Conditions: Lymphoma
Keywords: Follicular lymphoma non-Hodgkin lymphoma (NHL) phosphatidylinositol 3-kinase (PI3K) δ inhibitor
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 126
Healthy volunteers: no

Brief summary:
The purpose of this study is to assess the objective response rate of parsaclisib treatment in participants with relapsed or refractory follicular lymphoma.

Detailed description:

Arms:
arm 1: Participants received parsaclisib 20 mg once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to approximately 52 weeks. arm 2: Participants received parsaclisib 20 mg QD for 8 weeks followed by 2.5 mg QD for up to approximately 52 weeks.

Interventions: intervention 1: Parsaclisib
Intervention descriptions: intervention 1: Parsaclisib tablets administered orally with water and without regard to food

Protocol document:
Prot_000.pdf: 
Official Title: 
A Phase 2, Multicenter, Open-Label Study of INCB050465, a PI3Kδ Inhibitor 
in Relapsed or Refractory Follicular Lymphoma (CITADEL-203) 
NCT Number: 
NCT03126019 
Document Date: 
Clinical Study Protocol Amendment Version 9: 23 December 2019 


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CONFIDENTIAL 
 
Clinical Study Protocol 
 
INCB 50465-203 
A Phase 2, Multicenter, Open-Label Study of INCB050465, a PI3Kδ 
Inhibitor, in Relapsed or Refractory Follicular Lymphoma 
(CITADEL-203) 
 
Product: 
INCB050465 
IND Number: 
121,474 
EudraCT Number: 
2017-001624-22 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
01 MAR 2017 
Amendment (Version) 1: 
15 MAR 2017 
Amendment (Version) 2: 
15 AUG 2017 
Amendment (Version) 3: 
11 SEP 2017 
Amendment (Version) 4: 
25 OCT 2017 
Amendment (Version) 4-CAN: 
12 DEC 2017 
Amendment (Version) 5: 
17 JAN 2018 
Amendment (Version) 6: 
11 JUL 2018 
Amendment (Version) 7: 
04 SEP 2018 
Amendment (Version) 8: 
06 DEC 2018 
Amendment (Version) 9: 
23 DEC 2019 
 
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 50465-203 Protocol Amendment 9 (Version 9 dated 23 DEC 2019) 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, Multicenter, Open-Label Study of INCB050465, a PI3Kδ Inhibitor, in 
Relapsed or Refractory Follicular Lymphoma (CITADEL-203) 
Protocol Number:  INCB 50465-203 
Study Phase:  2 
Indication:   Relapsed or refractory follicular lymphoma 
 
Objectives 
Endpoints 
Primary 
To assess the efficacy of INCB050465 in terms of 
objective response rate (ORR) in subjects with 
relapsed or refractory follicular lymphoma (FL). 
ORR defined as the percentage of subjects with a 
complete response (CR) or partial response (PR) as 
defined by revised response criteria for lymphomas, 
as determined by an Independent Review Committee 
(IRC). 
Secondary 
To assess complete response rate (CRR). 
CRR defined as the percentage of subjects with a CR 
as defined by revised response criteria for 
lymphomas, as determined by an IRC. 
To assess the 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 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). 
OS defined as the time from the date of the first dose 
of study treatment until death from any cause. 
To assess 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 the diameters of all target 
lesion sizes. 
To characterize the safety and tolerability of 
INCB050465. 
Safety measured by clinical assessments, including 
vital signs and physical examinations, 12-lead 
electrocardiograms (ECGs), chemistry and 
hematology laboratory values, and adverse events 
(AEs). 


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This is a Phase 2, multicenter, open-label study of 120 subjects in which the first 50 subjects will be 
assigned at 1:1 ratio to 2 treatment groups:  Group A and Group B.  Subjects in treatment Group A will 
receive INCB050465 20 mg once daily for 8 weeks followed by 20 mg once weekly; subjects in 
treatment Group B will receive INCB050465 20 mg once daily for 8 weeks followed by 2.5 mg once 
daily.  The remaining 70 subjects will be allocated to one of the 2 treatment groups to better understand 
the safety and efficacy of that treatment regimen.  The treatment group will be selected after evaluation 
of emerging safety and efficacy data from this and other monotherapy studies of INCB050465 in NHL 
that are evaluating the same or similar dosing regimens and will be implemented after the first 
50 subjects are enrolled.  Subjects allocated to 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.  Furthermore, no changes will be made to the 
primary analysis. 
Subjects will be evaluated for ORR by an IRC and followed for CRR, DOR, PFS, OS, and safety.  
Subjects may receive treatment until disease progression, death, unacceptable toxicity, or consent 
withdrawal. 
An interim futility analysis is planned when the first 50 subjects (Group A and Group B combined) 
have been evaluated for response or have permanently discontinued study treatment because of disease 
progression, withdrawal of consent, or death.  The study will be terminated for futility if ≤ 18 of the 
50 subjects have responded (ie, CR or PR) based on assessments provided by the IRC; otherwise the 
study will continue.  A timely assessment of response will be performed to avoid the risk of 
overenrollment. 
Study Population:  Subjects with histologically confirmed diagnosis of FL (Grade 1, 2, or 3a) who 
have received at least 2 prior systemic therapies. 
Key Inclusion Criteria:   
• Aged 18 years or older. 
• Histologically confirmed, relapsed or refractory, follicular B-cell non-Hodgkin lymphoma (NHL) 
(FL) Grade 1, 2, and 3a. 
• Ineligible for hematopoietic stem cell transplant.  
• Must have been treated with at least 2 prior systemic therapies. 




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Estimated Duration of Participation:  Subject participation from screening through follow-up is 
expected to average approximately 25 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 52 weeks). 
• 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 120 subjects will be enrolled.  The first 50 subjects 
will be assigned at 1:1 to Group A (INCB050465 20 mg once daily for 8 weeks followed by 20 mg 
once weekly) and Group B (INCB050465 20 mg once daily for 8 weeks followed by INCB050465 
2.5 mg once daily).  The remaining 70 subjects will be assigned to the selected treatment group (ie, 
either treatment Group A or treatment Group B). 
Principal Coordinating Investigator:  
• United States:  
, MD, 
, USA 
• EU:  
, MD, PhD, 
, Czech Republic 
Statistical Methods: 
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 subjects in each category. 
Sample Size: 
Approximately 120 subjects will be enrolled and assigned to either treatment Group A or Group B.  If 
the true ORR is 51% for subjects in Group A and Group B, then with 120 total subjects, there is 
approximately 93% probability of observing the lower bound of the 95% confidence interval (CI) of 
ORR ≥ 35%.  
Primary Analysis: 
The ORR as determined by the IRC and its 95% exact binomial CIs will be calculated.  The primary 
efficacy analyses will be conducted when all subjects in the full analysis set who have achieved a 
response (ie, PR or CR) according to the IRC have had approximately 12 months of follow-up from the 
onset of response. 
Secondary Analyses:   
The CRR as determined by the IRC and its 95% exact binomial CIs will be calculated.  Kaplan-Meier 
estimation of median DOR (per IRC), PFS (per IRC), and OS will be provided with respective 
95% CIs.  Best percentage change from baseline in target lesions size will be summarized 
descriptively.  All safety data, including AEs, laboratory data, vital signs, and ECGs, will be 
summarized descriptively. 


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Level of Significance: 
There will not be any statistical comparison between the two groups.  Two-sided 95% CIs will be 
reported for all analyses when appropriate. 
Interim Analysis: 
An interim futility analysis is planned when the first 50 subjects (Group A and Group B combined) 
have been evaluated for response or have permanently discontinued study treatment because of disease 
progression, withdrawal of consent, or death.  The study will be terminated for futility if ≤ 18 of the 
50 subjects have responded (ie, CR or PR) based on assessments provided by the IRC; otherwise the 
study will continue. 
Independent Data Monitoring Committee:  An independent Data Monitoring Committee (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 ........................................................................................................13 
1. 
INTRODUCTION ......................................................................................................16 
1.1. 
Follicular Lymphoma .................................................................................................16 
1.2. 
Treatment for Follicular Lymphoma ..........................................................................17 
1.3. 
INCB050465 ...............................................................................................................17 
1.4. 
Study Rationale ...........................................................................................................19 
1.5. 
Potential Risks and Benefits of the Treatment Regimen ............................................20 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................21 
3. 
SUBJECT ELIGIBILITY ...........................................................................................22 
3.1. 
Subject Inclusion Criteria ...........................................................................................22 
3.2. 
Subject Exclusion Criteria ..........................................................................................23 
4. 
INVESTIGATIONAL PLAN .....................................................................................25 
4.1. 
Overall Study Design ..................................................................................................25 
4.2. 
Measures Taken to Avoid Bias ...................................................................................26 
4.3. 
Number of Subjects ....................................................................................................26 
4.3.1. 
Planned Number of Subjects ......................................................................................26 
4.3.2. 
Replacement of Subjects .............................................................................................26 
4.4. 
Duration of Treatment and Subject Participation .......................................................27 
4.5. 
Overall Study Duration ...............................................................................................27 
4.6. 
Study Termination ......................................................................................................27 
5. 
TREATMENT ............................................................................................................28 
5.1. 
Treatment Assignment ................................................................................................28 
5.1.1. 
Subject Numbering and Treatment Assignment .........................................................28 
5.1.2. 
Randomization and Blinding ......................................................................................28 
5.2. 
Study Treatment ..........................................................................................................28 
5.2.1. 
Description and Administration of INCB050465 .......................................................28 
5.2.2. 
Supply, Packaging, and Labeling ...............................................................................29 
5.2.3. 
Storage ........................................................................................................................29 
5.2.4. 
Instruction to Subjects for Handling INCB050465 ....................................................29 
5.3. 
Treatment Compliance ................................................................................................29 


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5.4. 
Treatment Interruptions and Adjustments ..................................................................30 
5.4.1. 
Criteria and Procedures for Dose Interruptions and Reductions of 
INCB050465 ...............................................................................................................30 
5.4.1.1. 
Dose Modifications .....................................................................................................30 
5.4.1.2. 
Supportive Care Guidelines for Diarrhea/Colitis .......................................................32 
5.4.1.3. 
Supportive Care Guidelines for Neutropenia and Thrombocytopenia .......................34 
5.4.1.4. 
Definition for Immune-Related Adverse Events ........................................................34 
5.5. 
Study Treatment Discontinuation ...............................................................................34 
5.5.1. 
Criteria for Study Treatment Discontinuation ............................................................34 
5.5.2. 
Procedures for Study Treatment Discontinuation .......................................................35 
5.6. 
Concomitant Medications ...........................................................................................35 
5.6.1. 
Pneumocystis Jirovecii Prophylaxis ...........................................................................35 
5.6.2. 
Restricted Medications ...............................................................................................36 
5.6.3. 
Prohibited Medications and Therapies .......................................................................36 
5.7. 
Criteria for Study Discontinuation ..............................................................................37 
5.8. 
Treatment After the End of the Study .........................................................................37 
6. 
STUDY ASSESSMENTS ..........................................................................................37 
6.1. 
Screening ....................................................................................................................41 
6.2. 
Treatment ....................................................................................................................42 
6.3. 
End of Treatment ........................................................................................................42 
6.4. 
Follow-Up ...................................................................................................................42 
6.4.1. 
Safety Follow-Up ........................................................................................................42 
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 .....................................................................................................43 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................44 
7.1. 
Administration of Informed Consent Form ................................................................44 
7.2. 
Interactive Response Technology Procedure ..............................................................44 
7.3. 
Demography and Medical History ..............................................................................44 
7.3.1. 
Demographics and Medical History ...........................................................................44 
7.4. 
Prior and Concomitant Medications and Procedures ..................................................44 
7.5. 
Safety Assessments .....................................................................................................45 


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7.5.1. 
Adverse Events ...........................................................................................................45 
7.5.2. 
Comprehensive Physical Examinations ......................................................................45 
7.5.2.1. 
Disease-Specific Physical Examination .....................................................................46 
7.5.3. 
Vital Signs ..................................................................................................................46 
7.5.4. 
Electrocardiograms .....................................................................................................46 
7.5.5. 
Eastern Cooperative Oncology Group Performance Status ........................................47 
7.5.6. 
Laboratory Assessments .............................................................................................47 
7.5.6.1. 
Chemistry and Hematology ........................................................................................47 
7.5.6.2. 
Pregnancy Testing ......................................................................................................47 
7.5.6.3. 
Serology ......................................................................................................................48 
7.5.6.4. 
HIV Screening Test ....................................................................................................48 
7.6. 
Efficacy Assessments .................................................................................................48 
7.6.1. 
Computed Tomography Scan or Magnetic Resonance Imaging ................................48 
7.6.2. 
Bone Marrow Examination .........................................................................................48 
 
49 
7.6.4. 
Independent Review Committee .................................................................................49 
 
49 
 
49 
 
50 
 
50 
 
50 
 
51 
 
51 
 
51 
 
51 
 
51 
7.9. 
Other Study Procedures ..............................................................................................51 
7.9.1. 
Distribution of Subject Reminder Cards .....................................................................51 
8. 
SAFETY MONITORING AND REPORTING .........................................................52 
8.1. 
Adverse Events ...........................................................................................................52 
8.1.1. 
Definitions ..................................................................................................................52 
8.1.2. 
Reporting ....................................................................................................................52 
8.2. 
Laboratory Test Abnormalities ...................................................................................54 


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8.3. 
Serious Adverse Events ..............................................................................................54 
8.3.1. 
Definitions ..................................................................................................................54 
8.3.2. 
Reporting ....................................................................................................................55 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................55 
8.5. 
Adverse Events of Special Interest .............................................................................56 
8.6. 
Pregnancy ...................................................................................................................56 
8.7. 
Warnings and Precautions ..........................................................................................57 
8.8. 
Independent Data Monitoring Committee ..................................................................57 
8.9. 
Product Complaints ....................................................................................................57 
9. 
STATISTICS ..............................................................................................................58 
9.1. 
Study Populations .......................................................................................................58 
9.2. 
Selection of Sample Size ............................................................................................58 
9.3. 
Level of Significance ..................................................................................................58 
9.4. 
Statistical Analyses .....................................................................................................58 
9.4.1. 
Efficacy Analyses .......................................................................................................58 
9.4.1.1. 
Primary Efficacy Analyses .........................................................................................58 
9.4.1.2. 
Secondary Efficacy Analyses .....................................................................................59 
 
60 
9.4.2. 
Safety Analyses ..........................................................................................................60 
9.4.2.1. 
Adverse Events ...........................................................................................................60 
9.4.2.2. 
Clinical Laboratory Tests ...........................................................................................60 
9.4.2.3. 
Vital Signs ..................................................................................................................61 
9.4.2.4. 
Electrocardiograms .....................................................................................................61 
9.4.2.5. 
Adverse Events of Special Interest .............................................................................61 
 
61 
 
61 
9.5. 
Analyses for the Data Monitoring Committee ............................................................62 
9.6. 
Interim Analysis ..........................................................................................................62 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ..........................................................................................................63 
10.1. 
Investigator Responsibilities .......................................................................................63 
10.2. 
Accountability, Handling, and Disposal of Study Drug .............................................64 
10.3. 
Data Management .......................................................................................................65 




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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 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
BID 
twice daily 
CI 
confidence interval 
 
 
CFR 
Code of Federal Regulations 
CMV 
cytomegalovirus 
CR 
complete response 
CRR 
complete response rate 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DLBCL 
diffuse large B-cell lymphoma 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EOT 
end of treatment 
EMA 
European Medicines Agency 
 
 
 
 
FDA 
Food and Drug Administration 
FL 
follicular lymphoma 
FLIPI 
Follicular Lymphoma International Prognostic Index 
GCP 
Good Clinical Practice 
HBs 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 


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Abbreviation 
Definition 
HL 
Hodgkin lymphoma 
 
 
HSCT 
hematopoietic stem cell transplant 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
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 
ITT 
intent-to-treat 
IWRS 
interactive web response system 
LD 
longest dimension 
LDi 
longest dimension transverse diameter of lesion 
LPD 
longest perpendicular dimension 
MedDRA 
Medical Dictionary for Regulatory Activities 
 
 
MRI 
magnetic resonance imaging 
NHL 
non-Hodgkin lymphoma 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease  
PFS 
progression-free survival 
PI3K 
phosphatidylinositol 3-kinase 
PJP 
Pneumocystis jiroveci pneumonia 
 
 
PP 
per protocol 
PPD 
cross-product of the longest transverse diameter and perpendicular diameter 
PR 
partial response 
QD 
once daily 
R-chemo 
rituximab + chemotherapy 
R-CHOP 
rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SCT 
stem cell transplant 


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Abbreviation 
Definition 
SD 
stable disease 
SDi 
shortest axis perpendicular to the longest transverse diameter 
SmPC 
Summary of Product Characteristics 
SPD 
sum of the product of the perpendicular diameters for multiple lesions 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
 
 




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1.2. 
Treatment for Follicular Lymphoma 
Some patients with early stage FL (Ann Harbor Stage I or II) who develop symptoms may be 
treated with radiation therapy alone.  Advanced stage (Ann Harbor Stage III-IV), Grade 1 to 3a 
FL is often treated according to the degree of tumor burden (low versus high) and the presence or 
absence of FL symptoms (eg, fever, night sweats, unexplained weight loss, etc).  Asymptomatic 
patients with a low tumor burden may be candidates for watchful waiting, whereas those with a 
high tumor burden may receive R-chemo.  Symptomatic patients with a low tumor burden may 
receive either single-agent rituximab or R-chemo, whereas patients with a high tumor burden 
may receive R-chemo with or without maintenance rituximab.  Although the majority of patients 
will respond to these first-line therapies, the natural history of FL is characterized by continuous 
relapse. 
There are several options for patients with FL that relapse after initial treatment (Kahl and 
Yang 2016).  The use of single-agent bendamustine was approved by the US FDA in 2008 for 
use in patients with indolent B-cell NHL that progressed within 6 months of treatment with 
rituximab (Treanda® 2013).  In 2016, the US FDA and the European Commission approved the 
use of obinutuzumab in combination with bendamustine followed by obinutuzumab maintenance 
in FL patients whose disease progressed within 6 months of prior rituximab-based therapy 
(Sehn et al 2016, Gazyva® 2016).  Stem cell transplant is another option available to some 
patients after relapse.    
The first-in-class PI3Kδ inhibitor idelalisib (Zydelig 2016) was granted accelerated approval in 
2014 by the US FDA based on a single-arm study enrolling FL subjects (N = 72) who were 
refractory to at least 2 prior therapies (Gopal et al 2014).  The approved indication was for the 
treatment of patients with relapsed follicular B-cell NHL who had received at least 2 prior 
systemic therapies.  Idelalisib was also approved in Europe, based on the same study, for adult 
patients with FL that is refractory to 2 prior lines of treatment.  In September of 2017, a pan 
PI3K inhibitor, copanlisib (Aliqopa 2017), was also granted accelerated approval by the US FDA 
based on a single-arm study enrolling FL subjects (N = 104) who had received at least 2 prior 
systemic therapies (Patnaik et al 2016).  The ORR for idelalisib in a double-refractory FL 
population was 54% (Zydelig 2016); the ORR for copanlisib in patients with relapsed or 
refractory FL who had received at least 2 prior therapies was 59% (Aliqopa 2017).  Other agents 
(eg, lenalidomide, venetoclax, ibrutinib) are being evaluated in clinical studies. 
1.3. 
INCB050465 
Phosphatidylinositol 3-kinases belong to a family of lipid signaling kinases that phosphorylate 
phosphoinositides of the inositol ring (Cantley 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. 


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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 INCB050465 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 (INCB050465 IB).  The IC90 for pAKT inhibition of Pfeiffer cells in human 
whole blood is 77nM (INCB050465 IB).  Preclinical toxicology studies supported evaluation of 
INCB050465 in human clinical studies (INCB050465 IB). 
INCB050465 is being evaluated as a monotherapy in a Phase 1/2, dose-escalation and expansion 
study (INCB 50465-101, NCT02018861, Phillips et al 2016).  As of 01 MAR 2017, data were 
available for 63 subjects who received INCB050465 administered orally QD or QD for 9 weeks 
followed by QW.  Starting in NOV 2016, subjects were switched to QW dosing if they had been 
on study treatment for > 9 weeks (Ramchandren et al 2017).  The median duration of treatment 
for all subjects was 114 days (range 7-520).  Nonhematological adverse events observed in 
≥ 20% of subjects were nausea (38%), diarrhea/colitis (35%), fatigue (29%), vomiting (27%), 
cough (24%), rash (22%), and dizziness (21%).  New or worsening Grade ≥ 3 anemia, 
thrombocytopenia, and neutropenia occurred in 5%, 10%, and 22% 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/colitis (n = 6) and hypotension (n = 3) and 
ventricular tachycardia, pyrexia, pneumonia, exfoliative dermatitis, syncope, and bacteremia 
(n = 2 each).  Twelve (19%) of the 63 subjects discontinued study treatment due to the following 
AEs:  diarrhea (n = 2), exfoliative dermatitis (n = 2), colitis, cytomegalovirus colitis, 
pneumonitis, rash, psoriasis, neutropenia, pneumonia, 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 01 MAR 2017, 28 objective responses as reported by investigators were observed in 
57 evaluable subjects with DLBCL, FL, HL, marginal zone lymphoma, chronic lymphocytic 
leukemia, and mantle cell lymphoma.  These results include 8 objective responses among the 
11 evaluable subjects with FL; all but 1 of the objective responses occurred by the time of the 
9-week disease assessment.  Among the 8 objective responses, 6 demonstrated > 75% reduction 
in their target lesions (see Figure 1).  The longest duration of study treatment among subjects 
with FL was approximately 14 months, with 3 of the evaluable subjects ongoing.   


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Figure 1: 
Best Percentage Change From Baseline in Target Lesion Size in Follicular 
Lymphoma Subjects From Study INCB 50465-101 
 
Note:  Of the 11 evaluable subjects, 1 subject did not have a complete, postbaseline disease assessment and is 
therefore not represented.  The best response for this subject was PD. 
Pharmacokinetics analysis showed the tmax is 0.5 to 1 hour, the terminal half-life is 
approximately 8 to 12 hours, and 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 
INCB050465 IB for further details. 
1.4. 
Study Rationale 
The PI3Kδ inhibitor idelalisib was approved for the treatment of patients in the United States 
with relapsed follicular B-cell NHL who have received at least 2 prior systemic therapies.  In 
September of 2017 the PI3K inhibitor copanlisib was also approved in the Unites States for the 
same patient population (Aliqopa 2017).  Idelalisib was approved in the European Union for the 
treatment of adult patients with FL that is refractory to 2 prior lines of treatment.  The population 
of patients that are refractory to 2 lines of systemic therapy is substantially smaller than the 
population that has relapsed or refractory disease after 2 prior systemic therapies.  The relapsed 
patient population is currently underserved by the available approved therapies and, like the 
double-refractory population, represents an unmet medical need.  This is especially true in 
patients that are ineligible for HSCT.  To address the unmet medical need of both populations, 
and to enroll the study in a timely fashion, the study will allow subjects who have either relapsed 
or refractory disease after at least 2 prior systemic therapies and who are ineligible for HSCT.  
INCB050465 is a potent and selective PI3Kδ inhibitor and has demonstrated rapid and deep 
objective responses in subjects with relapsed FL (see Section 1.3).   


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This study is designed to evaluate the ORR of INCB050465 in subjects with relapsed or 
refractory FL who have received at least 2 prior systemic therapies and who are ineligible for 
HSCT.  Given that copanlisib was recently granted accelerated approval in this patient 
population on the basis of ORR by the US FDA, idelalisib can no longer be considered the 
standard of care in the United States and consequently is not a relevant comparator for new PI3K 
inhibitors.  It is also not feasible to replace idelalisib with copanlisib, which is currently 
approved only in the United States.  Study INCB 50465-203 will therefore evaluate only 
INCB050465.   
Subjects will receive INCB050465 administered orally at a dose of 20 mg QD for 8 weeks.  
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 show that of the 11 NHL subjects who 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 or 2.5 mg QD of INCB050465.   
The 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 intravenously on Days 1, 8, 
and 15 of a 28-day cycle (Aliqopa 2017).   
The continuous QD regimen of INCB050465 has demonstrated prolonged responses in both 
aggressive and indolent NHL.  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).  The 2.5 mg QD regimen is proposed to 
provide approximately 86% inhibition of the PI3K pathway on average but could reduce the 
frequency of AEs that lead to study treatment withdrawal. 
1.5. 
Potential Risks and Benefits of the Treatment Regimen 
A summary of AEs, SAEs, and efficacy observed in the ongoing Study INCB 50465-101 is 
provided (Section 1.3).  Similar to other PI3K inhibitors, diarrhea/colitis, pneumonitis, 
infections, severe cutaneous reactions, and neutropenia were observed in Study 
INCB 50465-101.  In Study INCB 50465-101, 8 of the 11 evaluable subjects with FL had an 
objective response.  The longest duration on study treatment for these subjects was 
approximately 14 months.  Refer to the INCB050465 IB for additional information.   
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, and sunglasses. 


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
The study objectives and endpoints are presented in Table 1. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To assess the efficacy of INCB050465 in terms of 
ORR in subjects with relapsed or refractory FL. 
ORR defined as the percentage of subjects with a CR 
or PR as defined by revised response criteria for 
lymphomas, as determined by an IRC. 
Secondary 
To assess CRR. 
CRR defined as the percentage of subjects with a CR 
as defined by revised response criteria for lymphomas 
(Cheson et al 2014), as determined by an IRC. 
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 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 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 the diameters of all target lesion 
sizes. 
To characterize the safety and tolerability of 
INCB050465. 
Safety measured by clinical assessments, including 
vital signs and physical examinations, 12-lead ECGs, 
chemistry and hematology laboratory values, and AEs. 


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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. Aged 18 years or older. 
2. Histologically confirmed, relapsed or refractory, follicular B-cell NHL (FL) Grade 1, 2, 
and 3a. 
3. Ineligible for HSCT. 
4. Must have been treated with at least 2 prior systemic therapies. 
5. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy 
(defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the LD and ≥ 1.0 cm in 
the LPD) 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. ECOG performance status 0 to 2 (see Appendix C). 
8. Life expectancy ≥ 12 weeks. 
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 ≤ 2.5× ULN or ≤ 5 × ULN in the presence of liver metastases. 
f. Calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault Equation 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 > 45 years of age.) 
b. Woman of childbearing potential who has a negative serum pregnancy test (see 
Table 7) 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. Known histological transformation from indolent NHL to DLBCL. 
2. History of central nervous system lymphoma (either primary or metastatic).  
3. Prior treatment with idelalisib, other selective PI3Kδ inhibitors, or a pan-PI3K inhibitor. 
4. Prior treatment with a Bruton's tyrosine kinase inhibitor (eg, ibrutinib). 
5. Allogeneic SCT within the last 6 months, or autologous SCT within the last 3 months 
before the date of study treatment administration. 
6. Active graft-versus-host disease. 
7. 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 level ≤ 10 mg/day within 7 days of the date of study treatment administration.  
8. Receipt of anticancer medications or investigational drugs within the following intervals 
before the date of study treatment administration: 
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. < 2 weeks for any investigational agent or other anticancer medications. 
9. Prior treatment-related toxicities have not resolved to ≤ Grade 1 prior to study treatment 
administration except for stable chronic toxicities (≤ Grade 2) not expected to resolve 
(eg, stable Grade 2 peripheral neurotoxicity). 
10. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, 
immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor 
embolization).  


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11. Use or expected use during the study of any prohibited medications, including potent 
CYP3A4 inhibitors or inducers (see Appendix B and consult your local pharmacist) 
within 14 days or 5 half-lives (whichever is longer) before the date of study treatment 
administration. 
12. Significant concurrent, uncontrolled medical condition including, but not limited to, 
renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, 
cerebral, or psychiatric disease. 
13. 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. 
14. History of stroke or intracranial hemorrhage within 6 months of the date of study 
treatment administration. 
15. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or 
antiviral treatment, and exposure to a live vaccine within 30 days of study treatment 
administration. 
16. Known human immunodeficiency virus (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. 
17. Hepatitis B (HBV) or hepatitis C (HCV) infection:  Subjects positive for hepatitis B 
surface antigen (HBsAg) 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. 
18. 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.  
19. Current New York Heart Association Class II to IV congestive heart failure or 
uncontrolled arrhythmia. 
20. 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.  
21. Unable to swallow and retain oral medication, malabsorption syndrome, disease 
significantly affecting gastrointestinal function, total resection of the stomach or small 
bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete 
bowel obstruction. 
22. Known hypersensitivity or severe reaction to INCB050465 (IB) or any of the excipients. 
23. History of serious allergic reactions including anaphylaxis and toxic epidermal 
necrolysis. 


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24. Inadequate recovery from toxicity and/or complications from a major surgery before 
study treatment administration. 
25. Currently pregnant or breastfeeding. 
26. 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. 
27. Inability to comprehend or unwilling to sign the ICF. 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is a Phase 2, multicenter, open-label study evaluating 2 INCB050465 treatment regimens 
based on the primary endpoint of ORR.  Subjects with relapsed or refractory FL (Grades 1, 2, or 
3a) who have received at least 2 prior systemic therapies and who are ineligible for HSCT will 
be screened for eligibility.  A total of approximately 120 subjects will be enrolled.  The first 
50 subjects enrolled will be assigned at a 1:1 ratio to treatment Group A (INCB050465 20 mg 
QD for 8 weeks followed by 20 mg once weekly) and treatment Group B (INCB050465 20 mg 
QD for 8 weeks followed by INCB050465 2.5 mg QD; see Figure 2).  The remaining 70 subjects 
will be allocated to one of the 2 treatment groups to better understand the safety and efficacy of 
that treatment regimen.  The treatment group will be selected after evaluation of emerging safety 
and efficacy data from this and other monotherapy studies of INCB050465 in NHL that are 
evaluating the same or similar dosing regimens and will be implemented after the first 
50 subjects are enrolled.  Subjects allocated to 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.  Furthermore, no changes 
will be made to the primary analysis.  The study treatments will be administered orally. 
Subjects will be evaluated for ORR by an IRC and followed for CRR, DOR, PFS, OS, and 
safety.  Subjects may receive treatment until disease progression, death, unacceptable toxicity, or 
consent withdrawal. 
An interim futility analysis is planned when the first 50 subjects have been evaluated for 
response or have permanently discontinued study treatment because of disease progression, 
withdrawal of consent, or death.  The study will be terminated for futility if ≤ 18 of the 
50 subjects have responded (ie, CR or PR) based on assessments provided by the IRC; otherwise 
the study will continue.  A timely assessment of response will be performed to avoid the risk of 
overenrollment.  
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. 


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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 either 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. 
Figure 2: 
Study Design 
 
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 2009) guidelines; response will be assessed by an IRC using the 
Lugano classification (Cheson et al 2014). 
4.3. 
Number of Subjects 
4.3.1. 
Planned Number of Subjects 
The study will enroll approximately 120 subjects across approximately 90 sites.   
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).  Subject participation is expected to average 
approximately 25 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 1.0 year to accrue 120 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, according to the 
terms specified in the study contract.  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 or do so if required by a regulatory agency or 
upon advice from the IDMC.  If the study is terminated prematurely, then 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 to receive a subject 
number and 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. 
Study Treatment 
5.2.1. 
Description and Administration of INCB050465 
The description and administration of INCB050465 is presented in Table 2. 
Table 2: 
Description and Administration of INCB050465 
Compound name 
INCB050465 
Dosage strengths 
1 mg, 2.5 mg, 5 mg, and 20 mg 
Form 
Tablet 
Active compound  
INCB050465 
Route of administration 
Oral 
Dose and regimen for Group A 
20 mg QD for 8 weeks followed by 20 mg once weekly 
Dose and regimen for Group 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. 


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For QD administration, if a dose is missed by more than 12 hours, the subject should skip the 
dose and take the next scheduled dose at the usual time.  For once weekly dose regimen, if the 
dose is missed by more than 2 days, 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 tablets 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. 
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 treatments 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 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. 






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Table 4: 
Dose Levels and Reductions for INCB050465 
Timepoint 
Dose (Group A) 
Dose (Group B) 
Starting dose 
20 mg QD for 8 weeks 
(Day 1 through Day 56) 
20 mg QD for 8 weeks 
(Day 1 through Day 56) 
First dose reduction 
10 mg QD 
10 mg QD 
Second dose reduction 
5 mg QD 
5 mg QD 
Week 9 (Day 57) onward 
20 mg once weeklya 
2.5 mg QDb 
First dose reduction 
10 mg once weekly 
1 mg QDc 
Second dose reduction 
5 mg once weekly 
NA 
a All subjects will receive 20 mg once weekly at Week 9 (Day 57) regardless of prior dose level, unless a dose 
modification of a switch to a QW schedule before Week 9 is required for diarrhea/colitis management (see 
Table 5). 
b All subjects will receive 2.5 mg QD at Week 9 (Day 57) regardless of prior dose level, unless a dose modification 
of a switch to a QW schedule is required for diarrhea/colitis management (see Table 5). 
c Further dose modification due to diarrhea or colitis for subjects on 1 mg QD is permitted (see Table 5). 
5.4.1.2. 
Supportive Care Guidelines for Diarrhea/Colitis 
Subjects should be informed to immediately report to the investigator any event of diarrhea.  
Treatment with INCB050465 may be interrupted or modified according to the guidelines in 
Table 5 to allow for resolution of diarrhea/colitis. 
Subjects should receive appropriate supportive care measures as deemed necessary by the 
investigator.  For any Grade ≥ 1 diarrhea, subjects should be advised to drink liberal quantities of 
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). 


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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 5.4.1.2).  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 5.4.1.2).  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. 
• 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 5.4.1.2).  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. 


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5.4.1.3. 
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. 
5.4.1.4. 
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 and other PI3K inhibitors.  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 5.4.1.2.  For each 
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 permanently discontinue study treatment for any 1 of the following: 
• 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/PMD. 
• Further participation would be injurious to the subject's health or well-being, in the 
investigator's medical judgment. 
• The subject becomes pregnant. 


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• 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 situations: 
• 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 
If a subject 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 treatment–related toxicities resolve, return to baseline, or are deemed 
irreversible, whichever is longest. 
If a subject discontinues study treatment and actively withdraws consent for collection of all 
follow-up data, 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 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 2016).  Due to reports of cross-sensitivity between sulfonamides and 
dapsone, all subjects who have a known or suspected allergy to sulfonamides must receive either 


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inhaled pentamidine or atovaquone for PJP prophylaxis.  Prophylaxis should be given while 
subjects are receiving study treatment and should continue for 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.  Incyte may provide 
prophylactic agents where required by applicable law or regulation or under other limited 
circumstances when a subject may not otherwise have access to these therapies.  The contents of 
the label will be in accordance with all applicable regulatory requirements.  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 prednisolone 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.  
• Use of weak or moderate inducers or inhibitors of CYP3A4 (see Appendix B and 
consult your local pharmacist) is discouraged, and investigators should seek other 
options where possible. 
• For subjects receiving INC050465, 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). 
• 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 and Therapies 
• Use of potent inducers and inhibitors of CYP3A4 are prohibited (see Appendix B 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 30-day follow-up is prohibited. 
• Exposure to a live vaccine within 30 days of study treatment through 3 months after 
the last dose of INCB050465. 


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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. 
6. 
STUDY ASSESSMENTS 
See the schedule of assessments (Table 6) and schedule of laboratory assessments (Table 7) for 
the timing of all assessments.  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, respectively.  A table of clinical laboratory analytes to be assessed (Table 8) is 
provided.  The order of assessments is suggested by the order listed within the schedule of 
assessments.  See Sections 6 and 7 for instructions on each assessment.  Further details of study 
procedures and assessments can be found in the study reference manual.


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Table 6: 
Schedule of Assessments 
Procedure 
Section 
Screening 
Treatment 
EOT 
Follow-Up 
Safety 
Disease 
Survival 
Day -28 
to -1 
Day 1a 
Every 4 Weeks 
Through Week 48 
(± 3 Days) 
Every 12 Weeks 
From Week 48 
(± 1 Week) 
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 
7.3.1 
X 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.4 
X 
X 
X 
X 
X 
X 
 
 
AE assessment 
7.5.1 
X 
X 
X 
X 
X 
X 
 
 
Comprehensive physical exam 
7.5.2 
Xc 
 
 
 
X 
 
 
 
Disease-specific physical exam 
7.5.2.1 
 
X 
X 
X 
 
X 
 
 
Vital signs 
7.5.3 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG 
7.5.4 
X 
X 
Xd 
X 
X 
X 
 
 
ECOG status 
7.5.5 
X 
X 
X 
X 
X 
X 
 
 
CT/MRI scan 
7.6.1 
Xe 
 
Every 8 weeks through Week 24 
(± 1 week), then every 12 weeks through 
Week 96, and then every 24 weeks 
thereafter until PD 
 
 
Xb 
 
Bone marrow exam 
7.6.2 
Xf 
 
 
 
 
 
 
 
PJP prophylaxis  
5.6.1 
 
Xg 
 
 
Study drug dispensing 
5.1.1 
 
X 
X 
X 
 
 
 
 
Study drug compliance 
5.3 
 
X 
X 
X 
X 
 
 
 
Study drug administration at 
site 
7.7.1 
 
X 
Xh 
 
 
 
 
 
Disease follow-up 
6.4.2 
 
 
 
 
 
 
Xb 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
Xi 
a All procedures are to be performed before administration of study treatment. 
 
 
   


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c Height required at screening only. 
d Week 4, Week 12, and every 12 weeks thereafter.  See Section 7.5.4 for additional instructions. 
e If CT is not available, is not practicable, or is contraindicated, then an MRI may be substituted.  Every effort must be made to use the same modality for disease assessment 
throughout the study for each individual subject.  Lesion assessment must be done for the neck, chest, abdomen, and pelvis. 
f Required at baseline except for reasons provided in Section 7.6.2.  If disease is present in bone marrow at baseline, a bone marrow biopsy is required to confirm CR. 
g PJP prophylaxis will continue for 2 to 6 months after the last dose of study treatment. 
 
 
i May be conducted by phone or email. 


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Table 7: 
Schedule of Laboratory Assessments 
Laboratory Tests 
Section 
Screening 
Treatment 
EOT 
Safety Follow-Up 
Day -28 
to -1 
Day 1 
Every 4 Weeks 
Through Week 48 
(± 3 Days) 
Every 12 Weeks 
From Week 48 
(± 1 Week) 
Other 
EOT + 
30-35 Days 
Serum chemistries 
7.5.6.1 
X 
Xa 
X 
X 
 
X 
X 
Hematologyb 
7.5.6.1 
X 
Xa 
X 
X 
Xc 
X 
X 
Serology 
7.5.6.3 
X 
 
 
 
Xd 
X 
 
Serum pregnancy 
7.5.6.2 
Xe 
 
 
 
 
X 
X 
Urine pregnancy 
7.5.6.2 
 
 
 
 
Xf 
 
 
HIV testing 
7.5.6.4 
Xg 
 
 
 
 
 
 
Tumor biopsy 
7.8.5 
Xl 
 
 
 
Xl 
 
 
a Day 1 assessments may be omitted if the screening tests occurred in the preceding 7 days.  If needed, Day 1 blood draws should be performed before administration of study 
treatment. 
b Hematology samples will be collected every 2 weeks for the first 8 weeks. 
c Week 2 and Week 6 (± 3 days). 
d Samples for CMV DNA analysis only will be collected every 4 weeks from Day 1. 
e Only for females of childbearing potential; negative pregnancy test must be obtained within 14 days before administration of study treatment.  May be performed by the central 
laboratory or the investigative site laboratory. 
f Only for females of childbearing potential.  Must be conducted every 4 weeks from Day 1. 
g Optional for subjects enrolled in the United States. 
 
  
 
 
 
 
 
 
l Subjects must be willing to undergo an incisional or excisional lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival 
tissue.  An optional biopsy should be collected at the time of progression if possible but may be collected at other times for safety or efficacy. 


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Table 8: 
Laboratory Tests:  Required Analytes 
Serum Chemistries 
Hematology 
Serology 
Pregnancy Testing 
(Performed Locally) 
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) 
Indirect bilirubin (if total 
bilirubin is > ULN) 
Total protein 
Uric acid 
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 
HBsAg 
HBsAg antibody 
Hepatitis B core antibody 
HBV-DNA 
HCV antibody 
HCV-RNA 
CMV DNA 
HIV antibody 
(immunoassay)a 
Only for female 
subjects of 
childbearing potential 
(see Table 7). 
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 Optional for subjects enrolled in the United States. 
6.1. 
Screening 
Screening is the interval between signing the ICF and the date of study treatment administration 
(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 either centrally or locally. 
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. 


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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 study treatment administration (Day 1).  This day 
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 day and should occur within the visit windows outlined in 
the schedule of assessments (see Table 6 and Table 7) unless delayed for safety reasons.  
Subjects may receive treatment until disease progression, death, unacceptable toxicity, or consent 
withdrawal. 
6.3. 
End of Treatment 
There is no predefined EOT.  If a subject permanently discontinues study treatment, then the 
EOT visit should be conducted.  The subject should be encouraged to return for the safety 
follow-up visit. 
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 drug 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 drug, 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. 




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7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained 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. 
7.2. 
Interactive 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 enrollment, 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 Medical History 
Demographic data and a complete medical and medication history, including date of diagnosis of 
FL, histology, current staging, grade, sites of disease, prior surgery, radiation, and other details 
related to the disease under study will be collected. 
7.4. 
Prior and Concomitant Medications and Procedures 
Prior and concomitant medications and procedures will be reviewed to determine subject 
eligibility.  All concomitant medications and measures must be recorded in the eCRF, and any 
medication received or procedure performed within 30 days before enrollment and up to the end 
of study 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. 


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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. 
7.5. 
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 (see Section 8.1.2 and Section 8.3.2).  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 Examinations 
Clinically notable abnormalities that are considered clinically significant in the judgment of the 
investigator are to be reported as AEs. 
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) and the 
following organ or body system assessments:  skin; head, eyes, ears, nose, and throat; thyroid; 
lungs; cardiovascular system; abdomen (liver, spleen); extremities; lymph nodes; a brief 
neurological examination (eg, reflexes, strength, Romberg's test, vibration sense, and gross 
sensory perception); and body weight (within 1 lb or 0.5 kg). 


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7.5.2.1. 
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. 
7.5.3. 
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. 
7.5.4. 
Electrocardiograms 
All 12-lead ECGs will be performed with the subject in a recumbent or semirecumbent position 
after 5 minutes of rest.  Baseline ECGs will be obtained during screening using a single 
measurement but can be performed in triplicate if the single QTc measurement is 
> 450 milliseconds (corrected by Fridericia; see Section 3.2).  Electrocardiograms will also be 
obtained during the Day 1 visit (triplicate measurements) before the subject receives the first 
dose of study drug.  Triplicate ECGs will be performed predose and 1.5 hours (± 15 minutes) 
after receiving study treatment at the Week 4 visit.  When triplicate ECGs are being obtained, 
individual measurements should be performed 5 minutes (± 3 minutes) apart.  All 12-lead ECGs 
obtained at subsequent timepoints (single measurements) will be compared with the baseline 
12-lead ECGs as follows: 
• For ECG morphology, all postdose ECG recordings will be compared with Day 1 
predose ECGs. 
• For the calculation of changes in cardiac intervals (eg, QT interval), the intervals 
from the screening and Day 1 predose (triplicate) ECGs will be computed and 
averaged and used as the baseline for comparison of all postdose intervals. 
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. 
Twelve-lead ECGs will be acquired using an ECG analysis system with analysis and printing 
capabilities, as well as digital transmission capabilities to a central capture module at the ECG 
laboratory.  The investigator and research staff will receive adequate training by a qualified 
person on the use and operation of the analysis system.  The successful digital submission of a 
12-lead ECG, meeting quality standards, to the central ECG laboratory by the site must be 
ensured before enrollment of the first subject.  The study reference manual for procedures that 
must be followed for the recording and transmission of ECGs and the operator's manual with 
instructions for operating the digital capture module will be shipped to the site along with the 
device.  The 12-lead ECGs will be interpreted by the investigator at the site and will be used for 
immediate subject management.  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 


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Significant" is the responsibility of the investigator, in consultation with the sponsor's medical 
monitor, as appropriate.  Twelve-lead ECGs that are identified by the investigator as "Abnormal, 
Clinically Significant" will be sent to the sponsor's medical monitor for review.  
The overall ECG interpretation will be indicated by a flagging system that will help distinguish 
between a normal ECG, ECG abnormalities where no further investigation is required, and ECG 
abnormalities where study exclusion, further cardiovascular investigation, and/or prompt action 
may be necessary depending on the clinical context.  A suitable flag will be included in the 
"Overall ECG Interpretation" section of the report when an ECG is considered to be technically 
unacceptable or uninterpretable.  If several different abnormalities exist corresponding to 
different levels of flagging, then the label will reflect the most severe level.  Flagging by the 
central expert cardiologist of these significant abnormalities should only be regarded as a 
suggestion.  This service is intended to assist the investigator in his/her interpretation of the ECG 
and decision-making.  It is not intended to replace the investigator's expert judgment and 
knowledge of the subject's medical condition. 
7.5.5. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group performance status (Oken et al 1982; see Appendix C) will 
be assessed.  Performance status must be assessed by a medically qualified individual and 
recorded in the eCRF. 
7.5.6. 
Laboratory Assessments 
Blood draws for laboratory assessments will occur at study visits indicated (see Table 7).  
Specific laboratory assessments are provided (see Table 8). 
All laboratory assessments, including those conducted during unscheduled visits, will be 
performed at a central laboratory unless otherwise specified.   
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. 
7.5.6.1. 
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.  
7.5.6.2. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential (see Section 3.1) 
as shown (see Table 7).  At screening, the serum pregnancy test may be performed centrally or 
locally.  Urine pregnancy tests will be conducted as shown (see Table 7).  If a urine pregnancy 
test is positive, the results should be confirmed with a serum pregnancy test. 
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. 




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7.6.4. 
Independent Review Committee 
All 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 D) by 
independent reviewers as described in the Imaging Charter. 


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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 drugs. 
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 drugs.  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 
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 (NCI 2009) 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 


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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 
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. 


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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 5.4.1) 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. 
− 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. 


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8.3.2. 
Reporting 
Every SAE, regardless of suspected causality (eg, relationship to study drugs 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 drug, whichever is later) must be reported to the sponsor 
(or designee) within 24 hours of learning of its occurrence, unless otherwise specified by the 
Protocol.  Any SAEs occurring more than 30 days after the last dose of study drug should be 
reported to the sponsor or its designee only if the investigator suspects a causal relationship to 
the study treatment.   
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. 
If the SAE is not documented in the RSI section of IB for the study drug (new occurrence) 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. 


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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  
• Rash ≥ Grade 2 
• Intestinal perforation 
• Pneumonitis 
• Pneumocystis jirovecii infection 
• CMV infection 
• Herpes simplex virus infection 
• Varicella zoster virus infection 
• Exfoliative dermatitis 
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. 
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. 


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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 Investigator's Brochure (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 independent Data Monitoring Committee (IDMC) will be formed.  The IDMC 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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The primary efficacy analyses will be conducted when all subjects in the full analysis set who 
have achieved a response (ie, PR or CR) according to the IRC have had approximately 
12 months of follow-up from the onset of response. 
Subgroups will be formed based on the following subject characteristics and baseline variables: 
• Age:  ≤ 65 years, > 65 years 
• Gender:  male, female 
• Geographic region:  Europe, North America, Rest of World 
Subgroups may be further divided or combined based on emerging data.  The ORR and its 
95% CIs will be provided for each subgroup.  A forest plot will be created to summarize the 
variability in ORRs across subgroups. 
9.4.1.2. 
Secondary Efficacy Analyses 
Complete response rate is the percentage of subjects with a CR as defined by revised response 
criteria for lymphomas, as determined by an IRC.  The CRR determined by the IRC and its 
95% exact binomial CIs will be calculated.  
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 overall response, 
as determined by IRC.  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.  Kaplan-Meier estimation of median 
DOR per IRC and its 95% CIs will be provided.  
Progression-free survival is defined as the time from the date of the first dose of study drug to the 
first documented disease progression as determined by IRC, 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.  
Kaplan-Meier estimation of median PFS per IRC and its 95% CIs will be provided. 
Overall survival is defined as the time from the date of the 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 subject is last known to be alive.  The Kaplan-Meier estimation of median OS and its 
95% CIs will be provided.  
For subjects with measurable lesions at baseline, target lesion sizes will be measured by sum of 
the product of the diameters of all target lesions.  The best percentage change from baseline, 
defined as the largest decrease in target lesion sizes during the study, will be summarized 
descriptively.  Note that for subjects who only have increases in target lesion sizes from baseline, 
the smallest increase will be considered as the best change from baseline.  Target lesions 
considered "too small to measure" will be assigned a default value of 5 mm × 5 mm for purposes 




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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. 
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 
> 38ºC 
< 35ºC 
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 
analysis (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 when the first 50 subjects (Group A and Group B 
combined) have been evaluated for response or have permanently discontinued study treatment 
because of disease progression, withdrawal of consent, or death.  The study will be terminated 
for futility if ≤ 18 of the 50 subjects have responded (ie, CR or PR) based on assessments 
provided by the IRC; otherwise the study will continue.  A timely assessment of response will be 
performed to avoid the risk of overenrollment. 


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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. 
− 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. 


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• 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. 
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. 


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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 
plan's requirements. 
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 


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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 
Aliqopa [prescribing information] New York, NY: Bristol Myers Squibb; 2017. 
Barekman CL, Aguilera NS, Abbondanzo SL. Low-grade B-cell lymphoma with coexpression of 
both CD5 and CD10. A report of 3 cases. Arch Pathol Lab Med 2001;125:951-953. 
Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-1657. 
Casulo C, Byrtek M, Dawson KL, et al. Early relapse of follicular lymphoma after rituximab 
plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for 
death: an analysis from the National LymphoCare Study. J Clin Oncol 2015;33:2516-2522. 
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. 
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. 
Gazyva [prescribing information]. South San Francisco, CA: Genentech, Inc; 2016. 
Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed 
indolent lymphoma. N Engl J Med 2014;370:1008-1018. 
INCB050465 Investigator's Brochure (IB). Wilmington, DE: Incyte Corporation. 
Kahl BS, Yang DT. Follicular lymphoma: evolving therapeutic strategies. Blood 
2016;127:2055-2063. 
National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events Version 
4.03. 2009. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. Accessed May 21, 2016. 
National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: 
Non-Hodgkin's Lymphomas Version 4. 2014. https://www.nccn.org/about/nhl.pdf. Accessed 
July 8, 2016. 
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. 
Pastore A, Jurinovic V, Kridel R, et al. Integration of gene mutations in risk prognostication for 
patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective 
analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol 
2015;16:1111-1122. 
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. 


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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. 
Ramchandren R, Phillips T, Wertheim MS, et al. Ongoing phase 1/2 study of INCB050465 for 
relapsed/refractory (r/r) B-cell malignancies. Submitted to: 2017 ASCO Annual Meeting; 
June 6-7, 2017; Chicago, IL. 
Sehn LH, Chua N, Mayer J, et al. Obinutuzumab plus bendamustine versus bendamustine 
monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma 
(GADOLIN): a randomized, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol 
2016;17:1081-1903. 
Shankland KR, Armitage JO, Hancock BW. Non-Hodgkin lymphoma. Lancet 
2012;380:848-857. 
Solal-Céligny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index 
Blood 2004;104:1258-1265. 
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization 
classification of lymphoid neoplasms. Blood 2016;127:2375-2390. 
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. 
Treanda [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc; 2013. 
Zydelig [prescribing information]. Foster City, CA: Gilead Sciences, Inc; 2016. 


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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 ovulation 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable1 
• Intrauterine device (IUD)1 
• Intrauterine hormone-releasing system (IUS)1 
• Bilateral tubal occlusion1 
• Vasectomised partner1,2 
• Sexual abstinence3 
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  Contraception methods that in the context of this guidance are considered to have low user dependency. 
2  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.  
3  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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almorexant 
Hypnotics - Sedatives 
GSK1292263 
Other Antilipemics 
evacetrapid 
CETP inhibitors 
linagliptin 
Dipeptidyl Peptidase 4 Inhibitors 
grazoprevir (ingredient of Zepatier) 
Antivirals 
lacidipine 
Calcium Channel Blockers 
cranberry juice 
Food Products 
pazopanib 
Kinase Inhibitors 
fostamatinib 
Other 
everolimus 
Immunosuppressants 
blueberry juice 
Food Products 
flibanserin 
Central Nervous System Agents 
lapatinib 
Kinase Inhibitors 
brodalumab 
Immunomodulators Biologics 
AMD070 
Fusion Inhibitors  
alprazolam 
Benzodiazepines 
Tong Xin Luo 
Herbal Medications 
glecaprevir and pibrentasvir 
Antivirals 
bicalutamide 
Antiandrogens 
sitaxentan 
Endothelin Receptor Antagonists 
azithromycin 
Antibiotics 
obeticholic acid 
Miscellaneous Agents 
ginkgo 
Herbal Medications 
teriflunomide 
Other Immunomodulators 






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VIEKIRA PAK 
Antivirals  
dexamethasone 
Corticosteroids  
terbinafine 
Antifungals  
quercetin 
Food Products 
glycyrrhizin 
Herbal Medications  
aprepitant 
Neurokinin-1 Receptor Antagonists 
pretomanib (PA-824) 
Antibiotics  
safinamide 
MAO-B Inhibitors 
oritavancin 
Antibiotics  
AZD 7325 
Anxiolytics 
methylprednisolone 
Corticosteroids  
topiramate 
Anticonvulsants  


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APPENDIX C. 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 
Source:  Oken et al 1982. 






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APPENDIX E. FOLLICULAR LYMPHOMA INTERNATIONAL 
PROGNOSTIC INDEX 
 


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APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1: 
15 MAR 2017 
Amendment (Version) 2: 
15 AUG 2017 
Amendment (Version) 3: 
11 SEP 2017 
Amendment (Version) 4: 
25 OCT 2017 
Amendment (Version) 4-CAN: 
12 DEC 2017 
Amendment (Version) 5: 
17 JAN 2018 
Amendment (Version) 6: 
11 JUL 2018 
Amendment (Version) 7: 
04 SEP 2018 
Amendment (Version) 8: 
06 DEC 2018 
Amendment (Version) 9: 
23 DEC 2019 
Amendment 9 (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 5.4.1.2, 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. 


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3. Synopsis (Estimated Number of Subjects, Statistical Methods); Section 4.1, Overall 
Study Design; Section 4.3.1, Planned Number of Subjects; Section 4.5, Overall 
Duration; Section 9.2, Selection of Sample Size; Section 9.4.1.1, Primary Efficacy 
Analyses 
Description of change:  Increased the target enrollment from approximately 100 to 
approximately 120 subjects and changed the timing of the primary analysis. 
Rational for change:  To align with recommendations from the US FDA. 
4. 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. 
5. Synopsis (Study Schedule/Procedures); 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 reduce the burden of extra pharmacy visits for the subjects. 
6. Section 9.1, Study Populations 
Description of change:  Removed the PP population. 
Rationale for change:  For a single-arm, open-label study, the determination of subjects 
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. 
7. 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. 
8. 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 8 (06 DEC 2018) 
Overall Rationale for the Amendment:  The primary purpose of the amendment is to stop the 
1:1 allocation of subjects after the 50th subject has enrolled and to enroll the remaining 
50 subjects to only one of the 2 treatment regimens being evaluated. 
1. Synopsis; Section 4.1, Overall Study Design (Figure 2:  Study Design); Section 9.2, 
Selection of Sample Size 
Description of change:  Revised to state that after 50 subjects are enrolled, the 
remaining 50 subjects will be enrolled to only one of the 2 treatment regimens being 
evaluated in this study.  Patients allocated to the unselected treatment will be allowed to 
cross over. 
Rationale for change:  To increase the number of subjects administered one of the 
2 treatment regimens, leading to a better understanding of the long-term safety and 
efficacy of that treatment regimen. 
2. 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. 
3. 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 7 (04 SEP 2018) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to provide 
a list of CYP3A inhibitors and inducers. 
1. Section 3.2, Subject Exclusion Criteria;  Section 5.6.2, Restricted Medications; 
Section 5.6.3, Prohibited Medications and Therapies; Appendix B, CYP3A 
Inhibitors and Inducers 
Description of change:  Added tables of CYP3A inhibitors and inducers in Appendix B.  
These tables were updated and modified compared to the previous versions, which had 
been removed from Protocol Version 6 and placed in the Pharmacy Manual. 
Rationale for change:  These tables were returned to the Protocol by the request of the 
European Health Authority. 




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6. Section 7.4, Prior and Concomitant Medications and Procedures 
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. 
7. Section 3.2, Subject Exclusion Criteria; Section 5.6.2, Restricted Medications; 
Section 5.6.3, Prohibited Medications and Therapies; Appendix B, Cytochrome 
P450 Inhibitors and Cytochrome P450 Inducers 
Description of change:  Deleted Appendix B and references to Appendix B. 
Rationale for change:  Information was moved to the Pharmacy Manual. 
8. 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 5 (17 JAN 2018) 
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it neither significantly impacts the safety or physical/mental integrity of participants nor 
the scientific value of the study. 
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 6, Study Assessments (Table 6, 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. 
2. 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. 
3. Section 5.4.1.2, Supportive Care Guidelines for Neutropenia and Thrombocytopenia 
Description of change:  Provided instructions to investigators to remind subjects to 
report signs or symptoms of infection, bleeding, or sudden, extremely painful headaches. 
Rationale for change:  Requested by the US FDA. 
4. Section 5.6.2, Restricted Medications; Section 5.6.3, Prohibited Medications and 
Therapies 
Description of change: Radiation therapy was removed from Section 5.6.3 as it was 
redundant with Section 3.2 (exclusion criterion 10), which lists excluded, concurrent 
anticancer therapies.  A description of permitted radiotherapy was added to Section 5.6.2. 
The length of time a live vaccine is prohibited was added to Section 5.6.3. 
Rationale for change:  Administration of localized radiotherapy in cases of pain or 
impending compression fractures may be permitted to allow subjects who are otherwise 
benefitting to continue study treatment.  The length of time a live vaccine is prohibited 
was added to align with other clinical studies within the INCB050465 development 
program.. 


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7. Appendix A, Information Regarding Effectiveness of Contraceptive Methods 
Description of change:  Provided information for male contraception methods. 
Rationale for change:  Informational. 
8. 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-CAN (12 DEC 2017) 
Overall Rationale for the Amendment:   
To remove a criterion for study treatment discontinuation per Health Canada's request. 
1. 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:  To meet Health Canada requirements. 


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Amendment 4 (25 OCT 2017) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to remove the comparator arm (idelalisib) from the 
study. 
This amendment includes the changes to Protocol INCB 50465-203 Amendment 3 
(11 SEP 2017) summarized below.  A redline version of the amendment depicting the updated 
and previous text is also provided. 
1. Title; Synopsis; Section 1, Introduction; Section 2, Study Objectives and Endpoints; 
Section 3.2, Subject Exclusion Criteria; Section 4.1, Overall Study Design; 
Section 4.2, Measures Taken to Avoid Bias; Section 4.3.1, Planned Number of 
Subjects; Section 4.5, Overall Study Duration; Section 5.1.2, Randomization and 
Blinding; Section 5.2, Study Treatments; Section 5.4, Treatment Interruptions and 
Adjustments; Section 5.6, Concomitant Medications; Section 6, Study Assessments 
(Table 6, Schedule of Assessments; Table 7, Schedule of Laboratory Assessments); 
Section 6.1, Screening; Section 6.2, Treatment; Section 7.2, Interactive Response 
Technology Procedure; 7.4, Prior and Concomitant Medications and Procedures; 
7.5.6.1, Chemistry and Hematology; Section 7.6, Efficacy Assessments; Section 7.7.1, 
Blood Sample Collection; Section 9, Statistics; Appendix A, Information Regarding 
Effectiveness of Contraceptive Methods. 
Description of change:  The comparator arm, idelalisib, was removed from the study, 
allowing for removal of the biweekly assessments for ANC and liver enzymes required 
for idelalisib and reduction in the number of subjects from 180 to 100. 
Rationale for change:  A PI3K inhibitor, copanlisib, was recently granted accelerated 
approval by the US Food and Drug Administration in the patient population being 
evaluated in this study.  Therefore, the PI3Kδ inhibitor, idelalisib, can no longer be 
considered the standard of care in the US and consequently is not a relevant comparator 
for new PI3K inhibitors.  It is also not feasible to replace idelalisib with copanlisib, which 
is currently approved only in the US.  This change allows the number of subjects to be 
reduced from 180 to 100. 
2. Section 3.1, Inclusion Criteria 
Description of change:  Removed South Korea–specific age requirement. 
Rationale for change:  Study will not be conducted in South Korea 
3. Section 3.2, Subject Exclusion Criteria 
Description of change:  Exclusion criterion 17 (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. 


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4. Section 5.2.1.2, Supply, Packaging, and Labeling; Section 5.6.1, Pneumocystis 
Jirovecii Prophylaxis 
Description of change:  Moved text describing procurement of drugs required for PJP 
prophylaxis.   
Rationale for change:  Administrative. 
6. Appendix E, Lugano Classification for Response Assessment 
Description of change:  Removed the column describing PET-based criteria of response. 
Rationale for change:  The study is based on CT/MRI only. 
7. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment, including the addition of all summary of changes to Appendix G.  


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Amendment 3 (11 SEP 2017) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to address changes requested by the European 
Regulatory Agency. 
This amendment includes the changes to Protocol INCB 50465-203 Amendment 2 
(15 AUG 2017) summarized below.  A redline version of the amendment depicting the updated 
and previous text is also provided. 
2. Section 9.4.1.1, Primary Efficacy Analyses 
Description of change:  Added a description of the subgroup analysis, which will 
include subgroups based on age, gender, and geographic region that can be further 
divided or combined based on emerging data.   
Rationale for change:  Requested by the European Regulatory Agency. 


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Amendment 2 (15 AUG 2017) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to address changes requested by the European 
Regulatory Agency. 
This amendment includes the changes to Protocol INCB 50465-203 Amendment 1 
(15 MAR 2017) summarized below.  A redline version of the amendment depicting the updated 
and previous text is also provided. 
1. Title page 
Description of change:  The EudraCT number has been added (2017-001624-22). 
Rationale for change:  Informational. 
2. Synopsis; Section 6, Study Assessments (Table 7) 
Description of change:  The frequency of cytomegalovirus analysis was increased to 
every 4 weeks. 
Rationale for change:  Requested by European Regulatory Agency. 
3. Section 3.2, Subject Exclusion Criteria (criterion 16); Section 6, Study Assessments 
(Tables 7 and 8); Section 7.5.6.4, HIV Screening Test 
Description of change:  Revised to require that subjects enrolled outside the 
United States have an HIV test at screening. 
Rationale for change:  Requested by European Regulatory Agency. 
4. Section 5.4.2, Criteria and Procedures for Dose Interruptions or Adjustments of 
Idelalisib 
Description of change:  Clarified that investigators should follow the individual product 
package insert for safety assessments for idelalisib. 
Rationale for change:  Requested by European Regulatory Agency. 
5. Section 6, Study Assessments (Table 7) 
Description of change:  Stated that blood counts should be monitored at least weekly in 
subjects receiving either idelalisib or INCB050465 while ANC is < 1.0 × 109/L, and 
referenced the product package insert and Section 5.4, respectively. 
Rationale for change:  Requested by European Regulatory Agency. 
6. Section 6, Study Assessments (Table 7) 
Description of change:  Added a serum pregnancy test at the safety follow-up visit for 
women of child-bearing potential. 
Rationale for change:  Requested by European Regulatory Agency. 


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7. Appendix A, Information Regarding Effectiveness of Contraceptive Methods 
Description of change:  Revised to require that women receiving idelalisib who are 
using hormonal contraceptives add a barrier method as a second form of contraception, 
and removed the statement that the investigational medicinal products (IMP), which 
included INCB050465, may reduce the efficacy of hormonal contraceptives. 
Rationale for change:  The addition of a barrier method was requested by European 
Regulatory Agency per the SmPC.  The statement that the IMP may reduce the efficacy 
of hormonal contraceptives was removed as the IMP includes INCB050465, which unlike 
idelalisib, is not a CYP3A4 inhibitor and therefore has no effect on hormonal 
contraception. 
8. Synopsis; Section 2, Study Objectives and Endpoints (Table 1)  
Description of change:  The primary objective was revised to state the threshold for 
conducting a superiority analysis. 
Rationale for change:  Requested by European Regulatory Agency. 
9. Synopsis; Section 9, Statistics 
Description of change:  Clarified that descriptive summaries for categorical variables 
will include the number and percentage of subjects in each category, and that the 
descriptive summaries for continuous variables will include the number of observations, 
mean, standard deviation, median, minimum, and maximum. 
Rationale for change:  Requested by European Regulatory Agency. 
10. Synopsis; Section 9.4.1.1, Primary Efficacy Analyses 
Description of change:  Clarified that the point estimates and confidence intervals (CIs) 
will be calculated for the primary endpoint of objective response rate for INCB050465 
and idelalisib and their difference, and clarified the timing for the primary endpoint. 
Rationale for change:  Requested by European Regulatory Agency. 
11. Section 9.4.1.1, Primary Efficacy Analyses 
Description of change:  Clarified that subjects without sufficient baseline or on-study 
response assessment information to be adequately assessed for response status will be 
considered as nonresponders and included in the denominators in the calculations of 
ORR. 
Rationale for change:  Requested by European Regulatory Agency. 
12. Section 9.4.1.3, Other Efficacy Analyses 
Description of change:  Clarified that ORR, complete response rate (CRR), duration of 
response (DOR), progression-free survival (PFS), and overall survival (OS) will be 
summarized by treatment groups.  Point estimates and 95% CIs will be provided for ORR 
and CRR.  Kaplan-Meier estimations of median DOR, PFS, and OS and their 95% CIs 
will also be calculated for each group. 
Rationale for change: Requested by European Regulatory Agency. 
13. 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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5. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  Modified the HBV and HCV exclusion criteria. 
Rationale for change:  Based on emerging data from INCB 50465-101, INCB050465 
does not appear to cause liver toxicity.  The HBV and HCV exclusion criteria have been 
made consistent with criteria used for other PI3K inhibitors, which generally allows 
enrollment of subjects that have been infected with HBV or HCV, but excludes subjects 
with an active infection based on DNA or RNA tests, respectively. 
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. 

SAP_001.pdf: 
Official Title: 
A Phase 2, Multicenter, Open-Label Study of INCB050465, a PI3Kδ Inhibitor, 
in Relapsed or Refractory Follicular Lymphoma (CITADEL-203) 
NCT Number: 
NCT03126019 
Document Date: 
Statistical Analysis Plan Version 2: 28 January 2021 


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STATISTICAL ANALYSIS PLAN 
 
INCB 50465-203 
A Phase 2, Multicenter, Open-Label Study of INCB050465, a PI3Kδ 
Inhibitor, in Relapsed or Refractory Follicular Lymphoma 
(CITADEL-203) 
 
 
 
 
IND Number: 
121,474 
EudraCT Number: 
2017-001624-22 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment 9 dated 23 DEC 2019 
CRF Approval Date: 
13 NOV 2018 
SAP Version: 
Amendment 2 
SAP Author:  
, PhD 
 Biostatistics 
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.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives and Endpoints ...................................................................................8 
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 ...............................................................................................................14 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............14 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................14 
6.1.2. 
Disease History ...........................................................................................................14 


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6.1.3. 
Prior Therapy ..............................................................................................................15 
6.1.4. 
Medical History ..........................................................................................................15 
6.2. 
Disposition of Participants ..........................................................................................15 
6.3. 
Protocol Deviations ....................................................................................................15 
6.4. 
Exposure .....................................................................................................................15 
6.5. 
Study Drug Compliance .............................................................................................16 
6.6. 
Prior and Concomitant Medication .............................................................................16 
7. 
EFFICACY .................................................................................................................17 
7.1. 
Efficacy Hypotheses ...................................................................................................17 
7.2. 
Response Assessment .................................................................................................17 
7.3. 
Analysis of the Primary Efficacy Parameter ..............................................................17 
7.3.1. 
Best Overall Response and Overall Response Rate ...................................................17 
7.3.2. 
Subgroup Analyses for Objective Response Rate ......................................................18 
7.4. 
Analysis of the Secondary Efficacy Parameter ..........................................................19 
7.4.1. 
Complete Response Rate ............................................................................................19 
7.4.2. 
Duration of Response .................................................................................................19 
7.4.3. 
Progression-Free Survival ..........................................................................................19 
7.4.4. 
Overall Survival ..........................................................................................................21 
7.4.5. 
Best Percentage Change in Target Lesion Size ..........................................................21 
 
21 
 
21 
 
22 
 
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 
9.2.2. 
Adverse Events of Special Interest .............................................................................25 


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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 ..........................................................................................29 
9.3.4. 
Worsening Laboratory Events of Special Interest ......................................................29 
9.4. 
Vital Signs ..................................................................................................................29 
9.5. 
Electrocardiograms .....................................................................................................30 
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 ...............................................................................................................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 
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 
EWB 
emotional well-being 
 
 
 
 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FL 
follicular lymphoma 
FLIPI 
Follicular Lymphoma International Prognostic Index 
FWB 
functional well-being 
 
 
IDMC 
independent Data Monitoring Committee 
IRC 
Independent Review Committee 
LYMS 
lymphoma subscale 
MedDRA 
Medical Dictionary for Regulatory Activities  
 
 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
NE 
not evaluable 
NHL 
non-Hodgkin lymphoma 


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Abbreviation 
Term 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PFS 
progression-free survival 
PJP 
Pneumocystis jirovecii pneumonia 
 
c 
PP 
per protocol (population) 
PR 
partial response 
PT 
preferred term 
PWB 
physical well-being 
QD 
once daily 
QTcB 
QT interval corrected using Bazett's formula 
QTcF 
QT interval corrected using Fridericia's formula 
SAP 
Statistical Analysis Plan 
SD 
stable disease 
SOC 
system organ class 
SWB 
social/family well-being 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
WHO 
World Health Organization  


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1. 
INTRODUCTION 
This is a Phase 2, multicenter, open-label study designed to evaluate the efficacy and safety of 
2 INCB050465 treatment regimens in participants with relapsed or refractory FL who have 
received at least 2 prior systemic therapies. 
Section 1 of the Protocol provides a detailed description of the investigational product, target 
patient 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 50465-203 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, 
  
 
 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 50465-203 Protocol Amendment 9 dated 23 DEC 2019 and CRFs 
approved 13 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. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To assess the efficacy of INCB050465 in terms of ORR 
in participants with relapsed or refractory FL. 
ORR defined as the percentage of participants with a CR 
or PR as defined by revised response criteria for 
lymphomas (Cheson et al 2014), as determined by an 
IRC. 
Secondary 
To assess CRR. 
CRR defined as the percentage of participants with a CR 
as defined by revised response criteria for lymphomas 
(Cheson et al 2014), as determined by an IRC. 
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 (ie, CR or PR), as determined by radiographic 
disease assessment provided 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 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 the diameters of all target lesion sizes. 
To characterize the safety and tolerability of 
INCB050465. 
Safety measured by clinical assessments, including vital 
signs and physical examinations, 12-lead ECGs, 
chemistry and hematology laboratory values, and AEs. 


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Table 1: 
Objectives and Endpoints (Continued) 
3. 
STUDY DESIGN 
This is a Phase 2, multicenter, open-label study evaluating 2 INCB050465 treatment regimens 
based on the primary endpoint of ORR.  Participants with relapsed or refractory FL (Grades 1, 2, 
or 3a) who have received at least 2 prior systemic therapies and who are ineligible for 
hematopoietic stem cell transplant will be screened for eligibility.  A total of approximately 
120 participants will be enrolled.  The first 50 participants enrolled will be assigned at a 1:1 ratio 
to 2 study treatment regimens as follows (see Figure 1): 
• Group A:  INCB050465 20 mg QD for 8 weeks followed by 20 mg once weekly 
• Group B:  INCB050465 20 mg QD for 8 weeks followed by 2.5 mg QD 
The remaining 70 participants will be allocated to 1 of the 2 treatment groups to better 
understand the safety and efficacy of that treatment regimen.  The treatment group will be 
selected after evaluation of emerging safety and efficacy data from this and other monotherapy 
studies of INCB050465 in NHL, which are evaluating the same or similar dosing regimens, and 
will be implemented after the first 50 participants are enrolled.  Participants allocated to 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 may 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 CRR, DOR, PFS, OS, and safety. 
An interim futility analysis is planned when the first 50 participants (Group A and Group B 
combined) have been evaluated for response or have permanently discontinued study treatment 
because of disease progression, withdrawal of consent, or death.  The study will be terminated 


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for futility if ≤ 18 of the 50 participants have responded (ie, CR or PR) based on assessments 
provided by the IRC. 
Figure 1: 
Study Design 
 
3.1. 
Randomization 
Not applicable. 
3.2. 
Control of Type I Error 
There will not be any statistical comparison between the 2 treatment groups.  Two-sided 
95% CIs will be reported for all analyses when appropriate. 
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 
Approximately 120 participants will be enrolled and assigned to either treatment Group A or 
Group B.  The first 50 participants will be assigned at a 1:1 ratio to 2 treatment groups, and the 
remaining 70 participants will be allocated to the selected treatment group based on the emerging 
safety and efficacy data from this and other monotherapy studies of INCB050465 in NHL that 
are evaluating the same or similar dosing regimens.  If the true ORR is 51% for participants in 
Group A and Group B, then with 120 total participants, there is approximately 93% probability 
of observing the lower bound of the 95% CI of ORR ≥ 35%. 


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3.4. 
Schedule of Assessments 
See Protocol Amendment 9 dated 23 DEC 2019 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 
eCRF should be used in all relevant listings.  The following rules will be used for handling 
missing or partial dates for analyses requiring dates. 


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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. 
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, multicenter, open-label study.  For the purpose of analysis, the 20 mg once 
weekly dosing period in Group A and the 2.5 mg QD dosing period in Group B are considered 
maintenance dosing periods.  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.  There will not be 
any statistical comparison between the treatment groups. 
For participants who cross over from the initially assigned treatment regimen to the selected 
treatment regimen, if the crossover happens on/before the start of the maintenance 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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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 analyses of all efficacy data. 
5.3.3. 
Safety Population 
The safety population includes all participants enrolled in the study who received at least 1 dose 
of INCB050465. 
All safety analyses will be conducted using the safety population. 
 
 
 
 
 
 
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, weight, height, BMI, and geographic region.  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 grade, initial cytogenetics, initial Ann Arbor staging, initial FLIPI 
risk category, initial presence of B-symptoms, current grade, current cytogenetics, current 
Ann Arbor staging, current FLIPI risk category, current presence of B-symptoms, bone marrow 
involvement at baseline (Yes vs No), bulky disease at baseline (longest diameter ≥ 10 cm vs 
< 10 cm) at baseline by the IRC, and relapsed/refractory status to the most recent prior therapy 


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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 follows: 
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 malignancies under 
study will be summarized for the FAS.  Date and description of the surgery/procedure will be 
listed. 
Number of participants who had prior 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, and regimen and drug used with the transplant will be listed. 
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 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. 


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• 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]. 
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 CRF.  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 CRF. 
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 for each prior and concomitant medication 
will be summarized by WHO drug class and WHO drug PT. 


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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/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 will be 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 progression along 
with the reason(s) of disease progression (if applicable) for each participant, considering 
radiographic data and clinical data, will be provided by Clinical Reviewer.  These data will be 
used in the analyses of related efficacy endpoints. 
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, PR or CR) according to the IRC have had approximately 12 months of 
follow-up from the onset of response. 
7.3.1. 
Best Overall Response and Overall 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. 


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Best overall response as determined by the IRC will be descriptively summarized by treatment 
groups and combined.  The ORR as determined by the IRC will be estimated with 95% CIs.  
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 for those participants whose data are available: 
• Age:  < 65 years, ≥ 65 years 
• Gender:  male, female 
• Race: white, others 
• Geographic region:  Europe, North America, rest of world 
• Current FL grade:  1, 2, 3a 
• Current Ann Arbor Staging:  I-II, III-IV 
• Current FLIPI risk category:  low (0 - 1), intermediate (2), high (≥ 3) 
• Number of prior systemic therapy regimens:  < 3, ≥ 3 
• Bone marrow involvement at baseline:  yes, no, unknown 
• ECOG performance status:  ≤ 1 vs 2 
• Bulky disease at baseline:  longest diameter ≥ 10 cm vs < 10 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 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 ORR as determined by 
the IRC for participants across subgroups. 


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7.4. 
Analysis of the Secondary Efficacy Parameter 
7.4.1. 
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. 
7.4.2. 
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 per the IRC, the number of participants whose disease 
progressed per the IRC or who died, and the number of participants censored will be summarized 
by treatment groups and combined.  The Kaplan-Meier estimate of median DOR as determined 
by the IRC will be presented with its 95% CI, 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. 
7.4.3. 
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 
responses assessed by 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 


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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 two or 
more missed assessments 
Censored 
Date of last valid radiologic assessment (not NE 
and not missing) before the missed assessments 
NE = not evaluable. 
The number of participants whose disease progressed per the IRC or who died, and the number 
of participants censored will be summarized by treatment groups and combined.  The 
Kaplan-Meier estimate of median PFS as determined by the IRC will be presented with its 
95% CIs, 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 by treatment groups and combined.  The Kaplan-Meier estimate of median OS will 
be presented with its 95% CIs, 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 Percentage Change in Target Lesion Size 
For participants in the FAS 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 percentage 
change from baseline, defined as the largest decrease in target lesion sizes during the study, will 
be summarized by treatment groups and combined.  A waterfall plot of the best percentage 
change (2 treatment groups combined) 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, two radiologic reviewers will 
conduct separate reviews 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, but the date of initial response and/or the 
date of progression differ between Reviewers 1 and 2.  The adjudicator will select the read that 
he or she believes more accurately reflects 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 is no adjudication needed, data from Reviewer 1 will be used for the analysis.  An indicator 
will be 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 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 that a target lesion is unaccounted for in a particular postbaseline timepoint (ie, the 
assessment is missing or NE), then the overall sum of 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 the 
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 (v4.03; NCI 2010), Grades 1 through 5.  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 
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.  In addition, serious TEAEs will also be tabulated. 


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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 
• 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 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.   


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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.  
• 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 


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• 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 
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 decreasing 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 


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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  
• 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. 


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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. 
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 percentage change from baseline for vital signs, 
including weight, systolic blood pressure, diastolic blood pressure, pulse, body temperature, and 
respiratory rate 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 normal 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 


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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 percentage 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. 
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 when the first 50 participants (Group A and Group B 
combined) have been evaluated for response or have permanently discontinued study treatment 
because of disease progression, withdrawal of consent, or death.  The study will be terminated 
for futility if ≤ 18 of the 50 participants have responded (ie, CR or PR) based on assessments 
provided by the IRC; otherwise the study will continue.  The probability of stopping at interim 
for futility is 62.16% when the true response rate is 35% or 2.34% when the true response rate 
is 51%. 
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.  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. 
There is no efficacy interim analysis planned for the study. 


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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 
01 MAR 2019 
Amendment 1 
26 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 7.3.1 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 7.4.1 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. 
• Section 7.4.2 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 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. 


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Amendment 1 (26 AUG 2020) 
• Section 3 was modified to increase the target enrollment from approximately 100 to 
approximately 120 participants.  This change is to align with recommendations from 
FDA. 
• 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 add the all-screened population for the summary of 
analysis populations. 
• Section 6.1.2 was updated to add relapsed/refractory status to the most recent prior 
therapy 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 was updated to change the timing of the primary analysis to align with 
recommendations 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. 
• 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. 


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• 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 removed because 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 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-Verlag; 1997. 
National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events Version 
4.03. 2010.  


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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.  Standard tables will follow the conventions in the Standard Safety Tables v1.9.  Shells 
are provided for nonstandard tables in a separate document. 
The lists of tables, figures, and 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 
 
2.2.7 
Summary of Best Change in Target Lesion Size as Reported by 
Investigator 
FAS 
 


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Table No. 
Title 
Population 
Standard 
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 
3.2.7 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
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 Preferred 
Term in Decreasing Order of Frequency 
Safety 
X 
3.2.10 
Summary of INCB050465 Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.11 
Summary of INCB050465 Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA Preferred Term in Decreasing Order of 
Frequency 
Safety 
X 


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Table No. 
Title 
Population 
Standard 
3.2.12 
Summary of INCB050465 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 INCB050465 Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA System Organ Class 
and Preferred Term 
Safety 
X 
3.2.15 
Summary of INCB050465 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 
INCB050465 Dose Reduction by MedDRA System Organ Class and 
Preferred Term 
Safety 
X 
3.2.19 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB050465 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 INCB050465 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 
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 


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Table No. 
Title 
Population 
Standard 
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 
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 
Demographic and Baseline Characteristics 
2.4.2 
Disease History 
2.4.3 
Prior Systemic Therapy 
2.4.4 
Prior Radiation Treatment 


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Listing No. Title 
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  
 
  
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 
Fatal Adverse Events 
2.7.5 
Treatment-Related 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