Clinical trial NCT03235544
Conditions: Lymphoma
Keywords: Mantle cell lymphoma non-Hodgkin lymphoma Bruton's tyrosine kinase (BTK) phosphatidylinositol 3-kinase (PI3K)
Sponsor: Incyte Corporation
Start date: 2017-11-20; Completion date: 2024-04-30
Enrollment: 162 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy and safety of 2 parsaclisib treatment regimens in participants with relapsed or refractory mantle cell lymphoma (MCL) previously treated either with or without a Bruton's tyrosine kinase (BTK) inhibitor.

Detailed description:

Arms: arm 1: Participants received parsaclisib 20 mg tablets, orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks.

Participants who were exposed to ibrutinib before enrollment were included in this group. arm 2: Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks.

Participants who were exposed to ibrutinib before enrollment were included in this group. arm 3: Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks.

Participants who had not received a BTK inhibitor previously were included in this group. arm 4: Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks.

Participants who had not received a BTK inhibitor previously were included in this group.
Interventions: intervention 1: Parsaclisib
Intervention descriptions: intervention 1: Parsaclisib tablets administered orally with water and without regard to food.

Protocol documents:
Prot_000.pdf: 
Official Title: 
A Phase 2, Open-Label, 2-Cohort, Multicenter Study of INCB050465, a PI3Kδ 
Inhibitor, in Relapsed or Refractory Mantle Cell Lymphoma Previously 
Treated With or Without a BTK Inhibitor (CITADEL-205) 
NCT Number: 
NCT03235544 
Document Date: 
Clinical Study Protocol Version 7: 30 Jan 2020 


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Clinical Study Protocol 
INCB050465 
A Phase 2, Open-Label, 2-Cohort, Multicenter Study of 
INCB050465, a PI3Kδ Inhibitor, in Relapsed or Refractory Mantle 
Cell Lymphoma Previously Treated With or Without a BTK 
Inhibitor (CITADEL-205) 
Product: 
INCB050465 
IND Number: 
121,474 
EudraCT Number: 
2017-003148-19 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
05 MAY 2017 
Amendment (Version) 1: 
07 NOV 2017 
Amendment (Version) 2: 
31 JAN 2018 
Amendment (Version) 3: 
16 JUL 2018 
Amendment (Version) 4: 
07 DEC 2018 
Amendment (Version) 5: 
29 AUG 2019 
Amendment (Version) 6: 
23 DEC 2019 
Amendment (Version) 7: 
30 JAN 2020 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the 
US Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Corporation. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 50465-205 Protocol Amendment 7 (Version 7 dated 30 JAN 2020) and 
agree to conduct the study as outlined.  I agree to maintain the confidentiality of all information 
received or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 


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SYNOPSIS 
Name of Investigational Product:  INCB050465 
Title of Study:  A Phase 2, Open-Label, 2-Cohort, Multicenter Study of INCB050465, a PI3Kδ Inhibitor, 
in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a BTK Inhibitor 
(CITADEL-205) 
Protocol Number:  INCB 50465-205 
Study Phase:  2 
Indication:  Relapsed or refractory mantle cell lymphoma 
 
Objectives 
Endpoints 
Primary 
To assess the efficacy of INCB050465 
in terms of objective response rate 
(ORR) in subjects with mantle cell 
lymphoma (MCL) that is relapsed or 
refractory after at least 1 but no more 
than 3 prior systemic treatment 
regimens. 
ORR defined as the percentage of subjects with a complete response 
(CR) or partial response (PR) as determined by independent review 
committee (IRC) assessment of response according to computed 
tomography (CT)-based response criteria for lymphomas. 
Secondary 
To assess duration of response (DOR). 
DOR defined as the time from first documented evidence of CR or PR 
until disease progression or death from any cause among subjects who 
achieve an objective response, as determined by radiographic disease 
assessment provided by an IRC. 
To assess complete response rate 
(CRR). 
CRR defined as the percentage of subjects with a CR as defined by 
response criteria for lymphomas as determined by an IRC. 
To assess progression-free survival 
(PFS). 
PFS defined as the time from the date of the first dose of study 
treatment until the earliest date of disease progression, as determined 
by radiographic disease assessment provided by an IRC, or death 
from any cause. 
To assess overall survival (OS). 
Overall survival defined as the time from the date of the first dose of 
study treatment until death from any cause. 
To assess the best percentage change in 
target lesion size. 
Best percentage change in target lesion size from baseline, where 
target lesion size is measured by the sum of the product of diameters 
of all target lesion sizes. 
To characterize the safety and 
tolerability of INCB050465. 
Safety measured by adverse events (AEs), 12-lead electrocardiograms 
(ECGs), chemistry and hematology laboratory values, vital signs, and 
physical examinations. 
 


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Overall Study Design:  This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy 
and safety of 2 INCB050465 treatment regimens in relapsed or refractory MCL previously treated either 
with or without a Bruton's tyrosine kinase (BTK) inhibitor.  Subjects will be allocated to Cohort 1 or 
Cohort 2 as follows: 
• Cohort 1:  Subjects have previously received ibrutinib  
• Cohort 2:  Subjects have not previously received a BTK inhibitor  
Cohort 1 and Cohort 2 will have separate designs, conduct, and analyses. 
Subjects in Cohort 1 (n = 60) and Cohort 2 (n = 60) will be randomly allocated to one of 2 study 
treatment regimens as follows: 
• Treatment A:  INCB050465 20 mg once daily (QD) for 8 weeks followed by 20 mg once weekly 
• Treatment B:  INCB050465 20 mg QD for 8 weeks followed by 2.5 mg QD 
Subjects will be evaluated for response by an IRC and followed for safety, DOR, PFS and OS.  Subjects 
will receive treatment until disease progression, death, unacceptable toxicity, or consent withdrawal, 
whichever occurs first. 
For each of the 2 cohorts, an interim futility analysis is planned when the first 30 subjects have been 
treated and evaluated for response or permanently discontinued study treatment because of disease 
progression, withdrawal of consent, or death.  Cohort 1 will be terminated for futility if ≤ 3 of the 
30 subjects have responded (ie, CR or PR) based on assessments provided by the IRC.  Cohort 2 will be 
terminated for futility if ≤ 10 of the 30 subjects have responded (ie, CR or PR) based on assessments 
provided by the IRC.  A timely assessment of response will be performed to avoid the risk of 
overenrollment.  Safety will be evaluated by an Independent Data Monitoring Committee (IDMC). 
To better understand the safety and efficacy of INCB050465, a total of 70 additional subjects (30 subjects 
in Cohort 1 and 40 subjects in Cohort 2) will be enrolled into one of the 2 treatment regimens (A or B) 
being evaluated in this study.  The treatment regimen will be selected after enrollment is completed for 
either Cohort 1 or Cohort 2 (ie, 60 subjects enrolled) and after evaluation of emerging safety and efficacy 
data from this and other monotherapy studies of INCB050465 in NHL.  Once a treatment regimen is 
selected, the non-selected treatment regimen will be closed to further enrollment.  Subjects receiving the 
non-selected treatment regimen may switch to the selected treatment regimen or remain on their current 
treatment regimen, provided they have not met study treatment withdrawal criteria, and there are no 
safety concerns for their current treatment regimen.  There will be no re-baselining for subjects who 
switch treatment regimens, and all subjects will continue to follow the same assessment schedule. 
Cohort 1 will be closed to further enrollment by Protocol Amendment 7.  Subjects already enrolled in 
Cohort 1 will continue to receive study treatment per protocol. 




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Estimated Duration of Participation:  Subject participation from screening through follow-up is 
expected to average approximately 26 months, which includes the following: 
• A screening period lasting up to 28 days. 
• A treatment period lasting as long as the subject is receiving benefit, tolerating the regimen, and has not 
met withdrawal criteria (approximately 14 months). 
• A safety follow-up period lasting 30 to 35 days. 
• A disease and survival follow-up period until the end of the study. 
At the end of the study, subjects who have completed at least 24 months of study participation (starting 
from first dose of INCB050465), who remain on active study treatment, and who have no evidence of 
progressive disease will have the option to continue on monotherapy with INCB050465 provided within a 
rollover Protocol, as local law permits. 
Estimated Number of Subjects:  Approximately 190 subjects were planned to be enrolled and allocated 
to either Cohort 1 (received prior ibrutinib; n = 60-90) or Cohort 2 (have not received prior BTK 
inhibitor; n = 60-100).  Cohort 1 will be closed to further enrollment by Protocol Amendment 7 with 
approximately 50 subjects enrolled.  The estimated total number of subjects to be enrolled in the study is 
approximately 150. 
Principal Coordinating Investigator: 
United States:  
, MD, 
, USA  
EU:  
, MD, 
, Italy 
Statistical Methods: Data from Cohort 1 and Cohort 2 will be analyzed separately.  There will not be any 
statistical comparison between Cohort 1 and Cohort 2, and there will not be multiplicity adjustment 
between the cohorts. 
Sample Size: 
• Cohort 1:  up to 90 subjects were planned to be enrolled.  If the true ORR is 28%, then there is 
approximately 90% or 96% probability of observing the lower bound of the 95% confidence interval 
(CI) of ORR ≥ 12% with 60 or 90 subjects, respectively.  Cohort 1 will be closed to further enrollment 
with Protocol Amendment 7. 
• Cohort 2:  up to 100 subjects will be enrolled.  If the true ORR is 60%, then there is approximately 90% 
or 97% probability of observing the lower bound of the 95% CI of ORR ≥ 40% with 60 or 100 subjects, 
respectively. 
Primary Analysis:  For each of the 2 cohorts, the ORR as determined by the IRC and its 95% exact 
binomial CIs will be calculated. 
Secondary Analyses:  For each of the 2 cohorts, the Kaplan-Meier estimation of median DOR, PFS (per 
IRC), and OS will be presented with respective 95% CIs.  Complete response rate as determined by the 
IRC and its 95% exact binomial CIs will be calculated.  Best percentage change in target lesion size from 
baseline will be summarized descriptively.  All safety data, including AEs, laboratory data, vital signs, 
and ECGs, will be summarized descriptively. 
Level of Significance:  There will not be any statistical comparison between the 2 cohorts.  Within each 
of the 2 cohorts, 2-sided 95% CIs will be reported for all analyses when appropriate. 
Interim Analysis:  An interim futility analysis is planned for each of the cohorts when 30 subjects have 
been treated and evaluated for response or have permanently discontinued study treatment because of 
disease progression, withdrawal of consent, or death.  Cohort 1 will be terminated for futility if ≤ 3 of the 
30 subjects responded (ie, CR or PR) based on assessments provided by the IRC.  Cohort 2 will be 
terminated for futility if ≤ 10 of the 30 subjects responded (ie, CR or PR) based on assessments provided 
by the IRC. 
Data Monitoring Committee:  An IDMC will be established and will review data at predetermined 
intervals as specified in the IDMC charter. 


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TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................12 
1. 
INTRODUCTION ......................................................................................................14 
1.1. 
Mantle Cell Lymphoma ..............................................................................................14 
1.2. 
Treatment for Mantle Cell Lymphoma .......................................................................14 
1.3. 
INCB050465 ...............................................................................................................15 
1.4. 
Study Rationale ...........................................................................................................16 
1.5. 
Potential Risks and Benefits of the Treatment Regimen ............................................17 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................19 
3. 
SUBJECT ELIGIBILITY ...........................................................................................20 
3.1. 
Subject Inclusion Criteria ...........................................................................................20 
3.2. 
Subject Exclusion Criteria ..........................................................................................21 
4. 
INVESTIGATIONAL PLAN .....................................................................................23 
4.1. 
Overall Study Design ..................................................................................................23 
4.2. 
Measures Taken to Avoid Bias ...................................................................................25 
4.3. 
Number of Subjects ....................................................................................................25 
4.3.1. 
Planned Number of Subjects ......................................................................................25 
4.3.2. 
Replacement of Subjects .............................................................................................25 
4.4. 
Duration of Treatment and Subject Participation .......................................................26 
4.5. 
Overall Study Duration ...............................................................................................26 
4.6. 
Study Termination ......................................................................................................26 
5. 
TREATMENT ............................................................................................................27 
5.1. 
Treatment Assignment ................................................................................................27 
5.1.1. 
Subject Numbering and Treatment Assignment .........................................................27 
5.1.2. 
Randomization and Blinding ......................................................................................27 
5.2. 
INCB050465 ...............................................................................................................27 
5.2.1. 
Description and Administration ..................................................................................27 
5.2.2. 
Supply, Packaging, and Labeling ...............................................................................28 
5.2.3. 
Storage ........................................................................................................................28 
5.2.4. 
Instruction to Subjects for Handling INCB050465 ....................................................28 
5.3. 
Treatment Compliance ................................................................................................29 


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5.4. 
Treatment Interruptions and Adjustments ..................................................................29 
5.4.1. 
Criteria and Procedures for Dose Interruptions and Reductions of 
INCB050465 ...............................................................................................................29 
5.4.1.1. 
Dose Modifications .....................................................................................................29 
5.4.2. 
Supportive Care Guidelines for Diarrhea/Colitis .......................................................31 
5.4.3. 
Supportive Care Guidelines for Neutropenia and Thrombocytopenia .......................33 
5.4.4. 
Definition for Immune-Related Adverse Events ........................................................33 
5.5. 
Study Treatment Discontinuation ...............................................................................34 
5.5.1. 
Criteria for Study Treatment Discontinuation ............................................................34 
5.5.2. 
Procedures for Study Treatment Discontinuation .......................................................34 
5.6. 
Concomitant Medications ...........................................................................................35 
5.6.1. 
Pneumocystis Jirovecii Pneumonia Prophylaxis ........................................................35 
5.6.2. 
Restricted Medications ...............................................................................................35 
5.6.3. 
Prohibited Medications ...............................................................................................36 
5.7. 
Criteria for Study Discontinuation..............................................................................36 
5.8. 
Treatment After the End of the Study .........................................................................36 
6. 
STUDY ASSESSMENTS ..........................................................................................37 
6.1. 
Screening ....................................................................................................................42 
6.2. 
Treatment ....................................................................................................................42 
6.3. 
End of Treatment ........................................................................................................42 
6.4. 
Follow-Up ...................................................................................................................43 
6.4.1. 
Safety Follow-Up ........................................................................................................43 
6.4.2. 
Disease Status Follow-Up ...........................................................................................43 
6.4.3. 
Survival Follow-Up ....................................................................................................43 
6.5. 
End of Study ...............................................................................................................43 
6.6. 
Unscheduled Visits .....................................................................................................44 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................44 
7.1. 
Administration of Informed Consent Form ................................................................44 
7.2. 
Interactive Web Response Technology Procedure .....................................................44 
7.3. 
Demography and Medical History ..............................................................................44 
7.3.1. 
Demographics and General Medical History .............................................................44 
7.3.2. 
Disease Characteristics and Treatment History ..........................................................44 
7.4. 
Prior and Concomitant Medications and Procedures ..................................................45 


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7.5. 
Safety Assessments .....................................................................................................45 
7.5.1. 
Adverse Events ...........................................................................................................45 
7.5.2. 
Comprehensive Physical Examination .......................................................................45 
7.5.3. 
Disease-Specific Physical Examination .....................................................................46 
7.5.4. 
Vital Signs ..................................................................................................................46 
7.5.5. 
Electrocardiograms .....................................................................................................46 
7.5.5.1. 
Timed Electrocardiograms ..........................................................................................46 
7.5.6. 
ECOG Performance Status .........................................................................................47 
7.5.7. 
Laboratory Assessments .............................................................................................47 
7.5.7.1. 
Chemistry and Hematology ........................................................................................47 
7.5.7.2. 
Pregnancy Testing ......................................................................................................47 
7.5.7.3. 
Serology ......................................................................................................................47 
7.6. 
Efficacy Assessments .................................................................................................48 
7.6.1. 
Computed Tomography Scan or Magnetic Resonance Imaging ................................48 
7.6.2. 
Bone Marrow Examination .........................................................................................48 
 
48 
7.6.4. 
Independent Review Committee .................................................................................49 
 
49 
 
49 
 
49 
 
50 
 
50 
 
.50 
 
50 
 
50 
 
50 
 
51 
7.9. 
Other Study Procedures ..............................................................................................51 
7.9.1. 
Distribution of Subject Reminder Cards .....................................................................51 
7.9.2. 
Data Collection for Survival Follow-Up ....................................................................51 
8. 
SAFETY MONITORING AND REPORTING .........................................................51 
8.1. 
Adverse Events ...........................................................................................................51 
8.1.1. 
Definitions ..................................................................................................................51 


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8.1.2. 
Reporting ....................................................................................................................51 
8.2. 
Laboratory Test Abnormalities ...................................................................................53 
8.3. 
Serious Adverse Events ..............................................................................................53 
8.3.1. 
Definitions ..................................................................................................................53 
8.3.2. 
Reporting ....................................................................................................................54 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................55 
8.5. 
Adverse Events of Special Interest .............................................................................55 
8.6. 
Pregnancy ...................................................................................................................55 
8.7. 
Warnings and Precautions ..........................................................................................56 
8.8. 
Independent Data Monitoring Committee ..................................................................56 
8.9. 
Product Complaints ....................................................................................................56 
9. 
STATISTICS ..............................................................................................................57 
9.1. 
Study Populations .......................................................................................................57 
9.2. 
Selection of Sample Size ............................................................................................57 
9.3. 
Level of Significance ..................................................................................................57 
9.4. 
Statistical Analyses .....................................................................................................57 
9.4.1. 
Efficacy Analyses .......................................................................................................58 
9.4.1.1. 
Primary Efficacy Analyses .........................................................................................58 
9.4.1.2. 
Secondary Efficacy Analyses .....................................................................................58 
9.4.1.3. 
Other Efficacy Analyses .............................................................................................59 
9.4.2. 
Safety Analyses ..........................................................................................................59 
9.4.2.1. 
Adverse Events ...........................................................................................................59 
9.4.2.2. 
Clinical Laboratory Tests ...........................................................................................59 
9.4.2.3. 
Vital Signs ..................................................................................................................60 
9.4.2.4. 
Electrocardiograms .....................................................................................................60 
9.4.2.5. 
Adverse Events of Special Interest .............................................................................60 
 
60 
 
60 
9.5. 
Analyses for the Data Monitoring Committee ............................................................61 
9.6. 
Interim Analysis ..........................................................................................................61 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ..........................................................................................................61 
10.1. 
Investigator Responsibilities .......................................................................................61 




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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Abbreviation 
Definition 
AE 
adverse event 
AKT 
protein kinase B 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
BTK 
Bruton's tyrosine kinase 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
 
 
CMR 
complete metabolic response 
CMV 
cytomegalovirus 
CR 
complete response 
CRR 
complete response rate 
CSR 
Clinical Study Report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EOT 
end of treatment 
 
 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
 
 
IB 
Investigator's Brochure 


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Abbreviation 
Definition 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee 
IEC 
independent ethics committee 
IN 
Investigator Notification 
irAE 
immune-related adverse event 
IRB 
institutional review board 
IRC 
Independent Review Committee 
IV 
intravenously 
IWRS 
interactive web response system 
LD 
longest transverse diameter 
MCL 
mantle cell lymphoma 
MedDRA 
Medical Dictionary for Regulatory Activities 
 
 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin's lymphoma 
ORR 
objective response rate 
OS 
overall survival 
pAKT 
phosphorylated protein kinase B 
PD 
progressive disease 
PFS 
progression-free survival 
PI3K 
phosphoinositide 3-kinase 
PJP 
Pneumocystis jirovecii pneumonia 
 
 
PMR 
partial metabolic response 
PR 
partial response 
QD 
once daily 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SCT 
stem cell transplant 
SD 
stable disease 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
 
 


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1. 
INTRODUCTION 
1.1. 
Mantle Cell Lymphoma 
Non-Hodgkin lymphoma is the most common hematologic malignancy, with over 385,000 new 
cases diagnosed in 2012 (Torre et al 2015).  Incidence rates of NHL tend to be higher in North 
America, Western Europe, Northern Europe, and Australia compared with the rest of the world; 
it has been estimated that over 80,000 new cases of NHL and approximately 20,000 deaths due 
to NHL occurred in the United States in 2015 (Siegel et al 2015).  Between 1975 and 2010 the 
incidence of new cases of NHL in the United States has nearly doubled from 11.1 to 20.3 cases 
per 100,000 people, but the proportion of deaths has slowly decreased (NCI 2017). 
Mantle cell lymphoma accounts for approximately 3% to 6% of all NHL cases 
(Cheah et al 2016) in Western countries.  Approximately 3 of 4 patients are male, and the disease 
occurs approximately twice as frequently in Caucasians as compared with Blacks.  The median 
age at diagnosis is 68 years old (Schulz et al 2007).  The most common form of MCL, referred to 
as Classical MCL, is genetically characterized by the reciprocal translocation t(11;14)(q13;q32) 
(abbreviated as t(11;14)) that leads to the overexpression of CCND1, which drives tumor growth 
and division (Campo et al 2015).  Classical MCL is derived from mature B cells that carry no or 
few somatic mutations in the IGHV and express SOX11, a transcription factor.  Classical MCL 
is more aggressive than the less common form of MCL, which contains IGHV with somatic 
hypermutations and expresses SOX11at very low levels or not at all.  This subtype of MCL can 
become more aggressive with additional mutations in genes such as TP53 (Campo et al 2015).  
The median OS time for treated patients is approximately 8 to 10 years.  Currently available 
treatments are not considered curative (Schulz et al 2007); therefore, an unmet medical need 
exists for patients with MCL.  
1.2. 
Treatment for Mantle Cell Lymphoma 
Most patients with MCL (70%) have advanced stage disease at diagnosis (Argatoff et al 1997).  
There is currently no method to guide treatment, but the MIPI has been developed to facilitate 
risk-adapted treatment (Hoster et al 2008; see Appendix D).  The MIPI index is based on 
4 factors:  age, performance status, LDH levels, and leukocyte count.  Additional prognostic 
factors evaluated include Ki-67, gene expression profiling, MRD, MCL cell type, peripheral 
blood AMC at diagnosis, and beta2-microglobulin level (LLS 2014). 
Multiple approaches are used in the first-line treatment for MCL, but treatment typically consists 
of chemotherapy plus an immunotherapy (ie, chemoimmunotherapy).  Treatment options include 
conventional chemoimmunotherapy alone or followed by maintenance rituximab; conventional 
chemoimmunotherapy followed by high-dose chemotherapy and autologous hematological cell 
transplant; intensive chemoimmunotherapy; and conventional chemoimmunotherapy plus 
involved-field radiation therapy.  Unfortunately, none of these modalities is curative 
(Cheah et al 2016). 
Most patients will experience serial relapse and can use any number of approved therapies or 
unapproved therapies in clinical studies.  The best order of treatment for these therapies is not 
known, and choice of therapy will depend on a number of factors, including prior treatment, 


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patient comorbidities and performance status, and expected toxicities.  In the United States, 
approved therapies for MCL include ibrutinib, lenalidomide, and bortezomib.  Ibrutinib 
(Wang et al 2013), lenalidomide (Goy et al 2013), and bortezomib (Fisher et al 2006) received 
accelerated approval based on the ORRs observed in single-arm, Phase 2 studies; bortezomib (in 
combination with chemotherapy) was also approved in a randomized Phase 3 study of previously 
untreated subjects with MCL (Robak et al 2015).  In the EU, ibrutinib, lenalidomide, and 
temsirolimus (Hess et al 2009) are approved for adult subjects with relapsed or refractory MCL; 
bortezomib (in combination with chemotherapy) is approved for treatment of adult patients with 
previously untreated MCL who are unsuitable for hematopoietic SCT. 
The Phase 2 study of ibrutinib that led to approval in the United States and in the EU was 
conducted in subjects with MCL that had received a least 1 prior therapy.  This study enrolled 
111 subjects and demonstrated a 68% response rate and a median PFS of 13.9 months; 47% of 
subjects were alive at 2 years (Wang et al 2015).  Similar results were observed in a second study 
(Wang et al 2014).  Ibrutinib is currently being evaluated in a Phase 3 study in the first line in 
combination with bendamustine and rituximab. 
1.3. 
INCB050465 
Phosphatidylinositol 3-kinases belong to a family of lipid signaling kinases that phosphorylate 
phosphoinositides of the inositol ring (Cantley et al 2002).  Phosphatidylinositol 3-kinases are 
divided into 3 classes (Class I, II, and III) according to their structure, regulation, and substrate 
specificity.  Class I PI3Ks, which include PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, are dual-specificity 
lipid and protein kinases that catalyze the phosphorylation of phosphatidylinositol-4,5-
bisphosphate, giving rise to phosphatidylinositol-3,4,5-trisphosphate.  Phosphatidylinositol-
3,4,5-trisphosphate functions as a second messenger that controls a number of cellular processes, 
including growth, survival, adhesion, and migration.  The recognition that aberrant signal 
transduction occurs in malignant B-lymphocytes via the PI3K pathways resulting in disease 
progression has led to a focus on agents that modulate these signaling pathways.   
INCB050465 is a potent inhibitor of PI3Kδ (IC50 value = 1.1 ± 0.5 nM), with approximately 
20,000-fold selectivity for the other PI3K family members.  INCB050465 does not significantly 
inhibit (< 30% inhibition) a broad panel of kinases when tested at a concentration of 100 nM 
(refer to the Investigator's Brochure [IB]).  INCB050465 is potent (IC50 values of ≤ 10 nM) in 
cell-based assays relevant to the pathogenesis of B-cell malignancies, such as PI3Kδ-mediated 
signaling and growth of human B-cell lines.  This effect is not due to general cytotoxicity.  
Compared with inhibition of B-cell proliferation, INCB050465 is similarly potent in blocking 
helper T-cell differentiation but is > 100 times less potent in assays that measure effects on 
human T-cell and natural killer cell proliferation or monocyte function.  These data suggest that 
the impact of INCB050465 on the human immune system will largely be restricted to B-cell and 
helper T-cell differentiation (IB).  The IC90 for pAKT inhibition of Pfeiffer cells in human whole 
blood is 77 nM (IB).  Preclinical toxicology studies supported evaluation of INCB050465 in 
human clinical studies (IB). 
INCB050465 is being evaluated as a monotherapy in a Phase 1/2, dose-escalation and expansion 
study (INCB 50465-101, NCT02018861).  As of 18 AUG 2017, data were available for 
72 subjects who received INCB050465 administered orally at QD doses of 5 mg (n = 1), 10 mg 
(n = 3), 15 mg (n = 3), 20 mg (n = 34), 30 mg (n = 27), and 45 mg (n = 4).  The median duration 


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of treatment was 123 days (range:  7-690).  Adverse events observed in ≥ 20% of subjects were 
nausea (36%), diarrhea (35%), fatigue (31%), cough (24%), and vomiting (24%).  New or 
worsening Grade ≥ 3 anemia, thrombocytopenia, and neutropenia occurred in 7%, 10%, and 19% 
of subjects, respectively.  No Grade ≥ 3 nonhematological treatment-related AEs were reported 
in ≥ 10% of subjects.  Serious AEs that occurred in ≥ 2 subjects included diarrhea (n = 5); 
pyrexia (n = 4); colitis, hypotension, and sepsis (n = 3 each); pneumonia, exfoliative dermatitis, 
syncope, bacteremia, respiratory failure, bronchitis, urinary tract infection, and ventricular 
tachycardia (n = 2 each).  Fourteen (19%) of the 72 subjects discontinued study treatment due to 
the following 14 AEs:  diarrhea (n = 3); exfoliative dermatitis and colitis (n = 2 each); 
pneumonitis, rash, psoriasis, neutropenia, cytomegalovirus colitis, pleural effusion, and 
hypercalcemia (n = 1 each).  All but 1 of these events occurred after the 9-week disease 
assessment.  No liver function test abnormalities Grade > 1 were reported while subjects were 
receiving study treatment.  No dose-limiting toxicities were identified, and the maximum 
tolerated dose was not reached. 
As of 18 AUG 2017, 30 objective responses as reported by investigators were observed at doses 
≥ 10 mg QD in 55 subjects with diffuse large B-cell lymphoma, FL, marginal zone lymphoma, 
and MCL.  These results include 3 CR/CMR, 1 PR/PMR, and 1 SD in 5 ibrutinib-naïve subjects 
with MCL, and 1 CMR, 1 PMR, and 1 SD in 4 ibrutinib-experienced subjects with MCL.  All of 
these objective responses occurred by the time of the 9-week disease assessment.  At the time of 
the data cutoff, 5 of these subjects had been on study treatment at least 6 months, 4 of whom had 
been on study treatment at least 10 months.  The longest duration of study treatment among 
subjects with MCL was approximately 76 weeks, with 4 subjects ongoing. 
Pharmacokinetics analysis showed that the tmax is 0.5 to 1 hour, the terminal half-life is 
approximately 8 to 12 hours, and the exposure appeared to be dose-proportional between 5 mg 
QD and 45 mg QD at steady state.  The pharmacodynamic analyses demonstrated robust and 
sustained pathway inhibition at all dose levels tested (Phillips et al 2016).  Refer to the IB for 
further details. 
1.4. 
Study Rationale 
Multiple agents have been approved in the United States and the EU for the treatment of mantle 
cell lymphoma.  One of these agents, ibrutinib, is currently being evaluated in the first line in 
combination with bendamustine and rituximab, which could potentially create a relatively large 
population of subjects who have received ibrutinib.  Despite the unprecedented response 
observed with a targeted agent, a retrospective study conducted on 114 patients treated with 
ibrutinib showed a median OS after cessation of ibrutinib of 2.9 months (95% CI, 1.6-4.9).  The 
poor outcome for patients treated with ibrutinib demonstrates the need for new therapies in the 
post-ibrutinib setting (Martin et al 2016).  INCB050465 has demonstrated promising activity in 
relapsed or refractory subjects with MCL (see Section 1.3).  This study will evaluate 
INCB050465 for efficacy and safety in subjects with MCL who were previously treated with 
ibrutinib or who have not received any type of a BTK inhibitor.  


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All subjects will receive INCB050465 20 mg QD for 8 weeks followed by either 20 mg once 
weekly or 2.5 mg QD.  Based on an ex vivo whole blood assay, the 20 mg QD dose provides 
exposure ranging from approximately 2-fold above the IC90 at trough to 19-fold above the 
IC90 at peak.  Data as of 02 SEP 2016 showed that of the 11 NHL subjects that were 
administered 20 mg QD, 10 achieved an objective response at the time of first disease 
assessment (9 weeks).  However, among all evaluable subjects with an objective response 
(n = 20), 7 subjects (35%) discontinued study treatment due to an AE.  Consequently, after 
receiving 20 mg QD of INCB050465 for 8 weeks, subjects will receive either 20 mg once 
weekly (Treatment A) or 2.5 mg QD (Treatment B) of INCB050465. 
The 20 mg once-weekly regimen is proposed to maintain response while providing time off from 
pathway inhibition, which may reduce the frequency of AEs leading to study treatment 
withdrawal.  Pharmacodynamic data from Study INCB 50465-101 showed that a single dose of 
20 mg exhibited maximal inhibition of AKT in an ex vivo pharmacodynamic assay, and PK 
modeling suggests that 20 mg once weekly will 1) achieve maximal inhibition equivalent to 
approximately 10 × IC90, 2) exceed the IC90 for approximately 36 hours, and 3) have minimal to 
no inhibition for approximately half the dosing interval.  This once-weekly regimen is similar to 
that of another PI3K inhibitor (copanlisib), which is administered IV on Days 1, 8, and 15 of a 
28-day cycle and achieved 7 objective responses in 9 subjects with NHL (Patnaik et al 2016).  
Among the 51 subjects who received study treatment, 4 discontinued treatment due to an AE.  
There were 2 events of Grade 3 noninfectious pneumonitis, 1 event of Grade 3 diarrhea, and no 
events of colitis. 
The 2.5 mg QD regimen is proposed to provide enough exposure (estimated to be approximately 
1 × IC90 at peak) to maintain PI3K pathway inhibition but reduce the frequency of AEs that lead 
to study treatment withdrawal.  The continuous QD regimen has demonstrated prolonged 
responses in both aggressive and indolent NHL, and a continuous lower dose will be evaluated in 
this study.  One subject with FL who received a 10 mg QD dose achieved a complete metabolic 
response and remained on study treatment for approximately 13 months before withdrawing due 
to an AE (Grade 2 psoriasis). 
1.5. 
Potential Risks and Benefits of the Treatment Regimen 
INCB050465 has effects on the immune system.  Therefore, subjects in this study will be 
monitored closely for evidence of infections or new cancers, and study treatment administration 
will be discontinued if there is evidence of clinically significant infection or new cancer. 
Pneumocystis jirovecii pneumonia has not been reported with the use of INCB050465 as 
monotherapy.  However, PJP was reported for 1 subject administered INCB050465 in 
combination with pembrolizumab in Study INCB 39110-107 (NCT02646748).  All subjects in 
Study INCB 50465-205 will receive PJP prophylaxis.  Subjects will be asked to report all sulfa 
drug allergies, and those allergic to standard PJP prophylaxis with sulfonamide antibiotics will 
receive either inhaled pentamidine or atovaquone for PJP prophylaxis; these subjects will not be 
given dapsone. 


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As presented in Section 1.3, objective responses were reported in 30 of 55 NHL subjects, 
including 6 responses in 9 MCL subjects.  Adverse events were also observed in subjects 
administered INCB050465 (see Section 1.3).  Dose modification guidance and supportive care 
guidelines for diarrhea/colitis are implemented in this study.  INCB050465 monotherapy has also 
demonstrated efficacy in multiple tumor types including MCL (see Section 1.3). 
Based on safety and efficacy data from the ongoing Study INCB 50465-101, the treatment 
regimen for this study will be 20 mg QD for 8 weeks, followed by either 20 mg once weekly or 
2.5 mg QD of INCB050465.  As detailed in Section 1.3, these regimens are proposed to assess 
whether the frequency of AEs leading to treatment withdrawal will be reduced while maintaining 
PI3K pathway inhibition and maintenance of response. 
INCB050465 is metabolized primarily by CYP3A4; therefore, use of any potent CYP3A4 
inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of 
INCB050465 will be prohibited. 
The effects of INCB050465 on fetal development have not been evaluated, nor is it known 
whether INCB050465 passes into human breast milk; therefore, subjects who are pregnant or 
breastfeeding are excluded from participation in this study. 
There are no preclinical data available to date on the potential phototoxicity of INCB050465.  
Therefore, subjects enrolled in this study taking INCB050465 will be instructed by the site staff 
to take precaution to protect themselves from the sun/ultraviolet light.  This includes wearing 
long sleeves, long trousers, hats, sunscreen, and sunglasses. 


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
The objectives and endpoints described in Table 1 are applicable for both cohorts.  See 
Section 9.4 for details on the analysis of endpoints for each cohort. 
Table 1: 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To assess the efficacy of INCB050465 in terms of 
ORR in subjects in with MCL that is relapsed or 
refractory after at least 1 but no more than 3 prior 
systemic treatment regimens. 
ORR defined as the percentage of subjects with a CR or 
PR as determined by an IRC assessment of response 
according to CT-based response criteria for lymphomas 
(Cheson et al 2014). 
Secondary 
To assess DOR. 
DOR defined as the time from first documented evidence 
of CR or PR until disease progression or death from any 
cause among subjects who achieve an objective response, 
as determined by radiographic disease assessment 
provided by an IRC. 
To assess CRR. 
CRR defined as the percentage of subjects with a CR as 
defined by response criteria for lymphomas 
(Cheson et al 2014), as determined by an IRC. 
To assess PFS. 
PFS defined as the time from the date of the first dose of 
study treatment until the earliest date of disease 
progression, as determined by radiographic disease 
assessment provided by an IRC, or death from any cause. 
To assess OS. 
OS defined as the time from the date of the first dose of 
study treatment until death from any cause. 
To assess the best percentage change in target lesion 
size. 
Best percentage change in target lesion size from baseline, 
where target lesion size is measured by the sum of the 
product of diameters of all target lesion sizes. 
To characterize the safety and tolerability of 
INCB050465. 
Safety measured by AEs, 12-lead ECGs, chemistry and 
hematology laboratory values, vital signs, and physical 
examinations. 


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3. 
SUBJECT ELIGIBILITY 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or subject safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential. 
3.1. 
Subject Inclusion Criteria 
A subject who meets all of the following criteria may be included in the study: 
1. Men and women, aged 18 or older. 
2. Pathologically confirmed MCL, with documentation of either overexpression of 
cyclin D1 or t(11;14). 
3. Have received at least 1 but no more than 3 prior systemic treatment regimens. 
a. Subjects in Cohort 1 will have previously received ibrutinib. 
b. Subjects in Cohort 2 will not have previously received a BTK inhibitor (eg, ibrutinib). 
4. Documented failure to achieve at least PR with or documented disease progression after 
the most recent treatment regimen. 
5. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy 
(defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the LDi and ≥ 1.0 cm in 
the longest perpendicular diameter as assessed by CT or MRI. 
6. Subjects must be willing to undergo an incisional, excisional, or core needle lymph node 
or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available 
archival tissue. 
7. Life expectancy > 3 months. 
8. ECOG performance status 0 to 2 (see Appendix B). 
9. Adequate hematologic, hepatic, and renal function (values must not be achieved with 
growth factors): 
a. ANC ≥ 1.0 × 109/L. 
b. Hemoglobin ≥ 8.0 g/dL. 
c. Platelet count ≥ 50 × 109/L. 
d. Total bilirubin ≤ 1.5 × ULN.  Subjects with documented history of Gilbert’s 
syndrome and in whom total bilirubin elevations are accompanied by elevated 
indirect bilirubin are eligible. 
e. ALT/AST ≤ 3.0 × ULN or ≤ 5 × ULN in the presence of liver metastases. 
f. Calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault Equation 
(Cockcroft and Gault 1976) or the estimated glomerular filtration rate 
≥ 50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula. 


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10. Willingness to avoid pregnancy or fathering children based on the criteria below: 
a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or 
bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 45 years of age). 
b. Woman of childbearing potential who has a negative serum pregnancy test at 
screening and who agrees to take appropriate precautions to avoid pregnancy (with at 
least 99% certainty) from screening through safety follow-up.  Permitted methods that 
are at least 99% effective in preventing pregnancy (see Appendix A) should be 
communicated to the subject and their understanding confirmed. 
c. Man who agrees to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening through at least 93 days after the last dose of 
study treatment.  Permitted methods that are at least 99% effective in preventing 
pregnancy (see Appendix A) should be communicated to the subject and their 
understanding confirmed. 
3.2. 
Subject Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. History of central nervous system lymphoma (either primary or metastatic).  
2. Prior treatment with idelalisib, other selective PI3Kδ inhibitors, or a pan-PI3K inhibitor. 
3. Allogeneic SCT within the last 6 months, or autologous SCT within the last 3 months 
before the date of the first dose of study treatment. 
4. Active graft-versus-host disease. 
5. Use of immunosuppressive therapy within 28 days of the date of study treatment 
administration.  Immunosuppressive therapy includes, but is not limited to, 
cyclosporine A, tacrolimus, or high-dose corticosteroids.  Subjects receiving 
corticosteroids must be at a dose of ≤ 10 mg/day prednisone (or equivalent) within 7 days 
of the date of first study treatment administration.  
6. Receipt of anticancer medications or investigational drugs within the following intervals 
before the first dose of study treatment: 
a. < 10 weeks from completion of any radio- or toxin-immunoconjugates.  
b. < 6 weeks for mitomycin-C or nitrosoureas. 
c. < 4 weeks for immunotherapy. 
d. < 3 weeks for radiotherapy. 
e. < 3 days for ibrutinib. 
f. < 2 weeks for any investigational agent or other anticancer medications. 
7. Inadequate recovery from toxicity and/or complications from a major surgery before the 
date of the first dose of study treatment. 
8. Prior treatment-related toxicities have not resolved to NCI CTCAE v4.03 (NCI 2010) 
≤ Grade 1 before the date of the first dose of study treatment except for stable chronic 
toxicities (Grade ≤ 2) not expected to resolve (eg, stable Grade 2 peripheral 
neurotoxicity). 


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9. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, 
immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor 
embolization). 
10. Use or expected use during the study of any prohibited medications, including potent 
CYP3A4 inhibitors or inducers (please refer to the Pharmacy Manual and consult your 
local pharmacist) within 14 days or 5 half-lives (whichever is longer) before the date of 
study treatment administration. 
11. Significant concurrent, uncontrolled medical condition, including, but not limited to, 
renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, or 
psychiatric disease. 
12. Current or previous other malignancy within 3 years of study entry, except cured basal or 
squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, 
carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without 
sponsor approval. 
13. History of stroke or intracranial hemorrhage within 6 months of the date of study 
treatment administration. 
14. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or 
antiviral treatment or exposure to a live vaccine within 30 days of study treatment. 
15. Known HIV infection or positivity on immunoassay.  Note:  HIV screening test is 
optional for subjects enrolled in the United States, but subjects with known HIV infection 
in the United States will be excluded. 
16. Hepatitis B (HBV) or hepatitis C (HCV) infection:  Subjects positive for hepatitis B 
surface antigen or hepatitis B core antibody will be eligible if they are negative for 
HBV-DNA; these subjects should be considered for prophylactic antiviral therapy.  
Subjects positive for anti-HCV antibody will be eligible if they are negative for 
HCV-RNA 
17. Clinically significant cardiac disease, including unstable angina, acute myocardial 
infarction, and/or cardiac conduction issues within 6 months of the date of study 
treatment administration.  
18. Current New York Heart Association Class II to IV congestive heart failure or 
uncontrolled arrhythmia. 
19. Presence of an abnormal ECG that is clinically meaningful.  Screening QTc interval 
> 450 milliseconds is excluded (corrected by Fridericia).  In the event that a single QTc is 
> 450 milliseconds, the subject may enroll if the average QTc for 3 ECGs is 
< 450 milliseconds. 
20. Unable to swallow and retain oral medication, malabsorption syndrome, disease 
significantly affecting GI function, total resection of the stomach or small bowel, 
ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel 
obstruction. 
21. Known hypersensitivity or severe reaction to INCB050465 or its excipients (refer to 
the IB). 


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22. History of serious allergic reactions including anaphylaxis and toxic epidermal 
necrolysis. 
23. Currently pregnant or breastfeeding. 
24. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study treatment and attending required study 
visits; pose a significant risk to the subject; or interfere with interpretation of study data. 
25. Inability to comprehend or unwilling to sign the ICF (see Section 7.1). 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy and safety of 
2 INCB050465 treatment regimens in relapsed or refractory MCL previously treated either with 
or without a BTK inhibitor (see Figure 1).  A total of approximately 190 subjects were planned 
to be enrolled across 2 cohorts.  Cohort 1 will be closed to further enrollment by Protocol 
Amendment 7 with approximately 50 subjects enrolled.  The estimated total number of subjects 
to be enrolled in the study is approximately 150. 
Subjects with MCL who have received at least 1 but no more than 3 prior systemic treatment 
regimens will be screened for eligibility.  Subjects will be allocated to Cohort 1 or Cohort 2 as 
follows: 
• Cohort 1:  Subjects have previously received ibrutinib  
• Cohort 2:  Subjects have not previously received a BTK inhibitor  
Cohort 1 and Cohort 2 will have separate designs, conduct, and analyses. 
The first 60 subjects in each cohort who meet the eligibility criteria will be randomly allocated to 
1 of 2 study treatment regimens through the IWRS (see Section 5.1): 
• Treatment A:  INCB050465 20 mg QD for 8 weeks followed by 20 mg once weekly 
− Subjects in Cohort 1 receiving Treatment A will be referred to as Cohort 1A 
− Subjects in Cohort 2 receiving Treatment A will be referred to as Cohort 2A 
• Treatment B:  INCB050465 20 mg QD for 8 weeks followed by 2.5 mg QD 
− Subjects in Cohort 1 receiving Treatment B will be referred to as Cohort 1B 
− Subjects in Cohort 2 receiving Treatment B will be referred to as Cohort 2B 
To better understand the safety and efficacy of INCB050465, a total of 70 additional subjects 
(30 subjects in Cohort 1 and 40 subjects in Cohort 2) will be enrolled into one of the 2 treatment 
regimens (A or B) being evaluated in this study.  The treatment regimen will be selected after 
enrollment is completed for either Cohort 1 or Cohort 2 (ie, 60 subjects enrolled) and after 
evaluation of emerging safety and efficacy data from this and other monotherapy studies of 
INCB050465 in NHL.  Once a treatment regimen is selected, the nonselected treatment regimen 
will be closed to further enrollment.  Subjects receiving the nonselected treatment regimen may 


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switch to the selected treatment regimen or remain on their current treatment regimen, provided 
they have not met study treatment withdrawal criteria, and there are no safety concerns for their 
current treatment regimen.  There will be no re-baselining for subjects who switch treatment 
regimens, and all subjects will continue to follow the same assessment schedule. 
NOTE:  The primary, secondary, 
 objectives and endpoints described in 
Section 2 are applicable for both cohorts; however, the cohorts will be analyzed separately, when 
applicable, as detailed in Section 9. 
Subjects will receive treatment until disease progression, death, unacceptable toxicity, or consent 
withdrawal, whichever occurs first. 
Subjects will be monitored for safety and efficacy periodically until disease progression, death, 
unacceptable toxicity, or withdrawal of informed consent.  An IDMC will review safety data 
periodically as stated in the IDMC charter.  Subjects will be evaluated for ORR by an IRC, and 
followed for DOR, PFS, and OS.  
An interim futility analysis is planned for each of the cohorts when 30 subjects have been treated 
and have been evaluated for response or have permanently discontinued study treatment because 
of disease progression, withdrawal of consent, or death.  Cohort 1 will be terminated for futility 
if ≤ 3 of the 30 subjects responded (ie, CR or PR) based on assessments provided by the IRC.  
Cohort 2 will be terminated for futility if ≤ 10 of the 30 subjects have responded (ie, CR or PR) 
based on assessments provided by the IRC.  A timely assessment of response will be performed 
to avoid the risk of overenrollment. 
The IDMC determined that the futility boundary was not crossed at the interim analysis of 
Cohort 1 and that there were no safety issues preventing further enrollment.  However, the 
sponsor has concluded that the observed ORR is not clinically meaningful.  Therefore, Cohort 1 
will be closed to further enrollment by Protocol Amendment 7 with approximately 50 subjects 
enrolled.  Subjects already enrolled in Cohort 1 will continue to receive study treatment per 
protocol. 
After treatment discontinuation, subjects will be followed for safety and survival.  Subjects who 
have discontinued study treatment due to reasons other than disease progression will be followed 
for radiologic disease progression, the start of a new anticancer therapy, or death, whichever 
comes first.  It is expected that the final analysis will occur no later than 2 years after the first 
dose of INCB050465 is administered to the last subject treated. 


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Figure 1: 
Study Design of INCB 50465-205 
 
4.2. 
Measures Taken to Avoid Bias 
This is an open-label study; no comparisons will be made between subjects or against historical 
controls.  Measurements of safety and efficacy are objective measurements, and only 
comparisons to pretreatment conditions will be made.  Safety will be objectively assessed using 
NCI CTCAE v4.03 (NCI 2010) guidelines and reviewed by the IDMC.  Tumor response will be 
assessed by an IRC using the CT-based criteria of the Lugano classification (Cheson et al 2014). 
4.3. 
Number of Subjects 
4.3.1. 
Planned Number of Subjects 
The study was planned to enroll approximately 190 subjects at approximately 100 investigative 
sites globally.  Cohort 1 will be closed to further enrollment by Protocol Amendment 7 with 
approximately 50 subjects enrolled.  The estimated total number of subjects to be enrolled in the 
study is approximately 150. 
4.3.2. 
Replacement of Subjects 
No subjects will be replaced at any time during this study. 


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4.4. 
Duration of Treatment and Subject Participation 
After signing the ICF, screening assessments may be completed over a period of up to 28 days.  
Each subject enrolled in the study may continue to receive study treatment in continuous 28-day 
intervals.  If the subject discontinues study treatment, the treatment period will end, and the 
subject will enter the 30 to 35-day safety follow-up period, after which the subject will enter the 
survival follow-up period (see Section 6.4.3).  Subject participation is expected to average 
approximately 26 months. 
4.5. 
Overall Study Duration 
The study begins when the first subject signs the ICF.  The end of the study will occur when all 
subjects have discontinued from the study (see Section 5.7) or have completed at least 24 months 
of study participation (starting from the first dose of study treatment).  It is estimated that the 
study will take approximately 2 years to accrue 150 subjects and that the final analysis will be 
performed no later than 2 years after the first dose of study treatment is administered to the last 
subject treated.  Subjects who are still on study treatment and who have no evidence of 
progressive disease at the end of the study will have the option to continue on monotherapy with 
INCB050465 provided within a rollover Protocol, as local law permits (see Section 5.8). 
4.6. 
Study Termination 
The investigator retains the right to terminate study participation at any time for appropriate 
medical or organizational reasons.  The investigator is to notify the institutional review board 
(IRB)/independent ethics committee (IEC) in writing of the study's completion or early 
termination, send a copy of the notification to the sponsor or sponsor's designee, and retain 
1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, if required by a regulatory decision, or upon 
advice of the IDMC.  If the study is terminated prematurely, the sponsor will notify the 
investigators, the IRBs and IECs, and regulatory bodies of the decision and reason for 
termination of the study.  The IDMC will recommend termination of the study if warranted, as 
described in the IDMC charter (see also Section 9.5). 


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5. 
TREATMENT 
5.1. 
Treatment Assignment 
5.1.1. 
Subject Numbering and Treatment Assignment 
Study sites will enter subject demographic and baseline data into the IWRS in order to receive a 
subject number and random treatment allocation. 
All subject numbers will be 6 digits; the first 3 digits will be the site number, and the last 3 digits 
will be the subject's number.  This subject number will be maintained throughout the study and 
will not be reassigned.  Subjects who withdraw consent or discontinue from the study after being 
assigned a subject number will retain their initial number. 
Site staff will contact the IWRS to allocate the subject to treatment assignment and obtain the 
initial study treatment assignment.  The investigator or designee will select the assigned bottles 
of study treatment from their stock that correspond to the number provided by the IWRS and 
dispense the study treatment to the subject.  All subsequent dispensing of study treatment should 
follow this process.  Refer to the IWRS Manual for detailed information. 
If a subject is mistakenly given a bottle of study treatment that is not the bottle assigned by the 
IWRS, the IWRS help desk must be notified immediately.  The reason for the misallocation of 
the study treatment must be documented by the study site and reported to the IRB/IEC. 
For subjects who signed an ICF but are not allocated study treatment and for subjects who are 
allocated study treatment but were not treated, refer to the eCRF Completion Guidelines for 
instruction on which eCRFs to complete. 
5.1.2. 
Randomization and Blinding 
Not applicable. 
5.2. 
INCB050465 
5.2.1. 
Description and Administration 
Details of INCB050465 are shown in Table 2. 


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Table 2: 
Description and Administration of INCB050465 
Compound Name 
INCB050465 
Dose strengths 
1 mg, 2.5 mg, 5 mg, and 20 mg 
Form 
Tablet 
Active compound  
INCB050465  
Route of administration 
Oral 
Dose and regimen for Treatment A 
20 mg QD for 8 weeks followed by 20 mg once weekly 
Dose and regimen for Treatment B 
20 mg QD for 8 weeks followed by 2.5 mg QD 
Instructions 
INCB050465 will be taken orally with water without regard to 
food 
  
INCB050465 should be taken at approximately the same time 
each day. 
For QD administration, if a dose is missed by more than 12 hours, then the subject should skip 
the dose and take the next scheduled dose at the usual time.  For once-weekly administration, if 
the dose is missed by more than 2 days, then the subject should skip the dose and take the next 
scheduled dose. 
5.2.2. 
Supply, Packaging, and Labeling 
INCB050465 will be provided as 1 mg, 2.5 mg, 5 mg, and 20 mg tablets packaged in 
high-density polyethylene bottles.  No preparation is required. 
All Incyte investigational product labels will be in the local language and will comply with the 
legal requirements of each country. 
5.2.3. 
Storage 
Bottles of INCB050465 should be stored at ambient conditions (15°C-30°C or 59°F-86°F). 
5.2.4. 
Instruction to Subjects for Handling INCB050465 
The subject must be instructed in the handling of INCB050465 as follows: 
• To store study treatment at room temperature. 
• To remove from the study treatment bottle only the number of tablets needed at the 
time of administration. 
• Not to remove doses in advance of the next scheduled administration. 
• To make every effort to take doses on schedule. 
• To report any missed doses. 
• To keep INCB050465 in a safe place and out of reach of children. 
• To bring all used and unused study treatment kits to the site at each visit. 


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5.3. 
Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the subject by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with study treatment will be calculated by the sponsor based on the drug 
accountability documented by the site staff and monitored by the sponsor/designee (tablet 
counts).  Subjects will be instructed to bring all study treatments with them to the study visits in 
order for site personnel to conduct tablet counts to assess study treatment accountability.  The 
drug accountability documentation will be used by the sponsor to calculate treatment 
compliance. 
5.4. 
Treatment Interruptions and Adjustments 
5.4.1. 
Criteria and Procedures for Dose Interruptions and Reductions of INCB050465 
Treatment with INCB050465 may be interrupted for up to 14 days to allow for resolution of 
toxicity.  Subjects may resume treatment if no medical condition or other circumstance exists 
that, in the opinion of the investigator, would make the subject unsuitable for further 
participation in the study.  The treating investigator should contact the sponsor to discuss the 
case of any subject whose treatment has been interrupted for more than 14 days before restarting 
treatment with INCB050465. 
5.4.1.1. 
Dose Modifications 
Dose modification guidance for AEs that have been previously observed in subjects receiving 
INCB050465 or are potential class-effect AEs are provided (see Table 3 and Table 5).  The 
starting dose and dose reduction levels of INCB050465 are provided (see Table 4).  Individual 
decisions regarding dose interruption and reduction should be made using clinical judgment and 
in consultation with the sponsor's medical monitor, taking into account relatedness of the AE to 
the study treatment and the subject's underlying condition.  Adverse events that have a clear 
alternative explanation or transient (≤ 72 hours) abnormal laboratory values without associated 
clinically significant signs or symptoms may be exempt from dose reduction guidelines 






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clear fluids.  If sufficient oral fluid intake is not feasible, fluid and electrolytes should be 
substituted via IV infusion.  Subjects should try to eat 5 to 6 small meals per day; low-fat, high 
protein foods; and cooked instead of raw vegetables.  Subjects may supplement their diet with 
bananas, rice, applesauce, and toast to reduce the number of bowel movements and may also try 
crackers, gelatin, noodles, or oatmeal.  Subjects should avoid fried, fatty, greasy, or spicy foods; 
milk, milk products, and acidic drinks; high-fiber foods and foods that cause gas; and alcohol, 
caffeine, and herbal supplements (Coutré et al 2015). 
For each occurrence, attempts should be made to rule out other causes, such as metastatic disease 
or bacterial or viral infection (including CMV), which might require additional supportive care. 
It may be necessary to perform conditional procedures, such as colonoscopy with biopsy as part 
of evaluation of the event.  Note that several courses of steroid tapering may be necessary as 
symptoms may worsen when the steroid dose is decreased. 
Subjects should be carefully monitored for signs and symptoms of enterocolitis (such as diarrhea, 
abdominal pain or cramping, blood or mucus in stool, with or without fever) and of bowel 
perforation (such as peritoneal signs and ileus). 
Table 5: 
Guidelines for Dose Modification of INCB050465 for Diarrhea/Colitis 
ADVERSE EVENT 
ACTION TAKEN 
• Diarrhea (Grade 1). 
Step 1:  Treat with antimotility agents (eg, 4 mg loperamide followed by 2 mg 
every 4 hours or after every unformed stool) and initiate supportive care (see 
Section 5.4.2).  Monitor approximately every 48 hours until resolved.  If not 
improved after 48 hours, treat per guidance for Grade 2. 
• Diarrhea (Grade 2). 
Step 1:  Interrupt INCB050465.  Perform work-up for infection (including 
CMV, C. difficile, etc) immediately.  Initiate or continue supportive care (see 
Section 5.4.2).  Monitor approximately every 48 hours until resolution. 
Step 2:  If improved within 48 hours and/or infection* is confirmed, restart 
INCB050465 at the same schedule and dose after resolved to ≤ Grade 1 and 
continue to monitor. 
*For infectious diarrhea/colitis, follow institutional standard-of-care 
guidelines and restart INCB050465 according to clinical judgement after 
resolved to ≤ Grade 1.  Consult with medical monitor if needed. 
Step 3:  If not improved within 48 hours and infection is ruled out, start oral 
steroids, or consider IV steroids if participant is being given IV fluids.  If no 
improvement with oral steroids, switch to IV steroids. 
Step 4:  When diarrhea resolves to ≤ Grade 1, continue supportive care and 
taper steroids according to institutional standard of care.  When taper is 
complete (eg, no steroid or ≤ 10 mg/day prednisone or equivalent) and 
diarrhea is ≤ Grade 1, restart INCB050465 at the next lower dose with 
approval of the medical monitor (see Table 4 for dose levels). 
Step 5:  If Grade 2 diarrhea reoccurs, treat per guidance for diarrhea 
(≥ Grade 3)/noninfectious colitis. 
Step 6:  If ≥ Grade 2 diarrhea reoccurs a third time, permanently discontinue 
INCB050465. 


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Table 5: 
Guidelines for Dose Modification of INCB050465 for Diarrhea/Colitis 
(Continued) 
ADVERSE EVENT 
ACTION TAKEN 
• Diarrhea (≥ Grade 3). 
• Noninfectious colitis (any grade; 
confirmed or suspected). 
Step 1:  Interrupt INCB050465.  Perform work-up for infection (including 
CMV, C. difficile, etc) immediately.  Initiate or continue supportive care (see 
Section 5.4.2).  Consider colonoscopy with biopsy for diarrhea ≥ Grade 3 
and/or if symptomsa suggestive of colitis.  Monitor every 48 hours until 
resolution. 
Step 2:  If infection* is ruled out, start oral steroids, or consider IV steroids if 
participant is being given IV fluids.  If no improvement with oral steroids 
within 48 hours, switch to IV steroids. 
*For infectious diarrhea/colitis, follow institutional standard of care guidelines 
and restart parsaclisib according to clinical judgement after resolved to 
≤ Grade 1.  Consult with medical monitor if needed. 
Step 3:  When diarrhea/colitis resolves to ≤ Grade 1, continue supportive care 
and taper steroids according to institutional standard of care.  When taper is 
complete (eg, no steroid or ≤ 10 mg/day prednisone or equivalent) and 
diarrhea/colitis is ≤ Grade 1, restart INCB050465 as described herein and with 
approval of the medical monitor.  Continue to monitor. 
INCB050465 Current Dose 
Dose Modification 
Any dose with QD dosing 
20 mg QW regardless of 
Treatment A or B assignment 
20 or 10 mg QW 
Restart next lower dose 
5 mg QW 
Permanently discontinue 
Step 4:  If ≥ Grade 3 diarrhea/colitis (any grade) reoccurs, permanently 
discontinue INCB050465. 
a Diarrhea accompanied by abdominal pain and/or mucus or blood in stool. 
5.4.3. 
Supportive Care Guidelines for Neutropenia and Thrombocytopenia 
Neutropenia and thrombocytopenia appear to be PI3Kδ class-effect toxicities.  Investigators 
should ensure that subjects understand the need to seek medical care when they have conditions 
that could become life-threatening in the presence of cytopenias (eg, neutropenic fever or 
bleeding with low platelets).  Subjects should be instructed to report immediately any signs of 
infection, unexpected bleeding, or sudden, extremely painful headaches. 
5.4.4. 
Definition for Immune-Related Adverse Events 
Adverse events of a potential immunologic etiology, or irAEs, may be defined as an AE 
consistent with an immune phenomenon associated with study treatment exposure after all other 
etiologies have been eliminated.  Immune-related AEs may be expected based on previous 
experience with INCB050465.  Special attention should be paid to AEs that may be suggestive of 
potential irAEs.  Based on emerging data from the ongoing Study INCB 50465-101, most irAEs 
occur after the first 9 weeks of study treatment administration.  However, an irAE could occur at 
any time.  Suspected irAEs should be discussed with the medical monitor when possible. 
Subjects should receive appropriate supportive care measures as deemed necessary by the 
treating investigator.  Suggested supportive care measures for the management of drug-related 
AEs with potential immunologic etiology are outlined in Table 3 and Section 5.4.1.  For each 


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AE, attempts should be made to rule out other causes, including but not limited to metastatic 
disease or bacterial or viral infection, which might require specific supportive care. 
5.5. 
Study Treatment Discontinuation 
The decision to discontinue study treatment will not constitute study completion.  In the event 
that study treatment is discontinued, the treatment period will be considered complete, and the 
follow-up periods will begin. 
5.5.1. 
Criteria for Study Treatment Discontinuation 
Subjects must be withdrawn from study treatment for any 1 of following reasons: 
• The subject has experienced an unacceptable toxicity defined as follows: 
− Occurrence of an AE that is related to study treatment that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the subject's ability to 
continue study-specific procedures or is considered to not be in the subject's best 
interest. 
− Persistent AE requiring a delay of therapy for more than 2 weeks (14 days) unless 
a greater delay has been approved by the sponsor.  
• The subject is unable to tolerate study treatment. 
• The subject has an objective radiographic tumor response of PD. 
• Further participation would be injurious to the subject's health or well-being, in the 
investigator's medical judgment. 
• The subject becomes pregnant. 
• Informed consent is withdrawn.   
Note:  Consent withdrawn means that the subject can no longer be followed.  
Subjects may choose to discontinue study treatment and remain in the study to be 
followed for disease progression and survival per the schedule of assessments. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A subject may be discontinued from study treatment in the following situation:  
• If a subject is noncompliant with study procedures or study treatment administration 
in the investigator's opinion, then the sponsor should be consulted for instruction on 
handling the subject. 
5.5.2. 
Procedures for Study Treatment Discontinuation 
Reasonable efforts should be made to have the subject return for a follow-up visit.  These visits 
are described in Section 6.4.  The last date of the last dose of study treatment and the reason for 
subject withdrawal will be recorded in the eCRF. 


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If a subject permanently discontinues study treatment, then the following should occur: 
• The reason(s) for discontinuation must be documented in the subject's medical record 
and in the eCRF. 
• The EOT visit should be performed. 
− If the EOT visit coincides with a regular study visit, then the EOT evaluations 
will supersede those of that scheduled visit, and the data will be entered in the 
EOT visit in the eCRF. 
• The date of the EOT visit should be recorded in the IWRS. 
• Subjects must be followed for safety for no less than 30 days after the EOT visit or 
until study drug–related toxicities resolve, return to baseline, or are deemed 
irreversible, whichever is longest. 
If the subject discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data will be 
collected.  However, subjects may withdraw consent for study treatment but continue to be 
assessed for disease progression and survival per the schedule of assessments. 
5.6. 
Concomitant Medications 
All concomitant medications and treatments must be recorded in the eCRF.  Any prior 
medication received up to 30 days before the date of study treatment administration (Day 1) will 
be recorded in the eCRF.  Concomitant treatments and/or procedures that are required to manage 
a subject's medical condition during the study will also be recorded in the eCRF. 
5.6.1. 
Pneumocystis Jirovecii Pneumonia Prophylaxis 
All subjects are required to receive a standard PJP prophylaxis regimen determined by the 
investigator.  Examples of standard PJP prophylaxis therapies for this population include 
trimethoprim-sulfamethoxazole, atovaquone, dapsone with or without pyrimethamine, and 
pentamidine (NCCN 2017).  Due to reports of cross-sensitivity between sulfonamides and 
dapsone, all subjects who have a known or suspected allergy to sulfonamides must receive either 
inhaled pentamidine or atovaquone for PJP prophylaxis.  Prophylaxis should be given while 
subjects are receiving study treatment and should continue for at least 2 to 6 months after the last 
dose of study treatment. 
The prophylactic agents will be obtained from commercial supplies and will be reimbursed by 
Incyte.  Investigators are responsible for ensuring that subjects receive commercially available 
supplies of the selected prophylactic agents as required per Protocol.  Further details are 
available in the Pharmacy Manual. 
5.6.2. 
Restricted Medications 
• Use of systemic corticosteroid doses ≤ 10 mg/day prednisone (or equivalent) is 
permitted but discouraged from the screening visit through EOT. 
• Short courses of systemic corticosteroid doses > 10 mg/day prednisone or equivalent 
are permitted only in the case of severe or life-threatening complications that cannot 
be controlled with other drugs, but are otherwise discouraged from the screening visit 
through EOT. 


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• Use of weak or moderate inducers or inhibitors of CYP3A4 (please refer to the 
Pharmacy Manual and consult your local pharmacist) is discouraged, and 
investigators should seek other options where possible. 
• Use of P-glycoprotein substrates of clinical relevance should be used with caution 
(ie, aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, everolimus, 
fexofenadine, imatinib, lapatinib, maraviroc, nilotinib, posaconazole, ranolazine, 
saxagliptin, sirolimus, sitagliptin, talinolol, tolvaptan, topotecan) from the screening 
visit through EOT. 
• Localized radiotherapy will be permitted if administered as treatment for pain or 
impending compression fractures and with prior approval of the medical monitor. 
5.6.3. 
Prohibited Medications 
• Use of potent inducers and inhibitors of CYP3A4 are prohibited (please refer to the 
Pharmacy Manual and consult your local pharmacist).  Based on the low overall 
bioavailability of topical ketoconazole, there are no restrictions on topical 
ketoconazole. 
• Apart from the study treatments, the use of any anticancer medications as described 
(see Section 3.2) through the safety follow-up is prohibited. 
• Exposure to a live vaccine within 30 days of study treatment through 3 months after 
the last dose of INCB050465. 
5.7. 
Criteria for Study Discontinuation 
A subject will be discontinued from the study for any 1 of the following reasons: 
• The subject has died. 
• The subject is considered lost-to-follow-up when he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site (eg, after 3 telephone 
calls and/or a certified letter or local equivalent). 
• Informed consent is withdrawn. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB or IEC. 
5.8. 
Treatment After the End of the Study 
At the end of the study as defined in Section 6.5, subjects who have completed at least 24 months 
of study participation (starting from the first dose of study treatment), who remain on active 
study treatment, and who have no evidence of progressive disease will have the option to 
continue on monotherapy with INCB050465 provided within a rollover Protocol, as local law 
permits. 


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6. 
STUDY ASSESSMENTS 
All study assessments will be performed as indicated in the schedule of assessments (see 
Table 6), and all laboratory assessments will be performed as indicated in Table 7.  All 
assessments mandated throughout the study must be performed on a calendar schedule; delays in 
treatment administration will not delay performance of assessments.  By convention, Week 4, 
Week 8, Week 12, etc, means the completion of 4, 8, or 12 weeks. 
Table 8 presents a summary of clinical laboratory analytes to be assessed.  The order of 
assessments is suggested by the order of mention within the schedule.  See Section 7 for 
instructions on each assessment. 


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Table 6: 
Schedule of Assessments 
Procedure 
Section 
Screening 
Treatment 
EOT 
Follow-Up 
Days -28 
to -1 
Day 1a 
Every 4 Weeks 
Through Week 48 
(± 3 Days) 
Every 12 Weeks 
From Week 48 
(± 1 Week) 
Safety 
Disease 
Survival 
EOT + 
30-35 Days 
 
Every 12 Weeks 
(± 1 Week) 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
Contact IWRS 
7.2 
X 
X 
X 
X 
X 
 
 
 
Inclusion & exclusion criteria 
3 
X 
X 
 
 
 
 
 
 
Demography and medical history 
7.3 
X 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.4 
X 
X 
X 
X 
X 
X 
 
 
AE assessmentd 
7.5.1  
X 
X 
X 
X 
X 
X 
 
 
Comprehensive physical exam  
7.5.2 
Xe 
 
 
 
X 
 
 
 
Disease-specific physical exam 
7.5.3 
 
X 
X 
X 
 
X 
 
 
Vital signs 
7.5.4 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG 
7.5.5 
X 
Xf 
Xf 
X 
X 
X 
 
 
ECOG performance status 
7.5.6 
X 
X 
X 
X 
X 
X 
 
 
CT/MRI scan 
7.6.1 
X 
 
Every 8 weeks through Week 24  
(± 1 week), then every 12 weeks through 
Week 96, then every 24 weeks 
thereafter until PD 
 
 
Xc 
 
Bone marrow exam  
7.6.2 
Xg 
 
Xh 
 
 
Xh 
 
Prophylactic treatment for PJP 
5.6.1 
 
Xi 
 
 
 
Study treatment dispensing 
5.1.1 
 
X 
X 
X 
 
 
 
 
Study treatment compliance 
5.3 
 
X 
X 
X 
X 
 
 
 
INCB050465 administration 
5.2.1 
 
X 
X 
X 
 
 
 
 
Disease follow-up 
6.4.2 
 
 
 
 
 
 
Xc 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
Xj 
a All procedures are to be performed before administration of study treatment on Day 1. 
 
 
c Only for subjects who discontinued study treatment for a reason other than disease progression; radiologic imaging 
 
.  


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d Adverse events will be monitored from the time the subject signs the ICF until at least 30 days after the last dose of study treatment.  Serious AEs occurring more than 30 days 
after the last dose of study treatment should be reported to the sponsor or its designee if the investigator suspects a causal relationship to the study treatment.  Once detected, AEs 
should be followed until resolved or judged to be permanent. 
e Height required at screening only. 
f Timed triplicate ECGs will be obtained during the Day 1 visit (predose) and Week 4 visit (predose and 1.5 hours [± 15 minutes] after receiving study treatment).   
g Required at baseline except for reasons provided in Section 7.6.2. 
h If disease is present in bone marrow at baseline, a bone marrow biopsy will be required to confirm CR or may be performed as clinically indicated.   
i PJP prophylaxis should be given while subjects are receiving study treatment and continue for at least 2 to 6 months after the last dose of study treatment. 
j May be conducted by clinic visit, telephone, or email. 




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Table 8: 
Laboratory Tests:  Required Analytes 
Serum Chemistries 
Hematology 
Serology 
Albumin 
Alkaline phosphatase 
ALT 
AST  
Bicarbonate 
Blood urea nitrogen  
C-reactive protein 
Calcium 
Chloride  
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total bilirubin is > ULN) 
Total protein 
Uric acid 
Beta-2 microglobulina 
Complete blood count, including: 
Hemoglobin 
Hematocrit 
Platelet count (absolute) 
Red blood cell count 
White blood cell count 
 
Differential count, including: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
Absolute values must be provided for 
WBC differential laboratory results: 
Lymphocytes 
Neutrophils 
Hepatitis B surface antigen 
Hepatitis B surface antigen antibody 
Hepatitis B core antibody 
HBV-DNA 
HCV antibody 
HCV-RNA 
CMV DNA 
HIV antibody (immunoassay)b 
Pregnancy Testing 
Only for female subjects of childbearing potential. 
Pregnancy tests (serum or urine) should be repeated 
if required by local regulations. 
Note:  Additional tests may be required, as agreed by investigator and sponsor, based on emerging safety data. 
a Beta-2 microglobulin testing will be performed at screening only. 
b Optional for subjects enrolled in the United States. 


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6.1. 
Screening 
Screening is the interval between signing the ICF and the date of first dose of study treatment 
(Day 1).  Screening may not exceed 28 days.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process.  
Central laboratory results for serum chemistry, hematology, and serology will be used to 
determine eligibility.  Serum pregnancy tests may be performed centrally or at the investigative 
site laboratory. 
Procedures conducted as part of the subject's routine clinical management (eg, imaging study) 
and obtained before signing of informed consent may be used for screening or baseline purposes, 
provided that the procedure meets the Protocol-defined criteria and has been performed in the 
screening interval.  All information associated with eligibility requirements must be entered into 
the appropriate eCRF pages. 
Results from the screening visit evaluations will be reviewed by the investigator to confirm 
subject eligibility before enrollment or the administration of study drug.  Tests with results that 
fail eligibility requirements may be repeated during screening if the investigator believes the 
results to be in error.  For screening assessments that are repeated, the most recent available 
result before administration of study drug will be used to determine subject eligibility.  
Additionally, a subject who fails screening may repeat the screening process 1 time if the 
investigator believes there has been a change in eligibility status (eg, after recovery from an 
infection).  Such subjects will be assigned a new subject ID number. 
6.2. 
Treatment 
The treatment period begins on the date of first dose of study treatment (Day 1).  Day 1 must be 
no more than 28 days after the subject has signed the ICF.  Dates for subsequent study visits will 
be determined based on this date and should occur within the visit windows outlined in the 
schedule of assessments (see Table 6) unless delayed for safety reasons.  At Day 1, results from 
screening visit evaluations should be reviewed by the investigator to determine whether the 
subject continues to meet the eligibility requirements, as specified in the Protocol.  Subjects may 
receive treatment until disease progression, death, unacceptable toxicity, or consent withdrawal, 
whichever occurs first. 
6.3. 
End of Treatment 
There is no defined date of EOT.  When the subject permanently discontinues study treatment, 
then the EOT visit should be conducted.  If the EOT visit coincides with a regular study visit, the 
EOT evaluations will supersede those of that scheduled visit, and the data should be entered in 
the EOT visit in the eCRF.  The subject should be encouraged to return for the safety follow-up 
visit. 


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6.4. 
Follow-Up 
6.4.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 30 to 35 days after the EOT visit (or after the last dose of study 
treatment if the EOT visit was not performed).  Adverse events and SAEs must be reported up 
until at least 30 days after the last dose of study treatment, the date of the follow-up visit, or until 
toxicities resolve, return to baseline, or are deemed irreversible, whichever is longer.  Reasonable 
efforts should be made to have the subject return for the follow-up visit and report any AEs that 
may occur during this period.   
If a subject is scheduled to begin a new anticancer therapy before the end of the safety follow-up 
period, then the safety follow-up visit should be performed before new anticancer therapy is 
started.  Once new anticancer therapy has been initiated, the subject will move into the survival 
follow-up period. 
6.4.2. 
Disease Status Follow-Up 
Subjects who discontinue study treatment for a reason other than disease progression will 
continue to be followed for disease assessments by radiologic imaging per the schedule of 
assessments (see Table 6).  Every effort should be made to collect information regarding disease 
status until 1 of the following occurs: 
• The start of new antineoplastic therapy. 
• Disease progression. 
• Death. 
• The end of the study. 
6.4.3. 
Survival Follow-Up 
Once a subject has received the last dose of study treatment, confirmed disease progression, or 
starts a new anticancer therapy, the subject moves into the survival follow-up period and should 
be followed up every 12 weeks by a clinic visit, telephone, or e-mail.  The site will use 
continuing subject records to supply data on subsequent treatment regimens, 
 
, and OS in the eCRF. 
For subjects who do not intend to return to the study investigator for their ongoing care, 
follow-up should be maintained to assess for survival status until death, withdrawal of consent, 
or the end of the study, whichever occurs first. 
6.5. 
End of Study 
The end of the study will be when all subjects have met any of the study discontinuation criteria 
in Section 5.7 or have completed at least 24 months of study participation (starting from first 
dose of INCB050465). 
At the end of the study, subjects who have completed at least 24 months of study participation, 
who remain on active study treatment, and who have no evidence of progressive disease will 


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have the option to continue on monotherapy with INCB050465 provided within a rollover 
Protocol, as local law permits. 
6.6. 
Unscheduled Visits 
Unscheduled visits may be held at any time at the investigator's discretion, and appropriate 
clinical and laboratory measurements performed based on AEs or other findings. 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained voluntarily from the study subject before conducting 
any study-specific procedures using an ICF approved by the local IRB/IEC that contains all 
elements required by ICH E6 and describes the nature, scope, and possible consequences of the 
study in a form understandable to the study subject.  Local and institutional guidelines for ICF 
content and administration must be followed; the original signed ICF must be retained by the 
investigator, and a copy of the signed ICF must be provided to the study subject.  The informed 
consent process for each subject must be documented in writing within the subject source 
documentation.  Note that the subject can stop participating in the study at any time and for any 
reason, and the decision to stop participating in the study will have no penalty or loss of benefits 
to which the subject is otherwise entitled. 
7.2. 
Interactive Web Response Technology Procedure 
The IWRS will be contacted to obtain a subject ID number when a subject enters screening.  
Upon determining that the subject is eligible for study entry, the IWRS will be contacted to 
obtain the treatment assignment.  Additionally, the IWRS will be contacted at each regular study 
visit to update the study treatment supply (see Section 5.1.1 and Table 6). 
7.3. 
Demography and Medical History 
7.3.1. 
Demographics and General Medical History 
Demographic data and a general medical history will be collected. 
7.3.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and medication history, including date of diagnosis of MCL, 
histology, current staging, grade, sites of disease, prior antineoplastic therapy, surgery, radiation, 
and other details related to the disease under study, will be collected at screening. 


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For consideration of prior lines of therapy, a treatment is considered a new line of therapy if any 
of the following 3 conditions are met: 
• Start of a new line of treatment after discontinuation of a previous line:  If a treatment 
regimen is discontinued for any reason and a different regimen is started, it should be 
considered a new line of therapy.  A regimen is considered to have been discontinued 
if all the drugs in that given regimen have been stopped.  A regimen is not considered 
to have been discontinued if some of the drugs of the regimen, but not all, have been 
discontinued. 
• The unplanned addition or substitution of 1 or more drugs in an existing regimen: 
Unplanned addition of a new drug or switching to a different drug (or combination of 
drugs) due to any reason is considered a new line of therapy. 
• Stem cell transplant:  In subjects undergoing > 1 SCT, each SCT (autologous or 
allogeneic) should be considered a new line of therapy regardless of whether the 
conditioning regimen used is the same or different. 
Note:  A therapy administered before an SCT, the subsequent SCT, and planned 
maintenance therapy after the SCT is considered 1 line of therapy. 
7.4. 
Prior and Concomitant Medications and Procedures 
Prior and concomitant medications and procedures will be reviewed to determine subject 
eligibility.  All prior and concomitant medications and measures must be recorded in the eCRF, 
and any medication received or procedure performed within 30 days before enrollment and as 
indicated (see Table 6) will be recorded in the eCRF.  The medication record will be maintained 
after signing the ICF to document concomitant medications, including any changes to the dose or 
regimen.  Concomitant medications include any prescription, over-the-counter, or natural/herbal 
preparations taken or administered during the study period.  Concomitant treatments and/or 
procedures that are required to manage a subject's medical condition during the study will also be 
recorded in the eCRF. 
7.5. 
Safety Assessments 
7.5.1. 
Adverse Events 
Adverse events will be monitored from the time the subject signs the ICF.  Subjects will be 
instructed to report all AEs during the study and will be assessed for the occurrence of AEs 
throughout the study.  In order to avoid bias in eliciting AEs, subjects will be asked general, 
nonleading questions such as "How are you feeling?"  All AEs (serious and nonserious) must be 
recorded on the source documents and eCRFs regardless of the assumption of a causal 
relationship with the study drug.  The definition, reporting, and recording requirements for AEs 
are described in Section 8. 
7.5.2. 
Comprehensive Physical Examination 
Clinically notable abnormalities that are considered clinically significant in the judgment of the 
investigator are to be reported as AEs. 


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Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits. 
The comprehensive physical examination will include height (at screening only), body weight 
(within 1 lb or 0.5 kg), and assessment(s) of the following organ or body systems:  skin; head, 
eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; abdomen (liver, spleen); 
extremities; and lymph nodes; as well as a brief neurological examination (eg, reflexes, strength, 
Romberg's test, vibration sense, and gross sensory perception). 
7.5.3. 
Disease-Specific Physical Examination 
A disease-specific physical examination will be a symptom-directed evaluation and will include 
assessment(s) of the body systems or organs, as indicated by subject disease and symptoms, AEs, 
or other findings as determined by the investigator or designee.  A disease-specific physical 
examination must include a measurement of the subject's body weight (within 1 lb or 0.5 kg) and 
an evaluation of any AEs or symptoms that the subject has previously reported. 
7.5.4. 
Vital Signs 
Vital sign measurements include blood pressure, pulse, respiratory rate, and body temperature.  
Blood pressure and pulse will be taken with the subject in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest.  Clinically notable abnormalities that are considered 
clinically significant in the judgment of the investigator are to be reported as AEs. 
7.5.5. 
Electrocardiograms 
All 12-lead ECGs will be performed with the subject in a recumbent or semirecumbent position 
after 5 minutes of rest.  The 12-lead ECGs will be performed locally and be interpreted by the 
investigator at the site and used for immediate subject management.  Baseline ECGs obtained 
during screening can be performed using a single measurement; however, ECGs may be 
performed in triplicate if the single QTc measurement is > 450 milliseconds (corrected by 
Fridericia; see Section 3.2).  The decision to include or exclude a subject or discontinue a 
subject's participation in the study based on an ECG flagged as "Abnormal, Clinically 
Significant" is the responsibility of the investigator, in consultation with the sponsor's medical 
monitor, as appropriate.  If a single measurement demonstrates a QTc interval 
> 500 milliseconds, 2 more ECGs should be obtained over a brief period, and the averaged QTc 
intervals should be used to determine whether the study treatment should be interrupted (see 
Section 5.4.1). 
7.5.5.1. 
Timed Electrocardiograms 
Timed triplicate ECGs will be obtained during the Day 1 visit (predose) and at Week 4 (predose 
and 1.5 hours [± 15 minutes] after receiving study treatment).  When triplicate ECGs are being 
obtained, individual measurements should be performed 5 minutes (± 3 minutes) apart.  


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7.5.6. 
ECOG Performance Status 
Eastern Cooperative Oncology Group performance status (Oken et al 1982; see Appendix B) will 
be assessed.  Performance status must be assessed by a medically qualified individual and 
recorded in the eCRF. 
7.5.7. 
Laboratory Assessments 
Blood draws for laboratory assessments will occur at study visits indicated in the schedule of 
laboratory assessments (see Table 7).  Specific laboratory assessments are provided in Table 8. 
All laboratory assessments, including those conducted during unscheduled visits, will be 
performed at a central laboratory, with the exception of serum pregnancy testing at screening 
(see Section 7.5.7.2), which may be performed either centrally or locally.  If performed locally, 
the investigative site laboratory or an accredited local laboratory may be used. 
Note:  A local laboratory assessment (including reference ranges) will be entered into the eCRF 
only if there is no accompanying central laboratory assessment and the local laboratory 
assessment caused a change in patient management (eg, a dose interruption or reduction) or was 
an AE or SAE.  
7.5.7.1. 
Chemistry and Hematology 
All chemistry and hematology assessments (see Table 7 and Table 8) will be performed from 
blood samples collected using institutional best practices (refer to the Laboratory Manual). 
7.5.7.2. 
Pregnancy Testing 
A serum pregnancy test at screening will be required for all women of childbearing potential (see 
Section 3.1) as shown in Table 7 and can be performed either at the central or local laboratory. 
Urine pregnancy tests (performed locally) will be conducted as shown in Table 7.  If a urine 
pregnancy test is positive, the results should be confirmed with a serum pregnancy test 
(performed centrally).  If the serum pregnancy test is negative after a positive urine test, the 
investigator will assess the potential benefit/risk to the subject and determine whether it is in the 
subject's best interest to resume study treatment and continue participation in the study. 
7.5.7.3. 
Serology 
Serology assessments will be performed at a central laboratory (see Table 7 and Table 8). 
7.5.7.3.1. HIV Testing 
Subjects enrolled outside of the United States must have an HIV immunoassay test at screening 
to ensure negative HIV status (see Section 3.2).  HIV testing is optional for subjects enrolled in 
the United States.  




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7.6.4. 
Independent Review Committee 
All radiologic imaging (CT or MRI) will be submitted to the central radiology vendor for review.  
Imaging data and applicable clinical data will be reviewed and response assessed using the 
CT-based response criteria of the Lugano Classification (Cheson et al 2014; see Appendix C) by 
independent reviewers as described in the Imaging Charter. 




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7.9. 
Other Study Procedures 
7.9.1. 
Distribution of Subject Reminder Cards 
Subjects will be provided with a reminder card at each visit. 
The subject reminder card will indicate the date/time of the next visit and will also remind the 
subjects of which days they should not take their morning dose before coming to the clinic (see 
Section 7.7).  The reminder cards for the Week 4 visit will have an area on which the date and 
time of the last dose taken (from the previous day) and the time of their last meal before the visit 
should be recorded. 
7.9.2. 
Data Collection for Survival Follow-Up 
For subjects having entered the survival follow-up period of the study, the site will collect data 
as described (see Section 6.4.3). 
8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events 
8.1.1. 
Definitions 
For the purposes of this Protocol, an adverse event (AE) is defined as any untoward medical 
occurrence associated with the use of a drug in humans, whether or not considered drug related, 
that occurs after a subject provides informed consent.  Abnormal laboratory values or test results 
occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, 
are considered clinically meaningful, require therapy (eg, hematologic abnormality that requires 
transfusion), or require changes in the study drug(s). 
8.1.2. 
Reporting 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events form of the eCRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History form in the eCRF.  Monitoring for the occurrence of 
new AEs should be continued for at least 30 days after the last dose of study treatment.  Adverse 
events (including laboratory abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible rather than by individual underlying signs and symptoms.  When a 
clear diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. 
The term "disease progression" should be recorded as an AE/SAE only if there are no other 
identifiable AEs/SAEs associated with the disease progression at the time of reporting.  For 
events associated with disease progression, the relevant signs and symptoms should be reported 
using a diagnosis whenever possible rather than individual underlying signs and symptoms.  
When a clear diagnosis cannot be identified, each sign or symptom should be reported as a 


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separate AE.  If the events resulting from disease progression meet the criteria for an SAE 
(eg, resulted in hospitalization, a life-threatening event, or death), the specific event(s) should be 
reported as an SAE(s) as described in Section 8.3.2.  In both cases (ie, AEs or SAEs related to 
disease progression), it should be indicated that each event (reported as a diagnosis or as signs 
and symptoms) is related to disease progression on the Adverse Events form of the eCRF. 
The severity of AEs will be assessed using CTCAE v4.03 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to 
estimate the grade of severity: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
activities of daily living. 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily 
living. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death due to AE 
The occurrence of AEs should be sought by nondirective questioning of the subject during the 
screening process after signing the ICF and at each visit during the study.  Adverse events may 
also be detected when they are volunteered by the subject during the screening process or 
between visits, or through physical examination, laboratory test, or other assessments.  To the 
extent possible, each AE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 5). 
• Whether there is at least a reasonable possibility that the AE is related to the study 
treatment:  suspected (yes) or not suspected (no). 
• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug. 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, 
recovering/resolving, recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per serious adverse event (SAE) definition provided in 
Section 8.3.1. 
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements (see Section 8.3.2). 
All AEs should be treated appropriately.  If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on Adverse Event form and the treatment should 
be specified on the Prior/Concomitant Medications or Procedures and Non-Drug Therapy form 
in the eCRF. 
Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 


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changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves.  For example, 
2 separate AEs will be reported if a subject has Grade 1 diarrhea meeting the definition of an AE 
that lasts for 3 days before worsening to a Grade 3 severity.  The Grade 1 event will be reported 
as an AE with a start date equal to the day the event met the Grade 1 AE definition and a stop 
date equal to the day that the event increased in severity from Grade 1 to Grade 3.  The Grade 3 
event will also be reported as an AE, with the start date equal to the day the event changed in 
intensity from Grade 1 to Grade 3 and a stop date equal to the day that the event either changed 
severity again or resolved. 
8.2. 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes 
in study drug) should be recorded on the Adverse Event form in the eCRF.  Whenever possible, a 
diagnosis rather than a symptom should be provided (eg, "anemia" instead of "low hemoglobin").  
Laboratory abnormalities that meet the criteria for AEs should be followed until they have 
returned to normal or an adequate explanation of the abnormality is found.  When an abnormal 
laboratory test result corresponds to a sign or symptom of a previously reported AE, it is not 
necessary to separately record the laboratory test result as an additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 AE does not automatically indicate an SAE unless it meets the definition of 
serious, as defined in Section 8.3.1.  A dose modification for the laboratory abnormality may be 
required (see Section 5.4) and should not contribute to the designation of a laboratory test 
abnormality as an SAE. 
8.3. 
Serious Adverse Events 
8.3.1. 
Definitions 
An SAE is defined as an event that meets at least 1 of the following criteria: 
• Is fatal or life-threatening. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− A routine treatment or monitoring of the studied indication not associated with 
any deterioration in condition.  
− An elective surgery or preplanned treatment for a pre-existing condition that is 
unrelated to the indication under study and has not worsened since signing the 
ICF. 
− A treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE and not resulting in hospital admission. 


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− Any social reasons and respite care, in the absence of any deterioration in the 
subject's general condition. 
• Results in persistent or significant disability, incapacity, or a substantial disruption of 
a person's ability to conduct normal life functions. 
• Constitutes a congenital anomaly or birth defect. 
• Is considered to be an important medical event or a medically significant event that 
may not result in death, be immediately life-threatening, or require hospitalization but 
may be considered serious when, based on appropriate medical judgment, the event 
may jeopardize the subject or may require medical or surgical intervention to prevent 
1 of the outcomes listed above. 
8.3.2. 
Reporting 
Every SAE, regardless of suspected causality (eg, relationship to study drug(s) or study 
procedure or disease progression), occurring after the subject has signed the ICF through the last 
study visit (or 30 days after the last dose of study treatment, whichever is later) must be reported 
to the sponsor (or designee) within 24 hours of learning of its occurrences, unless otherwise 
specified by the Protocol.  Any SAEs occurring more than 30 days after the last dose of study 
treatment should be reported to the sponsor or its designee only if the investigator suspects a 
causal relationship to the study drug. 
Information about all SAEs is collected and recorded on the Adverse Event form of the eCRF.  
The investigator must assess and record the causal relationship of each SAE to the study 
treatment.   
The investigator must also complete the Incyte Serious Adverse Event Report Form, in English, 
and send the completed and signed form to the sponsor or designee within 24 hours of becoming 
aware of the SAE.  The investigator must provide a causality assessment, that is, assess whether 
there is at least a reasonable possibility that the SAE is related to the study treatment:  suspected 
(yes) or not suspected (no).  Refer to the Incyte Reference Guide for Completing the Serious 
Adverse Event Report Form. 
The contact information of the sponsor's study-specific representatives is listed in the 
investigator manual provided to each site.  The original copy of the SAE Report Form and the 
confirmation sheet must be kept at the study site. 
Investigational site personnel must report any new information regarding the SAE within 
24 hours of becoming aware of the information in the same manner that the initial SAE Report 
Form was sent.  Follow-up information is recorded on an amended or new SAE Report Form, 
with an indication that it is follow-up to the previously reported SAE and the date of the original 
report.  The follow-up report should include information that was not provided on the previous 
SAE Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or subject disposition (eg, continued or withdrew from study participation).  Each 
recurrence, complication, or progression of the original event should be reported as follow-up to 
that event, regardless of when it occurs. 


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If the SAE is not documented in the IB for the study drug (new occurrences) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification (IN) to inform all investigators involved in any 
study with the same drug that this SAE has been reported.  Suspected Unexpected Serious 
Adverse Reactions (SUSARs) will be collected and reported to the competent authorities and 
relevant ethics committees in accordance with Directive 2001/20/EC, or as per national 
regulatory requirements in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
8.5. 
Adverse Events of Special Interest 
Specific AEs, or groups of AEs, will be followed as part of standard safety monitoring activities. 
• ALT ≥ 5 × ULN 
• AST ≥ 5 × ULN 
• Colitis 
• Diarrhea Grade ≥ 2  
• Intestinal perforation 
• Rash Grade ≥ 2 
• Exfoliative dermatitis 
• Pneumonitis 
• PJP infection 
• CMV infection 
• Herpes simplex virus infection 
• Varicella zoster virus infection 
8.6. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a subject during maternal or paternal exposure to study drug, 
the following procedures should be followed in order to ensure subject safety: 
• The study drug must be discontinued immediately (female subjects only; see 
Section 5.4.1 for the maximum permitted duration of study drug interruption). 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 


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Data on fetal outcome and breastfeeding are collected for regulatory reporting and drug safety 
evaluation.  Follow-up should be conducted for each pregnancy to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications, by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy form 
and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up information 
should be recorded on the same form and should include an assessment of the possible causal 
relationship to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the 
first well-baby visit or the duration specified in local regulations, whichever is later.  Refer to the 
Incyte Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy must be recorded on the SAE report form and 
submitted to the sponsor or designee. 
8.7. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications (INs).  Any 
important new safety information should be discussed with the subject during the study, as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
8.8. 
Independent Data Monitoring Committee 
An IDMC will be formed and will consist of qualified individuals who are not involved with the 
conduct of the study.  The establishment, composition, roles, duties, and responsibilities of the 
IDMC are addressed in the approved IDMC charter. 
8.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be reported as described in Section 8.1.2 of this Protocol. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 




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9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Primary Efficacy Analyses 
Objective response rate is defined as the percentage of subjects with a CR or PR as determined 
by revised response criteria for lymphomas (Cheson et al 2014). 
The ORR as determined by the IRC and its 95% exact binomial CIs will be calculated.  This is 
considered the primary efficacy analysis for each of the 2 cohorts.  
The ORR as reported by the investigator and its 95% exact binomial CIs will also be calculated. 
Response data will be analyzed when all subjects in the full analysis set of the respective cohort 
have reached at least 1 postbaseline disease assessment or have progressed, withdrawn from the 
study, or died. 
9.4.1.2. 
Secondary Efficacy Analyses 
Duration of response is defined as the time from first documented evidence of CR or PR until 
disease progression or death due to any cause among subjects who achieve an objective response 
(ie, CR or PR) as determined by revised response criteria for lymphomas (Cheson et al 2014).  
For subjects who have not progressed and are still alive at the time of the analysis, DOR will be 
censored on the day of last evaluable disease assessment.  For subjects who have discontinued 
study or have started other anticancer treatment, DOR will be censored on the day of last 
evaluable disease assessment documenting absence of PD before the discontinuation or the start 
of the new anticancer treatment. 
Progression-free survival is defined as the time from the date of first dose of the study drug to the 
first documented disease progression, as determined by revised response criteria for lymphomas 
(Cheson et al 2014), or death due to any cause, whichever occurs first.  For subjects who have 
not progressed and are still alive at the time of the analysis, PFS will be censored on the day of 
last evaluable disease assessment.  For subjects who have discontinued study or have started 
other anticancer treatment, PFS will be censored on the day of last evaluable disease assessment 
documenting absence of PD before the discontinuation or the start of the new anticancer 
treatment.  For subjects who have no baseline or no postbaseline disease assessment, PFS will be 
censored with censored duration of 1 day. 
The Kaplan-Meier estimation of median DOR and PFS as determined by the IRC and its 
95% CIs will be provided. 
Complete response rate is defined as the percentage of subjects with a CR as determined by 
revised response criteria for lymphomas (Cheson et al 2014). 
The CRR as determined by the IRC and its 95% exact binomial CIs will be calculated. 
Overall survival is defined as the time from the date of first dose of study drug to death due to 
any cause.  For subjects who are still alive at the time of the analysis, OS will be censored on the 
date the subjects is last known to be alive.  The Kaplan-Meier estimation of median OS and its 
95% CIs will be provided. 
Target lesion size is measured by the sum of the product of diameters of all target lesion sizes.  
Best percentage change in target lesion size from baseline will be summarized descriptively. 


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9.4.1.3. 
Other Efficacy Analyses 
Analyses of ORR, DOR, CRR, and PFS as reported by the investigator will be summarized as 
described above.  
Analyses of ORR, DOR, CRR, PFS as determined by IRC and OS will also be summarized by 
treatment regimens (A or B) within each cohort.   
Health-related quality of life scales as well as change and percentage change from baseline will 
be summarized descriptively by visit. 
9.4.2. 
Safety Analyses 
9.4.2.1. 
Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug and within 30 days of the last administration of study drug.  Analysis of 
AEs will be limited to TEAEs, but data listings will include all AEs regardless of their timing to 
study drug administration.  Adverse events will be tabulated by the MedDRA preferred term and 
system organ class.  Severity of AEs will be based on the NCI CTCAE v4.03 using Grades 1 
through 5. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, the AE will be considered treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated. 
Number (%) of subjects reporting any TEAEs, any SAEs, any Grade 3 or 4 TEAEs, any 
treatment-related TEAEs, any treatment-related SAEs, any treatment-related Grade 3 or 4 
TEAEs, any fatal TEAE, and any TEAEs leading to treatment interruption/dose 
reduction/discontinuation will be summarized and tabulated by system organ class and preferred 
term. 
9.4.2.2. 
Clinical Laboratory Tests 
Laboratory data will be classified into Grades 1 through 4 using CTCAE v4.03 when applicable.  
The following summaries will be produced for the laboratory data: 
• Descriptive statistics of the value and change from baseline at each assessment time 
will be provided. 
• For laboratory parameters that have CTC grading, shift tables will be provided 
showing change in CTC grade from baseline to the worst grade postbaseline. 
• For laboratory parameters where CTC grades are not defined, shift tables from 
baseline to the worst postbaseline value will be produced using the low/normal/high 
classifications based on laboratory reference ranges. 
Categorical laboratory data will be tabulated by visit at baseline and postbaseline visits when 
necessary. 


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9.4.2.3. 
Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature) at each assessment time.  Vital sign 
results will be reviewed for clinically notable abnormalities (see Table 10), and subjects 
exhibiting clinically notable vital sign abnormalities will be listed.  A value will be considered an 
"alert" value if it is outside the established range and shows a > 25% change from baseline.  The 
abnormal values for subjects exhibiting alert vital sign abnormalities will be listed. 
Table 10: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35°C 
Respiratory rate 
> 24 breaths/min 
< 12 breaths/min 
9.4.2.4. 
Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Electrocardiogram results will be reviewed for clinically notable 
abnormalities according to predefined criteria (see Table 11).  Subjects exhibiting clinically 
notable ECG abnormalities will be listed. 
Table 11: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 450 msec 
< 295 msec 
PR 
> 220 msec 
< 75 msec 
QRS 
> 120 msec 
< 50 msec 
QT 
> 500 msec 
< 300 msec 
RR 
> 1330 msec 
< 600 msec 
QTcF = Fridericia correction. 
9.4.2.5. 
Adverse Events of Special Interest 
Adverse events of special interest (see Section 8.5) will be summarized as detailed in the 
Statistical Analysis Plan. 


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9.5. 
Analyses for the Data Monitoring Committee 
Preplanned analyses of safety will be provided to the IDMC as specified in the IDMC charter.  In 
addition, the IDMC will make recommendations to the sponsor at the planned interim futility 
analyses (see Section 9.6).  The process by which the IDMC will make recommendations and 
decisions will be documented in the IDMC Charter. 
9.6. 
Interim Analysis 
An interim futility analysis is planned for each of the cohorts when 30 subjects have been treated 
and have been evaluated for response or have permanently discontinued study treatment because 
of disease progression, withdrawal of consent, or death.  Cohort 1 will be terminated for futility 
if ≤ 3 of the 30 subjects responded (ie, CR or PR) based on assessments provided by the IRC.  
Cohort 2 will be terminated for futility if ≤ 10 of the 30 subjects responded (ie, CR or PR) based 
on assessments provided by the IRC. 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
10.1. 
Investigator Responsibilities 
This study will be performed in accordance with ethical principles that originate in the 
Declaration of Helsinki and conducted in adherence to the study Protocol; GCPs as defined in 
Title 21 of the US CFR Parts 11, 50, 54, 56, and 312; ICH E6 GCP consolidated guidelines; and 
local regulatory requirements as applicable to the study locations. 
The investigator will be responsible for: 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
subject records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all subjects. 


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− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
• Obtaining informed consent and ensuring that the study subjects' questions have been 
answered and the subjects fully understand study procedures: 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the subject.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to subject records. 
• Obtaining approval from the IRB/IEC before the start of the study and for any 
changes to the clinical study Protocol, important Protocol deviations, routine updates, 
and safety information in accordance with institutional requirements and local law. 
− The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements 
and with the policies and procedures established by the IRB/IEC. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling subjects who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 


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10.2. 
Accountability, Handling, and Disposal of Study Drug 
The investigator is responsible for drug accountability at the study site; however, some of the 
drug accountability duties may be assigned to an appropriate pharmacist or other designee.  
Inventory and accountability records must be maintained and readily available for inspection by 
the study monitor and are open to inspection at any time by any applicable regulatory authorities.  
The investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Subject use of the study drug including pill or unit counts from each supply 
dispensed. 
• Return of study drug to the investigator or designee by subjects. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the subjects were provided the specified 
study drug.  These records should include dates, quantities, and any available batch or serial 
numbers or unique code numbers assigned to the investigational product and study subjects. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional standard 
operating procedures.  If local procedures mandate on-site destruction of investigational supply, 
the site should (where local procedures allow) maintain the investigational supply until the study 
monitor inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site SOP. 
10.3. 
Data Management 
Data management will be performed in a validated database via an Electronic Data Capture 
(EDC) system.  All data entry, verification, and validation will be performed in accordance with 
the current standard operating procedures of the Data Management Department at the sponsor or 
its designee.  The database will be authorized for lock once all defined procedures are completed. 
The investigator will be provided with access to an EDC system so that an eCRF can be 
completed for each subject.  Entries made in the eCRF must be verifiable against source 
documents; if updates to the database are not possible, any discrepancies should be explained 
and documented.  The investigator will be responsible for reviewing all data and eCRF entries, 
and will sign and date the designated forms in each subject's eCRF, verifying that the 
information is true and correct.  The investigator is responsible for the review and approval of all 
query responses. 
Protocol deviations will be identified and recorded in the Protocol Deviation form of the eCRF.  
The study monitor will reference the Monitoring Plan in order to ensure that each issue identified 
is appropriately documented, reported, and resolved in a timely manner in accordance with the 
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10.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 
Subject names will not be supplied to the sponsor or its designee.  Only the subject number will 
be recorded in the eCRF; if the subject's name appears on any other document (eg, laboratory 
report), it must be obliterated on the copy of the document to be supplied to the sponsor or its 
designee.  Study findings stored on a computer will be stored in accordance with appropriate 
technical and organizational measures as required by local data protection laws. 
10.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 Code of Federal Regulations (CFR) Part 54 – Financial Disclosure by 
Clinical Investigators (ie, "covered studies") are required to submit a completed Clinical 
Investigator Financial Disclosure form that sufficiently details any financial interests and 
arrangements that apply.  For the purpose of this regulation, "clinical investigator" is defined as 
any investigator or subinvestigator who is directly involved in the treatment or evaluation of 
research subjects, including the spouse and each dependent child of the clinical investigator or 
subinvestigator.  These requirements apply to both US and foreign clinical investigators 
conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
10.6. 
Publication Policy 
By signing the study Protocol, the investigator and his or her institution agree that the results of 
the study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national 
and international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 


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11. 
REFERENCES 
Argatoff LH, Connors JM, Klasa RJ, Horsman DE, Gascoyne RD. Mantle cell lymphoma: a 
clinicopathologic study of 80 cases. Blood 1997;89:2067-2078. 
Campo E, Rule S. Mantle cell lymphoma: evolving management strategies. Blood 
2015;125:48-55. 
Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-1657. 
Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol 2016;34:1256-1269. 
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and 
response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin 
Oncol 2014;32:3059-3068. 
Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. September 15, 2014. http://www.hma.eu/ctfg.html. Accessed 
October 8, 2015. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron 1976;16:31-41. 
Coutré S, Barrientos JC, Brown JR, et al. Management of adverse events associated with 
idelalisib treatment: expert panel opinion. Leuk Lymphoma 2015;56:2779-2786. 
Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter phase II study of bortezomib in patients 
with relapsed or refractory mantle cell lymphoma. J Clin Oncol 2006;24:4867-4874. 
Ghielmini M, Zucca E. How I treat mantle cell lymphoma. Blood 2009;114:1469-1476. 
Goy A, Sinha R, Williams ME, et al. Single-agent lenalidomide in patients with mantle-cell 
lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 
(EMERGE) study. J Clin Oncol 2013;31:3688-3695. 
Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared 
with investigator's choice therapy for the treatment of relapsed or refractory mantle cell 
lymphoma. J Clin Oncol 2009;27:3822-3829. 
Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with 
advanced-stage mantle cell lymphoma. Blood 2008;111:558-565. 
INCB050465 Investigator's Brochure (IB). Wilmington, DE: Incyte Corporation. 
Leukemia & Lymphoma Society (LLS). Mantle Cell Lymphoma Facts. 2014. 
https://www.lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf. Accessed May 4, 
2017. 
Martin P, Maddocks K, Leonard JP, et al. Postibrutinib outcomes in patients with mantle cell 
lymphoma. Blood 2016;127:1559-1563. 
National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events Version 
4.03. 2010. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. Accessed February 1, 2017. 


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National Cancer Institute (NCI). Surveillance, Epidemiology, and End Results Program. 2017. 
http://seer.cancer.gov/statfacts/html/nhl.html. Accessed April 28, 2017.  
National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: 
B-cell lymphomas Version 1.2017. 2017. 
https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed February 1, 2017. 
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. 
Patnaik A, Appleman LJ, Tolcher AW, et al. First-in-human phase I study of copanlisib (BAY 
80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with 
advanced solid tumors and non-Hodgkin's lymphomas. Ann Oncol 2016;27:1928-1940. 
Phillips TJ, Ramchandren R, Wertheim MS, et al. An ongoing open-label Phase 1/2 study of 
INCB050465, a selective PI3Kδ inhibitor, in patients with previously treated b-cell 
malignancies. Presented at: 58th American Society of Hematology Annual Meeting and 
Exposition; December 3-6, 2016; San Diego, CA. 
Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell 
lymphoma. N Engl J Med 2015;372:944-953. 
Schulz H, Bohlius JF, Trelle S, et al. Immunochemotherapy with rituximab and overall survival 
in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl 
Cancer Inst 2007;99:706-714. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29. 
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. 
CA Cancer J Clin 2015;65:87-108. 
Wang ML, Blum KA, Martin P, et al. Long-term follow-up of MCL patients treated with single 
agent ibrutinib: updated safety and efficacy results. Blood 2015;126:739-745. 
Wang M, Goy A, Martin P, et al. Efficacy and safety of single-agent ibrutinib in patients with 
mantle cell lymphoma who progressed after bortezomib therapy. Blood 2014;124:Abstract 4471. 
Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory 
mantle-cell lymphoma. N Engl J Med 2013;369:507-516. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomised partner2,3 
• Sexual abstinence4 
For Male Subjects Participating in the Study: 
In addition to the aforementioned contraceptive methods, male subjects must also use a condom 
during intercourse from the time of first dose of study treatment and through at least 93 days 
after last dose of study treatment.  Males who have had a vasectomy qualify as having met the 
requirement for a highly effective birth control method. 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomised partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the 
surgical success.  
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
Source:  CTFG 2014. 


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APPENDIX B. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS 
Eastern Cooperative Oncology Group Performance Scores 
Grade 
Performance Status 
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work. 
2 
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 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 






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APPENDIX D. MANTLE CELL LYMPHOMA INTERNATIONAL 
PROGNOSTIC INDEX 
Points 
Age, y 
ECOG 
LDH, ULN 
WBC, 109/L 
0 
< 50 
0-1 
< 0.67 
< 6.700 
1 
50-59 
– 
0.67-0.99 
6.700-9.999 
2 
60-69 
2-4 
1.000-1.49 
1.000-14.999 
3 
≥ 70 
– 
≥ 1.5000 
≥ 15.000 
• For each prognostic factor, 0 to 3 points are given to each patient, and points are 
summed up to a maximum of 11.  Patients with 0 to 3 points in summary are 
classified as low risk, patients with 4 to 5 points as intermediate risk, and patients 
with 6 to 11 points as high risk.  ECOG performance status is weighted with 2 points 
if patients are unable to work or are bedridden (ECOG 2-4).  LDH is weighted 
according to the ratio to the ULN.  Thus, for an ULN of 240 U/L, the cutpoints were 
180 U/L, 240 U/L, and 360 U/L, for example. 
• – indicates not applicable. 


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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1: 
07 NOV 2017 
Amendment (Version) 2: 
31 JAN 2018 
Amendment (Version) 3: 
16 JUL 2018 
Amendment (Version) 4: 
07 DEC 2018 
Amendment (Version) 5: 
29 AUG 2019 
Amendment (Version) 6: 
23 DEC 2019 
Amendment (Version) 7: 
30 JAN 2020 
Amendment 7 (30 JAN 2020) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to close 
enrollment for Cohort 1 before reaching the target enrollment (n = 90). 
1. Synopsis (Overall Study Design, Estimated Number of Subjects, and Sample Size); 
Section 4.1, Overall Study Design (including Figure 1:  Study Design of 
INCB 50465-205); Section 4.3.1, Planned Number of Subjects; Section 4.5, Overall 
Study Duration; Section 9.2, Selection of Sample Size 
Description of change:  Text added stating that Cohort 1 will be closed to further 
enrollment. 
Rationale for change:  The IDMC determined that the futility boundary was not crossed 
at the interim analysis of Cohort 1 and that there were no safety issues preventing further 
enrollment.  However, the sponsor has concluded that the observed ORR is not clinically 
meaningful. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 6 (23 DEC 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to provide 
additional guidance on dose modification in the event of diarrhea and colitis and to define the 
end of the study, including the option to receive continued treatment with INCB050465 in a 
rollover protocol. 
1. Section 5.4.1.1, Dose Modifications (Table 3:  Guidelines for Interruption and 
Restarting INCB050465; Table 4:  Dose Levels and Reductions for INCB050465); 
Section 5.4.2, Supportive Care Guidelines for Diarrhea/Colitis (Table 5:  Guidelines 
for Dose Modification of INCB0050465 for Diarrhea/Colitis) 
Description of change:  Revision to text pertaining to interruptions and restarting 
INCB050465 for adverse events of diarrhea and colitis. 
Rationale for change:  To provide additional dose modifications of INCB050465 for 
diarrhea and colitis. 
2. Synopsis; Section 4.5, Overall Study Duration; Section 5.8, Treatment After the End 
of the Study; Section 6.5, End of Study 
Description of change:  Text and new section added to describe that subjects who are 
receiving active study treatment and have no evidence of progressive disease at the end of 
the study will have the option to continue on INCB050465 provided within a rollover 
Protocol. 
Rational for change:  To clarify what treatment options are available at the end of the 
study. 
3. Synopsis (Estimated Duration of Participation); Section 4.4, Duration of Treatment 
and Subject Participation; Section 4.5, Overall Study Duration; Section 5.7, Criteria 
for Study Discontinuation; Section 6.5, End of Study 
Description of change:  Text and new section added to define the following:  a) criteria 
for a subject to be discontinued from the study and b) the end of study. 
Rational for change:  To clarify when a subject will be discontinued from the study and 
when the study will end. 
4. Section 6, Study Assessments (Table 6:  Schedule of Assessments) 
Description of change:  Changed frequency of study treatment dispensation and 
assessment of compliance from every 4 weeks to every 12 weeks starting at Week 48. 
Rationale for change:  To align with the frequency of clinic visits after Week 48 
whereby reducing the burden of extra clinic visits for the subjects. 


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5. Section 9.4.2.4, Electrocardiograms (Table 11:  Criteria for Clinically Notable 
Electrocardiogram Abnormalities) 
Description of change:  Changed high threshold of QTcF interval from > 460 msec to 
> 450 msec for analysis purposes. 
Rationale for change:  To comply with the categories outlined in FDA Guidance for 
Industry (E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic 
Potential for Non-Antiarrhythmic Drugs) used to characterize outliers in QTc values. 
6. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 




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Amendment 4 (07 DEC 2018) 
Overall Rationale for the Amendment:  The primary purpose of the amendment is to increase 
the number of subjects in each cohort to better understand the safety and efficacy of 
INCB050465 administered at one of the two treatment regimens. 
1. Synopsis; Section 4.1, Overall Study Design (Figure 1:  Study Design of 
INCB 50465-205); Section 4.3.1, Planned Number of Subjects; Section 4.5, Overall 
Study Duration; Section 9.2, Selection of Sample Size; Section 9.4.1.1, Primary 
Efficacy Analyses 
Description of change:  Revised to state that an additional 30 subjects will be added to 
each cohort.  All additional subjects will be enrolled to the same treatment regimen.  
Subjects allocated to the unselected treatment regimen will be allowed to cross over.  The 
estimated time to enroll the study was updated from 1.5 years to 2 years. 
Rationale for change:  To better understand the safety and efficacy of INCB050465 
administered in the selected treatment regimen. 
2. Section 9.1, Study Populations 
Description of change:  Defined the efficacy evaluable analysis set, which will be used 
for the efficacy analysis in place of the full analysis set.  The PP population was also 
revised to include all subjects in the efficacy evaluable analysis set who were sufficiently 
compliant with the Protocol. 
Rationale for change:  To clarify the efficacy evaluable and PP study populations for 
analysis. 
3. Section 10.4, Data Privacy and Confidentiality of Study Records 
Description of change:  Revised language pertaining to the protection of personal data. 
Rationale for change:  To comply with the General Data Protection Regulation 
2016/679. 
4. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 




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6. Section 3.1, Subject Inclusion Criteria (Inclusion Criterion 9d) 
Description of change:  Inclusion Criterion 9d was revised to allow subjects whose total 
bilirubin values are > 1.5 × ULN to enroll if the elevation is due to Gilbert’s syndrome. 
Rationale for change:  Gilbert’s syndrome is a hereditary condition characterized by 
intermittent, unconjugated hyperbilirubinemia in the absence of hepatocellular damage 
and hemolysis.  Consistent with other PI3Kδ inhibitors, elevated bilirubin due to 
Gilbert’s syndrome is not expected to alter the risk/benefit profile for subjects taking 
INCB050465. 
7. Section 7.3.2, Disease Characteristics and Treatment History 
Description of change:  Added a definition for lines of therapy. 
Rationale for change:  Definitions were added to improve consistency for calculation of 
prior lines of therapy. 
8. Section 3.2, Subject Exclusion Criteria (Exclusion Criterion 10); Section 5.6.2, 
Restricted Medications; Section 5.6.3, Prohibited Medications; Appendix B, 
Cytochrome P450 and P-Glycoprotein Inhibitors and Cytochrome P450 Inducers 
Description of change:  Deleted appendix B. 
Rationale for change:  Moved information to Pharmacy Manual. 
9. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 2 (31 JAN 2018) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to institute hematology testing every 2 weeks for the 
first 8 weeks of dosing. 
1. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  Exclusion criterion 16 (liver disease) was updated. 
Rationale for change:  As there have been no reported HBV or HCV reactivations in 
INCB 50465-101, the exclusion criterion was amended to align with those of approved 
PI3K inhibitors. 
2. Synopsis; Section 6, Study Assessments (Table 7, Schedule of Laboratory 
Assessments) 
Description of change:  Study visits were added at Week 2 and Week 6 for hematology 
testing. 
Rationale for change:  Requested by the US FDA. 
3. Section 5.5.1, Criteria for Study Treatment Discontinuation 
Description of change:  The following bullet has been deleted from Section 5.5.1: 
If a subject is found not to have met eligibility criteria, then the medical monitor and 
investigator will collaborate to determine whether the subject should be withdrawn from 
the study. 
Rationale for change:  Requested by Health Canada. 
4. Section 5.4.3, Supportive Care Guidelines for Neutropenia and Thrombocytopenia 
Description of change:  Provided instructions to investigators to remind subject to report 
signs or symptoms of infection, bleeding, or sudden, extremely painful headaches. 
Rationale for change:  Requested by the US FDA. 
5. Section 5.6.1, Pneumocystis Jirovecii Pneumonia Prophylaxis 
Description of change:  Clarified language on how PJP prophylactic agents will be 
supplied. 
Rationale for change:  Incyte will not provide PJP prophylactic agents, but rather sites 
will be responsible for sourcing from commercial supply and Incyte will reimburse. 




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Amendment 1 (07 NOV 2017) 
The primary purpose of this amendment is to address changes requested by the European 
Regulatory Agency.  
1. Section 1.3, INCB050465; Section 1.5, Potential Risks and Benefits of the Treatment 
Regimen 
Description of change:  Updated emerging safety and efficacy data from 
INCB 50465-101. 
Rationale for change:  Requested by the European Regulatory Agency.  
2. Section 3.1, Subject Inclusion Criteria 
Description of change:  Clarified wording of inclusion criterion 3. 
Rationale for change:  Requested by the European Regulatory Agency. 
3. Section 3.2, Subject Exclusion Criteria (Criterion 25); Section 7.1, Administration of 
Informed Consent Form 
Description of change:  Clarified that subjects must voluntarily sign an informed 
consent, and that consent withdrawal by the subject would not result in a penalty or loss 
of benefits to which the subject is otherwise entitled. 
Rationale for change:  Requested by the European Regulatory Agency.  
4. Section 4.1, Overall Study Design 
Description of change:  Clarified the number of prior therapies allowed in the study. 
Rationale for change:  Corrected an error identified by the European Regulatory 
Agency. 
5. Synopsis; Section 4.1, Overall Study Design; Section 5.1.1, Subject Numbering and 
Treatment Assignment 
Description of change:  Clarified that subjects will be randomly allocated to Treatment 
A and Treatment B. 
Rationale for change:  Requested by the European Regulatory Agency.  
6. Section 4.6, Study Termination 
Description of change:  Clarified that investigators can terminate a subject's 
participation for appropriate medical or organizational reasons. 
Rationale for change:  Requested by the European Regulatory Agency.  
7. Section 6, Study Assessments (Table 5, Schedule of Assessments) 
Description of change:  Added a footnote to indicate that the IWRS will need to be 
contacted every 4 weeks until end of treatment to accommodate study treatment 
dispensing. 
Rationale for change:  Clarification. 



SAP_001.pdf: 
Official Title: 
A Phase 2, Open-Label, 2-Cohort, Multicenter Study of INCB050465, a PI3Kδ 
Inhibitor, in Relapsed or Refractory Mantle Cell Lymphoma Previously 
Treated With or Without a BTK Inhibitor (CITADEL-205) 
NCT Number: 
NCT03235544 
Document Date: 
Statistical Analysis Plan Version 2: 28 January 2021 


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Statistical Analysis Plan 
 
 
INCB 50465-205 
A Phase 2, Open-Label, 2-Cohort, Multicenter Study of 
INCB050465, a PI3Kδ Inhibitor, in Relapsed or Refractory Mantle 
Cell Lymphoma Previously Treated With or Without a BTK 
Inhibitor (CITADEL-205) 
 
 
 
 
 
IND Number: 
121,474 
EudraCT Number: 
2017-003148-19 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment 7 dated 30 JAN 2020 
CRF Approval Date: 
26 NOV 2018 
SAP Version: 
Amendment 2 
SAP Author:  
, PhD 
 
Date of Plan: 
28 JAN 2021 
 
 
This study is being conducted in compliance with good clinical practice, 
including the archiving of essential documents. 
 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................7 
2.1. 
Protocol and Case Report Form Version ......................................................................7 
2.2. 
Study Objectives and Endpoints ...................................................................................7 
3. 
STUDY DESIGN .........................................................................................................9 
3.1. 
Randomization ............................................................................................................10 
3.2. 
Control of Type I Error ...............................................................................................10 
3.3. 
Sample Size Considerations .......................................................................................10 
3.4. 
Schedule of Assessments ............................................................................................11 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................11 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................11 
4.1.1. 
Day 1 ...........................................................................................................................11 
4.1.2. 
Study Day ...................................................................................................................11 
4.1.3. 
Baseline Value ............................................................................................................11 
4.1.4. 
Handling of Missing and Incomplete Data .................................................................11 
4.2. 
Variable Definitions ....................................................................................................12 
4.2.1. 
Body Mass Index ........................................................................................................12 
4.2.2. 
Prior and Concomitant Medication .............................................................................13 
5. 
STATISTICAL METHODOLOGY ...........................................................................13 
5.1. 
General Methodology .................................................................................................13 
5.2. 
Treatment Groups .......................................................................................................13 
5.3. 
Analysis Populations ..................................................................................................14 
5.3.1. 
All-Screened Population .............................................................................................14 
5.3.2. 
Full Analysis Set .........................................................................................................14 
5.3.3. 
Safety Population ........................................................................................................14 
 
14 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................15 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............15 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................15 
6.1.2. 
Disease History ...........................................................................................................15 


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6.1.3. 
Prior Therapy ..............................................................................................................15 
6.1.4. 
Medical History ..........................................................................................................16 
6.2. 
Disposition of Participants ..........................................................................................16 
6.3. 
Protocol Deviations ....................................................................................................16 
6.4. 
Exposure .....................................................................................................................16 
6.5. 
Study Drug Compliance .............................................................................................16 
6.6. 
Prior and Concomitant Medication .............................................................................17 
7. 
EFFICACY .................................................................................................................17 
7.1. 
Efficacy Hypotheses ...................................................................................................17 
7.2. 
Response Assessment .................................................................................................17 
7.3. 
Analysis of the Primary Efficacy Parameter ..............................................................18 
7.3.1. 
Best Overall Response and Objective Response Rate ................................................18 
7.3.2. 
Subgroup Analyses for Objective Response Rate ......................................................18 
7.4. 
Analysis of the Secondary Efficacy Parameters .........................................................19 
7.4.1. 
Duration of Response .................................................................................................19 
7.4.2. 
Complete Response Rate ............................................................................................19 
7.4.3. 
Progression-Free Survival ..........................................................................................20 
7.4.4. 
Overall Survival ..........................................................................................................21 
7.4.5. 
Best Percent Change in Target Lesion Size ................................................................21 
 
21 
 
21 
 
22 
 
23 
 
23 
 
23 
 
 
23 
 
23 
 
24 
9. 
SAFETY AND TOLERABILITY ..............................................................................24 
9.1. 
General Considerations ...............................................................................................24 
9.2. 
Adverse Events ...........................................................................................................24 
9.2.1. 
Adverse Event Definitions ..........................................................................................24 


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9.2.2. 
Adverse Events of Special Interest .............................................................................24 
9.2.3. 
Adverse Event Summaries ..........................................................................................26 
9.3. 
Clinical Laboratory Tests ...........................................................................................28 
9.3.1. 
Laboratory Value Definitions .....................................................................................28 
9.3.2. 
Laboratory Value Summaries .....................................................................................28 
9.3.3. 
Potential Hy's Law Events ..........................................................................................28 
9.3.4. 
Worsening Laboratory Events of Special Interest ......................................................29 
9.4. 
Vital Signs ..................................................................................................................29 
9.5. 
Electrocardiograms .....................................................................................................29 
10. 
INTERIM ANALYSES ..............................................................................................30 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................31 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................31 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................31 
12. 
REFERENCES ...........................................................................................................34 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................35 
 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Evaluation and Censoring of Progression-Free Survival ............................................20 
 
22 
Table 4: 
Normal Ranges for Vital Sign Values ........................................................................29 
Table 5: 
Normal Ranges for Electrocardiogram Values ...........................................................30 
Table 6: 
Statistical Analysis Plan Versions ..............................................................................31 
 
LIST OF FIGURES 
Figure 1: 
Study Design of INCB 50465-205 .............................................................................10 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase  
BMI 
body mass index 
bpm 
beats per minute 
BTK 
Bruton's tyrosine kinase 
CI 
confidence interval 
 
 
CMV 
cytomegalovirus 
CR 
complete response 
CRF 
case report form 
CRR 
complete response rate 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EWB 
emotional well-being 
 
 
 
 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FWB 
functional well-being 
 
 
IDMC 
independent data monitoring committee 
IRC 
independent review committee 
LYMS 
lymphoma subscale 
MCL 
mantle cell lymphoma 
MedDRA 
Medical Dictionary for Regulatory Activities  
 
 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 


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Abbreviation 
Term 
NE 
not evaluable 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PFS 
progression-free survival 
PJP 
Pneumocystis jirovecii pneumonia 
 
tic 
PP 
per protocol (population) 
PR 
partial response 
PT 
preferred term 
PWB 
physical well-being 
QD 
once daily 
SAP 
Statistical Analysis Plan 
SD 
stable disease 
SOC 
system organ class 
SWB 
social/family well-being 
TEAE 
treatment-emergent adverse event 
 
 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy and safety of 
2 INCB050465 treatment regimens in relapsed or refractory MCL participants previously treated 
either with or without a BTK inhibitor. 
Section 1 of the Protocol provides a detailed description of the investigational product, target 
participant population, rationale for doses to be examined, and potential risks and benefits of 
treatment with INCB050465. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCB 50465-205 Protocol.  The scope of this plan includes the interim and final 
analyses that are planned and will be executed by the Department of Biostatistics or designee, 
  
 
 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 50465-205 Protocol Amendment 7 dated 30 JAN 2020 and CRFs 
approved 26 NOV 2018.  Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and CRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 


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Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To assess the efficacy of INCB050465 in 
terms of ORR in participants with MCL 
that is relapsed or refractory after at least 
1 but no more than 3 prior systemic 
treatment regimens. 
ORR defined as the percentage of participants with a CR or PR as 
determined by IRC assessment of response according to CT-based 
response criteria for lymphomas (Cheson et al 2014). 
Secondary 
To assess DOR. 
DOR defined as the time from first documented evidence of CR or PR 
until disease progression or death from any cause among participants 
who achieve an objective response, as determined by radiographic 
disease assessment provided by an IRC. 
To assess CRR. 
CRR defined as the percentage of participants with a CR as defined by 
response criteria for lymphomas (Cheson et al 2014), as determined by 
an IRC. 
To assess PFS. 
PFS defined as the time from the date of the first dose of study treatment 
until the earliest date of disease progression, as determined by 
radiographic disease assessment provided by an IRC, or death from any 
cause. 
To assess OS. 
OS defined as the time from the date of the first dose of study treatment 
until death from any cause. 
To assess the best percentage change in 
target lesion size. 
Best percentage change in target lesion size from baseline, where target 
lesion size is measured by the sum of the product of diameters of all 
target lesion sizes. 
To characterize the safety and 
tolerability of INCB050465. 
Safety measured by AEs, 12-lead ECGs, chemistry and hematology 
laboratory values, vital signs, and physical examinations. 


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3. 
STUDY DESIGN 
This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy and safety of 
2 INCB050465 treatment regimens in relapsed or refractory MCL previously treated either with 
or without a BTK inhibitor (see Figure 1).  Participants will be allocated to Cohort 1 or Cohort 2 
as follows: 
• Cohort 1:  Participants have previously received ibrutinib 
• Cohort 2:  Participants have not previously received a BTK inhibitor 
However, Cohort 1 was closed to further enrollment per Protocol Amendment (Version) 7.  
Cohort 1 and Cohort 2 will have separate designs, conduct, and analyses.  Participants enrolled in 
Cohort 1 and the first 60 participants in Cohort 2 will be further allocated to 1 of 2 study 
treatment regimens as follows: 
• Treatment A:  INCB050465 20 mg QD for 8 weeks followed by 20 mg once weekly 
• Treatment B:  INCB050465 20 mg QD for 8 weeks followed by 2.5 mg QD 
An interim futility analysis is planned for each of the cohorts when 30 participants have been 
treated and evaluated for response or have permanently discontinued study treatment because of 
disease progression, withdrawal of consent, or death.  Cohort 1 will be terminated for futility if 
≤ 3 of the 30 participants responded (ie, CR or PR) based on assessments provided by the IRC.  
Cohort 2 will be terminated for futility if ≤ 10 of the 30 participants have responded (ie, CR or 
PR) based on assessments provided by the IRC. 
To better understand the safety and efficacy of INCB050465, a total of 70 additional participants 
(30 participants in Cohort 1 and 40 participants in Cohort 2) will be enrolled into 1 of the 
2 treatment regimens being evaluated in this study.  The treatment regimen will be selected after 
enrollment is completed for either Cohort 1 or Cohort 2 (ie, 60 participants enrolled) and after 
evaluation of emerging safety and efficacy data from this and other monotherapy studies of 
INCB050465 in non-Hodgkin lymphoma.  Once a treatment regimen is selected, the nonselected 
treatment regimen will be closed to further enrollment.  Participants receiving the nonselected 
treatment regimen may switch to the selected treatment regimen or remain on their current 
treatment regimen, provided they have not met study-treatment withdrawal criteria and there are 
no safety concerns for their current treatment regimen.  There will be no rebaselining for 
participants who switch treatment regimens and all participants will continue to follow the same 
assessment schedule. 
Participants will receive treatment until disease progression, death, unacceptable toxicity, or 
consent withdrawal, whichever occurs first.  Participants will be evaluated for ORR by an IRC 
and followed for DOR, PFS, and OS. 


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Figure 1: 
Study Design of INCB 50465-205 
 
3.1. 
Randomization 
Not applicable. 
3.2. 
Control of Type I Error 
There will not be any statistical comparison between Cohorts 1 and Cohort 2.  Within each of the 
2 cohorts, there will not be any statistical comparison between the 2 treatment regimens, and 
2-sided 95% CIs will be reported for all analyses when appropriate. 
Within each cohort, no adjustment for alpha spending is considered as there are no plans to stop 
the study early for overwhelming efficacy.  An IDMC will be assembled to monitor safety data 
and study conduct on a regular and ongoing basis during the study.  The IDMC will also be 
charged with evaluating interim futility results.  See Section 10 for details regarding interim 
analyses conducted in this study. 
3.3. 
Sample Size Considerations 
Cohort 1 was closed to further enrollment with Protocol Amendment (Version) 7. 


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The study will enroll up to 100 participants into Cohort 2.  If the true ORR is 60%, then there is 
approximately 90% or 97% probability of observing the lower bound of the 95% CI of 
ORR ≥ 40% with 60 or 100 participants, respectively. 
3.4. 
Schedule of Assessments 
See Protocol Amendment 7 dated 30 JAN 2020 for a full description of all study procedures and 
assessment schedules for this study. 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study drug (INCB050465) is administered to the 
participants. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (Visit/Reporting Date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (Visit/Reporting Date – Day 1 date). 
A study day of –1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of 
INCB050465, unless otherwise defined. 
When scheduled assessments and unscheduled assessments occur on the same day and time of 
the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Handling of Missing and Incomplete Data  
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in this section or relevant sections.  The original reported dates collected on the 


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eCRF should be used in all relevant listings.  The following rules will be used for handling 
missing or partial dates for analyses requiring dates. 
When calculating time since initial diagnosis of cancer, partial diagnosis date will be handled in 
the calculation as follows: 
• If only the day is missing, then the first day of the month will be used. 
• If both the month and day are missing, then 01 JAN will be used. 
• Otherwise, the time since diagnosis will not be calculated. 
When the date of the last dose is used in deriving variables such as duration of treatment or 
TEAE flag, missing or partial date of last dose will be handled in the calculation as follows: 
• If only the day is missing, then the earlier date of the last day of the month or the date 
that the participant discontinued treatment will be used. 
• If both the month and day are missing, then the earlier date of 31 DEC of the year or 
the date that the participant discontinued treatment will be used. 
• Otherwise, the date that the participant discontinued treatment will be used as the date 
of the last dose. 
When calculating DOR, PFS, and OS, a partial date of death will be handled in the calculation as 
follows: 
• If mmyyyy for the last known alive date = mmyyyy for the death date, then the day 
after the last known alive date will be used. 
• If mmyyyy for the last known alive date < mmyyyy for the death date, then the first 
day of the death month will be used. 
• Otherwise, the partial death date will not be handled.  
When calculating time to onset or duration of a TEAE, a partial or missing AE onset/end date 
will be handled in the calculation as follows:  
• If only the day is missing, then the first day of the month or Day 1, whichever is later, 
will be used as the onset date; the earlier date of the last day of the month or the date 
that the participant discontinued study or died will be used as the end date. 
• If both the month and day are missing, then 01 JAN or Day 1, whichever is later, will 
be used as the onset date; the earlier date of 31 DEC or the date that the participant 
discontinued study or died will be used as the end date.  
• Otherwise, Day 1 will be used as the onset date, and the missing end date will not be 
handled. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2. 


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4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB050465. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first administration of INCB050465 and is ongoing throughout the 
study or ends on/after the date of first study drug administration. 
• On/after the date of first administration of INCB050465 and is ongoing or ends 
during the course of study. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCB050465.  In the listing, it will be indicated whether a 
medication is prior-only, concomitant-only, or both prior and concomitant medication. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 
5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9 or later) will be used 
for the generation of all tables, graphs, and statistical analyses.  Descriptive summaries for 
continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum.  Descriptive summaries for categorical 
variables will include the number and percentage of participants in each category. 
Interim analyses are planned for this study as defined in Section 10. 
5.2. 
Treatment Groups 
This is a Phase 2, open-label, 2-cohort study.  All analyses will be conducted independently for 
Cohort 1 and Cohort 2, and there will not be multiplicity adjustment between the cohorts.  
Within each cohort, there will not be any statistical comparison between the treatment groups. 
For analysis purposes, the 20 mg once weekly dosing period and the 2.5 mg QD dosing period in 
Group A and Group B, respectively, are considered maintenance dosing periods.  Within each of 
the 2 cohorts, data will be presented in summary tables by actual received treatment regimen and 
combined, with an exception for participants who cross over to the selected treatment regimen 
after the start of the maintenance dosing period.   
For participants who cross over from the initially assigned treatment regimen to the selected 
treatment regimen, if the crossover happens on/prior to the start of the maintenance dosing 
period then the participant will be summarized, according to the actual received treatment, in the 
selected treatment regimen; otherwise, the participant will be summarized in: 
• A separate treatment regimen (ie, Crossover) for the safety summaries during the 
maintenance dosing period (eg. summaries of TEAEs and exposure). 
• The initially assigned treatment regimen for all other summaries. 


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Per Protocol Amendment (Version) 7, Cohort 1 was closed to further enrollment.  If the number 
of participants who have enrolled in Cohort 1 is relatively few, summary tables will be replaced 
with listings.   
5.3. 
Analysis Populations 
5.3.1. 
All-Screened Population 
The all-screened population includes all participants who signed the informed consent form. 
The all-screened population will be used for the summary of analysis populations. 
5.3.2. 
Full Analysis Set 
The FAS includes all participants enrolled in the study who received at least 1 dose of 
INCB050465. 
The FAS will be used for the summary of demographics, baseline characteristics, participant 
disposition, and all efficacy data. 
5.3.3. 
Safety Population 
The safety population includes all enrolled participants who received at least 1 dose of 
INCB050465. 
All safety analyses will be conducted using the safety population. 
 
 
 
 
 
 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of planned tables, figures, and listings.  Sample data displays are 
included in a separate document. 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics will be summarized and listed for the FAS:  age, sex, race, 
ethnicity, geographic region, weight, height, and BMI.  Eastern Cooperative Oncology Group 
performance status at baseline will be summarized and listed for the FAS. 
6.1.2. 
Disease History 
Time since diagnosis, initial cytogenetics/expression analysis, current cytogenetics/expression 
analysis, initial Ann Arbor stage, current Ann Arbor stage, initial presence of B-symptoms, 
current presence of B-symptoms, current MIPI risk category, bone marrow involvement (yes vs 
no), bulky disease at baseline (longest diameter ≥ 10 cm vs 5-< 10 cm, vs < 5 cm) at baseline by 
the IRC, and relapsed/refractory status to the most recent prior therapy will be summarized and 
listed for all participants in the FAS.  Date of tumor marker tests and test results will be listed. 
Time since diagnosis will be calculated as: 
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25. 
6.1.3. 
Prior Therapy 
Number of prior systemic cancer therapy regimens will be summarized for all participants in the 
FAS.  The component drugs of prior systemic therapy regimens will be coded using the WHO 
Drug Dictionary.  Number and percentage of participants with each drug will be summarized by 
WHO drug class and WHO drug PT.  Regimen name, component drugs, start and stop date, route 
of the medication, best response, reason for discontinuation, and date of relapse/progression will 
be listed. 
Number of participants who received prior radiation will be summarized for the FAS.  
Anatomical location of the administration, start and stop date, and total dose will be listed. 
Number of participants who had prior surgery or surgical procedure for the cancer treatment will 
be summarized for the FAS.  Date and description of the surgery/procedure will be listed. 
Number of participants who had hematopoietic stem cell transplant will be summarized for the 
FAS.  Date of transplant, type of transplant, source of cells, line of therapy, best response, date of 
relapse/progression, regimen name, and drug used with the transplant will be listed. 


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6.1.4. 
Medical History 
Medical history will be coded to SOC and PT using MedDRA coding dictionary.  For 
participants in the FAS, medical history will be summarized by SOC and PT and listed. 
6.2. 
Disposition of Participants 
The number and percentage of participants who were treated, who were ongoing with study 
treatment, who discontinued study treatment with a primary reason for discontinuation, who 
were still in the study, and who withdrew from the study with a primary reason for withdrawal 
will be summarized and listed for the FAS. 
The number of participants enrolled by country and site will also be provided for the FAS. 
6.3. 
Protocol Deviations 
Protocol deviations recorded on the eCRF will be summarized and listed for the FAS. 
6.4. 
Exposure 
For participants in the safety population, exposure to INCB050465 will be summarized 
descriptively as the following: 
• Duration of treatment (days):  Date of last dose – date of first dose + 1. 
• Duration of treatment during the initial QD dosing period (days):  Date of last 
dose during initial QD dosing period – date of first dose + 1. 
• Duration of treatment during the maintenance dosing period (days):  Date of last 
dose – date of first dose during the maintenance dosing period + 1.  Crossover 
participants who switched to the selected treatment regimen after the start of the 
maintenance dosing period will be summarized in a separate group (ie, Crossover). 
• Average reported daily dose during the initial QD dosing period (mg/day):  Total 
reported dose taken during initial QD dosing period (mg) / duration of treatment 
during the initial QD dosing period (days). 
• Average reported daily dose during the maintenance dosing period (mg/day):  
Total reported dose taken during the maintenance dosing period (mg) / duration of 
treatment during the maintenance dosing period (days).  Crossover participants who 
switched to the selected treatment regimen after the start of the maintenance dosing 
period will be summarized in a separate group (ie, Crossover). 
• Dose modifications:  Number of participants who had dose reduction and 
interruption will be summarized.  The number of dose reductions and the number of 
interruptions for each participant will be summarized. 
6.5. 
Study Drug Compliance 
For participants in the safety population, overall compliance (%) for INCB050465 will be 
calculated for all participants as 
compliance (%) = 100  [total dose actually taken] / [total prescribed dose]. 


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The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 
The total actual dose taken will be calculated based on information entered on the Drug 
Accountability eCRF.  If there are dispensed drugs that have not been returned yet, the actual 
dose taken starting from the dispense date of the unreturned drugs will be imputed by the dose 
taken as reported on the Dosing eCRF. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary.  
Number and percentage of participants in the FAS population with each prior and concomitant 
medication will be summarized by WHO drug class and WHO drug PT. 
7. 
EFFICACY 
Appendix A provides a list of planned tables, figures, and listings.  Sample data displays are 
included in a separate document. 
7.1. 
Efficacy Hypotheses 
Not applicable. 
7.2. 
Response Assessment 
An objective assessment of disease status is required at baseline (screening) using the CT-based 
response criteria of the Lugano Classification (Cheson et al 2014).  Disease status will be 
subsequently assessed by CT or MRI every 8 weeks through Week 24, then every 12 weeks 
through Week 96, and then every 24 weeks thereafter until disease progression. 
Bone marrow examination is required as a baseline assessment at screening except for reasons 
provided in Section 7.6.2 of the Protocol.  If disease is present in bone marrow at baseline, a 
bone marrow examination will be required to confirm CR or may be performed as clinically 
indicated.  If the bone marrow does not have lymphoma involvement at baseline, a repeat 
marrow examination is not required to confirm indication of CR on imaging. 
Sites will use the CT-based response criteria of the Lugano Classification (Cheson et al 2014) to 
assess response to treatment locally.  At each postbaseline disease assessment, response will be 
collected in the eCRF as CR, PR, SD, PD, or NE. 
All imaging will be submitted to the IRC.  Imaging data and applicable clinical data will be 
reviewed and response assessed using the CT-based response criteria of the Lugano 
Classification (Cheson et al 2014) by independent reviewers as described in the Independent 
Review Charter.  An overall timepoint response at each postbaseline disease assessment, the best 
overall response, the date of initial response (if applicable), and the date of disease progression 
along with reason(s) of disease progression (if applicable) for each participant, considering 
radiographic data and clinical data, will be provided by the Clinical Reviewer.  These data will 
be used in the analyses of related efficacy endpoints. 


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7.3. 
Analysis of the Primary Efficacy Parameter 
The primary efficacy analyses will be conducted when all participants in the FAS who have 
achieved a response (ie, CR or PR) as determined by IRC have been followed approximately 
12 months from the onset of first response. 
7.3.1. 
Best Overall Response and Objective Response Rate 
For responses determined by the IRC, the best overall response for each participant will be 
provided by the Clinical Reviewer.  A participant is considered an objective responder if they 
have a best overall response of CR or PR. 
The ORR is the proportion of objective responders.  Participants who do not have sufficient 
baseline or on-study response assessment information to be adequately assessed for response 
status will be included in the denominators in the calculation of ORR. 
Best overall response as determined by the IRC will be summarized descriptively, and the ORR 
as determined by the IRC with 95% CIs will be calculated.  Confidence intervals will be 
calculated based on the exact method for binomial distributions. 
Because participants who switched to the selected treatment regimen after starting the 
maintenance dose received a mixture of the non-selected and selected maintenance regimens and 
could confound the efficacy evaluation of the non-selected treatment regimen, a sensitivity 
analysis of ORR as determined by IRC will be provided to summarize these crossover 
participants as a separate treatment regimen.  In addition, the number of participants who 
achieved best overall response as determined by IRC after the time of crossover along with the 
best overall response data will be presented under this separate treatment regimen. 
When applicable, sensitivity analysis of ORR as determined by the IRC may be provided 
excluding participants that do not have evaluable radiological images at baseline per the IRC. 
7.3.2. 
Subgroup Analyses for Objective Response Rate 
Subgroups will be formed based on the following participant characteristics and baseline 
variables: 
• Age:  < 65 years, ≥ 65 years 
• Sex:  male, female 
• Race:  White, others 
• Geographic region:  Europe, North America, rest of world 
• Number of prior systemic therapy regimens:  1, 2-3  
• Current Ann Arbor Staging:  I-II, III-IV 
• Bone marrow involvement at baseline:  yes, no, unknown 
• MIPI risk category:  low (0-3), intermediate (4-5), high (6-11) 
• ECOG performance status:  0, 1, 2 


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• Bulky disease at baseline:  longest diameter ≥ 10 cm vs 5- < 10 cm, vs < 5 cm at 
baseline by IRC 
• Relapsed/refractory status to the most recent prior therapy: relapsed, refractory, 
unknown 
Subgroups may be further divided or combined based on emerging data.  The ORR as 
determined by the IRC and its 95% exact binomial CIs will be provided for participants for each 
subgroup.  A forest plot will be created to summarize the variability in ORRs as determined by 
the IRC for participants across subgroups. 
7.4. 
Analysis of the Secondary Efficacy Parameters 
7.4.1. 
Duration of Response 
Duration of response is defined as the time from first documented evidence of CR or PR until 
disease progression or death due to any cause among participants who achieve an objective 
response (ie, CR or PR), as determined by revised response criteria for lymphomas (Cheson 
et al 2014).  For responses assessed by the IRC, the date of initial response and date of disease 
progression will be provided by the Clinical Reviewer for participants who have achieved best 
response of CR or PR.  Censoring of DOR will follow the same algorithm as the censoring of 
PFS (see Section 7.4.3). 
The total number of responders as determined by the IRC, the number of participants whose 
disease progressed as determined by the IRC or who died, and the number of participants 
censored will be summarized.  The Kaplan-Meier estimate of median DOR as determined by the 
IRC and its 95% CIs will be provided, with the CIs calculated using the generalization of 
Brookmeyer and Crowley's method (1982) with log-log transformation (Klein and 
Moeschberger 1997). 
A sensitivity analysis of DOR will be performed where response assessments after the time of 
crossover will be excluded from the determination of DOR for participants who switched to the 
selected treatment regimen after starting the maintenance dose.  Crossover participants who have 
not progressed at the time of crossover will be censored at the last valid radiologic assessment 
on/before the time of crossover.  Participants who failed to achieve a response of CR or PR 
on/before the time of crossover will not be considered as responders for this analysis. 
7.4.2. 
Complete Response Rate 
Complete response rate is the percentage of participants with a best overall response of CR as 
defined by revised response criteria for lymphomas (Cheson et al 2014).  For responses 
determined by the IRC, the best overall response for each participant will be provided by the 
Clinical Reviewer.  Participants who do not have sufficient baseline or on-study response 
assessment information to be adequately assessed for response status will be included in the 
denominators in the calculation of CRR. 
The CRR as determined by the IRC will be estimated with 95% CIs.  Confidence intervals will 
be calculated based on the exact method for binomial distributions. 
A sensitivity analysis of CRR will be provided to summarize participants who switched to the 
selected treatment regimen after starting the maintenance dose as a separate treatment regimen. 


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7.4.3. 
Progression-Free Survival 
Progression-free survival is defined as the time from the date of the first dose of the study drug to 
the first documented disease progression as determined by revised response criteria for 
lymphomas (Cheson et al 2014), or death due to any cause, whichever occurs first.  For response 
assessed by the IRC, date of disease progression will be provided by the Clinical Reviewer.  
Censoring for PFS will follow the algorithm outlined in Table 2, which is based on FDA 
Guidance for Industry:  Clinical Trial Endpoints for the Approval of Non-Small Cell Lung 
Cancer Drugs and Biologics (2015) and Guidance for Industry:  Clinical Trial Endpoints for the 
Approval of Cancer Drugs and Biologics (2018). 
Table 2: 
Evaluation and Censoring of Progression-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline tumor assessments 
Censored 
Day 1 
No valid postbaseline response 
assessments 
Censored 
Day 1 
Progression documented between 
scheduled response assessments 
Progressed 
Date of first overall response of PD 
No progression 
Censored 
Date of last valid radiologic assessment (not NE and not 
missing) 
Study discontinuation for 
undocumented progression 
Censored 
Date of last valid radiologic assessment (not NE and not 
missing) 
Study discontinuation for toxicity or 
other reason 
Censored 
Date of last valid radiologic assessment (not NE and not 
missing) 
New anticancer treatment started 
Censored 
Date of last valid radiologic assessment (not NE and not 
missing) on/before starting a new anticancer treatment 
Death before first progressive 
response assessment 
Progressed 
Date of death 
Death between adequate response 
assessments 
Progressed 
Date of death 
Death or progression after 2 or more 
missed assessments 
Censored 
Date of last valid radiologic assessment (not NE and not 
missing) before the missed assessments 
NE = not evaluable. 
The total number of participants whose disease progressed as determined by the IRC or who 
died, and the number of participants censored will be summarized.  The Kaplan-Meier estimate 
of median PFS as determined by the IRC and its 95% CIs will be provided, with the CIs 
calculated using the generalization of Brookmeyer and Crowley's method (1982) with log-log 
transformation (Klein and Moeschberger 1997).  Progression-free survival rates at 6, 12, 18, 24, 
and 36 months will also be provided with 95% CIs calculated using Greenwood's formula to 
estimate the standard error. 
A sensitivity analysis of PFS will be performed where response assessments after the time of 
crossover will be excluded from the determination of PFS for participants who switched to the 
selected treatment regimen after starting the maintenance dose.  Crossover participants who have 
not progressed at the time of crossover will be censored at the last valid radiologic assessment 
on/before the time of crossover. 


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7.4.4. 
Overall Survival 
Overall survival is defined as the time from the date of the first dose of study drug to death due 
to any cause.  For participants who are still alive at the time of the analysis, OS will be censored 
on the date the participant is last known to be alive. 
The number of participants who died and the number of participants censored will be 
summarized.  The Kaplan-Meier estimate of median OS and its 95% CIs will be presented with 
the CIs calculated using the generalization of Brookmeyer and Crowley's method (1982) with 
log-log transformation (Klein and Moeschberger 1997).  Survival rates at 6, 12, 18, 24, and 
36 months will also be provided with 95% CIs calculated using Greenwood's formula to estimate 
the standard error. 
7.4.5. 
Best Percent Change in Target Lesion Size 
For each participant with measurable lesions at baseline, target lesion sizes will be measured by 
the sum of the product of diameters of all target lesions.  The best percent change from baseline, 
defined as the largest decrease in target lesion sizes during the study, will be summarized, and a 
waterfall plot of the best percent change will be generated using data from the IRC.  Note that for 
participants who only have increases in target lesion sizes from baseline, the smallest increase 
will be considered as the best change from baseline.  For the IRC, there will be 2 radiologic 
reviewers for each participant.  An adjudication will be performed per the Independent Review 
Charter when Reviewers 1 and 2 disagree on the CT/MRI best overall response, or when best 
overall response is consistent and the date of initial response and/or the date of PD differ 
between Reviewers 1 and 2.  The adjudicator will choose the read that he or she believes most 
accurately represents the adjudication parameter(s) in question.  This is considered the "accepted 
read," and data from this reviewer will be used for the analysis.  When there was no adjudication 
needed, data from Reviewer 1 will be used for the analysis.  An indicator is provided to identify 
the read that is considered to be the accepted assessment in data from the IRC. 
Best change in target lesion size as reported by the investigator will also be summarized as 
described above.  Target lesions considered "too small to measure" will be assigned a default 
value of 5 mm × 5 mm for the purposes of this analysis.  Likewise, target lesions identified as 
"not present" at postbaseline assessments will be assigned 0 mm × 0 mm for this analysis.  In the 
event a target lesion is unaccounted for in a particular postbaseline timepoint (ie, assessment 
missing or NE), then the overall sum of the product of diameters for target lesions will not be 
evaluable for that postbaseline timepoint. 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of planned tables, figures, and listings.  Sample data displays are 
included in a separate document. 
9.1. 
General Considerations 
Summary tables may be replaced with listings when appropriate.  For instance, an AE frequency 
table may be replaced with a listing if it only contains a few unique preferred terms reported on 
relatively few participants. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug and within 30 days of the last administration of study drug regardless of 
starting new anti-lymphoma therapy.  Analysis of AEs (as discussed below) will be limited to 
TEAEs, but data listings will include all AEs regardless of their timing in relation to study drug 
administration.  For purposes of analysis, all AEs will be considered TEAEs unless the AE can 
unequivocally be defined as not treatment emergent. 
Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be graded 
using the NCI CTCAE.  CTCAE v4.03 is used for this study.  The CTCAE reporting guidelines 
and grading details are available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs.  If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated.  In addition, serious TEAEs will also be tabulated. 
9.2.2. 
Adverse Events of Special Interest 
The number of participants who experienced TEAEs of special interest listed below will be 
summarized by maximum severity. 
• Colitis 
• Diarrhea 
• Exfoliative dermatitis 


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• Febrile neutropenia 
• Rash 
• Intestinal perforation 
• Pneumonitis 
• Pneumonia 
• PJP infection 
• CMV infection 
• Herpes simplex  
• Varicella zoster virus infection 
The time to onset of a TEAE is defined as the interval between the date of first dose of study 
drug and the date of the first occurrence of a TEAE.  Participants who have not experienced a 
TEAE at the time of analysis will be right-censored at the earlier of 30 days after the last dose 
date and date of last study visit through the end of safety follow-up.  If participants have missing 
or partial last dose dates of study drug or onset date of a TEAE, the partial or missing dates will 
be handled using the rules explained in Section 4.1.4.   
Summaries of time to onset of new or worsening Grade 3 or higher AEs will be provided using 
descriptive statistics and the life-table method for rash, colitis, diarrhea, febrile neutropenia, 
pneumonia, herpes simplex, and varicella zoster virus infection.  In addition, summaries of time 
to onset of new or worsening AEs of any grade will be provided using descriptive statistics and 
the life-table method for colitis, diarrhea, exfoliative dermatitis, intestinal perforation, 
pneumonia, pneumonitis, PJP infection, CMV infection, herpes simplex, and varicella zoster 
virus infection.  Kaplan-Meier plots of time to onset of new or worsening Grade 3 or higher AEs 
will be provided for rash, colitis, and diarrhea.  In addition, Kaplan-Meier plots of time to onset 
of new or worsening AEs of any grade will be provided for colitis and diarrhea. 
Descriptive statistics of time to onset of these TEAEs of special interest are based on all 
participants who have experienced a TEAE at the time of analysis.  To summarize these TEAEs 
of special interest using the life-table method, the effective sample size is defined as the number 
of participants at the beginning of the interval minus half the participants censored in the 
interval.  The conditional proportion is calculated as the number of first events divided by the 
effective sample size in the interval.   
The longest duration of a TEAE of any grade is defined as the longest interval between the date 
of occurrence of a TEAE and the date of resolution.  The longest duration of a Grade 3 or higher 
TEAE is defined as the longest interval between the date of occurrence of a Grade 3 or higher 
TEAE and the date of improvement to Grade 2 or lower.  If participants have missing or partial 
onset/end date of a TEAE, the partial or missing dates will be handled using the rules explained 
in Section 4.1.4.  Participants who have missing end date of a TEAE at the time of analysis will 
be right-censored using the following algorithm: 
• If the TEAE is serious, then the participant will be censored at the earlier date of data 
cutoff, study discontinuation and death.  


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• If the TEAE is not serious,  
− 
If the participant is ongoing with study treatment, then the participant will be 
censored at the data cutoff date, OR  
− If the participant discontinued treatment, then the participant will be censored at 
date of safety follow-up visit, or 35 days after the end of treatment visit (or after 
the last dose if the end of treatment visit was not performed), whichever is later; 
the censored date will be truncated by the earlier date of data cutoff, study 
discontinuation, and death if beyond. 
Longest duration of new or worsening Grade 3 or higher colitis, diarrhea, rash, and febrile 
neutropenia will be summarized.  In addition, longest duration of new or worsening AEs of any 
grade will be summarized for colitis, diarrhea, and rash.  
The total number of participants whose TEAE of any grade resolved or whose Grade 3 or higher 
TEAE improved to Grade 2 or lower, and the number of participants censored will be 
summarized.  The Kaplan-Meier estimate of median time to resolution/improvement and its 
95% CIs will be provided, with the CIs calculated using the generalization of Brookmeyer and 
Crowley's method (1982) with log-log transformation (Klein and Moeschberger 1997).  
Resolution/improvement rates at selected timepoints will also be provided with 95% CIs 
calculated using Greenwood's formula to estimate the standard error. 
TEAEs of special interest to be summarized may be adjusted based on emerging data. 
9.2.3. 
Adverse Event Summaries 
Overall summaries of TEAEs by treatment regimen will be provided during the INCB050465 
initial QD dosing period, maintenance dosing period, and overall period (ie, all TEAEs 
regardless of the timing of occurrence).  These summaries will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any TEAEs related to INCB050465 
• Number (%) of participants reporting any Grade 3 or higher TEAEs related to 
INCB050465 
• Number (%) of participants reporting any serious TEAEs related to INCB050465 
• Number (%) of participants who had TEAE with fatal outcome 
• Number (%) of participants with INCB050465 dose reductions because of TEAEs 
• Number (%) of participants who temporarily interrupted INCB050465 because of 
TEAEs 
• Number (%) of participants who permanently discontinued INCB050465 because of 
TEAEs 


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The following summaries will be produced for TEAEs during the overall period by MedDRA 
term (if 10 or fewer participants appear in a table, a listing may be appropriate): 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of TEAEs by SOC, PT, and maximum severity 
• Summary of TEAEs by PT and maximum severity in decreasing order of frequency 
• Summary of Grade 3 or higher TEAEs by SOC and PT 
• Summary of Grade 3 or higher TEAEs by PT in decreasing order of frequency 
• Summary of serious TEAEs by SOC and PT 
• Summary of serious TEAEs by PT in descending order of frequency 
• Summary of INCB050465 treatment-related TEAEs by SOC and PT 
• Summary of INCB050465 treatment-related TEAEs by PT in decreasing order of 
frequency 
• Summary of INCB050465 treatment-related TEAEs by SOC, PT, and maximum 
severity 
• Summary of Grade 3 or higher INCB050465 treatment-related TEAEs by SOC and 
PT 
• Summary of INCB050465 treatment-related serious TEAEs by SOC and PT 
• Summary of TEAEs with a fatal outcome by SOC and PT 
• Summary of TEAEs leading to INCB050465 dose reduction by SOC and PT 
• Summary of TEAEs leading to INCB050465 dose interruption by SOC and PT 
• Summary of TEAEs leading to discontinuation of INCB050465 by SOC and PT 
• Summary of selected TEAEs of special interest by maximum severity 
• Summary of time to onset of selected TEAEs of special interest  
• Summary of time to onset of selected TEAEs of special interest:  life-table method 
• Summary of longest duration of selected TEAEs of special interest 
The following supporting summaries will be produced for TEAEs during the INCB050465 initial 
QD dosing period and the maintenance dosing period by MedDRA term.  For the supporting 
summaries during the maintenance dosing period, participants who cross over to the selected 
treatment regimen after the start of the maintenance dosing period will be summarized in a 
separate group (ie, Crossover): 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of TEAEs by PT and maximum severity in decreasing order of frequency 
• Summary of Grade 3 or higher TEAEs by PT in decreasing order of frequency  


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• Summary of serious TEAEs by PT in descending order of frequency 
• Summary of TEAEs with a fatal outcome by SOC and PT  
• Summary of TEAEs leading to discontinuation of INCB050465 by SOC and PT 
9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
Laboratory values and change from baseline values will be summarized descriptively by visit.  
Baseline will be determined according to Section 4.1.3.  If there are multiple values that meet the 
criteria for baseline, the value from the central laboratory has priority over the value from the 
local laboratory.  Thereafter, additional rules may be provided after consultation with the 
medical monitor to delineate which value will be defined as baseline. 
Laboratory test values will be assessed for severity based on the numerical component of 
CTCAE v4.03. 
9.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from central laboratories will be reported in SI 
units.  Any laboratory test results and associated normal ranges from local laboratories will be 
converted to SI units.   
When there are multiple laboratory nonmissing values for a participant's particular test at a 
scheduled visit, central laboratory values have higher priority over local laboratory values.  If a 
tie still exists, the laboratory value with the smallest laboratory sequence number will be used in 
by-visit summaries. 
Numeric laboratory values will be summarized descriptively in SI units, and non-numeric test 
values will be tabulated when necessary.  In addition, line graphs will be provided for ALT, 
AST, hemoglobin, platelet counts, leukocytes, neutrophils, and lymphocytes. 
Shift tables will be presented showing change in CTCAE grade from baseline to worst grade 
postbaseline.  Separate summaries for abnormally high and abnormally low laboratory values 
will be provided when the laboratory parameter has both high and low grading criteria.  The 
denominator for the percentage calculation will be the number of participants in the baseline 
category.  The number of participants who experienced worsening of laboratory abnormalities 
will be summarized by maximum postbaseline severity. 
9.3.3. 
Potential Hy's Law Events 
Participants with elevated ALT or AST > 3 × ULN range and alkaline phosphatase < 2 × ULN 
range accompanied by total bilirubin > 2 × ULN range at the same visit will be listed by 
treatment group. 


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9.3.4. 
Worsening Laboratory Events of Special Interest 
Laboratory events of special interest are listed below. 
• ALT increased 
• AST increased 
• Absolute neutrophil count decreased 
The time to onset of a worsening laboratory event is defined as the interval between the date of 
first dose of study drug and the date of the first occurrence of CTC grade worse than baseline for 
the laboratory event.  Participants who have not experienced a worsening laboratory event at the 
time of analysis will be right-censored at the last postbaseline study visit with nonmissing CTC 
grade of the laboratory event. 
Time to onset of worsening Grade 3 or 4 laboratory events of special interest will be summarized 
using descriptive statistics and the life-table method as described in Section 9.2.2, and the 
Kaplan-Meier plot of time to onset of worsening Grade 3 or 4 absolute neutrophil count 
decreased will be provided.  Laboratory events of special interest to be summarized may be 
adjusted based on emerging data. 
9.4. 
Vital Signs 
Values at each scheduled visit, change, and percent change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, body temperature, respiratory 
rate, and weight will be summarized descriptively. 
Normal ranges for vital sign values are defined in Table 4.  The abnormal values for participants 
exhibiting vital sign abnormalities will be listed along with their assigned treatment regimen.  
Alert vital signs are defined as an absolute value outside the defined range and percentage 
change greater than 25%.  Note that the definition of alert vital signs does not apply for body 
temperature and weight.  The abnormal values for participants exhibiting alert vital sign 
abnormalities will be listed. 
Table 4: 
Normal Ranges for Vital Sign Values 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
≤ 155 mmHg 
≥ 85 mmHg 
Diastolic blood pressure 
≤ 100 mmHg 
≥ 40 mmHg 
Pulse 
≤ 100 bpm 
≥ 45 bpm 
Temperature 
≤ 38°C 
≥ 35°C 
Respiratory rate 
≤ 24 breaths/min 
≥ 12 breaths/min 
9.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, QRS, QT, QTcB, QTcF, and RR intervals will be obtained for 
each participant during the study.  Values at each scheduled visit, change, and percent change 
from baseline will be summarized for each ECG parameter.  Baseline will be determined as the 
average of all nonmissing values before the first administration of INCB050465. 


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Normal ranges for ECG values are defined in Table 5.  Electrocardiogram values will also be 
considered abnormal if the absolute percentage change from baseline is more than 25% (30% for 
QRS interval).  Participants exhibiting ECG abnormalities will be listed with study visit and 
assigned treatment regimen.  Abnormal values for participants with alert ECG values, defined as 
both the absolute value and the percentage change from baseline being outside normal ranges, 
will be identified and listed.  Outliers of QT, QTcB, and QTcF values, defined as absolute values 
> 450 milliseconds or change from baseline > 30 milliseconds, will be summarized. 
Table 5: 
Normal Ranges for Electrocardiogram Values 
Parameter 
High Threshold 
Low Threshold 
PR 
≤ 220 ms 
≥ 75 ms 
QRS 
≤ 120 ms 
≥ 50 ms 
QT 
≤ 500 ms 
≥ 300 ms 
QTcB, QTcF 
≤ 450 ms 
≥ 295 ms 
RR 
≤ 1330 ms 
≥ 600 ms 
QTcB = Bazett's correction; QTcF = Fridericia's correction. 
10. 
INTERIM ANALYSES 
An interim futility analysis is planned for each of the cohorts when 30 participants have been 
treated and have been evaluated for response or have permanently discontinued study treatment 
because of disease progression, withdrawal of consent, or death. 
Cohort 1 will be terminated for futility if ≤ 3 of the 30 participants responded (ie, CR or PR) 
based on assessments provided by the IRC; otherwise, the study for Cohort 1 will continue.  The 
probability of stopping at interim for futility is 0.51 when the true response rate is 12%, 
0.12 when the true response rate is 20%, or 0.02 when the true response rate is 28%. 
Cohort 2 will be terminated for futility if ≤ 10 of the 30 participants responded (ie, CR or PR) 
based on assessments provided by the IRC; otherwise, the study for Cohort 2 will continue.  The 
probability of stopping at interim for futility is 0.29 when the true response rate is 40%, 
0.05 when the true response rate is 50%, or 0.003 when the true response rate is 60%. 
An IDMC will be charged with evaluating interim futility results.  The IDMC will consist of 
clinicians and an independent statistician.  The IDMC will make recommendations to the sponsor 
at the planned interim futility analysis for both cohorts.  The process by which the IDMC will 
make recommendations and decisions will be documented in the IDMC Charter.  Additional 
operational details of the interim analyses, including tables, figures, and listings provided to the 
IDMC, will be provided in the IDMC Charter. 


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11.
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN
All versions of the SAP are listed in Table 6. 
Table 6: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
04 FEB 2019 
Amendment 1 
27 AUG 2020 
Amendment 2 
28 JAN 2021 
11.1. 
Changes to Protocol-Defined Analyses 
The PP population was removed from the planned analysis.  For a single arm, open-label study, 
the determination of participants to be excluded from the PP population is post hoc and may not 
be done objectively; thus, analysis based on this population may not be meaningful. 
11.2. 
Changes to the Statistical Analysis Plan 
Amendment 2 (28 JAN 2021) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to comply 
with responses to comments provided by FDA regarding the Statistical Analysis Plan 
Amendment 1. 
•
Section 6.4 was updated to include the summary for the number of dose reductions and 
the number of dose interruptions of each participant.
•
Section 7.3 was updated to include the timing of primary efficacy analysis.
•
Section 7.3.1 was updated to include a sensitivity analysis of ORR that summarizes 
participants who switched to the selected dose after starting the maintenance dose in a 
separate treatment regimen and to include an additional analysis on the number of 
participants who achieved best overall response after the time of crossover along with the 
best overall response data for this separate treatment regimen.
•
Section 7.3.2 was revised to update the subgroup analysis by number of prior systemic 
therapy regimens at 1 vs 2-3, because historical clinical evidence suggests that third-line 
or later participants may have a poorer outcome compared with second-line participants 
in MCL.
•
Section 7.4.1 and Section 7.4.3 were updated to included sensitivity analyses where 
response assessments after the time of crossover will be excluded from the determination 
of DOR and PFS for participants who switched to the selected treatment regimen after 
starting the maintenance dose.
•
Section 7.4.2 was updated to include a sensitivity analysis of CRR by summarizing 
participants who switched to the selected dose after starting the maintenance dose in a 
separate treatment regimen. 


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• Section 9.2.1 was modified to clarify how AEs that occur after new anti-lymphoma 
therapy will be assessed. 
• Incorporation of minor changes.  Other minor changes have been incorporated 
throughout the SAP and are noted in the redline version of the amendment. 
Amendment 1 (27 AUG 2020) 
• Section 3 was revised to state that 40 additional participants will be added to Cohort 2 
rather than 30 additional participants, thus increasing the total number of participants 
in Cohort 2 from 90 to 100.  This change is to comply with recommendations from 
FDA to achieve a sufficient number of participants in Cohort 2 to support registration. 
• Section 4.1.4 was updated to include details of rules for handling partial/missing 
onset or end date of TEAEs in the calculation of time to onset or duration of a TEAE.  
Rules for partial/missing date of last dose were updated to include details for when 
both month and day are missing. 
• Section 5.2 was modified to provide details regarding how crossover participants will 
be summarized.  
• Section 5.3 was updated to remove the efficacy evaluable analysis set and use the 
FAS for all analyses of efficacy data.  This change is to comply with comments from 
FDA that any participants who received at least 1 dose should be included in the 
efficacy analyses for a single-arm trial.  The all-screened population was added for 
the summary of analysis populations.  
• Section 6.1.1 was modified to add geographic region to the summary of demographic 
and baseline characteristics because it is one of the subgroups used for analyses on 
ORR. 
• Section 6.1.2 was modified to remove summaries of tumor markers but only keep 
listings.  Relapsed/refractory status to the most recent prior therapy was added to the 
summary table of disease history because the response to last regimen before entering 
the study may be a prognostic factor for clinical outcomes.  
• Section 6.2 was modified to add summaries of participants who are ongoing with 
treatment or still in the study. 
• Section 6.4 was modified to change the calculations of duration of treatment and 
average dose during the maintenance dosing period because Group B with 2.5 mg QD 
was selected as the maintenance dose. 
• Section 7.3.1 was modified to replace the efficacy evaluable analysis set with the full 
analysis set.  This change is to align with Protocol Amendment 7 dated 30 JAN 2020 
and include all treated participants in the efficacy analyses to comply with comments 
from FDA.  
• Section 7.3.2 was modified to add "unknown" as a category for bone marrow 
involvement at baseline.  Relapsed/refractory status to the most recent prior therapy 
was added to the subgroup analysis because the response to last regimen before 
entering the study may be a prognostic factor for clinical outcomes. 


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• Section 7.4.3 was modified to update references of censoring for PFS. 
• Section 9.2.2 was updated to include details of analyses on time to onset of selected 
TEAEs of special interest.  Summaries of longest duration of selected TEAEs of 
special interest were added to have a better understanding of the safety profile in 
terms of duration of class-effect AEs as well as AEs influenced by treatment 
regimens.  "Grade 2 or higher" was changed to "Grade 3 or higher" for time to onset 
summary of rash.  This change was made to be consistent with other PI3K inhibitors, 
which highlighted more severe cutaneous reactions graded as Grade 3 or higher in the 
labeling.  "Herpes simplex virus infection" was changed to "herpes simplex" based on 
the MedDRA coding dictionary as a broader term.  Exfoliative dermatitis was added 
to the list of TEAEs of special interest. 
• Section 9.2.3 was updated to include summary of TEAEs by PT and maximum 
severity in decreasing order of frequency, summary of longest duration of selected 
TEAEs of special interest, and additional supporting summaries during the 
INCB050465 initial QD dosing period and the maintenance dosing period, which will 
provide supportive data of the safety profile of the maintenance dose.  Summary of 
nonserious TEAEs by SOC and PT was removedbecause it will not be used for the 
clinical study report but will be provided for result disclosure.  
• Section 9.3.2 was modified to include ALT and AST in the line graphs as additional 
supportive analyses for laboratory events of special interest. 
• Section 9.3.3 was added to identify potential Hy's law events to better monitor liver 
toxicity. 
• Section 9.3.4 was updated to align with the analysis plan for adverse events of special 
interest.  Summary of worsening of laboratory events of special interest was removed 
because this is covered by the summary of worsening of laboratory abnormalities. 
• Section 9.5 was updated to change the high threshold of QTcF and QTcB interval 
from 460 to 450 milliseconds for the purpose of analysis.  This change is to comply 
with the categories outlined in FDA Guidance for Industry (E14 Clinical Evaluation 
of QT/QTc Interval Prolongation and Proarrhythmic Potential for 
Non-Antiarrhythmic Drugs) used to characterize outliers in QTc values. 


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12. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and 
response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin 
Oncol 2014;32:3059-3068. 
Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data. New 
York, NY: Springer; 1997. 


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APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the Clinical Study 
Report for Cohort 1 and Cohort 2.  Outputs from Cohort 1 will have ".1" at the end of the 
numbering.  Outputs from Cohort 2 will have ".2" at the end of the numbering.  Shells are 
provided in a separate document for tables that are not in the Standard Safety Tables v1.9. 
The lists of tables, figures, listings and the shells are to be used as guidelines.  Modifications of 
the lists that do not otherwise affect the nature of the analysis will not warrant an amendment to 
the SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
Baseline and Demographic Characteristics 
 
1.1.1 
Analysis Populations 
All-Screened 
X 
1.1.2 
Summary of Participant Disposition 
FAS 
X 
1.1.3 
Summary of Number of Participants Enrolled by Country and Site 
FAS 
X 
1.1.4 
Summary of Protocol Deviations 
FAS 
X 
1.2.1 
Summary of Demographics and Baseline Characteristics 
FAS 
X 
1.3.1 
Summary of Baseline Disease Characteristics 
FAS 
X 
1.3.2 
Summary of Prior Cancer Therapy 
FAS 
 
1.3.3 
Summary of Prior Systematic Cancer Therapy by WHO Drug Class 
and Preferred Term 
FAS 
 
1.4.1 
Summary of Prior Medications 
FAS 
X 
1.4.2 
Summary of Concomitant Medications 
FAS 
X 
1.5.1 
Summary of General Medical History 
FAS 
X 
Efficacy 
 
2.1.1 
Summary of Best Overall Response and Objective/Complete 
Response Rate as Determined by Independent Review Committee 
FAS 
 
2.1.2 
Summary of Best Overall Response and Objective/Complete 
Response Rate as Reported by Investigator 
FAS 
 
2.1.3 
Summary of Best Overall Response and Objective Response Rate as 
Determined by Independent Review Committee by Subgroup 
FAS 
 
2.2.1 
Summary of Duration of Response as Determined by Independent 
Review Committee 
FAS 
 
2.2.2 
Summary of Duration of Response as Reported by Investigator 
FAS 
 
2.2.3 
Summary of Progression-Free Survival as Determined by 
Independent Review Committee 
FAS 
 
2.2.4 
Summary of Progression-Free Survival as Reported by Investigator 
FAS 
 
2.2.5 
Summary of Overall Survival 
FAS 
 
2.2.6 
Summary of Best Change in Target Lesion Size as Determined by 
Independent Review Committee 
FAS 
 


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Table No. 
Title 
Population 
Standard 
2.2.7 
Summary of Best Change in Target Lesion Size as Reported by 
Investigator 
FAS 
 
2.4.1 
Summary of Best Overall Response and Objective/Complete 
Response Rate as Determined by Independent Review Committee – 
Crossover as a Separate Treatment Group 
FAS 
 
2.4.2 
Summary of Best Overall Response and Objective/Complete 
Response Rate as Reported by Investigator – Crossover as a Separate 
Treatment Group 
FAS 
 
2.4.3 
Summary of Best Overall Response as Determined by Independent 
Review Committee for Crossover Participants 
FAS 
 
2.4.4 
Summary of Best Overall Response as Reported by Investigator for 
Crossover Participants 
FAS 
 
2.4.5 
Summary of Duration of Response as Determined by Independent 
Review Committee – Censoring Crossover Participants 
FAS 
 
2.4.6 
Summary of Duration of Response as Reported by Investigator – 
Censoring Crossover Participants 
FAS 
 
2.4.7 
Summary of Progression-Free Survival as Determined by 
Independent Review Committee – Censoring Crossover Participants 
FAS 
 
2.4.8 
Summary of Progression-Free Survival as Reported by Investigator – 
Censoring Crossover Participants 
FAS 
 
Safety 
 
3.1.1 
Summary of Exposure and Compliance 
Safety 
 
3.1.2 
Summary of Exposure and Average Daily Dose During Initial QD 
Dosing Period 
Safety 
 
3.1.3 
Summary of Exposure and Average Daily Dose During Maintenance 
Dosing Period 
Safety 
 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
X 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
X 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and Maximum Severity 
Safety 
X 
3.2.6 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term 
Safety 
X 


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Table No. 
Title 
Population 
Standard 
3.2.7 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.8 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.9 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.10 
Summary of Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.11 
Summary of Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.12 
Summary of Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class, Preferred Term, and Maximum 
Severity 
Safety 
X 
3.2.14 
Summary of Grade 3 or Higher Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term 
Safety 
X 
3.2.15 
Summary of Treatment-Related Serious Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.16 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term  
Safety 
X 
3.2.18 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Reduction by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.19 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.20 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by MedDRA System Organ Class and 
Preferred Term 
Safety 
X 
3.2.25 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term and Maximum Severity in Decreasing Order of 
Frequency 
Safety 
 
3.2.26 
Summary of Selected Treatment-Emergent Adverse Events of Special 
Interest by Maximum Severity 
Safety 
 
3.2.27 
Summary of Time to Onset of Selected Treatment-Emergent Adverse 
Events of Special Interest 
Safety 
 
3.2.28 
Summary of Time to Onset of Selected Treatment-Emergent Adverse 
Events of Special Interest : Life-Table Method 
Safety 
 
3.2.29 
Summary of Longest Duration of Selected Treatment-Emergent 
Adverse Events of Special Interest 
Safety 
 
3.3.1.1 
Summary of Laboratory Values - Hematology 
Safety 
X 
3.3.1.2 
Summary of Laboratory Values - Chemistry 
Safety 
X 
3.3.3.1 
Shift Summary of Hematology Laboratory Values in CTC Grade - To 
the Worst Abnormal Value  
Safety 
X 
3.3.3.2 
Shift Summary of Chemistry Laboratory Values in CTC Grade - To 
the Worst Abnormal Value 
Safety 
X 


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Table No. 
Title 
Population 
Standard 
3.3.3.4 
Treatment-Emergent Worsening of Laboratory Abnormalities - 
Hematology 
Safety 
X 
3.3.3.5 
Treatment-Emergent Worsening of Laboratory Abnormalities - 
Chemistry 
Safety 
X 
3.3.6 
Time to Onset of Treatment-Emergent Worsening of Laboratory 
Events of Special Interest 
Safety 
 
3.3.7 
Time to Onset of Treatment-Emergent Worsening of Laboratory 
Events of Special Interest: Life-Table Method 
Safety 
 
3.4.1 
Summary of Systolic Blood Pressure 
Safety 
X 
3.4.2 
Summary of Diastolic Blood Pressure  
Safety 
X 
3.4.3 
Summary of Pulse  
Safety 
X 
3.4.4 
Summary of Respiratory Rate 
Safety 
X 
3.4.5 
Summary of Body Temperature 
Safety 
X 
3.4.6 
Summary of Weight 
Safety 
X 
3.5.1 
Summary of PR Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.2 
Summary of QRS Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.3 
Summary of QT Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.4 
Summary of QTcB Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.5 
Summary of QTcF Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.6 
Summary of RR Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.8 
Summary of Outliers of QT, QTcB, and QTcF Interval Values From 
12-Lead ECG 
Safety 
X 
3.5.9 
Summary of Clinically Significant ECG Abnormality 
Safety 
X 
Figures 
Figure No. 
Title 
4.1.1 
Forest Plot of Objective Response Rate as Determined by Independent Review Committee 
4.2.1 
Kaplan-Meier Estimates of Duration of Response as Determined by Independent Review Committee 
4.2.2 
Kaplan-Meier Estimates of Duration of Response as Reported by Investigator 
4.2.3 
Kaplan-Meier Estimates of Progression-Free Survival as Determined by Independent Review 
Committee 
4.2.4 
Kaplan-Meier Estimates of Progression-Free Survival as Reported by Investigator 
4.2.5 
Kaplan-Meier Estimates of Overall Survival  
4.2.6 
Waterfall Plot of Best Percent Change in Sum of Target Lesions as Determined by Independent 
Review Committee 
4.2.7 
Waterfall Plot of Best Percent Change in Sum of Target Lesions as Reported by Investigator 
4.3.1 
Kaplan-Meier Estimates of Duration of Response as Determined by Independent Review Committee 
– Censoring Crossover Participants 
4.3.2 
Kaplan-Meier Estimates of Duration of Response as Reported by Investigator  – Censoring Crossover 
Participants 
4.3.3 
Kaplan-Meier Estimates of Progression-Free Survival as Determined by Independent Review 
Committee – Censoring Crossover Participants 


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Figure No. 
Title 
4.3.4 
Kaplan-Meier Estimates of Progression-Free Survival as Reported by Investigator – Censoring 
Crossover Participants 
4.5.1 
Kaplan-Meier Estimates of Time to Onset of Selected TEAEs of Special Interest 
4.5.2 
Kaplan-Meier Estimates of Longest Duration of Selected TEAEs of Special Interest 
4.6.1 
Line Graph of Mean Values Over Time for Selected Laboratory Values (Hemoglobin, Platelet 
Counts, Leukocytes, Neutrophils, and Lymphocytes) 
4.6.2 
Kaplan-Meier Estimates of Time to Onset of Selected Worsening Laboratory Events of Special 
Interest 
Listings 
Listing No. 
Title 
2.1.1 
Participant Enrollment and Disposition Status 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.2 
Protocol Deviations  
2.3 
Analysis Population 
2.4.1 
Demographics and Baseline Characteristics 
2.4.2 
Disease History 
2.4.3 
Prior Systemic Therapy 
2.4.4 
Prior Radiation Treatment 
2.4.5 
Prior Surgery or Surgical Procedure 
2.4.6 
Prior Stem Cell Transplant 
2.4.7 
Medical History 
2.4.8 
Prior and Concomitant Medication 
2.4.9 
Tumor Markers 
2.5.1 
Study Drug Compliance 
2.5.2 
Study Drug Administration 
2.6.1 
Best Overall Response, Duration of Response, and Progression-Free Survival per Independent 
Review Committee 
2.6.2 
Best Overall Response, Duration of Response, and Progression-Free Survival per Investigator 
2.6.3 
Overall Response Assessment by Visit per Independent Review Committee 
2.6.4 
Independent Review Committee Response Assessment:  Target Lesions 
2.6.5 
Independent Review Committee Response Assessment:  Nontarget Lesions 
2.6.6 
Independent Review Committee Response Assessment:  New Lesions  
2.6.7 
Overall Response Assessment by Visit per Investigator 
2.6.8 
Investigator Response Assessment:  Target Lesions  
2.6.9 
Investigator Response Assessment:  Nontarget Lesions  
2.6.10 
Investigator Response Assessment:  New Lesions  
2.6.11 
Deaths and Overall Survival 
2.6.12 
Bone Marrow Examination 


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Listing No. 
Title 
2.6.14 
Best Overall Response, Duration of Response, and Progression-Free Survival per Independent 
Review Committee – Censoring Crossover Participants 
2.6.15 
Best Overall Response, Duration of Response, and Progression-Free Survival per Investigator – 
Censoring Crossover Participants 
2.7.1 
Adverse Events 
2.7.2 
Serious Adverse Events 
2.7.3 
Grade 3 and Higher Adverse Events 
2.7.4 
Treatment Related Adverse Events 
2.7.5 
Fatal Adverse Events 
2.7.6 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of INCB050465 
2.8.1 
Clinical Laboratory Values - Hematology 
2.8.2 
Clinical Laboratory Values - Chemistry 
2.8.3 
Abnormal Clinical Laboratory Values - Hematology 
2.8.4 
Abnormal Clinical Laboratory Values - Chemistry 
2.8.5 
Potential Hy's Law Events 
2.9.1 
Vital Signs 
2.9.2 
Abnormal Vital Sign Values 
2.9.3 
Alert Vital Sign Values 
2.10.1 
12-Lead ECG Values 
2.10.2 
Abnormal 12-Lead ECG Values 
2.10.3 
Alert 12-Lead ECG Values