well tolerated in the 9 patients who have been dosed to date, and the 
cohort is currently being expanded. 
1.7 
Correlative Studies 
Inhibition of XPO1 results in nuclear retention of cargo proteins.  Biopsies from various tumors 
collected from patients before and during the first cycle of selinexor treatment and evaluated 
histologically by hematoloxylin and eosin (H&E) and immunostaining of XPO1 cargos shows 
evidence of PDn effects of selinexor.  H&E staining showed reduction in tumor burden based 
upon reduction in the number of tumor cells in the biopsies.  Selinexor-induced nuclear 
localization of TSPs was evident, including p53, p27, FOXO-3A, and IkB.  Reduction in the 
proliferation marker Ki67 with increases in apoptotic markers were also observed. 
2.0 
STUDY OBJECTIVES 
2.1 
Primary Objectives 
 
To determine the dose limiting toxicity (DLT) and maximum tolerated dose for KPT safety and 
the MTD and RP2D of selinexor administered with the standard dose of docetaxel in patients 
with advanced KRAS mutant NSCLC (docetaxel + selinexor cohort). 
 
2.2  
Secondary Objectives  
 
To evaluate the efficacy of selinexor monotherapy and in combination with docetaxel in patients 
with advanced KRAS mutant NSCLC   
2.3 
Exploratory Objectives 
 
To identify predictive and pharmacodynamic biomarkers of selinexor monotherapy and in 
combination with docetaxel. 
 
2.4 
Endpoints 
• Dose Limiting toxicity as defined in section 4.2 during the first cycle of study treatment and 
assessed per CTCAE v4.03. 
• Radiographic response per RECIST. 
 
 


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3.0 
Subject Eligibility 
Eligibility waivers are not permitted. Subjects must meet all of the inclusion and exclusion criteria to be 
registered to the study. Study treatment may not begin until a subject is registered.  
3.1 
Inclusion Criteria 
 
 
Inclusion Criteria: 
Patients must meet all of the following inclusion criteria to be eligible to enroll in this study: 
1. Written informed consent in accordance with federal, local, and institutional guidelines. The patient must 
provide informed consent prior to the first screening procedure.  However, the Investigator should not repeat 
procedures that are performed as part of standard of care (SOC), if they are within the screening window 
and are done prior to signing the ICF. 
2. Age ≥ 18 years 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1  
4. Histologically or cytologically confirmed advanced (stage 4, according to the American Joint Committee 
on Cancer [AJCC] version 7.0 Staging manual) NSCLC  
5. Molecular identification of a KRAS mutation (codons 12, 13, or 61 mutations detected by sequencing) by a 
CLIA-certified assay (source documentation required). 
6. Tissue available for analysis at time of enrollment for biomarker analysis:  10 unstained slides plus 1 H+E 
slide.  If archival tumor tissue is not available in select cases, subjects may be permitted to enroll on the 
study with prior approval of the study PI. 
7. At least one and up to two previous lines of systemic cytotoxic therapy for advanced NSCLC, of which one 
must have been a platinum-based doublet therapy.  Up to four total previous lines of systemic therapy 
(including immunotherapy and molecularly targeted therapy) for advanced NSCLC.  
8. Radiographic or clinical disease recurrence or progression during or after the last line of systemic therapy  
9. Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1500 cells/µL; hemoglobin ≥ 9 g/dL; 
platelets ≥ 100,000/µL.  Patients may be transfused with PRBCs up to 7 days prior to when enrollment 
labs are drawn to achieve Hgb ≥9.0 mg/dL. 
10. Adequate renal function (calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault 
equation) 
11. Adequate hepatic function (total bilirubin ≤ upper limit of normal [ULN], alanine aminotransferase [ALT] 
≤ 2 × ULN and aspartate aminotransferase [AST] ≤ 2 × ULN). ALT and/or AST may be ≤ 5 × ULN if due 
to liver metastases. If ALT or AST is > 2 and ≤ 5 × ULN in patients with liver metastases, alkaline 
phosphatase must be ≤ 2.5 × ULN (unless elevated alkaline phosphatase clearly due to skeletal—rather 
than hepatic—process; eg, normal GGT, presence of multiple bone metastases, absence of bulky and/or 
central liver metastases). Patients with Gilbert’s syndrome are allowed if total bilirubin ≤ 2 × ULN and 
direct bilirubin is ≤ ULN. 
12. Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly 
effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening. 
Male patients must use an effective barrier method of contraception if sexually active with a female of 
childbearing potential. For both male and female patients, effective methods of contraception must be used 
throughout the study and for 3 months following the last dose of study treatment. Female patients of child-


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bearing potential must have a negative serum pregnancy test at screening and agree to use 2 reliable methods 
of contraception throughout the study and for 3 months after their last dose of medication. Female patients 
are considered NOT of childbearing potential if they have a history of surgical sterility (including 
hysterectomy and/or bilateral oophorectomy, but not tubal ligation alone) or evidence of post-menopausal 
status defined as any of the following: 
• 
Natural menopause with last menses >1 year ago  
• 
Radiation-induced oophorectomy with last menses >1 year ago 
• 
Chemotherapy-induced 
menopause 
with 
last 
menses 
>1 
year 
ago.  
Male patients and their partners must use 2 reliable methods of contraception, at least one of them a barrier 
method (if sexually active with a female of child-bearing potential).   
13. Measurable disease according to RECIST v1.1 
14. Previously treated (surgery and/or radiation therapy) or untreated brain metastases are eligible, provided 
that patients are asymptomatic and not requiring escalating doses of corticosteroids. 
15. Previous treatment-associated clinically significant toxicities resolved to CTCAE grade ≤2 (except alopecia) 
or to their baseline.  NOTE: Prior immunotherapy-related endocrinopathy controlled with ongoing medical 
management (eg, hypothyroidism, adrenal insufficiency, diabetes) is permitted 
16. At least 3 weeks or 5 half-lives, whichever is shorter, since receiving systemic anticancer therapy, including 
investigational agents, prior to starting study therapy.  At least 2 weeks since receiving radiation therapy 
prior to starting study therapy 
 
 
 
3.2 
Exclusion Criteria 
Exclusion Criteria: 
Patients meeting any of the following exclusion criteria are not eligible to enroll in this study: 
1. Patients who are pregnant or lactating 
2. Major surgery (excluding skin biopsies and procedures for insertion of central venous access devices) within 
2 weeks of first dose of study drug 
3. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's 
opinion, could compromise the patient’s safety 
4. Concurrent active malignancy that would interfere with treatment administration or assessment in the 
opinion of the treating investigator 
5. Unstable cardiovascular function: 
• 
Symptomatic ischemia, or  
• 
Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-
arrhythmics is excluded; 1st degree AV block or asymptomatic LAFB/RBBB are not excluded; 
asymptomatic rate controlled atrial fibrillation is not excluded), or 
• 
Congestive heart failure (CHF) of NYHA Class ≥3, or 
• 
Myocardial infarction (MI) within 3 months 
6. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals 
within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral 
7. Pre-existing grade 3 or 4 neuropathy  
8. Active Hepatitis A, B or C infection  


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9. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study) 
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. Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound 
(NOTE: prior docetaxel exposure permitted in selinexor monotherapy cohort) 
12. Patients unwilling to comply with study protocol. 
 
4.0 
TREATMENT PLAN 
 
4.1 
Treatment Dosage and Administration 
 
4.1.1 Dosing Rational-combination therapy: 
 
Weekly selinexor dosing regimens were designed based on pharmacodynamic observations that 
the biological effects of oral selinexor have prolonged durations. Multiple clinical trials have 
employed weekly dosing regimens and have demonstrated both efficacy and tolerability.  
Maximum selinexor serum levels of 1-2 μM are typically achieved in cancer patients following 
selinexor oral doses of 40-100 mg (~25-60 mg/m2). An analysis of existing PK data from phase 1 
studies KCP-330-001 and KCP-330-002 supports the use of fixed, rather than body surface area 
(BSA) based dosing. In the combination setting, selinexor is typically recommended at a starting 
dose of 60 mg weekly across multiple indications, which is proposed as the starting dose in our 
study. Selinexor will be administered once weekly in combination with docetaxel starting one 
week before chemotherapy initiation. Preliminary safety information available for 1175 patients 
indicated that selinexor is generally well tolerated with the most frequent selinexor-related 
treatment-emergent 
adverse 
events 
including 
low-grade 
nausea, 
fatigue, 
anorexia, 
thrombocytopenia, and vomiting that were manageable with standard supportive care. 
 
4.1.2 Dosing Rationale—selinexor monotherapy: 
Initially two separate dose/schedule regimens will be evaluated:  60 mg PO twice weekly (N=6) 
and 80 mg PO once weekly (N=6). Both of these regimens have demonstrated efficacy and 
tolerability in earlier trials. Based on the totality of clinical data from these 12 patients, one of 
these regimens will be selected to complete an expansion cohort of 28 total patients. 
 
4.2 
Concomitant Medications: 
Commercially available docetaxel will be used for this study.  It will be supplied in accordance 
with applicable local laws and regulations. Docetaxel 60 or 75 mg/m2 depending on the dose level 
will be administered as a 1-hour IV infusion. The amount of docetaxel administered will be 
determined on Day 1 of each cycle by calculating the patient’s BSA. When calculating the dose of 
docetaxel, rounding the BSA according to institutional practice is permitted.  The dose of docetaxel 
may be capped at the dose corresponding to a BSA of 2 m2 if necessary to comply with institutional 
practices.  Premedication for docetaxel will follow the local institutional standard of care 
guidelines. 


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Concurrent therapy with any other approved or investigative anticancer therapeutic is not allowed. 
Other investigational agents should not be used during the study.  Use of any immunosuppressive 
agents during the study must be confirmed by the Sponsor- Investigator. 
Patients may continue their baseline medication(s). Patients will receive concomitant 
medications to treat symptoms, AEs, and intercurrent illnesses that are medically necessary as 
part of standard care. Medications to treat concomitant diseases such as diabetes, hypertension, 
etc., are allowed. All prescription, non-prescription, or over-the-counter medications, including 
herbal remedies, taken by the patient at entry and during the study must be clearly documented in 
the CRF.  The patients must be instructed that no additional medication will be allowed without 
the prior consent of the Investigator. In general, concomitant medications to control side effects 
of therapy may be given during treatment, with specific guidelines provided throughout the 
protocol.   
 
 
Table 3:  Pre-specified dosing levels of selinexor and docetaxel† 
 
Dose 
Level 
Dose of Selinexor (mg 
oral) 
 
Dose of Docetaxel 
(mg/m2 IV), every 3 
weeks 
1a 
60 once weekly 
75 
2a 
80 once weekly 
75 
3 
100 once weekly 
75 
-1 
40 once weekly 
75 
-2 
40 once weekly 
60 
 
aIf the maximum tolerated dose (MTD) is exceeded in Dose Levels 1, 2, or 3, docetaxel dose 
may be reduced to 60 mg/m2 and additional cohorts enrolled starting with the corresponding 
selinexor dose level and subsequent selinexor dose escalation (for Levels 1 and 2) as appropriate 
according to 3+3 dose escalation guidelines. If these cohorts are enrolled without exceeding the 
MTD, a subsequent cohort with docetaxel dose re-escalated to 75 mg/m2 every 21 days with 
concurrent myeloid growth factor support every cycle may be enrolled 
 
 
Table 4A. Selinexor monotherapy cohort dose levels—weekly dosing 
 
 
Dose 
Level 
Dose of Selinexor (mg 
oral) 
1 
80 once weekly 
-1 
60 once weekly 
-2 
40 once weekly 


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Table 4B. Selinexor monotherapy cohort dose levels—twice weekly dosing 
 
 
Dose 
Level 
Dose of Selinexor (mg 
oral) 
1 
60 twice weekly 
-1 
40 mg twice weekly 
-2 
60 mg once weekly 
 
 
4.3 
Toxicities and Dosing Delays/Dose Modifications 
Any subject who receives treatment on this protocol will be evaluable for toxicity. Each patient 
will be assessed for the development of toxicity according to the Time and Events table.  
Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events 
(CTCAE), version 4.03. Dose adjustments should be made according to the system showing the 
greatest degree of toxicity.  
 
4.4 
Dose Adjustments 
Patients who are experiencing low-grade tolerability symptoms and are deriving clinical benefit 
from the treatment, may receive a dose schedule reduction at the discretion of the PI. Patients 
whose dose or schedule is reduced may subsequently have their previous dose schedule adjusted 
upwards, according to the above guidelines, at the discretion of the PI. PI may consult with 
Karyopharm Therapeutics Inc. as necessary. If one of the therapeutic agents is withheld or 
discontinued for toxicity, the other agent may be continued. 
 
4.5 
Dose Limiting Toxicity (DLT) definition: 
DLT will include the following when considered to be at least possibly related to study drug 
administration: 
• 
> 1 missed doses (out of 4 doses) of study treatment during cycle 1 due to study treatment 
related toxicities 
• 
Discontinuation of study therapy before completion of Cycle 1, due to study-drug related 
toxicity 
 
Non-hematologic toxicity 
• 
Grade ≥ 3 nausea, vomiting, dehydration, diarrhea or fatigue lasting > 3 days despite 
optimal supportive medications 
• 
Any other Grade ≥3 non-hematological toxicity with the following exceptions: 
- 
Electrolyte abnormalities that are reversible and asymptomatic 
- 
Hair loss 


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- Grade 3 ALT, AST or alkaline phosphatase levels in the setting of baseline ≤ Grade 2 elevations 
from disease 
• 
Delay in initiating cycle 2 therapy for > 21 days. 
• 
Any other Grade 4 non-hematologic toxicity  
 
Hematologic toxicity 
• 
Febrile neutropenia (Grade ≥3, by definition) 
• 
Grade 4 neutropenia lasting > 7 days 
• 
Grade ≥ 3 thrombocytopenia with clinically significant bleeding, petechiae or purpura, or 
requiring  
transfusion  
To be evaluable for DLT, a patient must receive at least one dose of docetaxel and at least three 
of four doses of selinexor.  To be considered not to have experienced DLT, a patient must 
complete the first (28-day) cycle of treatment before a dose-escalation evaluation is made.  
Patients who are not evaluable for toxicity will be replaced.   
Although all toxicities at each course will be recorded, only adverse events thought possibly, 
probably, or definitely attributable to selinexor and docetaxel during the first treatment cycle will 
be used in the decision to dose escalate, expand, or de-escalate. In the absence of unacceptable 
toxicity, patients will be allowed to continue receiving selinexor in combination with docetaxel 
until disease progression.   
Exceptions to DLT: 
Adverse events that meet the above definitions but that are clearly unrelated to study drug will not 
be considered to be DLTs. 
In rare instances, an event may fall within the definition of a DLT, as defined above, but the event 
may be considered not to be a DLT (e.g., not be clinically meaningful). If this occurs, the Sponsor-
Investigator and the drug supplier will review the event and supporting data, and the reasons for 
not considering the event to be a DLT will be clearly documented with supporting rationale.  
In addition, other events may occur which do not meet the definition of a DLT but are of concern 
to the Sponsor-Investigator and the drug supplier and may be considered to be DLTs. 
 
 
4.6  
Safety Cohort Review 
The Investigator, in conjunction with the drug supplier, will determine whether a dose level will 
be re-opened, a cohort will be expanded, or if there will be a dose modification/escalation, etc. 
These discussions will occur during planned calls between the Investigators, study team, subsites 
team members, and Drug supplier and in weekly Phase 1 disease oriented team meetings. 
Escalation to the next dose level will occur only after three evaluable patients on the previous dose 
level have been observed for a complete 28 day cycle.  The Safety Assessment: End of Cycle 1 
form must be completed and provided to the UT Southwestern phase 1 QA Coordinator either via 
fax to the attention of Oluwaseyi Sowemimo and Payal Dixit at 214-648-1578 or scanned then 
emailed to oluwaseyi.sowemimo@utsouthwestern.edu and payal.dixit@utsouthwestern.edu.  This 
form will be reviewed by the Principal Investigator then submitted to the UTSW DSMC for review 


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and approval for dose escalation.  Allow at least 48 hours for the cycle 1 safety assessment review 
process and once approval to proceed to the next dose level has been received an email notification 
from the phase 1 manager will be sent.  Intra-patient dose escalation will be permitted. After 
completing one cycle (cycle 1) at the assigned dose, the cohort review committee can allow a 
patient to be moved to the latest defined safe dose if that patient has at least stable disease on their 
current dose and did not experience a dose limiting toxicity (DLT) at their assigned dose. 
This process will be followed until the RP2D is reached, at which time eligible patients will enter 
the Expansion Phase. 
 
4.7 
Dose Reduction and Supportive Care Guidelines 
Selinexor, a specific XPO1 inhibitor, alters a variety of tumor suppressors, cell cycle regulators, 
oncoproteins, and transcriptional factors. Given this complex mechanism, the relationship between 
dose and antitumor activity, as well as tolerability, is expected to be highly dependent on both 
tumoral and patient factors. Consistent with this, based on observations from the ongoing studies 
in patients with advanced hematological and solid tumors, selinexor shows a wide therapeutic 
range with antitumor activity from 12 to 120 mg. Therefore, in order to optimize the antitumor 
activity and tolerability, dose reductions and/or schedule modifications will be allowed as outlined 
below and in Table 4 and Table 5. For some AEs, dose interruption and/or reduction is 
recommended. See Table 5 for specific recommendations. 
While drug-related major organ toxicities are relatively uncommon, there are a number of 
constitutional side effects (and thrombocytopenia) that can limit dosing with selinexor. Therefore, 
patients should also be treated with supportive care to reduce toxicities. In addition, it should be 
noted that the constitutional side effects often attenuate over the first four to six weeks of dosing. 
Finally, some patients with rapid tumor responses experience significant fatigue, nausea, malaise 
and/or asthenia after 1 or more doses of selinexor. This effect has not been associated with typical 
markers of tumor lysis syndrome, but if suspected, assessment of tumor response is strongly 
recommended in order to better inform treatment recommendations. 
The CTCAE version 4.03 will be used for grading the severity of AEs; the study treatment 
modifications described below are applied according to this severity grading. Toxicity will be 
documented as described. If more than 1 type of toxicity occurs concurrently, the most severe 
grade will determine the modification. 
Each dose modification or treatment delay, as well as the reason, must be documented (Table 4 
and Table 5).  
Table 4 summarizes the starting doses (Dose Level 1) and preferred dose modifications (i.e., Dose 
Levels -1 through -3) for AEs listed in Table 5. General supportive care guidelines are provided in 
Section Error! Reference source not found.. 
 


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4.7.1 
Selinexor Dose Adjustment and Supportive Care Guidelines for AEs related to 
Selinexor 
Table 5 
Selinexor Supportive Care and Dose Adjustment Guidelinesa,b,c 
 
Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Fatigue (common) 
Grade 1 or 
Grade 2 lasting ≤ 7 days 
Maintain dose. Rule out other causes. If found to be anemic, 
consider transfusing for hemoglobin < 8 g/dL.   
Patients with significant fatigue after several doses of selinexor 
may have an ongoing antitumor response. Consider an 
unscheduled assessment of tumor response as part of the patient’s 
evaluation.  
Grade 2 lasting ≤7 days 
As per the 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, consider 
transfusing for hemoglobin < 8 g/dL.  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 ongoing antitumor response. Consider an 
unscheduled assessment of tumor response as part of the patient’s 
evaluation. As per the 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 a repeat 
nutritional consultation and utilize nutritional supplements (e.g., 
Ensure®, Boost®, etc.)  
For persistent symptoms, start appetite stimulants, such as 
olanzapine (2.5 to 5 mg PO every morning) or megesterol acetate 
(400 mg QD), per NCCN guidelines. 
Grade1 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 and 
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 a repeat nutritional consultation and utilize 
nutritional supplements (e.g., Ensure®, Boost®, etc.)  
Start appetite stimulants as above.   


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
Nausea, Acute (common) 
Grade 1 or 2 
(If intolerable or persistent 
Grade 2 not responsive to 
supportive care, follow 
guidelines for Grade 3) 
Maintain dose. Rule out other causes.  Utilize standard additional 
anti-nausea meds to supplement the protocol-required 5-HT3 
antagonists.   
Use additional anti-nausea medications to supplement the 
protocol-required 5-HT3 antagonist(s). Olanzapine 2.5 to 5 mg 
PO every morning, per NCCN guidelines, can mitigate nausea 
and anorexia. 
Grade 3 
Rule out other causes.  Utilize additional anti-nausea medications 
to supplement the protocol-required 5-HT3 antagonist(s).  
Olanzapine 2.5 to 5 mg PO every morning, 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 (common) 
Grade 1 (sodium levels 
< Normal to 130 mmol/L)  
Maintain dose. Rule out other causes including drug (e.g., 
diuretic) effects. 
Be certain that reported sodium level is corrected for concurrent 
hyperglycemia (serum glucose > 150 mg/dL).  
Treat hyponatremia per institutional guidelines including dietary 
review. 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 (e.g., 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.  
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 (e.g., 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 (common) 
Grade 1  
  
Maintain dose. Rule out other causes including drug effects.  
Treat per institutional guidelines with anti-diarrheals, such as 
loperamide. 


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
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. 
 
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, start 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 (i.e.,  50% marrow involvement) or pre-existing 
compromised marrow function (e.g., due to prior marrow-toxic 
therapy), or if there is baseline thrombocytopenia Grade 2-4, the 
Principal Investigator in consultation with the Sponsor - 
Investigator 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, start treatment with moderate to 
high doses of thrombopoietin stimulating agents as above. 
In cases where there is significant disease involvement in the 
bone marrow (i.e.,  50% marrow involvement) or pre-existing 
compromised marrow function (e.g., due to prior marrow-toxic 
therapy), the Investigator in consultation with the Sponsor-
Investigator 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, start treatment with moderate 
to high doses of thrombopoietin stimulating agents as above. 


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
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 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 Sponsor-Investigator. 
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. Initiate 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. 


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Toxicity and Intensity 
Supportive Care and Dose Adjustment Guidelines 
All dose modifications should be based on the worst preceding toxicity. 
aFor all ≥ Grade 3 hematological or non-hematological AEs that are NOT selinexor related, 
after consultation with the Sponsor-Investigator 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 Sponsor-
Investigator. 
 
cIf toxicities are suspected to be due to docetaxel rather than selinexor (eg, neutropenia occurring at 
expected intervals after chemotherapy), selinexor dose does not need to be modified. If, however, 
toxicities persist despite docetaxel dose modification and/or supportive care measures (as appropriate), 
then the selinexor dose should be modified. 
 
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 Sponsor-Investigator. 
 
 
4.7.1.1  
Conditions Not Requiring Selinexor Dose Reduction 
The following conditions are exceptions to the dose-modification guidelines. Selinexor dose does 
not need to be modified in the following cases: 
• Alopecia of any grade. 
• Electrolyte or serum analyte (e.g., urate) abnormalities that are 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. 
• Toxicities attributed to docetaxel. If, however, toxicities persist despite docetaxel dose 
modification and/or supportive care measures (as appropriate), then the selinexor dose should be 
modified. 
4.7.1.2  
Selinexor Dose Adjustment in the Setting of Infection 
Patients with active uncontrolled or suspected infections should have treatment withheld until the 
infection has clinically resolved and/or the patient is clinically stable. When ready to resume 
dosing, treatment may continue at the original dose. Patients may continue antibiotics for 
prolonged periods while re-initiating their treatment at the discretion of the Investigator.  
4.7.2 Missed or Vomited Doses 
Weekly selinexor dosing cohorts 
Missed Doses 
Missed doses should be managed as follows:  
• If a dose was missed, it may be given up to 48 hours after the planned dose and at least 36 hours 
before the next scheduled dose  


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• If a dose must be skipped (e.g., due to recommendation of treating physician), the next dose will 
be taken as per schedule. Doses should not be administered less than 36 hours apart and all missed 
and delayed doses should be documented. 
If a patient missed a full one- or two-week period of dosing for non-study drug-related events (e.g., 
a required medical procedure or an unanticipated personal emergency), the days missed will be 
replaced. For example, if patient missed Cycle 2 Day 7 to Cycle 2 Day 14, then the patient will 
start the next dosing on Cycle 2 Day 7 following the break. Similarly, if a patient misses Cycle 3 
Day 1 to Cycle 3 Day 15, then the patient will start the next dosing on Cycle 3 Day 1. In this 
fashion, laboratory and radiographic assessments remain appropriate for timing of the 
administration of anti-cancer therapy. 
Vomited Doses 
If a dose is vomited within 1 hour of ingestion, it will be replaced. If vomiting occurs more than 
1 hour after dosing, it will be considered a complete dose. 
 
Twice weekly selinexor dosing cohorts 
Missed Doses 
If a dose of selinexor is missed or delays, patients should take the next dose at the next regularly 
scheduled time. 
Vomited Doses 
If a patient vomits a dose of selinexor, the patient should not repeat the dose. The patient should 
take the next dose on the next regularly scheduled day. 
 
4.7.3 Docetaxel Dose Reduction and Supportive Care Guidelines 
Each cycle of chemotherapy may be delayed until the ANC is ≥ 1500 cells/μL and the platelet 
count is ≥ 100,000 cells/μL and hepatic function is acceptable. Institutional standard practices 
may be used to adjust doses for toxicity. However, in the absence of such standard practices, 
suggested dose adjustments for docetaxel-related hematologic and non-hematologic toxicities 
are provided in Table 6 and Table 7, respectively. 
 
NOTE:  If toxicities are suspected to be due to selinexor rather than docetaxel (eg, nausea 
occurring on a weekly basis, coinciding with selinexor dosing), docetaxel dose does not need to 
be modified. If, however, toxicities persist despite selinexor dose modification and/or supportive 
care measures (as appropriate), then the docetaxel dose should be modified. 
 
Anti-emetic prophylaxis and premedication for infusion reactions for docetaxel should follow 
institutional guidelines.  
 
Table 6. Dose Adjustments for Docetaxel-related Hematologic Toxicities 
 
Situation 
Recommended Docetaxel Dose 


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Starting Dose 
75mg/m2 
Starting Dose 
60mg/m2 
First episode of febrile neutropenia 
60 mg/m2 
50mg/m2 
Second episode of febrile neutropenia 
35 mg/m2 
 
35mg/m2 
ANC <500/mm3 
60 mg/m2 
50mg/m2 
Grade 4 thrombocytopenia or bleeding 
associated with thrombocytopenia 
 
60 mg/m2 
50mg/m2 
NOTE: In addition to or in place of docetaxel dose reductions for neutropenia, patients may 
receive myeloid growth factors (preferably PEG-filgrastim on Day 2 of subsequent cycles). 
 
Table 7. Dose Adjustments for Docetaxel-related Non-hematologic Non-neuropathic 
Toxicities 
 
NCI CTCAE 
Grade 
Recommended Docetaxel Dose 
Starting dose 75 mg/m2 
Starting dose 60 
mg/m2 
0 to 2 
75 mg/m2 
60 mg/m2 
3 (except alopecia) 
60 mg/m2 
50 mg/m2 
4 
35 mg/m2 
35 mg/m2 
NCI-CTCAE= National Cancer Institute (United States Common Terminology Criteria for 
Adverse events (Version 4.03).  
In addition to the dose adjustments, patients may receive supportive care as necessary.  Patients 
experiencing febrile neutropenia secondary to docetaxel chemotherapy may receive granulocyte 
colony stimulating factor therapy in association with subsequent chemotherapy doses. 
Erythropoietin may also be used as clinically indicated, along with other supportive care. 
4.8 
Supportive Care and Concomitant Therapy  
4.8.1 Required Antiemetics 
 
In order to minimize nausea, all patients should receive two anti-emetic prophylaxis. This includes 
(a) 5-hydroxytryptamine (5-HT3) antagonists (8 mg or equivalent) unless contraindicated, starting 
on C1D1 before the first dose of study treatment and continued 2 to 3 times daily thereafter, as 
needed, AND (b) olanzapine 5 mg (which can be increased to 10 mg) daily starting before the first 
dose of treatment and continued as needed. Alternative treatment may be provided if the patient 
does not tolerate 5-HT3 antagonists. 
 
4.8.2 Supportive Care Recommendations for Selinexor-Related Adverse Events 
 
Supportive measures for optimal medical care should be provided to all patients during 


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participation in this study. In addition to the required prophylactic therapy with 5-HT3 
antagonists (Section Error! Reference source not found.), supportive care per institutional 
guidelines and/or the National Comprehensive Cancer Network® (NCCN) Clinical Practice 
Guidelines in Oncology (NCCN Guidelines®) should be used as clinically indicated at the 
discretion of the Investigator. 
Supportive care guidelines for managing AEs are provided in Table 5. 
 
4.8.3 Non-study Related Concomitant Medication and Treatment 
Concomitant medications include any prescription or over-the-counter preparation, including 
vitamins, dietary supplements, over-the-counter medications, and oral herbal preparations taken 
during the study. Patients may continue their baseline medication(s). 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.  
 
 
4.8.4 Permitted Concomitant Medication  
Patients will receive concomitant medications to treat symptoms, AEs, and intercurrent illnesses 
that are medically necessary as part of standard care. Medications to treat concomitant diseases 
like diabetes, hypertension, etc., are allowed. 
 
4.8.5 Use of Blood Products 
Appropriate anti-coagulation is allowed during the study (e.g., 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 or granulocyte macrophage-colony stimulating factor, pegylated growth factors, 
and platelet stimulatory factors, in accordance with clinical practice or institutional guidelines prior 
to entry and throughout the study. 
 
4.9 
Other Modalities of Procedures 
4.9.1 
Radiation Treatment 
If clinically indicated, palliative radiation therapy to non-target lesions is permitted but study drugs 
should be held for ≥ 1 day before the start of palliative radiation therapy and ≥ 1 day following 
each dose of palliative radiation therapy. Treatment with selinexor shall not be discontinued solely 
due to palliative radiation.  


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4.9.2 Restrictions and Prohibited Medications 
Concurrent 
Therapies: 
Concurrent therapy with glucocorticoids as specified herein is allowed. Concurrent 
therapy with any other approved or investigative anticancer therapeutic is not allowed. Other 
investigational agents should not be used during the study.  Use of any immunosuppressive agents 
during the study must be confirmed by the Sponsor-Investigator.   
Diet: There are no dietary restrictions on this study.  Patients on selinexor should maintain 
adequate caloric and fluid intake. 
Medications: There are no longer any restrictions on the use of acetaminophen or acetaminophen-
containing products in combination with selinexor, EXCEPT on days on selinexor dosing, when 
acetaminophen must not exceed a total daily dose of 1 gram.   
Patients should not take glutathione (GSH)-, S-adenosylmethionine (SAM)-, or N-
acetylcysteine (NAC)-containing products during their participation in this study as these 
products may enhance the metabolism of selinexor. However, they are permitted if the patient 
has elevated liver function tests  Patients must report all prescription and non-prescription 
medicines to their physicians during this study 
4.9.3 Duration of Therapy 
Review of patient accrual onto recent studies suggests that the study should enroll 3-4 patients 
per month.  Accounting for variations in site activation time-lines, we estimate the duration of 
accrual to be over 36 months.   
4.9.4 Discontinuation Criteria 
4.9.4.1 Early Discontinuation of the Study 
The study may be discontinued at the sole discretion of the Sponsor-Investigator for any reason, 
including medical or ethical reasons affecting the continued performance of the study, or 
difficulties in the recruitment of patients.  
The Sponsor-Investigator, in conjunction with appropriate regulatory authorities, would then 
decide if the trial should be modified or terminated. 
4.9.4.2 Early Discontinuation of Individual Patients 
The Investigator may remove a patient from study treatment after consultation with the Sponsor-
Investigator for any of the following reasons: 
• Unacceptable AEs or toxicity that cannot be managed by supportive care (this must be linked in 
the study database to the AE or toxicity event to support discontinuation). 
• Any medically appropriate reason or significant protocol violation, in the opinion of the 
Investigator 
The Investigator must remove a patient from study treatment for any of the following reasons: 
• Disease progression  
• Patient elects to discontinue study treatment 
• Pregnancy 


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Patients may discontinue study treatment for any reason. Patients who elect to discontinue study 
treatment should be encouraged to continue in the study so that follow-up information on disease 
progression and survival status may be obtained. However, patients may elect to withdraw consent 
and decline further participation in the trial. 
 
4.9.5 Treatment Beyond Progression: 
In some instances, a patient may be deemed to be receiving benefit from study therapy despite 
RECIST progressive disease. In these cases, study treatment may be continued if the following 
criteria are met: 
• No ongoing intolerable treatment-related AEs 
• Patient informed of available treatment options  
• Case discussed with and decision to treat beyond progression approved by Study Chair 
NOTE: Patients in the selinexor monotherapy cohort may be treated with selinexor + docetaxel at 
the time of progression. In these cases, (a) the above criteria must be met, (b) the dose and schedule 
of selinexor + docetaxel will be based on the currently used regimen in the combination cohort, 
and (c) subsequent treatment administration (dose, schedule, etc) will be based on protocol 
guidance for the selinexor + docetaxel cohort. 
 
4.9.6 Removal Subjects from Protocol Therapy 
 
Subjects will be removed from therapy when any of the criteria listed in Section 5.5 apply. 
Notify the Principal Investigator,and document the reason for treatment discontinuation and the 
date of discontinuation. The subject should be followed-up per protocol.  
4.9.7 Subject Replacement 
To be evaluable for DLT, a patient must receive at least one dose of docetaxel and at least three 
of four doses of selinexor.  To be considered not to have experienced DLT, a patient must 
complete the first (28-day) cycle of treatment before a dose-escalation evaluation is made.  
Patients who are not evaluable for toxicity will be replaced.   
 
5.0 
Study Procedures 
5.1 
Screening/Baseline Procedures 
Assessments performed exclusively to determine eligibility for this study will be done only after 
obtaining informed consent. Assessments performed for clinical indications (not exclusively to 
determine study eligibility) may be used for baseline values even if the studies were done before 
informed consent was obtained. 
 
Screening will include the study procedures described below and will be performed within 28 
days prior to the start of therapy as summarized in Error! Reference source not found.. The 
Investigator should not repeat procedures that are performed as part of standard of care (SOC), if 


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they are within the screening window and are done prior to signing the ICF. Data from SOC 
procedures will be part of the patient's medical history and may be used for study purposes.  
Screening may be divided into two (or more) clinic visits at the discretion of the Investigator. The 
procedures to be performed during screening are listed below assuming such a division; however, 
the decision is up to the Investigator, as long as all procedures are performed. 
Screening (Performed within 4 weeks prior to start of study therapy)  
• A complete medical history (all significant conditions that have previously existed and are now 
resolved as well as current conditions) 
• Documentation of concomitant medications (including alternative medications) 
• Physical examination including body weight, height, and vital signs (heart rate, blood 
pressure, temperature) 
• BSA baseline calculation  
• Histological or cytological confirmation of NSCLC and molecular identification of KRAS 
mutation.  Molecular identification of a KRAS mutation (codons 12, 13, or 61 mutations detected 
by sequencing) is to be performed by a CLIA-certified assay (source documentation required) 
• Nutritional Consultation  
• Serum pregnancy test for women of childbearing potential (must be within 72 hours of 
administration of study treatment) 
• Urinalysis 
• CBC w/differential  
• Comprehensive Metabolic Panel (CMP) 
• Other Study Requirements will include: , PT/INR, PTT, Uric Acid,, , Magnesium, Phosphate, 
LDH,  
• Viral Hepatitis to include: HCV antibody, HAV IgM antibody, HBsAg, HBcAB IgM 
• CXR 
• EKG 
• ECOG performance status 
 
The following radiologic assessment will be performed within 4 weeks prior to study start: 
• CT/MRI scans of the chest and upper abdomen (CT scan with contract preferred) 
• RECIST Tumor Assessment Form 
Brain imaging will be performed only if clinically indicated (headache, focal neurological 
findings) or if known history of treated brain metastases. For patients with baseline abnormalities 
on brain imaging, brain imaging should be repeated every 4 cycles (ie, every 12 weeks) 


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Clinical Study Protocol: IST-USA-000000116600 
 
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5.2 
Procedures During Treatment 
 
5.2.1 Cycle 1 Day -7 (docetaxel + selinecor cohort only) 
 
• Limited physical examination including body weight, and vital signs (heart rate, blood pressure, 
temperature) 
• Serum pregnancy test for women of childbearing potential (must be within 72 hours of 
administration of study treatment) 
• CBC w/Differential  
• Comprehensive Metabolic Panel (CMP) 
• LDH 
• ECOG performance status 
• Documentation of concomitant medications (including alternative medications) 
• Toxicity assessment/Documentation of Adverse Events 
• Selinexor Dispensation 
• Provide Study Drug Diary 
• Blood draws for PD analysis will be performed pre-dose and 4 hours post-dose,  
 
5.2.2 Cycle 1 Day 1 
 
• Limited physical examination including body weight, height, and vital signs (heart rate, blood 
pressure, temperature) 
• BSA calculation  
• CBC w/Differential 
• Comprehensive Metabolic Panel (CMP) 
• LDH 
• Other Study Requirements will include: Uric Acid, Magnesium, Phosphate,   
• Documentation of concomitant medications (including alternative medications) 
• Toxicity assessment/Documentation of Adverse Events 
• Docetaxel administration (unless in the selixenor monotherapy cohort) 
• Selinexor Dispensation 
• Provide Study Drug Diary (selinexor monotherapy cohort) 
• Review patients dosing diary for dosing compliance (docetaxel + selinexor cohort) 
• Blood draws for PD analysis will be performed pre-dose and 4 hours post-dose 
 
5.2.3 Cycle 1 Day 3 or Cycle 1 Day 4 (contact) 
• Telephone call with patient to evaluate supportive care medications and adverse events, and to 
adjust supportive care as appropriate. The telephone contact with the patient must take place on 
C1D3 or C1D4 following the Cycle 1 Day 1 selinexor and docetaxel dosing.      
 
5.2.4 Cycle 1 Day 8 (±1 day) 
 


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• Limited Physical examination including body weight, and vital signs (heart  
 
rate, 
blood pressure, temperature) 
• CBC w/Differential 
• Comprehensive Metabolic Panel (CMP) 
• LDH 
• Review patients dosing diary for dosing compliance 
• Documentation of concomitant medications (including alternative medications) 
• Toxicity assessment/Documentation of Adverse Events 
 
5.2.5 Cycle 1 Day 15 (±1 day) 
 
• 
Limited Physical examination including body weight, and vital signs (heart rate, blood 
pressure, temperature) 
• 
CBC w/Differential 
• 
Comprehensive Metabolic Panel (CMP) 
• 
LDH 
• 
Review patients dosing diary for dosing compliance 
• 
Documentation of concomitant medications (including alternative medications) 
• 
Toxicity assessment/Documentation of Adverse Events 
 
5.2.6 Cycles ≥ 2 Day 1 + 3 days 
 
During these visits the following assessments will be completed: 
• Physical examination including body weight, height, and vital signs (heart rate, blood 
 
pressure, temperature) 
• 
BSA Calculation 
• 
ECOG performance status 
• 
CBC w/differential  
• 
Comprehensive Metabolic Panel (CMP)  
• 
LDH 
• 
Other Study Requirements will include: Uric Acid, Magnesium, Phosphate  
• 
Urinalysis  
• 
Coagulation tests – PT/INR, PTT 
• 
Documentation of concomitant medications (including alternative medications) 
• 
Toxicity assessment/Documentation of Adverse Events 
• 
Provide Study Drug Diary 
• 
Review patients dosing diary for dosing compliance 
• 
Docetaxel Administration (unless in the selinexor monotherapy cohort) 
• 
Blood draw for PD testing will be performed pre-dose (cycle 2 only) 
 
• 
Tumor assessment by RECIST 1.1 may be performed at any points Days 16-21 
; even-numbered  cycles only.  NOTE: for subjects who have been on treatment for one year or 
more, tumor assessment may be performed every 4 cycles. 


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5.3 
End-of-Treatment Visit (≥ 30 Days after Last Dose) 
Study procedures will be performed at 30 days (+/- 7 days) after the last dose of study medication 
for all patients, including early termination patients, as summarized below. 
• Assessment of adverse events 
• Documentation of concomitant medications (including alternative medications) 
• Physical examination including body weight, and vital signs (heart rate,  
 
 
 
blood pressure, temperature) 
• CBC w/differential  
• Comprehensive Metabolic Panel (CMP) 
• 
Other labs as follows: LDH, Uric Acid, Magnesium, Phosphate, EKG 
▪ Blood draw for PD testing 
 
5.4 
Follow-up Procedures 
After treatment discontinuation, a telephone call will be made to the patient (or the patient’s 
family) every 3 months to inquire about the patient’s NSCLC status, general health, and 
information on any antineoplastic therapies utilized since discontinuation of study treatment. 
Alternatively, review of medical records may be performed for collection of follow-up 
information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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5.5 
Schedule of Study Activities and Assessments   
Activity/Assessment  
 
 
Screening  
(28 days 
prior to 
start of 
treatment) 
Cycle 1 
Cycles ≥ 2 
End of 
cycle 2 
End-of-Treatment  
(EoT) Visit 
Survival  
Follow-up17 
(Every 3 mo.) 
 
 
Day 
-7 
Day 1 Day 
8 
Day 
15 
Day 1  
 
30 Days Post-Last 
Dose 
± 1 day 
+ 3 days 
 
± 7 days 
± 14 days 
Informed consent1 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical history2 
X 
 
 
 
 
 
 
 
 
Patient height  
X 
 
X 
 
 
X 
 
 
 
Patient weight 
X 
X 
X 
 
 
X 
 
X 
 
Body Surface Area 
(BSA)3 
X 
 
X 
 
 
X 
 
 
 
Vital signs4 
X 
X 
       X X 
X 
X 
 
X 
 
Physical examination, 
full5 
X 
 
 
 
 
X 
 
X 
 
Physical examination, 
limited6 
 
 
X 
X 
X 
X 
 
 
 
 
ECOG7 
X 
X 
 
 
 
X 
 
X 
 
12-lead ECG8 
X 
 
 
 
 
 
 
X 
 
Urinalysis9 
X 
 
 
 
 
X 
 
X9 
 
CBC with 
differential10 
X 
X 
X 
X 
X 
X 
 
X 
 


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Activity/Assessment  
 
 
Screening  
(28 days 
prior to 
start of 
treatment) 
Cycle 1 
Cycles ≥ 2 
End of 
cycle 2 
End-of-Treatment  
(EoT) Visit 
Survival  
Follow-up17 
(Every 3 mo.) 
 
Day 
-7 
Day 1 Day 
8 
Day 
15 
Day 1  
 
30 Days Post-Last 
Dose 
± 1 day 
+ 3 days 
 
± 7 days 
± 14 days 
Comprehensive 
Metabolic Panel 
(CMP)11 
X 
X 
       X X 
X 
X 
 
X 
 
LDH 
X 
X 
X 
X 
X 
X 
 
X 
 
Other Labs: 
• 
Uric Acid 
• 
Magnesium 
• 
Phosphorus 
X 
 
X 
 
 
X 
 
X 
 
CT/MRI scans (CT 
with contract preferred) 
• Chest 
• Upper 
Abdomen 12 
X 
 
 
 
 
 
X 
 
 
RECIST Tumor 
Assessment Form 
X 
 
 
 
 
 
X 
 
 
Brain imaging20  
X 
 
 
 
 
 
 
 
 
Chest radiograph13 
X 
 
 
 
 
 
 
 
 
Serum pregnancy 
test14 
X 
X 
 
 
 
 
 
 
 
Docetaxel 
administration21 
 
 
X 
 
 
       X 
 
 
 
Study drug dosing 
 
 
See Table 1 
 
 
 


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Activity/Assessment  
 
 
Screening  
(28 days 
prior to 
start of 
treatment) 
Cycle 1 
Cycles ≥ 2 
End of 
cycle 2 
End-of-Treatment  
(EoT) Visit 
Survival  
Follow-up17 
(Every 3 mo.) 
 
Day 
-7 
Day 1 Day 
8 
Day 
15 
Day 1  
 
30 Days Post-Last 
Dose 
± 1 day 
+ 3 days 
 
± 7 days 
± 14 days 
Provide Study Drug 
Dosing Diary 
 
X 
 
 
 
X 
 
 
 
Compliance Review 
of Study Drug Dosing 
Diary 
 
 
X 
X 
X 
X 
 
 
 
Blood draw for PD 
testing15 
 
X 
X 
 
 
X (C2 only) 
 
X 
 
Adverse events 
X 
X 
X 
X 
X 
X 
 
X 
 
Concomitant 
medication 
X 
X 
X 
X 
X 
X 
 
X 
 
Nutritional 
consultation19 
X 
 
 
 
 
 
 
 
 
Telephone contact16,17 
 
 
On 
C1D3 
or 
C1D4 
 
 
 
 
 
X 
Antineoplastic 
therapy after EoT 
treatment 
 
 
 
 
 
 
 
 
X 
Viral hepatitis labs18 
X 
 
 
 
 
 
 
 
 


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Abbreviations: BSA = body surface area; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EoT = End of 
Treatment (Visit); MM = multiple myeloma, PD = Pharmacodynamic; PK = Pharmacokinetic; QoL = Quality of Life; CBC = 
complete blood count;  
 
1 
Prior to the first study-specific measures. However, the Investigator should not repeat procedures that are performed as part of 
standard of care (SOC), if they are within the screening window and are done prior to signing the ICF. 
2 
Including details of all prior anti-NSCLC therapies. Includes baseline symptoms as well as a detailed history of prior cancer therapies, 
including start and stop dates, disease progression during or after therapy, as well as discontinuations due to intolerability or any other 
serious illness. 
3 
Body Surface Area (BSA) will be calculated (by Dubois 1916 or Mosteller 1987 method) during screening and on Day 1 of each cycle.  
When calculating the dose of Docetaxel, rounding the BSA according to instutitional practice is permitted.  The dose may be capped at 
the dose corresponding to a BSA of 2m2 if necessary to comply with institutional practices.  
4 
Blood pressure, pulse and temperature, unless this data was obtained during the vital signs assessment. 
5 
Full physical examination (PE) for baseline, start of every new cycle and EoT visit.  
6 
Limited PEs during the study should be symptom directed.  
7 
ECOG performance status assessments will be done on Day 1 of each Cycle, however the assessment for Cycle 1 Day 1 may be done 
during Screening or pre-dose C1 D-7. 
8 
ECG will be performed during Screening (or pre-dose Cycle 1 Day 1) and the EoT Visit.  
9 
Includes appearance, color, urine bilirubin, glucose, hemoglobin, ketones, pH, protein, specific gravity, and urobilinogen. Microscopy 
will only be performed if clinically indicated.  
10 CBC with differential includes hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, white blood cell (WBC) count, WBC differential, RBC count, lymphocytes, monocytes, neutrophils, 
eosinophils, basophils, platelets. WBC differential may be automated or manual as per institutional standards. Reticulocytes may be 
performed when clinically indicated 
11 Complete serum chemistry at Screening or Cycle 1 Day, then Day 1 of each Cycle and EoT visit.  Parameters to be assessed for complete 
serum chemistry are presented in Table 8 and include serum sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, ALT, 
AST, alkaline phosphatase, total bilirubin LDH, calcium, magnesium, phosphorus, total protein, albumin, , uric acid.  
1 
Limited chemistry for Cycle 1 (Day -7, Days 8 and 15).  Laboratory parameters to be assessed for limited serum chemistry are     
presented in Table 8 and include serum sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, ALT, AST, ALP, total 
bilirubin LDH. 
12 Disease status will be measured once at the end of every two cycles and as clinically indicated (±5 days). Response will be evaluated as 
per RECIST v1.1 criteria. Computed tomography (CT)/magnetic resonance imaging (MRI) scans for disease evaluation need not be 


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repeated at the final visit if one has been performed within 6 weeks of the final visit date. Baseline scans required within 4 weeks of 
study treatment initiation.  For subjects who have been on treatment for one year or more, tumor assessment may be performed every 4 
cycles. 
13 Both posteroanterior and lateral films should be obtained at baseline. Note that this test does not need to be repeated if results are 
available from a test performed within 30 days prior to start of therapy. This test serves as a baseline in the event that patients develop 
any adverse events during the study. 
14 For women of childbearing potential; negative serum hCG pregnancy test ≤ 3 days (72 hours) of Cycle 1 Day -7 
15 Blood draws for PD analysis will be performed Cycle 1 Day -7 pre-dose and 4 hours post-dose, Cycle 1 Day 1 pre-dose and 4 hours 
post-dose, Cycle 2 Day 1 pre-dose, and at end of treatment  
16 Telephone call (or visit) with patient to evaluate supportive care medications and adverse events, and to adjust supportive care as 
appropriate. The telephone contact with the patient must take place on C1D3 or C1D4 following the Cycle 1 Day 1 selinexor and 
docetaxel dosing. 
17 After study discontinuation, a telephone call will be made to the patient (or the patient’s family) every 3 months to inquire about the 
patient’s NSCLC status, well-being, and information on any antineoplastic therapies utilized since discontinuation of selinexor study 
treatment.  Alternatively, the medical record may be reviewed to obtain this information; if needed, a phone call will be made.  
18 Viral hepatitis labs includes HAV IgM antibody, HBsAg and HBcAb IgM and HCV antibody. 
19 Patients must be given nutritional consultation to discuss any food recommendations and strategies for managing potential nausea and 
appetite changes experienced with selinexor. This may be completed between enrollment and (or on) cycle 1 day -7. 
20 Brain imaging (preferably MRI) will be performed only if clinically indicated (headache, focal neurological findings) or if known history 
of treated brain metastases.   For patients with baseline abnormalities on brain imaging, brain imaging will be repeated every 4 cycles 
(ie, every 12 weeks).   Baseline scans required within 4 weeks of study treatment initiation.   
21 Docetaxel will not be administered in the selinexor monotherapy cohort 
 
 
 
 


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Table 1A: Dosing Schedule—combination therapy  
 
 
Cycle 1 
 
 
Cycles 1+ 
Treatment 
Week -1 
Week 1 
Week 2 
Week 3 
D-7 D-6 D-5 D-4 D-3 D-2 D-1 D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 D18 D19 D20 D21 
Selinexor 
X 
X 
X1 
X1 
Docetaxel 
X2 
1If a dose is missed, it may be given up to 48 hours after the planned dose and at least 36 hours before the next scheduled dose 
2Docetaxel may be administered up to 3 days after Day 1 of each cycle 
 
Table 2B: Dosing Schedule—selinexor monotherapy 
 
1Based on the totality of clinical data, after 6 patients are treated in each selinexor monotherapy cohort (weekly and twice weekly), 
one schedule will be selected for further study in the expansion cohort. 
2In the weekly dosing cohort, if a dose is missed, it may be given up to 48 hours after the planned dose and at least 36 hours before the 
next scheduled dose. 
3In the twice weekly dosing cohort, if a dose is missed or delayed, patients should take the next dose at the regularly scheduled time.  
 
Cycles 1+ 
Treatment1 
Week 1 
Week 2 
Week 3 
D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 D11 D12 D13 D14 D15 D16 D17 D18 D19 D20 D21 
Selinexor—weekly cohort 
X2 
X2 
X2 
Selinexor—twice weekly 
cohort 
X3 
X3 
X3 
X3 
X3 
X3 


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5.6 
Removal Subjects from Study 
Subjects can be taken off the study treatment and/or study at any time at their own request, or 
they may be withdrawn at the discretion of the investigator for safety, behavioral or 
administrative reasons. The reason(s) for discontinuation will be documented and may 
include: 
5.6.1 Subject voluntarily withdraws from treatment (follow-up permitted); 
5.6.2 Subject withdraws consent (termination of treatment and follow-up); 
5.6.3 Subject is unable to comply with protocol requirements; 
5.6.4 Subject demonstrates disease progression (unless continued treatment with study 
drug/treatment is deemed appropriate at the discretion of the investigator); 
5.6.5 Subject experiences toxicity that makes continuation in the protocol unsafe; 
5.6.6 Treating physician judges continuation on the study would not be in the subject’s best 
interest; 
5.6.7 Subject becomes pregnant (pregnancy to be reported along same timelines as a serious 
adverse event); 
5.6.8 Development of second malignancy (except for basal cell carcinoma or squamous cell 
carcinoma of the skin) that requires treatment, which would interfere with this study; 
5.6.9 Lost to follow-up. 
 
6.0 
MEASUREMENT OF EFFECT 
6.1 
Antitumor Effect 
 
Response and progression will be evaluated in this study using the new international criteria 
proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) Committee 
[Eur J Cancer. 2009;45(2):228-247]. Changes in only the largest diameter (unidimensional 
measurement) of the tumor lesions are used in the RECIST v1.1 criteria. 
 
6.2 
Definitions 
Evaluable for toxicity. All subjects will be evaluable for toxicity from the time of their first 
treatment with study therapy. 
 
Evaluable for objective response.  Only those subjects who have measurable disease present 
at baseline, have received at least one cycle of therapy, and have had their disease re-
evaluated will be considered evaluable for response. These subjects will have their response 
classified according to the definitions stated below. (Note: Subjects who exhibit objective 
disease progression prior to the end of cycle 1 will also be considered evaluable.) 
 
If using RECIST, state: 
 


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6.3 
Disease Parameters 
 
Measurable Disease: Tumor lesions: Must be accurately measured in at least one dimension 
(longest diameter in the plane of measurement is to be recorded) with a minimum size of: 
1. 10 mm by CT scan (CT scan slice thickness no greater than 5 mm) 
2. 10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable) 
3. 20 mm by chest x-ray. 
 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). Lymph nodes merit special mention since they 
are normal anatomical structures which may be visible by imaging even if not involved by 
tumor. Pathological nodes which are defined as measurable and may be identified as target 
lesions must meet the criterion of a short axis of ≥ 15 mm by CT scan. Only the short axis of 
these nodes will contribute to the baseline sum. The short axis of the node is the diameter 
normally used by radiologists to judge if a node is involved by solid tumor. Nodal size is 
normally reported as two dimensions in the plane in which the image is obtained (for CT 
scan this is almost always the axial plane; for MRI the plane of acquisition may be axial, 
sagittal or coronal). The smaller of these measures is the short axis. For example, an 
abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm and 
qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥ 10 mm but < 15 
mm) should be considered non-target lesions. Nodes that have a short axis < 10 mm are 
considered non-pathological and should not be recorded or followed. 
 
Note: Previously irradiated lesions are non-measurable except in cases of documented 
progression of the lesion since the completion of radiation therapy. 
 
Non-measurable disease.  
All other lesions are considered non-measurable, including small lesions (longest diameter < 
10mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis) as well as truly non-
measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic 
involvement of skin or lung, abdominal masses/abdominal organomegaly identified by 
physical exam that is not measurable by reproducible imaging techniques. 
 
Target lesions.  
All measurable lesions up to a maximum of five lesions total (and a maximum of two lesions 
per organ) representative of all involved organs should be identified as target lesions 
 
Non-target lesions. All other lesions (or sites of disease) including any measurable lesions 
over and above the five target lesions should be identified as non-target lesions and should 
also be recorded at baseline. Measurements of these lesions are not required, but the presence 
or absence of each should be noted throughout follow-up.  


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6.4 
Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers. 
All baseline evaluations should be performed as closely as possible to the beginning of 
treatment and not more than 28 days before the beginning of the treatment. 
 
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. Imaging-based evaluation is 
preferred to evaluation by clinical examination when both methods have been used to assess 
the antitumor effect of a treatment. 
 
Disease assessment via RECIST v1.11 will be performed at the end of even-numbered cycles 
beginning with Cycle 2 (Day 42); the assessment may be performed up to 5 days before Day 
42 (Day 38 - Day 42) but attempts should be made to conduct the assessment as close to Day 
42 as possible.  Disease assessment may be performed prior to initiation of the next cycle, but 
results must be available prior to initiation of treatment and must confirm continued eligibility 
for next cycle). Patients who require extended dose interruptions without disease progression 
(e.g. unacceptable toxicities) will remain on study and continue with tumor scans per schedule 
of assessments as specified until disease progression or start of alternative treatment.  
 
6.5 
Response Criteria 
Evaluation of Target Lesions 
Complete Response (CR): Disappearance of all target lesions.   Disappearance of all target 
lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in 
short axis to <10 mm (the sum may not be “0” if there are target nodes).  Determined by two 
separate observations conducted not less than 4 weeks apart. There can be no appearance of 
new lesions. 
Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of 
target lesions, taking as reference the baseline sum LD. There can be no appearance of new 
lesions. 
 
Progressive Disease (PD): > 20% increase in the SLD taking as reference the smallest SLD 
recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir.   
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum LD since the treatment started. There 
can be no unequivocal new lesions. 
Evaluation of Non-Target Lesions 
Complete Response (CR): Disappearance of all non-target lesions and normalization of 
tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). 
 


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 (Non-CR/Non-PD): Persistence of one or more non-target lesion(s) and/or maintenance of 
tumor marker level above the normal limits. 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions 
 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started). The subject’s best response assignment 
will depend on the achievement of both measurement and confirmation criteria. 
 
 
Time point response: patients 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 
Not evaluated 
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 
CR = complete response, NE = not evaluable, PD = progressive disease, PR = partial 
response, SD = stable disease. 
 
Time point response: patients with non-target disease only. 
Non-target lesions 
New lesions 
Overall response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response, NE = not evaluable, PD = progressive disease 
 
6.6 
Duration of Response 
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date 
that recurrent or progressive disease is objectively documented (taking as reference for 
progressive disease the smallest measurements recorded since the treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are first met for 
CR until the first date that recurrent disease is objectively documented. 
 
 


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Duration of stable disease: Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since 
the treatment started.  
 
6.7 
Progression-Free Survival 
 
Progression-free survival (PFS) is defined as the duration of time from start of treatment to 
time of progression. 
 
6.8 
Safety/tolerability 
 
Safety evaluations will be conducted at Cycle 1 Day -7 and Cycle 1 Day 1 and on Days 8 and 
15 of Cycle 1; Days 1 for Cycles ≥ 2, and the EoT Visit  
 
Analyses will be performed for all subjects having received at least one dose of study 
therapy. The study will use the CTCAE version 4.03 for reporting of adverse events.  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
 
7.0 
ADVERSE EVENTS 
7.1 
Experimental Therapy 
Adverse Events (AEs) will be coded using the MedDRA dictionary and displayed in tables and 
listings using System/Organ/Class (SOC) and Preferred Term.  
Analyses of AEs will be performed for those events that are considered to be treatment 
emergent AEs (TEAEs), defined as any AE with onset or worsening of a pre-existing condition 
on or after the first administration of study medication through 30 days following last dose or 
any event considered drug-related by the investigator through the end of the study. 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.  
AEs will be summarized by patient incidence rates. In all tabulations, a patient may contribute 
only once to the count for a given AE preferred term.  
The number and percentage of patients with TEAEs will be summarized, as well as the number 
and percentage of patients with TEAEs assessed by the Investigator as at least possibly related 
to treatment. The number and percentage of patients with any Grade ≥ 3 TEAE will be 
tabulated in the same manner. In the event a patient experiences repeated episodes of the same 
TEAE, the event with the highest severity and/or strongest causal relationship to study 
treatment will be used for purposes of tabulations.  
Serious AEs (SAEs) will also be tabulated.  
No formal hypothesis-testing analysis of AE incidence rates will be performed.  
All AEs (treatment emergent and post-treatment) will be listed in patient data listings.  
Separate by-patient listings will be provided for the following: patient deaths, SAEs, and AEs 
leading to withdrawal. 


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7.2 
Adverse Event Monitoring 
Adverse event data collection and reporting, which are required as part of every clinical trial, 
are done to ensure the safety of subjects enrolled in the studies as well as those who will 
enroll in future studies. Adverse events are assessed in a routine manner at scheduled times 
during a trial. Additionally, certain adverse events must be reported in an expedited manner 
to allow for optimal monitoring of subject safety and care.  
 
All subjects experiencing an adverse event, regardless of its relationship to study therapy, 
will be monitored until:  
➢ the adverse event resolves or the symptoms or signs that constitute the adverse event return 
to baseline or is stable in the opinion of the investigator;  
➢ there is a satisfactory explanation other than the study therapy for the changes observed; or 
➢ death. 
 
7.3 
Definitions 
 
An adverse event is defined as any untoward or unfavorable medical occurrence in a human 
research study participant, including any abnormal sign (for example, abnormal physical 
exam, imaging finding or clinically significant laboratory finding), symptom, clinical event, 
or disease, temporally associated with the subject’s participation in the research, whether or 
not it is considered related to the subject’s participation in the research. 
Adverse events encompass clinical, physical and psychological harms. Adverse events occur 
most commonly in the context of biomedical research, although on occasion, they can occur 
in the context of social and behavioral research. Adverse events may be expected or 
unexpected. 
Acute Adverse Events  
Adverse events occurring in the time period from the signing of the informed consent, 
through 30 days post treatment will be considered acute adverse events.   
Severity  
Adverse events will be graded by a numerical score according to the defined NCI Common 
Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. Adverse events not 
specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to 
the general guidelines provided by the NCI CTCAE and as outlined below.   
• 
Grade 1: Mild  
• 
Grade 2: Moderate 
• 
Grade 3: Severe or medically significant but not immediately life threatening 
• 
Grade 4: Life threatening consequences 
• 
Grade 5: Death related to the adverse event 
 


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Serious Adverse Events  
OHRP and UTSW HRPP define serious adverse events as those events, occurring at any 
dose, which meets any of the following criteria:  
• 
results in death; 
• 
is life-threatening (places the subject at immediate risk of death from the event as it 
occurred); 
• 
results in inpatient hospitalization1,2 or prolongation of existing hospitalization; 
• 
results in a persistent or significant disability/incapacity; 
• 
results in a congenital anomaly/birth defect; or 
• 
based upon appropriate medical judgment, may jeopardize the subject’s health and may 
require medical or surgical intervention to prevent one of the other outcomes listed in this 
definition. 
 
 
Note: A “Serious adverse event” is by definition an event that meets any of the above 
criteria. Serious adverse events may or may not be related to the research project. A serious 
adverse event determination does not require the event to be related to the research. That is, 
both events completely unrelated to the condition under study and events that are expected in 
the context of the condition under study may be serious adverse events, independent of 
relatedness to the study itself. As examples, a car accident requiring >24 hour inpatient 
admission to the hospital would be a serious adverse event for any research participant; 
likewise, in a study investigating end-stage cancer care, any hospitalization or death which 
occurs during the protocol-specified period of monitoring for adverse and serious adverse 
events would be a serious adverse event, even if the event observed is a primary clinical 
endpoint of the study. 
1Pre-planned hospitalizations or elective surgeries are not considered SAEs. Note: If events 
occur during a pre-planned hospitalization or surgery, that prolong the existing 
hospitalization, those events should be evaluated and/or reported as SAEs.   
2 NCI defines hospitalization for expedited AE reporting purposes as an inpatient hospital 
stay equal to or greater than 24 hours. Hospitalization is used as an indicator of the 
seriousness of the adverse event and should only be used for situations where the AE truly 
fits this definition and NOT for hospitalizations associated with less serious events. For 
example: a hospital visit where a patient is admitted for observation or minor treatment (e.g. 
hydration) and released in less than 24 hours. Furthermore, hospitalization for 
pharmacokinetic sampling is not an AE and therefore is not to be reported either as a routine 
AE or in an expedited report. 
7.4 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs): 
The phrase “unanticipated problems involving risks to subjects or others” is found, but not 
defined in the HHS regulations at 45 CFR 46, and the FDA regulations at 21 CFR 
56.108(b)(1) and 21 CFR 312.66. For device studies, part 812 uses the term unanticipated 
adverse device effect, which is defined in 21 CFR 812.3(s). Guidance from the regulatory 


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agencies considers unanticipated problems to include any incident, experience, or outcome 
that meets ALL three (3) of the following criteria: 
• 
Unexpected in terms of nature, severity or frequency given (a) the research procedures that 
are described in the protocol-related documents, such as the IRB-approved research protocol 
and informed consent document; and (b) the characteristics of the subject population being 
studied;  
 
 
 
 
AND 
• 
Related or possibly related to participation in the research (possibly related means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); 
 
AND  
• 
Suggests that the research places subjects or others at greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. Note: According to OHRP, if the adverse event is serious, it would always 
suggest a greater risk of harm. 
 
Follow-up  
All adverse events will be followed up according to good medical practices.  
  
7.5  
Steps to Determine If a Serious Adverse Event Requires Expedited Reporting to  
 
 
the SCCC DSMC 
 
Step 1: Identify the type of adverse event using the NCI Common Terminology Criteria for Adverse 
Events (CTCAE v4.03).  
 
Step 2: Grade the adverse event using the NCI CTCAE v4.03. 
 
Step 3: Determine whether the adverse event is related to the protocol therapy.  
Attribution categories are as follows: 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE may NOT be related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
Note: This includes all events that occur within 30 days of the last dose of protocol treatment 
or until another anti-cancer therapy is started (whichever occurs sooner) (i.e., 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).  
 
Step 4: 
Determine the prior experience of the adverse event. Expected events 
are those that have been previously identified as resulting from administration of the 
treatment. An adverse event is considered unexpected, for expedited reporting purposes only, 
when either the type of event or the severity of the event is not listed in: 
• the current known adverse events listed in the Agent Information Section of this protocol (if 
applicable); 


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• the drug package insert (if applicable); 
• the current Investigator’s Brochure (if applicable) 
• the Study Agent(s)/Therapy(ies) Background and Associated Known Toxicities 
section of this protocol 
 
7.6  
Reporting SAEs and UPIRSOs to the Simmons Comprehensive Cancer Center 
(SCCC) Data Safety Monitoring Committee (DSMC) 
 
SAEs and UPIRSOs at all sites, which occur in research subjects on protocols for which the 
SCCC is the DSMC of record require reporting to the DSMC regardless of whether IRB 
reporting is required. All SAEs occurring during the protocol-specified monitoring period 
and all UPIRSOs should be submitted to the SCCC DSMC within 5 business days of the 
study team members awareness of the event(s). In addition, for participating centers other 
than UTSW, local IRB guidance should be followed for local reporting of serious adverse 
events or unanticipated problems. 
 
The UTSW study PI is responsible for ensuring SAEs/UPIRSOs are submitted to the SCCC 
DSMC Coordinator. This may be facilitated by the IIT project manager, study team, sub-site 
or other designee. Hardcopies or electronic versions of the eIRB Reportable Event report; FDA 
Form #3500A forms, or other sponsor forms, if applicable; and/or any other supporting 
documentation available should be submitted to the DSMC Coordinator.  The DSMC 
Coordinator forwards the information onto the DSMC Chairman who determines if immediate 
action is required.  Follow-up eIRB reports, and all subsequent SAE or UPIRSO 
documentation that is available are also submitted to the DSMC Chair who determines if 
further action is required. (See Appendix III of the SCCC DSMC Plan for a template Serious 
Adverse Event Form which may be utilized). 
  
 
If the event occurs on a multi-institutional clinical trial coordinated by the UTSW Simmons 
Comprehensive Cancer Center, the IIT Project Manager or designee ensures that all 
participating sites are notified of the event and resulting action, according to FDA guidance 
for expedited reporting. DSMC Chairperson reviews all SAEs and UPIRSOs upon receipt 
from the DSMC Coordinator.  The DSMC Chairperson determines whether action is required 
and either takes action immediately, convenes a special DSMC session (physical or 
electronic), or defers the action until a regularly scheduled DSMC meeting.  
 
 
Written reports to: 
Investigator:  David Gerber, MD 
                       David.Gerber@utsouthwestern.edu 
                       c/o Phase 1 Manager 
                       5323 Harry Hines Blvd, NB2.402 
                       Dallas, Texas  75390 
                       214-648-1578 fax 
 
UTSW SCCC Data Safety Monitoring Committee Coordinator 
Email: SCCDSMC@utsouthwestern.edu 
 


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Fax: 214-648-5949 or deliver to BLB.306 
 
Completed and signed SAE report forms must be emailed or faxed to:  
Email : Pharmacovigilance@karyopharm.com  
Fax: 1-617-334-7617 
 
UTSW Institutional Review Board (IRB) 
Submit a Reportable Event via eIRB with a copy of the final sponsor report 
as attached supporting documentation (for coordinating center per 
institutional guidelines) 
 
Karyopharm Pharmaceuticals, Inc. Serious Adverse Event Reporting 
The Investigator will report all AEs (including all non-serious AEs) to Karyopharm 
Pharmacovigilance every 6 months in the form of line-listings.  The line listings required 
template will be provided by Karyopharm Therapeutics, Inc. 
 
Serious Adverse Events 
The investigator/coordinator shall report all SAEs, regardless of the causal relationship to the 
Karyopharm medications, occurring after the patient has signed informed consent until 30 days 
after the patient has stopped study treatment or until another anti-cancer therapy is started 
(whichever occurs sooner) to the Karyopharm Pharmacovigilance within 24 hours of 
awareness. A Karyopharm SAE Report Form template is provided for this purpose. For 
reporting any SAE to Karyopharm Pharmacovigilance Department, a completed and signed 
(by the Investigator) SAE Report Form will be submitted by the sponsor investigator or 
designee to Karyopharm Pharmacovigilance: 
 
Completed and signed SAE report forms must be emailed or faxed to:  
Email : Pharmacovigilance@karyopharm.com  
Fax: 1-617-334-7617 
 
 
 
Any SAE observed after the 30-day follow-up period should only be reported to Karyopharm 
if the Investigator suspects that the SAE has causal relationship to study treatment.  
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.  New information, recurrences, complications, or 
Pharmacovigilance 
Department 


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progression of the initial SAE must be reported as follow-up to the initial report within 24 
hours of the Investigator receiving the follow-up information. 
Investigators are responsible as applicable for notifying their appropriate Health Authorities, 
Institutional Review Board or Local and Central Ethics Committees (EC) of all SAEs in 
accordance with local regulations.  
Karyopharm Therapeutics will report applicable SAEs to other applicable Regulatory 
Agencies and Investigators utilizing the Karyopharm product, as may be required. 
 
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. 
 
Reporting Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) to 
the UTSW HRPP 
 
UTSW reportable event guidance applies to all research conducted by or on behalf of UT 
Southwestern, its affiliates, and investigators, sites, or institutions relying on the UT 
Southwestern IRB. Additional reporting requirements apply for research relying on a non-UT 
Southwestern IRB. 
 
According to UTSW HRPP policy, UPIRSOs are incidents, experiences, outcomes, etc. that 
meet ALL three (3) of the following criteria: 
1. Unexpected in nature, frequency, or severity (i.e., generally not expected in a subject’s 
underlying condition or not expected as a risk of the study; therefore, not included in the 
investigator’s brochure, protocol, or informed consent document),AND 
2. Probably or definitely related to participation in the research, AND 
3. Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized.  Note: According to OHRP, if the adverse event is serious, it would always 
suggest a greater risk of harm. 
 
For purposes of this policy, UPIRSOs include unanticipated adverse device effects (UADEs) 
and death or serious injury related to a humanitarian use device (HUD).  
 
UPIRSOs must be promptly reported to the UTSW HRPP within 5 working days of 
study team awareness. 
 
For research relying on a non-UT Southwestern IRB (external, central, or single IRB): 
 
Investigators relying on an external IRB who are conducting research on behalf of UT 


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Southwestern or its affiliates are responsible for submitting LOCAL UPIRSOs to the UT 
Southwestern IRB within 5 working days of study team awareness. Investigators must report 
to their relying IRB according to the relying IRB’s policy. In addition, the external IRB’s 
responses or determinations on these local events must be submitted to the UT Southwestern 
IRB within 10 working days of receipt. 
 
Events NOT meeting UPIRSO criteria: 
 
Events that do NOT meet UPIRSO criteria should be tracked, evaluated, summarized, and 
submitted to the UTSW HRPP/IRB at continuing review. 
 
For more information on UTSW HRPP/IRB reportable event policy, see 
https://www.utsouthwestern.edu/research/hrpp/quality-assurance/ 
 
7.7  
Unblinding Procedures 
Subjects or study personnel will are not blinded in this open-label trial. 
7.8 
Stopping Rules 
It is agreed that, for reasonable cause, either the Sponsor-Investigator or drug provider, may 
terminate the Investigator’s participation in this study after submission of a written notice. 
The drug provider may terminate the study at any time upon immediate notice for any reason 
including the drug provider’s belief that discontinuation of the study is necessary for patient 
safety. 
 
8.0 
DRUG/TREATMENT INFORMATION 
8.1 
Study Drugs 
The following drug(s) will be used in this study: 
Selinexor: Provided as 20 mg coated, immediate-release tablets for oral administration. 
 
Docetaxel: Commercially available docetaxel will be used for this study.  It will be supplied 
in accordance with applicable local laws and regulations. 
Docetaxel 60 mg/m2 or 75 mg/m2 depending on the dose level will be administered per 
institutional practice (generally as a 1-hour IV infusion). The amount of docetaxel 
administered will be determined on Day 1 of each cycle, or per intuitional guidelines, by 
calculating the patient’s BSA. When calculating the dose of docetaxel, rounding the BSA 
according to institutional practice is permitted.  The dose of docetaxel may be capped at the 
dose corresponding to a BSA of 2 m2 if necessary to comply with institutional practices.  
Premedication for docetaxel will follow the local institutional standard of care guidelines. 
 
 
 
8.2 
Placebo or Control 


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No placebo or control is being proposed. Historical control data (docetaxel monotherapy) 
will be used to compare responses and toxicities. 
8.3 
Labeling 
Each wallet-size blister package selinexor tablets will be labeled in accordance with current 
International Conference on Harmonization (ICH), Good Clinical Practice (GCP), and specific 
regulatory requirements, e.g., FDA, Health Canada, EMA, etc.  Blister packages and/or 
containers for take-home use may require additional in-pharmacy labeling with take-home and 
patient-specific instructions (such as exact dose) depending on country-specific regulations or 
laws.  
All treatments will be labeled in accordance with current International Conference on 
Harmonization (ICH), Good Clinical Practices (GCP), FDA, HC, and EMA regulations and 
guidelines. Labels will include the medication name, storage conditions, and batch number, 
and will comply with language and legal requirements of Canada, EU, and the US. 
8.4 
Dosing Information 
Selinexor dosing will be done based on the dose level the patient is receiving, ranging from 40 
mg weekly to 100 mg weekly (see Table 3).  When Selinexor is administered on the same day 
as Docetaxel, it may be administered at any time prior to the start of infusion. 
8.5 
Dosing Instructions for Patients 
Study medications will be dosed according to the schedules provided below and in Table 1. 
For doses of oral medications to be taken on non-clinic days, patients will be provided with 
medication to take home.  
Selinexor should be given with at least 120 mL (4 ounces) of fluids (water, milk, etc.) For 
details of drug formulation, preparation, and administration, please refer to Appendix 2. 
Selinexor tablets should be swallowed whole (not crushed) to prevent an increased risk of 
dermatologic toxicity if the powder comes in contact with skin. 
 
9.0 
CORRELATIVES/SPECIAL STUDIES 
9.1 
Sample Collection, Storage, and Shipping 
Information on sample collection, storage and shipping will be provided in the Lab Manual. 
9.2 
Pharmacodynamic Assessments 
Predictive and Pharmacodynamic Biomarkers:  If applicable, archival tumor tissue (10 
unstained slides plus 1 H+E slide) will be evaluated for predictive and pharmacodynamic 
biomarkers.  These may include but are not limited to the following:   YAP1, FSTL5, LATS 
1/2, and nuclear IkB expression.  Additionally, in patients for whom a post-progression biopsy 
is performed as standard of care, additional tumor tissue submission is requested.  These 
analyses are designed to identify early biomarkers predictive of benefit of selinexor and also 


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to demonstrate the in vivo specificity for molecular targeting of XPO1 cargo function via 
pharmacological blockade by selinexor. 
Blood draws for PD analysis will be performed pre-dose and 4 hours post-dose on Cycle 1 Day 
-7, Cycle 1 Day 1 pre-dose and 4 hours post-dose on Cycle 2 Day 1 and at end of treatment. 
10.0 
STATISTICAL CONSIDERATIONS 
This is a Phase 1/2 study.  UT Southwestern will be the coordinating center for this study; 
UT Southwestern will be responsible for registering patients and for maintaining a complete 
database of the study information.  
The design of this Phase 1/2 trial is described above; along with the definition of MTD and 
the rules for dose escalation.  
The toxicities observed at each dose level will be summarized in terms of type (organ 
affected or laboratory determination such as absolute neutrophil count), severity (by NCI 
CTCAE v4.0 and nadir or maximum values for the laboratory measures), time of onset (i.e., 
cycle number), duration, and reversibility or outcome.   
 
Tables will be created to summarize these toxicities and side effects by dose and by cycle. 
Toxicities will be reported for all patients receiving study drug. Baseline information (e.g., 
the extent of prior therapy) and demographic information will be presented to describe the 
patients treated in this Phase I study.  All responses will be reported.  Survival and time to 
failure will be summarized with Kaplan-Meier plots to describe the outcome of patients 
treated on this protocol. 
10.1 
Study Design/Study Endpoints 
 
10.2 
Sample Size and Accrual 
In the docetaxel plus selinexor cohort, depending on cohort expansion requirements, a total 
of 9-24 patients will be accrued to the dose-escalation phase 1 pilot trial.  A total of 35 
patients will be enrolled to this expansion cohort, for a total of 31-46 patients. For the 
selinexor monotherapy cohort, up to 28 patients will be accrued to the recommended 
monotherapy regimen (either 80 mg PO weekly or 60 mg PO twice weekly). Because the 
trial population will be drawn from a multi-institution base, it is anticipated that accrual will 
be completed over 36 months. 
In the docetaxel plus selinexor expansion cohort, enrollment of 35 patients will provide 90% 
power to detect an improvement in the primary endpoint of radiographic response rate from 
10% (historical control) to 35%, with a two-sided alpha of 0.05.  The sample size estimate is 
based on the exact one-sample binomial test for proportions. 
Of note, the trial is taking a conservative approach to generating assumptions for the primary 
endpoint analysis.  While reported response rates to docetaxel monotherapy have been as low 


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as 0% in KRAS mutant NSCLC,9 we are employing a value more closely resembling that in 
unselected NSCLC populations.10 
 
10.3 
Data Analyses 
 
10.3.1 Safety Population 
The safety population includes patients who have received at least one dose of docetaxel and 
at least one dose of selinexor. 
 
10.4 
Efficacy Analysis 
Tumor size will be assessed at baseline and every 2 cycles (ie, after 7 weeks for first 2 cycles, 
and then every 6 weeks) during the treatment period using the RECIST v1.1 criterion. 
 
10.5  Pharmacodynamic Variables 
As an exploratory endpoint, treatment efficacy (RR, PFS) will be correlated with correlative 
biomarkers. 
 
10.6  Safety Analysis 
The NCI CTCAE v4 will be used to collect data regarding safety events 
 
10.7 Laboratory Data 
The actual value and change from baseline for each on study evaluation will be summarized 
for each clinical laboratory parameter, including hematology and clinical chemistry, by arm, 
and for all study patients combined. In the event of repeat values, the last non-missing value 
per study day/time will be used.  
Severity of select clinical lab measures will be determined using CTCAE criteria (i.e., those 
measures that have a corresponding CTCAE grade classification). Labs with CTCAE Grades 
≥ 3 will be presented in a data listing. Shift tables that present changes from baseline to worst 
on-study values relative to CTCAE classification ranges will be produced.  
10.8 Vital Signs and Physical Examinations 
The actual value and change from baseline to each on-study evaluation will be summarized for 
vital signs for all study patients combined. By-patient listings of vital sign measurements will 
be presented in data listings.  
Physical examination results at screening will be summarized; all other abnormal physical 
examination data will be recorded. All examination findings will be presented in a data listing.  
 
 
 
 


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11.0 
STUDY MANAGEMENT 
 
11.1 
Conflict of Interest 
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by the UTSW COI Committee and IRB according to UTSW Policy on 
Conflicts of Interest.  All investigators will follow the University conflict of interest policy. 
 
11.2 
Institutional Review Board (IRB) Approval and Consent 
It is expected that the IRB will have the proper representation and function in accordance 
with federally mandated regulations. The IRB must approve the consent form and protocol. 
 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), and should adhere to Good Clinical Practice (GCP) and 
to ethical principles that have their origin in the Declaration of Helsinki. 
 
 
Before recruitment and enrollment onto this study, the subject will be given a full 
explanation of the study and will be given the opportunity to review the consent form. Each 
consent form must include all the relevant elements currently required by the FDA 
Regulations and local or state regulations. Once this essential information has been provided 
to the subject and the investigator is assured that the subject understands the implications of 
participating in the study, the subject will be asked to give consent to participate in the study 
by signing an IRB-approved consent form. 
 
Prior to a patient’s participation in the trial, the written informed consent form should be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion. 
 
 
11.3  Required Documentation (for multi-site studies) 
Before the study can be initiated at any sub-site, the following documentation must be 
provided to the Phase 1 Regulatory Associate, Ashish Shaha. 
 
• A copy of the official IRB approval letter for the protocol and informed consent 
• IRB membership list or Federal-wide Assurance letter 
• CVs and medical licensure for the principal investigator and any associate investigators 
who will be involved in the study 
• Form FDA 1572 appropriately filled out and signed with appropriate documentation 
(NOTE: this is required if {institution} holds the IND. Otherwise, the affiliate 
Investigator’s signature on the protocol is sufficient to ensure compliance) 
• A copy of the IRB-approved consent form 
• CAP and CLIA Laboratory certification numbers and institution lab normal values 
• Executed clinical research contract (or filed per institutional guidelines) 


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11.4 
Registration/Randomization Procedures 
 
 
For UT Southwestern Medical Center: 
The coordinating center for the trial will be UT Southwestern.  Patients who are candidates 
for registration into the study will be evaluated for eligibility by the Investigator once consent 
has been obtained to ensure that the inclusion and exclusion criteria have been satisfied and 
that the patient is eligible for participation in this clinical study.  The phase 1 research 
manager will confirm eligibility for all patients prior to receipt of the first dose of study drug.  
The completed patient eligibility verification registration form (Appendix 6) and 
inclusion/exclusion checklist (Appendix 7) will be provided to the phase 1 manager for 
review.  The manager will complete the dose level and patient ID assignment on the patient 
eligibility verification registration form (Appendix 6) and provide this completed form back 
to the study coordinator.   The site should maintain a log of all patients who are consented 
but do not qualify for the study or who do not receive study drug.  The reason for 
disqualification should be documented on the log. 
 
For Sub-Site Management: 
The coordinating center for the trial will be UT Southwestern.  Patients who are candidates 
for registration into the study will be approved by UTSW after confirmation of eligibility of 
the inclusion and exclusion criteria have been satisfied.  UTSW will confirm eligibility for all 
patients prior to receipt of the first dose of study drug.    
 
For patients who pass screening the following items will be required for registration: 
• 
copy of the signed patient treatment consent 
• 
completed patient eligibility verification registration form (Appendix 6)  
• 
completed inclusion/exclusion checklist (Appendix 7)  
• 
source documentation (which includes, but not limited to, pathology, labs, 
 
progress notes, etc) that confirms all eligibility items on the inclusion 
      -exclusion checklist has been met 
 
This information will be provided no later than 48 hours prior to the planned cycle 1 day 1 
treatment to allow adequate time for review.  These items can be faxed with the provided 
cover sheet (located in the study binder) to:  
 
  
 
 
  
Phase 1 QA Coordinator or Designee 
 
  
UT Southwestern 
 
  
Fax 214-648-1578  
 
The Phase 1 MQA Coordinator or Designee will complete the dose level and patient ID 
assignment on the patient eligibility verification registration form  and provide this 
completed form back within 48 hours of receipt of the package.    
 


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The site should maintain a log of all patients who are consented but do not qualify for the 
study or who do not receive study drug.  The reason for disqualification should be 
documented on the log. 
 
 
Upon confirmation of eligibility and enrollment as per the afore-mentioned instructions, the 
subject will be assigned a secondary number in the order of enrollment. For example, subject 
001 will become 001-01 upon enrollment. If subject 002 screen fails, and subject 003 is the 
next subject enrolled, subject 003 will become 003-02 and so-on.  
 
Note: For multi-center studies, suggest assigning a lead-in identifier for each site and 
defining in the protocol. For example, for a study which includes two sites, the first patient 
consented and enrolled at the first site will be subject 01-001-01. The second subject enrolled 
at the second site might be 02-003-02.] 
 
Each newly consented subject should be numbered using the schema provided above. Upon 
registration, the registrar will assign the additional registration/randomization code according 
to the numbering schema outlined above, which should then be entered as the patient study id 
in Velos upon updating the status to enrolled. 
 
The numbering schema should clearly identify the site number; the sequential number of the 
subject enrolled as well as the status of the subjects enrolled so that the number of subjects 
consented versus the number of subjects actually enrolled may be easily identified.   
11.5 
Patient Updates 
The sub-sites will be invited to participate in a monthly meeting teleconference conducted by 
the Phase 1 manager and Principal Investigator to discuss all active treatment patients.   In 
addition both UT Southwestern and all participating sub-sites will be expected to provide a 
weekly update in writing or via email to the phase 1 manager . The patient updates should 
include, but not limited to, the following information: 
 
Pt initials:   
Study ID: 
Cohort: 
Dose: 
Visit: (cycle/day) 
Date of visit:  
Summary of visit including AE’s with grades and attributions, labs, and any 
other pertinent information 
 
 
11.6   Data Management and Monitoring/Auditing 
The UTSW Simmons Comprehensive Cancer Center (SCC) Data Safety Monitoring 
Committee (DSMC) is responsible for monitoring data quality and patient safety for all 
UTSW SCCC clinical trials.  As part of that responsibility, the DSMC reviews all local 
serious adverse events and UPIRSOs in real time as they are reported.  The quality assurance 
activity for the Clinical Research Office provides for periodic auditing of clinical research 


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documents to ensure data integrity and regulatory compliance.  A copy of the DSMC plan is 
available upon request. 
The SCCC DSMC meets quarterly and conducts annual comprehensive reviews of ongoing 
clinical trials, for which it serves as the DSMC of record. The QAC works as part of the 
DSMC to conduct regular audits based on the level of risk. Audit findings are reviewed at the 
next available DSMC meeting.  In this way, frequency of DSMC monitoring is dependent 
upon the level of risk.  Risk level is determined by the DSMC Chairman and a number of 
factors such as the phase of the study; the type of investigational agent, device or intervention 
being studied; and monitoring required to ensure the safety of study subjects based on the 
associated risks of the study. Protocol-specific DSMC plans must be consistent with these 
principles. 
In order to facilitate remote source to case report form verification, the Simmons 
Comprehensive Cancer Center study team will require other institutions participating in this 
trial as sub-sites to enter data into the selected EDC system and upload selected de-identified 
source materials when instructed.  
 
Trial monitoring will be conducted according to the study specific monitoring plan. For 
guidance on creating a monitoring plan, refer to the UTSW SCCC IIT Management Manual.   
 
 
 
 
The UTSW Simmons Comprehensive Cancer Center (SCCC) Data Safety Monitoring 
Committee (DSMC) is responsible for monitoring data quality and patient safety for all 
UTSW SCCC clinical trials.  As part of that responsibility, the DSMC reviews all serious 
adverse events and UPIRSOs in real time as they are reported and reviews adverse events on 
a quarterly basis.  The quality assurance activity for the Clinical Research Office provides for 
periodic auditing of clinical research documents to ensure data integrity and regulatory 
compliance.  A copy of the DSMC plan is available upon request. 
 
The SCCC DSMC meets quarterly and conducts annual comprehensive reviews of ongoing 
clinical trials, for which it serves as the DSMC of record. The Quality Assurance Coordinator 
(QAC) works as part of the DSMC to conduct regular audits based on the level of risk. Audit 
findings are reviewed at the next available DSMC meeting.  In this way, frequency of DSMC 
monitoring is dependent upon the level of risk.  Risk level is determined by the DSMC 
Chairman and a number of factors such as the phase of the study; the type of investigational 
agent, device or intervention being studied; and monitoring required to ensure the safety of 
study subjects based on the associated risks of the study. Protocol-specific DSMC plans must 
be consistent with these principles.  
 
11.7 
Adherence to the Protocol 
 
Except for an emergency situation, in which proper care for the protection, safety, and well-
being of the study subject requires alternative treatment, the study shall be conducted exactly 
as described in the approved protocol.  


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11.7.1  Exceptions (also called single-subject exceptions or single-subject waivers): include 
any departure from IRB-approved research that is not due to an emergency and is: 
• intentional on part of the investigator; or 
• in the investigator’s control; or 
• not intended as a systemic change (e.g., single-subject exceptions to eligibility 
[inclusion/exclusion] criteria) 
 Reporting requirement*: Exceptions are non-emergency deviations that require 
prospective IRB approval before being implemented. Call the IRB if your request is 
urgent. If IRB approval is not obtained beforehand, this constitutes a major deviation. For 
eligibility waivers, studies which utilize the SCCC-DSMC as the DSMC of record must 
also obtain approval from the DSMC prior to submitting to IRB for approval.  
11.7.2 Emergency Deviations: include any departure from IRB-approved research that is 
necessary to:  
• avoid immediate apparent harm, or 
• protect the life or physical well-being of subjects or others 
 Reporting requirement*: Emergency deviations must be promptly reported to the IRB 
within 5 working days of occurrence. 
  
Serious Noncompliance (formerly called major deviations or violations): include any 
departure from IRB-approved research that: 
• 
Increase risk of harm to subjects; and/or 
• 
 
adversely affects the rights, safety, or welfare of subjects (any of which may also 
be an unanticipated problem); and/or  
• 
adversely affects the integrity of the data and research (i.e., substantially 
compromises the integrity, reliability, or validity of the research) 
 Reporting requirement*: Serious Noncompliance must be promptly reported 
tothe IRB within 5 working days of discovery. 
 
3.1.1 
Continuing Noncompliance: includes a pattern of repeated    noncompliance (in 
one or more protocols simultaneously, or over a period of time) which continues 
after initial discovery, including inadequate efforts to take or implement corrective 
or preventive action within a reasonable time frame. 
 Reporting requirement*: Continuing Noncompliance must be promptly 
reported to  
the IRB within 5 working days of discovery. 
 
11.6.5  
Noncompliance (that is neither serious nor continuing; formerly called 
minor deviations) any departure from IRB-approved research that: 
 
• Does not meet the definition of serious noncompliance or continuing 
noncompliance 
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continuing  should be tracked and summarized the next IRB continuing 
review, or the notice of study closure- whichever comes first.. 
 
*Reporting Requirements reflect UTSW HRPP/IRB guidelines; participating sites should 
follow the reporting guidelines for their IRB of record 
 
11.8 
Amendments to the Protocol 
Should amendments to the protocol be required, the amendments will be originated and 
documented by the Principal Investigator.  A summary of changes document outlining 
proposed changes as well as rationale for changes, when appropriate, is highly 
recommended.  When an amendment to the protocol substantially alters the study design or 
the potential risk to the patient, a revised consent form might be required.  
 
The written amendment, and if required the amended consent form, must be sent to 
the IRB for approval prior to implementation.  
11.9  Record Retention 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and approval, 
signed patient consent forms). 
 
Source documents include all recordings of observations or notations of clinical activities and 
all reports and records necessary for the evaluation and reconstruction of the clinical research 
study. 
 
Government agency regulations and directives require that the study investigator retain all 
study documentation pertaining to the conduct of a clinical trial. In the case of a study with a 
drug seeking regulatory approval and marketing, these documents shall be retained for at 
least two years after the last approval of marketing application in an International Conference 
on Harmonization (ICH) region. In all other cases, study documents should be kept on file 
until three years after the completion and final study report of this investigational study. 
11.10 Obligations of the Investigator 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki. The Principal Investigator is responsible for personally overseeing the treatment of 
all study patients. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol and 
all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during and after 
study completion. 
 
The Principal Investigator at each institution or site will be responsible for assuring that all 
the required data will be collected and entered onto the Case Report Forms. Periodically, 
monitoring visits may be conducted and the Principal Investigator will provide access to 
his/her original records to permit verification of proper entry of data. At the completion of 


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the study, all case report forms will be reviewed by the Principal Investigator and will require 
his/her final signature to verify the accuracy of the data. 
 
12.0  REFERENCES 
 
 
1. 
Arango NP, K. E, Zhao M, et al. Nuclear export inhibitor selinexor (KPT-330) 
demonstrates anti-tumor efficacy alone and in combination with chemotherapy in 
multiple breast cancer models. [abstract]. In: Proceedings of the 107th Annual Meeting 
of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. 
Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3075. 
2. 
Miyake T, Pradeep S, Wu SY, et al. XPO1/CRM1 Inhibition Causes Antitumor Effects 
by Mitochondrial Accumulation of eIF5A. Clin Cancer Res. 2015;21(14):3286-3297. 
3. 
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(2):228-247. 
4. 
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. 
5. 
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 
1987;317:1098Mutka 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. 
6. 
Blumenschein GR, Jr., Saintigny P, Liu S, et al. Comprehensive biomarker analysis 
and final efficacy results of sorafenib in the BATTLE trial. Clin Cancer Res. 
2013;19(24):6967-6975. 
7. 
AstraZeneca provides update on Phase III trial of Selumetinib in non-small cell lung 
cancer.  https://www.astrazeneca.com/media-centre/press-releases/2016/AstraZeneca-
provides-update-on-Phase-III-trial-of-Selumetinib-in-non-small-cell-lung-cancer-
09082016.html. Accessed September 13, 2016. 
8. 
Chen CI, Gutierrez M, Siegel DS, et al. Selinexor demonstrates marked synergy with 
dexamethasone (Sel-Dex) in pre-clinical models and in patients with heavily pretreated 
refractory multiple myeloma. 2014 ASH Annual Meeting, December 06 – 09, 2014, 
San Francisco. 
9. 
Tai YT, Landesman Y, Acharya C, et al. CRM1 inhibition induces tumor cell 
cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular 
mechanisms and therapeutic implications. Leukemia. 2014;28(1):155-65. 
10. 
Turner JG, Dawson J, Emmons MF, Cubitt CL, Kauffman M, Shacham S, Hazlehurst 
LA, Sullivan DM. CRM1 Inhibition Sensitizes Drug Resistant Human Myeloma Cells 
to Topoisomerase II and Proteasome Inhibitors both In Vitro and Ex Vivo. J Cancer. 
2013 Sep 10;4(8):614-25. 
11. 
Turner JG, Dawson J, Cubitt CL, Baz R, Sullivan DM. Inhibition of CRM1-dependent 
nuclear export sensitizes malignant cells to cytotoxic and targeted agents. Semin 
Cancer Biol. 2014 Aug;27C:62-73. 
12. 
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. 
CA Cancer J Clin. 2011;61(2):69-90. 
13. 
Ettinger DS, Akerley W, Bepler G, et al. Non-small cell lung cancer. J Natl Compr 
Canc Netw. 2010;8(7):740-801. 
14. 
Roberts PJ, Stinchcombe TE. KRAS mutation: should we test for it, and does it matter? 
J Clin Oncol. 2013;31(8):1112-1121. 


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15. 
Kim J et al.  XPO1-dependent nuclear export is a druggable vulnerability in KRAS 
mutant lung cancer.  Nature.  In press. 
16. 
Miyake TM, Pradeep S, Zand B, Dalton HJ, Wen Y, Armaitz Pena GN, Kauffman M, 
McCauley D, Shacham S, Wiktorowicz JE, Sood AK. Abstract 5541: therapeutic 
targeting of CRM1 in ovarian cancer. Cancer Res. 2013;73:5541. 
17. 
NCCN 
Guidelines 
for 
Supportive 
Care.  
https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#supportive. 
Accessed December 6, 2017. 
18. 
Janne PA, Shaw AT, Pereira JR, et al. Selumetinib plus docetaxel for KRAS-mutant 
advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, 
phase 2 study. Lancet Oncol. 2013;14(1):38-47. 
19. 
Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed 
versus docetaxel in patients with non-small-cell lung cancer previously treated with 
chemotherapy. J Clin Oncol. 2004;22(9):1589-1597. 
20. 
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. 
 
APPENDICES 
Appendix 1: Eastern Cooperative Oncology Group Performance Status 
Criteria 
 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity. Fully active, able to carry on all pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically 
strenuous activity, but ambulatory and able to carry out work 
of a light or sedentary nature (e.g., light housework, office 
work). 
2 
In bed < 50% of the time. Ambulatory and capable of all 
self-care, but unable to carry out any work activities. Up and 
about more than 50% of waking hours. 
3 
In bed > 50% of the time. Capable of only limited self-care, 
confined to bed or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any 
self-care. Totally confined to bed or chair. 
5 
Dead. 
Source: Oken MM et al  


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Appendix 2: Selinexor Formulation and Administration 
Description of Selinexor (KPT-330) 
Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor specifically 
blocks nuclear export by binding to the nuclear export protein XPO1. 
The chemical name is: (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-
(pyrazin-2-yl)acrylohydrazide 
The molecular formula is: C17H11F6N7O.  
The molecular weight is: 443.31. 
Form 
Selinexor will be supplied and administered as coated, immediate-release oral tablets in 20 mg 
tablets in wallet-sized blister packs of 12 tablets each.  
Storage and Stability 
Selinexor should be stored in a locked and secured area with access restricted to the site staff 
pharmacist or designee(s) at or below 30˚C (86˚F). Room temperature storage is 
recommended, refrigerated is acceptable. Tablets should not be stored frozen. 
Selinexor tablets are currently in on-going stability studies. The expiry will be based on 
concurrent stability studies and extended during the course of the study as further stability data 
becomes available. 
Handling 
Qualified personnel, familiar with procedures that minimize undue exposure to themselves and 
the environment, should undertake the preparation, handling, and safe disposal of the 
chemotherapeutic agent in a self-contained and protective environment. 
Availability 
Selinexor is an investigational agent and will be supplied free-of-charge from Karyopharm 
Therapeutics, Inc. 
Preparation 
No special preparation required. 
NOTE: Tablets of selinexor should not be crushed because of increased risk of dermatologic 
toxicity if powder comes in contact with skin. 
Administration 
Selinexor will be provided as tablets to be administered by mouth. Selinexor is to be taken 
within 30 minutes of solid food consumption together with at least 120 mL (4 ounces) of fluids 
(water, milk, etc.). 


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Ordering 
Drug order forms with all the needed contact information will be provided at the start of the 
trial, along with recommended initial and resupply stock orders. Orders submitted via e-mail 
will be filled within 5 business days of receipt.  
Accountability 
The investigator, or a responsible party designated by the investigator, must maintain a 
careful record of the inventory and disposition of the agent (investigational or free of charge) 
using the NCI Drug Accountability Record or another comparable drug accountability form. 
(see the Cancer Therapy Evaluation Program [CTEP] website at http://ctep.cancer.gov/ 
protocolDevelopment for the “Policy and Guidelines for Accountability and Storage of 
Investigational Agents” or to obtain a copy of the drug accountability form). 
Destruction and Return 
At the end of the study, unused supplies of selinexor should be destroyed and documented 
according to institutional policies.  
 


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Appendix 3: 
RECIST v1.1 criteria1 
EVALUATION OF LESIONS 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable 
as 
follows: 
 
Measurable 
 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter 
in the plane of measurement is to be recorded) with a minimum size of: 
1. 10 mm by CT scan (CT scan slice thickness no greater than 5 mm) 
2. 10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable) 
3. 20 mm by chest x-ray 
 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a 
lymph 
node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). Lymph nodes merit special mention since they 
are normal anatomical structures which may be visible by imaging even if not involved by 
tumor. Pathological nodes which are defined as measurable and may be identified as target 
lesions must meet the criterion of a short axis of ≥  15 mm by CT scan. Only the short axis 
of these nodes will contribute to the baseline sum. The short axis of the node is the diameter 
normally used by radiologists to judge if a node is involved by solid tumor. Nodal size is 
normally reported as two dimensions in the plane in which the image is obtained (for CT 
scan this is almost always the axial plane; for MRI the plane of acquisition may be axial, 
saggital or coronal). The smaller of these measures is the short axis. For example, an 
abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm and 
qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as 
the node measurement. All other pathological nodes (those with short axis ≥  10 mm but < 
15 mm) should be considered non-target lesions. Nodes that have a short axis < 10 mm are 
considered non-pathological and should not be recorded or followed. 
 
Non-Measurable 
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic 
involvement of skin or lung, abdominal masses/abdominal organomegaly identified by 
physical exam that is not measurable by reproducible imaging techniques. 
 
BASELINE DOCUMENTATION OF ‘TARGET’ AND ‘NON-TARGET’ LESIONS 


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When more than one measurable lesion is present at baseline all lesions up to a maximum 
of five lesions total (and a maximum of two lesions per organ) representative of all involved 
organs should be identified as target lesions and will be recorded and measured at baseline 
(this means in instances where patients have only one or two organ sites involved a 
maximum of two and four lesions respectively will be recorded). Target lesions should be 
selected on the basis of their size (lesions with the longest diameter), be representative of 
all involved organs, but in addition should be those that lend themselves to reproducible 
repeated measurements. It may be the case that, on occasion, the largest lesion does not 
lend itself to reproducible measurement in which circumstance the next largest lesion 
which can be measured reproducibly should be selected. A sum of the diameters (longest 
for non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculated 
and reported as the baseline sum diameters. If lymph nodes are to be included in the sum, 
then as noted above, only the short axis is added into the sum. The baseline sum diameters 
will be used as reference to further characterize any objective tumor regression in the 
measurable dimension of the disease. All other lesions (or sites of disease) including 
pathological lymph nodes should be identified as non-target lesions and should also be 
recorded at baseline. Measurements are not required and these lesions should be followed 
as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’(more details to follow). 
In addition, it is possible to record multiple nontarget lesions involving the same organ as 
a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ or 
‘multiple liver metastases’). 
 
RESPONSE CRITERIA 
Evaluation of Target Lesions 
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) must have reduction in short axis to < 10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target 
lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more 
new lesions is also considered progression). 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
 
Special Notes on the Assessment of Target Lesions 
Lymph nodes 
Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded (measured in the same anatomical plane as the baseline 
examination), even if the nodes regress to below 10 mm on study. This means that when 
lymph nodes are included as target lesions, the ‘sum’ of lesions may not be zero even if 
complete response criteria are met, since a normal lymph node is defined as having a short 
axis of < 10 mm. Case report forms or other data collection methods may therefore be 


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designed to have target nodal lesions recorded in a separate section where, in order to 
qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and PD, the 
actual short axis measurement of the nodes is to be included in the sum of target lesions. 
 
Target lesions that become ‘too small to measure’ 
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their 
actual measurements recorded at each subsequent evaluation, even when very small (eg, 2 
mm). However, sometimes lesions or lymph nodes which are recorded as target lesions at 
baseline become so faint on CT scan that the radiologist may not feel comfortable assigning 
an exact measure and may report them as being ‘too small to measure’. When this occurs 
it is important that a value be recorded on the case report form. If it is the opinion of the 
radiologist that the lesion has likely disappeared, the measurement should be recorded as 
0 mm. If the lesion is believed to be present and is faintly seen but too small to measure, a 
default value of 5 mm should be assigned (Note: It is less likely that this rule will be used 
for lymph nodes since they usually have a definable size when normal and are frequently 
surrounded by fat such as in the retroperitoneum; however, if a lymph node is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be 
assigned in this circumstance as well). This default value is derived from the 5 mm CT 
slice thickness (but should not be changed with varying CT slice thickness). The 
measurement of these lesions is potentially non-reproducible, therefore providing this 
default value will prevent false responses or progressions based upon measurement error. 
To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm. 
 
Lesions that split or coalesce on treatment 
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions 
should be added together to calculate the target lesion sum. Similarly, as lesions coalesce, 
a plane between them may be maintained that would aid in obtaining maximal diameter 
measurements of each individual lesion. If the lesions have truly coalesced such that they 
are no longer separable, the vector of the longest diameter in this instance should be the 
maximal longest diameter for the ‘coalesced lesion’. 
 
Evaluation of Non-Target Lesions 
This section provides the definitions of the criteria used to determine the tumor response 
for the group of non-target lesions. While some non-target lesions may actually be 
measurable, they need not be measured and instead should be assessed only qualitatively 
at the time points specified in the protocol. 
Complete Response (CR): Disappearance of all non-target lesions and normalization of 
tumor marker level. All lymph nodes must be non-pathological in size (< 10mm short axis). 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of 
tumor marker level above the normal limits. 
Progressive Disease (PD): Unequivocal progression (see comments below) of existing 
nontarget lesions. (Note: the appearance of one or more new lesions is also considered 
progression). 
 
Special Notes on Assessment of Progression of Non-Target Disease 


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The concept of progression of non-target disease requires additional explanation as 
follows: 
 
When the patient also has measurable disease 
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, 
there must be an overall level of substantial worsening in non-target disease such that, even 
in presence of SD or PR in target disease, the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy (further details below). A modest ‘increase’ 
in the size of one or more non-target lesions is usually not sufficient to qualify for 
unequivocal progression status. The designation of overall progression solely on the basis 
of change in non-target disease in the face of SD or PR of target disease will therefore be 
extremely rare. 
When the patient has only non-measurable disease 
This circumstance arises in some trials when it is not a criterion of study entry to have 
measurable disease. The same general concepts apply here as noted above, however, in this 
instance there is no measurable disease assessment to factor into the interpretation of an 
increase in non-measurable disease burden. Because worsening in non-target disease 
cannot be easily quantified (by definition: if all lesions are truly non-measurable) a useful 
test that can be applied when assessing patients for unequivocal progression is to consider 
if the increase in overall disease burden based on the change in non-measurable disease is 
comparable in magnitude to the increase that would be required to declare PD for 
measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable 
lesion). Examples include an increase in a pleural effusion from ‘trace’ to ‘large’, an 
increase in lymphangitic disease from localized to widespread, or may be described in 
protocols as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, 
the patient should be considered to have had overall PD at that point. While it would be 
ideal to have objective criteria to apply to non-measurable disease, the very nature of that 
disease makes it impossible to do so; therefore the increase must be substantial. 
 
New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some 
‘new’ bone lesions may be simply healing or flare of pre-existing lesions). This is 
particularly important when the patient’s baseline lesions show partial or complete 
response. For example, necrosis of a liver lesion may be reported on a CT scan report as a 
‘new’ cystic lesion, which it is not. A lesion identified on a follow-up study in an 
anatomical location that was not scanned at baseline is considered a new lesion and will 
indicate disease progression. An example of this is the patient who has visceral disease at 
baseline and while on study has a CT or MRI brain ordered which reveals metastases. The 
patient’s brain metastases are considered to be evidence of PD even if he/she did not have 
brain imaging at baseline. 
 


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If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm 
there is definitely a new lesion, then progression should be declared using the date of the 
initial scan. While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in 
assessment of progression (particularly possible ‘new’ disease). New lesions on the basis 
of FDG-PET imaging can be identified according to the following algorithm: 
1. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion. 
2. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the 
positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-
up 
CT scans are needed to determine if there is truly progression occurring at that site (if so, 
the 
date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-
PET 
at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on 
the 
basis of the anatomic images, this is not PD. 
 
Response Assessment 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the study treatment 
until the end of treatment taking into account any requirement for confirmation. The 
patient’s best overall response assignment will depend on the findings of both target and 
non-target disease and will also take into consideration the appearance of new lesions. 
Furthermore, depending on the nature of the study and the protocol requirements, it may 
also require confirmatory measurement. 
 
Time Point Response 
It is assumed that at each protocol specified time point, a response assessment occurs. The 
Table below provides a summary of the overall response status calculation at each time 
point for patients who have measurable disease at baseline. When patients have non-
measurable (therefore non-target) disease only, a different Table is to be used. 
 


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Best Overall Response 
Best response determination of complete or partial response requires confirmation: 
Complete or partial responses may be claimed only if the criteria for each are met at a 
subsequent time point of ≥ 4 weeks later.  
 
Special note on response assessment: When nodal disease is included in the sum of target 
lesions and the nodes decrease to ‘normal’ size (< 10 mm), they may still have a 
measurement reported on scans. This measurement should be recorded even though the 
nodes are normal in order not to overstate progression should it be based on increase in 
size of the nodes. As noted earlier, this means that patients with CR may not have a total 
sum of ‘zero’ on the case report form (CRF). 
 
 
 
 


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Confirmation Scans 
 
Verification of Response: To be assigned a status of CR or PR, changes in tumor 
measurements must be confirmed by consecutive repeat assessments that should be 
performed no less than 28 days after the criteria for response are first met. For this study, 
the next scheduled tumor assessment can meet this requirement. 
 
Verification of Progression: Progression of disease should be verified in cases where 
progression is equivocal. If repeat scans confirm PD, then progression should be declared 
using the date of the initial scan. If repeat scans do not confirm PD, then the subject is 
considered to not have progressive disease. 
 
 
 
 
 

ICF_001.pdf: 
Cover Page 
 
Official Title: 
An Investigator-sponsored, Phase 1/2 Trial of the Oral XPO1 
Inhibitor Selinexor (KPT-330) Monotherapy and in Combination 
With Docetaxel for Previously Treated, Advanced KRAS Mutant 
Non-small Cell Lung Cancer (NSCLC) 
NCT03095612 
 
Document Date:  01/30/2023  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


The University of Texas Southwestern Medical Center   
Parkland Health & Hospital System   
Children’s Medical Center   
Retina Foundation of the Southwest   
Texas Scottish Rite Hospital for Children   
Texas Health Presbyterian Hospital Dallas   
 
CONSENT TO PARTICIPATE IN RESEARCH   
 
Title of Research:  
An Investigator-Sponsored Phase 1/2 trial of the oral   
XPO1 inhibitor selinexor (KPT-330) monotherapy and in   
combination with docetaxel for previously treated,   
advanced KRAS mutant non-small cell lung cancer   
(NSCLC)   
 
Sponsor:  
UT Southwestern Medical Center   
 
 
Sponsor-Investigator:  
David E. Gerber, MD   
 
Drug Supplier/Funding Provider:  Karyopharm Therapeutics Inc.   
 
 
You may call the study doctors or research personnel during regular office hours at 214- 
648-4180.  At other times, you may call them at 214-645-4673.   
 
Instructions:   
Please  read  this consent  form  carefully  and  take  your time  making  a decision  about  
whether to participate.  As the researchers discuss this consent form with you, please ask  
him/her to explain any words or information that you do not clearly understand.  The  
purpose of the study, risks, inconveniences, discomforts, and other important information  
about the study are listed below.  If you decide to participate, you will be given a copy of  
this form to keep.   
 
Why is this study being done?   
This study is being done to evaluate the safety of the investigational study drug,   
selinexor alone or when given with docetaxel to patients who have been previously  
treated for advanced KRAS mutant lung cancer.    
 
Why is this considered research?    
This is a research study because selinexor is investigational and has not been approved  
by the U.S. Food and Drug Administration (FDA) for the treatment of non-small cell lung  
cancer.    
Docetaxel is an approved FDA drug for the treatment of advanced stage non-small cell  
lung cancer.    
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Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
The following definitions may help you understand this study:    
•  Standard medical care means the regular care you would receive from your   
personal doctor if you choose not to participate in this research.   
•  Researchers means the study doctor and research personnel at the University of   
Texas Southwestern Medical Center at Dallas and its affiliated hospitals.   
•  Pharmacodynamics (PD) control the effects the study drug will have on your   
body.     
•  Treatment cycle for this study is 21 days    
•  Dose Escalation – increase in the amount of study drug you will receive   
•  Dose Expansion – continuation of drug use at a specific dose   
 
Why am I being asked to take part in this research study?   
You are being asked to take part in this study because you have non-small cell lung  
cancer that may have a mutation (defect) in the KRAS gene in the tumor.    
 
If you agree to participate in this study, you may be foregoing your opportunity to   
receive FDA approved therapies for your type of cancer. Some of the therapies have  
demonstrated clinical benefit compared to the monotherapy docetaxel including    
PD-1/L1 inhibitors. For more information about alternative treatments, please ask your  
study doctor.    
 
Do I have to take part in this research study?   
No.  You have the right to choose whether you want to take part in this research study.    
If you decide to participate and later change your mind, you are free to stop participation  
at any time.   
 
If you decide not to take part in this research study it will not change your legal rights or  
the quality of health care that you receive at this center.   
 
How many people will take part in this study?   
About 30 people will take part in this study at UT Southwestern. This study also is taking  
place at a number of other medical facilities around the country.  There will be about 71- 
86 people participating in this research study throughout the United States.   
 
Dose escalation phase – Between 9 and 24 patients will be enrolled for this part.    
 
Dose expansion phase will have 3 cohorts:     
 
-   Approximately 35 patients will be enrolled for the combination docetaxel plus   
selixenor cohort.   
-  Approximately 34 patients will be enrolled into one of two selinexor monotherapy  
cohorts(once weekly or twice weekly dosing).     
 
 
 
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Patients will be enrolled to one of these 3 cohorts.  Initial enrollment will be open to the   
dose expansion combination cohort for treatment with docetaxel plus selinexor.  After   
IRB Approved Date: 1/30/2023  


 
 
 
this combination cohort is completed, patients will be randomly assigned to either   
selinexor monotherapy cohorts of once or twice weekly dosing. If you choose to   
participate, your physician or study member will confirm to which cohort you have been  
assigned.    
 
What is involved in the study?   
If you volunteer to take part in this research study, you will be asked to sign this consent  
form and will have the following tests and procedures.  Some of the procedures may be  
part of your standard medical care, but others are being done solely for the purpose of   
this study.   
 
Screening Procedures (Performed within -4 weeks prior to start of study therapy)    
 
To help decide if you qualify to be in this study, the researchers will ask you  
questions about your health, including medications you take and any surgical  
procedures you have had.   
 
You may also have to fill out certain forms or have the following exams, tests or  
procedures:   
 
•  We will confirm that you have KRAS mutant Lung Cancer.    
•  Your medical history and demographic data (this includes information about your   
gender, age, and race/ethnicity) will be recorded.   
•  You will be asked about any medications you are currently taking or have taken   
during the past 2 weeks and any symptoms you might be having.   
•  A Physical examination will be done which will include body weight, height, body   
surface area (BSA) measurement and vital signs (heart rate, blood pressure,   
temperature)   
•  A  performance  assessment  (your  ability  to  do  your  daily  activities)  will  also  be  
completed using the Eastern Cooperative Oncology Group (ECOG) Performance  
Status Scale.     
•  A urine sample will be taken for routine tests.   
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your   
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), coagulation (how well your blood clots),   
and how well your organs are functioning including your thyroid.   
•  A blood sample will be taken to check for hepatitis    
•  An electrocardiogram (EKG) which records the electrical activity of your heart will   
be performed twice.   
•  If you are a woman who is able to become pregnant, a blood sample will be   
collected to test if you are pregnant.   
•  A measurement of your tumor will be done by computed tomography scan (CT   
scan) or a magnetic resonance scan (MRI) of your chest and abdomen if you   
have not had one in the last 28 days.   
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•  A brain MRI will be performed if needed OR   
•  Chest x-ray   
•  Nutrition counseling to discuss food recommendations and strategies to lessen   
potential side effects   
•  Archival tumor tissue (tissue which has already been collected) will be obtained    
for biomarker testing    
 
If you are eligible (you are able to take part in the study), and agree to receive the  
study drug, you will need to come to the study site at various times to have   
procedures done as described below.   
 
Study Medication/Intervention   
This study consists of a 21-day treatment cycle of treatment.    
 
Docetaxel    
If you are enrolled to the combination cohort, you will receive docetaxel intravenously  
(through an IV) for 1 hour on the first day of each 21-day cycle (every 3 weeks) at the  
dose of either 60 or 75 mg/m2 throughout your study participation. However, if you   
experience bad effects and the researchers believe it may be related to docetaxel your  
dose may be lowered to 55 mg/m2 or you may be taken off the study.   
 
Selinexor (KPT-330)   
The study drug selinexor is provided in 20 mg tablets in blister packs of 12 tablets,   
which is to be taken orally (by mouth) once a week for the combination cohort or weekly  
monotherapy cohort and twice weekly for the twice weekly monotherapy cohort. The   
tablet should be taken with or within 30 minutes of a meal.     
 
In the combination cohort, the selinexor will be taken starting 1 week before your first  
docetaxel infusion. Selinexor (KPT-330) should be swallowed whole and should be   
taken with or within 30 minutes of a meal.  You will be instructed to take a specific   
number of tablets on certain days. You will be asked to keep a diary to write down the  
date and time each time you take the selinexor. You will also be asked to keep all of   
your blister packs of study drug (including the empty ones). Bring your blister pack(s)  
and your daily diary to the clinic so that ‘accountability’ can be done (a check to see   
whether you have taken your study drug as instructed).   
 
You will receive the same dose of selinexor throughout your participation in this study  
unless your dose is reduced because you are experiencing side effects.    
 
Below is a table of the dose levels that may be administered during this study. The   
amount of selinexor that will be given to you will be based on the time at which you are  
enrolled and which cohort is available for study participation. Your study doctor will tell  
you which dose you will receive before it is given to you.    
 
 
 
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Combination Selinexor and Docetaxel dose levels:   
 
 
 
 
 
 
 
 
 
 
 
 
Selinexor monotherapy cohort dose levels—weekly dosing:   
 
 
 
 
 
 
Selinexor monotherapy cohort dose levels—twice weekly dosing:   
 
 
 
 
 
*If you take acetaminophen (such as Tylenol) while you are on this study, you must not  
take more than 1 gram on the days you take the selinexor. Ask a study team member if  
you have any questions about the use of acetaminophen.    
 
Procedures and Evaluations during the Research   
If your study doctor decides you can be in the study, you can start treatment. You will   
have the following tests and evaluations during the study. For each cycle, the following  
will take place on the days indicated:   
 
Combination Selinexor and Docetaxel cohort  
Cycle 1 Day -7 (selinexor administration)   
This visit will be completed for Cycle 1 only.   
 
•  Limited physical examination including body weight,and vital signs (heart rate,  
blood pressure, temperature)   
•  If you are a woman who is able to become pregnant, a blood sample will be   
collected to test if you are pregnant. If you have had a pregnancy test within 3   
days before this visit, it may not need to be repeated.   
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 5 of 25  
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Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
Dose of Docetaxel  
(mg/m2 IV), every 3  
weeks   
1a   
60 once weekly   
75   
2a   
80 once weekly   
75   
3   
100 once weekly   
75   
-1   
40 once weekly   
75   
-2   
40 once weekly   
60   
Dose Level   
Dose of Selinexor (mg oral)   
1   
80 once weekly   
-1   
60 once weekly   
-2   
40 once weekly   
Dose Level   
Dose of Selinexor (mg oral)   
1   
60 twice weekly   
-1   
40 mg twice weekly   
-2   
60 mg once weekly   
Dose Level  
Dose of Selinexor (mg   
oral)   
IRB Approved Date: 1/30/2023  


 
 
 
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your  
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), and how well your organs are functioning.   
•  A performance assessment (your ability to do your daily activities) will also be   
completed using the Eastern Cooperative Oncology Group (ECOG) Performance   
Status Scale.     
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  If your lab values are acceptable and your doctor feels you are ready to start   
treatment, the selinexor will be dispensed and you will take your first dose in   
clinic.    
•  About 2.5 tablespoons of blood will be drawn for Pharmacodynamic (PD) testing  
before your take the selinexor in clinic, and 4 hours after you take the selinexor.    
•  Provide study drug dosing diary   
 
 
Cycle 1 Day 1 (docetaxel administration)   
•  Limited physical examination including body weight, height, body surface area   
(BSA) measurement and vital signs (heart rate, blood pressure, temperature)   
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your   
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), and how well your organs are functioning.   
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  You will take the selinexor in clinic.   
•  If your lab values are acceptable and your doctor feels you are ready to start   
treatment with docetaxel, docetaxel will be administered through IV   
•  About 2.5 tablespoons of blood will be drawn for Pharmacodynamic (PD) testing   
before your take the selinexor in clinic, and 4 hours after you take the selinexor.    
•  Drug accountability: review of pill diary and count all pills that are returned   
 
 
Cycle 1 Day 3 (contact)   
•  A member of the study team will contact (via telephone) you to see how you are   
feeling and to see if you have had any changes in medication.    
 
Cycle 1 Day 8 (±1 day)    
•  Limited physical examination including body weight, and vital signs (heart rate,   
blood pressure, temperature)   
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your   
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), and how well your organs are functioning.   
•  You will be asked about any medications you are currently taking   
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 6 of 25  
DO NOT DISCLOSE   
Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
•  You will be asked about how you are feeling and if you are having any side  
effects   
•  Drug accountability: review of pill diary and count all pills that are returned   
 
Cycle 1 Day 15 (±1 day)    
•  Limited physical examination including body weight, and vital signs (heart rate,   
blood pressure, temperature)   
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your   
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), and how well your organs are functioning.   
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  Drug accountability: review of pill diary and count all pills that are returned   
 
Cycles 2 and Subsequent Cycles Day 1 (docetaxel administration) ± 3 days   
•  Physical examination including body weight, height, body surface area (BSA)   
measurement and vital signs (heart rate, blood pressure, temperature)   
•  If you are a woman who is able to become pregnant, a blood sample will be   
collected to test if you are pregnant. If you have had a pregnancy test within 3   
days before this visit, it may not need to be repeated.    
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your  
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), coagulation (how well your blood clots),   
and how well your organs are functioning. Urine will be collected    
•  A performance assessment (your ability to do your daily activities) will also be  
completed using the Eastern Cooperative Oncology Group (ECOG) Performance  
Status Scale.     
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  You will take your dose of selinexor in clinic   
•  Cycle 2 only - About 2.5 tablespoons of blood will be drawn for   
Pharmacodynamic (PD) testing before your take the selinexor in clinic, and 4   
hours after you take the selinexor.    
•  Drug accountability: review of pill diary and count all pills that are returned   
•  Provide new study drug dosing diary   
 
After 7 weeks for first 2 cycles then every 6 weeks   
After 7 weeks for first 2 cycles then every 2 cycles you will have a CT or MRI scan of   
your chest and abdomen to how your disease is responding to treatment. If necessary,  
you may also be asked to have a MRI of your Brain.    
 
 
 
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 7 of 25  
DO NOT DISCLOSE   
Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
End-of-Treatment Visit (≥ 30 Days after Last Dose)   
Study procedures will be performed at 30 days (+/- 7 days) after the last dose of study  
medication for all patients, including early termination patients, as summarized below.   
 
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  A Physical examination will be done which will include body weight, and vital   
signs (heart rate, blood pressure, temperature)   
•  A performance assessment (your ability to do your daily activities) will also be   
completed using the Eastern Cooperative Oncology Group (ECOG) Performance  
Status Scale.     
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your  
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), coagulation (how well your blood clots),   
and how well your organs are functioning including your thyroid.   
•  An electrocardiogram (EKG) which records the electrical activity of your heart will  
be performed twice.   
•     
•  You will have blood collected (about 2.5 tablespoons) for biomarker   
(pharmacodynamic) testing.   
 
After Treatment - Biopsy   
If your doctor decides that you need an additional biopsy after you finish treatment on   
this study, we would like to collect a sample of the tissue. We are not requesting an   
additional biopsy to this one, only a sample of the archived tissue from this biopsy. The  
additional tumor sample analyses will help with further knowledge and understanding of  
the study treatment.    
 
Selinexor monotherapy cohorts (weekly and twice weekly dosing)   
Cycle 1 Day 1 (selinexor administration)   
•  Limited physical examination including body weight, height, body surface area   
(BSA) measurement and vital signs (heart rate, blood pressure, temperature)   
•  If you are a woman who is able to become pregnant, a blood sample will be   
collected to test if you are pregnant. If you have had a pregnancy test within 3   
days before this visit, it may not need to be repeated.   
•  A performance assessment (your ability to do your daily activities) will also be   
completed using the Eastern Cooperative Oncology Group (ECOG) Performance  
Status Scale.     
•  If your lab values are acceptable and your doctor feels you are ready to start   
treatment, the selinexor will be dispensed and you will take your first dose in   
clinic.    
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your  
blood counts (numbers of different types of cells in your blood), chemistries   
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 8 of 25  
DO NOT DISCLOSE   
Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
(elements and minerals in your body), and how well your organs are functioning.  
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  You will take the selinexor in clinic.   
•  Provide study drug dosing diary   
•  About 2.5 tablespoons of blood will be drawn for Pharmacodynamic (PD) testing   
before your take the selinexor in clinic, and 4 hours after you take the selinexor.    
 
 
Cycle 1 Day 3 (±1 day)   
•  A member of the study team will contact (via telephone) you to see how you are   
feeling and to see if you have had any changes in medication.    
•  You will take the selinexor dose (for monotherapy twice weekly cohort only)   
 
Cycle 1 Day 8 (±1 day)    
•  Limited physical examination including body weight, and vital signs (heart rate,   
blood pressure, temperature)   
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your   
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), and how well your organs are functioning.   
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  You will take the selinexor in clinic    
•  Drug accountability: review of pill diary and count all pills that are returned   
 
Cycle 1 Day 10 (±1 day; for monotherapy twice weekly cohort only)   
•  You will take the selinexor dose (for monotherapy twice weekly cohort only)   
 
Cycle 1 Day 15 (±1 day)    
•  Limited physical examination including body weight, and vital signs (heart rate,   
blood pressure, temperature)   
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your   
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), and how well your organs are functioning.   
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  You will take the selinexor in clinic    
•  Drug accountability: review of pill diary and count all pills that are returned   
Cycle 1 Day 17 (±1 day; for monotherapy twice weekly cohort only)  
•  You will take the selinexor dose    
 
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 9 of 25  
DO NOT DISCLOSE   
Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
Cycles 2 and Subsequent Cycles Day 1 (selinexor administration) ± 3 days   
•  Physical examination including body weight, height, body surface area (BSA)   
measurement and vital signs (heart rate, blood pressure, temperature)   
•  If you are a woman who is able to become pregnant, a blood sample will be   
collected to test if you are pregnant. If you have had a pregnancy test within 3   
days before this visit, it may not need to be repeated.    
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your  
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), coagulation (how well your blood clots),   
and how well your organs are functioning. Urine will be collected    
•  A performance assessment (your ability to do your daily activities) will also be  
completed using the Eastern Cooperative Oncology Group (ECOG) Performance  
Status Scale.     
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  You will take your dose of selinexor in clinic   
•  Cycle 2 only - About 2.5 tablespoons of blood will be drawn for   
Pharmacodynamic (PD) testing before your take the selinexor in clinic, and 4   
hours after you take the selinexor.    
•  Drug accountability: review of pill diary and count all pills that are returned   
•  Provide new study drug dosing diary   
 
Cycles 2 and Subsequent Cycles Day 3 (±3 days; for monotherapy twice weekly  
cohort only)   
•  You will take the selinexor dose    
 
Cycles 2 and Subsequent Cycles Day 8 (±3 days)    
•  You will take the selinexor dose    
 
Cycles 2 and Subsequent Cycles Day 10 (±3 day; for monotherapy twice weekly  
cohort only)   
•  You will take the selinexor dose   
 
Cycles 2 and Subsequent Cycles Day 15 (±3 days)    
•  You will take the selinexor dose   
 
Cycles 2 and Subsequent Cycles Day 17 (±3 days; for monotherapy twice weekly  
cohort only)   
•  You will take the selinexor dose    
 
After 7 weeks for first 2 cycles then every 6 weeks   
After 7 weeks for first 2 cycles then every 2 cycles you will have a CT or MRI scan of   
your chest and abdomen to how your disease is responding to treatment. If necessary,  
you may also be asked to have a MRI of your brain.    
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 10 of 25  
DO NOT DISCLOSE   
Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
End-of-Treatment Visit (≥ 30 Days after Last Dose)   
Study procedures will be performed at 30 days (+/- 7 days) after the last dose of study  
medication for all patients, including early termination patients, as summarized below.   
 
•  You will be asked about any medications you are currently taking   
•  You will be asked about how you are feeling and if you are having any side   
effects   
•  A Physical examination will be done which will include body weight, and vital   
signs (heart rate, blood pressure, temperature)   
•  A performance assessment (your ability to do your daily activities) will also be   
completed using the Eastern Cooperative Oncology Group (ECOG) Performance  
Status Scale.     
•  Blood samples (about 2 tablespoons) will be taken for routine tests to check your  
blood counts (numbers of different types of cells in your blood), chemistries   
(elements and minerals in your body), coagulation (how well your blood clots),   
and how well your organs are functioning including your thyroid.   
•  An electrocardiogram (EKG) which records the electrical activity of your heart will  
be performed twice.   
•  You will have blood collected (about 2.5 tablespoons) for biomarker   
(pharmacodynamic) testing.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
Page 11 of 25  
DO NOT DISCLOSE   
Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
After Treatment - Biopsy   
If your doctor decides that you need an additional biopsy after you finish treatment on   
this study, we would like to collect a sample of the tissue. We are not requesting an   
additional biopsy to this one, only a sample of the archived tissue from this biopsy. The  
additional tumor sample analyses will help with further knowledge and understanding of  
the study treatment.    
 
For all cohorts:  If you miss a dose, please contact your primary research personnel for  
this study or your study doctor to determine when next to resume dosing.    
 
If you are taken off study due to progression but are receiving clinical benefit, your  
doctor will let you know if you have the option to continue treatment.     
 
If you agree to have this additional tumor tissue collected for additional testing,  
please check the box next to Yes below.    
 
  Yes, I agree to the collection of these additional samples for additional  
testing.    
 
Initial: _________________________  
Date:__________________   
 
If you do not agree, please check the box next to No below:   
  No, I do not agree to the collection of these additional samples for  
additional testing.   
 
Initial: _________________________  
Date:__________________   
 
 
Follow-Up   
After you stop treatment, a study team member will call you or your family every 3   
months to see how you are doing and see if you have received any other treatment.   
 
How long can I expect to be in this study?   
The study is estimated to continue for 3 years. This is not the length of time you will stay  
in the study. The length of time you will stay in the study will be affected by several factors  
such as your response to treatment, whether you develop any clinically important side  
effects, or if you decide to withdraw consent.   
 
You can choose to stop participating for any reason at any time.  However, if you decide  
to stop participating in the study, we encourage you to tell the researchers.  You may be  
asked if you are willing to complete some study termination tests. Your authorization to   
use your health information will not expire and any data or samples collected before   
your withdrawal will continue to be used as necessary to preserve the integrity of the   
study, however no additional information or samples will be collected after you withdraw  
your authorization.   
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
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Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
 
What are the risks of the study?   
It is possible for any drug to cause side effects. You need to know and understand about  
side effects that could occur in this study before you agree to be a study participant. In  
addition  to  the  risks  listed  below,  there  may  be  risks  that  are  currently  unknown.  If  
significant new risks develop during the course of study that might affect your willingness  
to participate, information will be reported to you as soon as possible.   
 
Side Effects of Selinexor (KPT-330)    
 
Selinexor may cause one or more of the side effects listed below. In addition, there may  
be side effects that are not yet known that may occur. As of March 2022, Selinexor has  
been administered in over 4,475 patients. This information is based on data from cancer  
patients in other clinical trials with selinexor. You should tell your doctor or nurse right   
away about any possible side effects that you experience.   
 
 
Very common side effects (≥10%):    
In 100 people receiving selinexor more than 10 people may have:    
 
•  
Nausea   
•  
Fatigue   
•  
Decreased appetite   
•  
Thrombocytopenia – decrease in platelets, which help your blood clot    
•  
Anemia – decrease in red blood cells    
•  
Vomiting    
•  
Diarrhea    
•  
Hyponatremia – low sodium    
•  
Constipation   
•  
Dyspnea- shortness of breath   
•  
Neutropenia – decrease in neutrophils – a specific type of white blood cell that   
helps fight infections    
•  
Weight loss   
•  
Dizziness   
•  
Dysgeusia – change in taste    
•  
Blurred vision   
•  
Leucopenia – decrease in white blood cells    
•  
Dehydration   
•  
Asthenia- loss of energy; weakness   
•  
Fever   
•  
Cough   
•  
Abdominal pain   
•  
Swelling   
•  
Hypokalemia – low potassium   
•  
Hyperglycemia – elevated glucose (sugar) levels   
•  
Headache   
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Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
•  
Back pain   
•  
Insomnia (difficulty sleeping)   
•  
Pneumonia   
•  
Blood electrolyte imbalance (that may increase risk of seizure)   
•  
Cramps   
•  
Increased blood pressure   
•  
Creatinine Increased – increase of creatinine in the blood due to a reduction in   
kidney function, often related to dehydration   
 
 
Common side effects (≥1-10%):    
In 100 people receiving selinexor about 1 to 10 people may have:    
 
•  Confusion   
•  Febrile neutropenia – Fever in the absence of a normal white blood cell response   
that may mean you have an infection   
•  Sepsis- potentially life-threatening complication of an infection   
•  Dry mouth    
•  Swelling and sores in the mouth   
•  Syncope – fainting    
•  Cognitive disorder   
•  Urinary Tract Infection   
•  Bronchitis (infection of the tubes that car air to and from the lungs)   
•  Eye disorders (cataracts, visual disturbances and dry eye)   
Uncommon side effects (>0.1-1%):    
In 1,000 people receiving selinexor about 1 to 10 people may have:    
 
•  Altered behavior   
•  Tumor lysis syndrome – potentially a life-threatening side effect caused by the   
rapid breakdown of tumor cells and may cause irregular heartbeat, kidney failure  
or abnormal blood test results which included elevated uric acid level, elevated   
serum potassium and phosphorus levels, and a decreased calcium level.   
•  Nose bleeds   
 
Rare side effects (>0.01-0.1%):    
In 10,000 people receiving selinexor about 1 to 10 people may have:    
•  Acute cerebellar syndrome – symptoms can include a sudden loss of  
coordination, balance, or slurred speech   
Serious adverse effects (≥ 3 cases reported as related by the principal investigator)  
-  Acute kidney injury    
-  Aspartate aminotransferase increased – elevated liver enzyme level    
-  Bacteremia – bacterial infection in the blood    
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Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
-  Delirium – state of acute confusion    
-  Encephalopathy  –  brain  disease,  damage,  or  malfunction,  which  can  present   
different symptoms that range from mild, such as some memory loss or subtle  
personality changes, to severe, such as dementia, seizures, or coma.    
-  General physical health deterioration     
-  Hyperglycemia – elevated blood sugar level    
-  Hypotension – low blood pressure    
-  Pulmonary embolism – pulmonary embolism occurs when a clump of material,   
most often a blood clot, gets wedged into an artery in your lungs.    
-  Pyrexia – fever     
-  Septic shock    
-  Upper respiratory tract infection   
 
Side effects of selinexor (KPT-330) in COVID-19 patients (20 mg selinexor)   
-  In patients with severe disease, age ≥75 years and pre-existing illness, deaths   
were higher in the selinexor group compared to the placebo group. Treating   
doctors indicated that the deaths were due to COVID-19 and not related to study  
treatment.  In patients with less severe disease and who were younger than 75   
years of age, the deaths were comparable in patients who received selinexor or  
placebo.    
-  Other side effect such as i.e. nausea, vomiting, constipation, low sodium etc.   
were similar to what was observed in other patients treated with selinexor.   
 
Side Effects of Docetaxel   
Although not all of these side effects may occur, if they do occur they may need medical  
attention.   
 
Check with your doctor immediately if any of the following side effects occur:   
 
•  
Very common side effects (>10%): Burning, numbness, tingling, or pain in the  
arms, hands, legs, or feet    
•  swelling of the stomach, face, fingers, hands, feet, or lower legs    
•  unusual tiredness or weakness    
•  weight gain    
 
Uncommon side effects (>0.1-1%):    
•  Black, tarry stools    
•  blood in the urine or stools    
•  cough or hoarseness (accompanied by fever or chills)    
•  difficult or labored breathing    
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Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
•  difficult or painful urination (accompanied by fever or chills)    
•  difficulty with swallowing    
•  dizziness    
•  fast heartbeat    
•  fever or chills    
•  hives or skin rash    
•  itching, puffiness, face, lips, or tongue    
•  lower back or side pain (accompanied by fever or chills)    
•  noisy, rattling breathing    
•  pinpoint red spots on the skin    
•  red, scaly, swollen, or peeling areas of the skin (severe)    
•  tightness in the chest    
•  troubled breathing while at rest    
•  unusual bleeding or bruising    
 
Rare side effects (>0.01-0.1%):    
•  Chest pain or discomfort    
•  decreased blood pressure    
•  fast or irregular heartbeat    
•  increased blood pressure    
 
Risks of Neutropenia Associated with Selinexor and Docetaxel   
Some patients have experienced a decrease of a specific type of white blood cell called  
neutrophils (which help the body fight infections) after receiving selinexor + docetaxel.   
To help avoid this, you may be given a medication known as a myeloid growth factor.   
This decreases the possibility of infection by increasing the number of neutrophils in the  
blood. Your physician or healthcare provider will let you know if this is needed for your   
care.   
 
Study Procedure/Intervention   
Because of your participation in this study, you are at risk for the following side effects.  
You should discuss these with the researchers and your regular health care provider.    
 
Psychological Stress   
Some of the questions we will ask you as part of this study may make you feel   
uncomfortable.  You may refuse to answer any of the questions, take a break or stop  
your participation in this study at any time.   
 
Loss of Confidentiality   
Any time information is collected; there is a potential risk for loss of confidentiality.    
Every effort will be made to keep your information confidential; however, this cannot be  
guaranteed.    
 
Risks to Sperm, Embryo, Fetus or Breast-fed Infant   
Males: Being in this research may damage your sperm, which could cause harm to a  
child that you may father while on this study. If you take part in this study and are   
STU032017-003, Gerber, FormE-Consent, Mod_35, 01-30-23  
   
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Protocol Version: 4.0 dated 06Nov2020  
   
Risks update based on IB version 11.0 dated July 30, 2021    
IRB Approved Date: 1/30/2023  


 
 
 
sexually active, you must agree to use two forms of medically-acceptable birth control  
during the study and for 3 months following the last dose of study treatment.    
 
Medically-acceptable forms of birth control include:   
(1) surgical sterilization (vasectomy), or   
(2) a condom used with a spermicide (a substance that kills sperm).   
 
Females: If you are part of this study while pregnant or breast-feeding an infant, it is   
possible that you may expose the unborn child or infant to risks.  For that reason,   
pregnant and breast-feeding females cannot participate in the study.  If you can become  
pregnant, a blood pregnancy test will be done (using 1 teaspoon of blood drawn from a  
vein by needle-stick), and it must be negative before you participate in this study. If you  
take part in this study and you are sexually active, you and any person that you have   
sex with must use two forms of medically-acceptable birth control (contraceptives)   
during the study and for 3 months following the last dose of study treatment.    
 
Medically-acceptable birth control (contraceptives) includes:   
(1) surgical sterilization (such as hysterectomy or “tubes tied”),   
(2) approved hormonal contraceptives ( such as birth control pills, patch or ring;  
Depo-Provera, Implanon),   
(3) barrier methods (such as condom or diaphragm) used with a spermicide (a   
substance that kills sperm), or    
(4) an intrauterine device (IUD).   
If you do become pregnant during this study, you must tell the researchers immediately.   
 
Radiation exposure to a woman’s reproductive organs may harm an embryo or fetus.   
Also, if radioactive materials are used for certain types of scans, harm may come to an  
embryo, fetus, or an infant who is breast feeding.     
 
Pregnancy tests performed during the early stages of pregnancy do not always reveal   
pregnancy.  Therefore, radiation exposure that includes the reproductive organs will be  
limited to the first ten days after a woman who can become pregnant has begun her   
most recent menstrual period.  This is standard policy in clinics and hospitals within UT  
Southwestern.  This policy applies unless there is an important medical reason requiring  
radiation outside this time frame   
 
Risks of Radiation – Diagnostic Test   
The radiation dose that you will get from diagnostic tests is medically indicated for your  
condition and it is the same that you would get if you were not involved in this research  
study.   
 
Risks of Computed Tomography (CT) Imaging:   
CT imaging is a painless procedure that is safe for most people.  During the imaging,  
you will lie flat with your body in a long metal cylinder.  Some people who fear closed  
spaces may be frightened during the procedure.  You will be observed by the   
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operator(s) at all times during the procedure and can be assisted if necessary.  If you  
request, you can be moved out of the machine.  A small proportion of people develop  
short-lived reactions during the dye administration, including nausea, headache, hot   
flashes, and heart palpitations.  These symptoms usually resolve on their own within   
minutes.  A smaller group of people are actually allergic to the dye and may develop a  
rash, hives, difficulty breathing and in extreme cases, the person may stop breathing,  
the heart may stop, and the person may die.  You will be closely monitored during the  
procedure and if any allergic reaction develops, you will be treated immediately.   
 
Risk of MRI:   
The imager makes a loud, banging noise while it is taking pictures. Patients may   
experience nervousness from confinement in a tight space (claustrophobia). Patients   
may feel uneasy or experience some discomfort and fatigue from lying still on a moving  
table for a long period of time. There is the possibility that patients may have a rare or   
previously unknown complication.  There are no known effects from exposure to   
magnetic fields.     
 
MRI may not be appropriate if patients have permanent eyeliner or eyebrows or any   
pieces of metal in your body, such as the following:   
•  
heart pacemaker, heart valve replacement, or aortic clips   
•  
metal fragments in your eyes, skin, or elsewhere in your body   
•  
brain clips or pieces of metal used in aneurysm surgery or intercranial bypass   
•  
venous umbrella   
•  
pieces of metal in the body resulting from work as a sheet-metal worker or welder    
•  
clips placed in an internal organ   
•  
prosthetic devices, such as middle ear, eye, joint, or penile implants   
•  
joint replacement.   
•  
hearing aid that cannot be removed   
•  
neurostimulator    
•  
insulin pump   
•  
intrauterine device (IUD)   
•  
shunts or stents   
•  
metal mesh or coil implants   
•  
metal plate, pin, screws, or wires, or any other metal implants   
 
If you have a history of an implanted device or clips in your pelvis (involving your uterus  
or fallopian tubes) or under your skin, action as a contraceptive to prevent pregnancy,   
the MRI technologist will obtain specific information about the make and model of your  
implanted device to determine if it is safe for you to receive the MRI examination.   
 
The contrast agent you will receive is FDA-approved and used routinely for MRI   
exams.  It contains a material called Gadolinium (dye used to highlight organs or tissues  
during imaging).  The injection of Gadolinium may cause discomfort like headache,   
nausea, strange taste, or coldness at site of injection.  These symptoms occur in less   
than 1 out of 20 patients receiving Gadolinium and go away quickly.   There is a small   
risk of a severe allergic reaction that can cause breathing difficulties and/or low blood   
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pressure; these symptoms are extremely rare (approximately 1 in 10,000 to 1 in   
100,000 administrations).  In the unlikely event you experience these symptoms, a  
physician and nursing staff will be available to evaluate and, if necessary, provide  
treatment.    
 
People with severe kidney failure who receive Gadolinium (dye used to highlight organs  
or tissues during imaging) are at risk of developing a disorder called Nephrogenic   
Systemic Fibrosis (NSF).  This disease can cause wide spread tissue scarring or   
hardening (fibrosis). In rare cases NSF can lead to lung and heart problems and cause  
death. If you have severe kidney failure and receive gadolinium, the risk of developing   
NSF is 1-5%.  We may perform a blood test 30 days before your MRI to check how well  
your kidneys are working before you receive the Gadolinium. This test may be repeated  
closer to your MRI appointment if your medical condition has changed. If your kidneys   
are working at levels known to be at risk for NSF, you will not receive Gadolinium.  You  
will not receive Gadolinium for research purposes if you have sickle cell disease (a   
disease of the blood cells).    
 
Risks of Chest X-rays   
The x-ray will provide information about the status of your lungs, heart and chest wall.     
 
As part of this study you may have X-rays which involve exposure to radiation. The   
amount of radiation exposure you may receive from these standard diagnostic tests is  
considered small and will not adversely affect the treatment of your disease.   
 
Risks of Blood Drawing   
Risks associated with drawing blood from your arm include minimal discomfort and/or   
bruising.  Infection, excess bleeding, clotting, and/or fainting also are possible, although  
unlikely.   
 
You will have about 3 tablespoons of blood drawn at each visit because you are on this  
research study. The total amount of blood collected during the study depends on your  
length of participation.   
 
Other Risks   
There may possibly be other side effects that are unknown at this time. If you are   
concerned about other, unknown side effects, please discuss this with the researchers.   
 
How will risks be minimized or prevented?     
Prior to being treated on this study, your medical history and current medical conditions  
will be reviewed. You will be closely monitored at each cycle with blood tests and other  
physical assessments to ensure that any side effects are being monitored and treated   
appropriately.  Medication may be given to reduce side effects. Dose levels may be   
minimized for safety.    
 
What will my responsibilities be during the study?     
While you are part of this study, the researchers will follow you closely to determine   
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whether there are problems that need medical care.  It is your responsibility to do the   
following:   
•  Ask questions about anything you do not understand.   
•  Keep your appointments.   
•  Follow the researchers’ instructions.   
•  Let the researchers know if your telephone number or address changes.   
•  Store study materials and study drug in a secure place at home away from   
anyone who is unable to read and understand labels, especially children.   
•  Tell the researchers before you take any new medication, even if it is prescribed   
by another doctor for a different medical problem or something purchased over   
the counter.   
•  Tell your regular doctor about your participation in this study.   
•  Carry information about selinexor in your purse or wallet.   
•  Record the date and time on your study drug diary as directed by the study team  
•  Report to the researchers any injury or illnesses while you are on study even if   
you do not think it is related.    
 
If I agree to take part in this research study, will I be told of any new risks that   
may be found during the course of the study?   
Yes.  You will be told if any new information becomes available during the study that   
could cause you to change your mind about continuing to participate or that is important  
to your health or safety.   
 
What should I do if I think I am having problems?   
If you have unusual symptoms, pain, or any other problems while you are in the study,  
you should report them to the researchers right away.  Telephone numbers where they  
can be reached are listed on the first page of this consent form.   
 
If you have a sudden, serious problem, like difficulty breathing or severe pain, go to the  
nearest hospital emergency room, or call 911 (or the correct emergency telephone   
number in your area).  Tell emergency personnel about any medications you are taking,  
including any medications you are taking for this study.     
 
What are the possible benefits of this study?   
If you agree to take part in this study, there may or may not be direct benefits to you.   
The researchers cannot guarantee that you will benefit from participation in this   
research.   
 
We hope the information learned from this study will benefit others with non-small cell  
lung cancer in the future.  Information gained from this research could lead to better   
treatment.     
 
What options are available if I decide not to take part in this research study?   
You do not have to participate in this research to receive care for your medical problem.  
Instead of being in this study, you have the following options:   
•  Other type of treatment, either in a different study or without a study   
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Please talk to the researchers or your personal doctor about these options.    
 
Will I be paid if I take part in this research study?   
There are no funds available to pay for parking expenses, transportation to and from the  
research center, lost time away from work and other activities, lost wages, or child care  
expenses. You will not be paid for taking part in this research study.  Data obtained from  
this study may be used for commercial purposes.  It is the policy of Karyopharm   
Therapeutics, the drug provider, not to provide financial compensation to you should   
this occur.   
 
Will my insurance provider or I be charged for the costs of any part of this   
research study?   
No. Neither you, nor your insurance provider, will be charged for anything done only for  
this research study (i.e., the Screening Procedures, Experimental Procedures, or   
Monitoring/Follow-up Procedures described above).     
 
Selinexor will be provided free of charge while you are participating in this study.    
 
However, the standard medical care for your condition (care you would have received   
whether or not you were in this study) is your responsibility (or the responsibility of your  
insurance provider or governmental program).  You will be charged, in the standard   
manner, for any procedures performed for your standard medical care. You will be   
charged in the standard manner for the procedures and doctor visits, standard or care  
medications, chemotherapy infusions, routine laboratory blood work and draws, MRI,   
CT-Scans, pregnancy tests; urinalysis, and tumor biopsy.   
 
What will happen if I am harmed as a result of taking part in this study?   
It is important that you report any illness or injury to the research team listed at the top  
of this form immediately.   
 
Compensation for an injury resulting from your participation in this research is not  
available from the University of Texas Southwestern Medical Center at Dallas or  
Karyopharm Therapeutics Inc.   
 
You retain your legal rights during your participation in this research.   
 
Can I stop taking part in this research study?   
Yes.  If you decide to participate and later change your mind, you are free to stop taking  
part in the research study at any time.   
If you decide to stop taking part in this research study, it will not affect your relationship  
with the UT Southwestern staff or doctors.  Whether you participate or not will have no   
effect on your legal rights or the quality of your health care.   
 
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•  Supportive care without chemotherapy   
•  Palliative care (meant to sooth symptoms without curing)    
IRB Approved Date: 1/30/2023  


 
 
 
If you are a medical student, fellow, faculty, or staff at the Medical Center, your status  
will not be affected in any way.   
 
Your doctor is a research investigator in this study.  S/he is interested in both your   
medical care and the conduct of this research study.  At any time, you may discuss your  
care with another doctor who is not part of this research study.  You do not have to take  
part in any research study offered by your doctor.   
 
If I agree to take part in this research study, can I be removed from the study   
without my consent?   
Yes.  The researchers may decide to take you off this study if:   
•  Your medical problem remains unchanged or becomes worse.   
•  The researchers believe that participation in the research is no longer safe for   
you.   
•  The researchers believe that other treatment may be more helpful.   
•  The sponsor-investigator, drug supplier or the FDA stops the research for the   
safety of the participants.   
•  The sponsor-investigator cancels the research.   
•  You are unable to keep appointments or to follow the researcher’s instructions.   
 
Will my information be kept confidential?   
Medical information collected during this study and the results of any test or procedure  
that may affect your medical care may be included in your medical record. The   
information included in your medical record will be available to health care providers   
and authorized persons including your insurance company.   
 
You should know that certain organizations that may look at and/or copy your medical  
records for research, quality assurance, and data analysis include:   
 
•  Karyopharm Therapeutics Inc.and its representatives.    
 
•  Simmons Comprehensive Cancer Center Biomarker Research Core Laboratory:    
•  Simmons Comprehensive Cancer Center Phase 1 Disease Oriented Team and  
Data and Safety Monitoring Committee   
•  The UT Southwestern Institutional Review Board.    
 
•  Representative of government agencies, like the U.S. Food and Drug  
Administration, involved in keeping research safe for people.   
 
•  Representatives of domestic and foreign governmental and regulatory agencies.   
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as   
required by U.S. Law.  This Web site will not include information that can identify you.    
 
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At most, the Web site will include a summary of the results.  You can search this Web  
site at any time.   
 
In addition to this consent form, you will be asked to sign an "Authorization for Use and  
Disclosure of Protected Health Information."  This authorization will give more details   
about how your information will be used for this research study, and who may see   
and/or get copies of your information.   
 
Are there procedures I should follow after stopping participation in this research?  
Yes.  If you, the researchers, or the sponsor-investigator stops your participation in the   
research, you may be asked to do the following:   
 
•  Let the researchers know immediately that you wish to withdraw from the  
research.   
•  Return to the research center for tests that may be needed for your safety.  
•  Return any unused study materials, including empty containers.   
•  Discuss your future medical care, if any, with the researchers and/or your   
personal doctor.   
 
Whom do I call if I have questions or problems?   
For questions about the study, contact Dr. David Gerber at 214-648-4180 during regular  
business hours and at 214-645-4673 after hours and on weekends and holidays.     
 
For questions about your rights as a research participant, contact the UT Southwestern  
Medical Center Human Research Protection Program (HRPP) Office at 214-648-3060.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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SIGNATURES:   
 
YOU WILL BE GIVEN A COPY OF THIS CONSENT FORM TO KEEP.   
 
Your signature below certifies the following:   
 
•  You have read (or been read) the information provided above.   
•  You have received answers to all of your questions and have been told who to   
call if you have any more questions.   
•  You have freely decided to participate in this research.   
•  You understand that you are not giving up any of your legal rights.   
•  You understand that a copy of this signed consent document, information about   
this study, and the results of any test or procedure that may affect your medical  
care, may be included in your medical record.  Information in your medical   
record will be available to health care providers and authorized persons   
including your insurance company.   
 
 
____________________________________________    
   
Name of Participant (Printed)  
  
   
 
____________________________________________  ________  _______ AM / PM  
Signature of Participant  
Date  
Time   
 
 
 
Name of Person Obtaining Consent (Printed)  
  
   
 
____________________________________________  ________  _______ AM / PM  
Signature of Person Obtaining Consent  
Date  
Time   
 
 
 
 
 
 
 
 
 
 
 
 
 
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____________________________________________   
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Witness:   
 
I attest that the information in the consent form was accurately explained to, and   
apparently understood by the patient or the patient's legal authorized representative,  
and that informed consent was freely given by the patient or the patient’s legal   
authorized representative.   
 
 
____________________________  
  
  
     ________     _______AM / PM  
Name of Witness (Printed)   
  
  
  
  
Date    
Time   
 
__________________________                                       ________     _______AM / PM  
Signature of Witness                                                                Date                Time   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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