Conditions: Solid Tumors and Hematologic Malignancy
Keywords: solid tumor lymphoma BET bromodomain inhibitor BRD Diffuse large B-cell lymphoma (DLBCL) Burkitt's lymphoma c-MYC colorectal cancer Non-small cell lung cancer Pancreatic adenocarcinoma castration-resistant prostate cancer breast cancer NUT midline carcinoma leukemia acute myeloid leukemia (AML) myelodysplastic syndrome (MDS) myeloproliferative neoplasms myelofibrosis (MF) multiple myeloma (MM) MDS/MPN
Allocation:  | Intervention model: SEQUENTIAL
Enrollment: 69
Healthy volunteers: no

Brief summary:
This was a study of INCB054329 given to patients with advanced malignancies that were conducted in three treatment groups. Each treatment group had a dose escalation (Part 1) and a dose expansion (Part 3), two of the treatment groups also had an intra-patient dose titration (Part 2).

Detailed description:

Arms:
arm 1: None

Interventions: intervention 1: INCB054329 Monotherapy
Intervention descriptions: intervention 1: Initial cohort dose of INCB054329 monotherapy at the protocol-specified starting dose in the treatment group A (TGA), with subsequent cohort escalations in the three treatment groups (TGA, TGB, and TGC) based on protocol-specific criteria

Protocol document:
Prot_000.pdf: 
Incyte Corporation 
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Protocol INCB 54329-101 Amendment 2 
08 DEC 2016 
CONFIDENTIAL 
Clinical Study Protocol 
INCB 54329-101 / NCT02431260 
Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study 
of INCB054329 in Subjects With Advanced Malignancies 
Product: 
INCB054329 
IND Number: 
124,657 
Phase of Study: 
1/2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-off 
Wilmington, DE 19803 
Date of Protocol: 
21 JAN 2015 
Date of Amendment 1: 
01 JUL 2015 
Date of Amendment 2: 
08 DEC 2016 
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 50, 54, 56, 312, and Part 11 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 received and read the Investigator's Brochure for INCB054329.  I have read 
INCB 54329-101 Protocol Amendment 2 (dated 08 DEC 2016) 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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CONFIDENTIAL 
SYNOPSIS 
Name of Investigational Product:  INCB054329 
Title of Study:  Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054329 
in Subjects With Advanced Malignancies 
Protocol Number:  INCB 54329-101 
Study Phase:  1/2 
Primary Objectives: 
• To evaluate the safety and tolerability of INCB054329 in subjects with advanced malignancies. 
Secondary Objectives: 
• To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of INCB054329 in subjects with 
advanced malignancies. 
• To evaluate preliminary efficacy of INCB054329 in subjects with advanced malignancies. 
Overall Study Design: 
This is an open-label, dose-escalation study of the bromodomain extra-terminal (BET) inhibitor 
INCB054329 in subjects with advanced malignancies.  Subjects will receive once-daily (QD) doses of 
INCB054329 in 21-day cycles until withdrawal criteria are met (eg, toxicity, disease progression).  The 
study will be conducted in 3 parts: 
• Part 1 Dose Escalation will determine the maximum tolerated dose (MTD) of INCB054329 and/or a 
tolerated dose that reaches the desired target inhibition (ie, a pharmacologically active dose [PAD]). 
• Part 2 Dose Titration will determine the feasibility of intrasubject dose titration using Protocol-defined 
criteria. 
• Part 3 Dose Expansion will evaluate the doses and schedules selected in Part 1and Part 2 in subjects 
with select tumor types postulated to be particularly susceptible to BET inhibition (see inclusion 
criteria). 
Part 1 Dose Escalation 
The study will begin with open-label dose escalation in TGA, using a 3 + 3 design to determine the 
tolerated dose over a 21-day cycle.  Initially, subjects in Cohort 1 will receive a single dose of 
INCB054329 followed by a timed PK assessment to confirm exposure approximately 1 week before 
continuous administration is initiated.  The starting dose for continuous administration will be determined 
based on the exposures assessed at this PK assessment; this dose will be no higher than 15 mg. 
The dose-escalation portion of the study will be conducted in the following treatment groups: 
• Treatment Group A (TGA) will include subjects with any advanced solid tumor or lymphoma. 
• Treatment Group B (TGB) will include subjects with acute leukemia, myelodysplastic syndrome 
(MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), and myelofibrosis (MF). 
Escalation will begin with Cohort 1 (including the Day 0 single-dose PK assessment) in TGA; TGB will 
begin enrollment at the PAD (plasma concentration exceeding the PK which is projected to inhibit c-Myc 
level ≥ 50% for approximately 10 hours) or a tolerated dose identified in TGA at the discretion of the 
sponsor, and dose escalation will proceed independently to an MTD in each treatment group using a 3 + 3 
design.  Treatment Group C will open in Part 2 instead of Part 1.  Alternative dose regimens may be 
explored such as twice-daily (BID) or intermittent dose regimens, pending emerging PK, PD, and safety 


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CONFIDENTIAL 
data.  If there is a distinct discrepancy in tolerability among different disease types within the same 
treatment group, additional disease-specific dose-escalation schedules may be initiated.  
Each dose-escalation cohort will initially enroll at least 3 subjects.  If no dose-limiting toxicities (DLTs) 
are observed in the initial 3 subjects, the next cohort will begin enrollment at the next highest dose level.  
Dose increases between cohorts may be up to 2-fold until a Grade 2 toxicity is observed, after which dose 
increases will be limited to no more than 50% above the previous level.  If 1 DLT is observed in the first 
3 subjects in a cohort, at least 3 additional subjects will be enrolled in that cohort.  If a DLT occurs in 
one-third or more of the total cohort (ie, ≥ 2 of 6 subjects), then the MTD will be deemed to have been 
exceeded, and the next lower dose level will be deemed to be the tolerated dose.  Thus, the MTD will be 
defined as 1 dose level below that at which one-third or more of subjects in a particular cohort report 
DLTs.  If the Cohort 1 dose is not tolerated (≥ 2 of 6 subjects report a DLT), a dose de-escalation will be 
considered.  
If a PAD is reached before identifying the MTD, the PAD may be selected for use in the expansion 
cohort, at the discretion of the sponsor. 
Individual subjects within each cohort will undergo reductions/interruptions in INCB054329 
administration according to prescribed safety parameters. 
Part 2 Dose Titration 
Part 2 will enroll 2 treatment groups to investigate the feasibility of intrasubject dose titration with 
Protocol-defined criteria.  Part 2 TGA will enroll advanced solid tumors and lymphomas; Part 2 TGC will 
enroll multiple myeloma (MM).  The starting dose will be the highest tolerated dose with continuous BID 
dose administration identified in Part 1 TGA.  At the end of Cycle 1, if dose titration criteria are met, the 
dose may be increased to 25 mg BID on Day 1 of Cycle 2.  Dose escalation by ≤ 5 mg BID increments 
may be permitted after each subsequent cycle of treatment if the subject continues to meet the dose 
escalation criteria.  Dose interruptions, reductions, or termination may be implemented as described in the 
Dose Modification section of the Protocol.  Part 2 may also explore 1 or more alternate dose regimens 
that has been investigated in Part 1.  Part 2 TGA and TGC will simultaneously enroll at least 5 subjects 
and up to approximately 10 subjects per treatment group. 
Part 3 Dose Expansion 
Part 3 of the study will evaluate the dose selected in Part 1 and Part 2 in select tumor types at their 
respective recommended Phase 2 doses (RP2Ds); based on available data, a dose up to the MTD may be 
selected as the RP2D for use in each expansion cohort by the sponsor and investigators.  There will be 
three treatment groups in Part 3.  Part 3 TGA will enroll up to approximately 155 subjects with specified 
solid tumors or lymphoma, with a goal of enrolling 5 subjects per tumor type.  Part 3 TGB will enroll up 
to 60 subjects with acute leukemia, MDS, MDS/MPN, or MF.  Part 3 TGC will enroll up to 
approximately 15 subjects with MM.  Individual dose modifications (dose interruption, reduction, or 
termination) will be permitted according to Protocol-defined safety parameters.  Subjects will continue to 
receive INCB054329 in 21-day cycles until withdrawal criteria are met (eg, toxicity, disease progression). 
Study Drug, Dosage, and Mode of Administration: 
INCB054329 will be administered orally, in tablet form, QD in 21-day cycles.  Alternate administration, 
such as intermediate doses, alternate dosing schedules, or alternate formulations, may be implemented 
depending upon PK, PD, and safety results. 
Reference Therapy, Dosage, and Mode of Administration:  Not applicable. 
Study Population: 
Subjects with advanced malignancies who have failed at least 1 prior therapy or have no standard 
treatment options demonstrated to provide clinical benefit or who are intolerable to or refuse further 
standard treatments will be enrolled. 
 


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Key Inclusion Criteria: 
• Histologically confirmed diagnosis of advanced malignancy that, for Part 3 only, is measurable or 
evaluable: 
Part 1 Dose Escalation 
- TGA:  Any advanced solid tumor or lymphoma (Hodgkin or non-Hodgkin). 
- TGB:  Acute leukemia, MDS, MDS/MPN, or MF. 
Part 2 Dose Titration 
- TGA:  Any advanced solid tumor or lymphoma. 
- TGC:  MM. 
Part 3 Dose Expansion 
- TGA:  Diffuse large B-cell lymphoma (DLBCL ), Burkitt lymphoma (with c-MYC translocations ), 
CRC, NSCLC, PanC, CRPC, mBC, ovarian cancer      , NMC, other tumor with any pathway 
alteration relevant to BET protein signaling, such as MYC or SHH pathway activation. 
- TGB:  Acute myeloid leukemia (AML), MDS, MDS/MPN (including aCML, CMML, 
MDS/MPN-U, and RARS T), or MF. 
- TGC:  MM, defined as 1 or more of the following:  
 Serum M-protein ≥ 0.5 g/dL. 
 Urine M-protein ≥ 200 mg/24 hours. 
 Serum free light chain (FLC):  involved FLC level ≥ 10 mg/dL provided serum FLC ratio is 
abnormal. 
• Progressed following at least 1 line of prior therapy and there is no further established therapy that is 
known to provide clinical benefit (including subjects who are intolerant to or refuse the established 
therapy). 
- MM subjects must have relapsed from or have been refractory to ≥ 2 prior treatment regimens, 
including proteasome inhibitor and an immunomodulatory drug. 
- AML subjects are eligible if they have relapsed and/or refractory disease; if they are ≥ 65 years of 
age and are not candidates for or have refused standard chemotherapy; or if they have no established 
standard of care that is known to provide clinical benefit in the judgement of the investigator. 
- MF subjects must be resistant, refractory, or intolerant to ruxolitinib therapy.  
• Baseline archival tumor specimen available.  For solid tumors and lymphoma, a tumor block or 
25 unstained slides (15 minimum) from biopsy or resection of primary tumor or metastasis that are 
≤ 2 years old (≤ 1 year old and after completion of last treatment is preferred), or willingness to 
undergo a pretreatment tumor biopsy to obtain the specimen.  For acute leukemia, MDS, MDS/MPN, 
MF, or MM, at least 1 mL archival bone marrow aspirate material ≤ 1 year old and obtained since 
completion of the prior treatment regimen, or willingness to undergo a pretreatment bone marrow 
biopsy/aspirate to obtain the specimen.  If a biopsy is not possible or contraindicated, or the tissue 
requirement cannot be satisfied, this requirement may be waived with approval from the medical 
monitor.  
• Life expectancy > 12 weeks. 
• ECOG performance status: 
- Part 1 and Part 2:  0 or 1. 
- Part 3:  0, 1, or 2. 
 
 


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Key Exclusion Criteria: 
• Inadequate organ function demonstrated by any of the following: 
Part 1 Dose Escalation 
Laboratory Parameter 
TGA 
Hemoglobin (g/dL) 
< 10.0 
Platelet count (× 109/L) 
< 100 
Absolute neutrophil count (× 109/L) 
< 1.5 
Note:  No specific hematologic exclusion criteria apply for TGB.  
- Conjugated bilirubin > upper limit of normal (ULN; need only be tested if total bilirubin exceeds 
> 1.5 × ULN). 
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 × ULN. 
- Creatinine clearance < 50 mL/min based on Cockroft-Gault formula (< 30 mL/min for MM) or 
24-hour urinalysis. 
Part 2 Dose Titration and Part 3 Dose Expansion 
Laboratory Parameter 
TGA 
TGC 
Hemoglobin (g/dL) 
< 9.0 
< 8.0 
Platelet count (× 109/L) 
< 150 
< 100 
Absolute neutrophil count (× 109/L) 
< 1.5 
< 1.0 
Note:  No specific hematologic exclusion criteria apply for TGB in Part 2 and Part 3. 
- Total bilirubin ≥ 1.5 × institutional ULN (total bilirubin > 1.5 × ULN is acceptable if direct bilirubin 
≤ 1.2 × ULN or with a diagnosis of Gilbert's syndrome). 
- AST and ALT ≥ 2.5 × ULN or > 5 × ULN for subjects with extensive liver involvement. 
- Creatinine clearance < 40 mL/min based on Cockroft-Gault formula (< 30 mL/min for MM) or 
24-hour urinalysis. 
• Receipt of anticancer medications, antibodies, biologic, or investigational drugs within the following 
interval before the first administration of study drug: 
- < 6 weeks for mitomycin-C or nitrosoureas. 
- < 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any indication). 
- < 28 days for any antibodies or biological therapies. 
- < 5 half-lives for all other nonbiologic anticancer medications, or sponsor approval. 
- The following are allowed:   
 Hydroxyurea for controlling proliferative disease and low-dose corticosteroids (prednisone or the 
equivalent ≤ 10 mg per day).  
 Subjects with CRPC should be maintained on androgen deprivation, chemical or surgical, with a 
castrate level of testosterone documented (< 50 ng/dL) during the screening period. 
 
 
 
 
 Part 2 TGC and Part 3 TGC:  Receipt of less than 160 mg dexamethasone within 14 days before 
receiving the first dose of study drug. 
 Denosumab and zoledronic acid permitted to treat cancer-related bone diseases such as subjects 
with prostate or breast cancer. 
• Prior receipt of BET inhibitor. 
• Type 1 diabetes or uncontrolled Type 2 diabetes. 
• HbA1c > 8% (all subjects will have HbA1c test at screening). 


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CONFIDENTIAL 
• Prior radiotherapy within 2 weeks before first dose of study drug.  Palliative radiation treatment to 
noncentral nervous system, nonindex, or bone lesions performed less than 2 weeks before treatment 
initiation may be considered with medical monitor approval (a 1-week washout period is usually 
permitted). 
• Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have 
progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms 
attributable to brain/CNS metastases).  Subjects with previously treated and clinically stable brain/CNS 
metastases and off all corticosteroids for ≥ 2 weeks are eligible.  Primary CNS lymphoma will only be 
permitted in Part 3. 
• Known additional malignancy that is progressing or requires active treatment.  Exceptions include 
basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has 
undergone potentially curative therapy. 
Study Schedule/Procedures: 
Subjects will have regularly scheduled study visits at the clinical site as part of a 21-day cycle.  
Study visits are as follows: 
• Screening 
• Cycle 1:  Day 1, Day 2, Day 8 (± 3 days), Day 15 (± 3 days), Day 16  
• Cycles 2 and beyond:  Day 1 (± 3 days), Day 11 (± 4 days) 
• End of treatment (± 3 days) 
• Safety follow-up (end of treatment + 30 days [+ 7 days]) 
• Survival follow-up (end of treatment + every 9 weeks) 
Additionally, Part 1, Cohort 1 TGA will have a visit before the start of the full cycle to receive a single 
dose of study drug and PK testing (referred to as Day 0).  Cycle 1 Day 1 will commence approximately 
7 to 10 days later, upon evaluation of the Day 0 PK results. 
Local Laboratory Tests: 
Most study visits will include sample collection for hematology, chemistry, coagulation, and urinalysis 
testing to be conducted at a local laboratory.  Additionally, the screening visit will include hepatitis 
testing and fertility/pregnancy testing.  Subjects with diseases that are typically monitored through bone 
marrow examination will have bone marrow biopsy/aspirate at screening and as part of the disease 
response assessment performed by a local laboratory. 
Central Laboratory Tests: 
Pharmacodynamic and PK samples will be collected at some visits and shipped to the sponsor or designee 
for analysis. 
Clinical Assessments: 
Physical examinations, ECOG performance status, and tumor/disease response assessments will be 
performed by the investigative site.  Electrocardiograms (ECGs) will be performed at the site; data will be 
submitted to a central reader. 
An objective assessment of disease status will be performed at screening, appropriate to the malignancy 
type (eg, computed tomography [CT], magnetic resonance imaging [MRI], or positron emission 
tomography [PET]/CT [as applicable by subtype]).  Subsequently, disease measurable by CT, MRI, or 
PET/CT will be assessed approximately every 9 weeks for solid tumors and lymphoma.  For disease 
status assessed in bone marrow, on-treatment biopsies will occur on a limited schedule only if clinically 
indicated for the subject's diagnosis, if needed to confirm response, or, optionally, to assess PK or PD. 


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Primary Endpoint: 
• 
Safety and tolerability will be assessed by monitoring frequency, duration, and severity of AEs; 
through physical examinations; by evaluating changes in vital signs and ECGs; and through clinical 
laboratory blood and urine sample evaluations. 
Secondary Endpoints: 
• 
Pharmacokinetics of INCB054329, including Cmax, Tmax, Cmin, AUC0-t, and Cl/F at Days 1, 2, 8, 15, 
and 16 of Cycle 1, for subjects in Parts 1, 2, and 3 and any cycle where dose escalation occurs. 
• 
Pharmacodynamic profile of INCB054329 using a whole blood PD assay. 
• 
Evaluation of objective response rate (ORR), progression-free survival (PFS), duration of response 
(DOR), and overall survival (OS) for subjects in Parts 2 and 3. 
Planned Number of Subjects:  Part 1: Up to approximately 90 subjects; Part 2:  Up to approximately 20; 
Part 3: Up to approximately 230 subjects (TGA, 155; TGB, 60; and TGC, 15). 
Planned Number of Study Sites:  Approximately 12 sites. 
Principal Coordinating Investigator:  TBD 
Estimated Duration of Participation:    
Up to 28 days for screening, continuous treatment in consecutive 21-day cycles as long as subjects are 
receiving benefit and have not met any criteria for study withdrawal, and 30 to 37 days for safety 
follow-up.  It is estimated that an individual subject will participate for approximately 4-6 months on 
average. 
Statistical Methods: 
Sample size consideration:  Part 1 of the study is a standard dose-escalation design, and the sample size 
depends on the occurrence of safety findings as defined by DLT criteria.  Approximately 3 to 6 subjects 
will be enrolled in each cohort.  Part 2 may enroll up to approximately 20 subjects across 2 treatment 
groups.  Part 3 may enroll up to approximately 230 subjects across 3 treatment groups.  A cohort of 
5 subjects provides a > 80% chance of observing at least 1 responder if the underlying response rate is 
30%. 
Descriptive statistics (eg, mean, standard deviation, range) will be derived where appropriate.  Subject 
enrollment, disposition, demographics, and medical history will be summarized at baseline.  The rate of 
DLTs will be summarized for each cohort.  Dose exposure and intensity will be calculated for each 
cohort.  Safety and disease response data will be compared over time to assess change from baseline.  
Pharmacokinetic and PD data will be analyzed with appropriate standard nonlinear analytic software. 


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TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................16 
1. 
INTRODUCTION ......................................................................................................19 
1.1. 
Background .................................................................................................................19 
1.2. 
Pharmacology of INCB054329 ..................................................................................21 
1.2.1. 
Biochemical and Cellular Activity .............................................................................21 
1.2.2. 
Human Whole Blood Assays ......................................................................................21 
1.2.3. 
In Vivo Pharmacology .................................................................................................21 
1.3. 
Preclinical Drug Metabolism and Pharmacokinetics ..................................................22 
1.4. 
Study Rationale ...........................................................................................................23 
1.5. 
Preclinical Safety and Potential Risks ........................................................................23 
1.6. 
Route, Dose Regimen, and Treatment Period ............................................................24 
1.7. 
Clinical Experience With INCB054329 in Study INCB 54329-101 ..........................26 
1.7.1. 
Clinical Pharmacokinetics of INCB054329 in Study INCB 54329-101 ....................26 
1.7.2. 
Safety and Potential Risks of INCB054329 Based on Preliminary Clinical 
Experience in Study INCB 54329-101 .......................................................................28 
1.8. 
Rationale for Intrasubject Dose Titration in Part 2 .....................................................30 
1.8.1. 
Part 2 Dose Titration ...................................................................................................31 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................31 
2.1. 
Study Objectives .........................................................................................................31 
2.1.1. 
Primary Objective .......................................................................................................31 
2.1.2. 
Secondary Objectives .................................................................................................31 
 
31 
2.2. 
Study Endpoints ..........................................................................................................31 
2.2.1. 
Primary Endpoint ........................................................................................................31 
2.2.2. 
Secondary Endpoints ..................................................................................................31 
 
32 
3. 
SUBJECT ELIGIBILITY ...........................................................................................32 
3.1. 
Study Population .........................................................................................................32 
3.1.1. 
Part 1 Dose Escalation ................................................................................................32 
3.1.2. 
Part 2 Dose Titration ...................................................................................................32 
3.1.3. 
Part 3 Dose Expansion ................................................................................................32 


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3.2. 
Subject Inclusion Criteria ...........................................................................................33 
3.3. 
Subject Exclusion Criteria ..........................................................................................34 
4. 
INVESTIGATIONAL PLAN .....................................................................................37 
4.1. 
Overall Study Design ..................................................................................................37 
4.1.1. 
Part 1 Dose Escalation ................................................................................................38 
4.1.2. 
Part 2 Dose Titration ...................................................................................................39 
4.1.2.1. 
Dose Titration Criteria ................................................................................................40 
4.1.3. 
Part 3 Dose Expansion ................................................................................................40 
4.2. 
Measures Taken to Avoid Bias ...................................................................................41 
4.3. 
Number of Subjects ....................................................................................................41 
4.4. 
Study Termination ......................................................................................................41 
5. 
TREATMENT ............................................................................................................41 
5.1. 
Treatment Groups and Administration of Study Drug ...............................................41 
5.1.1. 
Study Drug ..................................................................................................................42 
5.1.2. 
Administration Instructions and Treatment Compliance ............................................42 
5.2. 
Randomization and Blinding ......................................................................................42 
5.3. 
Duration of Treatment and Subject Participation .......................................................42 
5.4. 
Treatment Compliance ................................................................................................42 
5.5. 
Dose-Limiting Toxicity and Maximum Tolerated Dose ............................................42 
5.6. 
Dose Modifications .....................................................................................................44 
5.6.1. 
Interruption and Restarting of Study Drug .................................................................44 
5.6.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................46 
5.6.3. 
Dose Increases ............................................................................................................46 
5.7. 
Withdrawal of Subjects From the Study .....................................................................46 
5.7.1. 
Withdrawal Criteria ....................................................................................................46 
5.7.2. 
Withdrawal Procedures ...............................................................................................47 
5.8. 
Concomitant Medications and Measures ....................................................................47 
5.9. 
Restricted Medications and Measures ........................................................................47 
5.10. 
Prohibited Medications and Measures ........................................................................48 
6. 
STUDY ASSESSMENTS ..........................................................................................48 
6.1. 
Screening Period .........................................................................................................56 
6.2. 
Treatment Period ........................................................................................................56 
6.2.1. 
Day 1 ...........................................................................................................................56 


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6.2.2. 
Day 0 (Part 1 TGA Cohort 1 Only) ............................................................................56 
6.2.3. 
Visit Scheduling ..........................................................................................................56 
6.3. 
Unscheduled Visits .....................................................................................................57 
6.4. 
End of Treatment ........................................................................................................57 
6.5. 
Follow-Up Period .......................................................................................................57 
6.5.1. 
Safety Follow-Up ........................................................................................................57 
6.5.2. 
Survival Follow-Up ....................................................................................................57 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................58 
7.1. 
Administration of Informed Consent Form ................................................................58 
7.2. 
Interactive Response Technology Procedure ..............................................................58 
7.3. 
Demography and History ............................................................................................58 
7.3.1. 
Demographics and Medical History ...........................................................................58 
7.3.2. 
Prior and Concomitant Medications ...........................................................................58 
7.4. 
Safety Assessments .....................................................................................................58 
7.4.1. 
Adverse Events ...........................................................................................................58 
7.4.2. 
Comprehensive Physical Examination .......................................................................59 
7.4.3. 
Targeted Physical Examination ..................................................................................59 
7.4.4. 
Vital Signs and Body Weight/Height .........................................................................59 
7.4.5. 
Twelve-Lead Electrocardiograms ...............................................................................59 
7.4.5.1. 
Electrocardiogram Procedures ....................................................................................59 
7.4.5.2. 
Additional Instruction for Timed Electrocardiograms ...............................................59 
7.4.6. 
Laboratory Assessments .............................................................................................59 
7.4.6.1. 
Pregnancy Testing ......................................................................................................60 
7.4.6.2. 
Serology (Hepatitis Testing) .......................................................................................60 
7.5. 
Efficacy/Disease Assessments ....................................................................................60 
7.5.1. 
Leukemia, MDS, MDS/MPN, MF, Lymphoma, and Multiple Myeloma:  
Bone Marrow Examination for Assessment of Disease Status ..................................61 
7.5.2. 
Immunophenotyping:  Leukemia and Lymphoma .....................................................62 
7.5.3. 
Leukemia, MDS, and MDS/MPN:  Peripheral Blood Blast Counts...........................62 
7.5.4. 
Multiple Myeloma:  Disease Assessment ...................................................................62 
7.5.5. 
Multiple Myeloma:  Skeletal Survey ..........................................................................62 
7.6. 
Performance and Quality-of-Life Assessments ..........................................................63 
7.7. 
Pharmacokinetic Assessments ....................................................................................63 


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7.7.1. 
Blood Sample Collection ............................................................................................63 
7.7.1.1. 
Untimed Pharmacokinetic Testing .............................................................................63 
7.7.1.2. 
Timed Pharmacokinetic Testing .................................................................................63 
7.7.1.3. 
Food-Effect Pharmacokinetic Testing ........................................................................64 
7.7.1.4. 
Bioanalytical Methodology ........................................................................................64 
7.7.2. 
Urine Sample Collection .............................................................................................64 
7.7.3. 
Pharmacodynamic 
 ........................................................64 
7.7.3.1. 
Tumor Biopsy (Treatment Group A) ..........................................................................64 
7.7.3.2. 
Bone Marrow Aspirate for PD 
 Assessment (Treatment 
Groups B and C) .........................................................................................................65 
7.7.3.3. 
Buccal Swab ...............................................................................................................65 
7.7.3.4. 
Plasma Pharmacodynamics ........................................................................................65 
7.7.3.5. 
Whole Blood Pharmacodynamics ...............................................................................65 
7.7.3.6. 
Whole Blood Correlative Studies ...............................................................................66 
7.7.3.7. 
Analyses ......................................................................................................................66 
7.8. 
Other Study Procedures ..............................................................................................66 
7.8.1. 
Administration of Study Drug in the Clinic ...............................................................66 
7.8.2. 
Dispensing Study Drug and Assessing Compliance ...................................................66 
7.8.3. 
Distribution of Subject Reminder Cards .....................................................................67 
7.8.4. 
Survival Follow-Up ....................................................................................................68 
8. 
SAFETY MONITORING AND REPORTING .........................................................68 
8.1. 
Adverse Events ...........................................................................................................68 
8.1.1. 
Definitions ..................................................................................................................68 
8.1.2. 
Reporting ....................................................................................................................68 
8.2. 
Laboratory Test Abnormalities ...................................................................................70 
8.2.1. 
Definitions and Reporting ...........................................................................................70 
8.3. 
Serious Adverse Events ..............................................................................................70 
8.3.1. 
Definitions ..................................................................................................................70 
8.3.2. 
Reporting ....................................................................................................................71 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................72 
8.5. 
Pregnancy ...................................................................................................................72 
8.6. 
Warnings and Precautions ..........................................................................................72 
8.7. 
Data Monitoring Committee .......................................................................................72 


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8.8. 
Product Complaints ....................................................................................................73 
9. 
STATISTICS ..............................................................................................................73 
9.1. 
Study Populations .......................................................................................................73 
9.2. 
Selection of Sample Size ............................................................................................73 
9.3. 
Level of Significance ..................................................................................................74 
9.4. 
Statistical Analyses .....................................................................................................74 
9.4.1. 
Definitions ..................................................................................................................74 
9.4.2. 
Primary Analyses ........................................................................................................74 
9.4.2.1. 
Adverse Events ...........................................................................................................74 
9.4.2.2. 
Clinical Laboratory Tests ...........................................................................................74 
9.4.2.3. 
Vital Signs ..................................................................................................................75 
9.4.2.4. 
Electrocardiograms .....................................................................................................75 
9.4.3. 
Secondary Analyses ....................................................................................................75 
9.4.3.1. 
Efficacy Analyses .......................................................................................................75 
9.4.4. 
Pharmacodynamic Analyses .......................................................................................76 
9.4.5. 
Pharmacokinetic Analyses ..........................................................................................76 
9.5. 
Analysis for Data Monitoring Committee ..................................................................76 
9.6. 
Interim Analysis ..........................................................................................................77 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ..........................................................................................................77 
10.1. 
Investigator Responsibilities .......................................................................................77 
10.2. 
Accountability, Handling, and Disposal of Study Drug .............................................78 
10.3. 
Data Management .......................................................................................................79 
10.4. 
Data Privacy and Confidentiality of Study Records ...................................................79 
10.5. 
Financial Disclosure ...................................................................................................80 
10.6. 
Publication Policy .......................................................................................................80 
11. 
LITERATURE REFERENCES..................................................................................81 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................84 
APPENDIX B. PHARMACOKINETIC ANALYTICAL PARAMETERS ..............................85 
APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS .......................................................................................86 
APPENDIX D. CYP3A4 INHIBITORS AND INDUCERS ......................................................87 


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APPENDIX E. CYP2C19 INHIBITORS AND INDUCERS .....................................................93 
APPENDIX F. INTERNATIONAL WORKING GROUP RESPONSE CRITERIA 
FOR ACUTE MYELOID LEUKEMIA .....................................................................96 
APPENDIX G. IWG RESPONSE CRITERIA FOR MYELODYSPLASTIC 
SYNDROME ..............................................................................................................97 
APPENDIX H. INTERNATIONAL CONSORTIUM PROPOSAL OF UNIFORM 
RESPONSE CRITERIA FOR 
MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS 
(MDS/MPN) IN ADULTS .........................................................................................98 
APPENDIX I. REVISED RESPONSE CRITERIA FOR MYELOFIBROSIS:  IWG-
MRT AND ELN CONSENSUS REPORT...............................................................101 
APPENDIX J. INTERNATIONAL UNIFORM RESPONSE CRITERIA FOR 
MULTIPLE MYELOMA .........................................................................................103 
APPENDIX K. CRITERIA FOR EVALUATING DISEASE RESPONSE AND 
PROGRESSION IN SUBJECTS WITH MULTIPLE MYELOMA 
TREATED BY HIGH-DOSE THERAPY AND HAEMOPOIETIC STEM 
CELL TRANSPLANTATION .................................................................................104 
APPENDIX L. RESPONSE CRITERIA FOR LYMPHOMA – THE LUGANO 
CLASSIFICATION ..................................................................................................105 
 


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LIST OF TABLES 
Table 1: 
Study INCB 54329-101 Part 1 Cohorts ......................................................................28 
Table 2: 
Summary of TEAEs (≥ 20% Subjects; All Grades, All Causality) ............................29 
Table 3: 
Summary of TEAEs ≥ Grade 3 (≥ 5% Subjects; All Causality) .................................30 
Table 4: 
Definition of Dose-Limiting Toxicity and Maximum Tolerated Dose ......................43 
Table 5: 
Guidelines for Interruption and Restarting of Study Drug .........................................44 
Table 6: 
Schedule of Study Assessments – Treatment Group A (Part 1, Part 2, and 
Part 3) ..........................................................................................................................49 
Table 7: 
Schedule of Study Assessments – Treatment Group B (Part 1 and Part 3) ................50 
Table 8: 
Schedule of Study Assessments – Treatment Group C (Part 2 and Part 3) ................51 
Table 9: 
Schedule of Laboratory Assessments – All Treatment Groups ..................................52 
Table 10: Laboratory Tests:  Required Analytes ........................................................................53 
Table 11: Laboratory Tests:  Required Analytes for Multiple Myeloma Subjects .....................54 
Table 12: Timed Assessments ....................................................................................................55 
Table 13: Probability of Dose Escalation by DLT Rate .............................................................73 
Table 14: Criteria for Clinically Notable Vital Signs Abnormalities .........................................75 
Table 15: Criteria for Clinically Notable Electrocardiograms ....................................................75 
 
LIST OF FIGURES 
Figure 1: 
Determining the Part 1 Treatment Group A Starting Dose ........................................25 
Figure 2: 
INCB054329 Pharmacokinetics at Steady State for Cohorts 1 to 10 .........................26 
Figure 3: 
INCB054329 Intersubject Variability in Pharmacokinetics Across Cohorts 1 
to 10 ............................................................................................................................27 
Figure 4: 
Maximum Platelet Change From Baseline Versus AUC on Day 1 for 
Individual Subjects Across Cohorts 1 to 10 ...............................................................27 
Figure 5: 
Study Design ...............................................................................................................37 
 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Term 
Explanation 
aCML 
atypical chronic myeloid leukemia 
AE 
adverse event 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
AST 
aspartate aminotransferase 
AR 
androgen receptor 
AUC 
area under the plasma or serum concentration-time curve 
BCLU 
B-cell lymphoma, unclassifiable 
BCRP 
breast cancer resistance protein/ABCG2 
BD 
bromodomain 
BET 
bromodomain and extra-terminal (protein) 
BID 
twice daily 
BRD 
bromodomain-containing protein 
BRDT 
bromodomain testis-specific protein 
CLL 
chronic lymphocytic leukemia 
CMML 
chronic myelomonocytic leukemia 
c-MYC 
cellular form of a regulator gene that can act as an oncogene (MYC) 
c-Myc 
transcription factor encoded by the c-MYC gene 
CNS 
central nervous system 
CR 
complete remission 
CRC 
colorectal cancer  
CRPC 
castration-resistant prostate cancer 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group (performance status assessment) 
eCRF 
electronic case report form  
ELN 
European LeukemiaNet 


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Term 
Explanation 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FDG 
[18F] fluorodeoxyglucose 
FISH 
fluorescence in situ hybridization 
FLC 
free light chain 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GLP 
Good Laboratory Practices 
HBV 
hepatitis B virus 
HBV-DNA 
hepatitis B virus deoxyribonucleic acid 
HCV 
hepatitis C virus 
HCV-RNA 
hepatitis C virus ribonucleic acid 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HNSTD 
highest non-severely toxic dose 
IC50 
half-maximal inhibitory concentration 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IN 
Investigator Notification 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
IWG-MRT 
International Working Group–Myeloproliferative Neoplasms Research and 
Treatment 
LDi 
longest diameter 
mBC 
metastatic breast cancer 
MDS 
myelodysplastic syndrome 
MDS/MPN 
myelodysplastic/myeloproliferative neoplasms 
MDS/MPN-U 
myelodysplastic/myeloproliferative neoplasms unclassifiable 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
myelofibrosis 
MM 
multiple myeloma 
MPN 
myeloproliferative neoplasms 
MRD 
minimal residual disease 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NF-ĸB 
nuclear factor kappa-light-chain-enhancer of activated B cells 


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Term 
Explanation 
NMC 
NUT midline carcinoma 
NOAEL 
no observed adverse effect level 
NSCLC 
non–small cell lung cancer 
NUT 
nuclear protein in testes 
OAT 
organic anion transporter 
OATP1 
organic anion transporter polypeptide 
OCT2 
organic cation transporter 
ORR 
objective response rate 
OS 
overall survival 
PanC 
pancreatic adenocarcinoma 
PAD 
pharmacologically active dose 
PD 
pharmacodynamic 
PET 
positron emission tomography 
PFS 
progression free survival 
P-gp 
P-glycoprotein  
PK 
pharmacokinetic 
QD 
once daily 
QOD 
every other day 
RARS-T 
refractory anemia with ring sideroblasts and thrombocytosis 
RNA 
ribonucleic acid 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SHH 
sonic hedgehog (cell pathway) 
STD10 
severely toxic dose in 10% of animals 
SUSAR 
suspected unexpected serious adverse reaction 
TGA 
Treatment Group A 
TGB 
Treatment Group B 
TGC 
Treatment Group C 
Tmax 
time to maximum plasma concentration 
ULN 
upper limit of normal  
WBC 
white blood cell 
 


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1. 
INTRODUCTION 
1.1. 
Background 
Central to the evolution of neoplastic cells is a changing pattern of gene expression that 
distinguishes cancer cells from their normal counterparts.  Activation of transcription factors that 
regulate oncogenic processes, including c-MYC and NF-ĸB is frequently observed in human 
cancers; however, direct targeting of these proteins has remained elusive.  Gene expression is 
also regulated at the level of chromatin by covalent modifications, including histone acetylation 
and methylation, which specify an epigenetic code that regulates the interactions of 
DNA-binding proteins, nucleosome remodeling complexes, and transcriptional regulators with 
chromatin (Portela and Esteller 2010).  Changes in epigenetic patterns translate to altered 
transcriptional profiles in malignant cells.  In many cases, altered epigenetic patterns arise from 
mutations in genes encoding epigenetic regulator proteins, and mutant epigenetic proteins can be 
bona fide oncogenes (You and Jones 2012).  Thus genetic and epigenetic mechanisms cooperate 
to promote the development and progression of cancer.  A key step in translating the epigenetic 
code is the recognition of modified histone residues by effector proteins that harbor specific 
interaction domains. 
The bromodomain (BD) and extra-terminal (BET) protein family is composed of 4 members 
(BRD2, BRD3, BRD4, and BRDT) that each have 2 BD modules (BD1 and BD2).  These BDs 
exhibit high selectivity for acetylated lysine residues in histones and other proteins.  The human 
genome encodes 61 distinct BDs, but the BET protein modules BD1 and BD2 are distinguishable 
from other BDs by their higher affinity for di-acetylated lysine motifs (Filippakopoulos and 
Knapp 2014).  Bromodomain-containing protein -T is restricted to germ cells; however, BRD2, 
BRD3, and BRD4 are ubiquitously expressed.  Bromodomain and extra-terminal proteins 
function as transcriptional regulators by binding to acetylation marks in chromatin at gene 
promoter and enhancer elements and recruiting transcription initiation and elongation complexes 
such as the Mediator co-activator complex, polymerase-associated factor complex, and super 
elongation complex (Wu and Chiang 2007, Dawson et al 2011).  Thus for many gene promoters 
and enhancers, BET proteins play a crucial role in linking acetylated chromatin marks to 
transcriptional activation. 
Although BET proteins are found to be associated with thousands of gene promoters and 
enhancers in the genome, functional studies have revealed that only a subset of these genes are 
significantly regulated by BET proteins.  Many of these genes contain "super enhancers" that are 
notable for binding of BRD4.  Transcriptional profiling data show that BRD4-dependent genes 
include many highly regulated genes involved in cell proliferation, differentiation, and survival; 
however, BRD4 does not regulate expression of constitutively expressed housekeeping genes 
(Mochizuki et al 2008, Delmore et al 2011).  In view of the critical role of BET in regulating 
expression of cell fate–determining and cell cycle–associated genes, targeted inhibition of BET 
proteins may have selective pharmacological effects on cancer cells. 
The carcinogenic role of the BET protein family is exemplified by a highly malignant, but rare, 
form of epithelial neoplasia called NUT midline carcinoma (NMC) in which a recurrent 
translocation of BRD3 or BRD4 with nuclear protein in testes (NUT) creates a novel fusion 
oncogene, BRD-NUT (French et al 2008).  Nuclear protein in testes midline carcinoma is 


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characterized by proliferation of undifferentiated epithelial cells resulting from aberrant 
transcriptional regulation by the mutant oncoprotein (Yan et al 2011).  Treatment with the 
BET-selective inhibitor JQ-1 displaces BRD-NUT from chromatin in patient-derived NMC cells, 
restores terminal squamous cell differentiation in vitro, and provides tumor growth suppression 
in vivo (Filippakopoulos et al 2010).  These data support the idea that altered gene transcription 
associated with BET activity in cancer cells is reversible and provide validation that BET protein 
inhibition can be efficacious against malignant cells. 
In preclinical studies, BET inhibitors have demonstrated efficacy across a wide range of 
hematologic cancer and solid tumor models.  Tumor types associated with dysregulation of 
transcription factors appear to be highly responsive to BET inhibition.  In particular, c-MYC is 
upregulated in many cancers secondarily (eg, carcinomas of the breast, colon, cervix, and lung) 
or directly through chromosomal translocations (eg, some myelomas, double-hit, and Burkitt 
lymphomas).  An example is found with the demonstration that KRAS mutations in non–small 
cell lung cancer (NSCLC) cells have been shown to maintain c-Myc activation, and treatment 
with a BET inhibitor induces apoptosis in these cells and promotes tumor regression in murine 
models (Shimamura et al 2013).  In another example, androgen receptor (AR)-dependent prostate 
cancer cells were highly sensitive to JQ-1 treatment (Wyce et al 2013, Asangani et al 2014), 
which appeared to be via JQ-1 downregulation of AR activity via BRD4, and resultant inhibition 
of growth-related target genes.  Furthermore, experiments using patient-derived cells from 
tumors associated with activation of the hedgehog (SHH)-GLI1 pathway, such as in some basal 
cell carcinomas and medulloblastomas, show that BET inhibition reduces growth and 
downregulates GLI target genes (Tang et al 2014).  These data suggest a therapeutic role for 
BET inhibitors across a wide range of solid tumor types and demonstrate that cancers derived 
from aberrant activity of lineage-determining transcription factors may be particularly 
responsive.  For a thorough discussion of preclinical cancer model data, refer to the IB. 
Finally targeting BET proteins may have effects beyond direct inhibition malignant cell growth.  
Bromodomain-containing protein 2, BRD3, and BRD4 have been shown to be critical for 
regulating the inflammatory response in several model systems (Belkina et al 2013, for 
example).  Bromodomain and extra-terminal inhibitors exhibited a protective effect in vivo 
against endotoxic shock by reducing the global inflammatory response (Nicodeme et al 2010).  
Mechanistically, BRD4 has been shown to facilitate transcription by the NF-ĸB complex 
(Huang et al 2009).  In lymphoma cells characterized by NF-ĸB pathway activation, BET 
inhibition reduces the NF-ĸB transcriptional signature, including proinflammatory genes 
interleukin (IL)-6 and IL-10 (Ceribelli et al 2014).  These studies demonstrate the potential for 
BET inhibition in reducing the inflammatory response.  Tumor-associated inflammation is a 
hallmark of cancer, and elevated levels of proinflammatory proteins including IL-6 have been 
shown to promote multiple aspects of tumorigenesis (Landskron et al 2014).  Thus, antitumor 
activity of BET inhibitors may result from modulation of inflammation in addition to direct 
effects on the tumor cell. 
In summary, inhibition of BET protein activity may have therapeutic utility in diseases such as 
cancer, where altered expression of growth promoting, proinflammatory, and survival genes 
contributes to the establishment and persistence of the oncogenic phenotype. 


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1.2. 
Pharmacology of INCB054329 
1.2.1. 
Biochemical and Cellular Activity 
INCB054329 is a selective inhibitor of BET proteins that is proposed for the treatment of 
advanced cancer.  The biochemical potency of INCB054329 to inhibit human BET proteins is 
determined by an in vitro assay that measures binding to a tetra-acetylated human H4 histone 
derived peptide.  Assays for BD1 and BD2 from each of the 4 BET proteins (8 total assays) have 
been established; potency of INCB054329 ranges from IC50 of 1.3 nM to 119 nM among the 
8 proteins and is fully reversible (refer to the IB).  For BRD4, the protein with the strongest 
association to cancer, the IC50 values for BD1 and BD2 are 28 ± 6.7 nM and 3.0 ± 1.0 nM, 
respectively. 
INCB054329 exhibits inhibitory activity in a wide array of cellular models spanning both 
hematologic and solid tumor histologies, with an IC50 around 200 nM or less in sensitive tumor 
types.  As a comparator, when T-cells from normal donors were stimulated with IL-2 in the 
presence of INCB054329, an IC50 of 1387 ± 242 nM (N = 33) was observed.  Among the 
activities observed are downregulation of BET-controlled genes (such as c-MYC).  The c-Myc 
nuclear transcription factor may be a key downstream target of BET inhibition.  Overexpression 
of c-Myc plays a critical role in malignant transformation, either as a mutant oncogene or by 
overexpression of the wild-type protein.  Overexpression of c-MYC, an important cell-cycle 
regulator, is observed in many malignancies, including carcinoma of the breast, colon, cervix, 
and lung, and in myeloid leukemias, among others (Chen et al 2014).  The down regulation of 
c-Myc and other proto-oncogenes may be the mechanism by which BET inhibition reduces cell 
viability and proliferation in hematologic and solid tumor cell lines, producing cell-cycle arrest 
and inducing apoptosis (refer to the IB).  Together, these data suggest INCB054329 is a strong 
cellular growth and viability inhibitor, with efficacy across a wide range of histologic tumor 
types. 
1.2.2. 
Human Whole Blood Assays  
To estimate the effect of INCB054329 on c-Myc protein in the presence of human serum 
proteins, a whole blood assay was developed.  INCB054329 treatment reduced c-Myc levels in 
KMS12BM cells spiked into human whole blood with an IC50 value of 92 nM ± 32 (N = 15) and 
an IC90 of 496 nM. 
To determine the effect of INCB054329 to suppress production of pro-inflammatory cytokines in 
human whole blood samples, an assay was developed to measure endogenous levels of MCP-1 
and MCP-3 proteins in blood stimulated ex vivo with lipopolysaccharide.  The IC50 values for 
suppression of MCP-1 and MCP-3 induction are 60 ± 13 and 42 ± 24 nM, respectively, for 
INCB054329 (n = 4 different donors).  These results are consistent with the IC50-value derived 
from the c-Myc whole blood assay (92 nM).  The MCP assay will be used to establish the 
pharmacodynamic (PD)/pharmacokinetic (PK) relationship in the present study. 
1.2.3. 
In Vivo Pharmacology 
To evaluate the in vivo effect of INCB054329, the RKO xenograft model of colon cancer was 
established in female Nu/Nu mice.  INCB054329 was administered by continuous infusion of 
0 (vehicle) 6, 30, or 45 mg/kg per day.  Dose-dependent suppression of tumor growth was 


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observed, with 39%, 59%, and 65% inhibition at 6, 30, and 45 mg/kg per day, respectively.  All 
dose levels were well tolerated.  Pharmacokinetic analysis showed that infusions of 30 or 
45 mg/kg per day covered the whole blood IC90 continuously, whereas 6 mg/kg per day covered 
the c-Myc whole blood IC50.  Therefore efficacy could be achieved when plasma levels of 
INCB054329 were constantly equivalent to or greater than the c-Myc whole blood IC50. 
The effect of different oral dose administration schedules was also evaluated in the MM1.S 
multiple myeloma (MM) model.  Once-daily (QD) and twice-daily schedules were evaluated 
using oral doses of 0 (vehicle), 25, 50, or 75 mg/kg.  Dose-dependent tumor growth inhibition 
was observed with both schedules (refer to the IB), and a maximum effect of 62% growth 
inhibition  was observed when the c-Myc whole blood IC50 was covered for at least 12 hours per 
day. 
To assess the relationship between plasma concentration of INCB054329 and suppression of 
c-Myc protein in tumors, the KMS12BM multiple myeloma xenograft model was used to enable  
a direct comparison with c-Myc suppression in the in vitro whole blood assay   At 3 hours 
postdose, peripheral blood and tumors were harvested for analysis of drug effect on c-Myc.  The 
in vivo observed IC50 value of 66 nM for c-Myc suppression by INCB054329 is consistent with 
the c-Myc in vitro whole blood IC50 value of 92 nM using KMS12BM-spiked whole blood. 
1.3. 
Preclinical Drug Metabolism and Pharmacokinetics 
The absorption, distribution, metabolism, and excretion of INCB054329 have been characterized 
in rats, dogs, and monkeys (refer to the IB).  INCB054329 exhibited species-dependent 
clearance.  In rats, the systemic clearance following intravenous administration was 
sex-dependent, with approximately 3-fold higher clearance in male rats compared with female 
rats, and this is attributed to sex-specific hepatic metabolism by CYP3A2 and CYP2C11.  The 
systemic clearance was high in dogs while low in cynomolgus monkeys.  The steady-state 
volume of distribution was moderate while the terminal elimination half-life was short in all 
3 species.  The renal excretion of intact INCB054329 was minimal across species, suggesting 
that INCB054329 is eliminated predominantly by metabolism.  Following oral administration, 
INCB054329 exhibited moderate-to-high oral bioavailability in the 3 species.  The AUC (see 
Appendix B) in female rats following oral administration was approximately 10-fold greater than 
that in male rats, consistent with the differences in systemic clearance and potential differences 
in presystemic clearance.  Based on allometric scaling, the terminal elimination half-life (t½) of 
INCB054329 in human is projected to be approximately 4 hr, and the oral bioavailability is 
projected to be 50%.  At a clinical dose of 50 mg QD, which is expected to cover the whole 
blood c-Myc IC50 (92 nM) over a period of 12 hours, the total steady-state plasma AUC is 
estimated to be approximately 3.1 μM·h and the Cmax is estimated to be approximately 0.5 μM. 
INCB054329 exhibits moderate in vitro permeability using Caco-2 monolayers.  INCB054329 
has moderate penetration across the rat blood-brain barrier, with steady state brain-to-plasma 
ratio of 0.35.  In vitro human serum and plasma protein binding of INCB054329 was moderate 
(unbound fraction of 24%), similar to that in preclinical species. 
Interactions of INCB054329 with uptake and efflux transporters were evaluated using in vitro 
systems.  INCB054329 is a weak inhibitor of the 5 uptake transporters (OCT2, OAT3, 
OATP1B1, OATP1B3 and OAT1) and the 2 efflux transporters (P-glycoprotein [P-gp] and 
breast cancer resistance protein [BCRP]), and no drug-drug interactions are expected based on 


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this inhibitory activity.  INCB054329 is not a substrate of P-gp but is a substrate of BCRP and 
therefore, it is possible that the PK profile of INCB054329 is affected by co-administration of 
potent BCRP inhibitors.  INCB054329 is primarily metabolized by CYP3A4 and to a lesser 
extent by CYP2C19.  In contrast to the rat, no sex-dependent differences have been reported for 
CYP3A4 and CYP2C19 in the human liver.  Further, in vitro studies conducted using liver 
microsomes from male and female subjects indicate similar qualitative and quantitative 
metabolism.  Therefore, the PK of INCB054329 is expected to be similar in male and female 
human subjects.  INCB054329 is an inhibitor of CYP2C19 with an IC50 value of 9 µM and is not 
an inhibitor of the other CYPs evaluated.  Based on the projected human PK at clinically relevant 
doses, no drug-drug interaction is expected based on CYP interactions.  The metabolism profile 
of INCB054329 in rat, monkey, and human in vitro liver preparations were qualitatively similar 
and M8 (INCB061050) was identified as the only major metabolite across all 3 species.  From 
the drug safety perspective, no glutathione adducts were detected upon incubation of 
INCB054329 in human liver microsomes, suggesting that INCB054329 does not generate any 
reactive metabolites.  Metabolites in plasma and urine from the rat and monkey 28-day 
toxicokinetic studies were similar to those observed in vitro. 
1.4. 
Study Rationale 
INCB054329 is an oral BET protein inhibitor that is being developed for patients with advanced 
malignancies.  The BET family of BD-containing proteins functions as transcriptional regulators 
binding to acetylation marks in chromatin at gene promoter and enhancer elements and recruiting 
transcription initiation and elongation complexes.  In tumor cells, aberrant patterns of epigenetic 
marks including acetylation underlie abnormal transcriptional regulation of genes involved in 
cellular proliferation, survival, differentiation, and migration, thereby promoting an oncogenic 
program.  Bromodomain and extra-terminal proteins are essential for the transcription of many of 
these genes; thus, inhibition of BET binding to chromatin may suppress oncogenic transcription 
in cancer cells.  Suppression of these oncogenic factors has the potential to inhibit the growth of 
a variety of tumor cell types and may be efficacious in the treatment of advanced malignancies.  
Thus, study subjects with advanced cancer and no proven treatment options are candidates for 
this study to determine preliminary safety and efficacy of INCB054329.  Furthermore, 
biochemical, tumor biomarker, and preclinical pharmacology studies have revealed that 
BET-inhibition may be useful in the treatment of a broad array of cancers, particularly those 
associated with activation of MYC, SHH, and RAS pathways, among others.  Preclinical data 
using INCB054329 as an inhibitor have demonstrated efficacy in these histologic subtypes, such 
as lymphomas with c-Myc dysfunction, MM, acute myeloid leukemia (AML), castration-
resistant prostate cancer (CRPC), colorectal cancer (CRC), pancreatic cancer (PanC), metastatic 
breast cancer (mBC), and particularly NMC, as discussed previously (refer to the IB).  Part 2 of 
the study will focus on this subset of solid tumors and hematologic malignancies that tend to be 
associated with these oncogenic profiles, to evaluate the efficacy of BET-inhibition. 
1.5. 
Preclinical Safety and Potential Risks 
Non-clinical safety studies with INCB054329 included single and repeat-dose studies of up to 
28 days in duration in rats and monkeys using a QD dose schedule.  An additional 28-day GLP 
study was conducted in the rat using an every other day (QoD) dose schedule.  The most 
prominent INCB054329-related findings in toxicology studies conducted in the rat and monkey 


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were gastrointestinal (GI) toxicity, bone marrow suppression, and lymphoid organ depletion; all 
of which are expected based on the mechanism of action of INCB054329.  Hematology changes 
associated with the bone marrow suppression and lymphoid depletion included decreases in 
circulating lymphocytes and platelets.  Serum chemistry alterations included increased glucose, 
as well as increased triglycerides and decreased protein which were likely due to poor nutritional 
status.  The GI toxicity was dose-limiting in the rat, and likely was the main contributor to 
mortality in this species.  Adverse GI toxicity was also noted in the monkey; but was not 
considered severe at any dose level evaluated.  The aforementioned toxicities exhibited evidence 
of reversibility and are readily clinically monitorable. 
Other direct, reversible, dose-dependent toxicities of INCB054329 were identified in the rat only 
and included ovarian follicular degeneration, hypospermatogenesis, degeneration of the incisor 
teeth, and histiocytosis of the lung.  The changes observed in the reproductive organs are most 
likely an effect of BRD2 and BRDT inhibition at higher dose levels used in the toxicity studies.  
Toxicity to teeth is not expected in adult human subjects.  INCB054329 was negative in the 
bacterial mutagenicity assay.  In vivo carcinogenicity, reproductive and developmental toxicity 
studies have not been performed.  For further detail on nonclinical findings refer to the IB. 
1.6. 
Route, Dose Regimen, and Treatment Period 
INCB054329 is being developed as a new investigational drug for oral administration.  Oral drug 
administration is generally the most convenient and cost-effective method of drug delivery for 
medications requiring continuous exposure.  INCB054329 tablets will be self-administered QD 
and will occur in continuous 21-day cycles until discontinuation criteria are met.  Alternate 
dosing schedules, intermediate doses, or alternate formulations may be implemented as PK, PD, 
and safety data emerge. 
According to the algorithms described in ICH S9 Guidance for Industry, Nonclinical Evaluation 
for Anticancer Pharmaceuticals (FDA 2010), the starting clinical dose for small molecules is 
often set at one-tenth the STD10 in rodents (severely toxic dose in 10% of animals), or one-sixth 
of the HNSTD (highest non-severely toxic dose) in non-rodents, with the most sensitive species 
used as a guide.  In vivo pharmacology studies in mice demonstrated greater efficacy in studies 
when INCB054329 was administered QD versus QoD.  An uninterrupted QD administration 
regimen is preferred to provide pharmacologic coverage of the target; there are no data to 
suggest that intermittent inhibition of BET activity would provide an improved therapeutic 
window.  Thus, initiation of Phase 1 clinical investigations using a QD schedule will have the 
greatest probability of providing a pharmacologically active regimen and potential clinical 
benefit to study subjects.  A dose up to 15 mg is proposed as the safe starting dose for the QD 
dose regimen, with a dose of 5 mg used for an initial single-dose PK assessment.  These dose 
levels are expected to be safe, based on the following: 
• Dose-limiting GI toxicity and bone marrow suppression observed in repeat-dose 
toxicology studies in both species appear to be reversible and clinically monitorable. 
• The proposed initial PK assessment single dose (5 mg) is based on one-tenth of the 
STD10 for the more sensitive species and sex (female rat) and is expected to be safe.  
This initial single dose will be used to characterize the exposure associated with 
5 mg. 


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• The starting dose for QD dose administration in this study will be determined by the 
exposure following the single dose with a ceiling of 0.7 µM·h, which is 
approximately 50% of the unbound AUC observed in male rats at the STD10 in the 
28-day QD dose study, and the unbound AUC of the male rat NOAEL (no observed 
adverse effect level) (Figure 1).  Calculated doses will be rounded down as needed to 
available pill strength, or as low as 2.5 mg. 
− Although greater toxicity was observed in female rats given equivalent or lower 
doses, this was attributed to higher exposure in female rats, and toxicity was 
similar at comparable exposures.  Thus, the exposure associated with male rat 
STD10 may be used to establish an appropriate target exposure for human 
subjects. 
• The starting QD dose will be capped at 15 mg, which is the human equivalent dose 
for one-tenth of the STD10 in male rats in the 28-day QD administration study. 
• In monkeys, doses as high as 12 mg/kg per day given QD for 28 days were clinically 
tolerated (ie, monkeys were less sensitive than rats).  The human equivalent dose of 
12 mg/kg per day in monkeys is approximately 230 mg/day.  This dose (12 mg/kg per 
day) was associated with an unbound AUC of 6.0 µM·h in males, and 7.8 µM·h in 
females, which is at least 27-fold higher than the exposure levels predicted for the QD 
dose (15 mg) in human subjects and approximately 10-fold higher than the ceiling 
exposure for the starting QD dose. 
Figure 1: 
Determining the Part 1 Treatment Group A Starting Dose 
 


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In summary, the toxicity of INCB054329 correlates well with exposure in preclinical studies.  
Study drug administration in Treatment Group A (TGA) Cohort 1 will begin with an initial PK 
assessment using a 5 mg single dose.  Following the PK assessment, continuous administration 
will be initiated using a starting dose ranging between 2.5 mg and 15 mg, keeping subjects below 
the exposure associated with the male rat STD10 while minimizing the number of subjects 
exposed to doses that are unlikely to provide clinical benefit (see Section 4.1.1). 
1.7. 
Clinical Experience With INCB054329 in Study INCB 54329-101 
1.7.1. 
Clinical Pharmacokinetics of INCB054329 in Study INCB 54329-101 
The pharmacokinetics of INCB054329 was evaluated following single and multiple doses of 
15 mg QD to 25 mg twice daily (BID).  Plasma concentrations of INCB054329 decline in a 
mono-exponential manner with mean terminal elimination half-life of approximately 2 hours 
with a range of 1.4 to 4.5 hours across cohorts (See Figure 2).  
The dosing schema of cohorts is described in Table 1.  
Figure 2: 
INCB054329 Pharmacokinetics at Steady State for Cohorts 1 to 10 
0
4
8
1 2
1 6
2 0
2 4
0 .1
1
1 0
1 0 0
1 0 0 0
T im e  (h )
C o n c  (n M )
1 5  m g  Q D  (d a ily ) (N = 4 )
IC 5 0
IC 9 0
2 2 .5  m g  Q D  (d a ily) (N = 4 )
1 5  m g  B ID  (d a ily) (N = 5 )
3 0  m g  Q D  (d a ily ) (N = 4 )
2 2 .5  m g  B ID (d a ily ) (N = 1 )
2 2 .5  m g  B ID  (5 d /2 d )
(N = 3 )
2 2 .5  m g  B ID  (7 d /7 d ) (N = 1 )
2 2 .5  m g  B ID (4 d /3 d ) (N = 4 )
2 0  m g  B ID  (d a ily) (N = 1 )
2 5  m g  B ID  (5 d /2 d )(N = 1 )
 
Note:  The dose (ie, 15 mg QD) and schedule (ie, daily) were the starting dose and schedule of each cohort.  
Treatment schedule 5d/2d, 4d/3d, and 7d/7d were study treatments 5 days on/2 days off, 4 days on/3 days off, and 
7 days on/7 days off, respectively.  The number N refers to the number of subjects in each cohort whose PK data 
were available for this analysis (see Table 1 for the total number of subjects enrolled in each cohort at the data 
cutoff). 
The pharmacokinetics of INCB054329 is characterized by high intersubject variability, which 
resulted in overlapping average drug exposure among the cohorts, presumably arising from 
variability in metabolic clearance.  Indeed, metabolic profile of plasma samples indicate high 
metabolite burden in subjects with low exposure and parent compound and vice versa.  The 


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calculated oral clearance of individual subjects is shown in Figure 3, illustrating > 100-fold 
variability.  
Figure 3: 
INCB054329 Intersubject Variability in Pharmacokinetics Across Cohorts 1 
to 10 
0
1 0
2 0
3 0
4 0
0
2 0 0
4 0 0
6 0 0
8 0 0
1 0 0 0
C L (L /h r)
 
The exposure-response relationship indicates that the decrease in platelets, which can be 
considered a pharmacodynamics marker, is well-predicted by AUC (Figure 4), such that 
exposures higher than ~2000 nM/hour were associated with significant thrombocytopenia 
(> 100,000/mL drop in platelets).  Therefore, for optimal pharmacology and safety, it may be 
best to titrate each subject to a dose that provides an exposure of ~1500 to ~2000 nM/hour, and 
this can be achieved by monitoring the change in platelets or other safety parameters within the 
first 21 days of continuous dose administration, because in most cases, the onset of platelet 
decreasing and nadir occurred in the first 21 days of treatment. 
Figure 4: 
Maximum Platelet Change From Baseline Versus AUC on Day 1 for 
Individual Subjects Across Cohorts 1 to 10 
0
5 0 0 0
1 0 0 0 0
1 5 0 0 0
- 3 0 0
- 2 0 0
- 1 0 0
0
1 0 0
A U C 0 -in f (h r * n M )
P latelet C hange
 
Based on the high intersubject variability in pharmacokinetics and the predictable relationship 
between exposure and platelet change, the protocol was amended to allow intrasubject dose 
titration (dose escalation or de-escalation) to establish an optimal dose for subjects in Part 2 and 
Part 3 TGA and TGC of the current protocol (Amendment 2).  


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1.7.2. 
Safety and Potential Risks of INCB054329 Based on Preliminary Clinical 
Experience in Study INCB 54329-101 
The first subject was enrolled in the study on 08 JUN 2015.  As of 17 OCT 2016, 48 subjects 
with various advanced solid tumors and lymphomas have been enrolled across 11 cohorts at 
various dose and schedules (Table 1). 
Table 1: 
Study INCB 54329-101 Part 1 Cohorts 
Cohort 1 
15 mg 
QD 
Cohort 2 
22.5 mg 
QD 
Cohort 3 
15 mg 
BID 
Cohort 4 
30 mg 
QD 
Cohort 5 
22.5 mg 
BID 
Cohort 6 
22.5 mg 
BID 5/2 
Cohort 7 
22.5 mg 
BID 4/3 
Cohort 8 
22.5 mg 
BID 7/7 
Cohort 9 
20 mg 
BID 
Cohort 10 
25 mg 
BID 5/2 
Cohort 11 
25 mg 
BID 7/7 
Totala 
4 
5 
6 
5 
3 
4 
4 
3 
7 
5 
2 
48 
a Treatment schedule 5/2 indicates 5 days on and 2 days off; 4/3 indicates 4 days on and 3 days off; 7/7 indicates 7 days on and 
7 days off.  The number in the second row indicates the total number of subjects enrolled in each cohort at the data cutoff date, 
including nonevaluable subjects. 
The enrollment started in Part 1 dose escalation with the 3 + 3 design, with a starting dose of 
15 mg on a once daily (QD) schedule.  Three dose-escalation cohorts using the QD schedule had 
been completed (Cohort 1, 15mg QD; Cohort 2, 22.5 mg QD; and Cohort 4, 30 mg QD).  During 
the DLT evaluation period (Cycle 1), no DLT was observed in Cohort 1 and 2; 1 DLT 
(Grade 4 thrombocytopenia) was observed in Cohort 4.  Enrollment in Cohort 4 was not 
expanded beyond the 3 evaluable subjects, due to the fact that the study drug demonstrated a 
shorter-than-projected half-life (t½).  The mean terminal phase t½ was approximately 2 hours 
based on PK data from the 3 QD cohorts (Section 1.7.1).  Therefore, the decision was made to 
switch to a twice daily (BID) dose regimen for subsequent cohorts in order to achieve a higher 
AUC.  Two dose-escalation cohorts using the BID continuous daily dosing schedule have been 
completed (Cohort 3, 15 mg BID, and Cohort 5, 22.5 mg BID).  During the DLT evaluation 
period, no DLT was observed in Cohort 3; 1 DLT (Grade 3 thrombocytopenia with bleeding) 
was observed in Cohort 5.  All 3 subjects in Cohort 5 experienced decreased platelets, 1 with 
Grade 3 thrombocytopenia with bleeding (DLT), 1 with Grade 4 thrombocytopenia (non-DLT 
because it occurred on Cycle 2 Day 1, beyond the DLT evaluation period), and 1 with Grade 2 
thrombocytopenia.  The sponsor and all of the investigators made the decision not to expand 
Cohort 5 further (ie, not to enroll any additional subjects beyond the 3) due to the observed 
extent of the overall thrombocytopenia in the cohort. 
A decision was also made to explore intermittent dose regimens to decrease the extent of platelet 
decreasing and/or to allow platelet recovery; the goal is not to totally avoid platelet decreasing, 
because myelosuppression, mainly thrombocytopenia, is considered an on-target effect of a 
BET/BRD inhibitor, due to the primary pharmacology of the study drug. 
Three cohorts with different intermittent dose regimens were initiated in parallel and have been 
completed (Cohort 6, 22.5 mg BID 5 days on/2 days off; Cohort 7, 22.5 mg BID 4 days 
on/3 days off; Cohort 8, 22.5 mg BID 7 days on/7 days off).  During the DLT evaluation period, 
no DLT was observed in these 3 intermittent dose regimen cohorts, and all 3 dose regimens were 
determined to be tolerated.  There were no G3 or G4 thrombocytopenia in these cohorts; 
however, some subjects did experience various degrees of platelets decreasing.  The decision 
was made to further dose escalate with 2 of the 3 intermittent schedules, 5 days on/2 days off and 
7 days on/2 days off.  Cohort 10 (25 mg BID 5 days on/2 days off) and Cohort 11 (25 mg BID 


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7 days on/7 days off) were initiated and enrollments are ongoing.  At the data cutoff date, all the 
slots in Cohorts 10 and 11 have been allocated and in screening. 
Examining all the cases of platelet decreasing/thrombocytopenia (all grades and all causality) 
showed that the majority of them had an onset time around Day 8 and had their large drop in 
platelet counts between Day 8 and Day 21 during Cycle 1. 
Based on available PK data (see Section 1.7.1), a decision was made to investigate the feasibility 
of intrasubject dose titration in Part 2 Dose Titration (see Section 1.8.1 for rationale).  In order to 
determine the optimal starting dose and schedule for intrasubject dose titration, in parallel to 
exploring various intermittent dosing schedules as described above, a new cohort with the 
starting dose of 20 mg BID continuous daily dosing was initiated (Cohort 9).  It is hypothesized 
that a continuous dose regimen may provide better duration of target inhibition and thus better 
efficacy.  No DLT was observed among the first 3 evaluable subjects in Cohort 9; therefore, the 
starting dose of 20 mg BID is determined to be tolerated.  Cohort 9 will enroll a total of 
6 evaluable subjects in order to further gather safety and tolerability information with this 
starting dose to be used in Parts 2 and 3.  At the data cutoff date, 7 subjects have been enrolled 
and 5 were evaluable.  Part 1 will stop enrollment once the ongoing cohorts, Cohorts 9, 10 and 
11, complete enrollment, and no new cohort will be initiated in Part 1. 
As of 17 OCT 2016, 48 subjects received treatment, 43 of them reported at least 1 
treatment-emerging adverse event (TEAE; all grades; Table 2).  These data were derived from 
the clinical database and were not cleaned or confirmed; thus, they should be considered 
preliminary and subject to change.  The most frequently reported TEAEs (≥ 20% prevalence) 
were fatigue, nausea, decreased appetite, constipation, thrombocytopenia, anemia, abdominal 
pain, and vomiting (Table 2).  The most common AEs ≥ Grade 3 (≥ 5% prevalence) were 
thrombocytopenia, anemia, and fatigue (Table 3).  Most cases of thrombocytopenia were 
considered related to study treatment.  Anemia and fatigue were mostly not related to study 
treatment but rather disease under study.  Most adverse events were mild, improved, or resolved 
with supportive care, and did not require dose interruption or modification.  There were 33 SAE 
events reported; most were considered not related to the study drug.  Five SAEs across 
3 subjects, thrombocytopenia (4) and anemia (1), were considered related to study treatment by 
investigators. 
Table 2: 
Summary of TEAEs (≥ 20% Subjects; All Grades, All Causality) 
Event 
Totala, % 
(N = 43) 
Fatigue 
19 (44.2) 
Nausea 
18 (41.9) 
Decreased appetite 
12 (27.9) 
Constipation 
11 (25.9) 
Thrombocytopenia 
11 (25.6) 
Anemia 
10 (23.3) 
Abdominal pain 
9 (20.9) 
Vomiting 
9 (20.9) 
a These data are based on 21 SEP 2016 data extraction, not confirmed, and subject to change. 


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Table 3: 
Summary of TEAEs ≥ Grade 3 (≥ 5% Subjects; All Causality) 
Adverse Events 
Totala, % 
(N = 43) 
Thrombocytopenia 
6 (14.0) 
Anemia 
5 (11.6) 
Fatigue 
3 (7.0) 
a These data are based on 21 SEP 2016 data extraction, not confirmed, and subject to change. 
1.8. 
Rationale for Intrasubject Dose Titration in Part 2 
According to the current available PK data (Section 1.7.1), there were larger than expected 
intersubject variabilities in drug exposure among all the subjects treated with the same starting 
dose, and this larger variability can be mostly explained by the larger than usual variability in 
metabolic clearance (Figure 3).  This occurred in every dose level/cohort tested so far, resulting 
in nonlinear and overlapping population PK among different dose levels/cohorts, which make it 
difficult or almost impossible to evaluable safety and tolerability, MTD, and PAD on a cohort by 
cohort/dose level by dose level basis.  Therefore, it was decided to stop 3 + 3 dose escalation in 
Part 1 TGA and to not open Part 1 TGC, which is hypothesized to have similar issues as in TGA.  
Because cytopenia is part of the disease manifestation of subjects in Part 1 TGB (acute leukemia, 
MDS/MPN, and MF) and thrombocytopenia will not be dose limiting in Part 1 TGB, it is 
hypothesized that subjects in Part 1 TGB will tolerate doses ≥ 20 mg BID; thus, the 3 + 3 dose 
escalation in Part 1 TGA will continue to determine PAD/MTD or the safe tolerable RP2D dose.  
Therefore, TGB will open in Part 1 dose escalation with Amendment 2. 
There was a strong correlation between the level of drug exposure and the severity of platelet 
decrease (Figure 4).  The majority of the cases of platelets decreasing occurred during the first 
cycle.  Therefore, the extent of platelet decreasing at the end of the first cycle can be used as a 
surrogate for drug exposure and as one of the criteria to determine the proper next dose level in 
the disease types where thrombocytopenia is usually not part of the disease manifestation. 
Because myelosuppression, including thrombocytopenia, is based on primary 
pharmacology/mechanism of action of BRD inhibition, it is hypothesized that the dose would be 
below optimal if no platelet decreasing is observed at that dose level. 
Based on the above, it is reasonable to employ intrasubject dose modulation to evaluate safety 
and tolerability on an individual basis in order to achieve an optimal drug exposure at which a 
certain level of platelet decreasing is observed and can be safely and adequately managed.  The 
tolerated level of platelet decreasing will be based on disease type/treatment group, and each 
treatment group will have different intrasubject dose-escalation criteria (Section 4.1.2.1).  Also, 
timed PK samples will be collected every time dose escalation occurs.  Based on correlation 
between AUC and platelet level change (Figure 4), it is hypothesized that the optimal AUC to be 
achieved will be approximately 1500 to 2000 nM/hour, and this can be achieved by monitoring 
the change in platelets or other safety parameters.  With intrasubject dose titration, it is possible 
to achieve an optimal dose and benefit/risk ratio on individual bases to maximize the chance for 
efficacy. 


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1.8.1. 
Part 2 Dose Titration 
The starting dose for both TGA and TGC in Part 2 will be the highest tolerated dose with 
continuous BID dose administration identified in Part 1 TGA; based on available data at the data 
cutoff date, a starting dose of 20 mg BID continuous dose administration  will be used.  At the 
end of Cycle 1, if dose titration criteria are met (Section 4.1.3), the dose may be increased to 
25 mg BID on Day 1 of Cycle 2.  Dose escalation by no more than 5 mg BID increments may be 
permitted after each subsequent cycle of treatment if the subject continues to meet the dose 
titration criteria.  Part 2 may also explore 1 or more alternate dose regimens that have been 
investigated in Part 1 (ie, alternate dose/schedules from Cohorts 6-8 and 10-11) or explore a 
starting dose < 20 mg BID, if 20 mg BID continuous dosing is considered not optimal pending 
emerging data. 
Dose interruptions, reductions, or termination may be implemented based on toxicity as 
described in the Protocol (Section 5.6).  Treatment will continue until treatment discontinuation 
criteria or study withdrawal criteria are met (Section 5.6.2 and Section 5.7) 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
• To evaluate the safety and tolerability of INCB054329 in subjects with advanced 
malignancies. 
2.1.2. 
Secondary Objectives 
• To evaluate the PK and PD of INCB054329 in subjects with advanced malignancies. 
• To evaluate preliminary efficacy of INCB054329 in subjects with advanced 
malignancies. 
 
2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoint 
• Safety and tolerability will be assessed by monitoring frequency, duration, and 
severity of AEs; through physical examinations; by evaluating changes in vital signs 
and ECGs; and through clinical laboratory blood and urine sample evaluations. 
2.2.2. 
Secondary Endpoints 
• Pharmacokinetics of INCB054329, including Cmax, Tmax, Cmin, AUC0-t, and Cl/F at 
Days 1, 2, 8, 15, and 16 of Cycle 1, for subjects in Parts 1, 2 and 3 and any cycle 
where dose escalation occurs. 


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• Pharmacodynamic profile of INCB054329 using a whole blood PD assay. 
• Evaluation of objective response rate (ORR), progression-free survival (PFS), 
duration of response (DOR), and overall survival (OS) for subjects in Part 2 and 
Part 3. 
3. 
SUBJECT ELIGIBILITY 
3.1. 
Study Population 
Subjects with advanced malignancies who have failed at least 1 prior therapy or have no standard 
treatment options demonstrated to provide clinical benefit or who are intolerable to or refuse 
further standard treatments will be enrolled. 
3.1.1. 
Part 1 Dose Escalation 
• Treatment Group A:  Any advanced solid tumor or lymphoma. 
• Treatment Group B (TGB):  Acute leukemia, myelodysplastic syndrome (MDS), 
myelodysplastic/myeloproliferative neoplasms (MDS/MPN; including atypical 
chronic myeloid leukemia [aCML], chronic myelomonocytic leukemia [CMML], 
MDS/MPN unclassifiable [MDS/MPN-U], and refractory anemia with ring 
sideroblasts and thrombocytosis [RARS-T]), and myelofibrosis (MF). 
3.1.2. 
Part 2 Dose Titration 
• TGA:  Any advanced solid tumor or lymphoma. 
• TGC:  MM. 
3.1.3. 
Part 3 Dose Expansion 
• TGA:  Diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (with c-MYC 
translocations), CRC, NSCLC, PanC, CRPC, mBC, ovarian cancer, NMC, other 
tumor with any pathway alteration relevant to BET protein signaling, such as MYC or 
SHH pathway activation. 
• TGB:  AML, MDS, MDS/MPN (including aCML, CMML, MDS/MPN-U, and 
RARS T), or MF. 
• TGC:  MM. 


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3.2. 
Subject Inclusion Criteria 
A subject who meets all of the following criteria may be included in the study:   
1. Men and women aged 18 years or older. 
2. Histologically confirmed diagnosis of advanced malignancy that, for Part 3 only, is 
measurable or evaluable: 
Part 1 Dose Escalation 
a. TGA:  Any advanced solid tumor or lymphoma (Hodgkin or non-Hodgkin). 
b. TGB:  Acute leukemia, MDS, MDS/MPN, or MF. 
Part 2 Dose Titration 
c. TGA:  Any advanced solid tumor or lymphoma. 
d. TGC:  MM. 
Part 3 Dose Expansion 
e. TGA:  Diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (with c-MYC 
translocations), CRC, NSCLC, PanC, CRPC, mBC, ovarian cancer, NMC, other 
tumor with any pathway alteration relevant to BET protein signaling, such as MYC or 
SHH pathway activation. 
f. TGB:  AML, MDS, MDS/MPN (including aCML, CMML, MDS/MPN-U, and 
RARS T), or MF. 
g. TGC:  MM, defined as 1 or more of the following: 
− Serum M-protein ≥ 0.5 g/dL. 
− Urine M-protein ≥ 200 mg/24 hours. 
− Serum free light chain (FLC):  involved FLC level ≥ 10 mg/dL provided serum 
FLC ratio is abnormal. 
3. Progressed following at least 1 line of prior therapy and there is no further established 
therapy that is known to provide clinical benefit (including subjects who are intolerant to 
or refuse the established therapy). 
a. MM subjects must have relapsed from or have been refractory to ≥ 2 prior treatment 
regimens, including proteasome inhibitor and an immunomodulatory drug. 
b. AML subjects are eligible if they have relapsed and/or refractory disease; if they are 
≥ 65 years of age and are not candidates for or have refused standard chemotherapy; 
or if they have no established standard of care that is known to provide clinical 
benefit in the judgement of the investigator. 
c. MF subjects must be resistant, refractory, or intolerant to ruxolitinib therapy. 
4. Baseline archival tumor specimen available.  For solid tumors and lymphoma, a tumor 
block or 25 unstained slides (15 minimum) from biopsy or resection of primary tumor or 
metastasis that are ≤ 2 years old (≤ 1 year old and after completion of last treatment is 
preferred), or willingness to undergo a pretreatment tumor biopsy to obtain the specimen.  
For acute leukemia, MDS, MDS/MPN, MF, or MM, at least 1 mL archival bone marrow 
aspirate material ≤ 1 year old and obtained since completion of the prior treatment 
regimen, or willingness to undergo a pretreatment bone marrow biopsy/aspirate to obtain 
the specimen.  If a biopsy is not possible or contraindicated, or the tissue requirement 


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cannot be satisfied, this requirement may be waived with approval from the medical 
monitor. 
5. Life expectancy > 12 weeks. 
6. ECOG performance status (Appendix C): 
a. Part 1 and Part 2:  0 or 1. 
b. Part 3:  0, 1, or 2. 
7. Women of childbearing potential (defined as women who have not undergone surgical 
sterilization with a hysterectomy and/or bilateral oophorectomy, and are not 
postmenopausal [as defined as ≥ 12 months of amenorrhea]) must have a negative serum 
pregnancy test at screening and immediately before the first dose of study drug. 
8. Men and women of childbearing potential must agree to take appropriate precautions to 
avoid pregnancy or fathering children (with at least 99% certainty) from screening 
through 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. 
9. Ability to comprehend and willingness to sign an Informed Consent Form (ICF). 
3.3. 
Subject Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Inadequate organ function demonstrated by any of the following: 
Part 1 Dose Escalation 
 
Laboratory Parameter 
TGA 
a. 
Hemoglobin (g/dL) 
< 10.0 
b. 
Platelet count (× 109/L) 
< 100 
c. 
Absolute neutrophil count (× 109/L) 
< 1.5 
Note: No specific hematologic exclusion criteria applicable for TGB. 
d. Conjugated bilirubin > upper limit of normal (ULN; need only be tested if total 
bilirubin exceeds > 1.5 × ULN). 
e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.2 × ULN. 
f. Creatinine clearance < 50 mL/min based on Cockroft-Gault formula (< 30 mL/min 
for MM) or 24-hour urinalysis. 
Part 2 Dose Titration and Part 3 Dose Expansion 
 
Laboratory Parameter 
TGA 
TGC 
g. 
Hemoglobin (g/dL) 
< 9.0 
< 8.0 
h. 
Platelet count (× 109/L) 
< 150 
< 100 
i. 
Absolute neutrophil count (× 109/L) 
< 1.5 
< 1.0 
Note:  No specific hematologic exclusion criteria apply for TGB in Part 2 and Part 3. 
j. Total bilirubin ≥ 1.5 × institutional ULN (total bilirubin > 1.5 × ULN is acceptable if 
direct bilirubin ≤ 1.2 × ULN or with a diagnosis of Gilbert's syndrome). 


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k. AST and ALT ≥ 2.5 × ULN, or > 5 × ULN for subjects with extensive liver 
involvement. 
l. Creatinine clearance < 40 mL/min based on Cockroft-Gault formula (< 30 mL/min 
for MM) or 24-hour urinalysis. 
2. Receipt of anticancer medications, antibodies, biologic, or investigational drugs within 
the following interval before the first administration of study drug: 
a. < 6 weeks for mitomycin-C or nitrosoureas. 
b. < 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any 
indication). 
c. < 28 days for any antibodies or biological therapies. 
d. < 5 half-lives for all other nonbiologic, anticancer medications, or sponsor approval. 
e. The following are allowed: 
− Hydroxyurea for controlling proliferative disease and low-dose corticosteroids 
(prednisone or the equivalent ≤ 10 mg per day). 
− Subjects with CRPC should be maintained on androgen deprivation, chemical or 
surgical, with a castrate level of testosterone documented (< 50 ng/dL) during the 
screening period. 
− 
 
 
 
 
− Part 2 TGC and Part 3 TGC:  Receipt of less than 160 mg dexamethasone within 
14 days before receiving the first dose of study drug. 
− Denosumab and zoledronic acid permitted to treat cancer-related bone diseases 
such as subjects with prostate or breast cancer. 
3. Unless approved by the medical monitor, may not have received an allogeneic 
hematopoietic stem cell transplant within 6 months before treatment, or have active 
graft-versus-host disease following allogeneic transplant, or have received 
immunosuppressive therapy (including, but not limited to, cyclosporine, tacrolimus, 
mycophenolate mofetil, or corticosteroids [in excess of 10 mg prednisone equivalent per 
day]) following allogeneic transplant within 2 weeks of Cycle 1 Day 1. 
4. Unless approved by the medical monitor, may not have received autologous 
hematopoietic stem cell transplant within 3 months before treatment. 
5. Prior receipt of any BET inhibitor.  
6. Type 1 diabetes or uncontrolled Type 2 diabetes  
7. HbA1c of > 8% (all subjects will have HbA1c test at screening).  
8. Prior radiotherapy within 2 weeks before first dose of study drug.  Palliative radiation 
treatment to noncentral nervous system, nonindex, or bone lesions performed less than 
2 weeks before treatment initiation may be considered with medical monitor approval (a 
1-week washout period is usually permitted). 
9. Known human immunodeficiency virus infection. 


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10. Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as defined in 
Section 7.4.6.2.   
11. Chronic or current active uncontrolled infectious disease requiring systemic antibiotic, 
antifungal, or antiviral treatment. 
12. Untreated brain or CNS metastases or brain/CNS metastases that have progressed (eg, 
evidence of new or enlarging brain metastasis or new neurological symptoms attributable 
to brain/CNS metastases).  Subjects with previously treated and clinically stable 
brain/CNS metastases and off all corticosteroids for ≥ 2 weeks are eligible.  Primary CNS 
lymphoma will only be permitted in Part 3. 
13. History or presence of abnormal electrocardiogram (ECG) which, in the investigator's 
opinion, is clinically meaningful.  A screening QTc interval of > 470 milliseconds is 
excluded.  For subjects with an intraventricular conduction delay (QRS interval 
≥ 120 msec) the JTc interval may be used in place of the QTc with sponsor approval.  
Subjects with left bundle branch block are excluded.  Subjects with QTc prolongation due 
to a pacemaker may enroll if the JT is normal or with medical monitor approval. 
14. History of clinically significant or uncontrolled cardiac disease, including unstable 
angina, acute myocardial infarction (MI), New York Heart Association (NYHA) Class III 
or IV congestive heart failure, or clinically significant arrhythmias not controlled by 
medication.  Subjects with a pacemaker and well-controlled rhythm for at least 1 month 
before first dose of study medication will be allowed. 
15. Known additional malignancy that is progressing or requires active treatment.  
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, 
or in situ cervical cancer that has undergone potentially curative therapy. 
16. History of allergic reactions to INCB054329, similar compounds, or the excipients of 
INCB054329. 
17. Unable or unwilling to swallow INCB054329 or significant GI disorder that could 
interfere with the absorption, metabolism, or excretion.  
18. Subjects unwilling to be transfused with blood components.  
19. Current condition requiring the use of a prohibited concomitant medication (see 
Section 5.10). 
20. Inadequate recovery from toxicity and/or complications from a major surgery before 
starting therapy. 
21. Women who are pregnant or nursing. 
22. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug and attending required study visits, 
pose a significant risk to the subject, or interfere with interpretation of study data. 
23. Any unresolved toxicity ≥ Grade 2 from previous anticancer therapy except for stable 
chronic toxicities (≤ Grade 2) not expected to resolve, such as stable Grade 2 peripheral 
neuropathy. 
24. Any sign of clinically significant bleeding. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is an open-label, dose-escalation study of INCB054329 in subjects with advanced 
malignancies.  Subjects will receive QD doses of INCB054329 continuously in 21-day cycles.  
Alternative schedules may be assessed if indicated by safety, PK, or PD data.  The study will be 
conducted in 3 parts (See Figure 5). 
• Part 1 Dose Escalation will determine the maximum tolerated dose (MTD) of 
INCB054329 and/or a tolerated dose that reaches the desired target inhibition (ie, a 
pharmacologically active dose [PAD]). 
• Part 2 Dose Titration will determine the feasibility of intrasubject dose titration using 
Protocol-defined criteria. 
• Part 3 Dose Expansion will evaluate the doses and schedules selected in Part 1 and 
Part 2 in subjects with select tumor types postulated to be particularly susceptible to 
BET inhibition (see inclusion criteria, Section 3.2). 
Figure 5: 
Study Design 
 


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4.1.1. 
Part 1 Dose Escalation 
The study will begin with open-label dose escalation in TGA, using a 3 + 3 design to determine 
the tolerated dose over a 21-day cycle.  Initially, subjects in Cohort 1 will receive a single dose 
of INCB054329 followed by a timed PK assessment to confirm exposure approximately 1 week 
before continuous administration is initiated (referred to as Day 0).  The starting dose for 
continuous administration will be determined based on the exposures assessed at this PK 
assessment; this dose will be no higher than 15 mg. 
The dose-escalation portion of the study will be conducted in the following treatment groups:  
• Treatment Group A (TGA) will include subjects with any advanced solid tumor or 
lymphoma. 
• Treatment Group B (TGB) will include subjects with acute leukemia, MDS, 
MDS/MPN, and MF. 
Escalation will begin with Cohort 1 (including the Day 0 single-dose PK assessment) in TGA. 
The Day 0 PK assessment will be used to establish exposure for the initial dose of 5 mg.  This 
exposure will determine the starting dose for the subject on Day 1, according to the formula 
described in Section 1.6.  It is anticipated that this will result in a 15 mg QD starting dose.  In the 
event that the 5 mg exposure projects a safe starting dose lower than 15 mg for a given subject, 
this subject will receive the calculated safe starting dose rounded down to the closest tablet 
strength.  Subsequent subjects in Cohort 1 will not receive a higher starting dose than any 
previous subject.  Thus subjects will have a starting dose chosen to produce a projected unbound 
exposure of ≤ 0.7 μM·h (based upon the subject with the highest exposure).  Previously enrolled 
subjects may continue at the dose at which they began on Day 1, because this dose has already 
been confirmed to result in an acceptable exposure in that subject.  The safety data (eg, 
dose-limiting toxicities [DLTs]) from all subjects in Cohort 1 will be evaluated as a group for 
purposes of establishing the safety for the dose level within the 3 + 3 design.  The dose level for 
the cohort will be considered to be that of the subject receiving the lowest starting dose in 
Cohort 1. 
Treatment Group B will begin enrollment at the PAD (plasma concentration exceeding the PK 
which is projected to inhibit c-Myc level ≥ 50% for approximately 10 hours) or a tolerated dose 
identified in TGA at the discretion of the sponsor, and dose escalation will proceed 
independently to an MTD in each treatment group using a 3 + 3 design.  Treatment Group C will 
open in Part 2 instead of Part 1 (see rationale in Section 1.8).  Alternative dose regimen(s) may 
be explored, such as BID or intermittent dose regimens, pending emerging PK, PD, and safety 
data.  If there is a distinct discrepancy in tolerability among different disease types within the 
same treatment group, additional disease-specific dose-escalation schedules may be initiated.   
Each dose-escalation cohort will initially enroll at least 3 subjects.  If no DLTs are observed in 
the initial 3 subjects, the next cohort will begin enrollment at the next highest dose level.  
Subjects not receiving at least 80% of the planned study drug doses during the first cycle (ie, 
≥ 17 of 21 doses during QD dosing or 34 of the 42 BID doses in Cycle 1) will be considered 
nonevaluable for purposes of determining the MTD (unless due to a DLT) and will be replaced.  
Cohorts may include an additional subject to ensure that enough evaluable subjects reach 
Day 21. 


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Dose increases between cohorts may be up to 2-fold until a Grade 2 toxicity is observed, after 
which dose increases will be limited to no more than 50% above the previous level.  Exceptions 
are toxicities with a clear alternative explanation or transient abnormal laboratory values without 
clinically significant signs or symptoms.  If 1 DLT (see Section 5.4) is observed in the first 
3 subjects in a cohort, at least 3 additional subjects will be enrolled in that cohort.  If a DLT 
occurs in one-third or more of the total cohort (ie, ≥ 2 of 6 subjects), then the MTD will be 
deemed to have been exceeded, and the next lower dose level will be deemed to be the tolerated 
dose.  Thus, the MTD will be defined as 1 dose level below that at which one-third or more of 
subjects in a particular cohort report DLTs.  If the Cohort 1 dose is not tolerated (≥ 2 of 
6 subjects report a DLT), dose de-escalation will be considered in order to identify a tolerated 
dose.  The next tested dose will be reduced by at least 25% (depending upon emerging PK and 
safety data).  Up to 4 total de-escalations may be explored if plasma concentrations are within 
pharmacologically active range. 
If a PAD (plasma concentration expected to inhibit c-Myc level ≥ 50% for approximately 
10 hours) is reached before identifying the MTD, the PAD may be selected for use in the 
expansion cohort (Part 3), at the discretion of the sponsor.  In the event that unique toxicities are 
observed relative to tumor type, the sponsor may elect to explore a split dose escalation to 
identify a category-specific MTD or PAD (eg, if the data suggest a different tolerability for 
lymphoid malignancies vs solid tumors).  The sponsor may implement alternate administration 
schedules or alternate formulations depending on PK, PD, and safety results.  Individual subjects 
within each cohort will undergo reductions/interruptions in INCB054329 administration 
according to prescribed safety parameters. 
4.1.2. 
Part 2 Dose Titration 
Due to emerging PK and PD data from the ongoing INCB 54329-101 study Part 1 TGA 
(Sections 1.7.1 and 1.7.2; larger than expected intersubject variability in drug exposure), Part 2 
will enroll 2 treatment groups to investigate the feasibility of intrasubject dose titration with 
Protocol-defined criteria (Section 4.1.2.1).  Part 2 TGA will enroll advanced solid tumors and 
lymphomas; Part 2 TGC will enroll multiple myeloma (MM).  The starting dose will be the 
highest tolerated dose with continuous BID dose administration identified in Part 1 TGA.  At the 
data cutoff date, the highest tolerated dose with continuous dose administration identified in 
Part 1 TGA was 20 mg BID, which will be used as the starting dose for Part 2 TGA and TGC; an 
alternative starting dose may be chosen pending emerging data.  Part 2 TGA and TGC will 
simultaneously enroll at least 5 subjects and up to approximately 10 subjects per treatment 
group.  At the end of Cycle 1, if dose titration criteria are met (Section 4.1.2.1), the dose may be 
increased to 25 mg BID on Day 1 of Cycle 2.  Dose escalation by ≤ 5 mg BID increments may 
be permitted after each subsequent cycle of treatment if the subject continues to meet the 
dose-escalation criteria.  Dose interruptions, reductions, or termination may be implemented as 
described in Section 5.6, Dose Modifications.  Once a treatment group is completed in Part 2, 
that individual treatment group may move into Part 3 without the other treatment group being 
completed in Part 2.  Part 2 may also explore 1 or more alternate dose regimens that has been 
investigated in Part 1 or may explore a starting dose of < 20 mg BID, if 20 mg BID dose 
administration is considered not optimal pending emerging data from Part 2. 


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4.1.2.1. 
Dose Titration Criteria  
Subjects must meet all the following criteria for dose escalation, including the ones applicable to 
all treatment groups (TGA/TGC) and the ones specific to each treatment group as outlined in the 
following: 
Dose titration applicable to TGA/TGC: 
• The subject must have received treatment for at least one 21-day cycle or at least 80% 
of the prescribed doses (34 of the 42 BID doses or ≥ 17 of the 21 days of treatment) 
during the dose-escalation evaluation period. 
• Each dose escalation is limited to ≤ 5 mg BID. 
• The Protocol eligibility criteria are met at the time of dose escalation. 
• The subject does not meet any DLT criteria (Section 5.5). 
• The subject does not meet any treatment discontinuation criteria (Section 5.7). 
• The subject is willing to submit to the key PK and safety assessments as required in 
Cycle 1, including PK, ECGs, safety laboratory assessments, targeted physical 
examinations, and vital signs.  
• In the opinion of the investigator, the subject does not have any concurrent condition 
or circumstance that would complicate the dose escalation or PK sampling or would 
pose increased risk to the subject. 
Dose titration applicable to TGA only: 
• Platelet level change from the baseline or the previous dose-escalation decision is 
≤ 30% drop AND the NADIR during the evaluation period is >100 × 109/L. 
Dose titration applicable to TGC only: 
• Platelet level change from the baseline or the previous dose escalation decision is 
≤ 30% drop AND the NADIR during the evaluation period > 75 × 109/L. 
4.1.3. 
Part 3 Dose Expansion 
Part 3 of the study will evaluate the dose selected in Part 1 and Part 2 in select tumor types at 
their respective recommended Phase 2 doses (RP2Ds); based on available data, a dose up to the 
MTD may be selected as the RP2D for use in each expansion cohort by the sponsor and 
investigators. 
Part 3 TGA will enroll up to approximately 135 subjects with specified solid tumors or 
lymphoma, with a goal of enrolling 5 subjects per tumor type.  If ≥ 1 out of 5 of the select tumor 
types demonstrates clinically meaningful benefit, enrollment in that select tumor type will then 
continue to enroll up to approximately 15 subjects with that tumor type.  If activity is not 
demonstrated, no further subjects will be treated within that particular tumor type.  Tumor types 
are as follows:  DLBCL, Burkitt lymphoma, CRC, NSCLC, PanC, CRPC, mBC, ovarian cancer, 
and NMC.  An additional group of up to approximately 20 subjects with any tumor known to 
have c-MYC or SHH pathway activation will also be enrolled, of whom no less than 5 will have 
DLBCL with a known aberration of MYC and BCL2 and/or BCL6 (ie, "double-hit" DLBCL) or 


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B-cell lymphoma, unclassifiable (BCLU) with features intermediate between DLBCL and 
Burkitt lymphoma.  This totals approximately 155 subjects for Part 3 TGA. 
Part 3 TGB will enroll up to 60 subjects with AML, MDS, MDS/MPN, or MF. 
Part 3 TGC will enroll up to approximately 15 subjects with measureable/evaluable MM. 
Individual dose modifications (dose interruption, reduction, or termination) will be permitted 
according to Protocol-defined safety parameters.  Subjects will continue to receive INCB054329 
in 21-day cycles until withdrawal criteria are met (eg, toxicity, disease progression).  Part 3 TGA 
(solid tumors and lymphoma) will also include a food-effect study for the first 12 subjects 
enrolled. 
4.2. 
Measures Taken to Avoid Bias 
This is an open-label study; no formal 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. 
4.3. 
Number of Subjects 
Part 1:  Up to approximately 90 subjects; Part 2:  Up to approximately 20; Part 3:  Up to 
approximately 230 subjects (TGA, 155; TGB, 60; and TGC, 15). 
4.4. 
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 IRB/IEC in writing of the 
study's completion or early termination, and send a copy of the notification to the sponsor or 
sponsor's designee and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, if required by regulatory decision, or upon 
review of emerging data.  If the study is terminated prematurely, the sponsor will notify the 
investigators, the IRBs and IECs, and regulatory bodies of the decision and reason for 
termination of the study. 
5. 
TREATMENT 
5.1. 
Treatment Groups and Administration of Study Drug 
In this study, subjects will be enrolled into Part 1, Part 2, Part 3 as described previously, with all 
subjects receiving INCB054329 (ie, the study drug).  Subjects will self-administer study drug at 
home, except on days when PK is assessed, using an oral QD/BID regimen that will vary by 
cohort, and will be prescribed and managed by the study investigator.  One cycle will be defined 
as 21 continuous days of planned study treatment; subjects will receive treatment in continuous 
cycles unless interrupted for safety reasons. 


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5.1.1. 
Study Drug 
INCB054329 drug product is formulated as immediate release (IR) tablets in strengths of 2.5 mg 
and 15 mg.  The tablets of both strengths are round and white to off-white in color and contain 
the active drug substance along with the excipients microcrystalline cellulose, sodium starch 
glycolate, and magnesium stearate.  Study drug tablets are packaged in high-density polyethylene 
(HDPE) bottles; no preparation is required.  Bottles should be stored at room temperature, 15°C 
to 30°C (59°F to 86°F) and closed tightly to protect the tablets from humidity.  See Section 10.2 
for details regarding the accountability, handling, and disposal of study drug.  All Incyte 
investigational product will be labeled with the following statement, "Caution:  New Drug—
Limited by the United States law to investigational use," or in accordance with local regulatory 
requirements as applicable. 
5.1.2. 
Administration Instructions and Treatment Compliance 
Subjects should be counseled by the investigator to maintain strict adherence to the study 
regimen as prescribed, and to keep a record of any missed doses.  The subject will be instructed 
to bring all unopened, empty, and opened/partially used bottles of study drug to each study visit, 
at which time compliance will be assessed (see Section 7.8.2). 
5.2. 
Randomization and Blinding 
Not applicable. 
5.3. 
Duration of Treatment and Subject Participation 
Up to 28 days for screening, continuous treatment in consecutive 21-day cycles as long as 
subjects are receiving benefit and have not met any criteria for study withdrawal, and 30 to 
37 days for safety follow-up.  It is estimated that an individual subject will participate for 
approximately 4 to 6 months on average (see Withdrawal Criteria, Section 5.7.1). 
5.4. 
Treatment Compliance 
Treatment compliance with all study-related medications and procedures should be emphasized 
to the subject by the site personnel, and appropriate steps should be taken to optimize compliance 
during the study.  Compliance with INCB054329 will be calculated, by the sponsor, based on the 
drug accountability documented by the site staff and monitored by the sponsor/designee (tablet 
counts).  Instructions for subjects and details for assessing compliance are provided in 
Section 7.8.2). 
5.5. 
Dose-Limiting Toxicity and Maximum Tolerated Dose 
Dose-limiting toxicity will be defined as any of the toxicities in Table 4 occurring up to and 
including Day 21 in subjects enrolled in Part 1.  In Part 2 and Part 3, DLTs will also be evaluated 
as part of the dose-titration criterion.  The DLTs include all AEs of the specified grades, 
regardless of investigator assessment of causality to the investigational product.  Only AEs with 
a clear alternative explanation (eg, due to disease progression) or transient laboratory values 
without associated clinically significant signs or symptoms (as determined by the investigator) 
can be deemed non-DLT. 


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Individual subject dose reductions may be made based on events observed at any time during 
treatment with INCB054329; however, for the purposes of dose cohort escalation/de-escalation, 
expanding a dose cohort, and determining the MTD, decisions will be made based on events that 
are observed from the Cycle 1 Day 1 through and including the final day of Cycle 1 (Day 21).  A 
lower MTD may subsequently be determined based on relevant toxicities that become evident 
after Day 21.  All DLTs will be assessed by the investigator using the current CTCAE v4.03 
criteria (NCI 2010). 
Table 4: 
Definition of Dose-Limiting Toxicity and Maximum Tolerated Dose 
DLTs Include the Following 
Nonhematologic DLTs  
• Any ≥ Grade 3 nonhematologic toxicity EXCEPT: 
- Transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or 
symptoms.  
- Nausea, vomiting, and diarrhea adequately controlled with medical therapy within 48 hours.  
- Asymptomatic changes in fasting cholesterol and triglycerides. 
- An event clearly associated with the underlying disease, disease progression, a concomitant 
medication, or comorbidity.  
- Singular or nonfasting elevations in blood glucose (ie, blood glucose excursions will be considered 
toxicities if fasting blood glucose is elevated on 2 separate occasions). 
Hematologic DLTs (TGA and TGC Only) 
• Grade 3 thrombocytopenia with bleeding requiring transfusion of packed red blood cells. 
• Grade 4 thrombocytopenia. 
• Febrile neutropenia (absolute neutrophil count < 1.0 × 109/L and fever > 101°F/38.5°C). 
• Grade 4 neutropenia that does not recover to ≤ Grade 2 in ≤ 7 days after interrupting study drug. 
• Grade 4 anemia. 
(Hematology results may be repeated once within 72 hours to confirm the result). 
Hematologic DLTs (TGB Only) 
• Grade 4 thrombocytopenia persisting for more than 6 weeks after initiation of treatment in subjects 
whose bone marrow assessment showed less than 5% blasts and no significant dysplasia. 
• Grade 4 neutropenia persistent for more than 6 weeks after initiation of treatment in subjects whose 
bone marrow assessment showed less than 5% blasts and no significant dysplasia. 
• Given the high frequency of prevalence of disease-related cytopenias and infectious complications for 
subjects in TGB, especially in AML and high-risk MDS population, events related to underlying 
disease, including but not limited to bleeding, infection, and febrile neutropenia, are not considered 
DLTs unless severity or duration is longer than that expected with standard-of-care treatment. 
MTD 
• MTD will be defined as 1 dose level below that at which ≥ one-third of subjects in a particular cohort 
report DLTs.  Dose-limiting toxicity will be defined as the any of the toxicities in this table occurring 
up to and including study Day 21 for Cycle 1 and any cycle where dose escalation occurs. 


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Dose-limiting toxicities will be followed until resolved to baseline or until stabilized for a 
minimum of 4 weeks.  During follow-up, subjects should be seen as often as medically indicated 
to assure safety.  In all cases, investigators are free to employ any measures or concomitant 
medications, following discussion with the sponsor (whenever possible), necessary to optimally 
treat the subject. 
5.6. 
Dose Modifications 
Subjects will be assigned a starting dose based upon the cohort in which they are enrolled.  Dose 
reductions for safety, restarts, or increases are to follow the guidance in this section. 
5.6.1. 
Interruption and Restarting of Study Drug 
Treatment with INCB054329 may be delayed up to 2 weeks (14 days) to allow for resolution of 
toxicity.  Subjects may resume treatment if no medical condition or other circumstance exists 
that, in the opinion of the investigator, would make the subject unsuitable for further 
participation in the study.  The treating investigator should contact the sponsor to discuss the 
case of any subject whose treatment has been delayed for more than 14 days before restarting 
treatment with INCB054329. 
Because subjects may enter the study with extensive pretreatment and/or severe bone marrow 
infiltration by the primary disease, these dose reduction rules are provided as guidelines (see 
Table 5).  Individual decisions regarding dose reduction should be made using clinical judgment 
and in consultation with the sponsor's medical monitor, taking into account relatedness of the AE 
to the study drug and the subject's underlying condition.  Adverse events that have a clear 
alternative explanation or transient (≤ 72 hours) abnormal laboratory values without associated 
clinically significant signs or symptoms may be exempt from dose-reduction rules. 
Table 5: 
Guidelines for Interruption and Restarting of Study Drug 
CHEMISTRY 
Adverse Event 
Action Taken 
• AST and/or ALT is > 3.0 × ULN AND 
< 5.0 × ULN for > 7days, OR 
• AST and/or ALT is > 5.0 AND < 20 × ULN. 
Note:  In subjects with liver metastasis-related 
elevations at baseline, contact sponsor to discuss 
clinical management and possible dose 
reductions. 
1. Interrupt study drug up to 2 weeks (14 days) until the toxicity 
has resolved to ≤ Grade 1 except by approval of the medical 
monitor. 
2. Restart study drug at same dose.  Monitor as clinically 
indicated.  
NB:  If criteria for dose interruption met again, upon restart of 
study drug, repeat Step 1, and restart study drug at next lower dose 
(or at 25% reduction, rounded down to the nearest strength).  
• ALT > 3.0 × ULN, ALP < 2 × ULN, and 
bilirubin ≥ 2.0 × ULN (Hy's Law) and no 
other immediately apparent possible cause of 
aminotransferase elevation and 
hyperbilirubinemia, including, but not limited 
to, viral hepatitis, pre-existing chronic or 
acute liver disease, or the administration of 
other drug(s) known to be hepatotoxic. 
1. Discontinue study drug. 


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Table 5: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
HEMATOLOGY 
Parameter 
Treatment Group/ 
Expansion Cohort 
Adverse 
Event 
Action Taken 
Platelet 
count 
(× 109/L) 
Part 1 TGA 
50 to 
< 75 
1. Hold until resolved to ≥ 75. 
2. Restart study drug at same dose and monitor. 
< 50 
1. Hold until resolved to ≥ 75. 
2. If recovery to ≥ 75 in ≤ 7 days, restart study drug at same 
dose and monitor.  If recovery to ≥ 75 in > 7 days, restart 
study drug at next lower dose and monitor. 
Part 2 and Part 3 
TGA and TGC 
25 to 
< 50 
1. Hold until resolved to ≥ 50. 
2. Restart study drug at same dose and monitor. 
< 25 
1. Hold until resolved to ≥ 50. 
2. If recovery to ≥ 50 in ≤ 7 days, restart study drug at same dose 
and monitor.  If recovery to ≥ 50 in > 7 days, restart study 
drug at next lower dose and monitor. 
Part 1 and Part 3 TGB 
 
Manage as per institutional standard relevant to the underlying 
disease.  Consult with the medical monitor for management 
outside of the institutional standard. 
Absolute 
neutrophil 
count 
(× 109/L) 
Part 1 TGA 
< 1.0 
1. Hold until resolved to ≥ 1.0. 
2. If recovery to ≥ 1.0 in ≤ 7 days, restart study drug at same 
dose and monitor.  If recovery to ≥ 1.0 in > 7 days, restart 
study drug at next lower dose and monitor. 
Part 2 and Part 3 
TGA and TGC 
< 0.5 
1. Hold until resolved to ≥ 0.5. 
2. If recovery to ≥ 0.5 in ≤ 7 days, restart study drug at same 
dose and monitor.  If recovery to ≥ 0.5 in > 7 days, restart 
study drug at next lower dose and monitor. 
Part 1 and Part 3 
TGB 
Manage as per institutional standard relevant to the underlying 
disease.  Consult with the medical monitor for management 
outside of the institutional standard. 
Hemoglobin  
(× 109/L) 
All parts  
TGA and TGC 
< 8.0 
1. Hold until resolved to ≥ 10.0; monitor CBC approximately 
every 3 days. 
2. Restart at next lower dose and monitor per Protocol.   
 
< 6.5 
Discontinue study treatment. 
 
Part 1 and Part 3 TGB 
Manage as per institutional standard relevant to the underlying 
disease.  Consult with the medical monitor for management 
outside of the institutional standard. 
OTHER TOXICITIES 
Adverse Event 
Action Taken 
• Any Grade 1 or Grade 2 toxicity. 
Continue study drug treatment and treat the toxicity; monitor as 
clinically indicated. 
• Any Grade 3 toxicity, if clinically significant 
and not manageable by supportive care. 
1. Interrupt study drug up to 2 weeks (14 days), until toxicity 
resolves to ≤ Grade 1. 
2. Restart study drug at same dose.  If assessed as related to 
study drug, restart study drug at next lower dose (or 25% 
reduction, whichever is the smaller increment, rounded down 
to the nearest pill strength); monitor as clinically indicated. 
• Any recurrent Grade 3 toxicity after 2 dose 
reductions. 
Discontinue study drug administration and follow-up per Protocol.  
(Exceptions require approval of sponsor.) 
• Any other Grade 4 toxicity. 
Discontinue study drug administration and follow-up per Protocol. 


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5.6.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying malignancy will be 
presumed to be related to study drug treatment and will require that the study drug be 
permanently discontinued.  Unacceptable toxicity is defined as follows: 
• Occurrence of an AE that is related to treatment with the study drug 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. 
• An AE requiring more than 2 dose reductions, if below the PAD of INCB054329. 
• Persistent AE requiring a delay of therapy for more than 2 weeks (14 days) unless a 
greater delay has been approved by the sponsor. 
5.6.3. 
Dose Increases 
For Parts 1 and 3 TGB, intrasubject dose escalation will be permitted with sponsor preapproval 
in the following circumstances: 
• The Protocol eligibility criteria are met at the time of escalation. 
• The subject has received ≥ 4 cycles of study drug without drug-related toxicity 
≥ Grade 2.  
• The next higher dose level has been determined to be safe based on the MTD criteria.  
• The subject is willing to submit to the visit schedule as required in Cycle 1, including 
PK, ECGs, safety laboratory assessments, physical examinations, and vital signs. 
• In the opinion of the investigator, the subject does not have any concurrent condition 
or circumstance that would complicate the dose escalation, PK sampling, or pose 
increased risk to the subject. 
For Parts 2 and 3, TGA and TGC, intrasubject dose escalation will follow the dose titration 
criteria (Section 4.1.2.1).  
5.7. 
Withdrawal of Subjects From the Study 
5.7.1. 
Withdrawal Criteria 
Subjects must be withdrawn from treatment with INCB054329 for the following reasons: 
• Further participation would be injurious to the subject's health or well-being, in the 
investigator's medical judgment. 
• The subject becomes pregnant. 
• Consent is withdrawn. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority or IRB/IEC. 
• Occurrence of an AE defined as unacceptable toxicity (see Section 5.6.2). 


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• Any AE (even if unrelated to treatment) requiring more than a 2-week delay in study 
drug, unless approved by the sponsor. 
• Disease progression has occurred. 
A subject may be withdrawn from study treatment as follows: 
• If, during the course of the study, a subject is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the subject should be withdrawn from the study  
• If a subject is noncompliant with study procedures or study drug administration in the 
opinion of the investigator, the sponsor should be consulted to determine whether to 
withdraw the subject from study treatment. 
5.7.2. 
Withdrawal Procedures 
When the decision is made to permanently discontinue the study drug (EOT) the treatment phase 
will be considered complete. 
If a subject is withdrawn from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal and the last dose of study drug must be documented in 
the subject's medical record and in the electronic case report form (eCRF). 
• The EOT visit should be performed (see Section 6.4). 
• Reasonable efforts should be made to have the subject return for the safety follow-up 
visit (see Section 6.5.1), and survival follow-up (see Section 6.5.2) will begin. 
• Regardless of the occurrence of the safety follow-up visit (scheduled for 30 to37 days 
after the last dose of study drug), the obligatory follow-up period is 30 days after the 
last dose of study drug was received.  Subjects must be followed for safety until any 
study drug-related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer. 
5.8. 
Concomitant Medications and Measures 
There are no mandatory concomitant medications or measures.  The investigator will provide 
care for the subject's medical condition according to institutional standards.  All concomitant 
medications and treatments or procedures conducted from 30 days before the first dose of study 
drug, through 30 days after the last dose of study drug are considered concomitant, and must be 
recorded in the eCRF. 
5.9. 
Restricted Medications and Measures 
Chronic glucocorticoid administration is discouraged; if required for medical management doses 
should not exceed 10 mg/day prednisone (or equivalent).  Acute administration of 
glucocorticoids for any indication should be recorded promptly in the eCRF. 


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Short courses of systemic corticosteroid doses ≤ 10 mg/day prednisone (or equivalent) are 
permitted (eg, for transfusion reaction prophylaxis) but discouraged from the screening visit 
through the EOT visit or last dose of study medication. 
The following require sponsor approval: 
• Hydroxyurea for controlling proliferative disease is permitted with medical monitor 
approval. 
• Because of the potential to influence the plasma concentration of the study drug 
(Suzuki et al 2009), the proton pump inhibitors (PPIs) omeprazole and lansoprazole 
are permitted only with sponsor approval and other PPIs are prohibited 
(Section 5.10).  Additionally, inhibitors or inducers of CYP2C19 (Appendix E), and 
moderate or weak inducers and inhibitors of CYP3A4 require sponsor approval; note 
that these include ticlopidine, clopidogrel, and oral contraceptives. 
• Additional timed PK testing following the schedule for Cycle 1 Day 15 may be 
required if subjects initiate or require a dose adjustment of inhibitors or inducers of 
CYP2C19 or CYP3A4, or of PPIs, during the study. 
These medications should be taken regularly rather than as needed. 
5.10. 
Prohibited Medications and Measures 
• Any anticancer medication other than the study drug.  Denosumab and zoledronic 
acid are permitted to treat cancer related bone diseases such as subject with prostate 
and breast cancer. 
• Any investigational study drug, for any indication. 
• Potent inhibitors or inducers of CYP3A4 (Appendix D) with the exception of topical 
ketoconazole, based on its low overall bioavailability. 
• BCRP (Breast Cancer Resistance Protein/ABCG2) inhibitors, specifically the 
following: 
− Eltrombopag 
− Cyclosporine 
− Rabeprazole, pantoprazole, or any similar PPIs (except as noted in Section 5.9) 
Other BCRP inhibitors include lapatinib, elvitegravir and cobicistat, protease 
inhibitors, and several investigative drugs.  All these are prohibited during the study 
for other reasons. 
6. 
STUDY ASSESSMENTS 
All study assessments will be performed as indicated in the schedule of assessments for TGA 
(Table 6), TGB (Table 7), and TGC (Table 8), and the schedule of laboratory assessments 
(Table 9).  Required analytes for laboratory tests are listed in Table 10 and Table 11, and timed 
assessments are provided in Table 12.  See Section 7 for instructions on how to conduct and 
record each assessment.


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Table 6: 
Schedule of Study Assessments – Treatment Group A (Part 1, Part 2, and Part 3) 
Visit Day (Range) 
Section 
Screening 
Cohort 1 
First 3 
Subjects Only 
(Section 6.2.2) 
Cycle 1a 
Cycles 2 and Beyond 
EOT 
Follow -Up 
Safety 
Survival 
D0 
D0 + 1 
D1 
D2 
D8 
D15 
D16 
D1 
D2 
D11 
± 3 
Days 
EOT + 
30 Days 
(+ 7 d) 
EOT + 
Every 
9 Weeks 
Evaluation/Window 
Day -28 to 
Day -1 
 
 
 
 
± 3 Days 
 
± 3 
Days 
 
± 4 
Days 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
3 
X 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Medical and cancer history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal swab  
7.7.3.3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor tissue 
7.7.3.1 
X 
 
 
 
Optional tumor biopsy during study, as medically indicated 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Xb 
X 
X 
 
Administer INCB054329 in clinicc 
7.8.1 
 
X 
 
X 
X 
X 
X 
X 
C2d 
C2d 
 
 
 
 
Contact IRT 
7.2 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
Drug dispense/compliance check 
7.8.2 
 
 
 
X 
 
X 
X 
 
X 
 
 
X 
 
 
Comprehensive physical exam 
7.4.2 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Targeted physical exam 
7.4.3 
 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
ECOG performance status 
7.6 
X 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
 
Vital signs/weight 
7.4.4 
Xe 
X 
X 
X 
X 
X 
X 
 
X 
 
 
X 
X 
 
12-lead ECG  
7.4.5.1 
X 
 
 
 
 
 
 
 
X 
 
 
X 
X 
 
Timed 12-lead ECG 
7.4.5.2 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
AE assessment 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Xb 
X 
X 
 
Laboratory assessmentsf 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
C2d 
X 
X 
X 
 
Efficacy/disease assessments  
7.5 
X 
 
 
Every 9 weeks from baseline assessment (± 1 week) until disease progression or until new 
treatment is initiated. 
Provide reminder card 
7.8.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
Survival follow-up 
7.8.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xb 
a For subjects in Part 2, study assessments including PK, timed 12-lead ECGs, safety laboratory assessments, targeted physical examinations, and vital signs/weight will follow the 
Cycle 1 schedule during the first 21 days after intrasubject dose escalation occurs. 
b May conduct assessment by phone. 
c On all other days, subjects will self-administer INCB054329 at home. 
d First 12 subjects in Part 3 TGA will participate in the food effect study in Cycle 2 only.  Food effect PK timepoints are as follows:  0.5, 1.0, 2, 4, 6, 8, and 24 hours postdose.  
See Section 7.7.1.3. 
e Also record height at screening. 
f Screen laboratory tests must be performed within 14 days before Cycle 1 Day 1.  If screening laboratory tests are performed within 3 days of Cycle 1 Day 1, they do not need to 
be repeated for Cycle 1 Day 1. 


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Table 7: 
Schedule of Study Assessments – Treatment Group B (Part 1 and Part 3) 
Visit Day (Range) 
Section 
Screening 
Cycle 1 
Cycles 2 and Beyond 
EOT 
Follow-Up 
Safety 
Survival 
Day -28 
to Day -1 
D1 
D2 
D8 
D15 
D16 
D1 
D11 
± 3 Days 
EOT + 30 Days  
(+ 7 d) 
EOT + Every 
9 Weeks 
Evaluation/Window 
 
 
± 3 Days 
 
± 3 Days 
± 4 Days 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
3 
X 
X 
 
 
 
 
 
 
 
 
 
Medical and cancer history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
Buccal swab  
7.7.3.3 
X 
 
 
 
 
 
 
 
 
 
 
Bone marrow biopsy and aspiratea 
7.5.1, 
7.7.3.2 
X 
After 3, 6, and 12 months on study when required for response assessment 
or if clinically indicated 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
 
Administer INCB054329 in clinicc 
7.8.1 
 
X 
X 
X 
X 
X 
 
 
 
 
 
Contact IRT 
7.2 
 
X 
 
 
 
 
X 
 
 
 
 
Drug dispense/compliance check 
7.8.2 
 
X 
 
X 
X 
 
X 
 
X 
 
 
Comprehensive physical exam 
7.4.2 
X 
 
 
 
 
 
 
 
X 
X 
 
Targeted physical exam 
7.4.3 
 
X 
X 
X 
X 
 
X 
 
 
 
 
ECOG performance status 
7.6 
X 
X 
 
 
 
 
X 
 
X 
 
 
Vital signs/weight 
7.4.4 
Xd 
X 
X 
X 
X 
 
X 
 
X 
X 
 
12-lead ECG 
7.4.5.1 
X 
 
 
 
 
 
X 
 
X 
X 
 
Timed 12-lead ECG 
7.4.5.2 
 
X 
 
 
X 
 
 
 
 
 
 
AE assessment 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
 
Laboratory assessments 
7.4.6 
X 
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
 
Immunophenotypingf 
7.5.2 
X 
When confirming response 
 
Efficacy/disease assessments  
7.5 
X 
X 
 
 
X 
 
 
X 
X 
 
 
Peripheral blood disease assessmentg 
7.5.3 
X 
X 
 
 
X 
 
X 
 
X 
 
 
Provide reminder card 
7.8.3 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Survival follow-up 
7.8.4 
 
 
 
 
 
 
 
 
 
 
Xb 
a Bone marrow biopsy and aspirate performed at screening and as clinically indicated or at Months 3, 6, 12, and yearly thereafter when required for response assessment.  If 
archival aspirate is available and meets criteria described in Section 3.2, this may be omitted at screening.  For AML subjects, bone marrow disease assessment during Cycle 2 is 
strongly recommended unless contraindicated. 
b May conduct assessment by phone. 
c On all other days, subjects will self-administer INCB054329 at home. 
d Also record height at screening. 
e Screen laboratory tests must be performed within 14 days before Cycle 1 Day 1.  If screening laboratory tests are performed within 3 days of Cycle 1 Day 1, they do not need to 
be repeated for Cycle 1 Day 1. 
f For subjects with AML leukemia, immunophenotyping should be performed at screening and to confirm response.  If appropriate to the histologic subtype, immunophenotyping 
may be conducted in subjects with lymphoma as part of routine standard of care and/or at response assessment. 
g Subjects will have peripheral blood disease status assessments at screening, Cycle 1 Day 1, Cycle 1 Day 15, Day 1 (± 3 days) of each subsequent cycle, and EOT and when 
clinically indicated.  If indicated (ie, disease monitored by imaging), subjects with MF will have imaging assessments every 9 weeks using the appropriate imaging modality (eg, 
MRI or CT for spleen measurement). 


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Table 8: Schedule of Study Assessments – Treatment Group C (Part 2 and Part 3) 
Visit Day (Range) 
Section 
Screening 
Cycle 1a 
Cycles 2 and Beyond 
EOT 
Follow -Up 
Safety 
Survival 
Day -28 
to Day -1 
D1 
D2 
D8 
D15 
D16 
D1 
D11 
± 3 Days 
EOT + 30 Days 
(+ 7 d) 
EOT + Every 
9 Weeks 
Evaluation/Window 
 
 
± 3 Days 
 
± 3 Days 
± 4 Days 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
3 
X 
X 
 
 
 
 
 
 
 
 
 
Medical and cancer history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
Buccal swab  
7.7.3.3 
X 
 
 
 
 
 
 
 
 
 
 
Bone marrow biopsy and aspirate 
7.5.1, 
7.7.3.2 
Xb 
Confirming CR and as clinically indicated 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
Xc 
X 
X 
 
Administer INCB054329 in clinicd 
7.8.1 
 
X 
X 
X 
X 
X 
 
 
 
 
 
Contact IRT 
7.2 
 
X 
 
 
 
 
X 
 
 
 
 
Drug dispense/compliance check 
7.8.2 
 
X 
 
X 
X 
 
X 
 
X 
 
 
Comprehensive physical exam 
7.4.2 
X 
 
 
 
 
 
 
 
X 
X 
 
Targeted physical exam 
7.4.3 
 
X 
X 
X 
X 
 
X 
 
 
 
 
ECOG performance status 
7.6 
X 
X 
 
 
 
 
X 
 
X 
 
 
Vital signs/weight 
7.4.4 
Xe 
X 
X 
X 
X 
 
X 
 
X 
X 
 
12-lead ECG  
7.4.5.1 
X 
 
 
 
 
 
X 
 
X 
X 
 
Timed 12-lead ECG 
7.4.5.2 
 
X 
 
 
X 
 
 
 
 
 
 
AE assessment 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
Xc 
X 
X 
 
Laboratory assessmentsf 
7.4.6 
X 
Xf 
X 
X 
X 
X 
X 
X 
X 
X 
 
MM disease assessmentsg 
7.5.1 
7.5.4 
X 
X 
 
 
X 
 
 
X 
X 
 
 
Skeletal survey 
7.5.5 
X 
At investigator discretion 
 
 
 
Provide reminder card 
7.8.3 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Survival follow-up 
7.8.4 
 
 
 
 
 
 
 
 
 
 
Xc 
a For subjects in Part 2, study assessments including PK, timed 12-lead ECGs, safety laboratory assessments, targeted physical examinations, and vital signs/weight will follow the 
Cycle 1 schedule during the first 21 days after intrasubject dose escalation occurs. 
b If archival aspirate is available and meets criteria described in Section 3.2, this may be omitted at screening. 
c May conduct assessment by phone. 
d On all other days subjects will self-administer INCB054329 at home. 
e Also record height at screening. 
f Screen laboratory tests must be performed within 14 days before Cycle 1 Day 1.  If screening laboratory tests are performed within 3 days of Cycle 1 Day 1, they do not need to 
be repeated for Cycle 1 Day 1. 
g Multiple myeloma disease assessments as per Section 7.5.4 and Table 11 should be performed at screening, Cycle 1 Day 1, Cycle 1 Day 15 (± 3 days),  Day 11 of each 
subsequent cycle (± 4 days), and EOT.  If screening MM disease assessment is performed within 7 days of Cycle 1 Day 1, it does not need to be repeated. 


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Table 9: 
Schedule of Laboratory Assessments – All Treatment Groups 
Visit Day (Range) 
Section 
Screening 
TGA/Cohort 1 
First 3 
Subjects Only 
Cycle 1 
Cycles 2 and Beyond 
EOT 
Safety Follow-Up 
D0 
D0 + 
1 
D1 
D2 
D8 
D15 
D16 
D1 
D2a 
D11 
± 3 
Days 
EOT + 30 Days 
(+ 7 d) 
Evaluation/Window 
Day -28 to 
Day -1 
 
 
 
 
 
 
 
± 3 Days 
 
± 4 
Days 
Overnight fast before 
assessments 
 
 
X 
 
X 
 
 
X 
 
Even cycles 
 
 
 
 
Comprehensive blood 
chemistries 
Table 10 
X 
X 
X 
Xb 
X 
X 
X 
 
X 
 
X 
X 
X 
Hematology with 
differential 
Table 10 
X 
X 
X 
Xb 
X 
X 
X 
 
X 
 
X 
X 
X 
Coagulation panel 
Table 10 
X 
X 
 
Xb 
 
X 
 
 
Even cycles 
 
 
X 
 
Lipids 
Table 10 
X 
 
 
Xb 
 
X 
 
 
Even cycles 
 
 
X 
X 
Urinalysis  
Table 10 
 
 
 
X 
 
X 
X 
 
Even cycles 
 
 
X 
X 
Serum pregnancy test  
7.4.6.1 
X 
Xc 
 
Xc 
 
 
 
 
 
 
 
 
X 
Hepatitis testing 
7.4.6.2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK – plasma (untimed) 
7.7.1.1 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
PD – correlatived  
7.7.3.6 
 
 
 
X 
 
 
 
 
X 
 
 
X 
 
PD – plasmad 
7.7.3.4 
 
X 
 
X 
 
 
X 
 
X 
 
 
X 
 
Detailed schedule for the following assessments is shown in Table 12. 
PK – plasma (timed) 
7.7.1.2 
 
X 
X 
X 
X 
Xe 
X 
X 
 
 
 
 
 
PK – food effect 
7.7.1.3 
 
 
 
 
 
 
 
 
C2a 
C2a 
First 12 subjects in Part 3 TGA only 
PD – whole bloodf  
7.7.3.5 
 
X 
X 
X 
X 
 
X 
X 
C2a 
C2a 
PK – urine 
7.7.2 
 
 
 
 
 
 
X 
 
 
 
 
 
 
a First 12 subjects in Part 3 TGA, Cycle 2 only.  See Section 7.7.1.3. 
b If completed 3 days before Cycle 1 Day 1, this laboratory assessment may be omitted. 
c If serum pregnancy completed 3 days before Cycle 1 Day 1, a urine pregnancy test may be performed. 
d Only collected at Cycles 2, 4, 7, 10, 13, and every third cycle thereafter. 
e Predose only. 
f Avoid scheduling on Fridays wherever possible, due to overnight shipment of whole blood samples. 


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Table 10: 
Laboratory Tests:  Required Analytes 
Blood Chemistries 
Hematology 
Serologya 
Albumin  
Alkaline phosphatase 
ALT 
AST  
Bicarbonate 
Blood urea nitrogen  
Calcium 
Chloride  
Creatinine 
HbA1cb 
Glucose 
Lactate dehydrogenase 
Magnesium 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total 
bilirubin is > ULN)c 
Total protein 
Uric acid 
Complete blood count, 
including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell count 
• White blood cell count 
 
Differential count, 
including:d 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
• Blasts 
 
Hepatitis B surface antibody 
Hepatitis B surface antigen 
Hepatitis B core antibody 
HBV-DNA 
HCV antibody 
HCV-RNA 
Pregnancy 
Female subjects of childbearing potential require 
a serum test at screening.  
 
Pregnancy tests (serum or urine) should be 
repeated during the study as required by local 
regulations.   
Coagulation 
Prothrombin time 
Activated partial thromboplastin time 
International normalized ratio 
Lipids 
Urinalysis With Microscopic Examination 
Total cholesterol 
Triglycerides 
Low-density lipoprotein 
High-density lipoprotein 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Urobilinogen 
a Hepatitis B and C viral loads by PCR assay only need to be assessed when respective serology results are positive.  Hepatitis B 
virus DNA does not need to be performed if the surface antibody is the only positive result. 
b HbA1c only needs to be performed once during  screening. 
c Direct bilirubin should only be performed when total bilirubin is > 1.5 × ULN and the subject does not have Gilbert's 
syndrome. 
d Absolute values must be provided for lymphocytes and neutrophils.  Blasts readings are required at intervals specified in 
Table 7 for disease where peripheral blast count is part of disease assessments such as lymphoma, leukemia, MDS, MDS/MPN, 
and MF. 


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Table 11: 
Laboratory Tests:  Required Analytes for Multiple Myeloma Subjects 
Routine Disease Assessment 
• Serum protein electrophoresis with quantitative M-protein 
• Urine protein electrophoresis with quantitative M-protein 
• Quantitative immunoglobulins 
• Serum-free light chains 
• Beta-2 microglobulin 
Baseline, Confirming CR, and as Clinically Indicated 
• Bone marrow aspirate and biopsy 
• FISH/cytogenetics 
FISH = fluorescence in situ hybridization. 
Note:  For subjects who do not show evidence of urine paraprotein at screening, only spot urine with urine protein electrophoresis 
is required; if the subject subsequently shows evidence of urine paraprotein, a 24-hour collection will be required along with 
the urine protein electrophoresis. 


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Table 12: 
Timed Assessments 
Visit 
Assessment 
Fasting 
Requirement 
HOLD 
AM 
Dose 
 
Time Postdose 
Predose 
Dose 
0.5 h 
± 5 min 
1 h 
± 15 min 
 
2 h 
± 15 min 
4 h 
± 15 min 
6 h 
± 30 min 
8 h 
± 30 min 
24 h 
± 30 min 
Cohort 1 first 3 subjects 
Day 0a 
Section 6.2.2 
ECG 
Fast overnight 
n/a 
3X 
♦ 
 
 
snack/
meal 
X 
X 
X 
 
 
PK plasma 
≤ 15 min 
after ECG 
X 
X 
≤ 15 min 
after ECG 
≤ 15 min 
after ECG 
X 
X 
X 
PD whole 
blood 
≤ 15 min 
after ECG 
X 
X 
≤ 15 min 
after ECG 
≤ 15 min 
after ECG 
X 
 
 
All treatment groups 
Day 1 
ECG 
Fast overnight 
n/a 
3X 
♦ 
 
 
snack/
meal 
X 
X 
X 
 
 
PK plasma 
≤ 15 min 
after ECG 
X 
X 
≤ 15 min 
after ECG 
≤ 15 min 
after ECG 
X 
X 
X 
PD whole 
blood 
≤ 15 min 
after ECG 
X 
X 
≤ 15 min 
after ECG 
≤ 15 min 
after ECG 
X 
 
 
 
Day 2  
Day 0 + 1a 
C1D16 
PK plasma 
none 
X 
X 
♦ 
 
 
 
 
 
 
 
X 
PD whole 
blood 
X 
 
 
 
 
 
 
 
 
C1D8 
PK plasma 
none 
X 
X 
♦ 
 
 
 
 
 
 
 
 
 
C1D15 
ECG 
Fast overnight 
X 
3X 
♦ 
 
 
snack/
meal 
X 
X 
X 
 
 
PK plasma 
X 
X 
X 
X 
X 
X 
X 
X 
PD whole 
blood 
X 
X 
X 
X 
X 
X 
 
 
Urine PK 
void 
Collect urine over 8 hours following study drug administration. 
 
Part 3 TGA only:  first 12 subjects (food effect) 
C2D1b 
PK plasma 
Fast overnight 
Xb 
X 
♦ 
X 
X 
 
X 
X 
X 
X 
X 
PD whole 
blood 
X 
X 
X 
X 
X 
X 
 
 
C2D2 
PK plasma 
none 
X 
X 
♦ 
 
 
 
 
 
 
 
PD whole 
blood 
 
 
 
 
 
 
 
a First 3 subjects in Part 1 TGA Cohort 1 only. 
b High-fat meal to be consumed within a 25-minute period, followed by study drug administration within 5 minutes of completing the meal. 


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6.1. 
Screening Period 
The screening period is the interval, up to a maximum of 28 days duration, between the signing 
of the ICF and the day that the treatment period begins (Day 1, or Day 0 as applicable, see 
Section 6.2).  Informed consent must be obtained before performing any study-specific 
procedures.  Assessments that are required to demonstrate eligibility may be performed over the 
course of 1 or more days during this period. 
Results from the screening visit evaluations will be reviewed to confirm subject eligibility before 
randomization or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during the screening period if the investigator believes the 
results to be in error.  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, 
following recovery from an infection). 
6.2. 
Treatment Period 
6.2.1. 
Day 1 
The treatment period begins on the day the subject receives the first dose of study drug; this is 
defined as Cycle 1 Day 1 (except Cohort 1 as noted below) and continues until a decision is 
made to permanently discontinue the study drug.  At Cycle 1 Day 1, results from screening 
period assessments should be reviewed to determine whether the subject continues to meet the 
eligibility requirements as specified in the Protocol.  See Section 7.4.6 for discussion of the 
timing of tests performed at Day 1. 
6.2.2. 
Day 0 (Part 1 TGA Cohort 1 Only) 
The first 3 subjects in Part 1 TGA Cohort 1 will be administered INCB054329 as a single dose of 
5 mg, followed by a timed PK analysis to confirm exposure; this will be identified as Day 0.  No 
further study drug will be dispensed or administered on Day 0.  Subjects will also return to the 
clinic the following day (Day 0 + 1) to collect safety laboratory samples and a 24-hour PK 
sample.  Cycle 1 Day 1 will begin for a given subject when the PK analysis for that subject is 
complete; this is expected to be 7 to 10 days after Day 0. 
6.2.3. 
Visit Scheduling  
Please note that unless it is unavoidable, the Day 1 and 15 study visits should not be conducted 
on Fridays or on the day before a national holiday, as fresh PD samples will be shipped overnight 
to the sponsor on the day of these visits.   
Dates for subsequent study visits will be determined based upon Cycle 1 Day 1 and should occur 
within ± 3 days of the scheduled date unless delayed for safety reasons.  If study drug 
administration must be interrupted at the beginning of a new planned cycle, the cycle will be 
delayed until the study drug can be restarted.  All planned assessments are shown in Table 6 
through Table 12.  Other clinical assessments, or PK/PD assessments, may be added if medically 
indicated or indicated by emerging data, to maintain safety.  
The visit on Day 11 of Cycle 2 and beyond is scheduled to assess safety and disease status in 
select malignancies only and is primarily a laboratory-only visit.  If the investigator deems there 


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is no medical need for the subject to be seen by the clinic staff, AEs and concomitant medication 
check may be conducted by phone contact with the subject.  
6.3. 
Unscheduled Visits 
Clinic visits, or diagnostic laboratory visits not prescribed in the Protocol may be performed at 
any time clinically indicated.  Results of assessments performed at these visits should be entered 
as "unscheduled" visits in the eCRF.  The sponsor may also request additional visits to be 
performed, if needed, based upon emerging safety data.   
6.4. 
End of Treatment 
If a decision is made that the subject will permanently discontinue study drug, the EOT visit 
should be conducted.  If the EOT visit coincides with a regular study visit, the EOT evaluations 
should be conducted in addition to those required for the regularly scheduled visit, and the data 
should be entered in the EOT visit in the eCRF.  The subject should be encouraged to return for 
the safety follow-up visit. 
6.5. 
Follow-Up Period 
6.5.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and 30 days after the last dose 
of study drug or the scheduled follow-up visit, whichever is later.  Reasonable efforts should be 
made to have the subject return for the safety follow-up visit, to be scheduled 30 to 37 days after 
the EOT visit (or after the last dose of study drug if the EOT visit was not performed) and to 
report any AEs that occur during this time.  Adverse events and serious adverse events (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.  
6.5.2. 
Survival Follow-Up 
After the subject has reached EOT (permanently discontinuing the study treatment), the survival 
follow-up period will begin.  See Section 7.8.4 for information to be collected during this 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.  The granting of informed consent for study participation must be 
documented in writing, using an ICF that contains all the 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; a copy of the signed ICF must be provided to the study subject.  Subjects of 
childbearing potential must agree to take appropriate measures to avoid pregnancy in order to 
participate in the study (Appendix A). 
7.2. 
Interactive Response Technology Procedure 
The investigator or designee will assign a subject ID number when a subject enters the screening 
period.  The IRT will be contacted at each visit at which study drug is dispensed to update the 
study drug supply.  Refer to the IRT manual for detailed instructions. 
7.3. 
Demography and History 
7.3.1. 
Demographics and Medical History 
Demographic data and a complete medical and medication history will be collected at screening.  
This will include a detailed history of prior medical and surgical therapies for the disease under 
study. 
7.3.2. 
Prior and Concomitant Medications 
Prior and concomitant (ongoing) medications will be reviewed to determine study eligibility.  
The medication record will be maintained after enrollment as documentation of 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, which begins 30 days before Day 1 and continues through 30 days after the last 
dose of study drug. 
7.4. 
Safety Assessments 
7.4.1. 
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 routinely for the occurrence of 
AEs during scheduled clinic visits.  Additionally, AEs may also be reported by subjects during 
phone contact in between clinic visits, or after treatment discontinuation.  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.  


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7.4.2. 
Comprehensive Physical Examination 
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 the following organ or body system 
assessments:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; 
abdomen (liver, spleen); extremities; lymph nodes; and a brief neurological examination. 
7.4.3. 
Targeted Physical Examination 
A targeted physical examination will be a symptom-directed evaluation conducted by the 
investigator or designee.  The targeted physical examination will include assessment of the body 
systems or organs, as indicated by subject symptoms, AEs, or other findings. 
7.4.4. 
Vital Signs and Body Weight/Height 
Vital sign measurements (blood pressure, pulse, respiratory rate, and body temperature) will be 
taken with the subject in the recumbent, semirecumbent, or sitting position after 5 minutes of 
rest.  Body weight will also be measured.  Height will be recorded at screening only. 
7.4.5. 
Twelve-Lead Electrocardiograms 
A central ECG vendor will be used.  The 12-lead ECGs will be interpreted by the investigator at 
the site for immediate subject management.  The trace will also be transmitted to the central 
ECG vendor for analysis by a central reader, and data archiving.  The decision to include or 
exclude a subject or withdraw a subject from the study based on an ECG flagged as "Abnormal, 
Clinically Significant" is the responsibility of the investigator, in consultation with the sponsor's 
medical monitor, as appropriate.  Any treatment emergent ECG finding occurring on study that is 
abnormal and clinically significant in the judgment of the investigator should be reported as an 
AE.  
7.4.5.1. 
Electrocardiogram Procedures 
All 12-lead ECGs will be performed with the subject in a recumbent position after 5 minutes of 
rest and should not be performed within 15 minutes after a blood collection. 
7.4.5.2. 
Additional Instruction for Timed Electrocardiograms 
Timed ECGs will be conducted before the clinic administration of study drug (predose) and 
using the schedule shown in Table 12.  Electrocardiograms conducted before administration 
(establishing the baseline for the day) should be performed in triplicate (see Table 12).  The 
ECGs should be conducted before, but within 15 minutes of, the PK blood collection at the 
corresponding timepoint.  The specified postdose timepoints may be adjusted based upon 
emerging PK data. 
7.4.6. 
Laboratory Assessments 
A laboratory local to the study site and subject will perform all clinical laboratory assessments 
for safety.  The investigative site will enter the local laboratory results and laboratory normal 


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ranges into the eCRF.  All local laboratory assessments (ie, blood chemistries, hematology 
assessments, coagulation tests, lipid testing, and urinalysis) should be performed using standard 
procedures on the days indicated in Table 9.  Table 10 lists the required laboratory tests in each 
category; additional testing may be required by the sponsor based on emerging safety data.  
Additional tests may also be performed if clinically indicated. 
On Day 1, laboratory data must be reviewed to confirm eligibility.  Laboratory samples collected 
for the Day 1 evaluation must be performed before dose administration on Day 1 or no more than 
3 days before Day 1 dose administration.  (This also applies to Day 0 for TGA/Cohort 1.)  After 
Cycle 1, predose laboratory procedures can be conducted up to 72 hours before study drug 
administration (within the 3-day study window), and results should be reviewed by the 
investigator or qualified designee and found to be acceptable before a new cycle of treatment is 
initiated. 
7.4.6.1. 
Pregnancy Testing 
Serum pregnancy tests, performed and analyzed by the site laboratory, are required before first 
dose of study drug as shown in Table 9.  Subsequently, pregnancy tests (either serum or urine) 
may be conducted as medically indicated or as required per local guidelines. 
If a subject inadvertently becomes pregnant while on treatment with INCB054329, the subject 
will immediately be withdrawn from treatment (see Section 8.5).  The site will contact the 
subject at least monthly and document the subject's status until the pregnancy has been 
completed or terminated.  The outcome of the pregnancy will be reported to the sponsor without 
delay and within 24 hours if the outcome is an SAE (eg, death, abortion, congenital anomaly, or 
other disabling or life-threatening complication to the mother or newborn).  The investigator will 
make every effort to obtain permission to follow the outcome of the pregnancy and report the 
condition of the fetus or newborn to the sponsor.  If a male subject impregnates his female 
partner, the study personnel at the site must be informed immediately and the pregnancy reported 
to the sponsor and followed as described above and in Section 8. 
7.4.6.2. 
Serology (Hepatitis Testing) 
Testing for hepatitis (detailed in Table 10) is required at screening, and results should be 
reviewed before Day 1 to confirm eligibility.  Generally hepatitis serology tests should be 
submitted early in the screening process because of the length of time needed to obtain the 
results.  If hepatitis B and/or C serology are positive, subjects will be required to undergo 
additional testing for HBV-DNA and HCV-RNA by PCR assay to assess active infection.  
Subject with chronic (carrier state) or cleared hepatitis B or C will be allowed to enroll.  For 
hepatitis B, chronic disease (carrier state) is defined as subjects with positive HBV surface 
antigen and positive HBV total core antibody but with negative HBV core antibody IgM and 
positive HBV antibody; these subjects would have low risk of liver damage. 
7.5. 
Efficacy/Disease Assessments 
Objective assessment of disease status is required, using appropriate disease-specific techniques, 
and the investigator's assessment will be used to determine responses and will be logged into the 
eCRF. 


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The following disease response criteria will be used, as applicable, for each of the malignancies 
included in this study: 
• AML:  International Working Group Response Criteria for Acute Myeloid Leukemia 
(Cheson et al 2003; Appendix F)  
• Lymphoma:  Response Criteria For Lymphoma – The Lugano Classification 
(Cheson et al 2014; Appendix L) 
• MDS:  International Working Group Response Criteria For Myelodysplastic 
Syndrome (Cheson et al 2006; Appendix G)  
• MDS/MPN:  International Consortium Proposal of Uniform Response Criteria for 
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) In Adults (Savona et al 
2015; Appendix H) 
• MF:  International Working Group–Myeloproliferative Neoplasms Research and 
Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report 
(Tefferi et al 2013; Appendix I) 
• MM:  International Uniform Response Criteria for Multiple Myeloma (Durie et al 
2006; Appendix J)  
• MM (minimal response only):  Criteria for Evaluating Disease Response and 
Progression in Patients With Multiple Myeloma Treated by High-Dose Therapy And 
Haemopoietic Stem Cell Transplantation (Blade et al 1998; Appendix K) 
• Solid tumors: RECIST 1.1 (Eisenhauer et al 2009) 
Efficacy assessments will be performed at screening (this will be considered the baseline disease 
assessments) and at the intervals defined in Table 6, Table 7, and Table 8 throughout the study.  
For diseases routinely assessed through imaging studies (ie, solid tumors, lymphoma, and MF [as 
applicable]), cycle delays should not interrupt the 9-week scan interval; thus tumor assessments 
and cycles may become out of sync.  Subjects in all treatment groups/cohorts who discontinue 
treatment for reasons other than disease progression should continue to have disease assessments 
performed and recorded every 9 weeks until they have experienced disease progression or started 
another treatment. 
7.5.1. 
Leukemia, MDS, MDS/MPN, MF, Lymphoma, and Multiple Myeloma:  Bone 
Marrow Examination for Assessment of Disease Status 
Bone marrow examination (aspirate and biopsy) is required at screening for subjects with 
diseases that are typically monitored though bone marrow examination, including leukemia, 
MDS, MM, MDS/MPN, and MF (bone marrow examination may be omitted if the criteria listed 
in Section 3.2 are met).  If disease status requires assessment with bone marrow aspirate or 
biopsy, subjects with leukemia, MDS, MDS/MPN, or MF should have a bone marrow aspirate 
and/or biopsy performed approximately 3, 6, and 12 months after Day 1 and then every 
12 months on the nearest Cycle Day 11 (± 7 days) after the first dose of treatment and as 
clinically indicated.  If possible, bone marrow examinations should be scheduled to coincide 
with other disease assessments, including peripheral blood or, for MF, imaging studies.  


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Subjects with MM only require a bone marrow examination to confirm CR, after 2 consecutive 
laboratory disease assessments (Table 11) demonstrating negative serum and/or urine 
immunofixation, and as clinically indicated. 
Subjects with lymphoma will not require a bone marrow examination at baseline if the subject 
had a bone marrow examination performed after the most recent prior therapy and/or a baseline 
PET or PET/CT shows that the subject does or does not have disease in the bone marrow in a 
patient with PET-avid disease.  If one of these conditions does not apply, a baseline bone marrow 
biopsy is required unless it would not affect disease assessment and medical monitor approval is 
obtained.  On-study bone marrow examinations are required if needed to confirm response.  
Data from the pathology report result from the bone marrow examination will be captured in the 
eCRF.  All bone marrow examinations should include a unilateral aspiration and biopsy with 
FISH and cytogenetic testing, when feasible.  Subjects may be enrolled based on a biopsy only 
when a "packed marrow" precludes aspiration at the discretion of the medical monitor.  Results 
of assessments performed under standard-of-care before the signing of ICF may be used as the 
baseline disease assessment in lieu of a study-specific procedure if performed within 60 days of 
the first dose of study drug (Cycle 1 Day 1). 
7.5.2. 
Immunophenotyping:  Leukemia and Lymphoma 
For subjects with leukemia, immunophenotyping appropriate to the underlying pathology will be 
conducted by flow cytometry at the local laboratory at screening and at subsequent times only as 
part of confirmation of response.  If appropriate to the histologic subtype, immunophenotyping 
may be conducted in subjects with lymphoma as part of routine standard of care and/or at 
response assessment.  Results will be captured in the eCRF. 
7.5.3. 
Leukemia, MDS, and MDS/MPN:  Peripheral Blood Blast Counts 
For disease assessment timepoints in leukemia, MDS, and MDS/MPN that do not correspond to 
a bone marrow examination, peripheral blood blast counts (appropriate to underlying pathology) 
will be evaluated by microscopic evaluation or other appropriate methodology and will be used 
as appropriate in conjunction with other parameters (eg, complete blood counts) in determining 
disease status. 
7.5.4. 
Multiple Myeloma:  Disease Assessment 
Multiple myeloma laboratory assessments should be performed as per Table 8 and Table 11.  
Test samples should be drawn or collected and brought in (eg, 24-hour urine, as applicable) for 
all of these tests at screening, Cycle 1 Day 1, Cycle 1 Day 15 (± 3 days), Day 11 of subsequent 
cycles (± 4 days), and EOT to assess for response status.  In addition, a bone marrow 
examination (aspirate and biopsy) will be required to confirm CR. 
7.5.5. 
Multiple Myeloma:  Skeletal Survey 
A series of x-rays will be conducted of the skull, long bones, spine, pelvis, and ribs.  Skeletal 
surveys should be conducted at screening and then subsequently at the investigator's discretion. 


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7.6. 
Performance and Quality-of-Life Assessments 
Performance status will be assessed using the ECOG performance status scale (Appendix C), 
according to the study schedule (Table 6, Table 7, and Table 8).  Quality-of-life assessment 
questionnaires will not be used in this study. 
7.7. 
Pharmacokinetic Assessments 
7.7.1. 
Blood Sample Collection 
Pharmacokinetic samples will be obtained at the visits indicated in the table of Laboratory 
Assessments (see Table 9) to evaluate plasma PK parameters as described in Appendix B.  For 
PK sample collection, the following will be recorded: 
• The exact date and time of the blood sample. 
• The date and time of the last dose of study drug before blood collection (if 
applicable).  
• The time of the most recent meal. 
Subjects will receive reminder cards in advance of the study visit providing instructions to 
prepare for the visit (see Section 7.8.3).  Instructions for plasma preparation and sample shipping 
will be provided in the Laboratory Manual. 
7.7.1.1. 
Untimed Pharmacokinetic Testing 
On days when the timing of plasma PK blood collection is not specified, the sample may be 
collected at any time during the study visit, irrespective of the time that the study drug was taken 
that day.  An effort should be made to vary the time between the last dose of study drug and the 
time of collection, from visit to visit. 
7.7.1.2. 
Timed Pharmacokinetic Testing 
Timed PK testing will be performed using the timepoints shown in Table 12.  The timing of PK 
sample collection may be coordinated with other timed tests (PD testing or ECG).  On these 
study dates, the subject should arrive at the research unit in the morning.  If study drug has been 
previously dispensed, the reminder card (see Section 7.8.3) will remind the subject to refrain 
from taking the study drug at home that day.  Subjects will also be reminded about fasting 
requirements, as applicable (see Table 12).  A trough (predose) PK sample will be collected early 
in the study visit, followed by administration of the study drug and subsequent timed blood 
samples.  The study drug will be administered with 240 mL of water.  Subjects should remain 
fasting from food or water for at least 1 hour postdose, after which a meal or snack may be 
consumed. 
Refer to the Laboratory Manual for PK timepoint sample collections.  Additional adjustments to 
the timing of postdose blood collection may be made based upon emerging PK/PD data, and 
additional sampling may be performed if emerging data suggest that drug exposure confirmation 
is required for subject safety; however, no more than 6 postdose timepoints will be used on a 
given day. 


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7.7.1.3. 
Food-Effect Pharmacokinetic Testing 
Pharmacokinetic testing for food effect on drug exposure will be performed on a subgroup of the 
first 12 subjects enrolled in Part 3 TGA, Cycle 2 only.  Subjects may be excused from the 
food-effect portion of the study if they are unable to consume the meal. 
Subjects will have been fasted from food (not including water) overnight for at least 8 hours.  A 
standardized high-fat, high-calorie breakfast will be given to these subjects approximately 
30 minutes before administration of study drug.  Subjects must consume the entire breakfast 
within 25 minutes, and study drug administration will begin 5 minutes after completing 
breakfast. 
The high-fat, high-calorie breakfast (50% kcal from fat) will consist of: 
• 2 eggs fried in butter 
• 2 strips of bacon 
• 1 English muffin with butter 
• 4 oz hash brown potatoes 
• 8 oz whole milk 
Alternative menus with the same caloric and fat content may be substituted with the prior 
approval of the study sponsor.  Refer to the Laboratory Manual for PK timepoint sample 
collections. 
7.7.1.4. 
Bioanalytical Methodology 
Plasma samples will be analytes by the sponsor, or designee, using a validated assay.  
  
Pharmacokinetic parameters that will be analyzed are shown in Appendix B, and the analysis 
methodology is described in Section 9.4.5. 
7.7.2. 
Urine Sample Collection 
Urine will be collected from each subject at Cycle 1 Day 15 after administration of INCB054329 
and a predose void.  Total urine will be collected over an 8-hour interval following study drug 
administration.  Urine containers should be kept at reduced temperature (refrigerated or ice bath) 
during collection.  After the interval, urine should be mixed thoroughly.  The total urine volume 
and the pH should be measured and recorded in the individual eCRF.  Shipping and handling 
instructions will be provided in the Laboratory Manual; samples will be analyzed by the sponsor 
or its designee for parameters described in Appendix B. 
7.7.3. 
Pharmacodynamic 
 
7.7.3.1. 
Tumor Biopsy (Treatment Group A) 
Subjects must have an archival tumor biopsy sample (obtained within the last year and after the 
last systemic treatment) or prior FoundationOne® HEME (Foundation Medicine, Inc., 
Cambridge, MA) available or be willing to undergo a pretreatment tumor biopsy at baseline.  A 
minimum of 15 slides must be available (25 are requested).  If prior FoundationOne® 


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(Foundation Medicine, Inc., Cambridge, MA) data are available and obtained using the tumor 
biopsy sample met the criteria as described above, less than 15 slides will be sufficient after 
discussing with the medical monitor.  If a biopsy is not possible or contraindicated, or the tissue 
requirement cannot be satisfied, this requirement may be waived with approval from the medical 
monitor.  Details and methods for obtaining, processing, and shipping the fresh tumor biopsy 
samples and for processing and shipping the archived tumor tissue samples will be provided in 
the Laboratory Manual for the study. 
Tumor lesions used for biopsy should not be selected as response assessment target lesions, 
unless there are no other lesions suitable.  If a response assessment target lesion is used for 
biopsy, the lesion must be ≥ 2 cm in the longest diameter. 
Optional fresh tumor tissue biopsy specimens may be obtained at any time during the study in 
subjects with accessible tumors to assess intratumoral changes that might be associated with 
safety, response, or resistance to treatment.  When a tumor biopsy is obtained on study, a sample 
of peripheral whole blood will also be collected for correlative studies. 
7.7.3.2. 
Bone Marrow Aspirate for PD 
 Assessment (Treatment Groups B 
and C) 
Subjects must have an archival bone marrow aspirate sample (obtained within 1 year of the start 
of treatment) available or be willing to undergo collection of a pretreatment sample at baseline.  
A minimum of 1.5 mL of sample must be available.  Archival material from the same sample 
used for baseline disease assessment may be provided if the requirements in Section 7.5.1 are 
met, or it may be from another sample collected in the prior year.  Details and methods for 
obtaining, processing, and shipping the fresh aspirate samples and for processing and shipping 
archived samples will be provided in the Laboratory Manual for the study. 
Optional fresh bone marrow specimens may be obtained at any time during the study in subjects 
to assess changes that might be associated with safety, response, or resistance to treatment. 
7.7.3.3. 
Buccal Swab 
A buccal swab will be performed at screening on all subjects with hematological malignancies as 
a source of nontumor genetic material.  Details of collection and shipping will be provided in the 
Laboratory Manual. 
7.7.3.4. 
Plasma Pharmacodynamics 
Pharmacodynamic samples will be collected according to the schedule shown in Table 9.  
Plasma will be isolated from these samples at the investigative site, using materials provided and 
instructions found in the Laboratory Manual; samples should be frozen and shipped as directed. 
7.7.3.5. 
Whole Blood Pharmacodynamics 
Whole blood PD samples will be generally collected in conjunction with the timed PK samples 
(see Table 12) for the measurement of drug effect (BET inhibition as evidenced by inhibition of 
c-Myc).  These samples must be shipped directly (unfrozen) to the sponsor, on the day of 
collection, for processing and analysis.  Please see the Laboratory Manual for detailed collection, 
handling, and shipping instructions. 


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Visits that include PD whole blood collection (see Table 9 and Table 12) should not, unless 
unavoidable, be conducted on Fridays or on the day before a national holiday, since fresh 
PD samples will be shipped overnight to the sponsor on the day of these visits.  
7.7.3.6. 
Whole Blood Correlative Studies 
Whole blood for correlative PD analysis will be collected as shown in Table 9.  The Laboratory 
Manual will provide detailed collection, handling, and shipping instructions. 
7.7.3.7. 
Analyses 
Tumor biopsy samples will be used by the sponsor, or designee, to investigate molecular 
signatures associated with response or resistance to treatment with the study drug.  DNA and/or 
RNA may be extracted from these samples to perform somatic mutation analysis and genetic 
expression analysis, including that of known oncogenes.  Chromosomal alterations may be 
examined.  
 
 
  
 
 
 
 
 
 
 
7.8. 
Other Study Procedures 
7.8.1. 
Administration of Study Drug in the Clinic 
Study drug will be administered in the study clinic on days when it is necessary to collect a 
trough (predose) sample and when timed postdose samples are collected (Table 9 and Table 12).  
Subjects should be given INCB054329 with 240 mL of water, and the exact time of the dose will 
be recorded.  All other days, the subject will self-administer the study drug at home. 
7.8.2. 
Dispensing Study Drug and Assessing Compliance 
Unless specified as a day for in-clinic administration, the subject will self-administer 
INCB054329 orally, with water, according to the dose and schedule prescribed by the 
investigator, from a supply dispensed by the investigative site.  An initial bulk supply of 
INCB054329 will be provided to investigative sites before enrollment of the first subject.  
Thereafter, the site staff will contact the IRT for resupply of INCB054329.  When dispensing to 
subjects, the investigator or designee will remove the appropriate quantity of study drug from 
their stock, dispense the medication, and enter the amount dispensed into the eCRF and drug 
accountability log.  The study subject will return all full, empty, and opened/partially used 


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bottles of study drug at the beginning of each treatment cycle, and a compliance check (tablet 
count) will be performed by the clinic staff at each visit indicated in Table 6, Table 7, and 
Table 8; therefore, appropriate steps should be taken to optimize compliance.  Each time the 
study drug is dispensed (or dose adjustment made), the IRT must be contacted (see Section 7.2) 
to maintain supply management. 
The subject should be specifically instructed in the handling of study drug as follows: 
• Store the study drug at room temperature, in a safe place, out of the reach of children. 
• Only remove from the bottle the amount of tablets needed at the time of 
administration.  (Do not remove doses in advance of the next scheduled dose.) 
• When taking the study drug at home, take the tablets with a glass of water, on an 
empty stomach each morning, or at least 2 hours after the last meal.  It is preferable to 
refrain from food or drink (other than water) for 1 hour after the dose. 
• If vomiting occurs after taking study drug, the vomited dose should not be replaced; 
simply take the study drug at next scheduled time. 
• Make every effort to take doses on schedule.  Generally the drug should be taken in 
the morning, but if missed at that time, it can be taken later the same day. 
• Report any missed doses. 
• Bring all used and unused study drug bottles to the site at each visit. 
7.8.3. 
Distribution of Subject Reminder Cards 
Subjects will be provided with subject reminder cards at each visit indicated in Table 6, Table 7, 
and Table 8.  The reminder card should supplement other written instructions that do not change 
from visit to visit (see Section 7.8.2) with information that will guide the subject in between 
specific study visits, such as: 
• Dose instructions for study drug (ie, number of tablets to be taken during the current 
cycle).  Note that extra caution and instruction may be required if there is more than 
1 dose strength needed to achieve the required dose. 
• Instructions for taking any prescribed concomitant medications. 
The reminder card should also provide instructions regarding the next study visit: 
• The date and time of the next visit.  
• Whether to TAKE or HOLD the morning dose of study drug before coming to the 
clinic. 
• Whether or not to fast overnight before the visit.  
The reminder card may also contain fields for the subject to record certain information such as 
the following: 
• The date and time of the last dose taken before the visit (this could be the morning of 
the visit or on the prior day, for Days 8 and 15 for example).  
• Dates of any known missed doses. 


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7.8.4. 
Survival Follow-Up 
During this period, survival status and information on current anticancer therapies should be 
obtained at least every 9 weeks following EOT.  Clinic records may be used as a reference if the 
subject is still under the investigator's care.  Alternatively, the subject should be contacted by 
telephone or email periodically from EOT until death, or the end of the study, whichever occurs 
first.  Attempts at contact should be made before the end of the 9-week interval, in anticipation 
of delayed communication.  A delay in subject response will not be considered a deviation; 
however every attempt should be made to successfully complete contact with the subject. 
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 the appearance of or 
worsening of any pre-existing undesirable sign(s), symptom(s), or medical condition(s) that 
occurs after a subject provides informed consent.  Abnormal laboratory values or test results 
occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, 
are considered clinically meaningful, require therapy (eg, hematologic abnormality that requires 
transfusion), or require changes in the study drug(s). 
8.1.2. 
Reporting 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events form of the eCRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History form in the eCRF.  Monitoring for the occurrence of 
new AEs should be continued for at least 30 days after the last dose of study drug.  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. 
"Disease progression" and events related to disease progression (based on investigators 
judgement), including death due to disease progression, should not be recorded as an AE or SAE.  
For example, if it is determined that disease progression resulted either in hospitalization, a life-
threatening event, or death, then the specific event(s) that led to the subject's hospitalization, life-
threatening event, or death should be reported as the AE(s) instead of "disease progression." 
Adverse events will be assessed according to the CTCAE v4.03.  The CTCAE Grade 5 severity 
(death) will not be used in this study; rather, AEs with an outcome of death will be reported as 
CTCAE Grade 4.  Adverse events leading to death will be recorded with the outcome of the 
event as "fatal."  If an event is not classified by CTCAE, the severity of the AE will be graded 
according to the Protocol-defined toxicity criteria and the scale below to estimate the grade of 
severity. 


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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. 
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 4). 
• The reasonable possibility that the AE is related to the study treatment:  related (yes) 
or unrelated (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 a concomitant medication or nondrug therapy is 
given, this action should be recorded on the AE and Prior/Concomitant Medications 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 it, 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, which 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.  For analysis purposes, this will be considered 1 AE 
for this subject and the maximum severity will be used. 


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8.2. 
Laboratory Test Abnormalities 
8.2.1. 
Definitions and Reporting 
Laboratory abnormalities that constitute an AE in their own right (are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes 
in study drug), should be recorded on the AE page of 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 (severe) AE does not automatically indicate an SAE unless it meets the definition 
of serious, as defined in Section 8.3.1, and/or per the investigator's discretion.  A dose 
modification for the laboratory abnormality may be required (see Section 5.6) 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 1 of the following criteria: 
• Is fatal or life-threatening (ie, immediate risk of dying). 
• Results in persistent or significant disability or incapacity. 
• Constitutes a congenital anomaly or birth defect. 
• Is clinically meaningful (ie, defined as an event that jeopardizes the subject or 
requires potential medical or surgical intervention to prevent 1 of the outcomes listed 
above). 
• Is considered meaningful by the investigator as an important medical event that may 
not result in death, be life-threatening, or require hospitalization, but may be 
considered an SAE when, based upon appropriate medical judgment, it may 
jeopardize the subject or may require medical or surgical intervention to prevent 1 of 
the outcomes listed in this definition. 
• 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 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 given above and not resulting in hospital admission. 


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− Any social reasons and respite care, in the absence of any deterioration in the 
subject's general condition. 
− Any SAEs that are expected due to the condition being treated, including if the 
SAE is a primary outcome measure, or where there has been a clear agreement 
with regulators not to consider these as SAEs, provided the information is 
collected elsewhere. 
8.3.2. 
Reporting 
To ensure subject safety, every SAE, regardless of suspected causality, occurring after the 
subject has signed the ICF and up to the last study visit, or up to 30 days after the subject has 
stopped study treatment, whichever is later, must be reported to the sponsor (or designee) within 
24 hours of learning of its occurrence.  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 drug.  Recurrent episodes, complications, or progression of the 
initial SAE must be reported as the follow-up to the original episode within 24 hours of the 
investigator receiving the information.  An SAE occurring at a different time interval or 
otherwise considered completely unrelated to a previously reported one should be reported 
separately as a new event.  Previously planned (before providing informed consent) surgeries 
should not be reported as SAEs unless the underlying medical condition worsens over the course 
of the study. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report form 
of the eCRF.  The investigator must assess and record the relationship of each SAE to each 
specific study drug when there is more than 1, complete the SAE Report Form in English, and 
send the completed and signed form to the sponsor or its designee within 24 hours.  The 
investigator must assess if there is a reasonable possibility that the SAE is related to the study 
treatment:  related (yes) or unrelated (no). 
Serious AEs related to concomitant medications/drug delivery systems are reported directly to 
the manufacturers of those drugs/devices in accordance with the package insert. 
The contact information of the sponsor's study-specific representatives are listed in the 
investigator manual provided to each site.  The original copy of the SAE Report Form and the 
fax confirmation sheet must be kept with the eCRF documentation at the study site. 
Follow-up information is sent to the same person to whom the original SAE Report Form was 
sent, using a new SAE Report Form stating that this is a follow-up to the previously reported 
SAE and providing the date of the original report.  Each recurrence, complication, or progression 
of the original event should be reported as a follow-up to that event regardless of when it occurs.  
The follow-up information should describe whether the event has resolved or continues, if and 
how it was treated, and whether the subject continued or withdrew from study participation, or if 
study drug was interrupted or discontinued. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, a 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 


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Adverse Reactions (SUSARs) will be collected and reported to the competent authorities and 
relevant ethics committees in accordance with Directive 2001/20/EC, or as per national 
regulatory requirements in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
8.5. 
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, the following procedures should occur: 
• The investigator must notify the sponsor or its designee immediately. 
• The study drug must be discontinued immediately (female subjects only; see 
Section 5.6.1 for the maximum permitted duration of study drug interruption). 
• The investigator must complete and submit the Pregnancy Initial and Follow-Up 
Report forms (as described below) to the sponsor or its designee. 
To ensure subject safety, each pregnancy in a subject during maternal or paternal 
exposures to study drug must be reported within 24 hours of learning of its occurrence.  
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 Study Pregnancy 
Form and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up 
should be recorded on the same form and should include an assessment of the possible 
relationship to the sponsor's study drug of any pregnancy outcome and follow-up to the first 
well-baby visit.  Any SAE occurring during pregnancy must be reported on the SAE Report 
Form and to the sponsor or its designee. 
8.6. 
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. 
8.7. 
Data Monitoring Committee 
Not applicable.  Safety data will be activity monitored by the sponsor in conjunction with the 
study investigators. 


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8.8. 
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 and any associated AEs via email or other written communication to the 
sponsor contact or respective manufacturer as noted in the packaging information. 
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. 
9. 
STATISTICS 
9.1. 
Study Populations 
The safety/efficacy evaluable population includes all subjects enrolled in the study who received 
at least 1 dose of study drug (INCB054329). 
The PK/PD evaluable population includes subjects having received at least 1 dose of 
INCB054329 and had at least 1 PK/PD sample collected and analyzed.  Data listings of study 
drug administration and sample records will be examined to identify subjects to be excluded 
from analyses of PK and/or PD data.  
9.2. 
Selection of Sample Size 
Part 1 of the study is a standard dose-escalation design, and the sample size depends on the 
occurrence of safety findings as defined by DLT criteria.  Approximately 3 to 6 subjects will be 
enrolled in each cohort.  Using this design, the probability of dose escalation for various DLT 
rates is given in Table 13. 
Table 13: 
Probability of Dose Escalation by DLT Rate 
True DLT Rate 
Probability of Dose Escalation 
10% 
90.6% 
20% 
70.9% 
30% 
49.4% 
40% 
30.9% 
50% 
17.2% 
60% 
8.2% 
For Part 2, at least 5 and up to 10 subjects per treatment group will be enrolled to investigate the 
feasibility of intrasubject dose titration in select solid tumors and lymphoma and multiple 
myeloma.  For Part 3, approximately 5 subjects will be enrolled for each tumor type (with the 
exception of the group including any tumor with a known aberration in c-MYC or other genes in 


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which BET proteins are relevant, which will enroll 20 subjects) providing a > 80% chance of 
observing at least 1 responder if the underlying response rate is 30%. 
9.3. 
Level of Significance 
All statistical analyses are exploratory.  Unless otherwise specified, all confidence intervals (CIs) 
provided will be at the 95% confidence level. 
9.4. 
Statistical Analyses 
Study endpoints will be evaluated using SAS® procedures for the generation of all tables, graphs, 
and statistical analyses.  Continuous variables will be summarized using means, medians, 
standard errors, minimums, and maximums.  Categorical variables will be summarized using 
frequency counts and percentages. 
9.4.1. 
Definitions 
Day 1 is the date at which the subject receives the first dose of study drug intended for 
continuous administration.  Baseline assessments are defined as the last nonmissing value before 
the first dose of study drug (on Day 1). 
9.4.2. 
Primary Analyses 
The clinical safety data (vital signs, ECGs, routine laboratory tests, and AEs) will be summarized 
using descriptive statistics (eg, mean, frequency, standard deviation, range) using the safety 
population.  Subject enrollment, disposition, demographics, and medical history will be 
summarized at baseline.  The rate of DLTs will be summarized for each cohort.  Dose exposure 
and intensity will be calculated for each cohort.  Safety and disease response data will be 
compared over time to assess change from baseline.  Pharmacokinetic and PD data will be 
analyzed with appropriate standard nonlinear analytic software. 
9.4.2.1. 
Adverse Events 
Adverse events will be tabulated by the MedDRA® preferred term and system organ class.  
Severity of AEs will be based on the CTCAE v4.03 criteria (NCI 2010).  The subset of AEs 
considered by the investigator to have a relationship to study drug will be considered to be 
treatment-related AEs.  If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered treatment-related.  The incidence of AEs and treatment-related 
AEs will be tabulated.  Adverse events for the first cohort in Part 1 will be summarized 
separately. 
9.4.2.2. 
Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory.  The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. 


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Laboratory data will be classified into CTCAE grades for AEs (CTCAE v4.03).  The following 
summaries will be produced for the laboratory data: 
• Number and percentage of subjects with worst postbaseline CTCAE grade (regardless 
of baseline value).  Each subject will be counted once for the worst grade observed 
postbaseline. 
• Shift tables using CTCAE grades to compare baseline to the worst postbaseline value 
will be produced with CTCAE grade. 
• For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value will be produced using the low/normal/high classifications 
based on laboratory reference ranges. 
9.4.2.3. 
Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs at each 
assessment time.  Subjects exhibiting clinically notable vital sign abnormalities (see Table 14) 
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 14: 
Criteria for Clinically Notable Vital Signs Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 45 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 24/min 
< 8/min 
9.4.2.4. 
Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Subjects exhibiting clinically notable abnormalities according to 
predefined criteria (see Table 15) will be listed.   
Table 15: 
Criteria for Clinically Notable Electrocardiograms 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 480 msec 
< 295 msec 
PR 
> 220 msec 
< 75 msec 
QRS 
> 120 msec 
< 50 msec 
QT 
> 500 msec 
< 300 msec 
RR 
> 1330 msec 
< 600 msec 
9.4.3. 
Secondary Analyses 
9.4.3.1. 
Efficacy Analyses 
Efficacy endpoints will be analyzed using the efficacy evaluable population.  The cohort in 
Part 1 having the same dose as the cohort in Part 2 may be pooled together with subjects in Part 2 
for analysis, other cohorts in Part 1 will only be tabulated with summary statistics.  


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Efficacy endpoints include the following: 
• The proportion of subjects who meet ORR criteria will be estimated with 95% 
confidence interval. 
• The DOR is defined as the difference between the end of response and the start of 
response for subjects who have at least 1 response measurement.  Subjects who 
discontinued before the end of the study or who are still responding at the time of data 
cut off will be censored at the last adequate assessment.  The DOR will be assessed 
using the Kaplan-Meier method if there are enough observations.  
• The PFS will be determined from the enrollment date until the earliest date of disease 
progression, as measured by investigator assessment, or death due to any cause.  
Subjects with no observed death or progression, or discontinued from the study 
without disease progression, will be censored at the date of last adequate assessment 
visit; PFS will be estimated using the Kaplan-Meier method if there are enough 
observations.  
• The OS will be defined as number of days from enrollment date to the date of death.  
Subjects with no observed death will be censored at their last date known to be alive.  
The OS will be estimated using the Kaplan-Meier method if there are enough 
observations. 
9.4.4. 
Pharmacodynamic Analyses 
All PD data will be tabulated with summary statistics.   
9.4.5. 
Pharmacokinetic Analyses 
Pharmacokinetic analysis of INCB054329 including Cmax, Tmax, Cmin, AUC0-t, and Cl/F 
(Appendix B) will be performed on samples collected at the specified timepoints.  The 
parameters will be calculated from the blood plasma concentrations of INCB054329 using 
standard noncompartmental (model-independent) PK methods and commercial software 
(Appendix B).  The PK parameters will be summarized by descriptive statistics by part and 
cohort.  The log-transformed PK parameters will be compared among the dose levels by using a 
1-factor ANOVA.  Dose-dependent parameters (Cmax and AUC) will be normalized to the lowest 
common dose before statistical comparisons.  Cmax and AUC will be evaluated using a power 
model, eg, AUC = α∙(doseβ) or equivalently, log(AUC) = log(α) + β∙log(dose), where linear dose 
proportionality is accepted if β is not significantly different from 1.  Attainment of steady state 
will be assessed separately for each cohort by comparing trough plasma concentrations on 
Days 8 and 15.  For the food-effect assessment, the log-transformed PK parameters will be 
compared between the fed and fasted treatments using an ANOVA for a 1-way crossover design.  
The geometric mean relative bioavailability and 90% CIs will be calculated for comparing Cmax 
and AUC between the fed (test) and fasted (reference) treatments.  Population PK methods may 
be employed if there are a sufficient number of plasma PK samples. 
9.5. 
Analysis for Data Monitoring Committee 
Not applicable. 


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9.6. 
Interim Analysis 
No interim analysis is planned. 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
10.1. 
Investigator Responsibilities 
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; GCPs as defined in 
Title 21 of the US Code of Federal Regulations Parts 50, 54, 56, 312, and Part 11; ICH E6 GCP 
consolidated guidelines; and other local regulatory requirements as applicable to the study 
location(s).  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. 
− Qualified representatives of the sponsor or its designee, study monitors, will 
monitor the study according to a predetermined monitoring plan.  The investigator 
must allow the study monitors to review all study materials and subject records at 
each monitoring visit. 
− 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 authorities may visit the investigator at any time during the 
development of an investigational product to conduct an inspection of the study 
and the site.  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. 
− 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 approve all changes to site-specific ICFs.  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, Protocol deviations, routine updates, and safety 
information in accordance with institutional requirements and local law. 
− When the sponsor or its designee provides the investigator with a safety report, 
the investigator is responsible for ensuring that the safety report is 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, the investigator 
may assign some of the drug accountability duties to an appropriate pharmacist or other 
designee.  Inventory and accountability records must be maintained and readily available for 
inspection by the study monitor and are open to inspection at any time by any applicable 
regulatory authorities.  The investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Subject use of the study drug including pill or unit counts from each supply 
dispensed. 
• Return of study drug to the investigator or designee by subjects. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the subjects were provided the correct 


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study drug specified.  These records should include dates, quantities, batch or serial numbers (if 
available), and the unique code numbers (if available) 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 the end of the study (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 must (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; 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 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 privacy laws 
and regulations.  The investigator and the sponsor, or its designee, are responsible for ensuring 
that sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
Subject names will not be supplied to the sponsor or its designee, if applicable.  Only the subject 
number and subject's initials will be recorded in the eCRF, where permitted; if the subject's name 
appears on any other document (eg, laboratory report), it must be obliterated on the copy of the 
document to be supplied to the sponsor or its designee.  Study findings stored on a computer will 
be stored in accordance with local data protection laws.  The subjects will be informed that 
representatives of the sponsor or its designee, IRB or IEC, or regulatory authorities may inspect 
their medical records to verify the information collected, and that all personal information made 


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available for inspection will be handled in strictest confidence and in accordance with 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 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. 
LITERATURE REFERENCES 
Asangani IA, Dommeti VL, Wang X, et al. Therapeutic targeting of BET bromodomain proteins 
in castration-resistant prostate cancer. Nature 2014;510:278-282 
Belkina AC, Nikolajczyk BS, Denis GV. BET protein function is required for inflammation: 
Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory 
responses. J Immunol 2013;190:3670-3678. 
Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in 
patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell 
transplantation. Br J Haematol 1998;102:1115-1123. 
Ceribelli M, Kelly PN, Shaffer AL, et al. Blockade of oncogenic IκB kinase activity in diffuse 
large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc Natl 
Acad Sci U S A 2014;111:11365-11370. 
Chen BJ, Wu,YL, Tanaka Y, Zhang W. Small molecules targeting c-Myc oncogene: promising 
anti-cancer therapeutics. Int J Biol Sci 2014;10:1084-1096. 
Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International 
Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and 
Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 
2003;21:4642-4649. 
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;30:3059-3068. 
Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification 
of the International Working Group (IWG) response criteria in myelodysplasia. Blood 
2006;108:419-425. 
Dawson MA, Prinjha RK, Dittmann A, et al. Inhibition of BET recruitment to chromatin as an 
effective treatment for MLL-fusion leukaemia. Nature 2011;478:529-533. 
Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy 
to target c-Myc. Cell 2011;146:904-917. 
Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple 
myeloma. Leukemia 2006;20:1467-1473. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-224. 
Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation. 
Nat Rev Drug Discov 2014;13:337-356. 
Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature 
2010;468:1067-1073. 


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French CA, Ramirez CL, Kolmakova J, et al. BRD-NUT oncoproteins: a family of closely 
related nuclear proteins that block epithelial differentiation and maintain the growth of 
carcinoma cells. Oncogene 2008;27:2237-2242. 
Huang B, Yang XD, Zhou MM, Ozato K, Chen LF. Brd4 coactivates transcriptional activation of 
NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 2009;29:1375-1387. 
INCB054329 Investigator's Brochure (IB). Wilmington, DE: Incyte Corporation. 
Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation 
and cytokines in the tumor microenvironment. J Immunol Res 2014;2014:149185. 
Mochizuki K, Nishiyama A, Jang MK, et al. The bromodomain protein Brd4 stimulates G1 gene 
transcription and promotes progression to S phase. J Biol Chem 2008;283:9040-9048. 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 
(CTCAE). June 14, 2010. 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 
November 21, 2016. 
Nicodeme E, Jeffrey KL, Schaefer U, et al. Suppression of inflammation by a synthetic histone 
mimic. Nature 2010;468:1119-1123. 
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. 
Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol 
2010;28:1057-1068. 
Savona MR, Malcovadi L, Komrokji R, et al. An international consortium proposal of uniform 
response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. 
Blood 2015;125:1857-1865. 
Shimamura T, Chen Z, Soucheray M, et al.  Efficacy of BET bromodomain inhibition in 
Kras-mutant non-small cell lung cancer. Clin Cancer Res 2013;19:6183-6192. 
Suzuki K, Doki K, Homma M, et al. Co-administration of proton pump inhibitors delays 
elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol 
2009;67:44-49. 
Tang Y, Gholamin S, Schubert S, et al. Epigenetic targeting of Hedgehog pathway 
transcriptional output through BET bromodomain inhibition. Nat Med 2014;20:732-740. 
Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International 
Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and 
European LeukemiaNet (ELN) consensus report. Blood 2013;122:1395-1398. 
Trussell J. Contraceptive failure in the United States. Contraception 2004;70:89-96. 
US Food and Drug Administration (FDA). Guidance for Industry: S9 Nonclinical Evaluation for 
Anticancer Pharmaceuticals. 2010. 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm085389.pdf. Accessed November 21, 
2016. 


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Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and 
transcriptional regulation. J Biol Chem 2007;282:13141-13145. 
Wyce A, Degenhardt Y, Bai Y, et al. Inhibition of BET bromodomain proteins as a therapeutic 
approach in prostate cancer. Oncotarget 2013;4:2419-2429. 
Yan J, Diaz J, Jiao J, Wang R, You J. Perturbation of BRD4 protein function by BRD4-NUT 
protein abrogates cellular differentiation in NUT midline carcinoma. J Biol Chem 
2011;286:27663-27675. 
You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 
2012;22:9-20. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods have been determined to be highly effective methods of contraception or 
birth control as defined in ICH (M3).  These are more than 99% effective (< 1% failure rate per 
year when used consistently and correctly) (Trussell 2004) and are permitted under this Protocol 
for use by the subject and his/her partner: 
• Complete abstinence from sexual intercourse 
− Only if in line with the preferred and usual lifestyle of the subject. 
− Periodic abstinence (eg. calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception.  
• Double barrier methods 
− Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal 
foam/gel/film/cream/suppository are acceptable. 
− A female condom and male condom should not be used together as friction 
between the 2 can result in either product failing. 
• Birth control patch or vaginal ring 
• Established oral, injectable, or implanted hormonal methods of contraceptives 
• Intrauterine system (IUS) or intrauterine device (IUD) 


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APPENDIX B. PHARMACOKINETIC ANALYTICAL PARAMETERS 
Cave 
Average steady-state plasma concentration (AUC0-12h/12h or 
AUC0-24h/24h) 
Cmax 
Maximum observed plasma concentration 
Cmin 
Minimum observed plasma concentration during the dosing interval 
Tmax 
Time to maximum plasma concentration 
AUC0-t 
Area under the single-dose plasma concentration-time curve from Hour 0 
to the last quantifiable measurable plasma concentration, calculated by the 
linear trapezoidal rule for increasing concentrations and the log 
trapezoidal rule for decreasing concentrations 
AUC0-τ (ie, 
AUC0-12h or 
AUC0-24h) 
Area under the steady-state plasma concentration-time curve over 
1 dosing interval (ie, from Hour 0 to 12 for twice-daily administration or 
from Hour 0 to 24 for QD administration), calculated by the linear 
trapezoidal rule for increasing concentrations and the log trapezoidal rule 
for decreasing concentrations 
λz 
Apparent terminal phase disposition rate constant, where λz is the 
magnitude of the slope of the linear regression of the log concentration 
versus time profile during the terminal phase 
t½ 
Apparent plasma terminal phase disposition half-life (whenever possible), 
where t½ = (ln2) / λz 
Cl/F 
Oral dose clearance 
Vz/F 
Apparent oral dose volume of distribution 
Fluctuation 
Steady-state fluctuation ([Cmax – Cmin]/Cave) 
In addition, the following PK parameters may be calculated, whenever possible, for each subject 
based on the urine INCB054329 concentrations: 
Ae 
Amount of drug excreted in the urine over sampling interval 
Clr 
Renal clearance, where Clr = Ae/AUC 
% Excreted or fe 
percent excreted in the urine, where % Excreted = 100 (Ae/dose) 


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APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
(ECOG) PERFORMANCE STATUS 
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 selfcare but unable to carry out any work activities.  Up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours  
4 
Completely disabled.  Cannot carry on any selfcare.  Totally confined to bed or chair  
5 
Dead  
Source:  Oken et al 1982. 


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APPENDIX D. CYP3A4 INHIBITORS AND INDUCERS 
Source:  University of Washington School of Pharmaceutics: Drug Interaction Database 
Program. 2002. http://www.druginteractioninfo.org. Accessed October 2016. Highlighted rows 
indicate recent additions to the list. 


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APPENDIX E. CYP2C19 INHIBITORS AND INDUCERS 
Source:  University of Washington School of Pharmaceutics: Drug Interaction Database 
Program. 2002. http://www.druginteractioninfo.org. Accessed October 2016 (inhibitors) and 
March 2015 (inducers).  Highlighted rows indicate recent additions to the list. 
 


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APPENDIX F. INTERNATIONAL WORKING GROUP RESPONSE 
CRITERIA FOR ACUTE MYELOID LEUKEMIA 
Response Category 
Response Definition 
Complete remission (CR)1 
Bone marrow blasts < 5 percent; absence of blasts with Auer rods; 
absence of extramedullary disease; absolute neutrophil 
count > 1.0 × 109/L (1000/μL); platelet count >100 × 109/L 
(100,000/μL); independence of red cell transfusions 
CR with incomplete recovery 
(CRi) 
All CR criteria except for residual neutropenia (< 1.0 × 109/L [1000/μL]) 
or thrombocytopenia (<100 × 109/L [100,000/µL]) 
Morphologic leukemia-free 
state 
Bone marrow blasts < 5 percent; absence of blasts with Auer rods; 
absence of extramedullary disease; no hematologic recovery required 
Partial remission (PR) 
All hematologic criteria of CR; decrease of bone marrow blast 
percentage to 5 to 25 percent; and decrease of pretreatment bone marrow 
blast percentage by at least 50 percent 
Cytogenetic CR (CRC) 
Reversion to a normal karyotype at the time of morphologic CR (or CRi) 
in cases with an abnormal karyotype at the time of diagnosis; based on 
the evaluation of 20 metaphase cells from bone marrow 
Molecular CR (CRm) 
No standard definition; depends on molecular target 
Treatment failure 
Resistant disease (RD)  
Failure to achieve CR or Cri or PR (Phase 1 trials); only includes 
patients surviving ≥ 7 days following completion of initial treatment, 
with evidence of persistent leukemia by blood and/or bone marrow 
examination 
Death in aplasia 
Deaths occurring ≥ 7 days following completion of initial treatment 
while cytopenic; with an aplastic or hypoplastic bone marrow obtained 
within 7 days of death, without evidence of persistent leukemia 
Death from indeterminate 
cause  
Deaths occurring before completion of therapy, or < 7 days following its 
completion; or deaths occurring ≥ 7 days following completion of initial 
therapy with no blasts in the blood, but no bone marrow examination 
available 
Relapse2 
Bone marrow blasts ≥ 5 percent; or reappearance of blasts in the blood; 
or development of extramedullary disease 
1 All criteria need to be fulfilled; marrow evaluation should be based on a count of 200 nucleated cells in an aspirate 
with spicules; if ambiguous, consider repeat exam after 5 to 7 days; flow cytometric evaluation may help to 
distinguish between persistent leukemia and regenerating normal marrow; a marrow biopsy should be performed 
in cases of dry tap, or if no spicules are obtained; no minimum duration of response required. 
2 In cases with low blast percentages (5 to 10 percent), a repeat marrow should be performed to confirm relapse.  
Appearance of new dysplastic changes should be closely monitored for emerging relapse.  In a patient who has 
been recently treated, dysplasia or a transient increase in blasts may reflect a chemotherapy effect and recovery of 
hematopoiesis.  Cytogenetics should be tested to distinguish true relapse from therapy-related MDS/AML. 
Source:  Cheson et al 2003. 


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APPENDIX G. IWG RESPONSE CRITERIA FOR MYELODYSPLASTIC 
SYNDROME 
Category 
Response Criteria (Responses Must Be at Least 4 Weeks in Duration) 
Complete remission (CR) 
Bone marrow:  ≤ 5% myeloblasts with normal maturation of all cell lines 
Persistent dysplasia will be noted 
Peripheral blood: 
Hemoglobin (Hgb) ≥ 11 g/dL, Platelets ≥ 100 × 109/L, Neutrophils ≥ 1.0 × 109/L 
Blasts 0% 
Partial remission (PR) 
All CR criteria if abnormal before treatment, except: 
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5% 
Cellularity and morphology not relevant 
Marrow CR 
Bone marrow:  ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment 
Peripheral blood:  if HI responses, they will be noted in addition to marrow CR 
Stable disease (SD) 
Failure to achieve at least PR, but no evidence of progression for > 8 weeks 
Treatment failure 
Death during treatment 
Disease progression characterized by worsening of cytopenias, increase in % of 
bone marrow blasts, or progression to a more advanced MDS FAB subtype than 
pretreatment 
Disease progression (PD) 
For patients with: 
- Less than 5% blasts:  ≥ 50% increase in blasts to > 5% blasts 
- 5%-10% blasts:  ≥ 50% increase in blasts to > 10% blasts 
- 10%-20% blasts:  ≥ 50% increase in blasts to > 20% blasts 
- 20%-30% blasts:  ≥ 50% increase in blasts to > 30% blasts 
Any of the following: 
- At least 50% decrement from maximum remission/response levels in 
granulocytes or platelets 
- Reduction in Hgb concentration by ≥ 2 g/dL  
- Transfusion dependence 
Disease transformation 
Transformation to AML (30% or more blasts) 
Relapse after CR or PR 
At least one of the following: 
- Return to pretreatment bone marrow blast % 
- Decrement of ≥ 50% from maximum remission/response levels in granulocytes 
or platelets 
- Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence 
CYTOGENETIC RESPONSE 
Complete 
Disappearance of the chromosomal abnormality without appearance of new ones 
Partial 
At least 50% reduction of the chromosomal abnormality 
HEMATOLOGICAL IMPROVEMENT (HI) 
Erythroid response (HI-E) 
(Pretreatment < 11 g/dL) 
Hgb increase by ≥ 1.5 g/dL 
Relevant reduction of units of RBC transfusions by an absolute number of at least 
4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in 
the previous 8 weeks.  Only RBC transfusions given for a Hgb of ≤ 9.0 g/dL 
pretreatment will count in the RBC transfusion evaluation 
Platelet response (HI-P) 
(Pretreatment < 100 × 109/L) 
Absolute increase of ≥ 30 × 109/L for patients starting with > 20 × 109/L 
Increase from < 20 × 109/L to > 20 × 109/L and by at least 100% 
Neutrophil response (HI-N) 
(Pretreatment < 1.0 × 109/L) 
At least 100% increase and an absolute increase of > 0.5 × 109/L 
Source:  Cheson et al 2006. 


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APPENDIX H. INTERNATIONAL CONSORTIUM PROPOSAL OF 
UNIFORM RESPONSE CRITERIA FOR 
MYELODYSPLASTIC/MYELOPROLIFERATIVE 
NEOPLASMS (MDS/MPN) IN ADULTS 
Response 
Subcategory 
Response Criteria 
Complete 
Remission (CR) 
• Presence of all of the following improvements: 
• Bone marrow:  ≤ 5% myeloblasts (including monocytic blast equivalent in case of 
CMML) with normal maturation of all cell lines and return to normal cellularity* 
• Osteomyelofibrosis absent or equal to "mild reticulin fibrosis" (≤ Grade 1 fibrosis)† 
• Peripheral blood‡ 
- 
WBC ≤ 10 × 109 cells/L 
- 
Hgb ≥ 11 g/dL 
- 
Platelets ≥ 100 × 109/L; ≤ 450 × 109/L 
- 
Neutrophils ≥ 1.0 × 109/L 
- 
Blasts 0% 
- 
Neutrophil precursors reduced to ≤ 2% 
- 
Monocytes ≤ 1 × 109/L 
• Extramedullary disease:  Complete resolution of extramedullary disease present before 
therapy (eg, cutaneous disease, disease-related serous effusions), including palpable 
hepatosplenomegaly 
Persistent low-level dysplasia is permitted given subjectivity of assignment of dysplasia* 
Complete 
Cytogenetic 
Remission  
Resolution of previously present chromosomal abnormality (known to be associated with 
myelodysplastic, syndrome myeloproliferative neoplasms, or MDS/MPN), as seen on classic 
karyotyping with minimal of 20 metaphases or FISH § 
Partial Remission 
(PR) 
Normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts (and 
blast equivalents) reduced by 50%, but remaining  > 5% of cellularity except in cases of 
MDS/MPN with ≤ 5% bone marrow blasts at baseline. 
Marrow Response 
• Optimal marrow response:  Presence of all marrow criteria necessary for CR without 
normalization of peripheral blood indices as presented above. 
• Partial marrow response:  Bone marrow blasts (and blast equivalents) reduced by 50%, but 
remaining > 5% of cellularity, or reduction in grading of reticulin fibrosis from baseline 
on at least 2 bone marrow evaluations spaced at least 2 months apart. 


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Response 
Subcategory 
Response Criteria 
Clinical Benefit 
Requires 1 of the following in the absence of progression or CR/partial response and 
independent of marrow response (cord blood response must be verified at ≥ 8 week) to be 
considered a clinical benefit: 
Erythroid response: 
• Hgb increase by ≥ 2.0 g/dL 
• Transfusion independence (TI) for > 8 week for patients requiring at least 4 packed red 
blood cell transfusions in the previous 8 weeks. 
• Only red blood cell transfusions given based on physician's judgment for a pretreatment 
Hgb of ≤ 8.5 g/dL will count in the red blood cell TI response evaluation|| 
Platelet response: 
• Transfusion independence when previously requiring platelet transfusions of at least a rate 
of 4 platelet transfusions in the previous 8 weeks. 
• Pretreatment ≤ 20 × 109/L:  increase from < 20 × 109/L to >20 × 109/L and by ≤ 100% 
• Pretreatment > 20 × 109/L but ≤ 100 × 109/L:  absolute increase of ≥ 30 × 109/L|| 
Neutrophil response: 
• Pretreatment ≤ 0.5 × 109/L:  at least 100% increase and an absolute increase ≥ 0.5 × 109/L 
• Pretreatment > 0.5 × 109/L and ≤ 1.0 × 109/L:  at least 50% increase and an absolute 
increase ≥ 0.5 × 109/L|| 
Spleen response: 
• Either a minimum 50% reduction in palpable splenomegaly of a spleen that is at least 
10 cm at baseline or a spleen that is palpable at more than 5 cm at baseline becomes not 
palpable becomes not palpable. 
* Presence of dysplastic changes, which may be interpreted within the scope of normal range of dysplastic changes, may still 
exist in the presence of CR as allowed in MDS IWG.  Marrow should exhibit age-adjusted normocellularity in CR. 
† If there is no significant fibrosis present on the initial bone marrow biopsy, a second biopsy is not required to prove resolution 
of fibrosis.  Grading of fibrosis in measurement of treatment response should be according to the European Consensus System. 
‡ Given the current lack of a validated tool to assess complete resolution of symptoms in MDS/MPN, "CR with resolution of 
symptoms" (a complete resolution of disease-related symptoms as noted by the MPN-SAF TSS in presence of CR) will be a 
provisional category of disease response. 
§ Loss of cytogenetic burden of disease by (via FISH or classic karyotyping) known to adversely affect prognosis is required to 
reach complete cytogenetic remission.  Decrease in the cytogenetic burden of disease must be by ≥ 50% (via FISH or classic 
karyotyping) to be indicative of a partial cytogenetic response.  Given variability of fluorescent probes used in FISH, 
cytogenetic normalization via FISH will depend on the performance characteristics of the specific probes used. 
|| Resolution of abnormal peripheral blood counts must persist for at least 2 separate analyses over at least 8 weeks.  In the case of 
proliferative MDS/MPN, CR will include resolution of thrombocytosis to a normal platelet count (150-450 × 109/L) and 
resolution of leukocytosis to WBC ≤ 10 × 109 cells/L but ≥ 1.5 × 109/L. Hemoglobin should be maintained > 11 g/dL and 
platelets ≥100 × 109/L without the support of transfusions.  Clinical benefit may occur when these changes occur in absence of 
other changes required for CR or marrow response.  Platelet and packed red blood cell TI would be considered for clinical 
benefit, and duration of TI should be monitored.  Reduction in myeloid precursors (promyelocytes, myelocytes, 
metamyelocytes, nucleated red blood cells) to less than appreciable levels (≤ 2%-3%) and/or 1 × 109/L monocytosis in the 
absence of infection, cytokine treatment, or other reactive causes. 


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Response 
Subcategory 
Response Criteria 
Progressive 
Disease 
Combination of 2 major criteria, 1 major and 2 minor criteria, or 3 minor criteria from list: 
 
Major criteria: 
Increase in blast count* 
• < 5% blasts:  ≥ 50% increase and to > 5% blasts 
• 5%-10% blasts:  ≥ 50% increase and to > 10% blasts 
• 10%-20% blasts:  ≥ 50% increase and to > 20% blasts 
• 20%-30% blasts:  ≥50% increase and to > 30% blasts† 
 
Evidence of cytogenetic evolution‡ 
• Appearance of a previously present or new cytogenetic abnormality in complete 
cytogenetic remission via FISH or classic karyotyping 
• Increase in cytogenetic burden of disease by ≥ 50% in partial cytogenetic remission via 
FISH or classic karyotyping 
 
New extramedullary disease 
• Worsening splenomegaly 
- 
Progressive splenomegaly that is defined by IWG-MRT:  the appearance of a 
previously absent splenomegaly that is palpable at > 5 cm below the left costal 
margin or a minimum 100% increase in palpable distance for baseline splenomegaly 
of 5-10 cm or a minimum 50% increase in palpable distance for baseline 
splenomegaly of > 10 cm. 
• Extramedullary disease outside of the spleen 
Minor criteria: 
• Transfusion dependence§ 
• Significant loss of maximal response on cytopenias ≥ 50% decrement from maximum 
remission/response in granulocytes or platelets. 
• Reduction in Hgb by ≥1.5g/dL from best response or from baseline as noted on complete 
blood count. 
• Evidence of clonal evolution (molecular)¶ 
* Blasts as measured from the bone marrow. 
† Patients with development of acute myeloid leukemia from MDS/MPN; 20%-30% blasts may be allowed on some clinical trials 
for patients with MDS/MPN. 
‡ Increase in cytogenetic burden of disease by ≥ 50% (via FISH or classic karyotyping).  Given variability of fluorescent probes 
used in FISH, cytogenetic normalization via FISH will depend on specific probes used. 
§ Transfusion dependency is defined by a history of at least 2 U of red blood cell transfusions in the past month for a hemoglobin 
level < 8.5 g/dL that was not associated with clinically overt bleeding.  Cytopenias resulting from therapy should not be 
considered in assessment of progression. 
¶ The identification of new abnormalities using single nucleotide polymorphism arrays or sequencing or a clearly significant 
increase in mutational burden of a previously detected abnormality.  Precise criteria for defining new abnormalities and what 
exactly constitutes a significant increase in mutational burden are open to interpretation; this criterion should be used 
conservatively based on current evidence. 
Source:  Savona et al 2015. 


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APPENDIX I. REVISED RESPONSE CRITERIA FOR 
MYELOFIBROSIS:  IWG-MRT AND ELN CONSENSUS 
REPORT 
Response 
Category 
Required Criteria 
(for all categories, benefit must last for ≥ 12 weeks to qualify as a response) 
Complete 
response 
• Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤ Grade 1 MF† 
• Hemoglobin ≥ 100 g/L and < UNL; neutrophil count ≥ 1 × 109/L and < UNL; 
• Platelet count ≥ 100 × 109/L and < UNL; < 2% immature myeloid cells‡ 
• Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH 
Partial response 
• Hemoglobin ≥100 g/L and < UNL; neutrophil count ≥ 1 × 109/L and < UNL; platelet count 
≥ 100 × 109/L and < UNL; < 2% immature myeloid cells‡ 
• Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH 
• Bone marrow:* Age-adjusted normocellularity; < 5% blasts; ≤ Grade 1 MF†, and 
peripheral blood:  Hemoglobin ≥ 85 but < 100 g/L and < UNL; neutrophil count 
≥ 1 × 109/L and < UNL; platelet count ≥ 50, but < 100 × 109/L and < UNL; < 2% immature 
myeloid cells‡ 
• Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH 
Clinical 
improvement 
• The achievement of anemia, spleen or symptoms response without progressive disease or 
increase in severity of anemia, thrombocytopenia, or neutropenia§ 
Anemia response  
• Transfusion-independent patients:  a ≥ 20 g/L increase in hemoglobin level|| 
• Transfusion-dependent patients:  becoming transfusion-independent¶ 
Spleen response# 
• Baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not 
palpable** or 
• Baseline splenomegaly that is palpable at > 10 cm, below the LCM, decreases by ≥ 50%** 
- 
Baseline splenomegaly that is palpable at < 5 cm, below the LCM, is not eligible for 
spleen response 
- 
Spleen response requires confirmation by MRI or computed tomography showing 
≥ 35% spleen volume reduction. 
Progressive 
disease‡‡ 
• Appearance of a new splenomegaly that is palpable at least 5 cm below the LCM or 
• ≥ 100% increase in palpable distance, below LCM, for baseline splenomegaly of 5-10 cm 
or 
• 50% increase in palpable distance, below LCM, for baseline splenomegaly of > 10 cm or 
• Leukemic transformation confirmed by a bone marrow blast count of ≥ 20% or 
• Peripheral blood blast content of ≥ 20% associated with an absolute blast count of 
≥ 1 × 109/L that lasts for at least 2 weeks 
Stable disease 
• Belonging to none of the above listed response categories. 
Relapse 
• No longer meeting criteria for at least CI after achieving CR, PR, or CI, or 
• Loss of anemia response persisting for at least 1 month, or 
• Loss of spleen response persisting for at least 1 month. 
EMH = extramedullary hematopoiesis (no evidence of EMH implies the absence of pathology- or imaging study-proven 
nonhepatosplenic EMH); LCM = left costal margin; UNL = upper normal limit. 
* Baseline and posttreatment bone marrow slides are to be interpreted at one sitting by a central review process.  Cytogenetic and 
molecular responses are not required for CR assignment. 
† Grading of MF is according to the European classification. 


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‡ Immature myeloid cells constitute blasts + promyelocytes + myelocytes + metamyelocytes + nucleated red blood cells.  In 
splenectomized patients, < 5% immature myeloid cells is allowed. 
§ See above for definitions of anemia response, spleen response, and progressive disease.  Increase in severity of anemia 
constitutes the occurrence of new transfusion dependency or a ≥ 20 g/L decrease in hemoglobin level from pretreatment 
baseline that lasts for at least 12 weeks.  Increase in severity of thrombocytopenia or neutropenia is defined as a 2-grade 
decline, from pretreatment baseline, in platelet count or absolute neutrophil count, according to the Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0.  In addition, assignment to CI requires a minimum platelet count of 
≥ 25,000 × 109/L and absolute neutrophil count of ≥ 0.5 × 109/L. 
|| Applicable only to patients with baseline hemoglobin of < 100 g/L.  In patients not meeting the strict criteria for transfusion 
dependency at the time of study enrollment (see as follows), but who have received transfusions within the previous month, the 
pretransfusion hemoglobin level should be used as the baseline. 
¶ Transfusion dependency before study enrollment is defined as transfusions of at least 6 units of packed red blood cells, in the 
12 weeks prior to study enrollment, for a hemoglobin level of < 85 g/L, in the absence of bleeding or treatment-induced 
anemia.  In addition, the most recent transfusion episode must have occurred in the 28 days prior to study enrollment.  
Response in transfusion-dependent patients requires absence of any packed red blood cell transfusions during any consecutive 
"rolling" 12-week interval during the treatment phase, capped by a hemoglobin level of ≥ 85 g/L. 
# In splenectomized patients, palpable hepatomegaly is substituted with the same measurement strategy. 
** Spleen or liver responses must be confirmed by imaging studies where a ≥ 35% reduction in spleen volume, as assessed by 
MRI or CT, is required.  Furthermore, a ≥ 35% volume reduction in the spleen or liver, by MRI or CT, constitutes a response 
regardless of what is reported with physical examination. 
‡‡ Progressive disease assignment for splenomegaly requires confirmation by MRI or computed tomography showing a ≥ 25% 
increase in spleen volume from baseline.  Baseline values for both physical examination and imaging studies refer to 
pretreatment baseline and not to posttreatment measurements. 
Source:  Tefferi et al 2013. 


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APPENDIX J. INTERNATIONAL UNIFORM RESPONSE CRITERIA 
FOR MULTIPLE MYELOMA 
Response 
Subcategory 
Response Criteria 
sCR 
CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow by 
immunohistochemistry or immunofluorescence.1 
CR 
Negative immunofixation on the serum and urine, disappearance of any soft tissue 
plasmacytomas, and < 5% plasma cells in bone marrow. 
VGPR 
Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or 
greater reduction in serum M-protein with urine M-protein level < 100 mg per 24 hours. 
PR 
• ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% 
or to < 200 mg per 24 hours. 
• If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference 
between involved and uninvolved FLC levels is required in place of the M-protein criteria. 
• If serum and urine M-protein and serum FLC are unmeasurable2, then ≥ 50% reduction in 
plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell 
percentage was ≥ 30%. 
• In addition to the above-listed criteria, if present at baseline, a ≥ 50% reduction in the size 
of soft tissue plasmacytomas is also required. 
SD 
Not meeting criteria for CR, VGPR, PR, MR, or PD. 
PD 
Any one or more of the following: 
• Increase of ≥ 25% from lowest response level in: 
- 
serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL) 
- 
urine M-component and/or (the absolute increase must be ≥ 200 mg/24 h) 
• Only in subjects without measurable serum and urine M-protein levels: the difference 
between involved and uninvolved FLC levels.  The absolute increase must be > 10 mg/dL. 
• Bone marrow plasma cell percentage:  the absolute % must be ≥ 10% 
• Definite development of new bone lesions or soft tissue plasmacytomas or definite increase 
in the size of existing bone lesions or soft tissue plasmacytomas. 
• Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) 
that can be attributed solely to the plasma cell proliferative disorder. 
CR = complete response; FLC = free light chain; PR = partial response; SD = stable disease; sCR = stringent complete response; 
VGPR = very good partial response. 
Note:  All response categories require 2 consecutive assessments made at any time before the institution of any new therapy; all 
categories also require no known evidence of progressive or new bone lesions if radiographic studies were performed.  
Radiographic studies are not required to satisfy these response requirements. 
1 Presence/absence of clonal cells is based upon the κ/λ ratio.  An abnormal κ/λ ratio by immunohistochemistry and/or 
immunofluorescence requires a minimum of 100 plasma cells for analysis.  An abnormal ratio reflecting presence of an 
abnormal clone is κ/λ of > 4:1 or < 1:2. 
2 Measurable disease:  serum M-protein ≥ 1 g/dL, urine M-protein > 200 mg/24 hr, or serum involved FLC levels > 10 mg/dL 
with a normal κ/λ ratio. 
3   For progressive disease, serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is 
≥ 5 g/dl. 
4   Relapse from CR has the 5% cutoff versus 10% for other categories of relapse. 
Source:  Durie et al 2006. 


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APPENDIX K. CRITERIA FOR EVALUATING DISEASE RESPONSE 
AND PROGRESSION IN SUBJECTS WITH MULTIPLE 
MYELOMA TREATED BY HIGH-DOSE THERAPY AND 
HAEMOPOIETIC STEM CELL TRANSPLANTATION 
Minimal 
Response 
• 
≥ 25% but ≤ 49% reduction of serum M-protein and reduction in 24-hour urine 
M-protein by 50% to 89%.  
• 
In addition to the above criteria, if present at baseline, 25% to 49% reduction 
in the size of soft tissue plasmacytomas is also required. 
• 
No increase in size or number of lytic bone lesions (development of 
compression fracture does not exclude response). 
Source:  Blade et al 1998. 


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APPENDIX L. RESPONSE CRITERIA FOR LYMPHOMA – THE 
LUGANO CLASSIFICATION 
Site 
PET–Based Response 
CT/MRI-Based Response 
 
Complete metabolic response 
Complete radiologic response 
(all of the following) 
Lymph nodes and 
extralymphatic 
sites 
Score 1, 2, or 3 with or without a residual 
mass on 5PS.a 
Target nodes/nodal masses must regress to 
≤ 1.5 cm in LDi. 
Nonmeasured 
lesion 
Not applicable. 
Absent. 
Organ enlargement 
Not applicable. 
Regress to normal. 
New lesions 
None. 
None. 
Bone marrow 
No evidence of FDG-avid disease in 
marrow. 
Normal by morphology; if indeterminate, IHC 
negative. 
 
Partial metabolic response 
Partial remission (all of the following) 
Lymph nodes and 
extralymphatic 
sites 
• Score 4 or 5.a with reduced uptake 
compared with baseline and residual 
mass(es) of any size. 
 
• ≥ 50% decrease in SPD of up to 6 target 
measurable nodes and extranodal sites. 
• When a lesion is too small to measure on CT, 
assign 5 mm × 5 mm as the default value. 
• When no longer visible, 0 × 0 mm. 
For a node > 5 mm × 5 mm but smaller than 
normal, use actual measurement for calculation. 
Nonmeasured 
lesions 
Not applicable. 
Absent/regressed, but no increase. 
Organ enlargement 
Not applicable. 
Spleen must have regressed by > 50% in length 
beyond normal. 
New lesions 
None. 
None. 
Bone marrow 
Residual uptake higher than uptake in 
normal marrow but reduced compared with 
baseline (diffuse uptake compatible with 
reactive changes from chemotherapy 
allowed).  If there are persistent focal 
changes in the marrow in the context of a 
nodal response, consideration should be 
given for further evaluation with MRI or 
biopsy at interval scan. 
Not applicable. 
 
No metabolic response 
Stable disease 
Target nodes/ 
nodal masses, 
extranodal lesions 
Score of 4 or 5.a with no significant change 
in FDG uptake from baseline at interim or 
EOT. 
< 50% decrease from baseline in SPD of up to 
6 dominant, measurable nodes and extranodal 
sites; no criteria for progressive disease are 
met. 
Nonmeasured 
lesions 
Not applicable. 
No increase consistent with progression. 
Organ enlargement 
Not applicable. 
No increase consistent with progression. 
New lesions 
None. 
None. 
Bone marrow 
No change from baseline. 
Not applicable. 


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Site 
PET-CT–Based Response 
CT-Based Response 
 
Progressive metabolic disease: 
Progressive disease (requires at least 1 of the 
following): 
Individual target 
nodes/nodal lesions 
Individual target nodes/nodal lesions: 
• Score 4 or 5.a with an increase in 
intensity of uptake from baseline and/or 
• New FDG-avid foci consistent with 
lymphoma at interim or EOT 
assessment. 
 
Extranodal lesions: 
• New FDG-avid foci consistent with 
lymphoma at interim or end-of-treatment 
assessment. 
 
New lesions: 
• New FDG-avid foci consistent with 
lymphoma rather than another etiology 
(eg, infection, inflammation).  If 
uncertain regarding etiology of new 
lesions, biopsy or interval scan may be 
considered. 
 
Bone marrow: 
• New or recurrent FDG-avid foci. 
PPD progression: 
• An individual node/lesion must be abnormal 
with all of the following:   
o LDi > 1.5 cm  
o Increase by ≥ 50% from PPD nadir 
o An increase in LDi or SDi from nadir 
 0.5 cm for lesions ≤ 2 cm 
 1.0 cm for lesions > 2 cm 
• In the setting of splenomegaly, the splenic 
length must increase by > 50% of the extent 
of its prior increase beyond baseline (eg, a 
15-cm spleen must increase to > 16 cm).  If 
no prior splenomegaly, must increase by at 
least 2 cm from baseline. 
• New or recurrent splenomegaly. 
• New or clear progression of preexisting 
nonmeasured lesions. 
• Regrowth of any previously resolved lesions. 
• A new node > 1.5 cm in any axis. 
• A new extranodal site > 1.0 cm in any axis; if 
< 1.0 cm in any axis, its presence must be 
unequivocal and must be attributable to 
lymphoma. 
• Assessable disease of any size unequivocally 
attributable to lymphoma. 
• New or recurrent involvement of the bone 
marrow. 
   5PS = 5-point scale; LDi = longest transverse diameter of lesion; MRI = magnetic resonance imaging; PPD = 
cross product of the LDi and perpendicular diameter; SDi = shortest axis perpendicular to the LDi; SPD = sum of 
the product of the perpendicular diameters for multiple lesions. 
a PET 5-point scale: 1, no uptake above background; 2, update ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 
4, uptake moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of uptake 
unlikely to be related to lymphoma. 
Source:  Cheson et al 2014. 

SAP_001.pdf: 
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Page 1 of 47 
INCB 54329-101 Statistical Analysis Plan 
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CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
INCB 54329-101 / NCT02431260 
A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability 
Study of INCB054329 in Subjects With Advanced Malignancies 
IND Number: 
124,657 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
INCB 54329-101 Amendment 2 dated 08 DEC 2016 
CRF Approval Date: 
01 MAY 2017 
SAP Version: 
Original 
SAP Author: 
 
 Biostatistics 
Date of Plan: 
05 APR 2018 
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 ..........................................................................................................7 
1. 
INTRODUCTION ......................................................................................................10 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS...............................10 
2.1. 
Protocol and Case Report Form Version ....................................................................10 
2.2. 
Study Objectives .........................................................................................................10 
2.2.1. 
Primary Objective .......................................................................................................10 
2.2.2. 
Secondary Objectives .................................................................................................10 
 
10 
2.3. 
Study Endpoints ..........................................................................................................11 
2.3.1. 
Primary Endpoint ........................................................................................................11 
2.3.2. 
Secondary Endpoints ..................................................................................................11 
 
11 
3. 
STUDY DESIGN .......................................................................................................11 
3.1. 
Randomization ............................................................................................................14 
3.2. 
Control of Type I Error ...............................................................................................14 
3.3. 
Sample Size Considerations .......................................................................................14 
3.3.1. 
Sample Size in Part 1 ..................................................................................................14 
3.3.2. 
Sample Size in Part 2 ..................................................................................................15 
3.3.3. 
Sample Size in Part 3 ..................................................................................................15 
3.4. 
Schedule of Assessments ............................................................................................15 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................16 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................16 
4.1.1. 
Day 1 ...........................................................................................................................16 
4.1.2. 
Study Day ...................................................................................................................16 
4.1.3. 
Baseline Value ............................................................................................................16 
4.1.4. 
Handling of Missing and Incomplete Data .................................................................16 
4.1.5. 
Cycle Length and Duration .........................................................................................17 
4.2. 
Variable Definitions ....................................................................................................18 
4.2.1. 
Age ..............................................................................................................................18 
4.2.2. 
Prior and Concomitant Medication .............................................................................18 
5. 
STATISTICAL METHODOLOGY ...........................................................................19 


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5.1. 
General Methodology .................................................................................................19 
5.2. 
Treatment Groups .......................................................................................................19 
5.3. 
Analysis Populations ..................................................................................................19 
5.3.1. 
Efficacy Evaluable Population ...................................................................................19 
5.3.2. 
Safety Population ........................................................................................................19 
5.3.3. 
Pharmacokinetic and Pharmacodynamic Evaluable Populations ...............................20 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................21 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............21 
6.1.1. 
Demographics .............................................................................................................21 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................21 
6.1.3. 
Prior Therapy ..............................................................................................................22 
6.1.4. 
Medical History ..........................................................................................................22 
6.2. 
Disposition of Subjects ...............................................................................................22 
6.3. 
Protocol Deviations and Violations ............................................................................22 
6.4. 
Exposure .....................................................................................................................22 
6.5. 
Study Drug Compliance .............................................................................................23 
6.6. 
Prior and Concomitant Medication .............................................................................23 
7. 
EFFICACY .................................................................................................................24 
7.1. 
General Considerations ...............................................................................................24 
7.2. 
Efficacy Hypotheses ...................................................................................................24 
7.3. 
Analysis of the Efficacy Parameter ............................................................................24 
7.3.1. 
Solid Tumors ..............................................................................................................24 
7.3.1.1. 
Response Assessment .................................................................................................24 
7.3.1.2. 
Best Overall Response and Objective Response Rate ................................................24 
7.3.1.3. 
Progression-Free Survival ..........................................................................................25 
7.3.1.4. 
Duration of Response .................................................................................................25 
7.3.1.5. 
Best Change in Target Lesion Size .............................................................................26 
7.3.2. 
Lymphoma ..................................................................................................................26 
7.3.2.1. 
Response Assessment .................................................................................................26 
7.3.2.2. 
Best Overall Response and Objective Response Rate ................................................26 
7.3.2.3. 
Progression-Free Survival ..........................................................................................27 
7.3.2.4. 
Duration of Response .................................................................................................27 


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7.3.2.5. 
Best Change in Target Lesion Size .............................................................................27 
7.3.3. 
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma ............................27 
7.3.3.1. 
Response Assessment .................................................................................................27 
7.3.3.2. 
Best Overall Response and Objective Response Rate ................................................28 
7.3.3.3. 
Progression-Free Survival ..........................................................................................28 
7.3.3.4. 
Duration of Response .................................................................................................28 
7.3.3.5. 
Change in Peripheral Blood Leukemic Cells ..............................................................28 
7.3.4. 
Acute Myeloid Leukemia ...........................................................................................28 
7.3.4.1. 
Response Assessment .................................................................................................28 
7.3.4.2. 
Best Overall Response and Objective Response Rate ................................................29 
7.3.4.3. 
Event-Free Survival ....................................................................................................29 
7.3.4.4. 
Duration of Response .................................................................................................30 
7.3.5. 
Myelodysplastic Syndrome ........................................................................................30 
7.3.5.1. 
Response Assessment .................................................................................................30 
7.3.5.2. 
Best Overall Response and Objective Response Rate ................................................31 
7.3.5.3. 
Event-Free Survival ....................................................................................................32 
7.3.5.4. 
Duration of Response .................................................................................................32 
7.3.6. 
Myelodysplastic Syndrome/Myeloproliferative Neoplasms ......................................32 
7.3.6.1. 
Response Assessment .................................................................................................32 
7.3.6.2. 
Best Overall Response and Objective Response Rate ................................................33 
7.3.6.3. 
Event-Free Survival ....................................................................................................33 
7.3.6.4. 
Duration of Response .................................................................................................33 
7.3.7. 
Myelofibrosis ..............................................................................................................34 
7.3.7.1. 
Response Assessment .................................................................................................34 
7.3.7.2. 
Best Overall Response and Objective Response Rate ................................................34 
7.3.7.3. 
Event-Free Survival ....................................................................................................35 
7.3.7.4. 
Duration of Response .................................................................................................35 
7.3.8. 
Multiple Myeloma ......................................................................................................35 
7.3.8.1. 
Response Assessment .................................................................................................35 
7.3.8.2. 
Best Overall Response and Objective Response Rate ................................................36 
7.3.8.3. 
Event-Free Survival ....................................................................................................36 
7.3.8.4. 
Duration of Response .................................................................................................36 
7.4. 
Analysis of Other Efficacy Variables .........................................................................36 


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7.4.1. 
Overall Survival ..........................................................................................................36 
7.4.2. 
Eastern Cooperative Oncology Group Performance Status ........................................37 
7.5. 
Pharmacokinetic Analyses ..........................................................................................37 
7.6. 
Pharmacodynamic Analyses .......................................................................................37 
8. 
SAFETY AND TOLERABILITY ..............................................................................38 
8.1. 
General Considerations ...............................................................................................38 
8.2. 
Adverse Events ...........................................................................................................38 
8.2.1. 
Adverse Event Definitions ..........................................................................................38 
8.2.2. 
Dose-Limiting Toxicities ............................................................................................39 
8.2.3. 
Maximum Tolerated Dose ..........................................................................................39 
8.2.4. 
Adverse Event Summaries ..........................................................................................39 
8.3. 
Clinical Laboratory Tests ...........................................................................................40 
8.3.1. 
Laboratory Value Definitions .....................................................................................40 
8.3.2. 
Laboratory Value Summaries .....................................................................................40 
8.4. 
Vital Signs ..................................................................................................................41 
8.5. 
Electrocardiograms .....................................................................................................42 
9. 
INTERIM ANALYSES ..............................................................................................42 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................42 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................42 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................42 
11. 
REFERENCES ...........................................................................................................43 
APPENDIX A. PLANNED TABLES AND FIGURES .............................................................44 
 


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LIST OF TABLES 
Table 1: 
Probability of Dose Escalation for Specific Dose-Limiting Toxicity Rates 
During 3 + 3 Dose Escalation .....................................................................................15 
Table 2: 
Evaluation and Censoring of Progression-Free Survival ............................................25 
Table 3: 
Evaluation and Censoring of Event-Free Survival .....................................................30 
Table 4: 
Confirmation of Complete Remission, Partial Remission, and Marrow 
Complete Remission for Myelodysplastic Syndrome ................................................31 
Table 5: 
Identification of Records for Postbaseline By-Visit Summaries ................................41 
Table 6: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................41 
Table 7: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................42 
Table 8: 
Statistical Analysis Plan Versions ..............................................................................42 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................12 
 


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CONFIDENTIAL 
LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
AML 
acute myeloid leukemia 
ANOVA 
analysis of variance 
AUC0-t 
AUC from time zero (predose) to time of last observed quantifiable concentration 
within a subject across all treatments  
BET 
bromodomain extra-terminal 
BID 
twice daily 
BOR 
best overall response 
CCyR 
complete cytogenetic response 
CI 
confidence interval 
Cl/F 
oral dose clearance  
CLL 
chronic lymphocytic leukemia 
Cmax 
maximum observed concentration  
Cmin 
minimum observed concentration  
CMR 
complete molecular response 
c-MYC 
cellular form of a regulator gene that can act as an oncogene (MYC) 
CR 
complete response 
CRF 
case report form 
CRi 
complete remission with incomplete recovery 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLBCL 
diffuse large B-cell lymphoma  
DLT 
dose-limiting toxicity 
DOR 
duration of response 
DSS 
Durie Salmon stage 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EFS 
event-free survival 
ELN 
European LeukemiaNet 
FDA 
Food and Drug Administration 
HI 
hematologic improvement 
HI-E 
hematologic improvement-erythroid response 
HI-N 
hematologic improvement-neutrophil response 
HI-P 
hematologic improvement-platelet response 
ICF 
informed consent form 


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CONFIDENTIAL 
Abbreviation 
Term 
IPSS 
International Prognostic Scoring System 
ISS 
International Staging System 
IWG 
International Working Group 
MDS 
myelodysplastic syndrome 
MDS/MPN 
myelodysplastic/myeloproliferative neoplasms 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
myelofibrosis 
MLFS 
morphologic leukemia-free state 
MM 
multiple myeloma 
MR 
minimal response 
MTD 
maximum tolerated dose 
NA 
not assessed 
NCI 
National Cancer Institute  
ND 
not done 
NE 
not evaluable 
NSCLC  
non–small cell lung cancer  
ORR 
objective response rate 
OS 
overall survival 
PAD 
pharmacologically active dose 
PCyR 
partial cytogenetic response 
PD 
progressive disease 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PMR 
partial molecular response 
PR 
partial response 
PT 
preferred term 
QD 
once daily 
QTcF 
QT interval corrected using Fridericia's formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sCR 
stringent complete response 
SD 
stable disease 
SLL 
small lymphocytic lymphoma 
SOC 
system organ class 


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Abbreviation 
Term 
TEAE 
treatment-emergent adverse event 
TGA 
Treatment Group A 
TGB 
Treatment Group B 
TGC 
Treatment Group C 
Tmax 
time of occurrence of Cmax 
VGPR 
very good partial response 
WHO 
World Health Organization 


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CONFIDENTIAL 
1. 
INTRODUCTION 
This is a Phase 1/2, open-label, dose-escalation study of the BET inhibitor INCB054329 in 
subjects with advanced malignancies.  Subjects will receive QD doses of INCB054329 in 21-day 
cycles until withdrawal criteria are met (eg, toxicity, disease progression).  Alternative dosing 
regimens may be explored based on emerging PK, pharmacodynamics, and safety data. 
The study will be conducted in 3 parts:  Part 1 Dose Escalation will determine the MTD of 
INCB054329 and/or a tolerated dose that reaches the desired target inhibition (ie, a PAD).  Part 2 
Dose Titration will determine the feasibility of intrasubject dose titration using Protocol-defined 
criteria.  Part 3 Dose Expansion will evaluate the doses and schedules selected in Part 1 and 
Part 2 in subjects with select tumor types postulated to be particularly susceptible to BET 
inhibition. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCB 54329-101 Protocol.  The scope of this plan includes analyses that are planned 
and will be executed by the Department of Biostatistics or designee, and the analyses of PK data.  
The 
 pharmacodynamics data are not described in this 
SAP. 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on Study INCB 54329-101 Amendment 2 dated 08 DEC 2016 and CRFs 
approved on 01 MAY 2017.  Unless superseded by an amendment, this SAP will be effective for 
all subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives 
2.2.1. 
Primary Objective 
 To evaluate the safety and tolerability of INCB054329 in subjects with advanced 
malignancies. 
2.2.2. 
Secondary Objectives 
 To evaluate the PK and pharmacodynamics of INCB054329 in subjects with 
advanced malignancies. 
 To evaluate preliminary efficacy of INCB054329 in subjects with advanced 
malignancies. 


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2.3. 
Study Endpoints 
2.3.1. 
Primary Endpoint 
 Safety and tolerability will be assessed by monitoring frequency, duration, and 
severity of AEs; through physical examinations; by evaluating changes in vital signs 
and ECGs; and through clinical laboratory blood and urine sample evaluations. 
2.3.2. 
Secondary Endpoints 
 Pharmacokinetics of INCB054329, including Cmax, Tmax, Cmin, AUC0-t, and Cl/F at 
Days 1, 2, 8, 15, and 16 of Cycle 1, for subjects in Parts 1, 2 and 3 and any cycle 
where dose escalation occurs. 
 Pharmacodynamic profile of INCB054329 using a whole blood pharmacodynamics 
assay. 
 Evaluation of ORR, PFS, DOR, and OS for subjects in Part 2 and Part 3. 
3. 
STUDY DESIGN 
This is a Phase 1/2, open-label, dose-escalation study of INCB054329 in subjects with advanced 
malignancies.  Subjects will receive QD doses of INCB054329 in 21-day cycles until withdrawal 
criteria are met (eg, toxicity, disease progression).  The study will be conducted in 3 parts: 
 Part 1 Dose Escalation will determine the MTD of INCB054329 and/or a tolerated 
dose that reaches the desired target inhibition (ie, a PAD). 
 Part 2 Dose Titration will determine the feasibility of intrasubject dose titration using 
Protocol-defined criteria. 
 Part 3 Dose Expansion will evaluate the doses and schedules selected in Part 1and 
Part 2 in subjects with select tumor types postulated to be particularly susceptible to 
BET inhibition (refer to Protocol Section 3.2, Subject Inclusion Criteria). 
The study design is shown in Figure 1. 


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Figure 1: 
Study Design 
 
Part 1 Dose Escalation 
The study will begin with open-label dose escalation in TGA, using a 3 + 3 design to determine 
the tolerated dose over a 21-day cycle.  Initially, subjects in Cohort 1 will receive a single dose 
of INCB054329 followed by a timed PK assessment to confirm exposure approximately 1 week 
before continuous administration is initiated (referred to as Day 0).  The starting dose for 
continuous administration will be determined based on the exposures assessed at this PK 
assessment; this dose will be no higher than 15 mg. 
The dose-escalation portion of the study will be conducted in the following treatment groups: 
 TGA will include subjects with any advanced solid tumor or lymphoma. 
 TGB will include subjects with acute leukemia, MDS, MDS/MPN, and MF. 
Escalation will begin with Cohort 1 (including the Day 0 single-dose PK assessment) in TGA.  
Treatment Group B will begin enrollment at the PAD (plasma concentration exceeding the PK 
which is projected to inhibit c-Myc level ≥ 50% for approximately 10 hours) or a tolerated dose 
identified in TGA at the discretion of the sponsor, and dose escalation will proceed 
independently to an MTD in each treatment group using a 3 + 3 design.  Treatment Group C will 
open in Part 2 instead of Part 1 (refer to the rationale in Protocol Section 1.8).  Alternative dose 
regimens may be explored, such as BID or intermittent dose regimens, pending emerging PK, 


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pharmacodynamics, and safety data.  If there is a distinct discrepancy in tolerability among 
different disease types within the same treatment group, additional disease-specific dose-
escalation schedules may be initiated. 
Each dose-escalation cohort will initially enroll at least 3 subjects.  If no DLTs are observed in 
the initial 3 subjects, the next cohort will begin enrollment at the next highest dose level.  
Subjects not receiving at least 80% of the planned study drug doses during the first cycle 
(ie, ≥ 17 of the 21 QD doses or 34 of the 42 BID doses in Cycle 1) will be considered 
nonevaluable for the purposes of determining the MTD (unless due to a DLT) and will be 
replaced.  Cohorts may include an additional subject to ensure that enough evaluable subjects 
reach Day 21. 
Dose increases between cohorts may be up to 2-fold until a Grade 2 toxicity is observed, after 
which dose increases will be limited to no more than 50% above the previous level.  If 1 DLT is 
observed in the first 3 subjects in a cohort, at least 3 additional subjects will be enrolled in that 
cohort.  If a DLT occurs in one-third or more of the total cohort (ie, ≥ 2 of 6 subjects), then the 
MTD will be deemed to have been exceeded, and the next lower dose level will be deemed to be 
the tolerated dose.  Thus, the MTD will be defined as 1 dose level below that at which one-third 
or more of subjects in a particular cohort report DLTs.  If the Cohort 1 dose is not tolerated 
(≥ 2 of 6 subjects report a DLT), a dose de-escalation will be considered. 
If a PAD is reached before identifying the MTD, the PAD may be selected for use in the 
expansion cohort (Part 3), at the discretion of the sponsor. 
Individual subjects within each cohort will undergo reductions/interruptions in INCB054329 
administration according to prescribed safety parameters. 
Part 2 Dose Titration 
Part 2 will enroll 2 treatment groups to investigate the feasibility of intrasubject dose titration 
with Protocol-defined criteria.  Part 2 TGA will enroll subjects with advanced solid tumors and 
lymphomas; Part 2 TGC will enroll subjects with MM.  The starting dose will be the highest 
tolerated dose with continuous BID dose administration identified in Part 1 TGA.  Based on 
emerging data, the starting dose for Part 2 TGA and TGC was 20 mg BID.  Part 2 TGA and TGC 
will simultaneously enroll at least 5 subjects and up to approximately 10 subjects each.  At the 
end of Cycle 1, if dose titration criteria are met (refer to Protocol Section 4.1.2.1), the dose may 
be increased to 25 mg BID on Day 1 of Cycle 2.  Dose escalation by ≤ 5 mg BID increments 
may be permitted after each subsequent cycle of treatment if the subject continues to meet the 
dose escalation criteria.  Dose interruptions, reductions, or termination may be implemented as 
described in Protocol Section 5.6.  Part 2 may also explore 1 or more alternate dose regimens. 
Part 3 Dose Expansion 
Part 3 of the study will evaluate the dose selected in Part 1 and Part 2 in select tumor types at 
their respective RP2Ds; based on available data, a dose up to the MTD may be selected as the 
RP2D for use in each expansion cohort by the sponsor and investigators.  There will be 
3 treatment groups in Part 3. 


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Part 3 TGA will enroll up to approximately 155 subjects with specified solid tumors or 
lymphoma, with a goal of enrolling 5 subjects per tumor type (DLBCL, Burkett lymphoma, 
colorectal cancer, NSCLC, pancreatic adenocarcinoma, castration-resistant prostate cancer, 
metastatic breast cancer, ovarian cancer, and NUT midline carcinoma); if ≥ 1 of the 5 subjects 
with a select tumor type demonstrates clinically meaningful benefit, enrollment for that tumor 
type would continue up to approximately 15 subjects.  An additional group of up to 
approximately 20 subjects with any tumor known to have c-MYC of sonic hedgehog pathway 
activation will also be enrolled, of whom no fewer than 5 will have DLBCL with a known 
aberration of MYC and BCL2 and/or BLC6 (ie, "double-hit" DLBCL) or B-cell lymphoma, 
unclassifiable with features intermediate between DLBCL and Burkitt lymphoma. 
Part 3 TGB will enroll up to 60 subjects with AML, MDS, MDS/MPN, or MF. 
Part 3 TGC will enroll up to approximately 15 subjects with MM. 
Individual dose modifications (dose interruption, reduction, or termination) will be permitted 
according to Protocol-defined safety parameters.  Subjects will continue to receive INCB054329 
in 21-day cycles until withdrawal criteria are met (eg, toxicity, disease progression).  Part 3 TGA 
(solid tumors and lymphoma) will also include a food-effect study for the first 12 subjects 
enrolled. 
3.1. 
Randomization 
Not applicable. 
3.2. 
Control of Type I Error 
All statistical analyses are exploratory in nature.  Unless otherwise specified, all CIs provided 
will be at the 95% confidence level. 
3.3. 
Sample Size Considerations 
3.3.1. 
Sample Size in Part 1 
In Part 1 of the study, the standard 3 + 3 dose escalation design will be used in 2 disease-specific 
treatment groups:  TGA and TGB.  Based on the design, within each treatment group, a 
minimum of 3 and up to 6 subjects will be enrolled at each dose level.  The total sample size in 
Part 1 will depend on the frequency of DLTs and the number of dose levels tested before the 
MTD or PAD is reached.  Up to 90 subjects will be treated in Part 1 of the study. 
During the 3 + 3 dose escalation in Part 1, the probabilities of dose escalation from that dose 
level for various DLT rates are given in Table 1. 


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Table 1: 
Probability of Dose Escalation for Specific Dose-Limiting Toxicity Rates 
During 3 + 3 Dose Escalation 
True DLT Rate 
Probability of Dose Escalation 
10% 
90.6% 
20% 
70.9% 
30% 
49.4% 
40% 
30.9% 
50% 
17.2% 
60% 
8.2% 
3.3.2. 
Sample Size in Part 2 
Part 2 will enroll 2 treatment groups, TGA and TGC, to investigate the feasibility of intrasubject 
dose titration.  Both TGA and TGC will simultaneously enroll at least 5 and up to approximately 
10 subjects each.  With 5 subjects enrolled, there is > 80% chance of observing at least 
1 responder if the true underlying response rate is 30%. 
3.3.3. 
Sample Size in Part 3 
Part 3 will enroll 3 treatment groups, TGA, TGB, and TGC, to evaluate the dose selected in 
Part 1 and Part 2 in select tumor types at their recommended Phase 2 doses.  Approximately 
5 subjects will be initially enrolled for each tumor type in TGA (with the exception of the group 
including any tumor with a known aberration in c-MYC or other genes in which BET proteins 
are relevant, which will enroll 20 subjects).  With 5 subjects enrolled, there is > 80% chance of 
observing at least 1 responder if the true underlying response rate is 30%. 
For each cancer type in TGB and TGC, at least 5 and up to approximately 15 subjects will be 
enrolled.  With 5 subjects enrolled, there is ≥ 80% chance of observing at least 1 responder if the 
true underlying response rate is 30%. 
3.4. 
Schedule of Assessments 
Refer to Study INCB 54329-101 Protocol Amendment 2 dated 08 DEC 2016 for a full 
description of all study procedures and assessment schedules for this study. 


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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
For analysis purpose, Day 1 is the date that the first dose of study drug (INCB054329) is 
administered to the subjects. 
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 
INCB054329, 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. 
Partial disease/cancer diagnosis date will be handled as follows: 
 If only the day is missing, then the imputed day will be the first day of the month. 
 If both the month and day are missing, then the imputed day and month will be 
01 JAN. 
 No imputation will be done if the date is completely missing. 


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Missing or partial date of last dose will be handled as follows: 
 If only the day is missing, then the imputed date of the last dose will be the earlier 
date of the first day of the month or the date that the subject discontinued treatment. 
 Otherwise, the date that the subject discontinued treatment will be used as the date of 
the last dose. 
For relevant efficacy endpoints, partial death date will be imputed as follows: 
 If mmyyyy for the last contact date = mmyyyy for the death date, then the death date 
will be set to the day after the last contact date. 
 If mmyyyy for the last contact date < mmyyyy for the death date, then the death date 
will be set to the first day of the death month. 
 Otherwise, the partial death date will not be imputed. 
For prior and concomitant medications: 
The start/stop dates recorded on the eCRF by the investigator and his or her research staff will be 
used to identify when a concomitant medication was taken during the study.  Any missing start 
date must be queried for resolution.  Unresolved missing start dates will be handled as follows: 
 If the date is completely missing, the medication will be considered both prior and 
concomitant. 
 If only the day is missing, and the last day of the month is before the first dose date 
on Day 1, then the concomitant medication will be considered as starting before 
Day 1, and the incomplete date will be imputed as the last day of the month. 
 If only the day is missing, and the first day of the month is after the first dose date on 
Day 1, then the concomitant medication will be considered as starting after Day 1, 
and the incomplete date will be imputed as the first day of the month. 
 If only the day is missing, and the month is equal to the month of the first dose date 
on Day 1, then the incomplete date will be imputed as the first day of the month. 
 If both the month and day are missing, and the last day of the year is before the first 
dose date on Day 1, then the concomitant medication will be considered as starting 
before Day 1, and the incomplete date will be imputed as the last day of the year.  
Otherwise, the incomplete date will be imputed as the first day of the year. 
4.1.5. 
Cycle Length and Duration 
For subjects not included in the Day 0 single-dose PK assessment, Cycle 1 Day 1 is the day that 
the first dose of study drug is administered.  For subjects in the Day 0 single-dose PK 
assessment, that is, the first 3 subjects of Cohort 1 in Part 1 TGA, Cycle 1 Day 1 is the day that 
the first dose is administered after the Day 0 dose.  Scheduled cycle length is 21 days. 
Actual Day 1 of subsequent cycles will correspond with the first day of administration of 
INCB054329 in that cycle; thus, treatment cycles may become out of sync with the originally 
planned schedule, and cycle length may be different from 21 days.  The date of the Day 1 of 
subsequent cycles recorded on the eCRF will be used as the Day 1 of the subsequent cycles. 


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4.2. 
Variable Definitions 
The following variables will only be calculated if not reported on the eCRF. 
4.2.1. 
Age 
Subject age will be calculated as the integer part of the number of years from date of birth to the 
date of signing the ICF, using the following formula: 
Age = integer part of (date of informed consent – date of birth + 1) / 365.25 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB054329. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
 Before the date of first administration of INCB054329 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 INCB054329 and is ongoing or ends 
during the course of study drug. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCB054329.  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. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9.4 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 subjects in each category. 
5.2. 
Treatment Groups 
This is a Phase 1/2, open-label, dose-escalation study.  The efficacy endpoints will be 
summarized by the appropriate disease subtype.  All other data, including baseline, disposition, 
and safety, will be summarized overall and by treatment group based on the dose regimen 
initially assigned.  In the event that several dose regimens tested are deemed substantially below 
the MTD, these doses may be combined for summary purposes. 
5.3. 
Analysis Populations 
5.3.1. 
Efficacy Evaluable Population 
The efficacy evaluable population includes all subjects enrolled in the study who received at 
least 1 dose of INCB054329 and had at least 1 postbaseline disease assessment or who 
discontinued treatment.  All efficacy analyses will be conducted using the efficacy evaluable 
population. 
Specific analysis populations to be used for analysis by cancer type may include the following 
subgroups: 
 Solid tumor efficacy evaluable population 
 Lymphoma efficacy evaluable population 
 AML efficacy evaluable population 
 MDS efficacy evaluable population 
 MDS/MPN efficacy evaluable population 
 MF efficacy evaluable population 
 MM efficacy evaluable population 
5.3.2. 
Safety Population 
The safety population includes all enrolled subjects who received at least 1 dose of 
INCB054329.  All safety analyses will be conducted using the safety population.  Analysis for 
demographics, baseline characteristics, disease history, and subject disposition will also be 
conducted using the safety population. 


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Specific analysis populations to be used for analysis by cancer type may include the following 
subgroups: 
 Solid tumor safety population 
 Lymphoma safety population 
 AML safety population 
 MDS safety population 
 MDS/MPN safety population 
 MF safety population 
 MM safety population 
5.3.3. 
Pharmacokinetic and Pharmacodynamic Evaluable Populations 
The PK evaluable population includes all subjects who received at least 1 dose of INCB054329 
and provided at least 1 postdose sample (1 PK measurement).  The study pharmacokineticist will 
review data listings of study drug administration and sample records to identify subjects to be 
excluded from PK analyses. 
The pharmacodynamic evaluable population includes all subjects who received at least 1 dose of 
INCB054329 and provided at least 1 postdose sample (1 pharmacodynamic measurement).  The 
study research investigator will review data listings of pharmacodynamic data and sample 
records to identify subjects to be excluded from pharmacodynamic analyses. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of data displays. 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
6.1.1. 
Demographics 
The following demographics will be summarized and listed for the safety population:  age, sex, 
race, ethnicity, height, and weight. 
6.1.2. 
Baseline Disease Characteristics and Disease History 
Baseline disease characteristics and disease history will be summarized and listed for all subjects 
in the safety population. 
For all subjects, ECOG performance status will be summarized and listed.  Manual palpation of 
the spleen and the result (for subjects with the applicable disease) and manual palpation of liver 
and the result (for subjects with the applicable disease) will also be summarized and listed. 
For subjects with solid tumors, time since initial diagnosis, solid tumor cancer type, stage at 
initial diagnosis, current stage, MYC rearrangement status and other tumor marker test results 
will be summarized and listed.  Summary may be provided by disease subtype if appropriate. 
For subjects with lymphoma, disease subtype, time since diagnosis, results from cytogenetic 
testing, Ann Arbor staging, presence of B-symptoms at baseline, and tumor marker test results 
will be summarized and listed.  For subjects with DLBCL subtype, International Prognostic 
Index will also be summarized and listed; for subjects with CLL or SLL subtypes, Rai staging 
will also be summarized and listed. 
For subjects with AML, time since initial diagnosis, AML disease category, WHO classification, 
ELN risk classification, presence of extramedullary disease, FLT3 and other tumor marker test 
results will be summarized and listed. 
For subjects with MDS, time since initial diagnosis, WHO classification, IPSS risk group, 
IPSS-R prognostic variable for bone marrow blasts, IPSS-R prognostic variable for cytogenetics, 
IPSS-R prognostic variable for hemoglobin/platelets/absolute neutrophils, and tumor marker test 
results will be summarized and listed. 
For subjects with MDS/MPN, time since initial diagnosis, MDS/MPN disease type, presence of 
extramedullary disease, and tumor marker test results will be summarized and listed. 
For subjects with MF, time since initial diagnosis, MF disease category, prior splenic irradiation, 
prognostic factors (only for primary MF), IWG risk level, and tumor marker test results will be 
summarized and listed. 
For subjects with MM, time since initial diagnosis, initial DSS, initial ISS stage, current DSS, 
current ISS stage, current myeloma type, light chain, light chain type, and tumor marker test 
results will be summarized and listed. 


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Time since diagnosis will be calculated as: 
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25 
6.1.3. 
Prior Therapy 
Prior therapy will be summarized and listed for all subjects in the safety population. 
Number of prior systemic cancer therapy regimens will be summarized.  Regimen name, 
component drugs, start and stop dates, purpose of the regimen, best response, reason for 
discontinuation, and date of relapse/progression will be listed. 
Number of subjects who received prior radiation will be summarized.  Radiotherapy type, 
location of administration, start and stop dates, total dose, and best response will be listed. 
Number of subjects who had prior surgery or surgical procedure for disease under study will be 
summarized.  Date, type, and description of the surgery/procedure will be listed. 
Number of subjects who had hematopoietic stem cell transplant will be summarized.  Date of 
transplant, type of transplant, source cell, line of therapy, best response, and the medication used 
with the transplant will be listed. 
6.1.4. 
Medical History 
For subjects in the safety population, medical history will be summarized by assigned treatment 
group.  This summation will include the number and percentage of subjects with significant 
medical history for each body system/organ class as documented on the eCRF. 
6.2. 
Disposition of Subjects 
The number and percentage of subjects who were treated, discontinued study treatment with a 
primary reason for discontinuation, and discontinued from the study with a primary reason for 
withdrawal will be summarized and listed for the safety population. 
6.3. 
Protocol Deviations and Violations 
Protocol deviations and violations recorded on the eCRF will be presented in the subject data 
listings. 
6.4. 
Exposure 
For subjects in the safety population, exposure to INCB054329 will be summarized descriptively 
as the number of cycles, duration of treatment, and average daily dose.  Study drug 
administration data will be listed. 
 Number of cycles with INCB054329:  Number of cycles with a nonzero dose of 
INCB054329. 
 Duration of treatment with INCB054329 (days):  Duration of treatment (days) = 
date of last dose of INCB054329 – date of first dose of INCB054329 + 1. 


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 Average daily dose of INCB054329 (mg/day):  total actual INCB054329 dose taken 
(mg) / duration of treatment with INCB054329 (days). 
The total actual dose taken will be calculated based on information entered on the 
drug accountability eCRF.  If there is dispensed drug that has not been returned, the 
actual dose taken starting from the dispense date of the unreturned drug will be 
imputed by the dose taken as reported on the dosing eCRF. 
6.5. 
Study Drug Compliance 
For subjects in the safety population, overall compliance (%) for INCB054329 will be calculated 
for all subjects as 
Compliance (%) = 100  [total dose actually taken (mg)] / [total prescribed dose (mg)] 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 
6.6. 
Prior and Concomitant Medication 
For subjects in the safety population, prior medications and concomitant medications will be 
coded using the WHO Drug Dictionary and summarized by WHO drug class and WHO drug 
term.  Results will be summarized as number and percentage of subjects with prior and 
concomitant medications by PT and WHO drug class. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. 
7.1. 
General Considerations 
All efficacy analyses will be performed using the efficacy evaluable population.  If there are less 
than 5 subjects for a disease subtype, efficacy data may be presented in data listings only. 
7.2. 
Efficacy Hypotheses 
Not applicable. 
7.3. 
Analysis of the Efficacy Parameter 
7.3.1. 
Solid Tumors 
7.3.1.1. 
Response Assessment 
Tumor assessment for subjects with solid tumors will be performed using RECIST v1.1 
(Eisenhauer et al 2009).  The investigator's assessment will be used to determine responses and 
will be logged into the eCRF. 
Response status per investigator's assessment for solid tumors will be recorded at each response 
assessment visit as CR, PR, SD, PD, NE, or NA. 
7.3.1.2. 
Best Overall Response and Objective Response Rate 
Best overall response for subjects with solid tumors is the best response recorded prior to and 
including the first PD, in the order of CR, PR, SD, PD, and NE.  In the case of SD, 
measurements must meet the SD criterion at least once on or after Day 42.  Subjects who fail to 
meet this criterion will have a BOR of PD if the next available assessment after the initial 
assessment indicates PD or a BOR of NE if there are no additional assessments available. 
A subject is considered a responder if the subject has a BOR of CR or PR. 
Objective response rate is the proportion of responders.  Subjects 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 calculations of ORR. 
Best overall response will be summarized descriptively.  Objective response rate will be 
estimated with 95% CIs.  Confidence intervals will be calculated based on the exact method for 
binomial distributions. 


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7.3.1.3. 
Progression-Free Survival 
Progression-free survival for solid tumors is defined as the length of time between the start of the 
study drug (Day 1) and the earlier of death or PD.  The date of PD will be the timepoint at which 
PD is first recorded.  Censoring for PFS will follow the algorithm outlined in Table 2, which is 
based on US FDA guidance (FDA 2007). 
The number of subjects who had PD or who died and the number of subjects censored will be 
summarized.  The Kaplan-Meier estimate of median PFS will be presented with its 95% CI. 
Table 2: 
Evaluation and Censoring of Progression-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline tumor assessments 
Censored 
Date of enrollment 
Progression documented between 
scheduled visits 
Progressed 
Earliest of: 
 Date of radiological assessment showing new 
lesion (if progression is based on new lesion); 
or 
 Date of last radiological assessment of 
measured lesions (if progression is based on 
increase in sum of measured lesions) 
No progression 
Censored 
Date of last valid radiologic assessment (not NE 
and not missing) 
Treatment discontinuation for 
undocumented progression 
Censored 
Date of last valid radiologic assessment (not NE 
and not missing) 
Treatment 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) 
Death before first progression 
assessment 
Progressed 
Date of death 
Death between adequate 
assessment visits 
Progressed 
Date of death 
Death or progression after more 
than 1 missed assessment 
Censored 
Date of last valid radiologic assessment (not NE 
and not missing) 
7.3.1.4. 
Duration of Response 
For responders, DOR for solid tumors is the time from the first response of CR or PR to the 
earlier of death or PD occurring after the first response of CR or PR.  The date of PD will be the 
timepoint at which PD is first recorded.  Censoring of DOR will follow the same algorithm as the 
censoring of PFS (Section 7.3.1.3). 
The total number of responders, the number of subjects who had PD or who died, and the 
number of subjects censored will be summarized.  The Kaplan-Meier estimate of median DOR 
will be presented with its 95% CI. 


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7.3.1.5. 
Best Change in Target Lesion Size 
For subjects with measurable lesions at baseline, target lesion sizes will be measured by sum of 
longest diameters.  The best percentage change from baseline, defined as the largest decrease in 
target lesion sizes during the study, will be summarized, and a waterfall plot of the best 
percentage change will be generated.  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 for 
purposes of this analysis.  Likewise, target lesions identified as "not present" at postbaseline 
assessments will be assigned 0 mm for this analysis.  In the event that a target lesions 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. 
7.3.2. 
Lymphoma 
7.3.2.1. 
Response Assessment 
Disease assessment for lymphoma subjects with subtypes other than CLL/SLL will be performed 
following Response Criteria for Lymphoma – The Lugano Classification (Cheson et al 2014).  
The investigator's assessment will be used to determine responses and will be logged into the 
eCRF. 
Response status per investigator's assessment by PET and/or CT/MRI for lymphoma will be 
recorded at each response assessment visit as CR, PR, SD, PD, NE, or ND. 
7.3.2.2. 
Best Overall Response and Objective Response Rate 
Best overall response for lymphoma is the best response recorded prior to and including the first 
PD, in the order of CR, PR, SD, PD, and NE.  In the case of SD, measurements must meet the 
SD criterion at least once on or after Day 42.  Subjects who fail to meet this criterion will have a 
BOR of PD if the next available assessment after the initial assessment indicates PD, or a BOR 
of NE if there are no additional assessments available. 
A subject is considered a responder if the subject has a BOR of CR or PR. 
Objective response rate is the proportion of responders.  Subjects 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 calculations of ORR. 
Best overall response will be summarized descriptively.  Objective response rate will be 
estimated with 95% CIs.  Confidence intervals will be calculated based on the exact method for 
binomial distributions. 


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7.3.2.3. 
Progression-Free Survival 
Progression-free survival for lymphoma is defined as the length of time between the start of the 
study drug (Day 1) and the earlier of death or PD.  The date of PD will be the timepoint at which 
PD is first recorded.  Censoring for PFS will follow the algorithm outlined in Table 2. 
The number of subjects who had PD or who died and the number of subjects censored will be 
summarized.  The Kaplan-Meier estimate of median PFS will be presented with its 95% CI. 
7.3.2.4. 
Duration of Response 
For responders, DOR for lymphoma is the time from the first response of CR or PR to the earlier 
of death or PD occurring after the first response of CR or PR.  The date of PD will be the 
timepoint at which PD is first recorded.  Censoring of DOR will follow the same algorithm as the 
censoring of PFS (Section 7.3.2.3). 
The total number of responders, the number of subjects who had PD or who died, and the 
number of subjects censored will be summarized.  The Kaplan-Meier estimate of median DOR 
will be presented with its 95% CI. 
7.3.2.5. 
Best Change in Target Lesion Size 
For subjects with measurable lesions at baseline, target lesion sizes will be measured by sum of 
product of diameters.  The best percentage change from baseline, defined as the largest decrease 
in target lesion sizes during the study, will be summarized, and a waterfall plot of the best 
percentage change will be generated.  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 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. 
7.3.3. 
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 
7.3.3.1. 
Response Assessment 
Disease assessment for lymphoma subjects with CLL/SLL subtype will be performed using the 
International Workshop on CLL criteria for CLL (Hallek et al 2008, Cheson et al 2012).  The 
investigator's assessment will be used to determine responses and will be logged into the eCRF. 
Response status per investigator's assessment for CLL/SLL will be recorded at each response 
assessment visit as CR, PR, SD, PD, or NE. 


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7.3.3.2. 
Best Overall Response and Objective Response Rate 
Best overall response for CLL/SLL is the best response recorded prior to and including the first 
PD, in the order of CR, PR, SD, PD, and NE. 
A subject is considered a responder if the subject has a BOR of CR or PR. 
Objective response rate is the proportion of responders.  Subjects 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 calculations of ORR. 
Best overall response will be summarized descriptively.  Objective response rate will be 
estimated with 95% CIs.  Confidence intervals will be calculated based on the exact method for 
binomial distributions. 
7.3.3.3. 
Progression-Free Survival 
Progression-free survival for CLL/SLL is defined as the length of time between the start of the 
study drug (Day 1) and the earlier of death or PD.  The date of PD will be the timepoint at which 
PD is first recorded.  Censoring for PFS will follow the algorithm outlined in Table 2. 
The number of subjects who had PD or who died and the number of subjects censored will be 
summarized.  The Kaplan-Meier estimate of median PFS will be presented with its 95% CI. 
7.3.3.4. 
Duration of Response 
For responders, DOR for CLL/SLL is the time from the first response of CR or PR to the earlier 
of death or PD occurring after the first response of CR or PR.  The date of PD will be the 
timepoint at which PD is first recorded.  Censoring of DOR will follow the same algorithm as the 
censoring of PFS (Section 7.3.3.3). 
The total number of responders, the number of subjects who had PD or who died, and the 
number of subjects censored will be summarized.  The Kaplan-Meier estimate of median DOR 
will be presented with its 95% CI. 
7.3.3.5. 
Change in Peripheral Blood Leukemic Cells 
For subjects with CLL/SLL, changes in peripheral blood leukemic cells, including neutrophils, 
platelets, hemoglobin, and lymphocytes, from baseline to each post-treatment assessment will be 
listed. 
7.3.4. 
Acute Myeloid Leukemia 
7.3.4.1. 
Response Assessment 
Disease assessment for subjects with AML will be performed following the IWG Response 
Criteria for AML (Cheson et al 2003).  The investigator's assessment will be used to determine 
responses and will be logged into the eCRF. 
Response status per investigator's assessment for AML will be recorded in terms of 3 aspects:  
(1) altering the natural history of the disease, (2) cytogenetic response, and (3) molecular 
response.  For altering the natural history of the disease, response status will be recorded at each 
response assessment as complete remission, CRi, MLFS, partial remission, peripheral blood blast 


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response, SD, treatment failure, relapse, or PD.  For cytogenetic response, response status will be 
recorded at each response assessment visit as CCyR, PCyR, no response, NA, or not applicable.  
For molecular response, response status will be recorded at each response assessment visit as 
CMR, PMR, no response, NA, or not applicable. 
7.3.4.2. 
Best Overall Response and Objective Response Rate 
7.3.4.2.1. Altering the Natural History of the Disease 
For AML, BOR based on altering the natural history of the disease is the best response recorded 
prior to and including the first progression, which consists of treatment failure, relapse, or PD, in 
the order of complete remission, CRi, MLFS, partial remission, peripheral blood blast response, 
SD, and progression. 
A subject is considered a responder if the subject has a BOR of complete remission, CRi, MLFS, 
or partial remission. 
Objective response rate is defined as the proportion of responders based on altering the natural 
history of the disease.  Subjects 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 calculations of ORR. 
Best overall response will be summarized descriptively.  Objective response rate will be 
estimated with 95% CIs.  Confidence intervals will be calculated based on the exact method for 
binomial distributions. 
7.3.4.2.2. Cytogenetic Response 
Cytogenetic response is applicable for subjects with abnormal karyotype at baseline.  Best 
overall response for cytogenetic response is the best response recorded prior to and including the 
time when first progression based on altering the natural history of the disease occurs, in the 
order of CCyR, PCyR, no response, or NA. 
Best overall response will be summarized descriptively.  Subjects with abnormal karyotype at 
baseline will be included in the denominators in the summary of BOR. 
7.3.4.2.3. Molecular Response 
Molecular response is applicable for subjects with molecular abnormality at baseline.  Best 
overall response for molecular response is the best response recorded prior to and including the 
time when first progression based on altering the natural history of the disease occurs, in the 
order of CMR, PMR, no response, or NA. 
Best overall response will be summarized descriptively.  Subjects with molecular abnormality at 
baseline will be included in the denominators in the summary of BOR. 
7.3.4.3. 
Event-Free Survival 
Event-free survival for AML is defined as the length of time between the start of the study drug 
(Day 1) and the earlier of death or progression.  The date of progression will be the timepoint at 
which progression is first recorded.  Censoring of EFS for AML will follow the algorithm 
outlined in Table 3. 


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The number of subjects who had progression or who died and the number of subjects censored 
will be summarized.  The Kaplan-Meier estimate of median EFS will be presented with its 95% 
CI. 
Table 3: 
Evaluation and Censoring of Event-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline disease assessments 
Censored 
Date of Day 1 
No valid postbaseline response 
assessments 
Censored 
Date of Day 1 
Event documented between 
scheduled response assessments 
Event 
Date of first overall assessment of event 
No event 
Censored 
Date of last valid disease assessment (not NE 
and not missing) 
Treatment discontinuation for 
undocumented event 
Censored 
Date of last valid disease assessment (not NE 
and not missing) 
Treatment discontinuation for 
toxicity or other reason 
Censored 
Date of last valid disease assessment (not NE 
and not missing) 
New anticancer treatment started 
Censored 
Date of last valid disease assessment (not NE 
and not missing) on/before starting a new 
anticancer treatment 
Death before first event response 
assessment or discontinuation from 
study 
Event 
Date of death 
Death between adequate response 
assessments 
Event 
Date of death 
7.3.4.4. 
Duration of Response 
For responders, DOR for AML is the time from the first response of complete remission, CRi, 
MLFS, or partial remission to the earlier of death or progression (ie, treatment failure, relapse, or 
PD) occurring after the first response of complete remission, CRi, MLFS, or partial remission.  
The date of progression will be the timepoint at which progression is first recorded.  Censoring 
of DOR will follow the same algorithm as the censoring of EFS (Section 7.3.4.3). 
The total number of responders, the number of subjects who had progression or who died, and 
the number of subjects censored will be summarized.  The Kaplan-Meier estimate of median 
DOR will be presented with its 95% CI. 
7.3.5. 
Myelodysplastic Syndrome 
7.3.5.1. 
Response Assessment 
Disease assessment for subjects with MDS will be performed following the IWG Response 
Criteria for MDS (Cheson et al 2006).  The investigator's assessment will be used to determine 
responses and will be logged into the eCRF. 


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Response status per investigator's assessment for MDS will be recorded in terms of 3 aspects:  
(1) altering the natural history of the disease, (2) cytogenetic response, and (3) HI.  For altering 
the natural history of the disease, response status will be recorded at each response assessment 
visit as complete remission, partial remission, marrow complete remission, SD, treatment failure, 
disease progression, disease transformation, or relapse after complete remission or partial 
remission.  For cytogenetic response, response status will be recorded at each response 
assessment visit as CCyR, PCyR, no response, or not applicable.  For HI, response status will be 
recorded at each response assessment visit as HI-E, HI-P, HI-N, or not applicable. 
7.3.5.2. 
Best Overall Response and Objective Response Rate 
7.3.5.2.1. Altering the Natural History of the Disease 
For MDS, BOR based on altering the natural history of the disease is the best response recorded 
prior to and including the time when first progression which consists of treatment failure, disease 
progression, disease transformation, and relapse after complete remission or partial remission 
occurs, in the order of complete remission, partial remission, marrow complete remission, SD, 
and progression.  When analysis requires the confirmation of complete remission, partial 
remission, or marrow complete remission, responses must be at least 4 weeks in duration, and the 
rule in Table 4 should be applied. 
Table 4: 
Confirmation of Complete Remission, Partial Remission, and Marrow 
Complete Remission for Myelodysplastic Syndrome 
First Assessment 
Subsequent Assessment at 4 or 
More Weeks Later 
Confirmed Response 
complete remission 
complete remission 
complete remission 
partial remission 
complete remission, or partial 
remission 
partial remission 
marrow complete remission 
complete remission, partial 
remission, or marrow complete 
remission 
marrow complete remission 
A subject is considered a responder if the subject has a BOR of complete remission, partial 
remission, or marrow complete remission. 
Objective response rate is defined as the proportion of responders based on altering the natural 
history of the disease.  Subjects 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 calculations of ORR. 
For non-confirmatory response, BOR will be summarized descriptively, and ORR will be 
estimated with 95% CIs. 
For confirmatory response, the best confirmed response of complete remission, partial remission, 
and marrow complete remission will be summarized descriptively, and the confirmed ORR will 
be estimated with 95% CIs. 
Confidence intervals will be calculated based on the exact method for binomial distributions. 


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7.3.5.2.2. Cytogenetic Response 
Cytogenetic response is applicable for subjects with abnormal karyotype at baseline.  Best 
overall response for cytogenetic response is the best response recorded prior to and including the 
time when the first progression based on altering the natural history of the disease occurs, in the 
order of CCyR, PCyR, or no response. 
Best overall response will be summarized descriptively.  Subjects with abnormal karyotype at 
baseline will be included in the denominators in the summary of BOR. 
7.3.5.2.3. Hematological Improvement 
The number of subjects who had at least 1 HI in postbaseline assessments along with the 
corresponding subcategories (ie, HI-E, HI-P, or HI-N) will be summarized descriptively. 
7.3.5.3. 
Event-Free Survival 
Event-free survival for MDS is defined as the length of time between the start of the study drug 
(Day 1) and the earlier of death or progression.  The date of progression will be the timepoint at 
which progression is first recorded.  Censoring of EFS for MDS will follow the algorithm 
outlined in Table 3. 
The number of subjects who had progression or who died and the number of subjects censored 
will be summarized.  The Kaplan-Meier estimate of median EFS will be presented with its 95% 
CI. 
7.3.5.4. 
Duration of Response 
For responders, DOR for MDS is the time from the first response of complete remission, partial 
remission, or marrow complete remission to the earlier of death or progression occurring after 
the first response of complete remission, partial remission, or marrow complete remission.  The 
date of progression will be the timepoint at which progression is first recorded.  Censoring of 
DOR will follow the same algorithm as the censoring of EFS (Section 7.3.5.3). 
The total number of responders, the number of subjects who had progression or who died, and 
the number of subjects censored will be summarized.  The Kaplan-Meier estimate of median 
DOR will be presented with its 95% CI. 
7.3.6. 
Myelodysplastic Syndrome/Myeloproliferative Neoplasms 
7.3.6.1. 
Response Assessment 
Disease assessment for subjects with MDS/MPN will be performed following the International 
Consortium Proposal of Uniform Response Criteria for MDS/MPN in Adults (Savona 
et al 2015).  The investigator's assessment will be used to determine responses and will be logged 
into the eCRF. 
Response status per investigator's assessment for MDS/MPN will be recorded in terms of 
2 aspects:  (1) altering the natural history of the disease and (2) cytogenetic response.  For 
altering the natural history of the disease, response status will be recorded at each response 
assessment visit as complete remission, partial remission, marrow response, clinical benefit, and 


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PD.  For cytogenetic response, response status will be recorded at each response assessment visit 
as CCyR, no response, or not applicable. 
7.3.6.2. 
Best Overall Response and Objective Response Rate 
7.3.6.2.1. Altering the Natural History of the Disease 
For MDS/MPN, BOR based on altering the natural history of the disease is the best response 
recorded prior to and including the first PD in the order of complete remission, partial remission, 
marrow response, clinical benefit, and PD. 
A subject is considered a responder if the subject has a BOR of complete remission, partial 
remission, or marrow response.  A subject who has an erythroid response, platelet response, 
neutrophil response, or spleen response (as described by Savona et al 2015) in the absence of 
progression or remission and independent of marrow response is considered to be receiving 
clinical benefit but not considered a responder. 
Objective response rate is defined as the proportion of responders based on altering the natural 
history of the disease.  Subjects 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 calculations of ORR. 
Best overall response will be summarized descriptively.  Objective response rate will be 
estimated with 95% CIs.  Confidence intervals will be calculated based on the exact method for 
binomial distributions. 
7.3.6.2.2. Cytogenetic Response 
Cytogenetic response is applicable for subjects with abnormal karyotype at baseline.  Best 
overall response for cytogenetic response is the best response recorded prior to and including the 
time when the first PD based on altering the natural history of the disease occurs, in the order of 
CCyR or no remission. 
Best overall response will be summarized descriptively.  Subjects with abnormal karyotype at 
baseline will be included in the denominators in the summary of BOR. 
7.3.6.3. 
Event-Free Survival 
Event-free survival for MDS/MPN is defined as the length of time between the start of the study 
drug (Day 1) and the earlier of death or PD.  The date of PD will be the timepoint at which PD is 
first recorded.  Censoring of EFS for MDS/MPN will follow the algorithm outlined in Table 3. 
The number of subjects who had PD or who died and the number of subjects censored will be 
summarized.  The Kaplan-Meier estimate of median EFS will be presented with its 95% CI. 
7.3.6.4. 
Duration of Response 
For responders, DOR for MDS/MPN is the time from the first response of complete remission, 
partial remission, or marrow response to the earlier of death or PD occurring after the first 
response of complete remission, partial remission, or marrow response.  The date of PD will be 
the timepoint at which PD is first recorded.  Censoring of DOR will follow the same algorithm as 
the censoring of EFS (Section 7.3.6.3). 


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The total number of responders, the number of subjects who had PD or who died, and the 
number of subjects censored will be summarized.  The Kaplan-Meier estimate of median DOR 
will be presented with its 95% CI. 
7.3.7. 
Myelofibrosis 
7.3.7.1. 
Response Assessment 
Disease assessment for subjects with MF will be performed following the revised Response 
Criteria for MF in the IWG–Myeloproliferative Neoplasms Research and Treatment and ELN 
consensus report (Tefferi et al 2013).  The investigator's assessment will be used to determine 
responses and will be logged into the eCRF. 
Response status per investigator's assessment for MF will be recorded in terms of 3 aspects:  
(1) altering the natural history of the disease, (2) anemia response, and (3) spleen response.  For 
altering the natural history of the disease, response status will be recorded at each response 
assessment visit as CR, PR, clinical improvement, SD, PD, or relapse.  For anemia response, 
response status will be recorded at each response assessment visit as a ≥ 20 g/L increase in 
hemoglobin level (for transfusion-independent subjects) or becoming transfusion-independent 
(for transfusion-dependent subjects).  For spleen response, response status will be recorded at 
each response assessment visit as baseline splenomegaly palpable at 5 to 10 cm below the LCM 
becoming not palpable or baseline splenomegaly palpable at > 10 cm below the LCM decreasing 
by ≥ 50%. 
7.3.7.2. 
Best Overall Response and Objective Response Rate 
7.3.7.2.1. Altering the Natural History of the Disease 
For subjects with MF, BOR based on altering the natural history of the disease is the best 
response recorded prior to and including the time of first progression which consists of PD or 
relapse, in the order of CR, PR, clinical improvement, SD, and progression.  When analysis 
requires the confirmation of CR or PR, responses must be at least 12 weeks in duration.  In this 
case, CR or PR can be confirmed only if the same or better responses as compared with the 
previous ones are met at each subsequent timepoint as specified in the Protocol until benefit lasts 
for ≥ 12 weeks. 
A subject is considered a responder if the subject has a BOR of CR or PR. 
Objective response rate is defined as the proportion of responders based on altering the natural 
history of the disease.  Subjects 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 calculations of ORR. 
For non-confirmatory response, BOR will be summarized descriptively, and ORR will be 
estimated with 95% CIs. 
For confirmatory response, the best confirmed response of CR and PR will be summarized 
descriptively, and the confirmed ORR will be estimated with 95% CIs. 
Confidence intervals will be calculated based on the exact method for binomial distributions. 


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7.3.7.2.2. Anemia Response 
Anemia response is applicable for subjects who are transfusion-dependent at baseline.  Best 
overall response for anemia response is the best anemia response recorded prior to and including 
the time when the first progression occurs for altering the natural history of disease, and in the 
order of:  transfusion-independent subjects (a ≥ 20 g/L increase in hemoglobin level), 
transfusion-dependent subjects (becoming transfusion-independent), or no anemia response. 
Best overall response will be summarized descriptively.  Subjects who are transfusion-dependent 
at baseline will be included in the denominators in the summary of BOR. 
7.3.7.2.3. Spleen Response 
Spleen response is applicable for subjects with baseline splenomegaly that is palpable at ≥ 5 cm 
below the LCM.  The number of subjects who had baseline splenomegaly palpable at 5 to 10 cm 
below the LCM that becomes not palpable or baseline splenomegaly palpable at > 10 cm below 
the LCM decreasing by ≥ 50% will be summarized.  Subjects with baseline splenomegaly that is 
palpable at ≥ 5 cm below the LCM will be included in the denominators in the summary of 
spleen response. 
7.3.7.3. 
Event-Free Survival 
Event-free survival for MF is defined as the length of time between the start of the study drug 
(Day 1) and the earlier of death or progression.  The date of progression will be the timepoint at 
which progression is first recorded.  Censoring of EFS for MF will follow the same algorithm 
outlined in Table 3. 
The number of subjects who had progression or who died and the number of subjects censored 
will be summarized.  The Kaplan-Meier estimate of median EFS will be presented with its 95% 
CI. 
7.3.7.4. 
Duration of Response 
For responders, DOR for MF is the time from the first response of CR, or PR to the earlier of 
death or progression occurring after the first response of CR or PR.  The date of progression will 
be the timepoint at which progression is first recorded.  Censoring of DOR will follow the same 
algorithm as the censoring of EFS (Section 7.3.7.3). 
The total number of responders, the number of subjects who had progression or who died, and 
the number of subjects censored will be summarized.  The Kaplan-Meier estimate of median 
DOR will be presented with its 95% CI. 
7.3.8. 
Multiple Myeloma 
7.3.8.1. 
Response Assessment 
Disease assessment for subjects with MM will be performed following the International Uniform 
Response Criteria for MM (Durie et al 2006) and Criteria for Evaluating Disease Response and 
Progression in Patients With MM Treated by High-Dose Therapy and Haemopoietic Stem Cell 
Transplantation (Blade et al 1998), which is for assessing MR only.  The investigator's 
assessment will be used to determine responses and will be logged into the eCRF. 


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Response status per investigator's assessment for MM will be recorded at each response 
assessment visit as sCR, CR, VGPR, PR, MR, SD, or PD. 
7.3.8.2. 
Best Overall Response and Objective Response Rate 
Best overall response for MM is the best response recorded prior to and including the first PD, in 
the order of sCR, CR, VGPR, PR, MR, SD, and PD.  A subject is considered a responder if they 
have a best overall response of sCR, CR, VGPR, or PR. 
Objective response rate is the proportion of responders.  Subjects 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 calculations of ORR. 
Best overall response will be summarized descriptively.  Objective response rate will be 
estimated with 95% CIs.  Confidence intervals will be calculated based on the exact method for 
binomial distributions. 
7.3.8.3. 
Event-Free Survival 
Event-free survival for MM is defined as the length of time between the start of the study drug 
(Day 1) and the earlier of death or PD.  The date of PD will be the timepoint at which PD is first 
recorded.  Censoring for PFS will follow the algorithm outlined in Table 3. 
The number of subjects who had PD or who died and the number of subjects censored will be 
summarized.  The Kaplan-Meier estimate of median EFS will be presented with its 95% CI. 
7.3.8.4. 
Duration of Response 
For responders, DOR for MM is the time from the first response of sCR, CR, VGPR, or PR to 
the earlier of death or PD occurring after the first response of sCR, CR, VGPR, or PR.  The date 
of PD will be the timepoint at which PD is first recorded.  Censoring of DOR will follow the 
same algorithm as the censoring of EFS (Section 7.3.8.3). 
The total number of responders, the number of subjects who had PD or who died, and the 
number of subjects censored will be summarized.  The Kaplan-Meier estimate of median DOR 
will be presented with its 95% CI. 
7.4. 
Analysis of Other Efficacy Variables 
7.4.1. 
Overall Survival 
Overall survival is defined as the time from the start of the study drug (Day 1) until death from 
any cause.  Date of death will be determined using the Death Report eCRFs.  Subjects who are 
lost to follow-up or still alive at the time of analysis will be right-censored at the date the subject 
was last known to be alive.  The last known alive date is defined as the later of the last study visit 
and the date the subject was last known to be alive. 
The number of subjects who died and the number of subjects censored will be summarized.  The 
Kaplan-Meier estimate of median OS will be presented with its 95% CI. 


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7.4.2. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group Performance status at scheduled assessment times will be 
summarized. 
7.5. 
Pharmacokinetic Analyses 
Pharmacokinetic analysis of INCB054329, including Cmax, Tmax, Cmin, AUC0-t, and Cl/F, will be 
performed on samples collected at the specified timepoints.  The parameters will be calculated 
from the blood plasma concentrations of INCB054329 using standard noncompartmental 
(model-independent) PK methods and commercial software.  The PK parameters will be 
summarized by descriptive statistics by part and cohort. 
The log-transformed PK parameters will be compared among the dose levels by using a 1-factor 
ANOVA.  Dose-dependent parameters (Cmax and AUC) will be normalized to the lowest 
common dose before statistical comparisons.  Cmax and AUC will be evaluated using a power 
model, for example, AUC = α∙(doseβ) or, equivalently, log(AUC) = log(α) + β∙log(dose), where 
linear dose proportionality is accepted if β is not significantly different from 1.  Attainment of 
steady-state will be assessed separately for each cohort by comparing trough plasma 
concentrations on Days 8 and 15. 
For the food-effect assessment, the log-transformed PK parameters will be compared between 
the fed and fasted treatments using an ANOVA for a 1-way crossover design.  The geometric 
mean relative bioavailability and 90% CIs will be calculated for comparing Cmax and AUC 
between the fed (test) and fasted (reference) treatments.  Population PK methods may be 
employed if there are a sufficient number of plasma PK samples. 
7.6. 
Pharmacodynamic Analyses 
Separate pharmacodynamic analyses may be provided by the Incyte Translational Sciences 
group. 


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CONFIDENTIAL 
8. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. 
8.1. 
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 PTs reported on relatively 
few subjects. 
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug.  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. 
Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be graded 
using the NCI CTCAE.  The CTCAE v4.03 is used for this study (NCI 2010).  The CTCAE 
reporting guidelines and grading details are available on the Cancer Therapy Evaluation Program 
website.  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 medical 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. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs.  If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related.  The incidence of AEs and treatment-
related AEs will be tabulated.  In addition, SAEs will also be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution.  Unresolved 
missing causality and severity will be handled according to the following rules: 
 An unresolved missing causality will be considered treatment-related. 
 An unresolved missing severity will be identified as an unknown severity. 


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For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment emergent.  Therefore, an unresolved missing onset date will be 
considered treatment emergent, with the following exceptions: 
 If the stop/resolution date is before the first dose administration date on Day 1, then 
the AE will be considered as not being treatment emergent. 
 If both the month and day are missing, and the last day of the year is before the first 
dose administration date on Day 1, then the AE will not be considered treatment 
emergent. 
 If only the day is missing, and the last day of the month is before the first dose 
administration date on Day 1, then the AE will not be considered treatment emergent. 
8.2.2. 
Dose-Limiting Toxicities 
Subjects with DLTs and the type of DLT will be listed. 
8.2.3. 
Maximum Tolerated Dose 
Maximum tolerated dose will be defined as 1 dose level below that at which one-third or more of 
subjects in a particular cohort have DLTs. 
8.2.4. 
Adverse Event Summaries 
An overall summary of AEs will include: 
 Number (%) of subjects reporting any TEAEs 
 Number (%) of subjects reporting any SAEs 
 Number (%) of subjects reporting any Grade 3 or 4 TEAEs 
 Number (%) of subjects reporting any TEAEs related to INCB054329 
 Number (%) of subjects who temporarily interrupted INCB054329 because of TEAEs 
 Number (%) of subjects who permanently discontinued INCB054329 because of 
TEAEs 
 Number (%) of subjects with INCB054329 dose reductions because of TEAEs 
 Number (%) of subjects who had a fatal TEAE 
The following summaries will be produced by MedDRA term (if 10 or fewer subjects 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 Grade 3 or 4 TEAEs by SOC and PT 
 Summary of INCB054329 treatment-related TEAEs by SOC and PT 


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 Summary of INCB054329 treatment-related TEAEs by SOC, PT, and maximum 
severity 
 Summary of TEAEs leading to death by SOC and PT 
 Summary of serious TEAEs by SOC and PT 
 Summary of serious TEAEs by PT in descending order of frequency 
 Summary of INCB054329 treatment-related SAEs by SOC and PT 
 Summary of TEAEs leading to INCB054329 dose reduction by SOC and PT 
 Summary of TEAEs leading to INCB054329 dose interruption by SOC and PT 
 Summary of TEAEs leading to discontinuation of INCB054329 by SOC and PT 
 Summary of nonserious TEAEs by SOC and PT 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
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, additional rules may be provided after consultation with the medical monitor 
to delineate which value will be defined as baseline. 
Laboratory test values outside the normal range will be assessed for severity based on CTCAE 
grade or similar criteria where clinical intervention is required for CTCAE grading.  The 
incidence of abnormal laboratory values and shift tables relative to baseline will be tabulated. 
8.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from local laboratories will be reported in SI units.  
All tests with numeric values will have a unique unit per test.  Any laboratory test results and 
associated normal ranges from local laboratories will be converted to SI units.  For the limited 
number of cases where the associated normal ranges from a local laboratory cannot be obtained 
despite due diligence, if query is unsuccessful at resolving the issue and analysis is mandatory, a 
set of standard normal ranges based on documented reference ranges will be applied to facilitate 
reporting the test results. 
When there are multiple laboratory nonmissing values for a subject's particular test within a visit 
window, the convention described in Table 5 will be used to determine the record used for 
by-visit tabulations and summaries. 


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Table 5: 
Identification of Records for Postbaseline By-Visit Summaries 
Priority 
Laboratory Visit 
Proximity to Visit 
Window 
Tiebreaker 
1 
Scheduled 
In-window 
Use smallest laboratory 
sequence number 
2 
Unscheduled 
In-window 
3 
Scheduled 
Out-of-window 
Numeric laboratory values will be summarized descriptively in SI units, and non-numeric test 
values will be tabulated when necessary.  In addition, line graphs and box-and-whisker plots will 
be provided for hemoglobin, platelet counts, white blood cells, and neutrophils. 
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 subjects in the baseline 
category. 
In cases where differentials of hematology parameters are obtained without corresponding 
absolute count data, efforts will be made to investigate if the conversion to an absolute value will 
lead to additional abnormalities.  This will be discussed with the clinical team regarding 
appropriate documentation and action. 
Categorical laboratory data will be tabulated by visit at baseline and postbaseline visits whenever 
it is appropriate. 
8.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, and body 
temperature will be summarized descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 6.  The abnormal 
values for subjects exhibiting clinically notable vital sign abnormalities will be listed along with 
their assigned treatment group.  Alert vital signs are defined as an absolute value outside the 
defined range and percentage change greater than 25%.  The abnormal values for subjects 
exhibiting alert vital sign abnormalities will be listed. 
Table 6: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 45 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 


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INCB 54329-101 Statistical Analysis Plan 
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CONFIDENTIAL 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, QRS, QT, QTcF, QTcB, and RR intervals will be obtained for 
each subject 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 INCB054329. 
Criteria for clinically notable ECG abnormalities are defined in Table 7.  Subjects exhibiting 
clinically notable ECG abnormalities will be listed with study visit and assigned treatment group.  
Abnormal values for subjects 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. 
Table 7: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 480 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 
QTcF = Fridericia correction. 
9. 
INTERIM ANALYSES 
There are no planned, formal interim analyses for this study.  Periodic review of accrued clinical 
data will be conducted by the sponsor.  Based on review of the most current safety data, the 
sponsor (in consultation with the study investigators and using the dose-escalation/de-escalation 
rules) will determine if and at what dose(s) additional subjects should be treated in the study. 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 8. 
Table 8: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
05 APR 2018 
10.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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INCB 54329-101 Statistical Analysis Plan 
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CONFIDENTIAL 
11. 
REFERENCES 
Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in 
patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell 
transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow 
Transplant. Br J Haematol 1998;102:1115-1123. 
Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International 
Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and 
Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 
2003;21:4642-4649. 
Cheson BD, Byrd JC, Rai KR, et al. Novel targeted agents and the need to refine clinical end 
points in chronic lymphocytic leukemia. J Clin Oncol 2012;30:2820-2822. 
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;20:3059-3068. 
Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification 
of the International Working Group (IWG) response criteria in myelodysplasia. Blood 
2006;108:419-425. 
Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple 
myeloma. Leukemia 2006;20:1467-1473. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. 
Food and Drug Administration (FDA). Guidance for Industry: Clinical Trial Endpoints for the 
Approval of Cancer Drugs and Biologics. 2007. 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071590.pdf. Accessed April 3, 2018. 
Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic 
lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic 
Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 
2008;111:5446-5456. 
National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03. 2010. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. Accessed April 3, 2018. 
Savona MR, Malcovadi L, Komrokji R, et al. An international consortium proposal of uniform 
response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. 
Blood 2015;125:1857-1865. 
Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International 
Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and 
European LeukemiaNet (ELN) consensus report. Blood 2013;122:1395-1398. 


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APPENDIX A. PLANNED TABLES AND FIGURES 
This appendix provides a list of the planned tables, listings, and figures for the clinical study 
report.  Standard tables will follow the conventions in the Standard Safety Tables initial version.  
In-text tables are identical in structure and content to appendix tables, but follow a Rich Text 
Format. 
The lists of tables, listings, and figures are to be used as guidelines.  Modifications of the list that 
do not otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
In-Text 
1.1.1 
Analysis Populations 
Safety 
X 
X 
1.1.2 
Summary of Subject Disposition 
Safety 
X 
X 
1.2.1 
Summary of Demographics 
Safety 
X 
X 
1.3.1.1.1 
Summary of Baseline Disease Characteristics and Disease 
History-Breast Cancer  
Safety 
 
X 
1.3.1.1.2 
Summary of Baseline Disease Characteristics and Disease 
History-Castration-Resistant Prostate Cancer  
Safety 
 
 
1.3.1.1.3 
Summary of Baseline Disease Characteristics and Disease 
History-Colorectal Cancer  
Safety 
 
X 
1.3.1.1.4 
Summary of Baseline Disease Characteristics and Disease 
History-Non–Small Cell Lung Cancer 
Safety 
 
 
1.3.1.1.5 
Summary of Baseline Disease Characteristics and Disease 
History-Nut Midline Carcinoma 
Safety 
 
X 
1.3.1.1.6 
Summary of Baseline Disease Characteristics and Disease 
History-Ovarian Cancer  
Safety 
 
 
1.3.1.1.7 
Summary of Baseline Disease Characteristics and Disease 
History-Pancreatic Cancer 
Safety 
 
 
1.3.1.1.8 
Summary of Baseline Disease Characteristics and Disease 
History-Other Solid Tumor  
Safety 
 
 
1.3.1.2 
Summary of Baseline Disease Characteristics and Disease 
History-Lymphoma 
Safety 
 
X 
1.3.1.3 
Summary of Baseline Disease Characteristics and Disease 
History-CLL/SLL 
Safety 
 
X 
1.3.1.4 
Summary of Baseline Disease Characteristics and Disease 
History-AML  
Safety 
 
X 
1.3.1.5 
Summary of Baseline Disease Characteristics and Disease 
History-MDS 
Safety 
 
X 
1.3.1.6 
Summary of Baseline Disease Characteristics and Disease 
History-MDS/MPN 
Safety 
 
X 
1.3.1.7 
Summary of Baseline Disease Characteristics and Disease 
History-MF 
Safety 
 
X 
1.3.1.8 
Summary of Baseline Disease Characteristics and Disease 
History-MM 
Safety 
 
X 
1.3.2 
Summary of Prior Cancer Therapy 
Safety 
 
 
1.3.3 
Summary of Prior Cancer Medications 
Safety 
X 
 
1.4.1 
Summary of Prior Medications 
Safety 
X 
 
1.4.2 
Summary of Concomitant Medications 
Safety 
X 
 
1.5.1 
Summary of General Medical History 
Safety 
X 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
2.1.1.1 
Summary of Best Response and Objective Response Rate-
Solid Tumor 
Efficacy 
Evaluable 
 
X 
2.1.1.2 
Summary of Best Response and Objective Response Rate-
Lymphoma 
Efficacy 
Evaluable 
 
X 
2.1.1.3 
Summary of Best Response and Objective Response Rate-
CLL/SLL 
Efficacy 
Evaluable 
 
X 
2.1.1.4 
Summary of Best Response and Objective Response Rate-
AML 
Efficacy 
Evaluable 
 
X 
2.1.1.5 
Summary of Best Response and Objective Response Rate-
MDS 
Efficacy 
Evaluable 
 
X 
2.1.1.6 
Summary of Best Response and Objective Response Rate-
MDS/MPN 
Efficacy 
Evaluable 
 
X 
2.1.1.7 
Summary of Best Response and Objective Response Rate-
MF 
Efficacy 
Evaluable 
 
X 
2.1.1.8 
Summary of Best Response and Objective Response Rate-
MM 
Efficacy 
Evaluable 
 
X 
2.2.1 
Summary of Overall Survival 
Efficacy 
Evaluable 
 
X 
2.2.2.1 
Summary of Progression-Free Survival 
Efficacy 
Evaluable 
 
X 
2.2.2.2 
Summary of Event-Free Survival 
Efficacy 
Evaluable 
 
X 
2.2.3 
Summary of Duration of Response 
Efficacy 
Evaluable 
 
X 
2.2.4 
Summary of Best Change in Target Lesion Size 
Efficacy 
Evaluable 
 
X 
2.3.1 
Summary of ECOG status 
Efficacy 
Evaluable 
 
 
3.1.1 
Summary of Exposure and Compliance 
Safety 
X 
X 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
X 
X 
3.2.2 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
X 
X 
3.2.3 
Summary of Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
X 
3.2.4 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class, Preferred Term, and 
Maximum Severity 
Safety 
X 
 
3.2.5 
Summary of Grade 3 or 4 Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
X 
3.2.6 
Summary of INCB054329 Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class 
and Preferred Term 
Safety 
X 
 
3.2.7 
Summary of INCB054329 Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class, 
Preferred Term, and Maximum Severity 
Safety 
X 
X 
3.2.8 
Summary of Treatment-Emergent Adverse Events Leading 
to Death by MedDRA System Organ Class and Preferred 
Term 
Safety 
X 
X 
3.2.9 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
X 
X 
3.2.10 
Summary of Serious Treatment-Emergent Adverse Events by 
Preferred Term in Decreasing Order of Frequency 
Safety 
X 
X 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.2.11 
Summary of INCB054329 Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term 
Safety 
X 
X 
3.2.12 
Summary of Treatment-Emergent Adverse Events Leading 
to INCB054329 Dose Reduction by MedDRA System Organ 
Class and Preferred Term 
Safety 
X 
 
3.2.13 
Summary of Treatment-Emergent Adverse Events Leading 
to INCB054329 Dose Interruption by MedDRA System 
Organ Class and Preferred Term 
Safety 
X 
 
3.2.14 
Summary of Treatment-Emergent Adverse Events Leading 
to Discontinuation of INCB054329 by MedDRA System 
Organ Class and Preferred Term 
Safety 
X 
X 
3.2.15 
Summary of Nonserious Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
 
3.3.1 
Summary of Laboratory Values – Hematology 
Safety 
X 
 
3.3.2 
Shift Summary of Hematology Laboratory Values in CTC 
Grade – to the Worst Abnormal Value 
Safety 
X 
X 
3.3.4 
Summary of Laboratory Values – Chemistry 
Safety 
X 
 
3.3.5 
Shift Summary of Chemistry Laboratory Values in CTC 
Grade – to the Worst Abnormal Value 
Safety 
X 
X 
3.3.7 
Summary of Laboratory Values – Coagulation 
Safety 
X 
 
3.3.8 
Shift Summary of Coagulation Laboratory Values in CTC 
Grade – to the Worst Abnormal Value 
Safety 
X 
 
3.3.9 
Summary of Laboratory Values – Urinalysis 
Safety 
X 
 
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 Body Weight 
Safety 
X 
 
3.5.1 
Summary of PR Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.2 
Summary of RR 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 QRS Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.6 
Summary of QTcF Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.7 
Summary of Outliers of QT and QTcF Interval Values From 
12-Lead ECG 
Safety 
X 
 
Figures 
Figure No. 
Title 
4.1.1 
Kaplan-Meier Estimates of Overall Survival 
4.2.1.1 
Kaplan-Meier Estimates of Progression-Free Survival 
4.2.1.2 
Kaplan-Meier Estimates of Event-Free Survival 
4.2.2 
Kaplan-Meier Estimates of Duration of Response 
4.3.3 
Waterfall Plot of Best Percentage Change in Sum of Target Lesions 
4.4.1  
Line Graph of Selected Laboratory Values by Study Visit  
4.4.2  
Box-and-Whisker Plot of Selected Laboratory Values by Study Visit  


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Listings 
Listing No. 
Title 
2.1.1 
Subject Enrollment and Disposition Status 
2.1.2 
Subject Inclusion and Exclusion Criteria Violations 
2.2.1 
Protocol Deviations and Violations 
2.3.1 
Analysis Populations 
2.4.1 
Demographic Characteristics 
2.4.2 
Baseline Disease Characteristics and Disease History 
2.4.3 
Prior Radiation Treatment 
2.4.4 
Prior Systemic Therapy 
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 
2.5.1 
Study Drug Administration and Compliance 
2.6.1 
Deaths 
2.6.2.1 
Best Overall Response, Duration of Response, Overall Survival, and Progression-Free Survival 
2.6.2.2 
Best Overall Response, Duration of Response, Overall Survival, and Event-Free Survival 
2.6.3 
Overall Response Assessment by Visit 
2.6.4 
Response Assessment:  Target Lesions 
2.6.5 
Response Assessment:  Non-Target Lesions 
2.6.6 
Response Assessment:  New Lesions 
2.6.7 
ECOG Status 
2.7.1 
Adverse Events 
2.7.2 
Dose-Limiting Toxicities 
2.7.3 
Serious Adverse Events 
2.7.4 
Grade 3 and Higher Adverse Events 
2.7.5 
Adverse Events Leading to Death 
2.7.6 
Treatment-Related Adverse Events 
2.7.7 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of INCB054329 
2.8.1 
Clinical Laboratory Values – Hematology 
2.8.2 
Clinical Laboratory Values – Chemistry 
2.8.3 
Clinical Laboratory Values – Coagulation 
2.8.4 
Clinical Laboratory Values – Urinalysis 
2.8.5 
Abnormal Clinical Laboratory Values – Hematology 
2.8.6 
Abnormal Clinical Laboratory Values – Chemistry 
2.8.7 
Abnormal Clinical Laboratory Values – Coagulation 
2.8.8 
Abnormal Clinical Laboratory Values – Urinalysis 
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 
 


Signature Manifest
Document Number: IC-STS-SAP-0104
Revision: 0
Title: INCB 54329-101 SAP Original
All dates and times are in Eastern Standard Time.
INCB 54329-101 SAP review/approval
Approval
Name/Signature
Title
Date
Meaning/Reason
05 Apr 2018, 10:40:36 AM
Approved
05 Apr 2018, 10:48:04 AM
Approved
05 Apr 2018, 10:50:44 AM
Approved
05 Apr 2018, 02:23:39 PM
Approved