Clinical trial NCT02265510
Conditions: Solid Tumors Advanced Malignancies Metastatic Cancer
Sponsor: Incyte Corporation
Start date: 2014-09-10; Completion date: 2019-02-27
Enrollment: 83 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: INCB052793 intervention 2: gemcitabine intervention 3: nab-paclitaxel intervention 4: dexamethasone intervention 5: Carfilzomib intervention 6: bortezomib intervention 7: lenalidomide intervention 8: azacitidine intervention 9: INCB052793 intervention 10: pomalidomide intervention 11: INCB050465 intervention 12: INCB039110
Intervention descriptions: intervention 1: Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria. intervention 2: Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency. intervention 3: nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency. intervention 4: Dexamethasone administered orally at the protocol-specified dose and frequency. intervention 5: Carfilzomib administered intravenously at the protocol-specified dose and frequency. intervention 6: Bortezomib administered intravenously or subcutaneously at the protocol-specified dose and frequency. intervention 7: Lenalidomide administered orally at the protocol-specified dose and frequency. intervention 8: Azacitidine administered subcutaneously at the protocol-specified dose and frequency. intervention 9: INCB052793 tablets administered orally at the protocol specified dose strength and frequency. intervention 10: Pomalidomide administered orally at the protocol-specified dose and frequency. intervention 11: INCB050465 tablets administered orally at the protocol specified dose strength and frequency. intervention 12: INCB039110 tablets administered orally at the protocol specified dose strength and frequency.

Protocol documents:
Prot_000.pdf: 
Incyte Corporation 
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Protocol INCB 52793-101 Amendment 9 
02 MAY 2017 
CONFIDENTIAL 
Clinical Study Protocol 
INCB 52793-101 / NCT02265510
A Phase 1/2 Open-Label, Dose-Escalation, Safety and Tolerability 
Study of INCB052793 in Subjects With Advanced Malignancies 
Product: 
INCB052793 in combination with INCB050465 and 
standard of care, and itacitinib (INCB039110) in 
combination with azacitidine 
IND Number: 
134,089 
Phase of Study: 
1/2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Date of Protocol: 
01 MAY 2014 
Date of Amendment 1: 
09 JUN 2014 
Date of Amendment 2: 
25 NOV 2014 
Date of Amendment 3: 
10 APR 2015 
Date of Amendment 4: 
13 MAY 2015 
Date of Amendment 5: 
02 MAR 2016 
Date of Amendment 6: 
05 APR 2016 
Date of Amendment 7: 
27 FEB 2017 
Date of Amendment 8: 
31 MAR 2017 
Date of Amendment 9: 
02 MAY 2017 
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 INCB052793.  I have read the 
INCB 52793-101 Protocol Amendment 9 (dated 02 MAY 2017) 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:  INCB052793 and in combination with INCB050465, itacitinib 
(INCB039110) 
Title of Study:  A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of 
INCB052793 in Subjects With Advanced Malignancies 
Protocol Number:  INCB 52793-101 
Study Phase:  1/2 
Primary Objectives: 
• Phase 1a:  To assess the safety and tolerability of INCB052793 in subjects with advanced 
malignancies and select doses for further evaluation. 
• Phase 1b:  To assess the safety and tolerability of INCB052793 in combination with standard therapies 
and the novel phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor INCB050465 in subjects with 
advanced malignancies. 
• Phase 2:  To evaluate the efficacy of INCB052793 in combination with azacitidine and of itacitinib in 
combination with azacitidine in subjects with acute myeloid leukemia (AML) and high-risk 
myelodysplastic syndromes (MDS) who have failed prior therapy with hypomethylating agents 
(HMA), based on overall response rate (ORR). 
Secondary Objectives: 
• To assess preliminary efficacy by assessing the ORR in subjects with advanced malignancies. 
• To assess the safety and tolerability of INCB052793 in combination in azacitidine and of itacitinib in 
combination with azacitidine in subjects with AML and high-risk MDS who have failed prior therapy 
with HMA. 
• To assess the pharmacokinetics (PK) of INCB052793 as monotherapy administered in the fasted state 
and the effect of food on the PK of INCB052793. 
• To assess the PK of INCB052793 when administered in combination with standard therapies and 
INCB050465 in subjects with advanced malignancies, to assess the PK of INCB050465 when 
administered in combination with INCB052793, and to asses the PK of itacitinib when administered in 
combination with azacitidine. 
Overall Study Design: 
The study will be conducted in 2 phases (Phase 1a/1b and Phase 2).  Phase 1a will be conducted with 
INCB052793 monotherapy dose escalation (Part 1) and dose expansion (Part 2).  Phase 1b will comprise 
treatment cohorts in which INCB052793 will be administered in combination with gemcitabine and 
nab-paclitaxel in select solid tumors (Cohort A); dexamethasone, carfilzomib, bortezomib, lenalidomide, 
and pomalidomide/dexamethasone in subjects with multiple myeloma (MM; Cohorts B, C, D, E, and G, 
respectively); azacitidine in subjects with AML or MDS (Cohort F), and INCB050465 in subjects with 
lymphomas (Cohort H), each including both a dose escalation (Part 1) and an optional dose expansion 
(Part 2).  Phase 2 will include 2 treatment cohorts in which subjects with AML and high-risk MDS who 
failed prior therapy with HMA will receive azacitidine in combination with INCB052793 (Cohort I) or 
in combination with itacitinib (Cohort J). 


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CONFIDENTIAL 
Phase 1a Monotherapy: 
Phase 1a will include Part 1 dose escalation starting with 25 mg once daily (QD) to determine the 
maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD) of single-agent 
INCB052793 in 2 treatment groups (A and B).  This dose will be chosen for further evaluation.  Part 2 
dose expansion will evaluate the chosen dose as monotherapy. 
Part 1 Dose Escalation:  The dose escalation will start with Treatment Group A (TGA; advanced or 
metastatic solid tumors) at 25 mg QD and consist of a 21-day cycle, with Cycle 1 Day 1 as the first day 
of treatment.  Open-label dose escalation will consist of an initial cohort using a 3 + 3 design with dose 
doubling until either Grade 2 or greater toxicities or unbound AUC at steady state exceeds the value 
(25.3 μM∙h) corresponding to the no-observed-adverse-effects level (NOAEL) in the most sensitive 
species evaluated in GLP toxicology studies (rat at 15 mg/kg).  Each dose level will be observed for a 
period of 21 days before enrolling the next cohort and administering the next dose level.  Treatment 
Group B (TGB; advanced hematologic malignancies) will follow the same dose-escalation design, 
beginning enrollment at the PAD when it is determined. 
Subjects who receive at least 17 of 21 days (or ≥ 80%) of fasted study drug at the level assigned to that 
cohort, or who experience a dose-limiting toxicity (DLT), will be considered evaluable for determining 
tolerability of dose.  Subjects enrolling but not meeting these criteria may be replaced in order to fill the 
cohort. 
The starting dose of INCB052793 (25 mg QD in TGA; PAD in TGB) will be escalated if 0 of the first 
3 evaluable subjects enrolled experience a DLT.  Increases to study drug will be up to 100% (ie, 25 mg, 
50 mg, 100 mg, and 150 mg) if there are no reported Grade 2 or greater toxicities and no subject has an 
unbound AUC at steady state that exceeds 25.3 μM∙h.  Otherwise, increases of study drug dose will be 
limited to no more than 50% in successive cohorts, using QD regimen (ie, 25 mg, 35 mg, 50 mg, 75 mg, 
100 mg, and 150 mg).  If no DLTs are observed in the initial 3 subjects, the next cohort will begin 
enrollment.  If 1 DLT is observed in the first 3 subjects, 3 additional subjects will be enrolled in the 
cohort.  If a DLT occurs in one-third or more of the total cohort (≥ 2 of 3 or 6), then the MTD will be 
deemed to have been exceeded, and the next lower dose level will be deemed to be the MTD.  If the 
dose-escalation increment has been 100%, then an intermediate lower dose level may be explored.  
Thus, the MTD will be defined as 1 dose level below that at which one-third or more of subjects in a 
particular cohort experience DLTs.  Dose-limiting toxicities occurring during the first 21 days of 
treatment will guide dose escalation and determination of the MTD; however, subjects who may have 
not experienced a DLT but who experienced intolerable, lower grade persistent toxicity determined to be 
due to study drug will be considered in the determination of the study drug dose in the expansion 
cohorts.  Only toxicities with a clear alternative explanation (ie, due to disease progression, comorbid 
condition, concomitant medication) can be deemed a non-DLT for determination of the PAD/MTD. 
Part 2 Dose Expansion:  The expansion may proceed with a PAD, the MTD or the highest dose tested 
if the MTD is not reached: 
• TGA (advanced or metastatic solid tumors) and TGB (advanced hematologic malignancies) of 
approximately 12 subjects each in 1 or 2 expansion dose levels (PAD and/or MTD or highest dose 
tested if MTD is not reached for each group) will be treated with the selected doses of INCB052793 as 
a single agent to further determine safety, tolerability, efficacy, PK, 
 in this population. 
• For both TGA and TGB, a study of the effect of food on the PK of INCB052793 will be conducted on 
this expanded cohort.  Results from the food-effect study will dictate whether study drug will be 
administered to subjects in the fasted or fed state in ongoing subjects in Phase 1a and Phase 1b. 
Phase 1b Combination Therapy: 
Phase 1b will comprise treatment cohorts evaluating INCB052793 when administered in combination 
with standard therapies for select solid tumors (Cohort A), MM (Cohorts B, C, D, E and G), AML/MDS 
(Cohort F) and with the PI3Kδ inhibitor INCB050465 in lymphoma (Cohort H).  Each treatment cohort 
will include 2 parts.  Part 1 is a 3 + 3 dose escalation that will evaluate increasing doses of INCB052793 


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in combination with standard-of-care agents and INCB050465 in select solid tumors and select advanced 
hematological malignancies.  Part 2 will be an optional expansion to further evaluate the safety and 
preliminary efficacy of the combination at the selected INCB052973 dose.  Timing for the initiation of 
Phase 1b enrollment will be determined by the sponsor based on the available safety/tolerability and 
PK/
 data from Phase 1a.  The sponsor may elect to open certain Phase 1b treatment cohorts before 
others or to not open specific cohorts. 
Enrollment into Cohorts A, C, D, E, G and H will not be conducted as per Amendment 7 of the Protocol. 
Part 1 Dose Escalation:  The starting dose of INCB052793 in each treatment cohort will be designated 
as Dose Level 1.  Dose Level 1 will be 50% to 100% of the PAD (maximum of 75% of MTD) in 
Phase 1a (rounded down to the next lowest dose based on available tablet strengths).  Dose escalation 
will proceed using a 3 + 3 design.  Each cohort will be observed for a minimum of 1 cycle before the 
next cohort begins enrollment.  Within each cohort, subjects will be considered nonevaluable for safety 
and replaced if they have received < 75% of the planned doses of study drug or standard therapy during 
the first cycle of treatment and they have not experienced a DLT.  If Dose Level 1 is deemed tolerable, 
the INCB052793 dose in the respective combination therapy may be escalated to Dose Level 2, which 
will be ≤ 50% higher than Dose Level 1.  Additional dose levels may be enrolled (ie, Dose Level 3, 
Dose Level 4, etc) until the MTD has been exceeded, with individual dose increases not to exceed 
≤ 50%.  If Dose Level 1 is deemed to have exceeded the MTD, Dose Level -1 of INCB052793 (defined 
as 50%-75% of Dose Level 1) may be evaluated. 
Part 2 Dose Expansion:  This portion will explore the safety, tolerability, PK, 
 and 
preliminary clinical activity of the regimen identified in the dose-escalation portion through an optional 
expansion cohort of approximately 12 subjects per cohort, to be treated at the combination doses 
selected in Part 1. 
Phase 2:  
Phase 2 will include 2 treatment cohorts in which subjects with AML and high-risk MDS who failed 
prior therapy with HMA will receive INCB052793 in combination with azacitidine (Cohort I) or 
itacitinib in combination with azacitidine (Cohort J).  A Simon 2-stage design will be used to evaluate 
the efficacy of the combination regimens in these cohorts.  The approximate numbers of subjects for 
Stage 1 and Stage 2 are described in the Statistics section of the Protocol.  If an insufficient number of 
responders are observed in the cohort at Stage 1, further enrollment in the cohort will be terminated. 
Study Drugs, Dosage, and Mode of Administration 
Phase 1a Monotherapy: 
INCB052793 tablets (5 mg or 25 mg strength) will be administered orally QD, but dose escalation can 
be switched to twice daily as determined by emerging PK 
 data.  The starting dose of 
INCB052793 will be 25 mg QD for TGA, and the PAD determined from TGA will be the starting dose 
for TGB subjects.  INCB052793 will be self-administered in the fasted state as a QD oral treatment 
beginning on Cycle 1 Day 1 and daily thereafter in continuous 21-day cycles.  Subjects will refrain from 
food consumption at least 2 hours before and 1 hour after study drug administration except on days 
when PK sampling is conducted, when subjects will refrain from food consumption at least 8 hours 
before and 1 hour after study drug or as indicated in the PK section.  The tolerated regimen(s) (including 
the MTD or PAD of INCB052793) defined during the dose escalation will be used in the expansion.  
One cycle will be defined as 21 continuous days of planned study treatment. 
Phase 1b Combination Therapy: 
The starting dose of INCB052793 (ie, Dose Level 1) in the Phase 1b combination therapy will be 
approximately 50% to 100% of the PAD identified in Phase 1a.  INCB052793 will be self-administered 
in the fasted state as a QD oral treatment beginning on Day 1 of Cycle 1, Day 1 of subsequent cycles, 
and daily thereafter in continuous 21-day (Cohorts D and H) or 28-day (all other cohorts) cycles.  
Subjects will refrain from food consumption at least 2 hours before and 1 hour after study drug 
administration except on days when serial PK 
 sampling is conducted, then subjects will refrain 


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from food consumption at least 8 hours before and 1 hour after study drug or as indicated in the PK 
section.  A dose of INCB052793 that was evaluated and determined to be safe and tolerable during 
Part 1 will be used in Part 2. 
Cohort A: 
• nab-Paclitaxel will be administered as an open-label commercial product at a starting dose of 
125 mg/m2 intravenously (IV) over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. 
• Gemcitabine will be administered as an open-label commercial product at a starting dose of 
1000 mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. 
Cohort B: 
• Dexamethasone will be administered as open-label commercial product at a starting dose of 40 mg 
administered orally weekly on Days 1, 8, 15, and 22 of each 28-day cycle.  If disease progression 
occurs after 1 or more cycles of the dexamethasone/INCB052793 combination, or if a response has 
not been achieved after 4 or more cycles (ie, stable disease), carfilzomib, bortezomib, or lenalidomide 
(at the discretion of the investigator) may be added to the regimen at a dose level that has been 
determined as safe and tolerable in the relevant treatment cohort (C, D, or E).  If an additional agent is 
added to the regimen, the subject will subsequently follow the schedule of assessments appropriate to 
that agent. 
Cohort C: 
• Carfilzomib will be administered IV as an open-label commercial product at a dose of 20 mg/m2 IV on 
Days 1 and 2 followed by 27 mg/m2 IV on Days 8, 9, 15, and 16 of Cycle 1 and for all doses of each 
28-day cycle thereafter.  If disease progression occurs after 1 or more cycles of the combination, or if a 
response has not been achieved after 4 cycles (ie, stable disease), dexamethasone 40 mg administered 
orally weekly may be added to the regimen.  After 12 cycles of carfilzomib treatment, subjects will 
transition to maintenance dosing on Days 1, 2, 15, and 16 of each 28-day cycle. 
Cohort D: 
• Bortezomib will be administered as an open-label commercial product at a dose of 1.3 mg/m2 IV or 
subcutaneously (SC) on Days 1, 4, 8, and 11 of each 21-day treatment cycle.  If disease progression 
occurs after 1 or more cycles of the combination, or if a response has not been achieved after 4 cycles 
(ie, stable disease), dexamethasone 40 mg administered orally weekly may be added to the regimen.  
After 8 cycles, subjects will transition to a maintenance schedule comprising 1 dose every 2 weeks. 
Cohort E: 
• Lenalidomide will be administered as an open-label commercial product at a starting dose of 25 mg 
administered orally QD on Days 1 through 21 of each 28-day cycle.  Lower dose levels of 
lenalidomide may be explored (eg, 10 mg, 15 mg, 20 mg) based on the safety/tolerability of the 
combination.  If disease progression occurs after 1 or more cycles of the combination, or if a response 
has not been achieved after 4 cycles (ie, stable disease), dexamethasone 40 mg administered orally 
weekly may be added to the regimen. 
Cohort F: 
• Azacitidine will be administered as an open-label commercial product at a dose of 75 mg/m2 SC for 
5 days, followed by 2 days of no treatment, then 75 mg/m2 for 2 days of each 28-day treatment cycle.  
Intravenous administration is permitted if SC administration is not tolerated.  
Cohort G 
• Pomalidomide will be administered as an open-label commercial product at a dose of 4 mg 
administered orally QD on Days 1 through 21 of each 28-day cycle.  Lower dose levels of 
pomalidomide may be explored (eg, 3 mg, 2 mg, 1mg) based on the safety/tolerability of the 
combination.  Dexamethasone will be coadministered at 40 mg orally weekly on Days 1, 8, 15, and 22 
of a 28-day cycle. 


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CONFIDENTIAL 
Cohort H 
• The starting dose of INCB050465 will be 20 mg QD.  Additional dose levels may be tested (eg, 30 mg 
or 15 mg) in combination with the recommended dose of INCB052793.  
Based on safety assessments, individual subjects may have dose interruptions and/or reductions of 
INCB052793 or the applicable combination agent(s) during the course of treatment. 
Phase 2:  
Cohort I 
• The starting dose of INCB052793 will be 35 mg QD.  
• Azacitidine will be administered as above (ie, Cohort F). 
Cohort J 
• The starting dose of itacitinib will be 300 mg QD.  
• Azacitidine will be administered as above (ie, Cohort F). 
Based on safety assessments, individual subjects may have dose interruptions and/or reductions of 
INCB052793, itacitinib, or the applicable combination agent(s) during the course of treatment.  
In Cohort J, the first 3 to 6 subjects will be monitored for occurrence of DLTs before enrollment of more 
subjects.  If this dose exceeds the MTD,  further subjects will be enrolled at 200 mg QD of itacitinib and 
monitored as above. 
Duration of Participation: 
Subjects will be treated in continuous 21-day cycles (Phase 1a and Phase 1b/Cohorts D and H) or 28-day 
cycles (Phase 1b/Cohorts A, B, C, E, F, and G, and Phase 2/Cohorts I and J) until they meet withdrawal 
criteria.  If the subject discontinues all study treatment, the treatment portion will end and the subject 
will enter the follow-up portion.  Study participation is expected to average about 6 months. 
Study Population: 
For Phase 1a monotherapy, the study population will consist of subjects diagnosed with an advanced 
malignancy who have failed, or are refractory to, available treatments.  
For Phase 1b combination therapy, the study population will consist of subjects with advanced or 
metastatic pancreatic adenocarcinoma (first or second line), triple-negative breast cancer (second line), 
or urothelial cancer (second line) provided the subject is a candidate for treatment with gemcitabine and 
nab-paclitaxel (Cohort A), relapsed or refractory MM (Cohorts B, C, D, E, and G), AML/MDS 
(Cohort F), or lymphoma (Cohort H). 
For Phase 2, the study population will consist of subjects with AML and high-risk MDS who failed prior 
therapy with HMA.  
Key Inclusion Criteria for Phase 1a: 
• Age 18 years or older 
• Histologically or cytologically confirmed solid tumor (TGA) or hematologic malignancy (TGB).  For 
Part 2 expansion, measurable or evaluable disease is required. 
• Life expectancy of 12 weeks or longer. 
• Must have received ≥ 1 prior treatment regimen and currently demonstrating progressive disease. 
• Must not be a candidate for potentially curative or standard-of-care approved therapy. 
Key Inclusion Criteria for Phase 1b: 
• Age 18 years or older 
• Cohort A:  Histologically or cytologically confirmed pancreatic adenocarcinoma, triple-negative 
breast cancer, or urothelial cancer with at least 1 measurable or evaluable target lesion. 


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Cohorts B, C, D, E, and G:  Histologically confirmed MM and measureable/evaluable disease as 
defined by 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. 
Cohort F:  Confirmed AML or MDS (International Prognostic Scoring System intermediate-1 or -2, 
or high-risk) or MDS/myeloproliferative neoplasm (MPN) overlap syndromes in accordance with 
WHO diagnostic criteria, including chronic myelomonocytic leukemia (CMML), atypical BCR-
ABL1–negative chronic myeloid leukemia, MDS/myeloproliferative neoplasm unclassifiable, and 
named refractory anemia with ring sideroblasts and thrombocytosis. 
Cohort H:  Individuals diagnosed with lymphomas who have failed or are refractory to available 
treatments.  
− Subjects must not currently be a candidate for potentially curative hematopoietic stem-cell transplant 
and/or high-intensity chemotherapy. 
• Prior therapy: 
Cohort A:  No more than 1 prior chemotherapy regimen for advanced or metastatic disease (not 
including neoadjuvant and/or adjuvant therapy). 
− There is no restriction on the number of prior nonmyelosuppressive targeted therapies; targeted 
therapy alone will not be considered chemotherapy for the purposes of this study. 
Cohorts B, C, D, E, and G:  Must have relapsed from or have been refractory to ≥ 2 prior treatment 
regimens, including a proteasome inhibitor and an immunomodulatory drug. 
Cohort F:  May have received any number of prior treatment regimens or be treatment-naive. 
Cohort H:  Must have relapsed from or have been refractory to available treatments. 
− Subjects who have previously been discontinued from the standard-of-care agent (Cohorts A-G) or  
PI3Kδ inhibitors (Cohort H) being used in a specific cohort due to toxicity or intolerance may not 
enroll in that cohort (eg, subjects previously intolerant to bortezomib may not enroll in Cohort D).  
Key Inclusion Criteria for Phase 2 (Cohorts I and J): 
• Age 18 years or older 
• Confirmed AML or high-risk MDS (International Prognostic Scoring System -2, or high risk) in 
accordance with WHO diagnostic criteria 
• Failure of prior therapy with HMA, defined as one of the following:  
− progression to AML 
− 50% increase in bone marrow blasts  
− relapsed disease after response 
− at least 4 cycles of treatment without clinical benefit (hematological improvement [HI] or better). 
Key Exclusion Criteria for Phase 1a, Phase 1b, and Phase 2: 
• Prior receipt of a selective JAK1 inhibitor (Phase 1a only; prior receipt of ruxolitinib is permitted). 
• Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) before 
receiving the first dose of study drug, except if approved by the sponsor's medical monitor. 
• Any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) before 
receiving the first dose of study drug (42 days for nitrosoureas) or with medical monitor approval 
EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent; steroid exception does not apply to 
Phase 1b/Cohort B or G)  and hydroxyurea to control blood counts.  


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• Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy and alopecia) from 
previous anticancer therapy. 
− Phase 1b/Cohort D may not have > Grade 1 peripheral neuropathy at baseline. 
• Known active central nervous system metastases and/or carcinomatous meningitis.  Subjects with 
previously treated brain metastases may participate provided they are stable (without evidence of 
progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic 
symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have 
not required steroids for at least 7 days before study treatment. 
• Eastern Cooperative Oncology Group (ECOG) performance status > 2. 
• Any of the following laboratory results at screening without transfusions and hematopoietic growth 
factor support (except Phase 1b/Cohort F and Phase 2/Cohorts I and J): 
Laboratory Parameter 
Phase 1a/TGA and  
Phase 1b/Cohort A 
Phase 1a/TGB and 
Phase 1b/Cohorts B through H 
Except F 
Hemoglobin (g/dL) 
< 10.0 
< 8.0 
Platelet count (109/L) 
< 100 
< 75 
Absolute neutrophil count (109/L) 
< 1.5 
< 1.0 
− No specific hematologic exclusion criteria apply to Phase 1b/Cohort F and Phase 2/Cohorts I and J. 
• Any of the following laboratory results at screening irrespective of causality, except if approved by the 
sponsor: 
− Conjugated bilirubin > 1.2 × upper limit of normal (ULN; need only be tested if total bilirubin 
exceeds > 1.5 × ULN).  In Phase 2, Cohorts I and J, Stage 2:  total bilirubin > 3 × ULN. 
− Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN if bone metastases are present and hepatic 
parenchymal metastases are absent). 
− Aspartate aminotransferase or alanine aminotransferase > 3.0 × ULN (> 2.0 × ULN for 
Phase 1a/Part 1 and Phase 1b/Part 1).  In Phase 2, Cohorts I and J, Stage 2:  subjects with any AST 
value. 
− Creatinine clearance of < 60 mL/min (30 mL/min for subjects with MM and subjects in Phase 2, 
Cohorts I and J, Stage 2) measured or calculated by Cockroft-Gault equation or estimated glomerular 
filtration rate < 60 mL/min/1.73 m2 (30 mL/min/1.73 m2 for subjects with MM and subjects in 
Phase 2, Cohorts I and J, Stage 2) using the Modification of Diet in Renal Disease (MDRD) formula. 
• Known human immunodeficiency virus infection. 
• Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation.  
Subject cannot be positive for HBV DNA, HCV RNA, hepatitis B surface antigen, or  
anti–hepatitis B core antibody, except if approved by the medical monitor. 
• Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone, carfilzomib, 
bortezomib, lenalidomide, pomalidomide, azacitidine, or PI3Kδ inhibitors (Phase 1b and Phase 2 only, 
as appropriate to treatment cohort). 
• Ongoing radiation therapy and/or radiation therapy administered within 15 days of enrollment; subject 
must not require corticosteroids and must have recovered from all ongoing radiotherapy-related 
toxicities. 
− Subjects who have received radiation to the spine, pelvis, ribs, or femur should be discussed with the 
sponsor, as extensive radiation to a marrow-forming region may compromise a subject's ability to 
tolerate myelosuppressive chemotherapy. 
• Current clinically active and uncontrolled infection of any etiology. 


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Study Schedule/Procedures: 
Subjects will have scheduled study visits as follows: 
Phase 1a Monotherapy: 
• Screening 
• Cycle 1 (21 days):  Days 1, 8, and 15 
• Subsequent cycles (21 Days):  Day 1 
• End of treatment 
• Follow-up 
Phase 1b and Phase 2 Combination Therapy: 
• Screening 
• Treatment cycles will be 21 or 28 days in length and will conform to the administration schedule of the 
relevant standard-of-care agent.  Subjects in Cohorts C or D may switch to a maintenance schedule 
after a defined number of cycles. 
• End of treatment 
• Follow-up 
Local laboratory tests:  Study visits will include sample collection for hematology, chemistry, urinalysis, 
serology, and coagulation tests to be conducted at a local laboratory.   
Central laboratory tests:  The screening visit will include fertility/pregnancy testing conducted at a 
central laboratory.  Additionally, study visits will include sample collection for expanded serum 
chemistry and serum pregnancy tests to be performed at a central laboratory.  
 PK 
samples will be collected at selected visits and shipped to Incyte or a central laboratory for analysis. 
Clinical assessments:  Electrocardiograms (ECGs), serial ECGs in Phase 1a/1b and Phase 2, physical 
examinations, ECOG performance status, disease assessments, and review of adverse events (AEs) will 
be performed by the investigative site. 
Disease status assessments:  An objective assessment of disease status will be performed at screening, 
appropriate to the malignancy type.  Subsequent disease assessments should be performed per schedules 
of assessments. 
Primary Endpoints: 
Phase 1a and 1b: 
• Safety and tolerability of INCB052793 monotherapy and in combination with standard therapies in 
select malignancies as assessed by summary of clinical laboratory assessments, 12-lead ECGs, and 
AEs. 
Phase 2: 
• ORR, defined as the proportion of subjects who achieve complete response (CR), CR with incomplete 
hematologic recovery, partial response, or HI, using the appropriate disease-specific criteria. 
Secondary Endpoints: 
• Response rates in those subjects with measurable disease as determined by investigator assessment of 
response. 
• Safety and tolerability of INCB052793 in combination within azacitidine and of itacitinib in 
combination with azacitidine in subjects with AML and high-risk MDS who have failed prior therapy 
with HMA, assessed by summary of clinical laboratory assessments, 12-lead ECGs, and AEs. 
• Pharmacokinetics of INCB052793 and itacitinib (Phase 1a, Phase 1b, and Phase 2) will be 
summarized. 


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• For Phase 1a Part 2 expansion portion (TGA and TGB), Cmax, Tmax, and AUC0-t for Cycle 1 Day 1 and 
Cmax, Tmax, Cmin, AUC0-t, and AUC0-τ for Cycle 1 Day 15, or Cmax, Tmax, Cmin, AUC0-t, and AUC0-τ  for 
Cycle 2 Day 1 in the case of food-effect evaluation. 
Planned Number of Subjects:  Up to approximately 141 subjects (36 subjects in Phase 1a, up to 
approximately 39 subjects in Phase 1b, and approximately 18-66 subjects in Phase 2). 
Planned Number of Study Sites: Approximately 15 sites. 
Estimated Study Duration:  58 months 
• Estimated date first subject screened:  July 2014 
• Estimated date first subject dosed:  August 2014 
• Estimated date last subject completed:  June 2019 
Statistical Methods:  Up to approximately 75 subjects will be enrolled in Phase 1a and Phase 1b.  
Approximately 18 to 66 subjects will be enrolled in Phase 2 based on the Simon 2-stage design.  
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.  The overall response rate will be summarized as well.   
Safety and disease response data will be compared over time to assess change from baseline, during 
treatment, and follow-up.  Pharmacokinetic 
 data will be analyzed with appropriate standard 
analytic software. 
 


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TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................22 
1. 
INTRODUCTION ......................................................................................................25 
1.1. 
Background .................................................................................................................25 
1.1.1. 
Janus Kinases in Oncology .........................................................................................25 
1.1.2. 
Pharmacology of INCB052793 ..................................................................................26 
1.1.3. 
Absorption, Distribution, Metabolism, Excretion and Disposition ............................27 
1.1.3.1. 
Absorption ..................................................................................................................27 
1.1.3.2. 
Distribution .................................................................................................................27 
1.1.3.3. 
Metabolism .................................................................................................................27 
1.1.3.4. 
Excretion .....................................................................................................................28 
1.1.3.5. 
Disposition ..................................................................................................................28 
1.2. 
Standard-of-Care Agents ............................................................................................28 
1.2.1. 
Gemcitabine ................................................................................................................28 
1.2.2. 
Gemcitabine Plus nab-Paclitaxel ................................................................................29 
1.2.3. 
Dexamethasone ...........................................................................................................30 
1.2.4. 
Carfilzomib .................................................................................................................30 
1.2.5. 
Bortezomib .................................................................................................................30 
1.2.6. 
Lenalidomide ..............................................................................................................31 
1.2.7. 
Azacitidine ..................................................................................................................31 
1.2.8. 
Pomalidomide .............................................................................................................32 
1.3. 
Overview of INCB050465 ..........................................................................................32 
1.3.1. 
Pharmacology of INCB050465 ..................................................................................32 
1.3.2. 
Nonclinical Drug Metabolism and Pharmacokinetics of INCB050465 .....................33 
1.3.3. 
Potential Risks of INCB050465 Based on Preclinical Safety ....................................33 
1.3.4. 
Clinical Summary of INCB050465 ............................................................................34 
1.3.5. 
Clinical Pharmacokinetics of INCB050465 ...............................................................35 
1.3.6. 
Overview of the Combination of INCB052793 and INCB050465 ............................35 
1.3.6.1. 
Rationale for Combining Inhibition of JAK1 and PI3Kδ ...........................................35 
1.3.6.2. 
Nonclinical Pharmacokinetics and Drug Metabolism of the Combination of 
INCB052793 and INCB050465 .................................................................................37 


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1.3.6.3. 
Clinical Summary of Combination Treatment With JAK1 Inhibition 
(Itacitinib [INCB039110]) and PI3Kδ Inhibition (INCB040093) ..............................37 
1.4. 
Overview of Itacitinib (INCB039110) ........................................................................37 
1.4.1. 
Pharmacology of Itacitinib .........................................................................................37 
1.4.2. 
Nonclinical Drug Metabolism and Pharmacokinetics of Itacitinib ............................38 
1.4.3. 
Potential Risks of Itacitinib Based on Preclinical Safety ...........................................39 
1.4.4. 
Clinical Summary of Itacitinib ...................................................................................39 
1.4.5. 
Clinical Pharmacokinetics of Itacitinib ......................................................................41 
1.5. 
Study Rationale ...........................................................................................................41 
1.6. 
Clinical Experience With INCB052793 .....................................................................43 
1.7. 
Potential Risks and Benefits .......................................................................................44 
1.7.1. 
Preclinical Safety ........................................................................................................44 
1.7.2. 
Potential Risks Related to INCB052793 and Itacitanib .............................................46 
1.7.3. 
Risks Related to Standard-of-Care Agents .................................................................47 
1.7.3.1. 
Gemcitabine ................................................................................................................47 
1.7.3.2. 
nab-Paclitaxel .............................................................................................................47 
1.7.3.3. 
Dexamethasone ...........................................................................................................47 
1.7.3.4. 
Carfilzomib .................................................................................................................47 
1.7.3.5. 
Bortezomib .................................................................................................................48 
1.7.3.6. 
Lenalidomide ..............................................................................................................48 
1.7.3.7. 
Pomalidomide .............................................................................................................48 
1.7.3.8. 
Azacitidine ..................................................................................................................49 
1.7.4. 
Potential Risks of Combination Therapy of INCB052793 and INCB050465 ...........49 
1.7.5. 
Risks Related to the Combination Regimens .............................................................50 
1.7.6. 
INCB052793 and Itacitinib Potential Benefits ...........................................................50 
1.8. 
Justification of Route, Dose Regimen, and Treatment Period ....................................50 
2. 
STUDY OBJECTIVES AND PURPOSE ..................................................................53 
2.1. 
Primary Objectives .....................................................................................................53 
2.2. 
Secondary Objectives .................................................................................................53 
 
53 
3. 
SUBJECT ELIGIBILITY ...........................................................................................54 
3.1. 
Study Population .........................................................................................................54 
3.2. 
Subject Inclusion Criteria for Phase 1a Monotherapy ................................................54 


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3.3. 
Subject Inclusion Criteria for Phase 1b and Phase 2 Combination Therapy ..............55 
3.4. 
Subject Exclusion Criteria for Phase 1a, Phase 1b, and Phase 2 ................................56 
4. 
INVESTIGATIONAL PLAN .....................................................................................59 
4.1. 
Overall Study Design ..................................................................................................59 
4.1.1. 
Phase 1a Monotherapy ................................................................................................61 
4.1.1.1. 
Phase 1a Part 1 Dose Escalation .................................................................................61 
4.1.1.2. 
Phase 1a Part 2 Dose Expansion .................................................................................61 
4.1.2. 
Phase 1b Combination Therapy ..................................................................................62 
4.1.2.1. 
Phase 1b Part 1 Dose Escalation .................................................................................62 
4.1.2.2. 
Phase 1b Part 2 Dose Expansion ................................................................................62 
4.1.3. 
Phase 2 ........................................................................................................................63 
4.2. 
Dose-Limiting Toxicity Rules ....................................................................................63 
4.2.1. 
Definition of Dose-Limiting Toxicities ......................................................................63 
4.3. 
Study Endpoints ..........................................................................................................65 
4.3.1. 
Primary Endpoints ......................................................................................................65 
4.3.2. 
Secondary Endpoints ..................................................................................................65 
 
66 
4.4. 
Measures Taken to Avoid Bias ...................................................................................66 
4.5. 
Number of Subjects ....................................................................................................66 
4.6. 
Study Termination ......................................................................................................66 
5. 
TREATMENT OF SUBJECTS ..................................................................................67 
5.1. 
Treatment Groups and Administration of Study Drug ...............................................67 
5.1.1. 
Phase 1a  Monotherapy ...............................................................................................67 
5.1.1.1. 
INCB052793 ...............................................................................................................67 
5.1.2. 
Phase 1b Combination Therapy ..................................................................................67 
5.1.2.1. 
INCB052793 ...............................................................................................................67 
5.1.2.2. 
nab-Paclitaxel .............................................................................................................67 
5.1.2.3. 
Gemcitabine ................................................................................................................67 
5.1.2.4. 
Dexamethasone ...........................................................................................................68 
5.1.2.5. 
Carfilzomib .................................................................................................................68 
5.1.2.6. 
Bortezomib .................................................................................................................68 
5.1.2.7. 
Lenalidomide ..............................................................................................................68 
5.1.2.8. 
Azacitidine ..................................................................................................................69 


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5.1.2.9. 
Pomalidomide .............................................................................................................69 
5.1.2.10. 
INCB050465 ...............................................................................................................69 
5.1.3. 
Phase 2 ........................................................................................................................69 
5.1.3.1. 
INCB052793 ...............................................................................................................69 
5.1.3.2. 
Itacitinib ......................................................................................................................69 
5.1.3.3. 
Azacitidine ..................................................................................................................70 
5.2. 
Treatment Compliance ................................................................................................70 
5.3. 
Randomization and Blinding ......................................................................................70 
5.4. 
Duration of Treatment and Subject Participation .......................................................70 
5.5. 
Rationale for Dose Modification ................................................................................70 
5.5.1. 
Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose ................70 
5.5.2. 
Follow-Up of Dose-Limiting Toxicities .....................................................................71 
5.5.3. 
Management of Dose-Limiting Toxicities or Other Urgent Situations ......................71 
5.6. 
Dose Adjustment of Study Drug.................................................................................71 
5.6.1. 
Planned Dose Adjustments .........................................................................................71 
5.6.2. 
Criteria and Procedures for Interruption .....................................................................72 
5.6.2.1. 
INCB052793, INCB050465, and Itacitinib Dose Interruption and Restart 
Guidelines ...................................................................................................................72 
5.6.2.2. 
Standard-of-Care Dose Interruptions ..........................................................................73 
5.6.3. 
Criteria for Permanent Discontinuation of Study Drug or Standard-of-Care 
Agents .........................................................................................................................74 
5.7. 
Withdrawal of Subjects From the Study Treatment ...................................................74 
5.7.1. 
Withdrawal Criteria ....................................................................................................74 
5.7.2. 
Withdrawal Procedures ...............................................................................................75 
5.8. 
Concomitant Medications and Measures ....................................................................75 
5.8.1. 
Growth Factor Support ...............................................................................................76 
5.9. 
Restricted Medications and Measures ........................................................................76 
5.10. 
Prohibited Medications and Measures ........................................................................76 
6. 
STUDY ASSESSMENTS ..........................................................................................76 
6.1. 
Screening Phase ........................................................................................................111 
6.2. 
Treatment Phase ........................................................................................................111 
6.3. 
End of Treatment ......................................................................................................111 
6.4. 
Follow-Up Phase ......................................................................................................112 


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6.4.1. 
Safety Follow-Up ......................................................................................................112 
6.4.2. 
Disease Status Follow-Up .........................................................................................112 
6.4.3. 
Survival Follow-Up ..................................................................................................112 
6.5. 
Unscheduled Visits ...................................................................................................112 
6.6. 
Early Termination .....................................................................................................112 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES .........................113 
7.1. 
Administration of Informed Consent Form ..............................................................113 
7.2. 
Interactive Response Technology Procedure ............................................................113 
7.3. 
Demography and History ..........................................................................................113 
7.3.1. 
Demographics and Medical History .........................................................................113 
7.3.2. 
Prior and Concomitant Medications .........................................................................113 
7.4. 
Safety Assessments ...................................................................................................113 
7.4.1. 
Adverse Events .........................................................................................................113 
7.4.2. 
Comprehensive Physical Examination .....................................................................114 
7.4.3. 
Targeted Physical Examination ................................................................................114 
7.4.4. 
Vital Signs ................................................................................................................114 
7.4.5. 
Electrocardiograms ...................................................................................................114 
7.4.5.1. 
Phase 1a Monotherapy Timed ECG .........................................................................114 
7.4.5.2. 
Phase 1b and Phase 2 Combination Therapy Timed ECG .......................................115 
7.4.6. 
Laboratory Assessments ...........................................................................................115 
7.4.6.1. 
Chemistry ..................................................................................................................115 
7.4.6.2. 
Expanded Chemistry .................................................................................................115 
7.4.6.3. 
Hematology ...............................................................................................................115 
7.4.6.4. 
Coagulation Panel .....................................................................................................116 
7.4.6.5. 
Urinalysis ..................................................................................................................116 
7.4.6.6. 
Pregnancy Testing ....................................................................................................116 
7.4.6.7. 
Serology ....................................................................................................................116 
7.4.6.8. 
Multiple Myeloma Disease Assessment ...................................................................116 
7.5. 
Disease Assessments ................................................................................................116 
7.5.1. 
Solid Tumors and Lymphoma:  CT Scan or MRI ....................................................117 
7.5.2. 
Lymphoma, AML/MDS, Multiple Myeloma, MDS/MPN, and MF ........................117 
7.5.3. 
Lymphoma:  FDG-PET or Combined PET-CT ........................................................117 


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7.5.4. 
AML, MDS, MDS/MPN, MF, Lymphoma, and MM:  Bone Marrow 
Examination ..............................................................................................................117 
7.5.5. 
Lymphoma and AML/MDS:  Immunophenotyping .................................................118 
7.5.6. 
Multiple Myeloma:  Skeletal Survey ........................................................................118 
7.6. 
Performance and Quality of Life Assessments .........................................................118 
7.7. 
Pharmacokinetic Assessments ..................................................................................119 
7.7.1. 
Blood Sample Collection ..........................................................................................119 
7.7.1.1. 
Pharmacokinetic Timed Instructions for Phase 1a ...................................................119 
7.7.1.2. 
Pharmacokinetic Instructions for Phase 1a Part 2 Dose Expansion Fed 
Administration (Cycle 2 Day 1 Only) ......................................................................119 
7.7.1.3. 
Pharmacokinetic Instructions for Phase 1b/Cohorts A Through H and 
Phase 2/Cohorts I and J .............................................................................................120 
7.7.2. 
Urine Sample Collection (Phase 1a Only) ................................................................121 
7.7.3. 
Bioanalytical Methodology and Analysis .................................................................121 
 
121 
 
121 
 
121 
 
122 
 
122 
 
122 
7.9. 
Other Study Procedures ............................................................................................123 
7.9.1. 
Administration of INCB052793 ...............................................................................123 
7.9.2. 
Administration of INCB050465 ...............................................................................123 
7.9.3. 
Administration of Itacitinib ......................................................................................123 
7.9.4. 
Dispensing of Study Drug ........................................................................................123 
7.9.5. 
nab-Paclitaxel Administration ..................................................................................124 
7.9.6. 
Gemcitabine Administration .....................................................................................124 
7.9.7. 
Dexamethasone Administration ................................................................................124 
7.9.8. 
Carfilzomib Administration ......................................................................................124 
7.9.9. 
Bortezomib Administration ......................................................................................124 
7.9.10. 
Lenalidomide Administration ...................................................................................124 
7.9.11. 
Azacitidine Administration .......................................................................................124 
7.9.12. 
Pomalidomide Administration ..................................................................................125 


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7.9.13. 
Administration of Supportive Care ...........................................................................125 
7.9.14. 
Assessment of Compliance With Study Drug ..........................................................125 
7.9.15. 
Distribution of Subject Reminder Cards ...................................................................125 
8. 
SAFETY MONITORING AND REPORTING .......................................................126 
8.1. 
Adverse Events .........................................................................................................126 
8.1.1. 
Definitions and Reporting .........................................................................................126 
8.2. 
Laboratory Test Abnormalities .................................................................................127 
8.2.1. 
Definitions and Reporting .........................................................................................127 
8.3. 
Serious Adverse Events ............................................................................................127 
8.3.1. 
Definitions ................................................................................................................127 
8.3.2. 
Reporting ..................................................................................................................128 
8.4. 
Emergency Unblinding of Treatment Assignment ...................................................129 
8.5. 
Pregnancy .................................................................................................................129 
8.6. 
Warnings and Precautions ........................................................................................130 
8.7. 
Data Monitoring Committee .....................................................................................130 
8.8. 
Adverse Events of Special Interest ...........................................................................130 
8.9. 
Product Complaints ..................................................................................................130 
9. 
STATISTICS ............................................................................................................131 
9.1. 
Study Populations .....................................................................................................131 
9.2. 
Selection of Sample Size ..........................................................................................131 
9.2.1. 
Sample Size for Phase 1a and Phase 1b ....................................................................131 
9.2.2. 
Sample Size for Phase 2 ...........................................................................................131 
9.3. 
Level of Significance ................................................................................................132 
9.4. 
Statistical Analyses ...................................................................................................132 
9.4.1. 
Primary Analyses ......................................................................................................132 
9.4.1.1. 
Phase 1a and 1b ........................................................................................................132 
9.4.1.2. 
Phase 2 ......................................................................................................................132 
9.4.2. 
Secondary Analyses ..................................................................................................132 
9.4.2.1. 
Baseline Demographics and Disposition of Subjects ...............................................132 
9.4.3. 
Other Analyses ..........................................................................................................132 
9.5. 
Data Monitoring Committee .....................................................................................133 
9.6. 
Interim Analysis ........................................................................................................133 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT .........................................133 


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10.1. 
Investigational Product Description .........................................................................133 
10.1.1. 
Packaging, Labeling, and Preparation of INCB052793 ...........................................133 
10.1.2. 
Storage and Stability of INCB052793 ......................................................................133 
10.1.3. 
Packaging, Labeling, and Preparation of INCB050465 ...........................................133 
10.1.4. 
Storage and Stability of INCB050465 ......................................................................133 
10.1.5. 
Packaging, Labeling, and Preparation of Itacitinib ..................................................133 
10.1.6. 
Storage and Stability of Itacitinib .............................................................................133 
10.2. 
Accountability, Handling, and Disposal of Study Drug ...........................................134 
11. 
STUDY ADMINISTRATION .................................................................................135 
11.1. 
Data Management .....................................................................................................135 
11.1.1. 
Data Collection .........................................................................................................135 
11.1.2. 
Data Management .....................................................................................................135 
11.2. 
Study Monitoring ......................................................................................................135 
11.3. 
Protocol Adherence ..................................................................................................136 
11.4. 
Financial Disclosure .................................................................................................136 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................137 
12.1. 
Sponsor Audits..........................................................................................................137 
12.2. 
Inspection by Regulatory Authorities .......................................................................137 
13. 
ETHICS ....................................................................................................................137 
13.1. 
Ethical Conduct of the Study ....................................................................................137 
13.2. 
Written Informed Consent ........................................................................................137 
13.3. 
Ethics Review ...........................................................................................................138 
13.4. 
Data Privacy ..............................................................................................................139 
14. 
DATA HANDLING AND RECORDKEEPING .....................................................139 
14.1. 
Inspection of Records ...............................................................................................139 
14.2. 
Retention of Records ................................................................................................139 
14.3. 
Confidentiality ..........................................................................................................140 
15. 
PUBLICATION POLICY ........................................................................................140 
16. 
REFERENCES .........................................................................................................141 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS .............................................................................147 
APPENDIX B. PHARMACOKINETIC ANALYTICAL PARAMETERS ............................148 
APPENDIX C. CYTOCHROME P450 3A4 INHIBITORS AND INDUCERS ......................149 


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APPENDIX D. INTERNATIONAL UNIFORM RESPONSE CRITERIA FOR 
MULTIPLE MYELOMA .........................................................................................154 
APPENDIX E. INTERNATIONAL WORKING GROUP RESPONSE CRITERIA 
FOR ACUTE MYELOID LEUKEMIA ...................................................................155 
APPENDIX F. IWG RESPONSE CRITERIA FOR MYELODYSPLASTIC 
SYNDROME ............................................................................................................156 
APPENDIX G. RESPONSE CRITERIA FOR LYMPHOMA – THE LUGANO 
CLASSIFICATION ..................................................................................................157 
APPENDIX H. INTERNATIONAL CONSORTIUM PROPOSAL OF UNIFORM 
RESPONSE CRITERIA FOR 
MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS 
(MDS/MPN) IN ADULTS .......................................................................................159 
APPENDIX I. REVISED RESPONSE CRITERIA FOR MYELOFIBROSIS:  IWG-
MRT AND ELN CONSENSUS REPORT...............................................................162 
 
LIST OF TABLES 
Table 1: 
Guidelines for Interruption and Restart of Study Drugs INCB052793, 
INCB050465, and Itacitinib........................................................................................72 
Table 2: 
Schedule of Assessments for Phase 1a Monotherapy (Dose Escalation and 
Expansion) ..................................................................................................................77 
Table 3: 
Laboratory Assessments for Phase 1a Monotherapy (Dose Escalation and 
Expansion) ..................................................................................................................80 
Table 4: 
Schedule of Assessments for Phase 1b/Cohort A Combination Therapy 
(Gemcitabine and nab-Paclitaxel) ..............................................................................81 
Table 5: 
Laboratory Assessments for Phase 1b/Cohort A Combination Therapy 
(Gemcitabine and nab-Paclitaxel) ..............................................................................82 
Table 6: 
Schedule of Assessments for Phase 1b/Cohort B Combination Therapy 
(Dexamethasone) ........................................................................................................83 
Table 7: 
Laboratory Assessments for Phase 1b/Cohort B Combination Therapy 
(Dexamethasone) ........................................................................................................85 
Table 8: 
Schedule of Assessments for Phase 1b/Cohort C Combination Therapy 
(Carfilzomib) ..............................................................................................................86 
Table 9: 
Laboratory Assessments for Phase 1b/Cohort C Combination Therapy 
(Carfilzomib) ..............................................................................................................88 
Table 10: Schedule of Assessments for Phase 1b/Cohort D Combination Therapy 
(Bortezomib) ...............................................................................................................89 
Table 11: Laboratory Assessments for Phase 1b/Cohort D Combination Therapy 
(Bortezomib) ...............................................................................................................91 


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Table 12: Schedule of Assessments for Phase 1b/Cohort E Combination Therapy 
(Lenalidomide) ...........................................................................................................92 
Table 13: Laboratory Assessments for Phase 1b/Cohort E Combination Therapy 
(Lenalidomide) ...........................................................................................................94 
Table 14: Schedule of Assessments for Phase 1b/Cohort F Combination Therapy 
(Azacitidine) ...............................................................................................................95 
Table 15: Laboratory Assessments for Phase 1b/Cohort F Combination Therapy 
(Azacitidine) ...............................................................................................................97 
Table 16:  Schedule of Assessments for Phase 1b/Cohort G Combination Therapy 
(Pomalidomide/Dexamethasone) ................................................................................98 
Table 17: Laboratory Assessments for Phase 1b/Cohort G Combination Therapy 
(Pomalidomide/Dexamethasone) ..............................................................................100 
Table 18: Schedule of Assessments for Phase 1b/Cohort H Combination Therapy 
(INCB052793 + INCB050465) ................................................................................101 
Table 19: Laboratory Assessments Phase 1b/Cohort H Combination Therapy 
(INCB052793 + INCB050465) ................................................................................103 
Table 20: Schedule of Assessments for Phase 2/Cohort I (INCB052793 With 
Azacitidine) ...............................................................................................................104 
Table 21: Laboratory Assessments for Phase 2/Cohort I (INCB052793 With 
Azacitidine) ...............................................................................................................106 
Table 22: Schedule of Assessments for Phase 2/Cohort J (Itacitinib With Azacitidine) ..........107 
Table 23: Laboratory Assessments for Phase 2/Cohort J (Itacitinib With Azacitidine) ...........109 
Table 24: Laboratory Tests:  Required Analytes ......................................................................110 
Table 25: ECOG Performance Status .......................................................................................118 
 
LIST OF FIGURES 
 
 
Figure 2: 
Study Design ...............................................................................................................60 
 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Term 
Explanation 
AE 
adverse event 
ALCL 
anaplastic large cell lymphoma 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the plasma or serum concentration-time curve 
BID 
twice daily 
BCRP 
Breast Cancer Resistant Protein 
CI 
confidence interval 
CFR 
Code of Federal Regulations 
Cmax  
maximum observed plasma or serum concentration 
CMML 
chronic myelomonocytic leukemia 
CR 
complete response 
CRi 
complete response with incomplete hematologic recovery 
CRF 
case report form  
CRP 
C-reactive protein 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
dCTP 
deoxycytidine triphosphate 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DMC 
Data Monitoring Committee 
 
 
EOT 
end of treatment 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
FDG-PET 
positron emission tomography using [18F] fluorodeoxyglucose 
FISH 
fluorescence in situ hybridization 
FLC 
free light chain 


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Term 
Explanation 
GCP 
Good Clinical Practice 
GCSF 
granulocyte colony-stimulating factor 
GFR 
glomerular filtration rate 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practices 
GVHD 
graft-versus-host disease 
HBV 
hepatitis B virus 
HBC 
hepatitis C virus 
hERG 
human ether-a-go-go related gene 
HI 
hematologic improvement 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HL 
Hodgkin lymphoma 
HMA 
hypomethylating agent 
HNSTD 
highest non-severely toxic dose 
IC50 
half maximal inhibitory concentration 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IL 
interleukin 
IMiD 
immunomodulatory drug 
IN 
Investigator Notification 
INR 
international normalized ratio 
IRB 
institutional review board 
IV 
intravenous 
IMWG 
International Myeloma Working Group 
JAK 
Janus kinase 
MDRD 
Modification of Diet in Renal Disease 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
myelofibrosis 
MPN 
myeloproliferative neoplasm 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MM 
multiple myeloma 
NCCN 
National Comprehensive Cancer Network 


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Term 
Explanation 
NHL 
non-Hodgkin lymphoma 
NOAEL 
no-observed-adverse-effects level 
NSCLC  
non–small cell lung cancer 
ORR 
objective response rate 
PAD 
pharmacologically active dose 
PJP 
Pneumocystis jiroveci pneumonia 
PD 
pharmacodynamics 
PET 
positron emission tomography 
PFS 
progression-free survival 
P-gp 
P-glycoprotein 
PI3K 
phosphatidylinositol 3-kinase 
PI3Kδ 
phosphatidylinositol 3-kinase δ 
PK 
Pharmacokinetic 
PO 
orally 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
PR 
partial response 
QTcF 
QT interval corrected using the Fridericia formula 
QD 
once daily 
RA 
rheumatoid arthritis 
SAE 
serious adverse event 
SC 
subcutaneously 
STAT 
signal transducers and activators of transcription 
STD10 
severely toxic dose in 10% of animals 
SCM 
stromal conditioned media 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TGA 
Treatment Group A 
TGB 
Treatment Group B 
Tmax 
time to maximum plasma concentration 
TYK 
tyrosine kinase 
ULN 
upper limit of normal  
Vdss 
volume of distribution at steady state 
WBC 
white blood cell 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
1.1. 
Background 
INCB052793 hydrochloride, referred to herein as INCB052793, is an inhibitor of the Janus 
kinase (JAK) family of protein tyrosine kinases (TYK), with selectivity for JAK1.  INCB052793 
is an investigational product that is in development for treatment of patients with advanced or 
metastatic cancer.  Janus kinases play an important role in signal transduction after cytokine and 
growth factor binding to their receptors.  Aberrant production of cytokines and growth factors 
has been associated with a number of cancers.  Additionally, the JAK/signal transducers and 
activators of transcription (STAT) pathway is a progrowth signaling pathway, direct or indirect 
activation of which has been observed in a variety of tumor types.  Therefore, JAK inhibitors 
represent potential therapeutic agents for these disease states. 
1.1.1. 
Janus Kinases in Oncology 
The JAK enzymes play an obligatory role in transducing intracellular signals generated by 
cytokine and growth factor receptors.  Upon cytokine and growth factor binding to their cognate 
receptors, tyrosine phosphorylation of the intracellular domains of the receptors by JAKs enables 
them to serve as docking sites for STAT transcription factors, which are also phosphorylated.  
Tyrosine phosphorylated STATs are released from the receptors, form homodimers, and 
translocate to the nucleus where they bind canonical sequences and modulate transcription of 
genes that regulate a number of cellular functions (Sansone and Bromberg 2012).  In contrast to 
normal cells, in which STAT tyrosine phosphorylation occurs transiently, STAT proteins, 
especially STAT3, are persistently phosphorylated in most malignancies (Sansone and Bromberg 
2012).  The persistent or constitutive phosphorylation of STAT3 in cancers may occur via a 
variety of mechanisms, including a) increased expression of cytokines and cytokine receptors, 
b) decreased expression of the negative regulatory proteins such as suppressors of cytokine 
signaling through promoter methylation, and c) loss of tyrosine phosphatases that 
dephosphorylate JAKs and STATs. 
Neoplastic progression involves JAK/STAT pathway activity through cell autonomous and 
non-cell autonomous mechanisms.  Cell autonomous mechanisms refer to tumor cell intrinsic 
alterations that facilitate the gain of neoplastic properties.  The ability of STAT3 to sustain cell 
proliferation and block apoptosis (Lesina et al 2011); mediate cell cycle progression during 
oncogenic stress (Toyonaga et al 2003, Thoennissen et al 2009); control invasiveness, metastasis, 
and angiogenesis; and confer chemotherapeutic resistance (Catlett-Falcone et al 1999) are major 
mechanisms contributing to cancer.  Non-cell autonomous mechanisms refer to the extrinsic 
effects mediated by tumor microenvironment, stroma, immune system, and stellate cells 
(Masamune et al 2005); these play an integral role in many cancers and are substantially shaped 
to a great extent by JAK/STAT signaling.  In addition, JAK/STAT-dependent inflammatory 
cytokines such as interleukin (IL)-6 and interferon gamma are critical mediators of cancer 
cachexia, a significant cause for cancer morbidity and mortality.  Based on this evidence, we 
hypothesize that inhibition of JAK kinases may directly affect malignant cell proliferation and 
may suppress the inflammatory state leading to improvements in nutritional status, fatigue, 
tolerance to therapy, and prolonged survival in patients with advanced cancers that are driven by 


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these intrinsic and extrinsic pathways influenced by STATs.  This hypothesis is supported by 
evidence that JAK/STAT inhibitors are able to slow tumor cell growth and prolong survival in 
in vivo models (Thoennissen et al 2009, Toyonaga et al 2003, Iwanski et al 2010, Burger et al 
2009, Li et al 2010). 
1.1.2. 
Pharmacology of INCB052793 
INCB052793 is a small molecule inhibitor of the JAK family of protein TYKs, with selectivity 
for JAK1, which is proposed for development for the treatment patients with advanced or 
metastatic cancer.  Janus kinases play an important role in signal transduction following cytokine 
and growth factor binding to their receptors.  Aberrant production of cytokines and growth 
factors has been associated with a number of cancers.  Additionally, the JAK/STAT pathway is a 
progrowth signaling pathway; direct or indirect activation of which has been observed in a 
variety of tumor types.  Therefore, JAK1 inhibition may be efficacious in these diseases. 
In vitro, INCB052793 potently inhibits JAK1 (IC50 = 1.8 nM), with 18 to > 800-fold selectivity 
over the other JAK family members, JAK2, JAK3, and TYK2.  INCB052793 also demonstrates 
JAK1 selectivity in cell-based assays.  In cell-based assays previously shown to be dependent on 
JAK1 activity, including IL-2 or IL-6 stimulated phosphorylation of STATs; INCB052793 
showed potent inhibition with IC50 values in the range of approximately 10-100 nM.  In human 
whole blood, INCB052793 inhibited IL-6–stimulated phosphorylated STAT3 (pSTAT3) with an 
IC50 value of 144 nM, and showed approximately 100-fold weaker activity in blocking pSTAT3 
induced by thrombopoietin, a cytokine that is known to signal through JAK2 homodimers 
(IC50 = 14110 nM).  In addition to its effects on JAK-mediated signaling, INCB052793 potently 
inhibited the production of proinflammatory factors (eg, IL-17, monocyte chemoattractant 
protein 1 [MCP-1]) induced by other cytokines, such as IL-23 and IL-6, with IC50 values in the 
range of approximately 10 to 100 nM.  Finally, INCB052793 was shown to block the cytokine-
dependent growth of tumor cell lines in vitro, with IC50 values in the range of 100nM to 250 nM.  
These results confirm that INCB052793 shows consistent pharmacological activity in cell-based 
assays and displays selectivity for JAK1 versus JAK2 in both biochemical and cellular assays. 
In vivo, INCB052793 potently and dose-dependently inhibited JAK/STAT signaling in a number 
of different tumor models, including pancreatic ductal adenocarcinomas.  As a single agent, 
treatment with INCB052793, when administered either by continuous infusion or by oral gavage, 
was sufficient to inhibit the growth of cytokine-dependent INA-6 myeloma.  Both the 
pharmacodynamic (PD) effects and tumor growth inhibitory activity were observed at plasma 
concentrations of INCB052793 below that required to inhibit JAK2 in a biologically relevant 
milieu in humans or rats.  These data are consistent with the concept that selective JAK1 
inhibition may be efficacious in a number of oncological diseases. 
In safety pharmacology assessments of INCB052793, including a series of in vitro binding and 
enzyme assays, respiratory and central nervous system (CNS) studies in rats, and in vitro the 
human ether-a-go-go related gene (hERG) and in vivo (conscious telemeterized dogs) 
cardiovascular studies, no adverse findings were noted.  Therefore, the risk associated with 
clinical administration of INCB052793, stemming from the pharmacology of this molecule, is 
expected to be low. 


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In summary, pharmacological data obtained in both in vitro and in vivo model systems support 
the potential utility of orally administered INCB052793 in the treatment of advanced or 
metastatic disease. 
1.1.3. 
Absorption, Distribution, Metabolism, Excretion and Disposition 
1.1.3.1. 
Absorption 
The in vitro permeability of INCB052793 across Caco-2 monolayers was moderate 
(5.7 × 10-6 cm/s).  INCB052793 is a substrate of both P-glycoprotein (P-gp) and Breast Cancer 
Resistant Protein (BCRP).  Since INCB052793 is a substrate of P-gp at concentrations below 
100 μM in vitro, it is unlikely that efflux by P-gp plays an important role in the oral absorption of 
INCB052793.  However, efflux by BCRP was not saturated at 100 μM in vitro.  Thus, BCRP 
may limit oral absorption at the lower proposed clinical dose.  In single dose, oral 
pharmacokinetic (PK) studies conducted in rats, dogs, and monkeys, INCB052793 was absorbed 
slowly in monkeys, with Tmax values of 3.5 hours, while this value was 0.75 hours and 0.94 hours 
in dogs and rats, respectively.  The absolute oral bioavailability was low in monkeys (19%) but 
high in dogs (84%) and was complete in rats. 
1.1.3.2. 
Distribution 
In single-dose, intravenous (IV) administration PK studies in rats, dogs, and monkeys, the 
apparent steady-state Vdss values of INCB052793 ranged from 0.902 to 1.77 L/kg, suggesting 
that INCB052793 is distributed slightly beyond the total volume of body water (0.7 L/kg) in 
these 3 preclinical species.   
INCB052793 exhibits low protein binding in rats, dogs, and human with the fraction unbound 
being approximately 50% and independent of substrate concentration.  In rats and beagle dogs, 
the fraction unbound was similar between in vitro- and ex vivo-sourced plasma.  The average 
ex vivo fraction unbound of INCB052793 in both rat and dog plasma was 55%, and the average 
in vitro fraction unbound of INCB052793 in human plasma and serum was 51 %.  The total brain 
concentration of INCB052793 after 4 hours of infusion was 11% of the corresponding total 
plasma concentration in the same rats, and the cerebrospinal fluid (CSF) concentration was 9.4% 
of the corresponding estimated unbound plasma concentration.  Therefore, based on observed 
concentrations in the brain and CSF, it is concluded that INCB052793 has limited penetration 
across the blood-brain-barrier in rats. 
Although INCB052793 is an inhibitor of P-gp, with an IC50 of 65.5 μM, potential for a clinical 
drug-drug interaction with a P-gp substrate is low at clinically relevant exposures.  However, 
INCB052793 is a substrate of both P-gp and BCRP, and hence a clinical drug interaction study 
with inhibitors of P-gp and BCRP may be warranted. 
1.1.3.3. 
Metabolism 
In PK studies, INCB052793 exhibited low systemic clearance in rats and beagle dogs but 
moderate systemic clearance in cynomolgus monkeys, corresponding to 20%, 21%, and 42% of 
hepatic blood flow in these species, respectively.  
In vitro metabolism studies showed that cytochrome P450 (CYP) 2D6, CYP3A4, UGT1A9, and 
UGT2B7 metabolize INCB052793.  INCB052793 was not a potent inhibitor of human liver 


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microsomal CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4-
mediated testosterone hydroxylation activity, with IC50 values > 25 μM, but was an inhibitor of 
CYP3A4-mediated midazolam hydroxylation activity, with an IC50 value of 13 μM.  There was 
no evidence of metabolism-dependent inhibition of CYP2C9, CYP2C19, CYP2D6, and 
CYP3A4.  Thus, INCB052793 is unlikely to cause clinical drug interactions via inhibition of 
CYPs at the proposed therapeutic dose (50 mg once daily [QD]).  Following repeated dose 
administration in rats and dogs, there was no evidence of auto-induction of clearance.  
The in vitro metabolism of INCB052793 in preclinical species was generally low to moderate, 
with the greatest amount of turnover noted in the monkey.  In the hepatic microsomal samples, 
S-9 fractions and hepatocyte incubations across all species, a total of 11 metabolites were 
detected by liquid chromatography-mass spectrometry (LC-MS).  The most abundant 
metabolites were oxidative metabolites M8 in monkey S-9 and hepatocytes, M4 in rat 
microsomes, and the glucuronide conjugate of INCB052793 (M13) in monkey hepatocytes.  
Overall, there were only minor quantitative and qualitative differences evident between the 
species.  There were no human-specific metabolites noted in the course of this investigation.  
Trace amounts of 2 glutathione conjugates were likely formed by in vitro rat metabolites M1 and 
M2, but these conjugates were not found in human liver microsomes. 
There were no major metabolites observed in rat plasma, but several metabolites were observed 
at trace levels.  In dog plasma, 2 major metabolites of INCB052793, M4 and M11, were 
identified with several metabolites being observed at trace levels.  A total of 7 metabolites of 
INCB052793 were found and characterized in urine samples from rats and dogs.  The most 
abundant metabolites were M4, M7, and M11 in rat urine, and M11 in dog urine. 
1.1.3.4. 
Excretion 
Based on PK studies with unlabeled INCB052793, the renal excretion of intact INCB052793 was 
low (less than or approximating the GFR in preclinical species), suggesting that active renal 
tubular secretion is not likely involved in the renal excretion of INCB052793 in these 3 species. 
1.1.3.5. 
Disposition 
Following IV administration of INCB052793, the total systemic clearance was low in rats 
(0.667 L/h/kg) and beagle dogs (0.396 L/h/kg) and moderate in monkeys (1.10 L/h/kg), which 
approximated 20%, 21%, and 42% of hepatic blood flow in these species, respectively.  After IV 
administration, INCB052793 had a moderate half-life in rats (3.5 hours) and dogs (3.1 hours), 
while this value was long in monkeys (6.8 hours). 
1.2. 
Standard-of-Care Agents 
1.2.1. 
Gemcitabine 
Gemcitabine is a nucleoside analog with structural similarity to cytarabine and is currently 
approved to treat breast cancer, non–small cell lung cancer (NSCLC), ovarian cancer, and 
pancreatic cancer either alone or in combination with other chemotherapy agents.  Gemcitabine 
has also shown efficacy in other tumor types and is currently being studied in various advanced 
and metastatic cancers. 


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Gemcitabine monotherapy was approved by the FDA in 1996 as first-line treatment for patients 
with locally advanced or metastatic adenocarcinoma of the pancreas that was previously treated 
with fluorouracil.  Clinical benefit and survival were used as the primary endpoints in a study 
that included 126 previously untreated patients randomly assigned to fluorouracil or gemcitabine 
(Argilés et al 2009, Burris et al 1997).  Although there were no confirmed objective responses in 
either group, gemcitabine was associated with significantly better clinical response (24% vs 5%) 
and 1-year survival (18% vs 2%).  Although monotherapy gemcitabine demonstrated 
improvement of overall survival in advanced or metastatic pancreatic cancer, gemcitabine is 
more commonly administered as part of a combination regimen in other tumor types. 
Gemcitabine is also approved for use in combination with cisplatin for the first-line treatment of 
patients with inoperable, locally advanced, or metastatic NSCLC, and in combination with 
paclitaxel for the treatment of metastatic breast cancer after failure of prior anthracycline-
containing adjuvant therapy.  The most recent approval is for the use of gemcitabine in 
combination with carboplatin in patients with advanced ovarian cancer.  All studies conducted 
showed a significant improvement in time to disease progression, progression-free survival 
(PFS), and objective tumor response in the gemcitabine treatment arm versus the comparator.  
Improvement in overall survival with gemcitabine has been demonstrated in NSCLC and 
metastatic breast cancer; however, no significant difference in overall survival was observed in 
combination with carboplatin in ovarian cancer. 
Gemcitabine exhibits cell phase specificity, primarily killing cells undergoing DNA synthesis 
and also blocking the progression of cells through the G1/S-phase boundary.  Gemcitabine is 
metabolized intracellularly by nucleoside kinases to the active diphosphate and triphosphate 
nucleosides.  Gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for 
catalyzing the reactions that generate the deoxynucleoside triphosphates for DNA synthesis; this 
inhibition causes a reduction in the concentrations of deoxynucleotides, including deoxycytidine 
triphosphate (dCTP).  Second, gemcitabine triphosphate competes with dCTP for incorporation 
into DNA.  A drug-drug interaction between INCB052793 and gemcitabine is not anticipated 
based on the mechanism of clearance of both compounds. 
1.2.2. 
Gemcitabine Plus nab-Paclitaxel 
Activity for gemcitabine in combination with nab-paclitaxel in pancreatic cancer has been shown 
in a Phase 2 study (Von Hoff et al 2011) and in a recently completed Phase 3 study 
(Von Hoff et al 2013).  In the Phase 3 study, among subjects treated with gemcitabine 
1000 mg/m2 with or without nab-paclitaxel 125 mg/m2 on Days 1, 8, and 15 of every 28-day 
cycle, nab-paclitaxel demonstrated a 31% reduction in the risk of progression or death, with a 
median PFS of 5.5 versus 3.7 months and an overall response rate of 23% compared to 7% with 
gemcitabine alone.  The most common Grade 3 or greater treatment-related adverse events (AEs) 
were neutropenia (38% vs 27%), fatigue (17% vs 7%), and neuropathy (17% vs 1%) in the 
combination arm versus the gemcitabine-only arm.  There was no difference in serious life-
threatening toxicity (4% in each arm). 
Gemcitabine in combination with paclitaxel has demonstrated activity in metastatic breast 
cancer, with improvements in PFS and overall survival (Park et al 2013).  The combination of 
gemcitabine and paclitaxel has also been used effectively in second-line urothelial cancer 
(Ikeda et al 2011, Albers et al 2011).  Thus, gemcitabine in combination with paclitaxel has 


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shown clinically meaningful antitumor activity in first- and/or second-line metastatic pancreatic, 
breast, and urothelial cancer.  Treatment with nab-paclitaxel delivers paclitaxel to the tumor as 
the active moiety, and treatment with nab-paclitaxel has been shown to permit greater dose 
intensity with reduced toxicity compared with paclitaxel (Abraxane 2013).  Thus, the 
combination of gemcitabine with nab-paclitaxel is currently being used in indications where the 
combination of gemcitabine with paclitaxel has shown activity. 
nab-Paclitaxel promotes the assembly and stability of microtubules, resulting in the inhibition of 
the normal dynamic reorganization of the microtubule network that is essential for vital 
interphase and mitotic cellular functions.  The PK of paclitaxel may also be altered in vivo as a 
result of interactions with compounds that are inducers or inhibitors of CYP2C8 and/or 
CYP3A4.  INCB052793 is primarily metabolized by CYP3A4 but is not an inducer or inhibitor 
of CYP3A4 at clinically relevant concentrations.  A metabolic drug-drug interaction between 
INCB052793 and nab-paclitaxel is not anticipated. 
1.2.3. 
Dexamethasone 
Dexamethasone is a synthetic adrenocortical steroid that is FDA-approved for use in several 
endocrine, inflammatory, and autoimmune conditions (Dexamethasone 2007), as well as 
palliative treatment for hematologic malignancies, including leukemia and lymphoma.  
Dexamethasone and other glucocorticoids exert apoptotic effects on myeloma cells, in part 
through inhibition of NF-κB activity (Greenstein et al 2002).  Pulse dexamethasone has been 
used as a single agent in the treatment of primary and relapsed/refractory multiple myeloma 
(MM) since the early 1980s (Facon et al 2006).  Overall single agent response rates of 43% 
(Alexanian et al 1992) and 21% (Alexanian et al 1986) have been reported in the primary and 
treatment refractory settings, respectively.  Dexamethasone is a weak inducer of CYP3A4, but it 
is not expected to exert pharmacologically significant or clinically relevant decreases in 
INCB052793 concentration. 
1.2.4. 
Carfilzomib 
Carfilzomib is a second-generation proteasome inhibitor that has been approved in the 
United States since 2012 for treatment of patients with relapsed and/or refractory MM 
(Kyprolis 2012).  Carfilzomib is structurally and mechanistically different from the dipeptide 
boronic acid proteasome inhibitor bortezomib, which has been approved since 2003 for use in 
the treatment of patients with MM.  Carfilzomib has demonstrated activity in relapsed or 
refractory MM both as a single agent (Siegel et al 2012) and in combination with other 
antimyeloma agents, including dexamethasone (Badros et al 2013) and immunomodulatory 
agents such as lenalidomide (Niesvizky et al 2013, Richardson et al 2014b, Papadopoulos et al 
2015).  Carfilzomib is a tetrapeptide with an epoxyketone and is metabolized by peptidases; a 
metabolic drug-drug interaction between INCB052793 and carfilzomib is not anticipated. 
1.2.5. 
Bortezomib 
Bortezomib is a proteasome inhibitor that has been approved in the United States since 2003 for 
treatment of patients with MM (Velcade 2014).  Bortezomib exerts a number of different 
antimyeloma effects, including disruption of the cell cycle and induction of apoptosis, alteration 
of the bone marrow microenvironment and inhibition of NF-κB (Field-Smith et al 2006).  The 
Phase 3 APEX  trial evaluating single-agent bortezomib versus high-dose dexamethasone in 


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relapsed MM reported partial and complete response (CR) rates of 43% and 9%, respectively, in 
the bortezomib group (Richardson et al 2007).  Single-agent bortezomib has also been 
demonstrated to prolong time to progression and overall survival relative to high-dose 
dexamethasone in patients with relapsed MM (Richardson et al 2007)  The addition of 
dexamethasone has also been shown to augment responses after disease progression or lack of 
response on single-agent bortezomib (Jagannath et al 2006).  Bortezomib is a substrate of CYP 
enzyme 3A4, 2C19, and 1A2, but is not an inhibitor or inducer.  A metabolic drug-drug 
interaction between INCB052793 and bortezomib is not anticipated. 
1.2.6. 
Lenalidomide 
Lenalidomide is a thalidomide analogue that has been FDA-approved for treatment of MM since 
2005 (Revlimid 2015).  Several mechanisms are known to be responsible for the antimyeloma 
activity of lenalidomide; these include immunomodulatory, anti-angiogenic, and direct 
antineoplastic effects (Kotla et al 2009).  Richardson et al (2006) demonstrated a single-agent 
overall response rate of 25% in relapsed/refractory MM; in subjects who did not achieve a 
response after 2 cycles, dexamethasone was added and the overall response rate in the 
combination group was 29%.  Two Phase 3 studies (Dimopoulos et al 2007, Weber et al 2007) 
evaluated the combination of lenalidomide and dexamethasone versus dexamethasone alone; 
these studies revealed an overall response rate of 60.2% versus 24% and 61% versus 19.9%, 
respectively.  Lenalidomide is a P-gp substrate but not an inhibitor, and it also is not a CYP 
inhibitor or inducer.  A metabolic drug-drug interaction between INCB052793 and lenalidomide 
is not anticipated. 
1.2.7. 
Azacitidine 
Azacitidine is a nucleoside metabolic inhibitor that is approved by the FDA for the treatment of 
patients with several different subtypes of myelodysplastic syndrome (MDS; Vidaza 2014).  
Azacitidine is thought to have 2 main mechanisms of antineoplastic action:  cytotoxicity, 
resulting from incorporation into RNA and DNA, and DNA hypomethylation, restoring normal 
growth control and differentiation in hematopoietic cells (Kaminskas et al 2005).  Several 
clinical studies have demonstrated the efficacy of azacitidine in MDS.  In a Phase 2 clinical 
study evaluating azacitidine versus supportive care in high-risk MDS, Silverman et al (2002) 
reported a 60% overall response rate (including hematologic improvement) for azacitidine as 
compared with 5% receiving supportive care.  Additionally, a Phase 3 study (Fenaux et al 2009) 
evaluating azacitidine versus conventional care in higher risk MDS revealed superior rates of 
hematological response (29% vs 12%) and hematological improvement (49% vs 29%) in the 
azacitidine group. 
Azacitidine is recommended as a low-intensity induction therapy in acute myeloid leukemia 
(AML), primarily in patients who are unfit for high- or intermediate-intensity regimens 
(NCCN Guidelines).  Although there has been limited investigation into the use of azacitidine in 
relapsed/refractory AML, Al-Ali et al (2012) reported a 10% overall response rate (including 
hematologic improvement) in subjects who were resistant to primary chemotherapy.  Azacitidine 
undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase.  
Cytochrome P450 enzyme induction or inhibition by azacitidine at clinically achievable plasma 
concentrations is unlikely, and metabolic drug-drug interaction between INCB052793, itacitinib, 
and azacitidine is not anticipated. 


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1.2.8. 
Pomalidomide 
Pomalidomide is approved for the treatment of MM (in combination with dexamethasone) in 
patients who have received at least 2 prior therapies, including lenalidomide and a proteasome 
inhibitor, and have demonstrated disease progression on or within 60 days of completion of the 
last therapy.  In the United States, approval was granted in 2013 on the basis of 2 Phase 2 clinical 
studies in which pomalidomide and dexamethasone showed objective response rate (ORR) of 
29% and 34%, respectively.  European Medicines Agency approval was granted later that year 
based on the results of the aforementioned Phase 2 clinical studies in addition to the results of a 
Phase 3 open-label study that compared the efficacy and safety of pomalidomide plus low-dose 
dexamethasone with high-dose dexamethasone, which benefits PFS (4.0 months vs 1.9 months), 
ORR (31% vs 10%), and overall survival (12.7 months vs 8.1 months).  The doses of 
pomalidomide (4 mg orally [PO] on Days 1 to 21 of each 28-day cycle) and dexamethasone 
(40 mg orally weekly on Days 1, 8, 15, and 22 of a 28-day cycle) used in each of the above 
studies are the recommended doses in the relevant approvals, with appropriate adjustments for 
toxicities.  
1.3. 
Overview of INCB050465 
INCB050465 represents a novel, potent, and selective inhibitor of the Class IA 
phosphatidylinositol 3-kinase (PI3K) enzymes, with selectivity for the delta isoform, which is 
proposed for development for treatment of hematological malignancies.  Because aberrant 
activation of phosphatidylinositol 3-kinase δ (PI3Kδ) has been associated with increased 
malignant B-cell proliferation and survival, its inhibition may be therapeutic for the treatment of 
such conditions.  
1.3.1. 
Pharmacology of INCB050465 
INCB050465 potently inhibits the PI3Kδ kinase (IC50 = 1.0 ± 0.5 nM), with approximately 
20,000-fold selectivity for the other PI3K family members and > 300-fold selectivity against a 
broad panel of 192 other kinases.  INCB050465 also showed no significant cross-reactivity 
(defined as > 50% inhibition of specific binding) when screened in vitro at 0.1 and 1.0 μM 
against approximately 70 receptors, ion channels, transporters, and enzymes.  Moreover, 
INCB050465 is potent (IC50 values of ≤ 10 nM) in cell-based assays relevant to the pathogenesis 
of B-cell malignancies, such as PI3Kδ-mediated signaling and growth of human B-cell lines.  
This effect is not due to general cytotoxicity, because 10 μM INCB050465 had no significant 
effect on the growth of nonlymphoid cell lines.  Compared to inhibition of B-cell proliferation, 
INCB050465 is similarly potent in blocking helper T-cell differentiation but is > 100 times less 
potent in assays that measure effects on human T-cell and natural killer cell proliferation or 
monocyte function.  
 
 
  In vivo, INCB050465 administration inhibited PI3Kδ signaling and tumor 
growth as a single agent in a dose-dependent manner in Pfeiffer xenograft models of non-
Hodgkin lymphoma (NHL). 
These data are further discussed in the INCB050465 Investigator's Brochure (IB). 


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1.3.2. 
Nonclinical Drug Metabolism and Pharmacokinetics of INCB050465 
The absorption, distribution, metabolism, and excretion of INCB050465 have been studied in 
rats, dogs, and monkeys.  INCB050465 exhibited low systemic clearance, a low to moderate 
volume of distribution, moderate (4 to ~9 hours) terminal half-life, and good absorption, with the 
absolute oral bioavailability ranging from 74% to 100%. 
After IV administration, INCB050465 displayed low systemic clearance, representing 26%, 2%, 
and 5% of the hepatic blood flow in rats, dogs, and monkeys, respectively.  The steady-state 
volume of distribution was moderate in rats (1.5 L/kg) but low in dogs (0.3 L/kg) and monkeys 
(0.8 L/kg), implying species differences.  The terminal elimination half-life ranged from 
4.0 hours (rat) to 9.3 hours (monkey).  The renal excretion of intact INCB050465 was minimal 
(< 2% across species).  INCB050465 has limited penetration across the rat blood-brain barrier. 
The in vitro permeability of INCB050465 across Caco-2 monolayers was low (0.99 × 10-6 cm/s).  
As INCB050465 is a substrate for P-gp at concentrations below 100 μM, oral absorption is not 
expected to be compromised by efflux at higher doses.  In single oral dose PK studies conducted 
in rats, dogs, and monkeys, INCB050465 was absorbed rapidly, with Tmax values ranging from 
0.3 to 2.5 hours.  After oral administration, the bioavailability of INCB050465 was complete in 
dogs (100%) and high in monkeys (80%) and rats (74%). 
The protein binding of INCB050465 was determined in serum and plasma obtained from rats, 
beagle dogs, and human (in vitro and ex vivo).  The in vitro fraction unbound of INCB050465 
was similar in plasma from dog and human (4.6% and 7.6%, respectively), with the fraction 
unbound somewhat higher in plasma from rat (23%).  For rats and beagle dogs, the average 
ex vivo fractions unbound of 16.5% and 3.5%, respectively, are used for safety margin 
calculations, while for humans, the average data from plasma and serum of 7.4% are used. 
INCB050465 is metabolized primarily by CYP3A4.  INCB050465 is not an inhibitor of the 
major CYPs evaluated, nor is it an inducer of CYP3A4.  In addition, there were no human-
specific metabolites noted using in vitro systems.  There is no evidence of chemical reactivity 
subsequent to metabolism. 
These data are further discussed in the INCB050465 IB. 
1.3.3. 
Potential Risks of INCB050465 Based on Preclinical Safety 
Based on findings in repeat-dose toxicity studies of INCB050465 in rats and dogs, lymphoid 
depletion and resulting immunosuppression represents a potential risk for humans. 
Repeat-dose toxicity of INCB050465 was evaluated after QD administration for 28 days in 
Sprague Dawley rats at doses of 10 mg/kg, 30 mg/kg, and 100 mg/kg per day, and beagle dogs at 
doses of 1 mg/kg, 3 mg/kg, and 15 mg/kg per day.  Recovery was evaluated after a 4-week 
nondosing period in both species. 
In both rats and dogs, immunosuppression (evident as minimal to marked depletion of lymphoid 
tissues, including thymus, lymph nodes, spleen, and gut-associate lymphoid tissue) was observed 
at all doses and considered to be consistent with the pharmacologic activity of INCB050465.  
The incidence and severity of these findings increased with dose. 
Moderate bone marrow depletion and/or fibrosis occurred in 2 female rats at 100 mg/kg per day 
(exposure at this dose in female rats is approximately 190-fold higher than projected human 


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exposure [unbound AUC] after 10 mg), no changes in bone marrow were observed in the rat at 
lower doses or at the end of the recovery period; also, there were no changes in bone marrow on 
the dog studies.  Septicemia/bacterial pancreatitis, considered secondary to immunosuppression, 
led to the death of 1 female rat at 100 mg/kg per day. 
Dose-related minimal to mild hypospermatogenesis was observed in male rats at 30 and 
100 mg/kg per day, which demonstrated recovery after 28 days. 
In dogs, effects secondary to immunosuppression included subacute inflammation in multiple 
tissues, including lymphoid tissue, gastrointestinal tract, liver, lungs, kidney, and bladder.  
Severe acute inflammation of the lung and gastrointestinal tract led to early death or sacrifice of 
1 female dog at 3 mg/kg per day and 1 male dog at 15 mg/kg per day, respectively. 
There were no findings in dogs indicative of any off-target toxicity.  Increases in alkaline 
phosphatase (ALP; 3.5- to 4-fold over control) and alanine aminotransferase (ALT; 1.7- to 
4.7-fold over control) were observed at 15 mg/kg per day and correlated with minimal to 
moderate, acute to subacute inflammation and minimal to mild single-cell necrosis attributed to 
immunosuppression and systemic spread of microbes.  Complete recovery for these changes was 
observed. 
Based on the severity of findings at higher doses, including bone marrow depletion/fibrosis in 
rats and secondary effects leading to early death in both species, the highest nonseverely toxic 
dose was considered to be 30 mg/kg per day in rats and 1 mg/kg per day in dogs.  These doses 
and associated exposures are well above the intended clinical starting dose in this study and the 
anticipated therapeutic dose in humans. 
In exploratory studies in rats, evidence of hepatotoxicity was seen.  These liver findings included 
periportal inflammatory cell infiltrates accompanied by minimal biliary hyperplasia and were 
observed at doses of ≥ 100 mg/kg per day.  These findings were not reproduced in a 28-day GLP 
study in doses less than 100 mg/kg per day.  Plasma exposures in rats administered ≥ 100 mg/kg 
per day were > 65-fold higher than the project clinical exposure at a dose of 10 mg QD. 
INCB050465 was not mutagenic or genotoxic in a bacterial reverse mutation assay, in vitro 
chromosomal aberrations study in human peripheral blood lymphocytes, or rat in vivo 
micronucleus assay. 
1.3.4. 
Clinical Summary of INCB050465 
INCB050465 is currently being evaluated in a Phase 1/2 study in subjects with previously treated 
B-cell malignancies.  As of 04 DEC 2015, 15 subjects have been treated in the dose escalation 
portion of Study INCB 50465-101.  No dose-limiting toxicities (DLTs) were seen during dose 
escalation of 5 mg QD (n = 1), 10 mg QD (n = 3), 15 mg QD (n = 3), 20 mg QD (n = 4), or 
30 mg QD (n = 4).  Dose-limiting toxicity observation is ongoing for the 45 mg QD cohort.  Four 
subjects discontinued treatment, 3 due to disease progression and 1 due to AE (Grade 2 
exfoliative dermatitis).  Seven Grade ≥ 3 treatment-emergent adverse events (TEAEs) were seen 
in 5 subjects:  anemia, bacteremia, Escherichia infection, neutropenia, sepsis, syncope, and white 
blood cell count decreased; none were considered treatment-related.  To date, only Grade 1 
transaminase elevations have been observed.  Target inhibition as assessed by pAKT levels in 
peripheral blood showed > 80% inhibition at trough in subjects receiving 5 mg, 10 mg, 15 mg, 
20 mg, or 30 mg QD of INCB050465.  Tumor responses have been observed in subjects with a 


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broad range of B-cell malignancies, receiving INCB050465 at a doses ranging from 10 to 30 mg 
QD.  Among 12 efficacy-evaluable subjects, responses were observed in diffuse large B-cell 
lymphoma (DLBCL; 2/5 subjects), follicular lymphoma (2/2), chronic lymphocytic lymphoma 
(CLL; 1/2), mantle cell lymphoma (1/1), and marginal zone lymphoma (1/1).  Clinical benefit 
was observed early in the course of treatment, and the longest duration of response was 17+ 
weeks.  Pharmacodynamic assays have demonstrated that maximum measurable target inhibition 
is also achieved with doses of > 10 mg QD.  Therefore, the pharmacologically active dose (PAD) 
has been reached for this compound. 
1.3.5. 
Clinical Pharmacokinetics of INCB050465 
Preliminary PK results are available from 13 subjects in 5 cohorts treated with INCB050465 
monotherapy in the ongoing Phase 1/2 study.  Following fasting oral administration, 
INCB050465 was absorbed rapidly, typically attaining peak plasma concentrations within 0.5 to 
1 hour after administration.  INCB050465 plasma concentrations subsequently declined in a 
monophasic or biphasic fashion with mean terminal-phase disposition t½ from 7.9 to 11.5 hours, 
similar to the 12 hours projected by preclinical data.  INCB050465 exhibited low oral-dose 
clearance ranged with mean values from 1.49 to 4.07 L/hr.  Though mean Cmax and AUC 
increased less than proportional on Cycle 1 Day 15, approximate dose proportionality was 
observed over 5 mg to 30 mg on Cycle 1 Day 1.  However, the caveats are (a) limited number of 
subjects, for example, N = 1 at 5 mg, (b) inter- as well as intra-individual variability within each 
dose group, and (c) relatively narrow dose range evaluated to date.  The mean trough 
concentrations on Cycle 1 Day 15 for all 5 cohorts exceeded the projected IC90 for inhibition of 
PI3Kδ signaling in tumor cells, and the steady state was reached on or before Cycle 1 Day 8. 
1.3.6. 
Overview of the Combination of INCB052793 and INCB050465 
1.3.6.1. 
Rationale for Combining Inhibition of JAK1 and PI3Kδ  
Janus kinase/STAT and PI3K pathways may contribute to driving tumor growth and survival in 
lymphomas, and combination therapies that block both pathways may prove more beneficial due 
to the central role that JAK-mediated cytokine signaling plays in augmenting BCR-mediated 
activation of the NF-κB pathway.  To test this hypothesis preclinically, a panel of DLBCL cell 
lines was grown in conditions to activate the JAK pathway.  These cells lines were exposed to 
the PI3Kδ inhibitor INCB040093, either alone or in combination with a panel of compounds that 
were shown to selectively inhibit JAK1 to examine their effects on cell proliferation and 
signaling.  The JAK pathway was not constitutively activated when grown in the absence of 
stromal conditioned media (SCM), IL-6, or IL-10 as assessed by the levels of pSTAT3, a direct 
downstream target of JAK proteins.  In addition, IL-6 or SCM, which contains predominantly 
IL-6, IL-8, and granulocyte-colony stimulating factor, failed to activate the pathway in the 
majority of cell lines.  In contrast, IL-10 activated the JAK/STAT pathway in the majority of cell 
lines tested, consistent with previous reports (Gupta et al 2012). 
 
 


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. 
JAK/STAT3 activation is characteristic of multiple T-cell lymphomas, including anaplastic large 
cell lymphoma (ALCL), peripheral T-cell lymphomas, and others.  In anaplastic lymphoma 
kinase–negative ALCL, 38% of cases were found to carry mutations leading to constitutive 
activation of the JAK/STAT3 pathway, including mutations of JAK1, STAT3, translocation 
(NFκB2-ROS1 and NFκB2-TYK2).  Similar findings were found in peripheral T-cell 
lymphomas and Sézary syndrome, which were found to harbor activating JAK or STAT 
mutations in 36% and 11%, respectively, of cases studied.  In vitro and in vivo studies 


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demonstrate sensitivity of these tumors to JAK1/JAK2 inhibition (Kiel et al 2015, Kiel et al 
2014). 
Clinically, the combination of PI3Kδ inhibition and JAK1 inhibition has been tested in Study 
INCB 40093-102.  Preliminary activity has been observed in subjects with NHL and Hodgkin 
lymphoma (HL) receiving INCB040093 monotherapy and combination treatment (data on file). 
1.3.6.2. 
Nonclinical Pharmacokinetics and Drug Metabolism of the Combination of 
INCB052793 and INCB050465 
Both INCB050465 and INCB052793 are metabolized predominately by CYP3A4 but neither 
appears to be an inducer or inhibitor of CYP3A4 at clinically relevant concentrations.  While 
both INCB050465 and INCB052793 are P-gp substrates, their efflux transport via P-gp is likely 
to be saturated at the doses proposed for clinical evaluation, and thus further inhibition of P-gp 
should have no effect on INCB050465 or INCB052793 absorption.  Therefore, a drug interaction 
between these compounds is unlikely in the setting of the proposed clinical study.  
Pharmacokinetics of INCB050465 and INCB052793 will be evaluated in subjects receiving both 
agents concurrently in Cohort H and compared with respective monotherapy data.  
1.3.6.3. 
Clinical Summary of Combination Treatment With JAK1 Inhibition (Itacitinib 
[INCB039110]) and PI3Kδ Inhibition (INCB040093) 
Study INCB 40093-102 is an ongoing, open-label, dose escalation, safety and tolerability study 
that has tested combination of another novel JAK1 inhibitor itacitinib and novel PI3Kδ inhibitor 
INCB040093.  As of 21 JUL 2015, 55 subjects had received treatment with the combination.  
Generally treatment was well-tolerated.  Grade ≥ 3 TEAEs occurring in > 1 subject were 
Pneumocystis jiroveci  pneumonia (PJP; n = 5; 9.6%); hyponatremia and hypoxia (n = 3 each; 
5.8%); and hypercalcemia and pneumonia (n = 2 each; 3.8%).  Overall response rate in evaluable 
subjects who received INCB040093 + itacitinib combination therapy was 60.0% for HL and 
27.3% for DLBCL.  Additional details can be found in the INCB052793 IB. 
1.4. 
Overview of Itacitinib (INCB039110) 
Itacitinib adipate (INCB039110 adipate, referred to herein as itacitinib), is a novel, potent, and 
selective inhibitor of the JAK family of protein TYKs with selectivity for JAK1.  Itacitinib is an 
investigational product that is proposed for development for treatment of MPNs, including 
myelofibrosis (MF); inflammatory diseases, including rheumatoid arthritis (RA) and psoriasis; 
graft-versus-host disease (GVHD); solid tumors; and B-cell malignancies. 
1.4.1. 
Pharmacology of Itacitinib 
Itacitinib potently inhibits JAK1 (half maximal inhibitory concentration [IC50] = 3.6 nM at 1 mM 
adenosine triphosphate concentration), with 22- to > 500-fold selectivity over the other JAK 
family members, JAK2, JAK3, and TYK2.  It does not significantly inhibit (< 30% inhibition) a 
broad panel of approximately 60 other kinases.  Itacitinib is also potent (IC50 values of 
approximately 10 nM to 350 nM) in cytokine-driven cell-based assays.  This effect is not due to 
general cytotoxicity.  Itacitinib also inhibits the growth of the cytokine-dependent cell line 
INA-6.  Itacitinib potently inhibits the phosphorylation of signal transducer and activator of 
STAT proteins and the production of proinflammatory factors induced by other cytokines, such 


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as IL-23 and IL-6, with IC50 values of approximately 30 nM to 100 nM.  In contrast, itacitinib 
shows less inhibition in cell-based assays dependent on JAK2, with IC50 values of approximately 
1 μM or greater, 
  In in vivo models of 
JAK-dependent malignancy, itacitinib impedes subcutaneous tumor growth of INA-6 cells 
expressing wild-type JAKs when administered by continuous infusion, achieving plasma 
concentrations well below those necessary to inhibit JAK2.  Oral itacitinib also reduced 
splenomegaly in a model of JAK2 V617F-driven neoplasia relevant to MF. 
Itacitinib did not demonstrate off-target activity or any activity in a number of non-JAK family 
kinases.  In rat safety pharmacology studies, adverse findings, noted only at 1000 mg/kg, 
included a transient decrease in locomotor activity, a slight decrease in body temperature, and 
suppression of respiratory function.  In a cardiovascular study in dogs, ≥ 60 mg/kg produced a 
potentially adverse lowering of arterial pressure, compensatory higher heart rate, and an increase 
in core body temperature; the no-observed-adverse-effects level (NOAEL) was 30 mg/kg.  The 
IC50 for inhibition of the hERG channel was 65.3 µM. 
Additional information can be found in the itacitinib IB. 
1.4.2. 
Nonclinical Drug Metabolism and Pharmacokinetics of Itacitinib 
In vitro and in vivo studies were conducted to characterize the absorption, distribution, 
metabolism, and excretion profile of itacitinib.  In single-dose PK studies in rats, dogs, and 
monkeys, orally administered itacitinib was rapidly absorbed (tmax ≤ 2.0 hours).  Oral 
bioavailability was low in monkeys, moderate in dogs, and high in rats.  After IV administration, 
itacitinib had a short half-life (≤ 1.2 hours) in all 3 species.  Total systemic clearance was high in 
rats (100%) and low to moderate in dogs and monkeys (31%-37%).  The Vdss in rats was greater 
than in dogs and monkeys, suggesting greater tissue distribution in rats.  Itacitinib has minimal 
penetration across the blood-brain barrier in rats.  Protein binding in plasma and serum from rats, 
dogs, and humans was moderate, and the fraction unbound was independent of itacitinib 
concentration. 
In multiple-dose toxicokinetic studies in rats and dogs, the Cmax and AUC values generally 
increased with dose.  No sex differences were observed in dogs; however, plasma exposure in 
female rats was more than 2-fold higher than that of males.  This difference was likely attributed 
to metabolism of itacitinib via male-specific CYP3A2.  The mean Cmax and AUC values were 
decreased after multiple-dose administration in rats, but the mechanism is unclear. 
CYP3A4 is the major isozyme responsible for the metabolism of itacitinib in human liver 
microsomes.  In a cultured human hepatocyte assay, itacitinib did not induce CYP1A2, CYP2B6, 
or CYP3A4/5 activity or mRNA levels, suggesting that the potential to induce P450 in clinical 
studies is low.  In vitro assays indicated that itacitinib is a substrate of P glycoprotein and BCRP.  
In addition, the potential for itacitinib to cause clinical drug-drug interactions through CYP 
inhibition is low based on IC50 values. 
In rats and dogs, excretion was rapid and complete after a single oral dose of 14C-itacitinib.  In 
rats, approximately 25%, 55%, and 20% of total radioactivity was excreted in urine, feces, and 
bile, respectively.  In dogs, feces were the main elimination pathway (70%-80% of total 
recovered radioactivity), while urinary excretion accounted for < 20%.  The major analyte 


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present in plasma and urine from all species studied was the parent compound.  Itacitinib-derived 
radioactivity did not preferentially partition into the blood of rats and dogs. 
In the rat quantitative whole-body autoradiography study, pigmented and nonpigmented male 
rats showed similar tissue distribution, except that concentrations in the pigmented eye uveal 
tract were substantially higher than in that of the nonpigmented rat, indicating an association of 
14C-itacitinib–derived radioactivity with melanin.  The highest concentrations of radioactivity 
were found in the alimentary canal contents, bile, and urinary bladder contents, suggesting that 
biliary and renal excretion were both routes of elimination. 
These data are further discussed in the itacitinib IB. 
1.4.3. 
Potential Risks of Itacitinib Based on Preclinical Safety 
Single oral doses of itacitinib up to 2000 mg/kg in rats and up to 1000 mg/kg in dogs produced 
no adverse effects.  In multiple-dose studies in rats, dose-related body weight decreases and 
lower food consumption were noted.  Pharmacology-related alterations in the multiple-dose rat 
studies included reversible lowering of white blood cell (WBC) count, reversible lymphoid 
depletion in lymphoid tissues, and reduction in bone marrow cellularity.  The NOAEL in the 
6-month rat study was 300 mg/kg per day.  In dogs, GI inflammation was the DLT in multiple-
dose studies of up to 3 months in duration.  In the 6- and 9-month dog studies, generalized 
demodicosis, an effect secondary to the immunosuppressive effect of itacitinib, was the DLT.  
The NOAEL in the 9-month study was 10 mg/kg per day.  When itacitinib was administered to 
pregnant rats and rabbits, fetotoxicity and fetal malformations and variations were observed at 
the highest dose levels tested; these effects were considered secondary to severe maternal 
toxicity at the same dose levels. 
Genetic toxicity assessments, including a bacterial reverse mutation assay, in vitro chromosomal 
aberrations study in primary human peripheral blood lymphocytes, and in vivo micronucleus 
study in rats, indicate that itacitinib lacks potential for genotoxicity. 
For additional information, refer to the itacitinib IB. 
1.4.4. 
Clinical Summary of Itacitinib 
Itacitinib is an investigational product that has been studied in subjects with underlying 
rheumatologic/inflammatory conditions, solid tumors, and hematologic malignancies.  The 
explored doses ranged from 100 mg QD to 600 mg twice daily (BID).  It is currently in 
development for the treatment of MPNs (including MF), GVHD, and solid and hematologic 
malignancies. 
Adverse events that have been reported by more than 5% of healthy subjects receiving itacitinib 
in an individual study included fatigue, headache, neutropenia, nausea, contact dermatitis, 
ecchymosis, reticulocyte count decreased, excoriation, and nasal congestion.  Adverse events 
reported by more than 10% of subjects in the MF study included anemia, fatigue, 
thrombocytopenia/platelet count decreased, upper respiratory tract infection, nausea, 
constipation, diarrhea, cough, peripheral edema, pyrexia, dyspnea, dizziness, pain in extremity, 
night sweats, abdominal pain, arthralgia, contusion, headache, pruritus, and vomiting.  The only 
adverse event reported by more than 10% of itacitinib-treated subjects with an inflammatory 


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condition was nasopharyngitis in the psoriasis study; there were no TEAEs reported by more 
than 10% of subjects with RA. 
Serious AEs (SAEs) reported in more than 1 subject in an individual monotherapy study 
included the following:  pneumonia (5 MF subjects), anemia (5 MF subjects), pyrexia (2 MF 
subjects), congestive cardiac failure (3 MF subjects), leukocytosis (2 subjects), chest pain (2 MF 
subjects), acute renal failure (2 MF subjects), urinary tract infection (2 MF subjects), GI/upper 
GI hemorrhage (2 MF subjects), and hypotension (2 subjects). 
No events of PJP have been reported in subjects receiving itacitinib monotherapy. 
Itacitinib is also tested in combination with chemotherapy, PI3K delta inhibitors (INCB040093 
and INCB050465) and as well as epacadostat (IDO-1 inhibitor), pembrolizumab, and 
corticosteroids. 
Clinical experience with itacitinib as of 13 DEC 2016 is based on administration to 777 safety 
evaluable subjects.  This includes 493 subjects who received itacitinib as a monotherapy, 
including healthy subjects (284) and subjects with MF (87), chronic plaque psoriasis (38), and 
RA (84).  Also, 64 subjects with solid tumors received itacitinib in combination with 
chemotherapy; 78 subjects with lymphoid malignancies received itacitinib in combination with 
the PI3Kδ inhibitor, INCB040093; 38 subjects with solid tumors or lymphoid malignancies 
received itacitinib in combination with another PI3Kδ inhibitor, INCB050465; 35 subjects with 
solid tumors received itacitinib in combination with pembrolizumab, 40 subjects with solid 
tumors received itacitinib in combination with epacadostat; and 29 subjects with acute GVHD 
received itacitinib in combination with corticosteroids.  Duration of exposure to itacitinib in 
subjects has reached up to approximately 209 weeks in subjects with MF.  Chemotherapy 
combinations have been administered for up to 52 weeks; combination treatment with 
INCB040093 has been administered for up to 138 weeks; combination treatment with 
INCB050465 has been administered for up to 38 weeks; combination treatment with epacadostat 
has been administered for up to 32 weeks, combination treatment with pembrolizumab has been 
administered for up to 36 weeks; and combination treatment with corticosteroids has been 
administered for up to 40 weeks. 
Serious AEs have been reported in subjects with solid tumors (33 subjects; 56.4%), lymphoid 
malignancies (43 subjects; 50.6%), MF (33 subjects; 37.9%), and RA (2 subjects; 2.4%). 
As a result of itacitinib-mediated immunomodulation, an increased incidence of infections could 
possibly occur with itacitinib monotherapy.  Strict clinical monitoring is indicated to identify and 
treat infections in study subjects should they occur. 
Because of the potential for myelosuppression, subjects will have hematologic parameters 
closely monitored during initial clinical studies.  If there are clinically relevant declines in 
hematology parameters, therapy may be interrupted until resolution or discontinuation.  As 
itacitinib also has the potential to cause WBC margination (ie, a transient decrease in absolute 
neutrophil count), assessment of hematology parameters should be performed before study drug 
administration at all applicable study visits. 
Itacitinib showed signs of efficacy in subjects with MF in monotherapy, as well as in 
combination with PI3K delta inhibitors in subjects with B-cell malignancies. 
Additional information can be found in the itacitinib IB. 


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1.4.5. 
Clinical Pharmacokinetics of Itacitinib 
Following a single dose of 300 mg itacitinib (3 × 100 mg tablets) in healthy volunteers, there 
was a 46% increase in Cmax but only a 17% increase in total exposure (AUC0-∞) when 
administered with a medium-fat meal.  The nonclinically significant impact on total exposure 
when administered with a medium-fat meal supported the administration of itacitinib without 
regard to food.  A preliminary analysis comparing single doses of 100 mg (1 × 100 mg), 200 mg 
(2 × 100 mg), and 300 mg (3 × 100 mg; fasted) demonstrated that exposures increase in a 
greater-than-proportional manner. 
Following multiple-dose administration of itacitinib 400 BID or 800 QD with a medium-fat 
meal, steady state was generally reached after 48 hours.  Compared with Day 1, there was 
approximately 60% and 15% accumulation in AUC0-τ for the 400 mg BID and 800 QD doses, 
respectively, following a medium-fat meal.  The highest total daily exposure after multiple-dose 
administration was achieved after administration of 600 mg BID (29.0 μM·h [calculated as 2 × 
AUC0-12]).  Mean half-life of itacitinib is generally reported in the range of 3 to 9 hours with an 
overall mean of approximately 5 hours.  After itacitinib 400 mg BID and 800 mg QD 
administration with a medium-fat meal, the intersubject CV% ranged from 25% to 34% for Cmax 
and 23% to 40% for AUC0-τ. 
Study INCB 39110-230 where itacitinib was administred in monotherapy orally as 100 mg BID, 
200 mg BID, and 600 mg QD for up to 24 weeks to subject wih MF, the PK of itacitinib were 
characterized after multiple doses using the following sampling scheme:  predose (Day 1 and 
Weeks 4, 12, and 24), and 1, 2, and 4 hours postdose (Weeks 4, 12, and 24).  Itacitinib attained 
peak plasma concentrations with a median tmax of 2 to 4 hours.  Steady state was achieved by 
Week 4.  For increasing dose from 100 mg BID to 200 mg BID, itacitinib plasma exposures 
(Cmax and AUC) appeared to be linear with regard to dose.  Itacitinib exposures in subjects with 
primary or secondary MF were similar to those in healthy volunteers and subjects with stable, 
chronic plaque psoriasis.  Refer to the itacitinib IB for more details. 
1.5. 
Study Rationale 
Several lines of evidence converge to support a significant role for JAK/STAT biology in the 
pathogenesis and clinical course of solid tumors and hematologic malignancies, and the 
hypothesis that JAK inhibition may be an effective therapeutic strategy in these diseases.  Janus 
kinase/STAT activation has been shown to mediate tumor growth and survival, as well as 
resistance to chemotherapy in several tumor models, including pancreatic cancer 
(Catlett-Falcone et al 1999, Toyonaga et al 2003, Thoennissen et al 2009, Lesina et al 2011, 
Sansone and Bromberg 2012), MM (Burger et al 2009, Li et al 2010), and AML/MDS 
(Cook et al 2014, Spiekermann et al 2001). 
The JAK/STAT pathway can become activated within pancreatic tumor cells either through 
mechanisms intrinsic to the cancer cells themselves (Fukushima et al 2003, Komazaki et al 2004, 
Fukuda et al 2011, Lesina et al 2011) or through complex stromal interaction with the tumor 
microenvironment (Bromberg and Wang 2009, Galm et al 2003).  These interactions are 
mediated to a large extent through cytokine networks that either directly or indirectly signal 
through JAK/STAT dependent pathways.  For example, paracrine sources of IL-6 from cancer-
associated fibroblasts or myeloid cells can induce autocrine production of IL-6 and activation of 
STAT3 in tumor cells (Sansone and Bromberg 2012).  Although precise mechanisms remain 


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unknown, it is clear that pancreatic cancer induces a systemic inflammatory response, possibly 
through inflammatory cytokine production by pancreatic tumor cells themselves (Bromberg and 
Wang 2009, Wigmore et al 2002) or by cytokines produced in the local inflammatory milieu 
(Protti and De Monte 2013).  This systemic inflammatory response is largely mediated through 
JAK/STAT-dependent cytokine signaling and may contribute to local tumor growth.  Perhaps 
more importantly, however, it may be a marker for the stromal inflammatory milieu in the tumor, 
and is itself associated with systemic manifestations such as the cachexia syndrome (Fearon et al 
2013), which has independent prognostic significance in this disease.  Thus, JAK/STAT 
signaling may contribute to the course of pancreatic cancer through tumor cell intrinsic 
mechanisms or through both the local and systemic effects of inflammatory cytokines.  In turn, 
systemic inflammation may be directly involved in the systemic manifestations of the disease, 
such as cachexia, as well as a marker of JAK/STAT activation locally within the tumor. 
Similarly, the interaction of MM cells with the microenvironment has been demonstrated to be 
crucial for the pathogenesis of MM and supports autocrine and paracrine signaling by a number 
of growth factors and cytokines, including IL-6.  IL-6 and its soluble agonistic receptor, sIL-6R, 
are elevated in MM patients and have been associated with poor prognosis (Lauta 2003).  Ligand 
binding results predominantly in activation of JAK1, leading to the phosphorylation of 
downstream effectors (eg, STATs).  Additionally, in MM, epigenetic silencing of an 
autoregulatory feedback loop mediated by members of the SOCS (silencer of cytokine signaling) 
family has been documented in the majority of MM patients analyzed and is thought to 
contribute to a net increase in aberrant JAK-STAT pathway activation (Galm et al 2003).  Hence, 
selective inhibition of JAK1 kinase activity in MM may provide therapeutic benefit to patients 
who currently do not have curative medicinal alternatives. 
Preclinically, INCB052793 inhibited growth of the MM cell line, INA-6, with an IC50 of 
238 ± 29 nM (n = 6), demonstrating that inhibition of JAK1 by INCB052793 abrogated the 
IL-6/JAK/STAT3 signaling pathway and induced cell death in the JAK/STAT-dependent INA-6 
cell line.  In addition, immune-compromised mice bearing well established subcutaneous INA-6 
tumors that were dosed with INCB052793 demonstrated dose-dependent suppression of 
JAK/STAT signaling and a reduction in tumor growth. 
Treatment outcomes in AML are poor.  Despite various cytotoxic drug combinations and 
targeted therapies, disease recurrence is common.  Cytokine stimulation induces proliferation 
and growth of AML blasts, and high levels of cytokines have been associated with poor 
prognosis in AML (Faderl et al 2005).  The JAK/STAT pathway has been recognized as one of 
the most important signaling pathways downstream of cytokine receptors.  Therefore, targeting 
this pathway with a JAK/STAT inhibitor may provide a way to influence the cytokine 
stimulation and proliferation of myeloid blast cells.  Preclinical data published suggest that a 
JAK can inhibit AML cell proliferation by inhibiting STAT 3, 5 and induction of caspase-
dependent apoptosis (Faderl et al 2005). 
Subjects with high risk MDS who have failed prior therapy with hypomethylating agents (HMA) 
have no available standard of care.  The median overall survival after azacitidine or decitabine 
failure in patients with MDS is 5.6 and 4.3 months respectively (Prébet et al 2011, Jabbour et al 
2010, Duong et al 2013).  The median OS of MDS subjects who developed secondary AML after 
azacitidine failure is 3.4 months (Prébet et al 2012). 


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Objective responses based on bone marrow and peripheral blood evaluation have been observed 
among subjects with AML/MDS who have previously failed treatment with HMA who were 
treated in Phase 1b part Cohort F (INCB052793 in combination with azacitidine).  Based on 
unaudited data among 10 subject who who have previously failed treatment with HMA, 
3 experienced complete marrow response without hematologic recovery.  Of these, 2 were taken 
off study to undergo allogenetic transplantation.  Another subject experienced reduction of bone 
marrow blasts from 70% to 10%.  Therefore, in Phase 2 of this study, we will futher evaluate the 
efficacy and safety of INCB052793 and itacitinib in combination with azacitidine in this patient 
population.  Testing 2 JAK1 inhibitors (INCB052793 and itacitinib) in 2 parallel cohorts will 
allow selection of the JAK1 inhitor that shows a more promising efficacy and safety in 
combination with azacitidine in this patient population. 
1.6. 
Clinical Experience With INCB052793 
As of the data cutoff date (19 JUN 2016), 34 subjects in Study INCB 52793-101 have received 
INCB052793 monotherapy (up to 100 mg QD), and 16 subjects have received INCB052793 (up 
to 35 mg QD) in combination with a standard-of-care anticancer agent (dexamethasone or 
azacitidine).  INCB052793 has been administered in combination with dexamethasone to 
6 subjects (Cohort B) with MM and in combination with azacitidine to 10 subjects (Cohort F) 
with AML or MDS.  The median duration of treatment was 56 days for INCB052793 
monotherapy and 57.5 days in combination with standard-of-care anticancer agents 
(dexamethasone or azacitidine). 
Based on preliminary, unaudited data as of the data cutoff (19 JUN 2016), all subjects given 
INCB052793 monotherapy reported at least 1 TEAE.  Three subjects (8.8%) given monotherapy 
had a fatal TEAE (respiratory failure for 2 subjects at 50 mg QD and a small intestinal 
obstruction for 1 subject at 75 mg QD).  Ten subjects (29.4%) given INCB052793 monotherapy 
reported an SAE during the study; 5 of the SAEs (febrile neutropenia and platelet count 
decreased [observed at 50 mg QD], and dehydration, nausea, and vomiting for 1 subject at 
100 mg QD) were considered by the investigator to be possibly treatment-related.  
Thrombocytopenia/platelet count decreased was the most frequently reported TEAE (44.1%) in 
subjects given INCB052793 monotherapy.  Treatment-related TEAEs were reported for 70.6% 
of subjects given INCB052793 monotherapy; the most frequently reported treatment-related 
TEAE was thrombocytopenia/platelet count decreased (41.2%).  Treatment-emergent AEs of 
Grade 3 or higher were noted in 58.8% of subjects given INCB052793 monotherapy; the most 
frequently reported ≥ Grade 3 TEAEs were hematologic or respiratory in nature.  One subject 
given INCB052793 monotherapy discontinued treatment because of death caused by disease 
progression (with a fatal TEAE of respiratory failure), and 1 subject discontinued treatment 
because of multiple TEAEs. 
For subjects given INCB052793 in combination with the standard-of-care anticancer agents, 
dexamethasone (Cohort B) or azacitidine (Cohort F), 1 subject in Cohort B and no subjects in 
Cohort F had a fatal TEAE (respiratory arrest) as of the data cutoff date.  Eight subjects (50.0%) 
given combination therapy reported an SAE during the study; 4 of these subjects (25.0%; all in 
Cohort F [azacitidine]) reported SAEs of febrile neutropenia.  All other SAEs in subjects given 
INCB052793 with a standard-of-care anticancer agent were noted in 1 subject each.  Serious 
AEs of pneumonia and sepsis for 1 subject in Cohort B were considered by the investigator to be 


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possibly related to treatment with INCB052793 and dexamethasone.  Fourteen subjects (87.5%) 
given INCB052793 with a standard-of-care anticancer agent reported at least 1 TEAE.  The most 
frequently reported TEAEs (37.5%) were fatigue and injection site reaction.  Other TEAEs 
reported in at least 20% of subjects were febrile neutropenia, thrombocytopenia/platelet count 
decreased, and oropharyngeal pain.  Nine subjects (56.3%) given INCB052793 in combination 
with dexamethasone (Cohort B) or azacitidine (Cohort F) had TEAEs related to INCB052793 
treatment.  The most frequently reported INCB052793-related TEAEs in subjects given 
combination therapy were thrombocytopenia/platelet count decreased and fatigue (25.0% of 
subjects each).  Other INCB052793-related TEAEs in ≥ 10% of subjects given combination 
therapy included neutropenia/neutrophil count decreased (18.8%) and alanine aminotransferase 
increased and aspartate aminotransferase (AST) increased (12.5% each).  Ten subjects (62.5%) 
had TEAEs of Grade 3 or higher.  The majority of ≥ Grade 3 TEAEs were hematologic in nature.  
Two subjects given INCB052793 in combination with a standard-of-care anticancer agent (both 
in Cohort F) discontinued treatment because of a TEAE.  No subject given INCB052793 in 
combination with a standard-of-care anticancer agent discontinued treatment because of death.  
One subject in Cohort B (INCB052793 25 mg plus dexamethasone) had Grade 3 
thrombocytopenia that was considered to be a DLT; this cohort has been expanded to 6 subjects.  
Among 10 subjects in Cohort F (INCB052793 plus azacitidine) at dose levels of 25 mg or 35 mg 
(5 subjects each), none had a DLT. 
No clinically meaningful differences in safety have been observed since this data cutoff to date. 
Preliminary, unaudited PK data show that, following multiple-dose oral administration, 
INCB052793 was absorbed rapidly and typically attained peak plasma concentrations within 
0.5 to 2 hours after administration.  INCB052793 exhibited low oral dose clearance, with mean 
clearance of 9.00 L/h and 14.4 L/h over the range from 15 mg QD to 100 mg QD.  INCB052793 
PK steady-state was attained before Day 8.  The dose proportionality on steady-state exposure 
appeared to be observed over the range from 15 mg QD to 100 mg QD in Phase 1a.  
Coadministration of dexamethasone or azacitidine did not appear to affect the PK of 
INCB052793 when compared with 25 mg QD and 35 mg QD monotherapy. 
1.7. 
Potential Risks and Benefits 
1.7.1. 
Preclinical Safety 
The toxicological profile of INCB052793 was characterized in single- and multiple-dose oral 
studies of up to 28 days in duration in rats and dogs, and in in vitro and in vivo genetic 
toxicology studies. 
The most prominent findings following repeat-dose exposure in both rats and dogs consisted of 
lymphoid depletion of multiple lymphoid organs including lymph nodes, spleen, thymus, 
bronchus-associated lymphoid tissue (BALT), and gut-associated lymphoid tissue (GALT).  The 
incidence and severity of these findings were dose-related.  Reduced bone marrow cellularity, 
with an associated increase in adipocyte population, was also observed to be dose-dependent in 
incidence and severity.  Clinical pathology, immunophenotyping, and bone marrow cytology 
evaluations revealed alterations that were generally reflective of the pharmacological effects of 
INCB052793 on lymphoid organs.  


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Effects secondary to immunosuppression led to the death of 1 female dog given INCB052793 at 
15 mg/kg per day (primary cause of death was bronchioloalveolar inflammation with bacterial 
colonization) and 1 male rat given INCB052793 at 75 mg/kg per day (cause of death was 
pyelonephritis with bacterial colonization).  An additional male rat given 75 mg/kg per day was 
found dead; although the cause of death was not clear, severe lymphoid system changes likely 
contributed to the death of this animal.  Skin ulceration of the cervical region was noted in 
female rats given ≥ 15 mg/kg per day and male rats given 75 mg/kg per day.  These lesions may 
have initiated from rats rubbing their necks on their feeding containers, and sustained 
immunosuppression resulting from INCB052793 administration likely exacerbated this lesion.  
This lesion appeared recoverable.  A lowering of red cell mass and circulating reticulocyte count, 
coupled with a slight reduction in the erythroid component of the bone marrow (dogs only), may 
be reflective of JAK2 inhibition.  Although all of the aforementioned findings were primary or 
secondary pharmacological effects, these findings were considered to be adverse (excessive) 
based on both severity and incidence (rats given 75 mg/kg per day) or based on the adverse 
nature of the effects secondary to JAK inhibition (dogs given 15 mg/kg per day). 
There was no evidence of off-target toxicity of INCB052793 in dogs.  In rats, reversible 
minimal-to-mild hyperostosis was observed in animals given 75 mg/kg per day.  Ovarian 
hemorrhage and luteal cysts were noted in female rats given ≥ 15 mg/kg per day, and a single 
female given 5 mg/kg per day had mild corpus luteal hemorrhage.  Ovarian changes persisted 
through the recovery period. 
According to the algorithms described in ICH S9 Guidance for Industry (ICH 2010), the starting 
clinical dose for  small molecules is often set at 1/10 the severely toxic dose in 10% of the 
animals (STD10) in rodents, or 1/6 the highest non-severely toxic dose (HNSTD) in non-rodents.  
INCB052793 is pharmacologically active in both rats and dogs.  Because adverse findings in 
both rats and dogs were primarily related to pharmacological effects on the lymphoid system, 
both species are appropriate for consideration of the starting clinical dose.  Based on the 28-day 
study in rats, severe toxicity was observed at 75 mg/kg per day; therefore, this dose level was 
considered to approximate the rat STD10.  The human equivalent dose associated with 
75 mg/kg per day based on standard body surface area conversion is 720 mg, and 1/10 this dose 
is 72 mg.  In the 28-day dog study, the HNSTD was considered to be 5 mg/kg per day based on 
the severity of lymphoid depletion at higher doses and secondary effects leading to early 
euthanasia of 1 female dog given 15 mg/kg per day.  The human equivalent dose associated with 
5 mg/kg per day is 162 mg; 1/6th of this dose is 27 mg. 
INCB052793 was not mutagenic in a bacterial mutagenicity assay.  INCB052793 was not 
clastogenic in the presence or absence of S9 metabolic activation in an in vitro chromosome 
aberration assay in human peripheral blood lymphocytes, however numerical aberrations were 
noted in both the absence and presence of S9 in this assay.  An increase in micronuclei in bone 
marrow of rats administered high doses of INCB052793 together with the polyploidy response 
noted in the chromosome aberration assay suggests that INCB052793 is aneugenic (an aneugen 
is an agent that affects cell division and the mitotic spindle apparatus resulting in the loss or gain 
of whole chromosomes). 
For potential risks of itacitinib based on preclinical studies, see Section 1.4.3 and the 
itacitinib IB. 


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1.7.2. 
Potential Risks Related to INCB052793 and Itacitanib 
In repeat-dose studies in both rat and dog, reversible decreases in circulating lymphocytes and/or 
reticulocytes and red cell mass parameters were observed.  Microscopically, reversible decreases 
in lymphocytes in various lymphoid organs and hypocellularity of the bone marrow have been 
described.  The changes seen in red cell mass parameters are likely due to JAK2 inhibition at the 
higher doses used in toxicology studies.  The incidence and severity of these histologic findings 
were considered adverse at the highest dose of 75 mg/kg per day evaluated in the 28-day rat 
study.  In the 28-day dog study, 15 mg/kg per day was considered to be an adverse dose level 
based on the severity of secondary pharmacological effects.  Effects on the lymphoid organs and 
bone marrow are expected based on the mechanism of action of INCB052793.  Reversibility of 
the pharmacological effects has been demonstrated pre-clinically, and would be expected to 
occur in a clinical setting. 
All subjects will have hematologic parameters closely monitored during the study.  Therapy will 
be withdrawn or dosing interrupted until resolution if there are clinically relevant declines in 
hematology parameters.  Dose-modification criteria in regards to changes in hematologic 
parameters are specified in Table 1. 
Off-target toxicities were noted in the 28-day rat study and included ovarian hemorrhage and 
luteal cysts in females given ≥ 15 mg/kg per day.  It should be emphasized that the corpora lutea 
are nonfunctional at the time of luteolysis, the point at which the cysts appear to be forming.  The 
appearance of large numbers of normal-appearing ovarian follicles with all stages of ovum 
development represented suggests that reproductive function is not impacted by INCB052793 
treatment.  Therefore, this finding is not expected to pose a risk to women of childbearing 
potential. 
Reversible minimal-to-mild hyperostosis in the distal femoral metaphysis was observed in rats 
given 75 mg/kg per day.  This lesion was not observed in any animals given 5 or 15 mg/kg per 
day.  The rat ovarian and bone findings are not expected to pose a risk to humans as the plasma 
exposures associated with a dose of 75 mg/kg per day, where hyperostosis and a high incidence 
of ovarian perturbations occurred, are 20- and 33-fold greater in males and females, respectively, 
than the projected human exposure at a maximum proposed dose of 150 mg QD. 
An increase in micronuclei in bone marrow of rats administered INCB052793 at 1000 and 
2000 mg/kg, together with the polyploidy response noted in the chromosome aberration assay, 
suggests that INCB052793 is aneugenic.  In contrast to mutagens, aneugens typically exhibit a 
threshold response (Bentley et al 2000, Henderson et al 2000); therefore, an estimation of risk 
can be obtained from calculation of a safety margin.  In the rat micronucleus study, a dose level 
of 500 mg/kg did not produce micronuclei, and at this dose level the plasma exposure is 85-fold 
greater than the estimated exposure at a maximum dose level of 150 mg INCB052793 to be 
studied in humans.  Therefore, based on the collective evidence, INCB052793 is not expected to 
present a genotoxic risk to humans at the intended dose levels in this study. 
Additional information can be found in the INCB052793 IB. 
Potential risks related to itacitinib are discussed in Section 1.4.4 and the itacitinib IB. 


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1.7.3. 
Risks Related to Standard-of-Care Agents 
1.7.3.1. 
Gemcitabine 
Myelosuppression is the principal DLT with gemcitabine therapy.  Gemcitabine can suppress 
bone marrow function as manifested by leukopenia, thrombocytopenia, and anemia, and 
myelosuppression is usually the DLT in clinical studies.  Subjects should be monitored for 
myelosuppression during therapy.  Dose adjustments for hematologic toxicity are frequently 
needed.  The most common adverse reactions for single-agent (≥ 20%) gemcitabine are nausea 
and vomiting; anemia; increased ALT, AST, and ALP; neutropenia; leukopenia; proteinuria; 
fever; hematuria; rash; thrombocytopenia; and dyspnea.  Prolongation of the infusion time 
beyond 60 minutes and more frequent dosing, compared to weekly dosing, has been shown to 
increase toxicity.  A complete discussion of risks associated with gemcitabine can be found at 
http://dailymed.nlm.nih.gov/. 
1.7.3.2. 
nab-Paclitaxel 
Myelosuppression is the principal DLT with nab-paclitaxel therapy.  nab-Paclitaxel can suppress 
bone marrow function, as manifested by leukopenia, thrombocytopenia, and anemia, and 
myelosuppression is usually the DLT in clinical studies.  Subjects should be monitored for 
myelosuppression during therapy.  Dose adjustments for hematologic toxicity are frequently 
needed.  The most common adverse reactions for single-agent (≥ 20%) nab-paclitaxel are 
neutropenia, peripheral neuropathy, infections, and electrocardiogram (ECG) abnormalities.  A 
complete discussion of risks associated with nab-paclitaxel can be found at 
http://dailymed.nlm.nih.gov/. 
1.7.3.3. 
Dexamethasone 
The most common adverse reactions associated with the use of dexamethasone include insomnia, 
fluid retention, weight gain, dyspepsia, impaired wound healing, and hyperglycemia.  Less 
common adverse reactions include opportunistic infection or viral reactivation secondary to 
immunosuppression, mood instability, depression, hypokalemia, hypertension, rash, 
lightheadedness, headache, and hot flashes.  Severe adverse effects are typically managed 
through interruption of dexamethasone dosing and supportive measures.  A complete discussion 
of risks associated with dexamethasone can be found at http://dailymed.nlm.nih.gov/. 
1.7.3.4. 
Carfilzomib 
The principal DLT associated with the use of carfilzomib is thrombocytopenia, with a reported 
overall incidence of 36%; Grade 4 thrombocytopenia has been reported in 10% of subjects across 
several clinical studies.  Subjects will be monitored for platelet count before each dose of 
carfilzomib.  Other hematologic AEs that have been reported at a ≥ 20% overall incidence 
include anemia, lymphopenia, and neutropenia, with a Grade 3 or 4 incidence of 22.4%, 18.1%, 
and 11.3%, respectively.  Common nonhematologic toxicities reported at an overall incidence of 
≥ 20% include fatigue, nausea, dyspnea, cough, headache, increased creatinine, peripheral 
edema, upper respiratory infection, vomiting, constipation, and back pain.  Use of carfilzomib 
has also been associated with tumor lysis syndrome and infusion reactions.  Premedication with 
dexamethasone and hydration before dosing will be required, consistent with the 


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recommendations in the product label.  A complete discussion of risks associated with 
dexamethasone can be found at http://dailymed.nlm.nih.gov/. 
1.7.3.5. 
Bortezomib 
The principal dose limiting adverse reaction associated with the use of bortezomib is sensory 
peripheral neuropathy, which is typically characterized by a burning sensation, paresthesias, 
numbness, and/or neuropathic pain.  Peripheral neuropathy of Grade 1 or higher is observed in 
≥ 30% of patients taking bortezomib.  It is often reversible in the majority of patients after 
treatment withdrawal and/or dose reduction.  Subjects will be monitored for symptoms of 
neuropathy, such as a burning sensation, hyperesthesia, paresthesia, discomfort, neuropathic 
pain, or weakness.  Thrombocytopenia has been observed in ≥ 30% of patients, with a 5% 
incidence of Grade 4 thrombocytopenia.  Clinical studies have reported platelet count nadir 
levels of 40% of baseline.  Other common adverse reactions associated with the use of 
bortezomib (≥ 20%) are asthenic conditions, nausea, diarrhea, constipation, appetite decreased, 
pyrexia, vomiting, and anemia.  A complete discussion of risks associated with bortezomib can 
be found at http://dailymed.nlm.nih.gov/. 
1.7.3.6. 
Lenalidomide 
Myelosuppression is the primary DLT observed with lenalidomide therapy, typically manifesting 
as thrombocytopenia and/or neutropenia.  Hematologic toxicities are reversible and are managed 
through dose interruptions and/or reductions.  The rate of thrombocytopenia and neutropenia 
have each been reported at a ≥ 30% incidence in clinical studies.  Subjects will have blood 
counts monitored weekly during the first cycle of treatment and no less than monthly thereafter.  
Use of lenalidomide is also associated with venous thromboembolic events, with a reported deep 
vein thrombosis and pulmonary embolism rate of 7.4% and 3.7%, respectively.  
Thromboprophylaxis will be instituted as indicated.  Other common adverse reactions associated 
with the use of lenalidomide (≥ 20%) in patients with MM include fatigue, constipation, rash, 
pyrexia, anemia, peripheral edema, and nausea.  Lenalidomide is an analogue of thalidomide, 
which a known teratogen.  Preclinical studies of lenalidomide have also revealed teratogenic 
properties in monkeys; thus, use during pregnancy is contraindicated.  A complete discussion of 
risks associated with lenalidomide can be found at http://dailymed.nlm.nih.gov/. 
1.7.3.7. 
Pomalidomide 
Myelosuppression is the primary risk associated with pomalidomide therapy, typically 
manifesting as neutropenia (53% overall) and anemia (38% overall); thrombocytopenia (26% 
overall) is observed less frequently than other hematologic toxicities.  Subjects will have blood 
counts monitored weekly during the first cycle of treatment and biweekly thereafter.  Consistent 
with other agents in this class, use of pomalidomide is also associated with venous 
thromboembolic events, with a reported deep vein thrombosis and pulmonary embolism rate of 
approximately 3%.  Thromboprophylaxis will be instituted as indicated by the pomalidomide 
package insert (Pomalyst 2015).  Other common adverse reactions associated with the use of 
pomalidomide (≥ 30%) in patients with MM include fatigue, constipation, diarrhea, nausea, 
asthenia, back pain, upper respiratory tract infection, and dyspnea.  Pomalidomide is an analogue 
of thalidomide, which a known teratogen; thus, use during pregnancy is contraindicated.  Refer 
to the Pomalyst® US package insert (Pomalyst 2015) for additional details. 


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1.7.3.8. 
Azacitidine 
The primary DLT observed with azacitidine therapy is myelosuppression, typically manifesting 
as leukopenia, anemia, thrombocytopenia, and/or neutropenia.  Hematologic toxicities are 
reversible and are managed through dose interruptions and/or reductions.  Subjects will have 
blood counts monitored weekly during the first cycle of treatment and before starting each course 
of therapy thereafter, at minimum.  Azacitidine has also been associated with severe adverse 
reactions, including hepatic coma and renal failure.  Subjects with significant baseline hepatic or 
renal impairment are excluded from this clinical study.  Additional adverse reactions associated 
with the use of azacitidine (≥ 20%) include nausea, vomiting, constipation, diarrhea, fever, 
dyspnea, petechiae, and ecchymosis.  A complete discussion of risks associated with azacitidine 
can be found at http://dailymed.nlm.nih.gov/. 
1.7.4. 
Potential Risks of Combination Therapy of INCB052793 and INCB050465 
Incyte is proposing to study 2 investigational drugs, INCB052793 and INCB050465, in 
combination for the treatment of relapsed/refractory lymphomas.  The principle toxicity of 
inhibiting both PI3Kδ and JAK1 pathways is expected to be reversible effects on immune 
function.  Combined inhibition may adversely affect both B-cell and T-cell immune function 
with resultant increased risk of a variety of infections.  Subjects will be closely monitored for 
bacterial infections, viral reactivation, and opportunistic infections, and treatment will be 
interrupted for infections that can be easily managed with antibiotic therapy and discontinued for 
infections that are serious or require prolonged antibiotic therapy.   
Study INCB 40093-102 is combining another PI3Kδ inhibitor, INCB040093, with the JAK1 
inhibitor itacitinib (see Section 1.3.6.1).  Five cases of PJP have been reported by subjects 
receiving this combination therapy.  Therefore, all subjects receiving combination therapy with 
INCB052793 and INCB050465 in this study must receive PJP prophylaxis.  Serum (1,3)-β-D-
glucan will be monitored each cycle throughout the study and approximately 3 months after 
discontinuation of the combination as a tool for early diagnosis of PJP.  If serum (1,3)-β-D is 
> 80 pg/mL, correlation should be made with clinical and radiological findings.  Infectious 
disease consultation may be obtained, and the subject should be managed according to the local 
guidelines for suspected cases of PJP.  If PJP is confirmed, the subject should be discontinued 
from the study and managed according to local guidelines.  Viral reactivation (ie, shingles) was 
also observed in subjects receiving INCB040093 monotherapy and combination therapy with 
itacitinib. 
Effects on white blood cell, red blood cell, and platelet counts could result from JAK1 inhibition 
and result in infections, anemia, or thrombocytopenia requiring transfusions, which may be more 
likely in subjects with lymphomas that are refractory to recent therapy or transplantation. 
INCB050465 has been shown to affect hematologic parameters; however, cytopenias are not 
expected to be worse with combination PI3Kδ and JAK1 inhibition.  In the study combining 
itacitinib with INCB040093, anemia has occurred in 14.3% of subjects receiving INCB040093 
monotherapy and 16.4% of subjects receiving combination therapy.  Neutropenia has occurred in 
18.4% of subjects receiving monotherapy and 27.3% of subjects receiving combination therapy; 
thrombocytopenia was reported in 4.1% of subjects receiving INCB040093 monotherapy 
compared with an incidence of 36.4% of subjects receiving combination therapy. 


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Idelalisib is another PI3Kδ inhibitor approved by the FDA in July 2014 for treatment of 
relapsed/refractory follicular lymphoma and relapsed small lymphocytic lymphoma and for 
treatment of CLL in combination with rituximab.  Severe toxicities seen with the use of this 
agent include hepatotoxicity (fatal or serious occurring in 14%), fatal and/or serious diarrhea or 
colitis (14%), intestinal perforation, and pneumonitis.  Based on experience with idelalisib and 
INCB040093, hepatotoxicity is a risk with this class of agents.  Preclinically, hepatotoxicity with 
INCB050465 was only seen at plasma exposures > 65-fold higher than the projected clinical 
exposure at 10 mg QD.  The pharmacophore of INCB050465 is different from both idelalisib and 
INCB040093, which are similar to each other. 
1.7.5. 
Risks Related to the Combination Regimens 
These medications individually or in combination may impact the function of the bone marrow, 
particularly the development of neutropenia, anemia, and thrombocytopenia in a dose-dependent 
manner.  The pharmacologically targeted doses of INCB052793 and itacitinib that will be used 
in this study are not expected to result in a substantial myelosuppressive effect; however, the 
risks of concomitant INCB052793, itacitinib, and other agents that induce myelosuppression are 
unknown.  Hematology parameters will be closely monitored in all study subjects and are 
expected to be reversible.  In addition, all AEs will be monitored to identify occurrences of new 
safety signals, or potentiation of any side effects that may overlap with the side effects that are 
intrinsic to the standard-of-care agent being used.  As indicated in Sections 1.2, 1.3, and 1.4, the 
risk of a metabolic drug interaction between INCB052793, itacitinib, and the proposed 
combination agents is low. 
1.7.6. 
INCB052793 and Itacitinib Potential Benefits 
INCB052793 represents a novel, potent compound with approximately 100-fold selectivity for 
JAK1 versus other JAKs, whereas itacitinib, another potent compound, inhibits JAK1 with 22-to 
> 500-fold selectivity over the other JAK family members.  Because JAKs have been shown to 
be activated in many malignancies, inhibition may provide a method to treat these diseases either 
alone or in combination with chemotherapeutics or other targeted therapies.  The degree of JAK1 
inhibition that is being targeted in the current study may result in clinical benefit. 
1.8. 
Justification of Route, Dose Regimen, and Treatment Period 
Oral drug administration is generally the most convenient and cost-effective method of drug 
delivery for medications requiring continuous exposure.  In Phase 1a, one cycle will be defined 
as 21 continuous days of treatment; treatment for subjects will consist of repeating 21-day 
cycles.  In Phase 1b and Phase 2, 1 cycle will be defined as 21 continuous days (Phase 1b 
Cohorts D and H) or 28 continuous days (Phase 1b Cohorts A, B, C, E, F, and G; Phase 2 
Cohorts I and J) of treatment; treatment for subjects will consist of repeating 21- or 28-day 
cycles, appropriate to the treatment arm. 
In Phase 1a Part 1, the dose sequence will be a repeated ascending dose design intended to obtain 
safety, tolerability, PK, 
 information for INCB052793 following multiple doses in 
subjects.  The initial starting dose for Phase 1a Part 1 of this study will be 25 mg QD, which is 
based on review of preclinical safety and toxicology studies.  If warranted, lower dose levels 
may be explored during Part 1 to further evaluate the safety, PK, 
 profile of INCB052793.  


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The DLTs seen in the preclinical studies are reversible with cessation of dosing, and subjects will 
be closely monitored for potential safety signals.  Previous experience with JAK inhibitors has 
shown that the neutropenic and thrombocytopenic toxicities are usually apparent during the first 
2 weeks of study drug administration.  Based on this information, a 21-day (Phase 1a and 
Phase 1b/Cohorts D and H) to 28-day (Phase 1b/ Cohort A, B, C, E, F, and G) cycle will provide 
an adequate time frame for evaluation of DLTs and determination of the maximum tolerated 
dose (MTD).  In addition, safety will be closely monitored beyond the 21-day and 28-day cycles 
and throughout the study. 
In Phase 1b/Cohort A, the nab-paclitaxel/gemcitabine regimen chosen for this study is 
appropriate to the patient population and is consistent with established guidelines 
(Masamune et al 2005, Mehta 2010, NCCN Guidelines) in which 125 mg/m2 and 1000 mg/m2, 
respectively, every week for 3 weeks every 28 days has been shown to be generally both 
tolerated and effective.  The recently completed Phase 3 study of the safety and efficacy of 
nab-paclitaxel/gemcitabine combination in pancreatic cancer (Von Hoff et al 2013) indicated 
that dose reductions of nab-paclitaxel (41%) and gemcitabine (47%) may be clinically indicated. 
In Phase 1b/Cohort B, the dexamethasone dose and frequency selected for use in this study is 
consistent with those evaluated in other clinical studies (Rajkumar et al 2010, Richardson et al 
2014a), in which dexamethasone was administered in combination with 1 or more antimyeloma 
agents. 
In Phase 1b/Cohort C, the carfilzomib regimen selected for use in this study (20 mg/m2 IV on 
Days 1 and 2 followed by 27 mg/m2 IV on Days 8, 9, 15, and 16 of Cycle 1 and for all doses of 
each 28-day cycle thereafter) is appropriate to the patient population and has found to be 
tolerable and active both as a single agent (Alsina et al 2012) and in combination with other 
agents (Stewart et al 2015). 
In Phase 1b/Cohort D, the bortezomib regimen is appropriate to the patient population and 
consistent with the product label (Velcade 2014) and established guidelines (NCCN Guidelines) 
of 1.3 mg/m2 IV or subcutaneously (SC) on Days 1, 4, 8, and 11 of each 21-day treatment cycle. 
In Phase 1b/Cohort E, the starting lenalidomide dose level and frequency are appropriate to the 
patient population and consistent with the product label (Revlimid 2015) and established 
guidelines (NCCN Guidelines) in which 25 mg administered orally QD on Days 1 through 21 of 
each 28-day cycle has been shown to be and effective and generally tolerated. 
In Phase 1b/Cohort F, the azacitidine regimen selected for use in this study (75 mg/m2 SC for 
5 days, followed by 2 days of no treatment, then 75 mg/m2 for 2 days of each 28-day treatment 
cycle) is appropriate to the patient population.  The tolerability and activity of this regimen has 
been established (Lyons et al 2009, García-Delgado et al 2014) as an acceptable alternative to the 
recommended dosing schedule of Days 1 to 7 of each 28-day treatment cycle. 
In Phase 1b/Cohort G, the doses of pomalidomide (4 mg PO on Days 1 to 21 of each 28-day 
cycle) and dexamethasone (40 mg once per day PO on Days 1, 8, 15, and 22 of a 28-day cycle) 
are the recommended doses in the pomalidomide label (Pomalyst 2015). 
In Phase 1b/Cohort H, the initial dose level of INCB050465 is 20 mg QD.  This dose level has 
been evaluated in the ongoing INCB 50465-101 study (Section 1.3) and has been determined to 


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be safe in a dose escalation cohort including 4 subjects; dose levels up to 30 mg QD since have 
been evaluated with no DLTs observed to date at any dose level. 
In Phase 2/Cohort I, the dose of INCB052793 used in combination with azacitidine is 35 mg QD.  
For the selected azacitibine regimen, refer to the Phase 1b/Cohort F above. 
In Phase 2/Cohort J, the dose of itacitinib used in combination with azacitidine is 300 mg QD.  
The first 3 to 6 subjects enrolled in this cohort will be monitored for occurrence of DLTs before 
enrolment of more subjects.  If this dose exceeds the MTD, new subjects will be enrolled at 
200 mg QD and monitored as above. 
For the selected azacitibine regimen, refer to the Phase 1b/Cohort F above. 
Doses of INCB052793 selected for evaluation in Phase 1b will be based on the safety established 
in Phase 1a, and likewise the dose selected for evaluation in Phase 2 will be based on safety and 
signs of efficacy established in Phase 1b.  For the treatment of advanced malignancies, the 
maximum individually tolerated dose of INCB052793 that spares inhibition of JAK2 should 
provide the best chance of efficacy while minimizing the potential for side effects (eg, 
myelosuppression). 
The itacitinib dose is based on the favorable efficacy and tolerability observed at that dose level 
in several studies.  Details can be found in the itacitinib IB. 
The Phase 1a portion of the study will continue to assess INCB052793 safety, PK, 
 and 
antitumor activities to explore the therapeutic index of INCB052793 monotherapy and establish 
range of PADs for the combination portion.  The intention is provide patients with unmet 
medical need with more efficacious treatment but not incur added toxicities. 


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2. 
STUDY OBJECTIVES AND PURPOSE 
2.1. 
Primary Objectives 
• Phase 1a:  To assess the safety and tolerability of INCB052793 in subjects with 
advanced malignancies and select doses for further evaluation. 
• Phase 1b:  To assess the safety and tolerability of INCB052793 in combination with 
standard therapies and the novel PI3Kδ inhibitor INCB050465 in subjects with 
advanced malignancies. 
• Phase 2:  To evaluate the efficacy of INCB052793 in combination with azacitidine 
and of itacitinib in combination with azacitidine in subjects with AML and high-risk 
MDS who have failed prior therapy with HMA, based on ORR. 
2.2. 
Secondary Objectives 
• To assess preliminary efficacy by assessing the ORR in subjects with advanced 
malignancies. 
• To assess the safety and tolerability of INCB052793 in combination in azacitidine 
and of itacitinib in combination with azacitidine in subjects with AML and high-risk 
MDS who have failed prior therapy with HMA. 
• To assess the PK of INCB052793 as monotherapy administered in the fasted state and 
the effect of food on the PK of INCB052793. 
• To assess the PK of INCB052793 when administered in combination with standard 
therapies and INCB050465 in subjects with advanced malignancies, to assess the PK 
of INCB050465 when administered in combination with INCB052793, and to assess 
the PK of itacitinib when administered in combination with azacitidine. 


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3. 
SUBJECT ELIGIBILITY 
3.1. 
Study Population 
Individuals diagnosed with histologically or cytologically confirmed malignancies specified 
below will be enrolled in the study. 
Phase 1a Monotherapy:  In Part 1 dose escalation and Part 2 dose expansion, subjects 
diagnosed with an advanced malignancy who have failed or are refractory to available treatments 
will be enrolled. 
Phase 1b Combination Therapy:  Subjects diagnosed with advanced or metastatic solid 
tumors, limited to pancreatic adenocarcinoma (first or second line), triple-negative breast cancer 
(second line), or urothelial cancer (second line; Cohort A); relapsed or refractory MM 
(Cohorts B, C, D, E, and G); AML/MDS (Cohort F); or lymphoma (Cohort H) will be enrolled. 
Phase 2:  Subjects diagnosed with AML and high-risk MDS subjects who failed prior therapy 
with HMA. 
3.2. 
Subject Inclusion Criteria for Phase 1a Monotherapy 
The following criteria are required for inclusion in Phase 1a of the study: 
1. Age 18 years or older. 
2. Histologically or cytologically confirmed solid tumor (TGA) or hematologic malignancy 
(TGB).  For Part 2 expansion, measurable or evaluable disease is required. 
3. Life expectancy of 12 weeks or longer. 
4. Must have received ≥ 1 prior treatment regimen and currently demonstrating progressive 
disease. 
5. Must not be a candidate for potentially curative or standard-of-care approved therapy. 
6. Female subjects of childbearing potential (defined as women who have not undergone 
surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and are not 
postmenopausal, defined as ≥ 12 months of amenorrhea) must have a negative serum 
pregnancy test at screening.  All female subjects of childbearing potential must agree to 
take appropriate precautions to avoid pregnancy (with at least 99% certainty) from 
screening through follow-up.  (Note:  Permitted methods that are at least 99% effective in 
preventing pregnancy [see Appendix A] should be communicated to the subjects and 
their understanding confirmed). 
7. Men must agree to take appropriate precautions to avoid fathering a child (with at least 
99% certainty) from screening through follow-up.  (Note:  Permitted methods that are at 
least 99% effective in preventing pregnancy [Appendix A] should be communicated to 
the subjects and their understanding confirmed.) 
8. Ability to comprehend and willingness to provide informed consent. 


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3.3. 
Subject Inclusion Criteria for Phase 1b and Phase 2 Combination 
Therapy 
The following criteria are required for inclusion in Phase 1b and Phase 2 of the study: 
1. Age 18 years or older. 
2. Phase 1b: 
Cohort A:  Histologically or cytologically confirmed pancreatic adenocarcinoma, 
triple-negative breast cancer, or urothelial cancer with at least 1 measurable or evaluable 
target lesion. 
Cohorts B, C, D, E, and G:  Histologically confirmed MM and measureable/evaluable 
disease as defined by 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. 
Cohort F:  Confirmed AML or MDS (International Prognostic Scoring System 
intermediate-1, intermediate-2, or high-risk) or MDS/myeloproliferative neoplasms 
(MPN) overlap syndromes in accordance with WHO diagnostic criteria, including 
chronic myelomonocytic leukemia (CMML), atypical BCR-ABL1–negative chronic 
myeloid leukemia, MDS/MPN unclassifiable, and named refractory anemia with ring 
sideroblasts and thrombocytosis. 
Cohort H:  Individuals diagnosed with lymphoma. 
− Subjects must not currently be a candidate for potentially curative hematopoietic 
stem-cell transplant and/or high-intensity chemotherapy. 
Phase 2: 
Cohorts I and J: 
− Confirmed AML or high-risk MDS (International Prognostic Scoring System -2, 
or high risk) in accordance with WHO diagnostic criteria. 
3. Life expectancy of 12 weeks or longer. 
4. Prior therapy Phase 1b: 
Cohort A:  No more than 1 prior chemotherapy regimen for advanced or metastatic 
disease (not including neoadjuvant and/or adjuvant therapy). 
− There is no restriction on the number of prior nonmyelosuppressive targeted 
therapies; targeted therapy alone will not be considered chemotherapy for the 
purposes of this study. 
Cohorts B, C, D, E, and G:  Must have relapsed from or have been refractory to 
≥ 2 prior treatment regimens, including a proteasome inhibitor and an 
immunomodulatory drug (IMiD). 


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Cohort F:  May have received any number of prior treatment regimens or be 
treatment-naive. 
Cohort H:  Must have relapsed from or have been refractory to available treatments. 
− Subjects who have previously been discontinued from the standard-of-care agent 
(Cohorts A-G) or  PI3Kδ inhibitors (Cohort H) being used in a specific cohort due 
to toxicity or intolerance may not enroll in that cohort (eg, subjects previously 
intolerant to bortezomib may not enroll in Cohort D). 
Prior therapy Phase 2: 
Cohorts I and J:  Must have failed prior therapy with HMA.  Failure of prior therapy 
with HMA is defined as one of the below:  
− progression to AML 
− 50% increase in bone marrow blasts. 
− relapsed disease after response 
− at least 4 cycles of treatment without clinical benefit (hematologic improvement 
[HI] or better) 
5. Female subjects of childbearing potential (defined as women who have not undergone 
surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and are not 
postmenopausal, defined as ≥ 12 months of amenorrhea) must have a negative serum 
pregnancy test at screening (additional requirements for Cohort E are specified in 
Table 13).  All female subjects of childbearing potential must agree to take appropriate 
precautions to avoid pregnancy (with at least 99% certainty) from screening through 
follow-up if of childbearing potential.  (Note: Permitted methods that are at least 99% 
effective in preventing pregnancy [see Appendix A] should be communicated to the 
subjects and their understanding confirmed). 
6. Men must agree to take appropriate precautions to avoid fathering a child (with at least 
99% certainty) from screening through follow-up.  (Note:  Permitted methods that are at 
least 99% effective in preventing pregnancy [Appendix A] should be communicated to 
the subjects and their understanding confirmed.) 
7. Ability to comprehend and willingness to provide informed consent. 
3.4. 
Subject Exclusion Criteria for Phase 1a, Phase 1b, and Phase 2 
If met, any of the following criteria will lead to subject exclusion from the study: 
1. Current pregnancy or breastfeeding. 
2. Prior receipt of a selective JAK1 inhibitor (Phase 1a only; prior receipt of ruxolitinib is 
permitted. 
3. Known hypersensitivity to any of the active substances or any of their excipients, 
including INCB052793, INCB050465, gemcitabine, nab-paclitaxel, dexamethasone, 
carfilzomib, bortezomib, lenalidomide, or azacitidine (Phase 1b and Phase 2 only, as 
appropriate to treatment cohort). 


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4. Received an investigational study drug within 28 days or 5 half-lives (whichever is 
longer) before receiving their first dose of study drug, except if approved by the sponsor's 
medical monitor. 
5. Any approved anticancer medications within 21 days or 5 half-lives (whichever is longer) 
before receiving the first dose of study drug (42 days for nitrosoureas) or with medical 
monitor approval EXCEPT steroids at ≤ 10 mg prednisone daily (or equivalent; steroid 
exception does not apply to Phase 1b/Cohort B or G) and hydroxyurea to control blood 
counts. 
6. Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy and 
alopecia) from previous anticancer therapy.  
− Phase 1b/Cohort D may not have > Grade 1 peripheral neuropathy at baseline. 
7. Known active central nervous system metastases and/or carcinomatous meningitis.  
Subjects with previously treated brain metastases may participate provided they are stable 
(without evidence of progression by imaging for at least 4 weeks before the first dose of 
study treatment and any neurologic symptoms have returned to baseline), have no 
evidence of new or enlarging brain metastases, and have not required steroids for at least 
7 days before study treatment. 
8. Eastern Cooperative Oncology Group (ECOG) performance status > 2. 
9. Any of the following laboratory results at screening without transfusions and 
hematopoietic growth factor support (except Phase 1b/Cohort F and Phase 2/Cohorts I 
and J): 
Laboratory Parameter 
Phase 1a/TGA and 
Phase 1b/Cohort A 
Phase 1a/TGB and Phase 1b/Cohorts B 
Through H Except F 
Hemoglobin (g/dL) 
< 10.0 
< 8.0 
Platelet count (109/L) 
< 100 
< 75 
Absolute neutrophil count (109/L) 
< 1.5 
< 1.0 
− No specific hematologic exclusion criteria apply to Phase 1b/Cohort F and 
Phase 2/Cohorts I and J 
10. Any of the following laboratory results at screening irrespective of causality, except if 
approved by the sponsor: 
− Conjugated bilirubin > 1.2 × upper limit of normal (ULN; need only be tested if 
total bilirubin exceeds > 1.5 × ULN).  In Phase 2, Cohorts I and J, Stage 2:  total 
bilirubin > 3 × ULN. 
− Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN if bone metastases are present 
and hepatic parenchymal metastases are absent). 
− AST or ALT > 3.0 × ULN (> 2.0 × ULN for Phase 1a/Part 1 and Phase 1b/Part 1).  
In Phase 2, Cohorts I and J, Stage 2:  subjects with any AST value. 
− Creatinine clearance of < 60 mL/min (30 mL/min for subjects with MM and 
subjects in Phase 2, Cohorts I and J, Stage 2) measured or calculated by Cockroft-


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Gault equation or estimated GFR < 60 mL/min/1.73 m2 (30 mL/min/1.73 m2 for 
subjects with MM and subjects in Phase 2, Cohorts I and J, Stage 2) using the 
Modification of Diet in Renal Disease (MDRD) formula. 
11. Known human immunodeficiency virus infection.  
12. Evidence of HBV or HCV infection or risk of reactivation.  Subject cannot be positive for 
HBV DNA, HCV RNA, hepatitis B surface antigen, or anti–hepatitis B core antibody, 
except if approved by the medical monitor. 
13. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically 
meaningful.  Screening QTcF interval > 450 milliseconds (> 480 msec for subjects in 
Phase 2, Cohorts I and J, Stage 2) is excluded.  
14. History of major stomach or intestinal surgery, or malabsorption syndrome (eg, Crohn's 
or chronic pancreatitis) that would, by clinical judgment, affect the absorption of study 
drug. 
15. Use of any potent CYP3A4 inhibitor (see Appendix C) within 14 days or 5 half-lives 
(whichever is longer) of the first study drug. 
16. Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone, 
carfilzomib, bortezomib, lenalidomide, pomalidomide, azacitidine, or PI3Kδ inhibitor 
(Phase 1b and Phase 2 only, as appropriate to treatment cohort). 
17. Ongoing radiation therapy and/or radiation therapy administered within 15 days of 
enrollment; subject must not require corticosteroids and must have recovered from all 
ongoing radiotherapy-related toxicities. 
− Subjects who have received radiation to the spine, pelvis, ribs, or femur should be 
discussed with the sponsor, as extensive radiation to a marrow-forming region 
may compromise a subject's ability to tolerate myelosuppressive chemotherapy. 
18. Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the 
administrative schedule and study evaluations, including the ability to swallow an oral 
agent. 
19. Any serious medical condition that, in the opinion of the investigator, would pose a 
significant risk to the subject or interfere with the interpretation of the study data.  
20. Current clinically active and uncontrolled infection of any etiology. 
21. Subjects with baseline serum (1,3)-β-D-glucan values > 60 pg/mL (Cohort H only). 


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4. 
INVESTIGATIONAL PLAN 
The investigational agent in this study is INCB052793, hereafter referred to as study drug.  All 
study subjects will receive the study drug in an open-label manner as an oral, self-administered 
agent. 
4.1. 
Overall Study Design 
The study will be conducted in 2 phases (Phase 1a/1b and Phase 2).  Phase 1a will be conducted 
with INCB052793 monotherapy dose escalation (Part 1) and dose expansion (Part 2).  Phase 1b 
will comprise treatment cohorts in which INCB052793 will be administered in combination with 
gemcitabine and nab-paclitaxel in select solid tumors (Cohort A); dexamethasone, carfilzomib, 
bortezomib, lenalidomide, and pomalidomide/dexamethasone in subjects with MM (Cohorts B, 
C, D,  E, and G, respectively); azacitidine in subjects with AML or MDS (Cohort F), and 
INCB050465 in subjects with lymphoma (Cohort H), each including both a dose escalation 
(Part 1) and an optional dose expansion (Part 2).  Phase 2 will include 2 treatment cohorts in 
which subjects with AML and high-risk MDS who failed prior therapy with HMA will receive 
azacitidine in combination with INCB052793 (Cohort I) or in combination with itacitinib 
(Cohort J).  Those cohorts will use a Simon 2-stage design to evaluate the efficacy of the 
combination regimens.  The approximate numbers of subjects for Stage 1 and Stage 2 are 
described in Section 9.  If an insufficient number of responders are observed in the cohort at 
Stage 1, further enrollment in the cohort will be terminated; see Figure 2). 


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Figure 2: 
Study Design 
 
 
* The first 3-6 subjects enrolled in Cohort J will be monitored for occurrence of DLTs before enrollment of more subjects.  If this 
dose exceeds the MTD, the subjects enrolled at this dose level will not be analyzed for efficacy and will be replaced with new 
subjects enrolled at 200 mg QD and will be monitored as above.  If this dose is not tolerable, the cohort will be discontinued. 


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4.1.1. 
Phase 1a Monotherapy 
Phase 1a will include Part 1 dose escalation starting with 25 mg QD to determine the MTD 
and/or PAD of single-agent INCB052793 in 2 treatment groups (TGA and TGB).  This dose will 
be chosen for further evaluation.  Part 2 dose expansion will evaluate the chosen dose as 
monotherapy. 
4.1.1.1. 
Phase 1a Part 1 Dose Escalation 
The dose escalation will start with TGA (advanced or metastatic solid tumors) at 25 mg QD and 
consist of a 21-day cycle, with Cycle 1 Day 1 as the first day of treatment.  Open-label dose 
escalation will consist of an initial cohort using a 3 + 3 design with dose doubling until either 
Grade 2 or greater toxicities or unbound AUC at steady state exceeds the value (25.3 μM∙h) 
corresponding to the NOAEL in the most sensitive species evaluated in GLP toxicology studies 
(rat at 15 mg/kg).  Each dose level will be observed for a period of 21 days before enrolling the 
next cohort and administering the next dose level.  Treatment Group B (advanced hematologic 
malignancies) will follow the same 3 + 3 dose-escalation design, beginning enrollment at the 
PAD when it is determined.  If warranted, lower dose levels may be explored during the dose 
escalation to further evaluate the safety, PK, 
 profile of INCB052793. 
Subjects who receive at least 17 of 21 days (or ≥ 80%) of fasted study drug at the level assigned 
to that cohort, or who experience a DLT, will be considered evaluable for determining 
tolerability of dose (see Section 4.2).  Subjects enrolling but not meeting these criteria may be 
replaced in order to fill the cohort. 
The starting dose of INCB052793 (25 mg QD in TGA; PAD in TGB) will be escalated if 0 of the 
first 3 evaluable subjects enrolled experience a DLT.  Increases to study drug will be up to 100% 
(ie, 25 mg, 50 mg, 100 mg, and 150 mg) if there are no reported Grade 2 or greater toxicities and 
no subject has an unbound AUC at steady state that exceeds 25.3 μM∙h.  Otherwise, increases of 
study drug dose will be limited to no more than 50% in successive cohorts, using QD regimen 
(ie, 25 mg, 35 mg, 50 mg, 75 mg, 100 mg, and 150 mg).  If no DLTs are observed in the initial 
3 subjects, the next cohort will begin enrollment.  If 1 DLT is observed in the first 3 subjects, 
3 additional subjects will be enrolled in the cohort. 
4.1.1.2. 
Phase 1a Part 2 Dose Expansion 
The expansion may proceed with a PAD, the MTD, or the highest dose tested if the MTD is not 
reached: 
• TGA (advanced or metastatic solid tumors) and TGB (advanced hematologic 
malignancies) of approximately 12 subjects each in 1 or 2 expansion dose levels 
(PAD and/or MTD or highest dose tested if MTD is not reached for each group 
tested) will be treated with the selected doses of INCB052793 as a single agent to 
further determine safety, tolerability, efficacy, PK, 
 in this population. 
• For both TGA and TGB, a study of the effect of food on the PK of INCB052793 will 
be conducted on this expanded cohort.  Results from the food-effect study will dictate 
whether study drug will be administered to subjects in the fasted or fed state in 
ongoing subjects in Phase 1a and Phase 1b. 


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4.1.2. 
Phase 1b Combination Therapy 
Phase 1b will comprise treatment cohorts evaluating INCB052793 when administered in 
combination with standard therapies for select solid tumors (Cohort A), MM (Cohorts B, C, D, 
E, and G), AML/MDS (Cohort F), and with the novel PI3Kδ inhibitor INCB050465 in 
lymphoma (Cohort H).  Each treatment cohort will include 2 parts.  Part 1 is a 3 + 3 dose 
escalation that will evaluate increasing doses of INCB052793 in combination with 
standard-of-care agents or INCB050465 in select solid tumors, MM, AML/MDS, and 
lymphoma.  Part 2 will be an optional expansion to further evaluate the safety and preliminary 
efficacy of the combination at the selected INCB052973 dose.  Timing for the initiation of 
Phase 1b enrollment will be determined by the sponsor based on the available safety/tolerability 
and PK/
 data from Phase 1a.  The sponsor may elect to open certain Phase 1b treatment 
cohorts before others or to not open specific cohorts. 
Enrollment into Cohorts A, C, D, E, G, and H will not be conducted as per Amendment 7 of the 
Protocol. 
If a subject does not meet eligibility criteria for the next treatment cohort in sequence due to a 
specific criterion (eg, pre-existing ≥ Grade 2 peripheral neuropathy excluding the subject from 
Cohort D), the subject will be enrolled into the next open cohort. 
4.1.2.1. 
Phase 1b Part 1 Dose Escalation 
The starting dose of INCB052793 in each treatment cohort will be designated as Dose Level 1.  
Dose Level 1 will be approximately 50% to 100% of a PAD (maximum of 75% of MTD) in 
Phase 1a (rounded down to the next lowest dose based on available tablet strengths).  Dose 
escalation will proceed using a 3 + 3 design as described in Section 4.2.  Each cohort will be 
observed for a minimum of 1 cycle before the next cohort begins enrollment.  Within each 
cohort, subjects will be considered nonevaluable for safety and replaced if they have received 
< 75% of the planned doses of study drug or standard therapy during the first cycle of treatment 
and they have not experienced a DLT.  If Dose Level 1 is deemed tolerable, the INCB052793 
dose in the respective combination therapy may be escalated to Dose Level 2, which will be 
≤ 50% higher than Dose Level 1.  Additional dose levels may be enrolled (ie, Dose Level 3, 
Dose Level 4, etc) until the MTD has been exceeded, with individual dose increases not to 
exceed ≤ 50%.  If Dose Level 1 is deemed to have exceeded the MTD, Dose Level -1 of 
INCB052793 (defined as 50%-75% of Dose Level 1) may be evaluated. 
The initial dose of INCB050465 will be 20 mg QD in Cohort H.  This dose level is considered a 
PAD.  However, based on emerging PK, 
 safety, and efficacy data, subjects may be enrolled 
at a different dose (eg, 30 mg or 15 mg) in combination with the recommended dose of 
INCB052793.  The individual dose increases will not to exceed 50%.  The MTD of monotherapy 
for both agents will not be exceeded. 
4.1.2.2. 
Phase 1b Part 2 Dose Expansion 
This portion will explore the safety, tolerability, PK, 
 and preliminary clinical 
activity of the regimen identified in the dose-escalation portion through an optional expansion 
cohort of approximately 12 subjects per cohort, to be treated at the combination doses selected in 
Part 1. 


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4.1.3. 
Phase 2 
Phase 2 includes 2 treatment cohorts in which subjects with AML and high-risk MDS who failed 
prior therapy with HMA will receive azacitidine in combination with INCB052793 35 mg QD 
(Cohort I) or in combination with itacitinib 300 mg QD (Cohort J).  The first 3 to 6 subjects 
enrolled in Cohort J in Stage 1 will be followed for occurrence of DLTs before enrollment of 
more subjects.  If this dose exceeds the MTD, the subjects enrolled at this dose level will not be 
analyzed for efficacy and will be replaced with new subjects enrolled at 200 mg QD and 
followed as above.  If 200 mg is not tolerable, further enrollment in the cohort will be 
terminated. 
Enrollment into Cohorts I and J will proceed in sequence (eg. first subject enrolled in Cohort I, 
next subject enrolled in Cohort J, etc) until both cohorts have been fully enrolled. 
A Simon 2-stage design will be used to evaluate the efficacy of the combination regimens in 
these cohorts.  The approximate numbers of subjects for Stage 1 and Stage 2 are specified in 
Figure 2 and described in more detail in Section 9.  If an insufficient number of responders are 
observed in the cohort at Stage 1, further enrollment in the cohort will be terminated. 
4.2. 
Dose-Limiting Toxicity Rules 
For Phase 1a/Part 1 and Phase 1b/Part 1, if no DLTs are observed in the initial 3 subjects, the 
next cohort will begin enrollment.  If 1 DLT is observed in the first 3 subjects, 3 additional 
subjects will be enrolled in the cohort.  If a DLT occurs in one-third or more of the total cohort 
(≥ 2 of 3 or 6), then the MTD will be deemed to have been exceeded, and the next lower dose 
level will be deemed to be the MTD.  If the dose-escalation increment has been 100%, then an 
intermediate lower dose level may be explored.  Thus, the MTD will be defined as 1 dose level 
below that at which one-third or more of subjects in a particular cohort experience DLTs.  
Dose-limiting toxicities occurring during the first 21- or 28-day treatment cycle will guide dose 
escalation and determination of the MTD; however, subjects who may have not experienced a 
DLT but who experienced intolerable, lower grade persistent toxicity determined to be due to 
study drug will be considered in the determination of the study drug dose in the expansion 
cohorts.  Likewise, when an additional agent is added after disease progression or absence of 
response (eg, dexamethasone may be added to INCB052793/lenalidomide), subjects will be 
observed for DLTs and persistent toxicities in this setting in same manner as the dose-escalation 
portion, and the drug will be similarly dose reduced or discontinued as indicated.  Only toxicities 
with a clear alternative explanation (ie, due to disease progression, comorbid condition, 
concomitant medication) can be deemed a non-DLT for determination of the PAD/MTD. 
In Phase 2, subjects will receive azacitidine in combination with INCB052793 35 mg QD 
(Cohort I) or in combination with itacitinib 300 mg QD (Cohort J).  See Section 4.1.3 for more 
details. 
4.2.1. 
Definition of Dose-Limiting Toxicities 
Specific AEs occurring during Cycle 1 of the study, or in the first cycle of treatment in which an 
additional agent is added to the combination in the setting of prolonged stable disease or 
progressive disease (Phase 1b Cohorts B, C, D and E only), will be considered to be DLTs if 
they are not clearly related to the underlying disease or its progression, comorbidity, and 


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concomitant medication.  Dose-limiting toxicities occurring during the first cycle will guide dose 
escalation and determination of the MTD.  Subjects who may have not experienced a DLT but 
who experienced intolerable, lower grade persistent toxicity determined to be due to study drug 
or have experienced recurrent dose interruptions and/or reductions will be considered in the 
determination of the study drug dose in the expansion cohorts.  A DLT will be defined as an AE 
that is new in onset and meets any of the following criteria, using the NCI CTCAE v4.03 toxicity 
grading scale: 
Hematologic Toxicities: 
 
 
Phase 1a and Phase 1b/Cohorts A through H (except F): 
• Grade 3 thrombocytopenia with bleeding requiring transfusion. 
• Grade 4 thrombocytopenia. 
• Grade 4 neutropenia. 
− Note:  For solid tumors only:  Grade 3 neutropenia is not considered a DLT; 
however, it may contribute to defining the MTD if more than two-thirds of 
subjects in a cohort (eg, 3 of 3 subjects or ≥ 5 of 6 subjects) experience 
neutropenia lasting  ≥ 3 days after interruption of INCB052793. 
• Grade 4 anemia. 
• Febrile neutropenia (ANC < 1.0 × 109/L with a single temperature of > 38.3°C 
(101°F) or a sustained temperature of ≥ 38°C (100.4°F) for > 1 hour. 
Phase 1b/Cohort F and Phase 2: 
• Grade 4 thrombocytopenia or requirement for platelet transfusion 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 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. 
Nonhematologic Toxicities: 
• Grade 2 peripheral neuropathy with pain (except Phase 1b/Cohort D). 
• Any ≥ Grade 3 nonhematologic toxicity EXCEPT: 
− Grade 3 nausea, vomiting, and diarrhea adequately controlled with medical 
therapy in ≤ 72 hours. 
− Fasting glucose > 250 mg/dL occurring within 3 days after dexamethasone 
administration (exception not applicable in Phase 2). 


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− Total bilirubin ≥ 2.0 × ULN to ≤ 3.0 × ULN that reverses to baseline within 
7 days and Grade 3 ALP, AST, or ALT that reverses to baseline within 7 days, 
except cases meeting the criteria for Hy's Law described below.  Grade 3 and 4 
ALP elevations in subjects with bone metastasis.  Note:  All Grade 3 bilirubin 
elevations regardless of duration will be considered a DLT in Phase 2. 
• Liver abnormalities meeting the criteria for Hy's Law (ALT or AST > 3 × ULN and 
total bilirubin > 2 × ULN, without initial findings of cholestasis (elevated serum 
ALP) 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.  
Subjects who experience a Grade 4 nonhematologic DLT should discontinue treatment.  Dose-
finding decisions will consider all available data, including the safety profile of prior cohorts.  
The decision for the subsequent cohorts and rationale will be documented in writing.  Selected 
dose cohorts may have additional subjects added in order to further assess safety, PK, 
. 
Each cohort will be observed for a minimum of either 21 days (Phase 1a and Phase 1b/Cohorts D 
and H) or 28 days (Phase 1b/Cohorts A, B, C, E, F, and G) before the next cohort begins 
enrollment.  Within each cohort, subjects will be considered nonevaluable for safety and 
replaced if they have not experienced a DLT and:  a) they have not received the specified dose of 
INCB052793 for at least 17 of 21 doses in Phase 1a and 75% of the planned doses of study drug 
or standard therapy during the first cycle of treatment in Phase 1b (unless the drug hold was due 
to a DLT).  Additional subjects may be enrolled to ensure there are enough evaluable subjects for 
safety. 
In Phase 2, a Simon 2-stage design will be used for Cohorts I and J.  In addition, the first 3 to 
6 subjects enrolled in Cohort J in Stage 1 will be followed for occurrence of DLTs before 
enrollment of more subjects.  See Section 4.1.3 for more details. 
4.3. 
Study Endpoints 
4.3.1. 
Primary Endpoints 
Phase 1a and 1b: 
• Safety and tolerability of INCB052793 monotherapy and in combination with 
standard therapies in select malignancies as assessed by summary of clinical 
laboratory assessments, 12-lead ECGs, and AEs.  
Phase 2: 
• ORR, defined as the proportion of subjects who achieve CR, CR with incomplete 
hematologic recovery (CRi), partial response (PR), or HI, using the appropriate 
disease-specific criteria. 
4.3.2. 
Secondary Endpoints 
• Response rates in those subjects with measurable disease as determined by 
investigator assessment of response. 


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• Safety and tolerability of INCB052793 in combination with azacitidine and of 
itacitinib in combination with azacitidine in subjects with AML and high-risk MDS 
who have failed prior therapy with HMA, assessed by summary of clinical laboratory 
assessments, 12-lead ECGs, and AEs. 
• Pharmacokinetics of INCB052793 and itacitinib (Phase 1a, Phase 1b, and Phase 2) 
will be summarized.   
• For Phase 1a Part 2 expansion portion (TGA and TGB), Cmax, Tmax, and AUC0-t for 
Cycle 1 Day 1 and Cmax, Tmax, Cmin, AUC0-t, and AUC0-τ for Cycle 1 Day 15, or Cmax, 
Tmax, Cmin, AUC0-t, and AUC0-τ for Cycle 2 Day 1 in the case of food-effect 
evaluation. 
 
4.4. 
Measures Taken to Avoid Bias 
This is an open-label study; no comparisons will be made between subjects or against historical 
controls.  Measurements of safety and efficacy are objective measurements, and only 
comparisons to pretreatment conditions are made.   
4.5. 
Number of Subjects 
Up to approximately 141 subjects may be enrolled, with 36 subjects in Phase 1a, up to 
approximately 39 subjects in Phase 1b, and approximately 18 to 66 subjects in Phase 2.  The 
number of subjects in Phase 2 will depend on the observed tolerability and the number of 
responders. 
4.6. 
Study Termination 
The sponsor may terminate the study electively or if required by regulatory decision.  If the study 
is terminated prematurely, the sponsor will notify the investigators, the institutional review 
boards (IRBs) and/or independent ethics committees (IECs), and regulatory bodies of the 
decision and the reason for termination of the study. 
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 or 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. 


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5. 
TREATMENT OF SUBJECTS 
5.1. 
Treatment Groups and Administration of Study Drug 
5.1.1. 
Phase 1a  Monotherapy 
5.1.1.1. 
INCB052793 
Subjects will self-administer INCB052793 orally with water; according to a QD morning 
regimen as directed by the investigator (dosing may be switched to BID dosing based on 
emerging PK 
 data).  INCB052793 will be taken on an empty stomach by refraining from 
food consumption for 2 hours before and 1 hour after study drug administration except on days 
when PK samples are collected (see Section 7.7 for PK dosing instructions), when it will be 
taken after an overnight fast of at least 8 hours.  Subjects will take study drug at the clinic after 
the hematology sample is drawn on clinic days when a hematology sample is obtained.  One 
cycle will be defined as 21 continuous days of planned study treatment; subjects will receive 
treatment in continuous cycles. 
5.1.2. 
Phase 1b Combination Therapy 
5.1.2.1. 
INCB052793 
Subjects will self-administer INCB052793 orally with water according to a QD morning regimen 
as directed by the investigator (dosing may be switched to BID dosing based on emerging PK 
 data).  INCB052793 will be taken on an empty stomach by refraining from food 
consumption for 2 hours before and 1 hour after study drug administration, except on days when 
PK samples are taken (see Section 7.7).  Subjects will take study drug at the clinic after the 
hematology sample is drawn on clinic days when a hematology sample is obtained.  One cycle 
will be defined as 21 (Cohorts D and H) or 28 (Cohorts A, B, C, E, F, and G) continuous days of 
planned study treatment. 
5.1.2.2. 
nab-Paclitaxel 
nab-Paclitaxel (Abraxane®) 125 mg/m2 should be administered as a 30-minute IV infusion once 
weekly for 3 consecutive weeks out of every 4 weeks (on Days 1, 8, and 15 of each 28-day 
cycle).  Although the starting dose of nab-paclitaxel in Phase 1b will be 125 mg/m2; a lower dose 
of 100 mg/m2 may be explored if necessary. 
5.1.2.3. 
Gemcitabine 
Gemcitabine (Gemzar® or equivalent) 1000 mg/m2 should be administered as a 30-minute IV 
infusion once weekly for 3 consecutive weeks out of every 4 weeks (on Days 1, 8, and 15 of 
each 28-day cycle).  The infusion of gemcitabine must begin after completion of the 
nab-paclitaxel infusion.  Increased toxicity has been observed if gemcitabine is administered 
more frequently than once weekly or infusions that last longer than 60 minutes.  The starting 
dose of gemcitabine in Phase 1b will be 1000 mg/m2; a lower dose of 750 mg/m2 may be 
explored if necessary. 


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5.1.2.4. 
Dexamethasone 
Dexamethasone will be administered as open-label commercial product at a starting dose of 
40 mg administered orally weekly on Days 1, 8, 15, and 22 of each 28-day cycle, without regard 
to food.  Dose adjustments for toxicity will be permitted at the discretion of the investigator.  
After 4 or more cycles of stable disease, or if disease progression occurs after 1 or more cycles of 
the combination, carfilzomib, bortezomib or lenalidomide (at the discretion of the investigator) 
may be added to the regimen at a dose level that has been determined as safe and tolerable in the 
relevant treatment cohort (C, D, or E).  If an additional agent is added to the regimen, the subject 
will subsequently follow the schedule of assessments appropriate to that agent. 
5.1.2.5. 
Carfilzomib 
Carfilzomib (Kyprolis 2012) will be administered as an open-label commercial product at a dose 
of 20 mg/m2 IV on Days 1 and 2 followed by 27 mg/m2 IV on Days 8, 9, 15, and 16 of Cycle 1 
and for all doses of each 28-day cycle thereafter.  After 4 or more cycles of stable disease, or if 
disease progression occurs after 1 or more cycles of the combination, dexamethasone 40 mg 
administered orally weekly may be added to the regimen and continued until study withdrawal.  
The sponsor may implement weekly dexamethasone into combination from Cycle 1, based on 
emerging data either by an administrative memorandum or a Protocol amendment.  After 
12 cycles of treatment, subjects will transition to maintenance dosing on Days 1, 2, 15, and 16 of 
each 28-day cycle.  Antiviral prophylaxis should be implemented as needed, per institutional 
standard.  Dose adjustments for toxicity will be permitted at the discretion of the investigator.  
 
 
5.1.2.6. 
Bortezomib 
Bortezomib (Velcade 2014) will be administered as an open-label commercial product at a 
starting dose of 1.3 mg/m2 IV or SC on Days 1, 4, 8, and 11 of each 21-day treatment cycle.  
After 4 or more cycles of stable disease, or if disease progression occurs after 1 or more cycles of 
the combination, dexamethasone 40 mg administered orally weekly may be added to the regimen 
and continued until study withdrawal.  The sponsor may implement weekly dexamethasone into 
combination from Cycle 1, based on emerging data either by an administrative memorandum or 
a Protocol amendment.  After 8 cycles, subjects may transition to a maintenance schedule 
comprising 1 dose every 2 weeks.  Antiviral prophylaxis should be implemented as needed, per 
institutional standard.  Dose adjustments for toxicity will be permitted at the discretion of the 
investigator. 
5.1.2.7. 
Lenalidomide 
Lenalidomide (Revlimid 2015) will be administered as an open-label commercial product at a 
starting dose of 25 mg administered orally QD on Days 1 to 21 of each 28-day cycle.  Lower 
dose levels of lenalidomide may be explored (eg, 10 mg, 15 mg, 20 mg) based on the 
safety/tolerability of the combination.  After 4 or more cycles of stable disease, or if disease 
progression occurs after 1 or more cycles of the combination, dexamethasone 40 mg 
administered orally weekly may be added to the regimen until study withdrawal.  The sponsor 
may implement weekly dexamethasone into combination from Cycle 1, based on emerging data 
either by an administrative memorandum or a Protocol amendment.  Dose adjustments for 


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toxicity will be permitted at the discretion of the investigator.  Antithrombotic prophylaxis 
should be implemented as needed, per institutional standard.  Dose adjustments for toxicity will 
be permitted at the discretion of the investigator. 
5.1.2.8. 
Azacitidine 
Azacitidine (Vidaza 2014) will be administered as an open-label commercial product at a dose of 
75 mg/m2 SC for 5 days, followed by 2 days of no treatment, then 75 mg/m2 for 2 days of each 
28-day treatment cycle.  Dose adjustments for toxicity will be permitted at the discretion of the 
investigator.  Intravenous administration is allowed if SC administration is not tolerated. 
5.1.2.9. 
Pomalidomide 
Pomalidomide will be administered as an open-label commercial product at a dose of 4 mg 
administered orally QD on Days 1 through 21 of each 28-day cycle.  Lower dose levels of 
pomalidomide may be explored (eg, 3 mg, 2 mg, 1 mg) based on the safety/tolerability of the 
combination.  Dose adjustments for toxicity will be permitted at the discretion of the 
investigator.  Dexamethasone will be coadministered at 40 mg orally weekly on Days 1, 8, 15, 
and 22 of each 28-day cycle. 
5.1.2.10. INCB050465 
The initial starting dose of INCB050465 will be 20 mg QD.  Subjects may be enrolled at a 
different dose (eg, 30 mg or 15 mg) based on emerging data.  Subjects will self-administer 
INCB050465 using an oral daily QD regimen, as instructed by the investigator.  INCB050465 
should be administered in the clinic on days when PK sampling is performed as per Table 19.  
INCB050465 should be taken on an empty stomach if possible, and subjects should refrain from 
food consumption during the period 2 hours before and 1 hour after INCB050465 administration. 
5.1.3. 
Phase 2 
5.1.3.1. 
INCB052793 
The dose of INCB052793 in Phase 2 will be 35 mg QD.  Subjects will self-administer 
INCB052793 orally with water according to a QD morning regimen as directed by the 
investigator (dosing may be switched to BID dosing based on emerging PK 
 data).  
INCB052793 will be taken on an empty stomach by refraining from food consumption for 
2 hours before and 1 hour after study drug administration, except on days when PK samples are 
taken (see Section 7.7).  Subjects will take study drug at the clinic after the hematology sample is 
drawn on clinic days when a hematology sample is obtained.  One cycle will be defined 28 days 
of continuous days of planned study treatment. 
5.1.3.2. 
Itacitinib 
The starting dose of itacitinib in Phase 2 will be 300 mg QD.  Subjects may be enrolled at a 
different dose (eg, 200 mg QD) based on emerging data.  Subjects will self-administer itacitinib 
orally with water according to a QD morning regimen as directed by the investigator.  Itacitinib 
may be taken without regard to food except on days when PK samples are drawn (see 
Section 7.7).  Subjects will take study drug at the clinic after the hematology sample is drawn on 


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clinic days when a hematology sample is obtained.  One cycle will be defined as 28 days of 
continuous days of planned study treatment. 
5.1.3.3. 
Azacitidine 
Azacitidine will be administered as described in Section 5.1.2.8. 
5.2. 
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 or doses taken nonfasted.  
Subjects 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. 
5.3. 
Randomization and Blinding 
 In Phase 2, enrollment into Cohorts I and J will proceed in sequence (eg, first subject enrolled in 
Cohort I, next subject enrolled in Cohort J, etc) until both cohorts have been fully enrolled. 
5.4. 
Duration of Treatment and Subject Participation 
Subjects will be treated in continuous 21-day cycles (Phase 1a and Phase 1b/Cohorts D and H) or 
28-day cycles (Phase 1b/Cohorts A, B, C, E, F, and G, and Phase 2/Cohorts I and J) until they 
meet withdrawal criteria as described in Section 5.7.1.  If the subject discontinues all study 
treatment, the treatment portion will end, and the subject will enter the follow-up portion (see 
Section 6.4).  Study participation is expected to average about 6 months. 
5.5. 
Rationale for Dose Modification 
Selections and modifications to study drug doses are planned for dose-escalation cohorts.  Also, 
dose interruptions and modifications may occur for individual study subjects.  The identification 
of DLTs will define the doses used in planned cohorts.  Further, the occurrence of DLTs and 
other toxicities (related or unrelated to study drug) will guide decisions for treatment 
interruptions and discontinuation for individual subjects. 
In Phase 1a, subjects enrolled in the dose-escalation portion of the study will have the option of 
escalating to a dose found to be tolerated in a subsequent cohort (See Section 5.6.1). 
5.5.1. 
Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose 
A DLT will be defined as the occurrence of any of the toxicities occurring during the first cycle 
of treatment, or in the first cycle of treatment in which an additional agent is added to the 
combination in the setting of prolonged stable disease or progressive disease.  The DLTs include 
AEs that are new in onset and are of the specified grades (see Section 4.2.1), regardless of 
investigator assessment of causality to the investigational product.  Only toxicities with a clear 
alternative explanation (eg, due to disease progression, comorbidities, and concomitant 
medications) can be deemed a non-DLT.  Subjects who may have not experienced a DLT but 
who experienced intolerable, lower grade persistent toxicity determined to be due to study drug 
or have experienced recurrent dose interruptions and/or reductions will be considered in the 
determination of the study drug dose in the expansion cohorts. 


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Individual subject dose reductions may be made based on events observed at any time during 
treatment with INCB052793 and itacitinib; however, for the purposes of dose escalation/ 
de-escalation, expanding a dose cohort, and determining the MTD of INCB052793 and itacitinib, 
decisions will be made based on events that are observed from the first day of INCB052793 and 
itacitinib administration through and including the final day of Cycle 1. 
All DLTs will be assessed by the investigator using the current CTCAE v4.03 criteria 
(NCI 2010). 
5.5.2. 
Follow-Up of Dose-Limiting Toxicities 
Any DLT should be followed until it resolves to baseline or appears to have stabilized for a 
minimum of 4 weeks.  During follow-up, subjects should be seen as often as medically indicated 
to assure safety. 
5.5.3. 
Management of Dose-Limiting Toxicities or Other Urgent Situations 
In all cases investigators are free to use any measures or concomitant medications, following 
discussion with the sponsor (whenever possible), necessary to optimally treat the subject. 
5.6. 
Dose Adjustment of Study Drug 
5.6.1. 
Planned Dose Adjustments 
Intrasubject dose escalation will be allowed in Phase 1a or Phase 1b, provided that the following 
criteria are met: 
• The Protocol eligibility criteria are met at the time of escalation. 
• The subject has received 2 cycles of study drug and standard-of-care agent (as 
applicable) and has not experienced toxicity ≥ Grade 2 that is NOT from the 
underlying malignancy. 
• The next dose level has been determined to be safe based on DLT rules. 
• The subject is willing to repeat all assessments as per Cycle 1, including the PK 
sampling and ECG schedule as in Cycle 1. 
• 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 pose 
increased risk to the subject. 
• The intrasubject dose escalation has been approved by the sponsor. 
In Phase 2,  the first 3 to 6 subjects enrolled in Cohort J will be monitored for occurrence of 
DLTs before enrollment of more subjects.  If this dose exceeds the MTD, the subjects enrolled at 
this dose level will not be analyzed for efficacy and will be replaced with new subjects enrolled 
at 200 mg QD and will be monitored as above.  If this dose is not tolerable, the cohort will be 
discontinued. 


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5.6.2. 
Criteria and Procedures for Interruption 
Treatment with INCB052793, INCB050465, and itacitinib may be delayed up to 2 weeks 
(14 days) to allow for resolution of toxicity or performance of a medical procedure (eg, radiation 
therapy to an individual lesion with otherwise disease stability).  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's medical monitor to discuss the case of any subject 
whose treatment has been delayed for more than 14 days before restarting treatment with 
INCB052793, INCB050465, and/or itacitinib (see Table 1). 
5.6.2.1. 
INCB052793, INCB050465, and Itacitinib Dose Interruption and Restart 
Guidelines 
Because subjects may enter the study with extensive pretreatment, these dose reduction and 
interruption rules are provided as guidelines (see Table 1).  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.  Subjects receiving dose 
reductions (but not meeting DLT criteria) during the first cycle for that cohort will not be 
considered evaluable for the purposes of determining the MTD and will be replaced. 
Table 1: 
Guidelines for Interruption and Restart of Study Drugs INCB052793, 
INCB050465, and Itacitinib 
Toxicity/CTCAE Grade 
Action Taken 
Chemistry: 
• Total bilirubin > 3.0 × ULN 
• AST and/or ALT > 3.0 × ULN 
• ALP ≥ 2.5 × ULN 
Note:  In subjects with bone metastasis-related 
elevations at baseline, contact sponsor to discuss 
clinical management and possible dose 
reductions. 
Step 1:  Interrupt study drug(s) up to 2 weeks (14 days) until the 
toxicity has resolved to ≤ Grade 1 except by approval of the 
medical monitor. 
Step 2:  Restart study drug(s) at next lower dose (or at 25% 
reduction if in expansion cohort, rounded down to the nearest 
pill strength); monitor as clinically indicated.a   
 
Chemistry: 
• ALT > 3.0 × ULN, ALP < 2 × ULN, and 
bilirubin ≥ 2.0 × ULN (Hy's Law) 
Discontinue treatment. 
Hematology: 
Phase 1a/TGA and Phase 1b/Cohort A: 
• ANC < 1.0 × 109/L  
• Platelet count 50 to < 75 × 109/L  
 
 
Phase 1a/TGB and Phase 1b/Cohorts B 
through H (except F): 
• ANC < 0.5 × 109/L  
• Platelet count  25 to < 50 × 109/L 
Phase 1a/TGA and Phase 1b/Cohort A: 
Step 1:  Hold until resolved to ≥ 1.0 × 109/L ANC or 
≥ 75 × 109/L platelets. 
Step 2:  Restart study drug at same dose and monitor as 
clinically indicated. 
 
Phase 1a/TGB and Phase 1b/Cohorts B through H (except 
F): 
Step 1:  Hold until resolved to ≥ 0.5 × 109/L ANC or 
≥ 50 × 109/L platelets. 
Step 2:  Restart study drug(s) at same dose and monitor as 
clinically indicated. 


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Table 1: 
Guidelines for Interruption and Restart of Study Drugs INCB052793, 
INCB050465, and Itacitinib (Continued) 
Toxicity/CTCAE Grade 
Action Taken 
Phase 1a/TGA and Phase 1b/Cohort A: 
• Grade 4 ANC (< 0.5 × 109/L) OR ≥ Grade 3 
ANC with an oral temperature of at least 
38.5°C OR with ≥ Grade 3 infection 
• Platelet count < 50 × 109/L 
 
 
Phase 1a/TGB and Phase 1b/Cohorts B 
through H (except F): 
• Grade 4 ANC (< 0.5 × 109/L) and 1 or more 
of the following: 
− Oral temperature of at least 38.5°C 
− ≥ Grade 3 infection 
• Platelet count < 25 × 109/L  
Phase 1a/TGA and Phase 1b/Cohort A: 
Step 1:  Hold until resolved to ≥ 1.0 × 109/L ANC or 75 × 109/L 
platelets. 
Step 2:  Restart study drug at next lower dose (or 25% reduction 
if in expansion cohort, rounded down to the nearest tablet 
strength); monitor as clinically indicated.a 
 
Phase 1a/TGB and Phase 1b/Cohorts B through H (except 
F): 
Step 1:  Hold until resolved to ≥ 0.5 × 109/L ANC and afebrile 
or ≥ 50 × 109/L platelets. 
Step 2:  Restart study drug(s) at next lower dose (or 25% 
reduction if in expansion cohort, rounded down to the nearest 
tablet strength); monitor as clinically indicated.a 
Phase 1b/Cohort F and Phase 2/Cohorts I 
and J: 
• ≥ 50% decrease from baseline platelet count 
(Subjects with baseline platelet 
count < 75 × 109/L only) 
• ≥ 50% decrease from baseline ANC (Subjects 
in Phase 1b/Cohort F and Phase 2/ 
Cohorts I and J with baseline ANC < 1.0 × 
109/L only)  
Step 1:  Evaluate  underlying disease based on peripheral blood 
and bone marrow assessment as needed 
Step 2:  Consider dose interruption if cytopenias are NOT due to 
underlying disease or treatment with azacitidine. 
Step 3:  Restart study drug at next lower dose (or 25% reduction 
if in expansion cohort, rounded down to the nearest tablet 
strength); monitor as clinically indicated.a 
Other toxicities: 
 
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 
Step 1:  Interrupt study drug up to 2 weeks (14 days) until 
toxicity resolves to ≤ Grade 1. 
Step 2:  Restart study drug at next lower dose (or 25% reduction 
if in expansion cohort, rounded down to the nearest pill 
strength); monitor as clinically indicated.a 
Any recurrent Grade 3 toxicity after 2 dose 
reductions 
Discontinue study drug treatment and follow-up per Protocol.   
Any other Grade 4 toxicity 
Discontinue study drug treatment.   
a Only 2 dose reductions are permitted. 
5.6.2.2. 
Standard-of-Care Dose Interruptions 
Dose interruptions and adjustments for standard-of-care agents in Phase 1b and Phase 2 of the 
study will be at the discretion of the investigator, in accordance with the package insert and 
applicable treatment guidelines (eg, NCCN Guidelines).  In the event that > 2 dose reductions of 
any standard-of-care agent are required, the subject should be withdrawn from the study as per 
Section 5.6.3. 


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5.6.3. 
Criteria for Permanent Discontinuation of Study Drug or Standard-of-Care 
Agents 
The occurrence of unacceptable toxicity not from the underlying malignancy will require that the 
study drug be permanently discontinued.  Unacceptable toxicity is defined as: 
• Occurrence of an AE that is not clearly unrelated 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. 
• Toxicity requiring > 2 dose reductions of INCB052793, itacitinib, or standard-of-care 
therapy.  Subjects enrolled in Phase 1b and Phase 2 who have required > 2 reductions 
of the standard-of-care agent may remain on INCB052793 monotherapy with sponsor 
approval. 
• Persistent toxicity requiring a delay of therapy for > 2 weeks (14 days). 
• Confirmed prolongation of QTcF by > 60 milliseconds or QTcF > 500 milliseconds 
confirmed by repeat ECG from baseline. 
5.7. 
Withdrawal of Subjects From the Study Treatment 
After discontinuation of study treatment, all subjects will remain in the follow-up phase of the 
study for the collection of safety, subsequent anticancer therapies, and survival, as detailed in 
Section 6.4.  Additionally, subjects who discontinue study treatment without disease progression 
will continue to have disease assessments until disease progression, until the subject begins a 
new anticancer treatment, or death (see Section 6.4). 
5.7.1. 
Withdrawal Criteria 
Subjects must be withdrawn from the study treatment 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 is unwilling to continue receiving study treatment. 
• 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 or IEC. 
• Unacceptable toxicity has occurred (see Section 5.6.3). 
• Disease progression has occurred except in the circumstance where, in the setting of 
otherwise stable disease, a medical procedure or radiation therapy is required to a 
single lesion, with medical monitor approval.  Subjects in Phase 1b/Cohort B may 
remain on study if a proteasome inhibitor or IMiD (as per Section 5.1.2.4) is added to 
the regimen.  Subjects in Cohorts C, D, and E may remain on study after disease 
progression if dexamethasone is added to the regimen (as per Sections 5.1.2.5, 
5.1.2.6, and 5.1.2.7). 


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A subject may be withdrawn from the study:  
• If during the course of the study, a subject is found not to have met eligibility criteria.  
The sponsor's medical monitor, in collaboration with the investigator, will determine 
if the subject should be withdrawn from the study.  See Section 11.3. 
• If a subject is noncompliant in the opinion of the investigator.  The sponsor should be 
consulted for instructions on handling the subject. 
5.7.2. 
Withdrawal Procedures 
The decision to discontinue study treatment (ie, INCB052793/standard-of-care agent) will not 
constitute study withdrawal or study completion (see Section 5.7).  In the event that the decision 
is made to discontinue study treatment, the treatment phase will be considered complete and the 
follow-up phase will begin (see Section 6.4). 
Upon discontinuation of study treatment, the end-of-treatment (EOT) visit should be completed 
as outlined in the schedules of assessments (Table 2, Table 4, Table 6, Table 8, Table 10, 
Table 12, Table 14, Table 16, Table 18, Table 20, and Table 22).  The date of the last dose of 
study drug will be recorded in the case report form (CRF), and the reason for subject withdrawal 
will be recorded. 
If the subject discontinues study treatment and actively withdraws consent for collection of 
follow-up data (ie, safety, disease assessments, subsequent anticancer treatments and survival), 
then no additional data collection should occur; however, subjects will have the option of 
withdrawing consent for study treatment but continuing in the follow-up phase of the study for 
collection of subsequent safety, disease assessments, anticancer treatments and survival.  The 
date the subject was withdrawn from the study and the specific reason for withdrawal will be 
recorded in the CRF. 
Once the decision is made to permanently discontinue the study treatment, the following steps 
should be followed: 
• The study monitor or sponsor must be notified. 
• The reasons for withdrawal and the date of last dose of study drug must be 
documented in the subject's medical record and CRF. 
• The EOT visit should be performed. 
• Subjects must be followed for safety through the time of the follow-up visit or until 
study drug-related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer. 
Reasonable efforts should be made to have the subject return for a safety follow-up, disease 
status follow-up, and survival follow-up visits.  These visits are described in Section 6.4. 
5.8. 
Concomitant Medications and Measures 
All concomitant medications and treatments must be recorded in the CRF.  Any prior medication 
received up to 30 days before enrollment (Cycle 1 Day 1) will be recorded in the CRF as well as 
any concomitant treatments/procedures that are required to manage a subject's medical condition 
during the study. 


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5.8.1. 
Growth Factor Support 
The use of growth factors to treat emerging neutropenia should be based on American Society of 
Clinical Oncology guidelines for the use of WBC growth factors (Smith et al 2006) and the 
investigator's clinical judgment.  The sponsor recognizes that JAK inhibition may reduce the 
effectiveness of growth factor support and recommends that appropriate measures are taken 
relative to withholding study drug in the setting of treatment-emergent neutropenia requiring 
GCSF. 
5.9. 
Restricted Medications and Measures 
• Use of systemic corticosteroid doses > 10 mg/day prednisone (or equivalent) is not 
permitted from the screening visit through the EOT visit except for transient use of 
< 3 days.  For subjects enrolled in Phase 1b/Cohort B, C, D, or E who are receiving 
therapeutic doses of dexamethasone (ie, 40 mg weekly), no additional corticosteroids 
should be administered. 
• Use of moderate inducers or inhibitors of CYP3A4 (see Appendix C) should be used 
with caution, and investigators should seek other options where possible. 
• P-glycoprotein substrates of clinical relevance should be used with caution. 
• Phase 1b/Cohort E and G (lenalidomide and pomalidomide) only:  Erythropoietic 
agents, or other agents that may increase the risk of thrombosis, such as estrogen 
containing therapies, should be used with caution. 
5.10. 
Prohibited Medications and Measures 
• Any concomitant use of a JAK inhibitor. 
• Phase 1b/Cohort H only:  any concomitant use of a PI3K inhibitor. 
• Use of potent inducers and inhibitors of CYP3A4 (see Appendix C). 
6. 
STUDY ASSESSMENTS 
Study and laboratory assessments will be performed as indicated in Table 2 and Table 3 
(Phase 1a), Table 4 through Table 19 (Phase 1b), and Table 20 through Table 23 (Phase 2).  The 
sponsor may request to have scans sent to a centralized reader.  
 
  For instructions on all assessments, 
see Section 7. 


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Table 2: 
Schedule of Assessments for Phase 1a Monotherapy (Dose Escalation and Expansion) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (21-Day Cycles) 
 
Follow-Up Phase 
Cycle 1a 
Subsequent 
Cycles 
Safety 
Follow-Up 
Disease Status 
Follow-Up 
Survival 
Follow-Up 
Day -28  
to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 1 
± 3 Days 
EOT 
30-35 Days 
After EOT 
Every 8 Weeks 
(± 7 Days) 
After EOT 
Every 
12 Weeks 
(± 7 Days) 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
Review inclusion/ 
exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
Demography and 
medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/ 
body weightb 
7.4.2 
7.4.3 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGc 
7.4.5 
X 
X 
 
 
X 
X 
 
 
 
Timed ECGc 
7.4.5.1 
 
X 
 
X 
 
 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
X 
X 
 
 
 
Review of AEsd 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 administer 
in clinice 
7.7.1.1 
7.9.1 
 
X 
X 
X 
X 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
X 
X 
X 
X 
 
 
 
Distribute reminder 
cards 
7.9.15 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease  status 
6.4.2 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
X 
DISEASE ASSESSMENTS 
AML, MDS, 
MDS/MPN, MF, and 
MM response 
assessment f 
7.5,  
7.4.6.8 
X 
X 
 
 
X 
X 
 
 
 
 


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Table 2: 
Schedule of Assessments for Phase 1a Monotherapy (Continued) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (21-Day Cycles) 
EOT 
Follow-Up Phase 
Cycle 1a 
Subsequent 
Cycles 
Safety 
Follow-Up 
Disease Status 
Follow-Up 
Survival 
Follow-Up 
Day -28 
to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 1 
± 3 Days 
30-35 Days 
After EOT 
Every 8 Weeks 
(± 7 Days) 
After EOT 
Every 
12 Weeks 
(± 7 Days) 
Immunophenotypingg 
7.5.5 
X 
 
 
 
Xg 
 
 
 
 
Solid tumors/lymphoma 
(CT/MRI/FDG-PET)h 
7.5.1, 
7.5.3 
X 
 
 
 
X 
X 
 
X 
 
Skeletal survey  
(MM only)i 
7.5.6 
X 
X (investigator discretion) 
 
 
 
Bone marrow aspirate 
and biopsy (hematologic 
malignancies only)j 
7.5.4 
X 
 
 
 
X 
 
 
 
 
TUMOR TISSUE BIOPSY/ARCHIVAL TISSUE COLLECTION 
Tumor tissue biopsyk 
7.8.4 
X 
X 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
CT = computed tomography; FDG-PET = positron emission tomography using [18F] fluorodeoxyglucose; FISH = fluorescence in situ hybridization; MRI = magnetic resonance 
imaging; PET = positron emission tomography. 
a Subjects who escalate their doses will have assessments done as per Cycle 1, including laboratory assessments. 
b Comprehensive physical examination at screening; targeted physical examination thereafter.  Body weight will be taken at each visit.  Height is measured at screening only. 
c Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; timed triplicate ECGs will be performed predose and 1 and 2 hours postdose on Cycle 1 
Day 1 and Cycle 1 Day 15.  The ECGs should be conducted before, but within, 15 minutes of the PK blood draw at the corresponding timepoint. 
d Subjects must be followed for AEs for 30 days (+ 5 days) after the EOT visit (or after the last dose of study drug if the EOT visit was not performed.) 
e Study drug will be administered in a fasted state of 2 hours predose and 1 hour postdose with the following exception:  on days with PK 
 sampling, subjects will fast 
8 hours before and 1 hour after study drug administration.  Study drug should be administered in the clinic on days where there are PK 
 collections as outlined in 
Sections 7.7 and 7.8.  Otherwise, the study drug will be self-administered by the subject.  
f For subjects with MM, response assessments should be performed as per Section 7.4.6.8 at screening, on Day 1 of each cycle (± 7 days) for the first 12 months of study 
participation followed by every 12 weeks (every 4 cycles), and EOT.  For subjects with AML/MDS/MPN, response assessments should be performed on Day 1 of each cycle and 
at EOT.  In subjects who discontinue study drug without confirmed disease progression, a response assessment should be performed at the time of treatment discontinuation (ie, 
date of discontinuation ± 4-week window).  For subjects who discontinue treatment for reasons other than disease progression, every effort should be made to continue 
monitoring their disease status until (1) start of new anticancer therapy, (2) documented disease progression, (3) death, or (4) the end of study, whichever occurs first.  See 
Section 7.5. 
g For subjects with lymphomas and AML/MDS, immunophenotyping should be performed at screening, Cycle 2 Day 1, and to confirm a CR. 
h Computed tomography, MRI, FDG-PET, and/or PET/CT (appropriate to disease type) will be conducted every 6 weeks (every 2 cycles) for the first 12 months of study 
participation, followed by every 12 weeks (every 4 cycles) until the subject enters into the disease status follow-up phase.  Treatment cycles may be delayed; therefore, tumor 
assessments may be delayed as well to synchronize with treatment cycles regardless if treatment is delayed due to safety (± 10-day window).  For subjects who discontinue 
treatment for reasons other than disease progression, every effort should be made to continue monitoring their disease status, including, if applicable, radiographic disease 
imaging until 1) start of new anticancer therapy, 2) documented disease progression, 3) death, or 4) the end of study, whichever comes first. 
i Skeletal survey should be conducted at screening and subsequently at the discretion of the investigator. 


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j Subjects with AML, MDS, and MPN should have a bone marrow aspirate at screening and approximately 3, 6, and 12 months after Day 1 and then every 12 months on the 
nearest Cycle Day 1 (± 7 days) after the first dose of treatment and as clinically indicated.  For subjects with lymphoma (with exceptions noted in Section 7.5.4) and MM, a bone 
marrow examination should be conducted at screening and only if confirming a CR unless otherwise clinically indicated.  Fluorescence in situ hybridization and cytogenetic 
testing should be performed, when feasible, as per institutional standard.  Bone marrow biopsy should be obtained if needed for disease evaluation (eg, if there are no spicules in 
the aspirate or in case aspirate cannot be obtained). 
k Fresh bone marrow aspirate sample is required at baseline for subjects in TGB only.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a 
bone marrow examination is otherwise performed to assess disease status.  Lymphoma subjects in whom a baseline bone marrow biopsy/aspirate is not required as per 
Section 7.5.4 are exempt from this requirement. 


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Table 3: 
Laboratory Assessments for Phase 1a Monotherapy (Dose Escalation and Expansion) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (21-Day Cycles) 
EOT 
Safety  
Follow-Up 
Cycle 1 
Cycle 2 
Subsequent 
Cycles 
(± 3 Days) 
Day -28 to -
1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 1 
Day 1 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
 
 
 
X 
X 
X 
 
Urinalysisb 
7.4.6.5 
X 
 
 
 
X 
X 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry 
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyc 
7.4.6.6 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)d 
7.7.1.1 
 
X 
Xd 
X 
Xd 
 
 
 
PK TIMEDe 
7.7.1.1 
 
X 
 
X 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine sample collection (6-hour)j 
7.7.2 
 
 
 
X 
 
 
 
 
a Study drug should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening, Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles  7, 10, etc); and at EOT.  
c For women of childbearing potential:  local urine pregnancy tests can be done throughout the course of the study at the investigator's discretion. 
d Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (food-effect only) require trough (predose) and timed PK (see footnote e).  Day 8 collection is trough (predose) only.  No 
timed sampling required at this visit.  Collect trough before morning dose of study drug.  Study drug administration will occur in the clinic.  Subjects should refrain from eating 
8 hours before arriving at the clinic and 1 hour after study drug administration.  Cycle 2 Day 1 PK samples will only be collected from subjects in the Phase 1a Part 2 expansion 
food-effect cohort (See Section 7.7.1.2). 
e Timed PK:  Collect samples predose and 0.5, 1, 2, 4, and 6 hours postdose.  Study drug administration will occur in the clinic.  Subjects should refrain from eating 8 hours before 
arriving at the clinic and 1 hour after study drug administration.  Cycle 2 Day 1 PK samples will only be collected from subjects in the Phase 1a Part 2 expansion food-effect 
cohort (see Section 7.7.1.2).  
 
 
 
 
 
 
 
 
 
 
j Total urine will be collected over a 6-hour interval after study drug administration for Phase 1a only (see Section 7.7.2). 


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Table 4: 
Schedule of Assessments for Phase 1b/Cohort A Combination Therapy (Gemcitabine and nab-Paclitaxel) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Follow-Up Phase 
Cycle 1 
Subsequent 
Cycles  
(± 3 Days) 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 22 
± 3 Days Day 1 
Days 8 
and 15 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weighta 
7.4.2, 7.4.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG 
7.4.5 
X 
Xb 
 
Xb 
 
X 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
CT or MRI 
7.5.1 
X 
 
 
 
 
Xc 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
X 
 
 
 
 
 
INCB052793 dose at sited 
7.9.1 
 
X 
X 
X 
 
 
 
 
 
 
 
Administration of nab-paclitaxel  
7.9.5 
 
X 
X 
X 
 
X 
X 
 
 
 
 
Administration of gemcitabine  
7.9.6 
 
X 
X 
X 
 
X 
X 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
X 
a Comprehensive physical examination at screening; targeted physical examination thereafter.  Body weight will be taken at each visit.  Height will be measured at screening only. 
b Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; triplicate ECGs will be performed predose and 1 and 2 hours postdose on both Cycle 1 Day 1 
and Day 15.  
c A CT (chest, abdomen, and pelvis) or MRI will be conducted every 8 weeks.  Treatment cycles may be delayed; therefore, tumor assessments may be delayed as well to 
synchronize with treatment cycles.  Visit window is ± 10 days. 
d Study drug will be administered in a fasted state of 2 hours predose and 1 hour postdose with the following exception:  on days with PK 
 sampling, subjects will fast 
8 hours before and 1 hour after study drug administration. 


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Table 5: Laboratory Assessments for Phase 1b/Cohort A Combination Therapy (Gemcitabine and nab-Paclitaxel) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Safety 
Follow-Up 
Cycle 1 
Subsequent Cycles 
(± 3 Days) 
Day 
-28 to -1 
Day 1 
Day 8 
Day 15 
Day 22 
Day 1 
Days 8 
and 15 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
 
 
 
 
X 
 
X 
 
Urinalysisb 
7.4.6.5 
X 
 
 
 
 
X 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyc 
7.4.6.6 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)d 
7.7.1 
 
X 
X 
X 
 
 
 
 
 
PK plasma TIMEDe 
7.7.1 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Study drug, gemcitabine, and nab-paclitaxel should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and at EOT. 
c For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy 
tests can be done throughout the course of the study at the investigator's discretion. 
d Predose collection of PK trough on Cycle 1 Day 1, 8, and 15. 
e Collect PK timed samples at 0.5, 1, 2, 3, and 5 hours after the start of nab-paclitaxel and gemcitabine infusion.  See Section 7.7.1.3 for specific instructions on timings after 
nab-paclitaxel and gemcitabine administration. 
 
  
  
 
 


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Table 6: 
Schedule of Assessments for Phase 1b/Cohort B Combination Therapy (Dexamethasone) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Follow-Up Phase 
Cycle 1 
Subsequent 
Cycles 
(± 3 Days) 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 22 
± 3 Days Day 1 Day 15a 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightb 
7.4.2, 7.4.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGc 
7.4.5 
X 
Xc 
 
Xc 
 
X 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
X 
 
X 
X 
 
 
MM disease assessmentd 
7.4.6.8, 
7.5.2 
X 
X 
 
 
 
X 
 
X 
 
 
 
Bone marrow examinatione 
7.5.4 
X 
X (confirming CR) 
 
 
 
 
Skeletal surveyf 
7.5.6 
X 
X (investigator discretion) 
 
 
 
 
Tumor tissue biopsyg 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
X 
 
 
 
 
 
INCB052793 dose at siteh 
7.9.1 
 
X 
X 
 
 
 
 
 
 
 
 
Administration of dexamethasonei 
7.9.7 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
X 
a Day 15 assessments not required from Cycle 4 onward. 
b Comprehensive physical examination at screening; targeted physical examination thereafter.  Body weight will be taken at each visit corresponding with a physical examination.  
Height will be measured at screening only. 
c Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; triplicate ECGs will be performed predose and 1 and 2 hours postdose on both Cycle 1 Day 1 
and Day 15. 


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d Multiple myeloma disease assessments as per Section 7.4.6.8 should be performed at screening, Day 1 of each cycle (± 7 days) for the first 12 months of study participation 
followed by every 12 weeks (every 3 cycles), and EOT.  If the screening MM disease assessment is performed within 7 days of Cycle 1 Day 1, it does not need to be repeated. 
e A bone marrow examination should be conducted at screening and only if confirming a CR unless otherwise clinically indicated.  Fluorescence in situ hybridization and 
cytogenetic testing should be performed when feasible, as per institutional standard. 
f Skeletal survey should be conducted at screening and subsequently at the discretion of the investigator. 
g A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
h Study drug will be administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 Day 15), 
when subjects will fast 8 hours before and 1 hour after study drug administration. 
i Dexamethasone will be administered at a starting dose of 40 mg administered orally weekly on Days 1, 8, 15, and 22 of each 28-day cycle.  Administration should take place in 
the clinic for all Cycle 1 doses and for all subsequent doses that correspond to a scheduled study visit (ie, Days 1 and 15 of each cycle); all other doses will be self-administered. 


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Table 7: 
Laboratory Assessments for Phase 1b/Cohort B Combination Therapy (Dexamethasone) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Safety 
Follow-Up 
Cycle 1 
Subsequent Cycles 
(± 3 Days) 
Day 
-28 to -1 
Day 1 
Day 8 
Day 15 
Day 22 
Day 1 
Day 15 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
 
 
 
 
X 
 
X 
 
Urinalysisb 
7.4.6.5 
X 
 
 
 
 
X 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyc 
7.4.6.6 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)d 
7.7.1 
 
X 
X 
X 
 
 
 
 
 
PK plasma TIMEDe 
7.7.1 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a INCB052793 and dexamethasone should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1 and every third cycle thereafter (7, 10, etc); and at EOT. 
c For women of childbearing potential, serum pregnancy testing should be performed at screening, on Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine 
pregnancy tests can be done throughout the course of the study at the investigator's discretion.  
d Predose collection of PK on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15. 
e Collect PK timed samples at 0.5, 1, 2, 4, and 8 hours after dexamethasone administration.  Study drug administration should be simultaneous with dexamethasone dosing at 
Cycle 1 Day 1 and Cycle 1 Day 15.  
f Collect before dexamethasone administration on Cycle 1 Day 1.  Subsequently, PD plasma samples will be collected on Cycle 2 Day 1, Cycle 4 Day 1, and every fourth cycle 
thereafter without regard to food or study drug dosing. 
g Whole blood for biomarkers will be collected on Cycle 1 Day 1 (predose), Cycle 2 Day 1, and Cycle 4 Day 1. 


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Table 8: 
Schedule of Assessments for Phase 1b/Cohort C Combination Therapy (Carfilzomib) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase 
(± 1 Day)a 
(28-Day Cycles) 
EOT 
Follow-Up Phase 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day -28 
to -1 
Day  1 Day  2 Day 8 Day  9 Day 15 Day 16 Day 22b 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightc 
7.4.2, 
7.4.3 
X 
X 
 
X 
 
Xc 
 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGd 
7.4.5 
X 
Xd 
 
 
 
Xd 
 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
MM disease assessmente 
7.4.6.8, 
7.5.2 
X 
X 
 
 
 
 
 
 
X 
 
 
 
Bone marrow examinationf 
7.5.4 
X 
X (confirming CR) 
 
 
 
 
Skeletal surveyg 
7.5.6 
X 
X (investigator discretion) 
 
 
 
 
Tumor tissue biopsyh 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
 
 
 
 
 
 
 
INCB052793 dose at sitei,j 
7.9.1 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Administration of carfilzomibk 
7.9.8 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Administration of dexamethasonel 
7.9.7 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
 
X 
 
X 
 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
 
X 
 
X 
 
 
X 
 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
 
X 
a After 12 treatment cycles, subjects will receive maintenance dosing on Days 1, 2, 15, and 16 of each 28-day cycle.  No visits or assessments will be required on Day 8 or 9. 
b Day 22 assessments are performed in Cycle 1 only. 
c Comprehensive physical examination at screening; targeted physical examination thereafter.  Day 15 physical examination not required from Cycle 4 onward.  Body weight will 
be taken at each visit corresponding with a physical examination.  Height will be measured at screening only. 
d Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; triplicate ECGs will be performed predose and 1 and 2 hours postdose on both Cycle 1 Day 1 
and Day 15. 


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e Multiple myeloma disease assessments as per Section 7.4.6.8 should be performed at screening, Day 1 of each cycle (± 7 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. 
f A bone marrow examination should be conducted at screening and only if confirming a CR unless otherwise clinically indicated.  Fluorescence in situ hybridization and 
cytogenetic testing should be performed, when feasible, as per institutional standard. 
g Skeletal survey should be conducted at screening and subsequently at the discretion of the investigator. 
h A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
i Study drug will be self-administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 
Day 15), when subjects will fast 8 hours before and 1 hour after study drug administration. 
j Dosing at site only required during Cycle 1. 
k Carfilzomib will be administered on Days 1, 2, 8, 9, 15, and 16 of each 28-day treatment cycle as specified in Section 5.1.2.5.  From Cycle 4 onward, subjects are only required 
to receive carfilzomib at the investigative site on Day 1 of each cycle.  All other carfilzomib doses and study assessments may be performed at a local clinic.  Data from local 
clinic assessments do not need to be entered into the CRF. 
l If disease progression occurs after 1 or more cycles or if a response has not been achieved after 4 cycles (ie, stable disease), dexamethasone 40 mg self-administered orally 
weekly (Days 1, 8, 15, and 22 of each cycle) may be added to the regimen and continued until study withdrawal. 


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Table 9: 
Laboratory Assessments for Phase 1b/Cohort C Combination Therapy (Carfilzomib) 
Local Laboratory Tests 
Protocol Section 
Screening 
Phase 
Treatment Phase 
(28-Day Cycles) 
EOT 
Safety 
Follow-Up 
Day 
-28 to -1 
Day 1 
Day 8 
Day 15 
Day 22a 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
Hematologyb 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelc 
7.4.6.4 
X 
Xc 
 
 
 
X 
 
Urinalysisc 
7.4.6.5 
X 
Xc 
 
 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyd 
7.4.6.6 
X 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)e 
7.7.1 
 
X 
X 
X 
 
 
 
PK plasma TIMEDf 
7.7.1 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
a Day 22 assessments are performed in Cycle 1 only; visit window is ± 2 days. 
b INCB052793 and carfilzomib should be held on clinic visit days until after the hematology sample is obtained. 
c Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycle 7, 10, etc); and at EOT. 
d For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy 
tests can be done throughout the course of the study at the investigator's discretion. 
e Predose collection of PK on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15. 
f Collect PK timed samples at 5 minutes, 0.5, 1, 2, 4, and 8 hours after the end of the carfilzomib administration.  Study drug dose should be simultaneous with the beginning of 
the carfilzomib administration at Cycle 1 Day 1 and Cycle 1 Day 15. 
 
 
 
 


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Table 10: 
Schedule of Assessments for Phase 1b/Cohort D Combination Therapy (Bortezomib) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase 
Cycles 1-8 (21-Day Cycles) 
(± 2 Days)a 
Maintenance 
Phaseb  
(± 3 Days) 
EOT 
Follow-Up Phase 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day 1 
Day  4 
Day 8 
Day 11 
Every 2 
Weeks 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightc 
7.4.2, 
7.4.3 
X 
X 
 
Xc 
 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGd 
7.4.5 
X 
X 
 
X 
 
X 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
X 
X 
X 
 
 
MM disease assessmente 
7.4.6.8, 
7.5.2 
X 
X 
 
 
 
X 
X 
 
 
 
Bone marrow examinationf 
7.5.4 
X 
X (confirming CR) 
 
 
 
 
Skeletal surveyg 
7.5.6 
X 
X (investigator discretion) 
 
 
 
 
Tumor tissue biopsyh 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
X 
 
 
 
 
INCB052793 dose at sitei,j 
7.9.1 
 
X 
 
X 
 
 
 
 
 
 
Administration of bortezomibk 
7.9.9 
 
X 
X 
X 
X 
X 
 
 
 
 
Administration of dexamethasonel 
7.9.7 
 
X 
 
X 
 
X 
 
 
 
 
Assess compliance 
7.9.14 
 
 
X 
X 
X 
X 
 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
X 
a From Cycle 4 onward, subjects are only required to receive bortezomib at the investigative site on Day 1 of each cycle.  All other bortezomib doses and study assessments may 
be performed at a local clinic.  Data from local clinic assessments do not need to be entered into the CRF. 
b After 8 cycles of bortezomib, subjects may initiate maintenance dosing at a schedule of once every 2 weeks, as per Section 5.1.2.6. 


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c Comprehensive physical examination at screening; targeted physical examination thereafter.  Day 8 physical examination is not required from Cycle 4 onward.  Body weight will 
be taken at each visit corresponding with a physical examination.  Height will be measured at screening only. 
d Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; triplicate ECGs will be performed predose and 1 and 2 hours postdose on both Cycle 1 Day 1 
and Day 8. 
e Multiple myeloma disease assessments as per Section 7.4.6.8 should be performed at screening, Day 1 of each cycle, every 4 weeks during the maintenance phase, and EOT.  If 
screening MM disease assessment is performed within 7 days of Cycle 1 Day 1, it does not need to be repeated. 
f A bone marrow examination should be conducted at screening and only if confirming a CR unless otherwise clinically indicated.  Fluorescence in situ hybridization and 
cytogenetic testing should be performed, when feasible, as per institutional standard. 
g Skeletal survey should be conducted at screening and subsequently at the discretion of the investigator. 
h A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
i Study drug will be self-administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 
Day 8), when subjects will fast 8 hours before and 1 hour after study drug administration. 
j Dosing at site only required during Cycle 1. 
k Bortezomib will be administered on Days 1, 4, 8, and 11 of each 21-day treatment cycle for up to 8 cycles as specified in Section 5.1.2.6.  Subsequently, subjects may transition 
to maintenance dosing every other week. 
l If disease progression occurs after 1 or more cycles or if a response has not been achieved after 4 cycles (ie, stable disease), dexamethasone at 40 mg self-administered orally 
weekly (Day 1, Day 8, and Day 15 of each cycle) may be added to the regimen and continued until study withdrawal. 


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CONFIDENTIAL 
Table 11: 
Laboratory Assessments for Phase 1b/Cohort D Combination Therapy (Bortezomib) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase 
(Cycles 1-8) (21-Day Cycles) 
Maintenance 
Phase 
EOT 
Safety 
Follow-Up 
Day -28  
to -1 
Day 1 
Day 4 
Day 8 
Day 11 
Every 
2 Weeks 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
X 
 
 
 
X 
X 
 
Urinalysisb 
7.4.6.5 
X 
X 
 
 
 
X 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
 
X 
 
X 
X 
X 
Serum pregnancyc 
7.4.6.6 
X 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)d 
7.7.1 
 
X 
 
X 
 
 
 
 
PK plasma TIMEDe 
7.7.1 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a INCB052793 and bortezomib should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening, Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc) during the treatment phase and 
every 6 weeks during the maintenance phase; and at EOT. 
c For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2) during the treatment phase, every 
6 weeks during the maintenance phase, and EOT.  Local urine pregnancy tests can be done throughout the course of the study at the investigator's discretion. 
d Predose collection of PK trough on Cycle 1 Day 1 and Cycle 1 Day 8. 
e Collect PK timed samples at 5 minutes, 0.5, 1, 2, 4, 6, and 8 hours after bortezomib administration.  Study drug should be administered immediately before the bortezomib dose 
at Cycle 1 Day 1 and Cycle 1 Day 8. 
 
 
 
 
 
 


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CONFIDENTIAL 
Table 12: 
Schedule of Assessments for Phase 1b/Cohort E Combination Therapy (Lenalidomide) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Follow-Up Phase 
Cycle 1 
Subsequent 
Cycles  (± 3 
Days) 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 22 
± 3 Days Day 1 Day 15a 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightb 
7.4.2, 7.4.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGc 
7.4.5 
X 
Xb 
 
Xb 
 
X 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
X 
 
X 
X 
 
 
MM disease assessmentd 
7.4.6.8, 7.5.2 
X 
X 
 
 
 
X 
 
X 
 
 
 
Bone marrow examinatione 
7.5.4 
X 
X (confirming CR) 
 
 
 
 
Skeletal surveyf 
7.5.6 
X 
X (investigator discretion) 
 
 
 
 
Tumor tissue biopsyg 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
X 
 
 
 
 
 
INCB052793 dose at siteh 
7.9.1 
 
X 
X 
X 
 
 
 
 
 
 
 
Administration of lenalidomide 
at sitei 
7.9.10 
 
X 
X 
X 
 
 
 
 
 
 
 
Administration of dexamethasonej 
7.9.7 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
X 
a Day 15 assessments not required from Cycle 4 onward. 
b Comprehensive physical examination at screening; targeted physical examination thereafter.  Body weight will be taken at each visit corresponding with a physical examination.  
Height will be measured at screening only. 


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CONFIDENTIAL 
c Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; triplicate ECGs will be performed predose and 1 and 2 hours postdose on both Cycle 1 Day 1 
and Day 15. 
d Multiple myeloma disease assessments as per Section 7.4.6.8 should be performed at screening, Day 1 of each cycle (± 7 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. 
e A bone marrow examination should be conducted at screening and only if confirming a CR unless otherwise clinically indicated.  Fluorescence in situ hybridization and 
cytogenetic testing should be performed, when feasible, as per institutional standard. 
f Skeletal survey should be conducted at screening and subsequently at the discretion of the investigator. 
g A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
h Study drug will be administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 Day 15), 
when subjects will fast 8 hours before and 1 hour after study drug administration. 
i Lenalidomide will be administered orally QD on Days 1 to 21 of each 28-day cycle, as per Section 5.1.2.7.  Administration should take place in the clinic for all Cycle 1 doses 
(ie, Cycle 1 Day 1, Day 8, and Day 15); all other doses will be self-administered. 
j If disease progression occurs after 1 or more cycles or if a response has not been achieved after 4 cycles (ie, stable disease), dexamethasone at 40 mg self-administered orally 
weekly (Days 1, 8, 15, and 22) may be added to the regimen and continued until study withdrawal. 


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CONFIDENTIAL 
Table 13: 
Laboratory Assessments for Phase 1b/Cohort E Combination Therapy (Lenalidomide) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Safety 
Follow-Up 
Cycle 1 
Subsequent Cycles 
(± 3 Days) 
Day 
-28 to -1 
Day 1 
Day 8 
Day 15 
Day 22 
Day 1 
Day 15 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
 
 
 
 
X 
 
X 
 
Urinalysisb 
7.4.6.5 
X 
 
 
 
 
X 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum/urine pregnancyc 
7.4.6.6 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)d 
7.7.1 
 
X 
X 
X 
 
 
 
 
 
PK plasma TIMEDe 
7.7.1 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a INCB052793 and lenalidomide should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and at EOT. 
c For women of childbearing potential, serum pregnancy testing will be performed 10 to 14 days before the anticipated initiation of treatment, weekly during Cycle 1, on Day 1 of 
each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy tests are required at Cycle 1 Day 1 and may be repeated throughout the course of the study at the 
investigator's discretion. 
d Predose collection of PK on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15. 
e Collect PK timed samples at 0.5, 1, 2, 4, and 8 hours after lenalidomide administration.  Study drug administration should be simultaneous with lenalidomide dosing at Cycle 1 
Day 1 and Cycle 1 Day 15. 
 
 
 
 


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Table 14: 
Schedule of Assessments for Phase 1b/Cohort F Combination Therapy (Azacitidine) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (All Cycles) 
(± 1 Day) (28-Day Cycles)a 
EOT 
Follow-Up Phase 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day 
5 
Day 
8 
Day 
9 
Day 
15 
Day 
22b 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightc 
7.4.2, 
7.4.3 
X 
X 
 
 
 
 
Xc 
 
Xc 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGd 
7.4.5 
X 
Xd 
 
 
 
Xd 
 
 
 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
AML/MDS disease assessmente 
7.5.2 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
Bone marrow examinationf 
7.5.4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunophenotypingg 
7.5.5 
X 
X (confirming CR) 
 
 
 
 
Tumor tissue biopsyh 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
INCB052793 dose at sitei 
7.9.1 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
Administration of azacitidinej 
7.9.11 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
a From Cycle 4 onward, subjects are only required to receive azacitidine at the investigative site on Day 1 of each cycle.  All other azacitidine doses and study assessments may be 
performed at a local clinic.  Day 15 assessments are not required beginning with Cycle 4.  Data from local clinic assessments do not need to be entered into the CRF. 
b Day 22 assessments are performed in Cycle 1 only. 
c Comprehensive physical examination at screening; targeted physical examination thereafter.  Day 8 and 15 physical examination is not required from Cycle 4 onward.  Body 
weight will be taken at each visit corresponding with a physical examination.  Height will be measured at screening only. 


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d Electrocardiograms will be performed at screening, Days 1 and 5 of Cycle 1, Day 1 of each subsequent cycle, and EOT; triplicate ECGs will be performed predose and 1 and 
2 hours postdose on both Cycle 1 Day 1 and Day 5. 
e AML/MDS response assessments should be performed at screening, on Day 1 (± 7 days) of each cycle for the first 12 months of the study participation followed by every 
12 weeks (every 3 cycles), and EOT.  If screening disease assessment is performed within 7 days of Cycle 1 Day 1, it does not need to be repeated. 
f A bone marrow examination will be conducted approximately 3, 6, and 12 months after Day 1 and then every 12 months on the nearest Cycle Day 1 (± 2 days) after the first dose 
of treatment and as clinically indicated.  Fluorescence in situ hybridization and cytogenetic testing should be performed, when feasible, as per institutional standard. 
g Immunophenotyping should be performed at screening, Cycle 2 Day 1, and to confirm a CR. 
h A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
i Study drug will be self-administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 
Day 5), when subjects will fast 8 hours before and 1 hour after study drug administration in the clinic. 
j Azacitidine will be administered at a dose of 75 mg/m2 SC for 5 days, followed by 2 days of no treatment, then 75 mg/m2 for 2 days of each 28-day treatment cycle.  Intravenous 
administration is allowed if SC administration is not tolerated. 
k After 12 months of study participation, study assessments are conducted every 12 weeks/3 cycles.   
 


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Table 15: 
Laboratory Assessments for Phase 1b/Cohort F Combination Therapy (Azacitidine) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Safety Follow-Up 
Day 
-28 to -1 
Day 1 
Day 5 
Day 8 
Day 15 
Day 22a 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyb 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelc 
7.4.6.4 
X 
Xc 
 
 
 
 
X 
 
Urinalysisc 
7.4.6.5 
X 
Xc 
 
 
 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyd 
7.4.6.6 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)e 
7.7.1 
 
X 
X 
 
 
 
 
 
PK plasma TIMEDf 
7.7.1 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Day 22 assessments are performed in Cycle 1 only; visit window is ± 2 days. 
b INCB052793 and azacitidine should be held on clinic visit days until after the hematology sample is obtained. 
c Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and at EOT. 
d For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy 
tests can be done throughout the course of the study at the investigator's discretion. 
e Predose collection of PK on Cycle 1 Day 1 and Cycle 1 Day 5. 
f Collect PK timed samples at 5 minutes, 0.5, 1, 2, 4, and 8 hours after azacitidine administration.  Study drug dose should be simultaneous with the beginning of the azacitidine 
administration at Cycle 1 Day 1 and Cycle 1 Day 5. 
 
 
 
 


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Table 16:  
Schedule of Assessments for Phase 1b/Cohort G Combination Therapy (Pomalidomide/Dexamethasone) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Follow-Up Phase 
Cycle 1 
Subsequent 
Cycles 
(± 3 Days) 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 22 
± 3 Days 
Day 1 
Day 15a 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightb 
7.4.2, 
7.4.3 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGc 
7.4.5 
X 
Xb 
 
Xb 
 
X 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
X 
 
X 
X 
 
 
MM disease assessmentd 
7.4.6.8, 
7.5.2 
X 
X 
 
 
 
X 
 
X 
 
 
 
Bone marrow examinatione 
7.5.4 
X 
X (confirming CR) 
 
 
 
 
Skeletal surveyf 
7.5.6 
X 
X (investigator discretion) 
 
 
 
 
Tumor tissue biopsyg 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
X 
 
 
 
 
 
INCB052793 dose at siteh 
7.9.1 
 
X 
X 
X 
 
 
 
 
 
 
 
Administration of pomalidomide 
at sitei 
7.9.12 
 
X 
 
X 
 
 
 
 
 
 
 
Administration of dexamethasone 
at sitej 
7.9.7 
 
X 
X 
X 
X 
 
 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
X 
X 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
X 
a Day 15 assessments not required from Cycle 4 onward. 
b Comprehensive physical examination at screening; targeted physical examination thereafter.  Body weight will be taken at each visit corresponding with a physical examination.  
Height will be measured at screening only. 


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c Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; triplicate ECGs will be performed predose and 1 and 2 hours postdose on both Cycle 1 Day 1 
and Day 15. 
d Multiple myeloma disease assessments as per Section 7.4.6.8 should be performed at screening, Day 1 of each cycle (± 7 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. 
e A bone marrow examination should be conducted at screening and only if confirming a CR unless otherwise clinically indicated.  Fluorescence in situ hybridization and 
cytogenetic testing should be performed, when feasible, as per institutional standard. 
f Skeletal survey should be conducted at screening and subsequently at the discretion of the investigator. 
g A bone marrow aspirate sample is required at baseline.  A fresh bone marrow examination (including aspirate) must be performed before first study drug dose.  An optional bone 
marrow aspirate may be obtained at any time during the study, if a bone marrow examination is otherwise performed to assess disease status. 
h Study drug will be administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 Day 15), 
when subjects will fast 8 hours before and 1 hour after study drug administration. 
i Pomalidomide will be administered orally QD on Days 1 to 21 of each 28-day cycle, as per Section 5.1.2.9.  Administration should take place in the clinic at Cycle 1 Day 1, and 
Day 15; all other doses will be self-administered. 
j Dexamethasone will be administered at a starting dose of 40 mg orally on a weekly basis on study Days 1, 8, 15, and 22 of each 28-day cycle.  Administration should take place 
in the clinic at Cycle 1 Day 1, Day 8, Day 15, and Day 22; all other doses will be self-administered. 


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Table 17: 
Laboratory Assessments for Phase 1b/Cohort G Combination Therapy (Pomalidomide/Dexamethasone) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles) 
EOT 
Safety 
Follow-Up 
Cycle 1 
Subsequent Cycles 
(± 3 Days) 
Day 
-28 to -1 
Day 1 
Day 8 
Day 15 
Day 22 
Day 1 
Day 15 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
 
 
 
 
X 
 
X 
 
Urinalysisb 
7.4.6.5 
X 
 
 
 
 
X 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
 
Central Laboratory Samples 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum/urine pregnancyc 
7.4.6.6 
X 
X 
X 
X 
X 
X 
 
X 
 
PK plasma trough (predose)d 
7.7.1 
 
X 
X 
X 
 
 
 
 
 
PK plasma TIMEDe 
7.7.1 
 
X 
 
X 
 
 
 
 
 
a INCB052793, pomalidomide, and dexamethasone should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and at EOT. 
c For women of childbearing potential, serum pregnancy testing will be performed 10 to 14 days before the anticipated initiation of treatment, weekly during Cycle 1, on Day 1 of 
each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy tests are required at Cycle 1 Day 1 and may be repeated throughout the course of the study at the 
investigator's discretion. 
d Predose collection of PK on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15. 
e Collect PK timed samples at 0.5, 1, 2, 4, and 8 hours after pomalidomide administration.  Study drug administration should be simultaneous with pomalidomide dosing at 
Cycle 1 Day 1 and Cycle 1 Day 15. 
 
 
 
 


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Table 18: 
Schedule of Assessments for Phase 1b/Cohort H Combination Therapy (INCB052793 + INCB050465) 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase (21-Day Cycles) 
 
Follow-Up Phase 
Cycle 1 
Subsequent 
Cycles 
Safety 
Follow-Up 
Disease Status 
Follow-Up 
Survival 
Follow-Up 
Day -28  
to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 1 
± 3 Days 
EOT 
30-35 Days 
After EOTa 
Every 8 Weeks 
(± 7 Days) 
After EOT 
Every 
12 Weeks 
(± 7 Days) 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
Review inclusion/ exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightb 
7.4.2  
7.4.3 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
X 
X 
X 
 
 
12-lead ECGc 
7.4.5 
X 
X 
 
X 
X 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
X 
X 
X 
X 
Xc 
 
 
Bone marrow examinationd 
7.5.4 
X 
 
 
 
 
 
 
 
 
Lymph node biopsy/archival tissuee 
7.8.4 
X 
X 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
Efficacy/disease assessmentf 
7.5.2  
7.5.3 
X 
 
 
 
 
 
 
 
 
Review of AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 administer in clinicg 
7.9.1 
 
X 
X 
X 
 
 
 
 
 
INCB050465 administer in clinicg 
7.9.2 
 
X 
X 
X 
 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
X 
X 
X 
X 
 
 
 
Poststudy disease  status 
6.4.2 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
X 
a In addition to laboratory assessments at the safety follow-up visit, serum (1,3)-β-D-glucan will be assessed at 3 months ± 1 week after EOT. 
b Comprehensive physical examination at screening; targeted physical examination thereafter.  Body weight will be taken at each visit.  Height is measured at screening only. 
c Electrocardiograms will be performed at screening, Day 1 of each cycle, and EOT; timed triplicate ECGs will be performed predose and 1 and 2 hours postdose on Cycle 1 
Day 1 and Day 15.  The ECGs should be conducted before, but within 15 minutes of, the PK blood draw at the corresponding timepoint. 
d A bone marrow biopsy will be performed on all subjects at screening (with exceptions noted) as outlined in Section 7.5.4. 


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e A lymph node biopsy for genetic material will be collected on all subjects at screening.  Archival tissue may be submitted if available and if criteria in Section 7.8.4 are met 
(eg, archival tissue obtained after completion of last treatment regimen).  If a biopsy is performed during the treatment phase to assess disease status, to confirm response or 
progression, or if otherwise clinically indicated, a sample of the biopsy will optionally be provided to the sponsor. 
f Computed tomography, MRI, FDG-PET, and/or PET/CT (appropriate to histology) will be conducted every 6 weeks (every 2 cycles) until the subject enters into the disease 
status follow-up phase.  Treatment cycles may be delayed; therefore, tumor assessments may be delayed as well to synchronize with treatment cycles regardless if treatment is 
delayed due to safety (± 10-day window).  For subjects who discontinue treatment for reasons other than disease progression, every effort should be made to continue monitoring 
their disease status, including, if applicable, radiographic disease imaging until 1) start of new anticancer therapy, 2) documented disease progression, 3) death, or 4) the end of 
study, whichever comes first. 
g Study drug will be administered in a fasted state of 2 hours predose and 1 hour postdose with the following exception:  On days with PK 
 sampling, subjects will fast 
8 hours before and 1 hour after study drug administration.  Study drug should be administered in the clinic on days where there are PK 
 collections as outlined in 
Sections 7.7.1 and 7.8.  Otherwise, the study drug will be self-administered by the subject.  


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Table 19: 
Laboratory Assessments Phase 1b/Cohort H Combination Therapy (INCB052793 + INCB050465) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (21-Day Cycles) 
EOT 
Safety  
Follow-Up 
Cycle 1 
Subsequent Cycles 
(± 3 Days) 
Day -28 to -1 
Day 1 
Day 8 
± 3 Days 
Day 15 
± 3 Days 
Day 1 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
Hematologya 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelb 
7.4.6.4 
X 
 
 
 
X 
X 
 
Urinalysisb 
7.4.6.5 
X 
 
 
 
X 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
Central Laboratory Samples 
Serum (1,3)-β-D-glucanc 
 
X 
 
 
 
X 
X 
X 
Expanded serum chemistry 
7.4.6.2 
X 
X 
 
 
X 
X 
X 
Serum/urine pregnancyd 
7.4.6.6 
X 
 
 
 
X 
X 
 
PK TIMEDe, f 
7.7.1 
 
X 
 
X 
 
 
 
a INCB052793 and INCB050465 should be held on clinic visit days until after the hematology sample is obtained. 
b Urinalysis and coagulation panel are required at screening, Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles  7, 10, etc); and at EOT.  
c Serum (1,3)-β-D-glucan required at Day 1 of each cycle (from Cycle 2 onward), EOT, safety follow-up, and at 3 months ± 1 week after EOT.  
d For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy 
tests can be done throughout the course of the study at the investigator's discretion. 
e Day 1 and Day 15 (predose) and timed PK (see footnote f).  Collect trough before morning dose of study drug.  Study drug administration will occur in the clinic.  Subjects 
should refrain from eating 8 hours before arriving at the clinic and 1 hour after study drug administration. 
f Timed PK:  Collect samples predose and 0.5, 1, 2, 4, 6, and 8 hours postdose.  Study drug administration will occur in the clinic.  Subjects should refrain from eating 8 hours 
before arriving at the clinic and 1 hour after study drug administration. 
 
 
 
 
 
 
 
 


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Table 20: 
Schedule of Assessments for Phase 2/Cohort I (INCB052793 With Azacitidine) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (All Cycles) 
(± 1 Day) (28-Day Cycles)a 
EOT 
Follow-Up Phase 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day 
5 
Day 
8 
Day 
9 
Day 
15 
Day 
22b 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightc 
7.4.2, 
7.4.3 
X 
X 
 
 
 
 
Xc 
 
Xc 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGd 
7.4.5 
X 
Xd 
 
 
 
Xd 
 
 
 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
AML/MDS disease assessmente 
7.5.2 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
Bone marrow examinationf 
7.5.4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunophenotypingg 
7.5.5 
X 
X (confirming CR) 
 
 
 
 
Tumor tissue biopsyh 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
INCB052793 dispensing 
7.9.4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
INCB052793 dose at sitei 
7.9.1 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
Administration of azacitidinej 
7.9.11 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
a From Cycle 4 onward, subjects are only required to receive azacitidine at the investigative site on Day 1 of each cycle.  All other azacitidine doses and study assessments may be 
performed at a local clinic.  Day 15 assessments are not required beginning with Cycle 4.  Data from local clinic assessments do not need to be entered into the CRF. 
b Day 22 assessments are performed in Cycle 1 only. 
c Comprehensive physical examination at screening; targeted physical examination thereafter.  Day 8 and 15 physical examination is not required from Cycle 4 onward.  Body 
weight will be taken at each visit corresponding with a physical examination.  Height will be measured at screening only. 


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d Electrocardiograms will be performed at screening, Days 1 and 5 of Cycle 1, Day 1 of each subsequent cycle, and EOT; triplicate ECGs will be performed predose and 1 and 
2 hours postdose on both Cycle 1 Day 1 and Day 5. 
e AML/MDS response assessments should be performed at screening, on Day 1 (± 7 days) of each cycle for the first 12 months of the study participation followed by every 
12 weeks (every 3 cycles), and EOT.  If screening disease assessment is performed within 7 days of Cycle 1 Day 1, it does not need to be repeated. 
f A bone marrow examination will be conducted approximately 3, 6, and 12 months after Day 1 and then every 12 months on the nearest Cycle Day 1 (± 2 days) after the first dose 
of treatment and as clinically indicated.  Fluorescence in situ hybridization and cytogenetic testing should be performed, when feasible, as per institutional standard. 
g Immunophenotyping should be performed at screening, Cycle 2 Day 1, and to confirm a CR. 
h A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
i Study drug will be self-administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 
Day 5), when subjects will fast 8 hours before and 1 hour after study drug administration in the clinic. 
j Azacitidine will be administered at a dose of 75 mg/m2 SC for 5 days, followed by 2 days of no treatment, then 75 mg/m2 for 2 days of each 28-day treatment cycle.  Intravenous 
administration is allowed if SC administration is not tolerated. 
k After 12 months of study participation, study assessments are conducted every 12 weeks/3 cycles. 


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Table 21: 
Laboratory Assessments for Phase 2/Cohort I (INCB052793 With Azacitidine) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles)  
EOT 
Safety Follow-Up 
Day 
-28 to -1 
Day 1 
Day 5 
Day 8 
Day 15 
Day 22a 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyb 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelc 
7.4.6.4 
X 
Xc 
 
 
 
 
X 
 
Urinalysisc 
7.4.6.5 
X 
Xc 
 
 
 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyd 
7.4.6.6 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)e 
7.7.1 
 
X 
X 
 
 
 
 
 
PK plasma TIMEDf 
7.7.1 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Day 22 assessments are performed in Cycle 1 only; visit window is ± 2 days. 
b INCB052793 and azacitidine should be held on clinic visit days until after the hematology sample is obtained. 
c Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and at EOT. 
d For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy 
tests can be done throughout the course of the study at the investigator's discretion. 
e Predose collection of PK on Cycle 1 Day 1 and Cycle 1 Day 5. 
f Collect PK timed samples at 5 minutes, 0.5, 1, 2, 4, and 8 hours after azacitidine administration.  Study drug dose should be simultaneous with the beginning of the azacitidine 
administration at Cycle 1 Day 1 and Cycle 1 Day 5. 
 
 
 
 
 


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Table 22: 
Schedule of Assessments for Phase 2/Cohort J (Itacitinib With Azacitidine) 
Procedure 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (All Cycles) 
(± 1 Day) (28-Day Cycles)a 
EOT 
Follow-Up Phase 
Safety 
Follow-Up 
Disease 
Follow-Up 
Survival 
Follow-Up 
Day  
-28 to -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day 
5 
Day 
8 
Day 
9 
Day 
15 
Day 
22b 
30-35 Days 
After EOT 
Every 
8 Weeks 
Every 
12 Weeks 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review inclusion/exclusion criteria 
3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and medical history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.3.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examination/body weightc 
7.4.2, 
7.4.3 
X 
X 
 
 
 
 
Xc 
 
Xc 
X 
X 
X 
 
 
Vital signs 
7.4.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGd 
7.4.5 
X 
Xd 
 
 
 
Xd 
 
 
 
 
X 
 
 
 
Laboratory tests 
7.4.6 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
ECOG status 
7.6 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
AML/MDS disease assessmente 
7.5.2 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
Bone marrow examinationf 
7.5.4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunophenotypingg 
7.5.5 
X 
X (confirming CR) 
 
 
 
 
Tumor tissue biopsyh 
7.8.4 
X 
X 
 
 
 
 
Buccal swab 
7.8.5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review AEs 
7.4.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Itacitinib dispensing 
7.9.4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Itacitinib dose at sitei 
7.9.3  
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
Administration of azacitidinei 
7.9.11 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Assess compliance 
7.9.14 
 
X 
 
 
 
 
 
X 
X 
X 
X 
 
 
 
Distribute reminder cards 
7.9.15 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Poststudy disease status 
6.4.2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Survival follow-up 
6.4.3 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
a From Cycle 4 onward, subjects are only required to receive azacitidine at the investigative site on Day 1 of each cycle.  All other azacitidine doses and study assessments may be 
performed at a local clinic.  Day 15 assessments are not required beginning with Cycle 4.  Data from local clinic assessments do not need to be entered into the CRF. 
b Day 22 assessments are performed in Cycle 1 only. 
c Comprehensive physical examination at screening; targeted physical examination thereafter.  Day 8 and 15 physical examination is not required from Cycle 4 onward.  Body 
weight will be taken at each visit corresponding with a physical examination.  Height will be measured at screening only. 


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d Electrocardiograms will be performed at screening, Days 1 and 5 of Cycle 1, Day 1 of each subsequent cycle, and EOT; triplicate ECGs will be performed predose and 1 and 
2 hours postdose on both Cycle 1 Day 1 and Day 5. 
e AML/MDS response assessments should be performed at screening, on Day 1 (± 7 days) of each cycle for the first 12 months of the study participation followed by every 
12 weeks (every 3 cycles), and at EOT.  If screening disease assessment is performed within 7 days of Cycle 1 Day 1, it does not need to be repeated. 
f A bone marrow examination will be conducted approximately 3, 6, and 12 months after Day 1 and then every 12 months on the nearest Cycle Day 1 (± 2 days) after the first dose 
of treatment and as clinically indicated.  Fluorescence in situ hybridization and cytogenetic testing should be performed, when feasible, as per institutional standard. 
g Immunophenotyping should be performed at screening, Cycle 2 Day 1, and to confirm a CR. 
h A bone marrow aspirate sample is required at baseline.  An optional fresh bone marrow aspirate may be obtained at any time during the study, if a bone marrow examination is 
otherwise performed to assess disease status. 
i Study drug will be self-administered in a fasted state of 2 hours predose and 1 hour postdose with the exception of days with serial PK sampling (Cycle 1 Day 1 and Cycle 1 
Day 5), when subjects will fast 8 hours before and 1 hour after study drug administration in the clinic. 
j Azacitidine will be administered at a dose of 75 mg/m2 SC for 5 days, followed by 2 days of no treatment, then 75 mg/m2 for 2 days of each 28-day treatment cycle.  Intravenous 
administration is allowed if SC administration is not tolerated. 
k After 12 months of study participation, study assessments are conducted every 12 weeks/3 cycles. 


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Table 23: 
Laboratory Assessments for Phase 2/Cohort J (Itacitinib With Azacitidine) 
Local Laboratory Tests 
Protocol 
Section 
Screening 
Phase 
Treatment Phase (28-Day Cycles)  
EOT 
Safety Follow-Up 
Day 
-28 to -1 
Day 1 
Day 5 
Day 8 
Day 15 
Day 22a 
30-35 Days 
After EOT 
Serum chemistry 
7.4.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyb 
7.4.6.3 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panelc 
7.4.6.4 
X 
Xc 
 
 
 
 
X 
 
Urinalysisc 
7.4.6.5 
X 
Xc 
 
 
 
 
X 
 
Hepatitis serology 
7.4.6.7 
X 
 
 
 
 
 
 
 
Central Laboratory Samples 
 
 
 
 
 
 
 
 
 
Expanded serum chemistry  
7.4.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancyd 
7.4.6.6 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK plasma trough (predose)e 
7.7.1 
 
X 
X 
 
 
 
 
 
PK plasma TIMEDf 
7.7.1 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Day 22 assessments are performed in Cycle 1 only; visit window is ± 2 days. 
b Itacitinib and azacitidine should be held on clinic visit days until after the hematology sample is obtained. 
c Urinalysis and coagulation panel are required at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and at EOT. 
d For women of childbearing potential, serum pregnancy testing should be performed at screening, Day 1 of each cycle (beginning with Cycle 2), and EOT.  Local urine pregnancy 
tests can be done throughout the course of the study at the investigator's discretion. 
e Predose collection of PK on Cycle 1 Day 1 and Cycle 1 Day 5. 
f Collect PK timed samples at 5 minutes, 0.5, 1, 2, 4, and 8 hours after azacitidine administration.  Study drug dose should be simultaneous with the beginning of the azacitidine 
administration at Cycle 1 Day 1 and Cycle 1 Day 5. 
 
 
 
 


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Table 24: 
Laboratory Tests:  Required Analytes 
Serum Chemistry 
Serology 
Hematology 
Urinalysis 
Coagulation 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatinine 
Glucose 
LDH 
Magnesium 
Phosphate  
Potassium  
Sodium  
Total bilirubin 
Direct (conjugated) bilirubin 
(required only if total 
bilirubin is abnormal) 
Total serum protein 
Total cholesterol  
Triglycerides 
Hepatitis B surface 
antigen 
Anti-hepatitis Bc  
HBV-DNA 
Anti-hepatitis C  
HCV-RNA 
Hemoglobin 
Hematocrit 
Platelet count 
Red blood cell count 
WBC count 
Differential cell count 
(absolute and %): 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
• Reticulocytes 
Color/appearance 
pH 
Specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Blood 
Protein 
Microscopic analysis 
PT 
PTT 
INR 
OTHER 
MM subjects: 
1.  Beta-2 microglobulin 
2.  Serum protein electrophoresis 
including M-protein quantitation, 
urine protein electrophoresis 
including M-protein quantitation, 
quantitative immunoglobulins, 
serum free light chains 
 
Lymphoma and AML/MDS 
Subjects: 
Immunophenotyping  
 
Cohort H: 
Serum (1,3)-β-D-glucan 
Females Only 
Expanded 
Serum 
Chemistries 
Serum 
pregnancy 
 
CRP 
CRP = C-reactive protein; GGT = gamma glutamyl transferase; IgG = immunoglobulin G; INR = international normalized ratio; LDH = lactose dehydrogenase; PT = prothrombin 
time; PTT = partial thromboplastin time. 
Note:  Additional tests may be required, as agreed by investigator and sponsor, based on emerging safety data.


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6.1. 
Screening Phase 
The screening phase is the interval between the signing of the ICF and the day the subject is 
enrolled in the study (Cycle 1 Day 1).  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 phase.  The maximum screening period 
is 28 days. 
Results from the screening visit evaluations will be reviewed to confirm subject eligibility before 
randomization or the administration of study drug on Cycle 1 Day 1 of both Phase 1a 
monotherapy and Phase 1b and Phase 2 combination therapy.  Tests with results that fail 
eligibility requirements may be repeated once during the screening phase 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, after recovery from an infection). 
Additionally, baseline assessments of clinical condition and disease status will be determined 
during the screening phase.  Disease assessments appropriate to the type of malignancy will be 
performed and recorded in the CRF. 
6.2. 
Treatment Phase 
Treatment begins on the day that the subject is enrolled in the study and receives the first dose of 
study drugs; this is defined as Cycle 1 Day 1.  Dates for subsequent study visits will be 
determined based on this day and should occur within the allowable visit window of the 
scheduled date unless delayed for safety reasons.  At Cycle 1 Day 1, results from screening visit 
evaluations should be reviewed to determine if the subject continues to meet the eligibility 
requirements as specified in the Protocol. 
During the treatment phase, regular study visits (physician visits) will occur weekly during the 
first treatment cycle (ie, Days 1, 8, and 15 of Cycle 1) and thereafter at the beginning of each 
21-day treatment cycle for Phase 1a.  For Phase 1b, study visits will occur at the intervals 
specified in Table 2, Table 4, Table 6, Table 8, Table 10, Table 12, Table 14, Table 16, and 
Table 18 (as applicable to study phase and treatment cohort). Study visits occurring in Phase 2 
are specified in Table 20 and Table 22.  
At certain study visits as indicated in Table 2, Table 4, Table 6, Table 8, Table 10, Table 12, 
Table 14, Table 16, Table 18, Table 20, and Table 22, subjects will have fasted for at least 
8 hours, recorded the time of the previous study drug administration and time of last meal, and 
withheld the dose of the study drug.  At these visits, PK 
 sampling will be conducted. 
6.3. 
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 
will supersede those of that scheduled visit, and the data should be entered in the EOT page in 
the CRF.  The subject should be encouraged to return for the follow-up visits. 


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6.4. 
Follow-Up Phase 
6.4.1. 
Safety Follow-Up  
The safety follow-up phase is the interval between the EOT visit and the scheduled safety 
follow-up visit.  Adverse events and SAEs must be reported up until at least 30 days after the last 
dose of study drug, the date of the safety follow-up visit, or until study drug–related toxicities 
resolve, return to baseline, or are deemed irreversible, whichever is longer.  Reasonable efforts 
should be made to have the subject return for the follow-up visit and report any AEs that may 
occur during this phase. 
6.4.2. 
Disease Status Follow-Up 
Subjects who discontinue study treatment for a reason other than disease progression will move 
into the disease status follow-up phase and should be assessed at the intervals specified 
(± 1 week) in Table 2, Table 4, Table 6, Table 8, Table 10, Table 12, Table 14, Table 16, 
Table 18, Table 20, and Table 22 (as applicable to study phase and treatment cohort), utilizing 
the respective disease assessment criteria to monitor disease status.  Every effort should be made 
to collect information regarding disease status until: 
• The start of new antineoplastic therapy   
• Disease progression  
• Death  
• Withdrawal of consent 
• End of the study  
6.4.3. 
Survival Follow-Up 
Once a subject has confirmed disease progression or starts a new anticancer therapy, the subject 
moves into the survival follow-up phase and should be contacted by telephone, email, or visit at 
least every 12 weeks (± 1 week) to assess for survival status until death, withdrawal of consent, 
or the end of the study, whichever occurs first. 
6.5. 
Unscheduled Visits 
Unscheduled visits may occur at any time as medically warranted.  Any assessments performed 
during those visits should be recorded in the CRF. 
6.6. 
Early Termination 
The sponsor may terminate the study electively or if required by regulatory decision.  If the study 
is terminated prematurely, the sponsor will notify the investigators, the institutional review 
boards (IRBs) and/or independent ethics committees (IECs), and regulatory bodies of the 
decision and the reason for termination of the study. 


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7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
Required assessments/procedures listed here will be captured on the CRF. 
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 (see Appendix A).  Subjects who have standard-of-care procedures 
performed within a particular time frame outside of the screening window may not have to repeat 
these procedures, but only with the approval of the sponsor medical monitor. 
7.2. 
Interactive Response Technology Procedure 
Not applicable. 
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.  
Cohorts that include subjects with MM (Phase 1a/TGA and Phase 1b/Cohorts B through E and 
G) will also collect up to approximately 3 months of serum/urine m-protein and/or free light 
chain values (as applicable) that immediately precede the initiation of study treatment.  This will 
include complete documentation of the history of medical or surgical treatment for the 
malignancy under study. 
7.3.2. 
Prior and Concomitant Medications 
Prior and/or ongoing medications will be reviewed during screening to determine study 
eligibility and will continue to be recorded throughout the duration of the study.  The medication 
record will be maintained following enrollment, including any changes to the dose or regimen.  
Prior/concomitant medications include any prescription, over-the-counter, or natural/herbal 
preparations taken or administered during 30 days before Cycle 1 Day 1 and throughout the 
study period through safety follow-up. 
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 for the occurrence of AEs 
through the safety follow-up visit.  Treatment-emergent AEs will be referred to as AEs that occur 


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from day of study drug administration.  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 CRFs regardless of the assumption of 
a causal relationship with the study drug.  The definition, reporting, and recording requirements 
for AEs are described in Section 8. 
7.4.2. 
Comprehensive Physical Examination 
A comprehensive physical examination will be performed at the times indicated in the Schedule 
of Assessments (Table 2, Table 4, Table 6, Table 8, Table 10, Table 12, Table 14, Table 16, 
Table 18, Table 20, and Table 22).  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.  The 
screening assessment should also include a measurement of height and body weight.  Body 
weight should be collected at each visit.  Spleen measurements for applicable tumor types may 
be obtained from either scan or manual measurements.  However, the procedure for 
measurement must remain consistent throughout the study.  Measurements will be captured in 
the CRF. 
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(s) of the 
body systems or organs, as indicated by subject symptoms, AEs, or other findings.   
7.4.4. 
Vital Signs 
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. 
7.4.5. 
Electrocardiograms 
Single 12-lead ECGs will be conducted at screening, Day 1 of each cycle, and EOT.  In addition, 
timed ECGs will be conducted in Phase 1a (see Section 7.4.5.1) and Phase 1b and Phase 2 (see 
Section 7.4.5.2).  All 12-lead ECGs will be performed with the subject in a recumbent or 
semirecumbent position after 5 minutes of rest.  The 12-lead ECGs may be interpreted by the 
investigator at the site and used for immediate subject management.  The decision to include or 
exclude a subject or withdraw a subject from the study based on an ECG flagged as "Abnormal, 
Clinically Meaningful" is the responsibility of the investigator in consultation with the sponsor's 
medical monitor, as appropriate.  All ECGs will be collected and analyzed centrally.  
7.4.5.1. 
Phase 1a Monotherapy Timed ECG  
In both TGA and TGB, triplicate ECGs will be performed predose and 1 and 2 hours postdose on 
Cycle 1 Day 1 and Cycle 1 Day 15.  The third (last) of the triplicate ECGs should be completed 


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before, but within, 15 minutes of the PK blood draw at the corresponding timepoint, where 
applicable.  Where a timed ECG assessment does not correlate with a PK blood draw, it can be 
completed within ± 15 minutes of the target timepoint.  The specified postdose timepoint may be 
adjusted based on emerging PK data. 
7.4.5.2. 
Phase 1b and Phase 2 Combination Therapy Timed ECG 
Triplicate ECGs will be performed predose and 1 and 2 hours postdose on Cycle 1 Day 1 and 
Day 15 (Phase 1b Cohorts A, B, C, E, G, and H), Cycle 1 Day 1 and Day 5 (Phase 1b Cohort F 
and Phase 2 Cohorts I and J), and Cycle 1 Day 1 and Day 8 (Phase 1b Cohort D).  The third (last) 
of the triplicate ECGs should be completed before, but within, 15 minutes of the PK blood draw 
at the corresponding timepoint, where applicable.  Where a timed ECG assessment does not 
correlate with a PK blood draw, it can be completed within ± 15 minutes of the target timepoint.  
The specified postdose timepoint may be adjusted based on emerging PK data. 
7.4.6. 
Laboratory Assessments 
A laboratory local to the study site and subject may perform all clinical laboratory assessments 
for safety (eg, serum chemistry and hematology assessments, urinalysis, serology) as well as the 
MM response and immunophenotyping assessments.  A central laboratory will perform the 
serum pregnancy tests at screening and the expanded serum chemistry testing throughout the 
study.  The investigative site will enter the local safety laboratory results and laboratory normal 
ranges into the CRF.  All local laboratory assessments should be performed using standard 
procedures on the days indicated in Table 3, Table 5, Table 7, Table 9, Table 11, Table 13, 
Table 15, Table 17,Table 19, Table 21, and Table 23 (as applicable to study phase and treatment 
cohort).  Table 24 lists the required laboratory tests.  Additional tests may be performed if 
clinically indicated. 
7.4.6.1. 
Chemistry 
A panel of standard serum chemistries and expanded serum chemistries will be performed as 
indicated in Table 3, Table 5, Table 7, Table 9, Table 11, Table 13, Table 15, Table 17, Table 19, 
Table 21, and Table 23 (as applicable to study phase and treatment cohort); required analytes for 
this panel are listed in Table 24. 
7.4.6.2. 
Expanded Chemistry 
Serum markers of nutritional and systemic inflammatory response status will be performed as 
outlined in Table 3, Table 5, Table 7, Table 9, Table 11, Table 13, Table 15, Table 17, and 
Table 19, Table 21, and Table 23 (as applicable to study phase and treatment cohort).  A list of 
required analytes is found in Table 24.  Expanded serum chemistries will be performed from 
blood samples collected without respect to food intake (ie, nonfasted). 
7.4.6.3. 
Hematology 
Hematology will be performed as indicated in Table 3, Table 5, Table 7, Table 9, Table 11, 
Table 13, Table 15, Table 17, Table 19, Table 21, and Table 23 (as applicable to study phase and 
treatment cohort); required analytes are listed in Table 24.  Subjects will take study drug at the 


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clinic after the hematology sample is drawn on clinic days when a hematology sample is 
obtained. 
7.4.6.4. 
Coagulation Panel 
A coagulation panel including PT and INR will be measured at screening; Cycle 2 Day 1, 
Cycle 4 Day 1, and every third cycle thereafter (Cycles 7, 10, etc); and EOT.  Subjects who are 
taking anticoagulant therapy will be monitored per local institutional guidelines. 
7.4.6.5. 
Urinalysis 
Complete urinalysis will be performed at screening; Cycle 2 Day 1, Cycle 4 Day 1, and every 
third cycle thereafter (Cycles  7, 10, etc); and at EOT, as indicated in Table 3, Table 5, Table 7, 
Table 9, Table 11, Table 13, Table 15, Table 17,Table 19, Table 21, and Table 23 (as applicable 
to study phase and treatment cohort); required analyses are listed in Table 24. 
7.4.6.6. 
Pregnancy Testing 
A serum pregnancy test will be required for all female subjects of childbearing potential at 
screening, Day 1 of each cycle starting with Cycle 2 (Phase 1b and Phase 2), and EOT.  
Phase 1b/Treatment Cohort E will have weekly serum pregnancy testing performed during 
Cycle 1.  Subsequently, urine pregnancy tests will be conducted only as medically indicated or 
per country-specific requirements.  Urine pregnancy tests will be performed locally. 
7.4.6.7. 
Serology 
Serology will be performed on all subjects at screening to rule out hepatitis infection; required 
analytes are shown in Table 24. 
7.4.6.8. 
Multiple Myeloma Disease Assessment 
Multiple myeloma laboratory assessments will include serum protein electrophoresis (including 
quantitative M-protein), 24-hour urine protein, urine protein electrophoresis (including 
quantitative M-protein), quantitative immunoglobulins, serum free light chains, and beta-2 
microglobulin.  Tests samples should be drawn or collected and brought in (24-hour urine) for all 
of these tests at screening, Day 1 of subsequent cycles for the first 12 months of the study 
participation followed by every 12 weeks, and EOT to assess for response in MM subjects.  For 
subjects who do not show evidence of urine paraprotein at screening, spot urine with urine 
protein electrophoresis will only be required, but if the subject subsequently shows evidence of 
urine paraprotein, a 24-hour collection will be required along with the urine protein 
electrophoresis.  In addition, a bone marrow (aspirate and biopsy) will be required to confirm CR 
(IMWG criteria, Durie et al 2006, Appendix D). 
7.5. 
Disease Assessments 
Treatment cycles may be delayed; therefore, disease assessments may be delayed as well to 
synchronize with treatment cycles.  A disease assessment may be performed as an unscheduled 
procedure if clinically indicated.  For subjects who discontinue treatment for reasons other than 
disease progression, every effort should be made to continue monitoring their disease status until 


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(1) start of new anticancer therapy, (2) documented disease progression, (3) death, or (4) the end 
of study, whichever occurs first. 
7.5.1. 
Solid Tumors and Lymphoma:  CT Scan or MRI 
Objective assessment of tumor status is required using appropriate disease-specific techniques, 
and the investigator's assessment will be used to determine responses and will be recorded in the 
CRF.  For solid tumors, the RECIST v1.1 (Eisenhauer et al 2009) will be used, and the 
recommended method for measuring and following tumor burden will be CT scan, to include the 
chest, abdomen, and pelvis.  Alternative modalities may be substituted for a CT scan at the 
discretion of the investigator, provided that the same modality is used throughout the study and 
the methodology is consistent with RECIST v1.1. 
7.5.2. 
Lymphoma, AML/MDS, Multiple Myeloma, MDS/MPN, and MF 
For lymphoma, response assessments will be based on the Lugano Classification (Cheson et al 
2014; Appendix G).  For AML/MDS, MM, MDS/MPN, response assessments will be based on 
international uniform response criteria for the respective disease states (Cheson et al 2003 
[AML; Appendix E], Cheson et al 2006 [MDS; Appendix F], Durie et al 2006 [MM;  
Appendix D], Savona et al 2015 [MDS/MPN, Appendix H]).  Myelofibrosis response 
assessments will use the IWG-MRT and ELN consensus report (Tefferi et al 2013; Appendix I). 
7.5.3. 
Lymphoma:  FDG-PET or Combined PET-CT 
If FDG-PET or combined PET-CT is used as a functional imaging tool for staging or response 
assessment of lymphoma as a part of the standard of care, the results obtained during any study 
phase will be captured in the CRF. 
7.5.4. 
AML, MDS, MDS/MPN, MF, Lymphoma, and MM:  Bone Marrow 
Examination 
Bone marrow examination (aspirate and biopsy) is required at screening for Phase 1a/TGB and 
all Phase 1b and Phase 2 subjects with AML, MDS, MDS/MPN, MF, and MM (bone marrow 
examination may be omitted only with approval of the medical monitor).  These subjects should 
have a follow-up bone marrow aspirate and biopsy performed approximately 3, 6, and 12 months 
after Day 1 and then every 12 months on the nearest Cycle Day 1 (± 7 days) after the first dose 
of treatment and as clinically indicated. 
Subjects with MM only require a follow-up bone marrow examination to confirm CR, after 
2 consecutive laboratory disease assessments demonstrating negative serum and/or urine 
immunofixation. 
Lymphoma subjects in Phase 1a/TGB or Phase 1b/Cohort H 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 the results showed lymphoma involvement of the bone 
marrow and/or a baseline PET or PET/CT shows that the subject does have FDG-avid disease in 
the bone marrow.  If 1 of these conditions does not apply, a baseline bone marrow biopsy is 
required. 


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Data from the pathology report result from the bone marrow examination will be captured in the 
CRF.  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 decision of the medical monitor.  Results of 
assessments performed under standard-of-care before the signing of informed consent may be 
used as the baseline assessment in lieu of a study-specific procedure IF performed within 60 days 
of the first dose of study drug (Cycle 1 Day 1) and if adequate archive material is available. 
Data from the pathology report result from the bone marrow examination will be captured in the 
CRF.  All bone marrow examinations should include a unilateral aspiration and biopsy with 
FISH and cytogenetic testing, when feasible. 
7.5.5. 
Lymphoma and AML/MDS:  Immunophenotyping 
For subjects with relevant hematologic malignancies (lymphoma, AML/MDS), 
immunophenotyping appropriate to the underlying pathology will be conducted by flow 
cytometry at the local laboratory at screening and Cycle 2 Day 1 and at subsequent times only as 
part of confirmation of CR.  Results will be captured in the CRF. 
7.5.6. 
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 discretion. 
7.6. 
Performance and Quality of Life Assessments 
The ECOG performance status (Table 25 ) must be assessed by a medically qualified individual 
and recorded in the CRF at the visits indicated in Table 2, Table 4, Table 6, Table 8, Table 10, 
Table 12, Table 14, Table 16, Table 18, Table 20, and Table 22 (as applicable to study phase and 
treatment cohort). 
Table 25: 
ECOG Performance Status 
Grade 
Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature (eg, light house work, office work). 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up and 
about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 
Source:  Oken et al 1982. 


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7.7. 
Pharmacokinetic Assessments 
7.7.1. 
Blood Sample Collection 
Pharmacokinetic plasma samples will be obtained via whole blood at the visits indicated in 
Table 3, Table 5, Table 7, Table 9, Table 11, Table 13, Table 15, Table 17, Table 19, Table 21, 
and Table 23 (as applicable to study phase and treatment cohort); collection times and windows 
are described in Section 7.7.1.1, Section 7.7.1.2, and Section 7.7.1.3.  The exact date and time of 
the PK blood draws will be recorded in the CRF along with the date and time of the last dose of 
study drug preceding the blood draw and the time of the most recent meal.  Instructions for 
sample preparation and shipping will be provided in the Laboratory Manual.  Subjects will 
receive reminder cards in advance of the study visit providing instruction to hold the dose of 
study drug on the day of the visit and a place to record the time of the prior dose of study drug 
and time of the most recent meal or snack consumed. 
7.7.1.1. 
Pharmacokinetic Timed Instructions for Phase 1a 
On Cycle 1 Days 1, 8, and 15 and on Cycle 2 Day 1 for food-effect, study subjects will refrain 
from taking the study drug in the morning before arriving at the research unit.  Subjects should 
not have consumed any food within 8 hours before arriving at the research unit.  A trough 
(predose) PK sample (30-minute window) should be drawn at each of the PK visits.  Following 
the trough PK sample, the subject should take the assigned dose of study drug, and subsequent 
timed samples will be taken.  Food should be withheld until 1 hour after study drug 
administration.  If a subject mistakenly takes their morning dose at home before coming to the 
clinic, the PK sampling should be rescheduled at their earliest convenience. 
The initial schedule for timed postdose samples (on Cycle 1 Days 1 and 15 and Cycle 2 Day 1 
[food effect only]) will be as follows: 
• 0.5 hour (± 5 minutes) 
• 1 hour (± 10 minutes) 
• 2 hours (± 15 minutes) 
• 4 hours (± 15 minutes) 
• 6 hours (± 30 minutes) 
Adjustments to the timing of blood sampling postdose may be made based on emerging PK data; 
however, no more than 6 postdose timepoints will be used, and the maximum scheduled 
timepoint will be no greater than 6 hours postdose. 
7.7.1.2. 
Pharmacokinetic Instructions for Phase 1a Part 2 Dose Expansion Fed 
Administration (Cycle 2 Day 1 Only) 
On Cycle 2 Day 1, study subjects in TGA and TGB, in only the expansion cohort (Part 2), will 
be required to undergo PK testing after study drug administration in the fed state.  If 2 expansion 
cohorts are enrolled in either treatment group, the food-effect study will be performed on the 
PAD dose level cohort.  It is expected that subjects will consume 100% of the meal. 


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Pharmacokinetic testing conducted on Cycle 2 Day 1 will be similar to that on Cycle 1 Day 15 
with respect to the timing of sample collection and evaluations.  Subjects may be excused from 
the food-effect part of the study if they are unable to consume the meal or feel they are unable to 
consume the meal. 
Subjects receiving INCB052793 in the fed state 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 the study medication.  
Subjects must consume the entire breakfast within 30 minutes (no window after 30 minutes), and 
study drug will be administered 5 minutes after completing breakfast.  If the subject does not 
complete the meal or is unable to retain the meal, there is no need to collect the PK samples.  It is 
best to avoid antinausea medication before the meal or dose.  
The high-fat, high-calorie breakfast (50% kcal from fat) will consist of the following: 
• 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 prior approval 
of the study sponsor. 
7.7.1.3. 
Pharmacokinetic Instructions for Phase 1b/Cohorts A Through H and 
Phase 2/Cohorts I and J 
Subjects enrolled in Phase 1b/Cohorts B through H and Phase 2/Cohorts I and J will have PK 
assessments performed at the timepoints indicated in Table 3, Table 5, Table 7, Table 9, 
Table 11, Table 13, Table 15, Table 17, Table 19, Table 21, and Table 23.  Collection of PK 
samples at Cycle 1 Day 1 will be performed as needed per sponsor decision based on the 
emerging PK data.  Otherwise, coadministration will begin on Cycle 1 Day 1, and no extra 
samples will be collected from subjects.  Sampling windows for each timepoint are as follows 
and are all relative to the end of the standard-of-care agent administration (ie, after the SC 
injection[s] or IV push).  The timepoints below may not apply to every treatment cohort. 
• T0:  predose (just before standard-of-care agent administration) 
• T5m:  5 minutes ± 1 minute 
• T0.5h:  30 minutes ± 5 minutes 
• T1.0h:  1 hour ± 5 minutes 
• T2.0h:  2 hours ± 10 minutes 
• T4.0h:  4 hours ± 15 minutes 
• T6.0h:  6 hours ± 30 minutes  
• T8.0h:  8 hours ± 30 minutes 


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7.7.2. 
Urine Sample Collection (Phase 1a Only) 
Urine will be collected from each subject at Cycle 1 Day 15 after administration of INCB052793 
and a predose void.  Total urine will be collected over a 6-hour interval after 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 CRF.  Duplicate 5 mL urine 
aliquots (ie, Urine Aliquot A and Urine Aliquot B) should be transferred into the prelabeled, 
polypropylene storage containers and frozen at or below -20°C.  Shipping and handling 
instructions will be provided in the Laboratory Manual. 
7.7.3. 
Bioanalytical Methodology and Analysis 
The plasma samples will be analyzed for INCB052793 and INCB050465 by a validated assay.  
 
  These samples will be 
analyzed by Incyte Corporation (Wilmington, DE) or its designee. 
Pharmacokinetic parameters will be calculated from the plasma concentrations of INCB052793 
and INCB050465 according to the model-independent approach.  Refer to Appendix B for a 
detailed list and description of the PK parameters. 


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7.9. 
Other Study Procedures 
7.9.1. 
Administration of INCB052793 
Subjects will self-administer INCB052793 orally with water according to a QD morning regimen 
as directed by the investigator.  INCB052793 will be taken on an empty stomach by refraining 
from food consumption for 2 hours before and 1 hour after study drug administration except on 
days when PK 
 sampling is conducted, then subject will refrain from food consumption at 
least 8 hours before and 1 hour after study drug or as indicated in the PK section.  Subjects will 
take study drug at the clinic after the hematology sample is drawn on clinic days when a 
hematology sample is obtained.  Updated information will be provided if emerging PK and 
food-effect data suggest that an improved PK profile may be achieved by administering 
INCB052793 with food. 
Study drug will be administered in the study clinic on days as indicated in Table 2, Table 4, 
Table 6, Table 8, Table 10, Table 12, Table 14, Table 16, Table 18, and Table 20. 
7.9.2. 
Administration of INCB050465 
Subjects will self-administer INCB050465 tablets orally with water, according to a QD regimen 
as directed by the investigator.  INCB050465 will be taken on an empty stomach by refraining 
from food consumption for 2 hours before and 1 hour after study drug administration except on 
days when PK 
 sampling is conducted, then subject will refrain from food consumption at 
least 8 hours before and 1 hour after study drug or as indicated in the PK section.  Updated 
information will be provided if emerging PK and food-effect data suggest that an improved PK 
profile may be achieved by administering INCB050465 with food.  Study drug will be 
administered in the study clinic on days as indicated in Table 18. 
7.9.3. 
Administration of Itacitinib 
Subjects will self-administer itacitinib tablets orally with water, according to a QD regimen as 
directed by the investigator.  Itacitanib will be taken without regard to food except on days when 
PK samples are drawn; on those days, subjects should be instructed to fast and refrain from 
taking itacitinib until PK samples are collected; see details in Table 22. 
Study drug will be administered in the study clinic on days as indicated in Table 22. 
7.9.4. 
Dispensing of Study Drug 
An initial supply of INCB052793, INCB050465 (applicable to Cohort H only), and itacitinib 
(applicable to Cohort J only) will be provided to investigative sites before enrollment of the first 
subject.  Thereafter, the site staff will contact the sponsor or its designee for resupply of 
INCB052793, INCB050465, and itacitinib (as applicable).  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 CRF and drug accountability 
log.  Full details will be provided in the Study Manual. 


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7.9.5. 
nab-Paclitaxel Administration 
Commercial supplies of nab-paclitaxel will be supplied by the institution's pharmacy and 
administered in the clinic as either 100 mg/m2 or 125 mg/m2 IV over 30 minutes) on Days 1, 8, 
and 15 of each 28-day cycle.  Refer to http://dailymed.nlm.nih.gov/dailymed/about.cfm for 
additional information. 
7.9.6. 
Gemcitabine Administration 
Commercial supplies of gemcitabine will be supplied by the institution's pharmacy and 
administered in the clinic as 1000 mg/m2 IV (starting dose) over 30 minutes on Days 1, 8, and 15 
of each 28-day cycle.  Refer to http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional 
information. 
7.9.7. 
Dexamethasone Administration 
Commercial supplies of dexamethasone will be supplied by the institution's pharmacy and 
administered at a starting dose of 40 mg administered orally weekly on Days 1, 8, 15, and 22 of 
each 28-day cycle (or Days 1, 8, 15 of each 21-day cycle if being administered with bortezomib 
in Phase 1b/Cohort D), without regard to food.  Dexamethasone will be administered in the clinic 
on for all Cycle 1 doses (Days 1, 8, 15, 22) and for all subsequent doses that correspond to a 
scheduled visit (Days 1 and 15) for Phase 1b/Cohort B.  Subjects will self-administer 
dexamethasone at the prescribed schedule when not visiting the clinic.  Refer to 
http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional information. 
7.9.8. 
Carfilzomib Administration 
Commercial supplies of carfilzomib will be supplied by the institution's pharmacy and 
administered in the clinic at a starting dose of 20 mg/m2 IV on Days 1 and 2 followed by 
27 mg/m2 IV on Days 8, 9, 15, and 16 of Cycle 1 and for all doses of each 28-day cycle 
thereafter.  Refer to http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional information. 
7.9.9. 
Bortezomib Administration 
Commercial supplies of bortezomib will be supplied by the institution's pharmacy and 
administered in the clinic at a starting dose of 1.3 mg/m2 IV or SC on Days 1, 4, 8, and 11 of 
each 21-day cycle.  Refer to http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional 
information. 
7.9.10. 
Lenalidomide Administration 
Commercial supplies of lenalidomide will be supplied by the institution's pharmacy and 
administered in the clinic on Cycle 1 Days 1, 8, and 15 as per Table 13.  Subjects will 
self-administer lenalidomide at the prescribed schedule when not visiting the clinic.  Refer to 
http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional information. 
7.9.11. 
Azacitidine Administration 
Commercial supplies of azacitidine will be supplied by the institution's pharmacy and 
administered in the clinic at a starting dose of 75 mg/m2 SC for 5 days, followed by 2 days of no 


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treatment, then 75 mg/m2 for 2 days of each 28-day treatment cycle.  Refer to 
http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional information. 
7.9.12. 
Pomalidomide Administration 
Commercial supplies of pomalidomide will be supplied by the institution's pharmacy and 
administered in the clinic on Cycle 1 Days 1 and 15 (per Table 17).  Subjects will self-administer 
pomalidomide at the prescribed schedule when not visiting the clinic.  Dexamethasone will be 
coadministered at 40 mg once per day PO on Days 1, 8, 15, and 22 of each 28-day cycle.  Refer 
to http://dailymed.nlm.nih.gov/dailymed/about.cfm for additional information. 
7.9.13. 
Administration of Supportive Care 
Supportive care, including GCSF for treatment of chemotherapy-induced neutropenia, will be 
supplied by the institution's pharmacy and administered according to the package insert and 
institutional guidelines.   
7.9.14. 
Assessment of Compliance With Study Drug 
The study subject will return all full, empty, and opened/partially used 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; therefore, appropriate steps should be taken to optimize 
compliance. 
7.9.15. 
Distribution of Subject Reminder Cards 
Subjects will be provided with subject reminder cards at each visit.  The subject reminder cards 
will indicate the date and time of the next visit.  The reminder cards will have a field for the 
subject to enter the date and time of the last dose taken before the visit and to record the time of 
the last meal when required to support the PK/
 analysis.  Reminder cards will inform the 
subject when to refrain from taking the study drug at home in the morning before the clinic visit.  
All necessary instructions, such as those for study drug administration, concomitant medications, 
and laboratory tests, should be provided to the subject in writing on this reminder card, or on 
accompanying written materials.  After 4 treatment cycles, if the subject has been 100% 
compliant with study visits/requirements, subject reminder cards may be omitted at the discretion 
of the study staff. 


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8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events 
8.1.1. 
Definitions and Reporting 
Treatment-emergent AEs are defined as any AE that occurs from the day a subject begins study 
drug.  
For the purposes of this Protocol, an AE is defined as the appearance of (or worsening of any 
pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur 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). 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events page of the CRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History page of the CRF.  Adverse event monitoring 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" should not be recorded as an AE itself unless there are no other 
identifiable AEs associated with the disease progression at the time of reporting.  For events 
associated with disease progression, the relevant signs and symptoms should be reported using a 
diagnosis whenever possible rather than individual underlying signs and symptoms.  When a 
clear diagnosis cannot be identified, each sign or symptom should be reported as a separate AE.  
If the events resulting from disease progression meet the criteria for an SAE (eg, resulted in 
hospitalization, a life-threatening event, or death), the specific event(s) should be reported as an 
SAE(s) as described in Section 8.3.2.  In both cases (ie, AEs or SAEs related to disease 
progression), it should be indicated that each event (reported as a diagnosis or as signs and 
symptoms) is related to disease progression on the Adverse Events form of the CRF. 
Adverse events will be assessed according to the CTCAE v4.03.  The CTCAE severity Grade 5 
(death) will not be used in this study; rather, information about deaths will be collected as an 
outcome of the event.  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. 
As far as possible, each AE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 4). 
• Reasonable possibility that the AE is related to the study treatment:  unrelated (no) or 
related (yes). 


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• Start and end dates, unless unresolved at final examination. 
• Action taken with respect to study drug (eg, none, dose adjusted, temporarily 
interrupted, permanently discontinued, unknown, not applicable). 
• Outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• Whether it is serious, as per 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 pages of the 
CRF. 
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. 
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 CRF.  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, as per CTCAE, 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 interruption or adjustment 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. 


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• Is clinically meaningful (ie, defined as an event that jeopardizes the subject or 
requires potential medical or surgical intervention to prevent one of the outcomes 
listed above).  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 a SAE when, based upon appropriate medical judgment, it may 
jeopardize the subject or may require medical or surgical intervention to prevent one 
of the outcomes listed in this definition. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition.  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. 
− 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. 
− 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 experienced after this period should be 
reported to the sponsor (or 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 
follow-up 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.  When other 
drugs are used in combination with the study drug, the relationship to study drug can be assessed 
for the Incyte study drug alone, the marketed product alone (used in combination with the study 
drug), or as a combination of the Incyte product with the marketed product. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form.  The investigator must assess and record the relationship of each SAE to each specific 
study drug (if there is more than one), complete the SAE Report Form in English, and send the 
completed, signed form by fax within 24 hours to the sponsor or its designee.  The investigator 
must assess if there is a reasonable possibility that the SAE is related to the study treatment:  
unrelated (no) or related (yes). 


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Serious AEs related to unblinded comparator drugs or concomitant medications/drug delivery 
systems are reported directly to the manufacturers of those drugs/devices in accordance with the 
package insert. 
The telephone and facsimile number of the sponsor's contact persons, specific to the study, are 
listed in the investigator folder provided to each site.  The original copy of the SAE Report Form 
and the fax confirmation sheet must be kept with the CRF 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 giving 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 previously documented in the IB for the study drug (new occurrence) and is 
thought to be related to the sponsor's study drug, a sponsor's associate may urgently require 
further information from the investigator for reporting to health authorities. 
The sponsor or its designee may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same drug that this SAE has been reported.  
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with Directive 
2001/20/EC, or as per national regulatory requirements in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
8.5. 
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. 
• The subject must be withdrawn from the study. 
• The EOT visit evaluations must be performed. 
• The investigator must complete and submit the Pregnancy Initial and Follow-Up 
Report forms to the sponsor or its designee. 
• A serum pregnancy test must be performed to confirm the urine pregnancy test result.  
(The serum test should be performed at the investigative site to ensure the test will be 
performed promptly and the result available immediately for review.) 


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If a negative serum test does not confirm the urine pregnancy test result, then: 
• The investigator will use his or her expert judgment, based on an assessment of the 
potential benefit/risk to the subject, to determine if it is in the subject's best interest to 
resume study drug and continue participation in the study. 
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 to each pregnancy should be conducted 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 experienced during pregnancy must be reported on the SAE 
Report Form and to the sponsor or its designee. 
8.6. 
Warnings and Precautions 
No evidence available at the time of the approval of this study Protocol indicated that special 
warnings or precautions were appropriate, other than those noted in the provided 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 needed.  If new, significant risks are identified, they will be added 
to the ICF. 
8.7. 
Data Monitoring Committee 
There will be no formal external Data Monitoring Committee for this open-label Phase 1/2 study.  
Approximately weekly the sponsor will conduct telephone conferences with investigators in 
order to review cohort-specific data and overall safety data from prior cohorts (if applicable), and 
to agree on dose escalation, de-escalation, and cohort expansion decisions. 
8.8. 
Adverse Events of Special Interest 
Not applicable. 
8.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported. 


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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 
Incyte contact. 
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 
Efficacy/Safety Evaluable:  All subjects exposed to at least 1 dose of study drug. 
Pharmacokinetic/
 Evaluable:  Subjects who receive at least 1 dose of study 
drug and provide at least 1 postdose blood sample for PK/
 assessments.  The study 
pharmacokineticist will review data listings of subject dosing and sample records to identify 
subjects to be excluded from the analysis. 
The Efficacy/Safety Evaluable population will be used for the summary of baseline, disposition, 
efficacy, and safety analyses.  The PK/
 Evaluable population will be used in the summary of 
all PK/
 data. 
9.2. 
Selection of Sample Size 
9.2.1. 
Sample Size for Phase 1a and Phase 1b 
The sample size was based on the adequacy of subjects (36 for Phase 1a and up to approximately 
39 in Phase 1b) for dose escalation to determine the MTD and expansion evaluation.  It was not 
based on statistical power calculations. 
9.2.2. 
Sample Size for Phase 2 
The sample size for each cohort will be guided by the Simon 2-stage design (Simon 1989), using 
a 1-sided Type I error of 0.10 and power of 80%.  Let P0 denote a clinically uninteresting 
response rate (eg, for subjects with AML and high-risk MDS who failed prior therapy with 
HMA, P0 = 26%).  In order to determine whether a target response rate (eg, 46%, which 
represents a 20% improvement) is likely, an initial number of subjects (eg, 9) will be treated at 
Stage 1.  If  ≤ 2 subjects have responses among these 9 subjects, it will be concluded that the true 
response rate is unlikely to be greater than or equal to the target rate, and no more subjects will 
be enrolled in that treatment group.  Otherwise, if at least 3 subjects have responses among the 
Stage 1 subjects, 24 additional subjects will be treated in Stage 2 to estimate the response rate.  
At the end of Stage 2, if ≤ 11 subjects have responded among a total of 33 subjects, the study 
drug will be declared nonpromising.  In other words, after the study is finished, if there is a 
sufficient number of responses in the 2 stages combined, the study drug is considered promising; 
otherwise it is considered nonpromising.  Approximately 66 subjects will be enrolled for Cohort 
I and Cohort J in Phase 2. 


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9.3. 
Level of Significance 
Not applicable.  No formal efficacy hypotheses will be tested.  All confidence intervals (CIs) will 
be 95%. 
9.4. 
Statistical Analyses 
9.4.1. 
Primary Analyses 
9.4.1.1. 
Phase 1a and 1b 
Safety analyses will be conducted for the safety evaluable population.  Adverse events will be 
coded by the Medical Dictionary for Regulatory Activities, and incidences will be tabulated by 
preferred term and system organ class for all events, related events, and events of Grade 3 or 
higher.  Quantitative safety variables and their changes from baseline (laboratory tests, vital 
signs, etc) will be summarized with descriptive statistics.  Clinically notable abnormal values 
will be flagged and tabulated based on predefined criteria.  The rate of DLTs will be summarized 
for each cohort. 
9.4.1.2. 
Phase 2 
The proportion of subjects with response by IWG response criteria for AML and IWG response 
criteria for MDS will be summarized. 
A subject is considered a responder if the subject achieves CR, Cri, PR, or HI at any postbaseline 
visit.  The proportion of responders will be estimated with 95% CIs; the CIs will be calculated 
based on the exact method for binomial distributions. 
9.4.2. 
Secondary Analyses 
The proportion of subjects with response by RECIST v1.1 criteria for solid tumors, the Lugano 
Classification criteria for malignant lymphoma, and the International Uniform Response Criteria 
for MM, IWG response criteria for AML, and IWG response criteria for MDS will be 
summarized.  The proportion of responders will be estimated with 95% CIs; the CIs will be 
calculated based on the exact method for binomial distributions. 
Pharmacokinetic 
 data will be analyzed with appropriate standard nonlinear analytic 
software. 
9.4.2.1. 
Baseline Demographics and Disposition of Subjects 
Descriptive statistics (eg, mean, standard deviation, range) will be derived where appropriate.  
Subject demographics and medical history will be summarized at baseline.  The number and 
percentage of subjects who were enrolled and treated, who completed the study, who 
discontinued study drug, and who were withdrawn from the study with a primary reason for 
withdrawal, will be summarized for the safety population.  The number of subjects enrolled by 
site will also be provided.   
9.4.3. 
Other Analyses 
Not applicable. 


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9.5. 
Data Monitoring Committee 
Not applicable 
9.6. 
Interim Analysis 
No interim analysis is planned. 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Investigational Product Description 
10.1.1. 
Packaging, Labeling, and Preparation of INCB052793 
INCB052793 tablets (5 mg or 25 mg strength) will be administered orally QD, but dose 
escalation can be switched to twice daily as determined by emerging PK 
 data.  All 
bottles of Incyte investigational product contain the following language:  "Caution:  New Drug—
Limited by Federal Law to Investigational Use." 
10.1.2. 
Storage and Stability of INCB052793 
INCB052793 tablets are stable for at least 2 months at ambient and accelerated storage 
conditions of 40°C/75% relative humidity.  Stability studies are ongoing, and drug product 
should be stored under ambient conditions. 
10.1.3. 
Packaging, Labeling, and Preparation of INCB050465 
INCB050465 tablets are provided in high-density polyethylene bottles; no preparation is 
required.  All bottles of Incyte investigational product contain the following language:  "Caution:  
New Drug—Limited by Federal Law to Investigational Use." 
10.1.4. 
Storage and Stability of INCB050465 
INCB050465 drug product should be stored under ambient conditions at 15°C to 30°C (59°F to 
86°F). 
10.1.5. 
Packaging, Labeling, and Preparation of Itacitinib 
Itacitinib will be provided to sites as 100 mg tablets packaged in high-density polyethylene 
bottles as applicable by Incyte.  No preparation is required. 
All Incyte investigational product labels will be in the local language and will comply with the 
legal requirements of each country and will state "Caution:  New Drug—Limited by Federal (or 
United States) law to investigational use." 
10.1.6. 
Storage and Stability of Itacitinib 
Itacitinib should be stored at ambient conditions (15°C to 30°C, or 59°F to 86°F) as per the 
itacitinib IB. 


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10.2. 
Accountability, Handling, and Disposal of Study Drug 
Responsibility for drug accountability at the study site rests with the investigator; 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 will be expected to collect and retain all used, unused, and partially 
used containers of study drug until the end of the study.  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. 
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. 
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 
study drug specified. 
Completed accountability records will be archived by the site.  At the completion 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 site destruction of investigational supply, prior written approval 
must be obtained from Incyte. 


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11. 
STUDY ADMINISTRATION 
11.1. 
Data Management 
11.1.1. 
Data Collection 
The investigator will be provided with a CRF for each subject.  Entries made in the CRF must be 
verifiable against source documents; any discrepancies should be explained and documented.  
The investigator will be responsible for reviewing all data and CRF entries and will sign and date 
the designated pages in each subject's CRF, verifying that the information is true and correct.  
The investigator is responsible for the review and approval of all responses. 
11.1.2. 
Data Management 
Data management will be performed from CRFs.  All CRF data will be entered into a validated 
database.  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. 
11.2. 
Study Monitoring 
Qualified representatives of the sponsor or its designee, "study monitors," will monitor the study 
according to a predetermined monitoring plan.  Monitoring visits provide the sponsor with the 
opportunity to: 
• Evaluate the progress of the study. 
• Verify the accuracy and completeness of CRFs. 
• Assure that all Protocol requirements, applicable laws and/or regulations, and 
investigator's obligations are being fulfilled. 
• Resolve any inconsistencies in the study records. 
The investigator must allow the study monitors to periodically review, at mutually convenient 
times during the study and after the study has been completed, all CRFs and office, hospital, and 
laboratory records supporting the participation of each subject in the study.  The CRFs and other 
documentation supporting the study must be kept up-to-date by the investigator and the research 
staff at the investigative site.  These study materials must be available for review by the study 
monitor, and/or other qualified representatives of the sponsor or its designee, at each monitoring 
visit. 
The study monitor will review the various records of the study (CRFs, subject medical and 
laboratory records, and other pertinent data).  The study monitor will verify the CRF data against 
original source documentation for accuracy and completeness.  The study monitor will identify 
data discrepancies and collaborate with the investigator and research staff to resolve the 
discrepancies in a timely manner.  Protocol deviations will also be identified and recorded on a 
"Protocol Deviation Log."  The study monitor will follow an "Issue Escalation" plan in order to 
ensure that each issue identified during a monitoring visit is appropriately documented, reported, 
and resolved in a timely manner in accordance with the plan's requirements. 


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11.3. 
Protocol Adherence 
The principal investigator must obtain IRB or IEC approval for the investigation.  Initial IRB or 
IEC approval and all materials approved by the IRB or IEC for this study including the subject 
ICF and recruitment materials must be maintained by the investigator and made available for 
inspection. 
Each investigator must adhere to the Protocol as described in this document and agree that 
changes to the Protocol, with the exception of medical emergencies, must be discussed and 
approved, firstly, by the sponsor or its designee and, secondly, by the IRB or IEC.  Each 
investigator is responsible for enrolling subjects who have met the Protocol inclusion and 
exclusion criteria.  The IRB or IEC that granted original approval, or the IRB or IEC currently 
responsible for overseeing the conduct of the study, must be notified of all changes in and 
deviations from the Protocol that may increase risk to the subject, and/or that may adversely 
affect the rights of the subject or validity of the investigation.  The investigator must send a copy 
of the approval letter from the IRB or IEC to the sponsor or its designee and retain the original in 
the site study regulatory file. 
Major eligibility deviations must be reported to the IRB or IEC in accordance with the IRB or 
IEC requirements.  During the course of the study, the monitor must notify the sponsor or its 
designee of subjects found not to have met eligibility criteria.  The medical monitor, in 
collaboration with the investigator, will determine if the subject should be withdrawn from the 
study. 
11.4. 
Financial Disclosure 
All clinical investigators participating in clinical studies subject to FDA Regulation Title 21 
Code of Federal Regulations (CFR) Part 54 – Financial Disclosure by Clinical Investigators, are 
required before study initiation to submit a completed Clinical Investigator Financial Disclosure 
Request 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 sub 
investigator who is directly involved in the treatment or evaluation of research subjects, 
including the spouse and each dependent child of the clinical investigator.  These requirements 
apply to both US and foreign clinical investigators conducting covered clinical studies. 
Any new investigators or sub investigators added to the covered clinical study during its conduct 
must also submit a completed Clinical Investigator Financial Disclosure Request 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 obligation to report to the 
sponsor or its designee any changes to the financial information previously reported.  The 
clinical investigators will also be reminded that they must report any changes in their financial 
information for a period of 1 year after completion of the covered clinical study. 


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12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
12.1. 
Sponsor Audits 
At some point during the study, individuals from the sponsor's Quality Assurance department 
and/or their authorized representative may visit the investigator's site to conduct an audit of the 
study.  The purpose of this visit will be to determine the investigator's adherence to the Protocol, 
applicable regulations, and the sponsor's procedures, in addition to assessing the accuracy of the 
study data.  Before initiating this audit, the investigator will be contacted by the sponsor to 
arrange a convenient time for this visit.  The investigator and staff are expected to cooperate with 
the auditors and allow access to all subject records supporting the CRFs and other study-related 
documents. 
12.2. 
Inspection by Regulatory Authorities 
At some point during the investigational product's development program, a regulatory authority 
may visit the investigator 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 CRFs and other study-related documents.  The investigator must immediately 
notify the sponsor when contacted by any regulatory authority for purposes of conducting an 
inspection. 
13. 
ETHICS 
13.1. 
Ethical Conduct of the Study 
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 CFR Parts 50, 54 56, 312, and Part 11, as well as ICH GCP consolidated 
guidelines (E6) and applicable regulatory requirements. 
13.2. 
Written Informed Consent 
Informed consent documentation that includes both information about the study and the ICF will 
be prepared and given to the subject.  This document will contain all elements required by the 
ICH E6 Guideline for GCP and any additional elements required by local regulations.  The 
document must be in a language understandable to the subject and must specify who informed 
the subject.  Where required by local law, the person who informs the subject must be a 
physician. 
The principal investigator at each center will ensure that the subject is given full and adequate 
verbal and written information about the nature, purpose, and the possible risk and benefit of the 
study.  Subjects must also be notified that they are free to discontinue study drug and withdraw 
from the study at any time.  The subject should be given the opportunity to ask questions and 
allowed time to consider the information provided. 


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The subject's signed and dated ICF must be obtained before conducting any study procedures.  
The principal investigator must maintain the original, signed ICF.  A copy of the signed ICF 
must be given to the subject.  The investigator should inform the subject's primary physician 
about the subject's participation in the study if the subject has a primary physician and if the 
subject agrees to the primary physician being informed. 
Preparation of the ICF is the responsibility of the investigator and must include all elements 
required by the ICH GCP, and applicable regulatory requirements, and must adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.  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.  Before the beginning of the study, 
the IRB or IEC must provide the investigator with written approval/favorable opinion of the 
written ICF and any other information to be provided to the subjects. 
13.3. 
Ethics Review 
It is the responsibility of the investigator to assure that all aspects of the ethics review are 
conducted in accordance with the Declaration of Helsinki as described in the ICH E6:  Guideline 
for GCP, and/or local laws, whichever provides the greatest level of protection for the study 
participants.  The Protocol and any information supplied to the subject to obtain informed 
consent, including written ICFs, subject recruitment procedures (eg, advertisements), and written 
information to be provided to subjects (information leaflets), must be reviewed and approved by 
a qualified IRB/IEC before enrollment of participants in the study.  Before initiation of the study, 
the sponsor or its designee must receive documentation of the IRB or IEC approval, which 
specifically identifies the study/protocol, and a list of the committee members. 
The principal investigator is responsible for informing the IRB or IEC of any amendment to the 
Protocol in accordance with local requirements.  Protocol amendments and revisions to the ICF 
must be submitted to and approved by the IRB or IEC. 
Investigators must submit progress reports to the IRB or IEC in accordance with the IRB or IEC 
requirements and local regulations.  Annual re-approval of the study must be obtained.  Copies 
of progress reports and annual re-approvals must be sent to the sponsor or its designee. 
The principal investigator is also responsible for providing the IRB or IEC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  The sponsor or its designee will provide this information to the principal investigator. 
When the sponsor or its designee provides the investigator with a safety report, the investigator 
must promptly forward a copy to the IRB or IEC. 
After completion or termination of the study, the investigator must submit a final report to the 
IRB or IEC and to the sponsor or its designee. 
The investigator, as part of the records retention requirements for the study, must maintain 
documentation of all submissions, correspondence, and approvals to and from the IRB or IEC. 
Each clinical investigator is responsible to conduct the study in accordance with the Protocol, all 
applicable laws, regulations, and GCP according to ICH guidelines. 


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13.4. 
Data Privacy 
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. 
14. 
DATA HANDLING AND RECORDKEEPING 
14.1. 
Inspection of Records 
The sponsor or its designee will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study.  The investigator agrees to allow the monitor 
to inspect the drug storage area, study drug stocks, drug accountability records, subject charts 
and study source documents, and other records relative to study conduct. 
The investigator must ensure that all records pertaining to the conduct of the clinical study (as 
listed above) are adequately maintained for a period of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or at least 2 years have elapsed since the formal termination of 
clinical development of the investigational product. 
14.2. 
Retention of Records 
The principal investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved, 2 years following the 
termination of the test article for investigation.  If it becomes necessary for the sponsor or the 
regulatory authority to review any documentation relating to the study, the investigator must 
permit access to such records. 
The investigator must not destroy any records associated with the study without receiving 
approval from Incyte.  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. 
Whenever possible, an original recording of an observation must be retained as the source 
document.  However, a photocopy of a record is acceptable, provided it is legible and is a 
verified copy of the original document. 
All CRF 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 CRF data and 
audit trail. 


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14.3. 
Confidentiality 
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 CRF, 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 
available for inspection will be handled in strictest confidence and in accordance with local data 
protection laws. 
15. 
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.  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.  The signed agreement is 
retained by the sponsor or its designee. 


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Jagannath S, Richardson PG, Barlogie B, et al. Bortezomib in combination with dexamethasone 
for the treatment of patients with relapsed and/or refractory multiple myeloma with less than 
optimal response to bortezomib alone. Haematologica 2006;91:929-934. 
Kaminskas E, Farrell AT, Wang YC. FDA drug approval summary: azacitidine (5-azacytidine, 
Vidaza™) for injectable suspension. Oncologist 2005;10:176-182. 
Kiel MJ, Sahasrabuddhe AA, Rolland DC, et al. Genomic analyses reveal recurrent mutations in 
epigenetic modifiers and the JAK-STAT pathway in Sézary syndrome. Nature Commun 
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Kiel MJ, Velusamy T, Rolland D, et al. Integrated genomic sequencing reveals mutational 
landscape of T-cell prolymphocytic leukemia. Blood 2014;124:1460-1472. 
Komazaki T, Nagai H, Emi M, et al. Hypermethylation-associated inactivation of the SOCS-1 
gene, a JAK/STAT inhibitor, in human pancreatic cancers. Jpn J Clin Oncol 2004;34:191–194. 
Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological 
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Kyprolis [package insert]. South San Francisco, CA: Onyx Pharmaceuticals; 2012. 
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Lauta VM. A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and 
therapeutic implications. Cancer 2003;97:2440-2452. 
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Mehta SP. Palliative chemotherapy for pancreatic malignancies. Surg Clin North Am 
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Prébet T, Gore SD, Thépot S, et al. Outcome of acute myeloid leukaemia following 
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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomised partner2,3 
• Sexual abstinence4 
 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomised partner is a highly effective method provided of avoiding pregnancy that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the 
surgical success.  
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
Source:  CTFG 2014. 


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APPENDIX B. 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 
Area under the plasma concentration-time curve over 1 
dosing interval (eg, 0 to 12 hours or 0 to 24 hours) 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) 
Pharmacokinetic calculations will be performed, if appropriate, using commercial software such 
as WinNonlin® (Pharsight Corporation, Cary, NC).  Additional details of analyses will be 
described in the data analysis plan. 


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APPENDIX C. CYTOCHROME P450 3A4 INHIBITORS AND INDUCERS 
University of Washington School of Pharmaceutics: Drug Interaction Database Program. 2002. 
http://www.druginteractioninfo.org. Accessed May 2015.  Highlighted rows indicate recent 
additions to the lists at the time the database search was performed. 


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In Vivo CYP3A Inhibitors 
 


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In Vivo CYP3A Inducers 
 


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APPENDIX D. 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 immunofluorescence1 
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 
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. 
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. 
Source:  Durie et al 2006. 


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APPENDIX E. 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 F. IWG RESPONSE CRITERIA FOR MYELODYSPLASTIC 
SYNDROME 
Category 
Response Criteria (responses must be at least 4 wk) 
Complete remission (CR) 
Bone marrow:  ≤ 5% myeloblasts with normal maturation of all cell lines 
Persistent dysplasia will be noted 
Peripheral blood: 
Hemoglobin ≥ 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 hemoglobin (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 G. 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 5PSa. 
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 5a 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 5a 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 one of 
the following): 
Individual 
target 
nodes/nodal 
lesions 
Individual target nodes/nodal lesions: 
• Score 4 or 5a 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. 
Source:  Cheson et al 2014. 


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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 
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.a 
• Osteomyelofibrosis absent or equal to "mild reticulin fibrosis" (≤ Grade 1 fibrosis).b 
• Peripheral blood:c 
- 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..a 
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.d 
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.e 
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..e 
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..e 
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. 
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:f 
• < 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.g 
Evidence of cytogenetic evolution:h 
• 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. 


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Response 
Subcategory 
Response Criteria 
 
Minor criteria: 
• Transfusion dependence.i 
• 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).j 
CMML = chronic myelomonocytic leukemia; CR = complete remission; FISH = fluorescence in situ hybridization; IWG-MRT = 
International Working Group for Myelofibrosis Research and Treatment; MDS = myelodysplastic syndrome; MPN = 
myeloproliferative neoplasm; MPN-SAF = Myeloproliferative Neoplasm Symptom Assessment Form; PR = partial remission; 
TI = transfusion independence; TSS = Total Symptom Score; WBC = white blood cell. 
.a 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. 
.b 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. 
:c 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. 
.d 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. 
.e 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. 
:f Blasts as measured from the bone marrow. 
.g 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. 
:h 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. 
.i 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. 
.j 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) 
CR 
• Bone marrow:a  Age-adjusted normocellularity; < 5% blasts; ≤ Grade 1 MF.b 
• Hemoglobin ≥ 100 g/L and < UNL; neutrophil count ≥ 1 × 109/L and < UNL. 
• Platelet count ≥ 100 × 109/L and < UNL; < 2% immature myeloid cells.c 
• Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH. 
PR 
• Hemoglobin ≥ 100 g/L and < UNL; neutrophil count ≥ 1 × 109/L and < UNL; platelet 
count ≥ 100 × 109/L and < UNL; < 2% immature myeloid cells.d 
• Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH. 
• Bone marrow:a  Age-adjusted normocellularity; < 5% blasts; ≤ Grade 1 MFe, 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.f 
• Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH. 
CI 
• The achievement of anemia, spleen or symptoms response without progressive disease or 
increase in severity of anemia, thrombocytopenia, or neutropenia.g 
Anemia response  • Transfusion-independent patients:  a ≥ 20 g/L increase in hemoglobin level.h 
• Transfusion-dependent patients:  becoming transfusion-independent.i 
Spleen response 
• Baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpablej or 
• Baseline splenomegaly that is palpable at > 10 cm, below the LCM, decreases by ≥ 50%.j 
- 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 
diseasek 
• 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. 
CI = clinical improvement; CR = complete remission; CT = computed tomography; EMH = extramedullary hematopoiesis; LCM 
= left costal margin; MF = myelofibrosis; MRI = magnetic resonance imaging; PR = partial remission; PRBC = packed red 
blood cells; UNL = upper normal limit. 
a Baseline and post-treatment bone marrow slides are to be interpreted at 1 sitting by a central review process.  Cytogenetic and 
molecular responses are not required for CR assignment. 


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.b Grading of MF is according to the European classification. 
.c Immature myeloid cells constitute blasts + promyelocytes + myelocytes + metamyelocytes + nucleated red blood cells.  In 
splenectomized patients, < 5% immature myeloid cells is allowed. 
.d Immature myeloid cells constitute blasts + promyelocytes + myelocytes + metamyelocytes + nucleated red blood cells.  In 
splenectomized patients, < 5% immature myeloid cells is allowed. 
e Grading of MF is according to the European classification. 
.f Immature myeloid cells constitute blasts + promyelocytes + myelocytes + metamyelocytes + nucleated red blood cells.  In 
splenectomized patients, < 5% immature myeloid cells is allowed. 
.g 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 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. 
.h 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. 
.i Transfusion dependency before study enrollment is defined as transfusions of at least 6 units of PRBC, 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 PRBC transfusions during any consecutive "rolling" 12 week interval during the 
treatment phase, capped by a hemoglobin level of ≥ 85 g/L. 
j 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. 
k Progressive disease assignment for splenomegaly requires confirmation by MRI or CT 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. 


Signature Manifest
Document Number: IC-DEV-PROT-AMEND-0239
Revision: 0
Title: INCB 52793-101 Protocol Amendment 9
All dates and times are in Eastern Standard Time.
APPROVAL: 52793-101 Amendment 9
Approval and Release
Name/Signature
Title
Date
Meaning/Reason
 
 
02 May 2017, 12:05:09 PM
Approved
 
02 May 2017, 12:51:55 PM
Approved
03 May 2017, 10:13:04 AM
Approved
 
 04 May 2017, 04:06:59 AM
Approved
Page 1 of 1
Signature Manifest
5/4/2017

SAP_001.pdf: 
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INCB 52793-101 Statistical Analysis Plan 
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CONFIDENTIAL 
Statistical Analysis Plan 
INCB 52793-101 / NCT02265510
A Phase 1/2, Open-Label, Dose-Escalation, Safety and 
Tolerability Study of INCB052793 in Subjects With 
Advanced Malignancies 
IND Number: 
134,089 
Sponsor:
Incyte Corporation
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment 9 dated 02 MAY 2017 
CRF Approval Date: 
01 NOV 2017 
SAP Version: 
Original 
SAP Author:  
, 
 
Date of Plan: 
28 MAY 2019 
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 ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS .................................9 
2.1. 
Protocol and Case Report Form Version ......................................................................9 
2.2. 
Study Objectives ...........................................................................................................9 
2.2.1. 
Primary Objectives .......................................................................................................9 
2.2.2. 
Secondary Objectives ...................................................................................................9 
 
9 
2.3. 
Study Endpoints ..........................................................................................................10 
2.3.1. 
Primary Endpoints ......................................................................................................10 
2.3.2. 
Secondary Endpoints ..................................................................................................10 
 
10 
3. 
STUDY DESIGN .......................................................................................................11 
3.1. 
Randomization ............................................................................................................13 
3.2. 
Control of Type I Error ...............................................................................................13 
3.3. 
Sample Size Considerations .......................................................................................13 
3.3.1. 
Sample Size in Phase 1a .............................................................................................13 
3.3.2. 
Sample Size in Phase 1b .............................................................................................13 
3.3.3. 
Sample Size in Phase 2 ...............................................................................................14 
3.4. 
Schedule of Assessments ............................................................................................14 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................15 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................15 
4.1.1. 
Day 1 ...........................................................................................................................15 
4.1.2. 
Study Day ...................................................................................................................15 
4.1.3. 
Baseline Value ............................................................................................................15 
4.1.4. 
Handling of Missing and Incomplete Data .................................................................16 
4.1.5. 
Cycle Length and Duration .........................................................................................16 
4.2. 
Variable Definitions ....................................................................................................17 
4.2.1. 
Body Mass Index ........................................................................................................17 
4.2.2. 
Body Surface Area ......................................................................................................17 


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4.2.3. 
Prior and Concomitant Medication .............................................................................17 
5. 
STATISTICAL METHODOLOGY ...........................................................................18 
5.1. 
General Methodology .................................................................................................18 
5.2. 
Treatment Groups .......................................................................................................18 
5.3. 
Analysis Populations ..................................................................................................18 
5.3.1. 
Efficacy/Safety Evaluable Population ........................................................................18 
5.3.2. 
Dose Escalation Tolerability Evaluable Populations ..................................................18 
5.3.3. 
Pharmacokinetic Evaluable Populations .....................................................................19 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................19 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............19 
6.1.1. 
Demographics .............................................................................................................19 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................19 
6.1.3. 
Prior Therapy ..............................................................................................................20 
6.1.4. 
Medical History ..........................................................................................................20 
6.2. 
Disposition of Subjects ...............................................................................................20 
6.3. 
Protocol Deviations ....................................................................................................20 
6.4. 
Exposure .....................................................................................................................20 
6.4.1. 
Exposure for INCB052793 .........................................................................................20 
6.4.2. 
Exposure for Itacitinib ................................................................................................21 
6.4.3. 
Exposure for Dexamethasone .....................................................................................21 
6.4.4. 
Exposure for Azacitidine ............................................................................................21 
6.5. 
Study Drug Compliance .............................................................................................21 
6.6. 
Prior and Concomitant Medication .............................................................................22 
7. 
EFFICACY .................................................................................................................22 
7.1. 
General Considerations ...............................................................................................22 
7.2. 
Efficacy Hypotheses ...................................................................................................22 
7.3. 
Analysis of the Efficacy Parameter ............................................................................22 
7.3.1. 
Solid Tumors ..............................................................................................................22 
7.3.1.1. 
Response Assessment .................................................................................................22 
7.3.1.2. 
Best Overall Response and Objective Response Rate ................................................22 
7.3.2. 
Lymphoma ..................................................................................................................23 
7.3.2.1. 
Response Assessment .................................................................................................23 


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7.3.2.2. 
Best Overall Response and Objective Response Rate ................................................23 
7.3.3. 
Acute Myeloid Leukemia ...........................................................................................24 
7.3.3.1. 
Response Assessment .................................................................................................24 
7.3.3.2. 
Best Overall Response and Objective Response Rate ................................................24 
7.3.4. 
Myelodysplastic Syndrome ........................................................................................24 
7.3.4.1. 
Response Assessment .................................................................................................24 
7.3.4.2. 
Best Overall Response and Objective Response Rate ................................................24 
7.3.5. 
Myelodysplastic Syndrome/Myeloproliferative Neoplasms ......................................25 
7.3.5.1. 
Response Assessment .................................................................................................25 
7.3.5.2. 
Best Overall Response and Objective Response Rate ................................................25 
7.3.6. 
Multiple Myeloma ......................................................................................................25 
7.3.6.1. 
Response Assessment .................................................................................................25 
7.3.6.2. 
Best Overall Response and Objective Response Rate ................................................26 
7.4. 
Analysis of Other Efficacy Variables .........................................................................26 
7.4.1. 
Eastern Cooperative Oncology Group Performance Status ........................................26 
7.5. 
Pharmacokinetic Analyses ..........................................................................................26 
8. 
SAFETY AND TOLERABILITY ..............................................................................27 
8.1. 
General Considerations ...............................................................................................27 
8.2. 
Adverse Events ...........................................................................................................27 
8.2.1. 
Adverse Event Definitions ..........................................................................................27 
8.2.2. 
Dose-Limiting Toxicities ............................................................................................27 
8.2.3. 
Maximum Tolerated Dose ..........................................................................................27 
8.2.4. 
Adverse Event Summaries ..........................................................................................28 
8.3. 
Clinical Laboratory Tests ...........................................................................................29 
8.3.1. 
Laboratory Value Definitions .....................................................................................29 
8.3.2. 
Laboratory Value Summaries .....................................................................................30 
8.4. 
Vital Signs ..................................................................................................................30 
8.5. 
Electrocardiograms .....................................................................................................30 
9. 
INTERIM ANALYSES ..............................................................................................31 
9.1. 
Overview of Interim Analyses ....................................................................................31 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................32 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................32 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................32 


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11. 
REFERENCES ...........................................................................................................33 
APPENDIX A.  PLANNED TABLES, FIGURES, AND LISTINGS ........................................34 
 
LIST OF TABLES 
Table 1: 
Probability of Dose Escalation for Specific Dose-Limiting Toxicity Rates 
During 3 + 3 Dose Escalation .....................................................................................13 
Table 2: 
Normal Ranges for Vital Sign Values ........................................................................30 
Table 3: 
Normal Ranges for Electrocardiogram Values ...........................................................31 
Table 4: 
Statistical Analysis Plan Versions ..............................................................................32 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................12 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
AML 
acute myeloid leukemia 
BMI 
body mass index 
BOR 
best overall response 
bpm 
beats per minute 
BSA 
body surface area 
CI 
confidence interval 
CR 
complete response 
CRF 
case report form 
CRi 
complete remission with incomplete hematologic recovery 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose-limiting toxicity 
 
DSS 
Durie Salmon stage 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
ELN 
European LeukemiaNET 
FDA 
Food and Drug Administration 
HMA 
hypomethylating agents 
HR 
heart rate 
IPSS-R 
International Prognostic Scoring System Risk 
ISS 
international staging system 
IWG 
International Working Group 
JAK 
Janus kinase 
MDS 
myelodysplastic syndrome 
MDS/MPN 
myelodysplastic/myeloproliferative neoplasms 
MedDRA 
Medical Dictionary for Regulatory Activities 
MLFS 
morphologic leukemia-free state 
MM 
multiple myeloma 
MR 
minimal response 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 


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Abbreviation 
Definition 
NA 
not assessed 
ND 
not done/not applicable 
NE 
not evaluable 
ORR 
objective response rate 
OS 
overall survival 
PAD 
pharmacologically active dose 
PD 
progressive disease 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PR 
partial response 
PT 
preferred term 
QD 
once daily 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAP 
Statistical Analysis Plan 
sCR 
stringent complete response 
SD 
stable disease 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TG 
treatment group 
VGPR 
very good partial response 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
This is a Phase 1/2, open-label, dose-escalation study of the JAK inhibitor INCB052793 as a 
monotherapy and combination therapy in subjects with advanced malignancies.  The study will 
be conducted in 2 phases (Phase 1a/1b and Phase 2).  Phase 1a will be conducted with 
INCB052793 monotherapy dose escalation (Part 1) and dose expansion (Part 2).  Phase 1b will 
comprise treatment cohorts in which INCB052793 will be administered in combination with 
gemcitabine and nab-paclitaxel in select solid tumors (Cohort A); dexamethasone, carfilzomib, 
bortezomib, lenalidomide, and pomalidomide/dexamethasone in subjects with MM (Cohorts B, 
C, D, E, and G, respectively); azacitidine in subjects with AML or MDS (Cohort F), and 
INCB050465 in subjects with lymphoma (Cohort H), each including both a dose escalation 
(Part 1) and an optional dose expansion (Part 2).  Phase 2 will include 2 treatment cohorts in 
which subjects with AML and high-risk MDS who failed prior therapy with HMA will receive 
azacitidine in combination with INCB052793 (Cohort I) or in combination with itacitinib 
(Cohort J). 
Section 1 of the Protocol provides a detailed description of the investigational product, target 
patient population, rationale for doses to be examined, and potential risks and benefits of 
treatment with INCB052793, gemcitabine, nab-paclitaxel, dexamethasone, carfilzomib, 
bortezomib, lenalidomide, pomalidomide, azacitidine, INCB050465, and itacitinib. 
This study was prematurely terminated for lack of efficacy.  Cohorts A, C, D, E, G, and H were 
never opened to enrollment. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Protocol.  The scope of this plan includes the final analyses that are planned and will be 
executed by the Department of Biostatistics or designee, and the analyses of PK data. 
 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 52793-101 Protocol Amendment 9 dated 02 MAY 2017 and CRFs 
approved 01 NOV 2017.  Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and CRF versions. 
2.2. 
Study Objectives 
2.2.1. 
Primary Objectives 
 Phase 1a:  To assess the safety and tolerability of INCB052793 in subjects with 
advanced malignancies and select doses for further evaluation. 
 Phase 1b:  To assess the safety and tolerability of INCB052793 in combination with 
standard therapies and the novel phosphatidylinositol 3-kinase δ inhibitor 
INCB050465 in subjects with advanced malignancies. 
 Phase 2:  To evaluate the efficacy of INCB052793 in combination with azacitidine 
and of itacitinib in combination with azacitidine in subjects with AML and high-risk 
MDS who have failed prior therapy with HMA, based on ORR. 
2.2.2. 
Secondary Objectives 
 To assess preliminary efficacy by assessing the ORR in subjects with advanced 
malignancies. 
 To assess the safety and tolerability of INCB052793 in combination in azacitidine 
and of itacitinib in combination with azacitidine in subjects with AML and high-risk 
MDS who have failed prior therapy with HMA. 
 To assess the PK of INCB052793 as monotherapy administered in the fasted state and 
the effect of food on the PK of INCB052793. 
 To assess the PK of INCB052793 when administered in combination with standard 
therapies and INCB050465 in subjects with advanced malignancies, to assess the 
PK of INCB050465 when administered in combination with INCB052793, and to 
assess the PK of itacitinib when administered in combination with azacitidine. 


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2.3. 
Study Endpoints 
2.3.1. 
Primary Endpoints 
 Phase 1a and 1b:  Safety and tolerability of INCB052793 monotherapy and in 
combination with standard therapies in select malignancies as assessed by summary 
of clinical laboratory assessments, 12-lead ECGs, and AEs. 
 Phase 2:  ORR, defined as the proportion of subjects who achieve CR, CRi, PR, or 
hematologic improvement using the appropriate disease-specific criteria. 
2.3.2. 
Secondary Endpoints 
 Response rates in those subjects with measurable disease as determined by 
investigator assessment of response. 
 Safety and tolerability of INCB052793 in combination with azacitidine and of 
itacitinib in combination with azacitidine in subjects with AML and high-risk MDS 
who have failed prior therapy with HMA, assessed by summary of clinical laboratory 
assessments, 12-lead ECGs, and AEs. 
 Pharmacokinetics of INCB052793 and itacitinib (Phase 1a, Phase 1b, and Phase 2) 
will be summarized. 
 For Phase 1a Part 2 expansion portion (TGA and TGB), Cmax, Tmax, and AUC0-t for 
Cycle 1 Day 1 and Cmax, Tmax, Cmin, AUC0-t, and AUC0-τ for Cycle 1 Day 15, or Cmax, 
Tmax, Cmin, AUC0-t, and AUC0-τ for Cycle 2 Day 1 in the case of food-effect 
evaluation. 


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3. 
STUDY DESIGN 
This is a Phase 1/2, open-label, dose-escalation study of the JAK inhibitor INCB052793 as a 
monotherapy and combination therapy in subjects with advanced malignancies.  The study will 
be conducted in 2 phases (Phase 1a/1b and Phase 2).  Phase 1a will be conducted with 
INCB052793 monotherapy dose escalation (Part 1) and dose expansion (Part 2).  Phase 1b will 
comprise treatment cohorts in which INCB052793 will be administered in combination with 
dexamethasone in subjects with MM (Cohort B) and azacitidine in subjects with AML or MDS 
(Cohort F), each including both a dose escalation (Part 1) and an optional dose expansion 
(Part 2).  Phase 2 will include 2 treatment cohorts in which subjects with AML and high-risk 
MDS who failed prior therapy with HMA will receive azacitidine in combination with 
INCB052793 (Cohort I) or in combination with itacitinib (Cohort J).  Cohort I and Cohort J will 
use a Simon 2-stage design (1989) to evaluate the efficacy of the combination regimens.  If an 
insufficient number of responders are observed in the cohort at Stage 1, further enrollment in the 
cohort will be terminated. 
This study was prematurely terminated for lack of efficacy.  Cohorts A, C, D, E, G, and H were 
never opened to enrollment. 
The study design is shown in Figure 1.  Details of the study design are in Section 4 of the 
Protocol. 


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Figure 1: 
Study Design 
 
 


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3.1. 
Randomization 
Not applicable. 
3.2. 
Control of Type I Error 
For the primary efficacy endpoint in Phase 2, the 1-sided Type I error will be controlled at 
0.10 for each individual cohort expansion.  Note that this level of significance does not account 
for the multiple expansion cohorts.  For other endpoints, CIs will be reported at a 
95% confidence level. 
3.3. 
Sample Size Considerations 
3.3.1. 
Sample Size in Phase 1a 
In Part 1 of Phase 1a of the study, a 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 of Phase 1a will depend on the frequency of DLTs and the number of dose levels 
tested before the MTD or PAD is reached.  During the 3 + 3 dose escalation part, the 
probabilities of dose escalation from that dose level for various DLT rates are given in Table 1. 
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% 
Part 2 of Phase 1a will be the dose expansion part for TGA and TGB and up to 12 subjects may 
be enrolled in each expansion cohort.  With 12 subjects enrolled, there is > 85% chance of 
observing at least 1 responder if the true underlying response rate is 15%. 
Phase 1a of the study will enroll up to 36 subjects. 
3.3.2. 
Sample Size in Phase 1b 
In Part 1 of Phase 1b of the study, the standard 3 + 3 dose escalation design will be used in 
Cohorts B and F.  Based on the design, within each cohort, a minimum of 3 and up to 6 subjects 
will be enrolled at each dose level.  The total sample size in Part 1 of Phase 1b will depend on 
the frequency of DLTs and the number of dose levels tested before the MTD or PAD is reached.  
During the 3 + 3 dose escalation part, the probabilities of dose escalation from that dose level for 
various DLT rates are given in Table 1. 


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Part 2 of Phase 1b will be the dose expansion part for each cohort and up to 12 subjects may be 
enrolled in each expansion cohort.  With 12 subjects enrolled, there is > 85% chance of 
observing at least 1 responder if the true underlying response rate is 15%. 
Phase 1b of the study will enroll up to 39 subjects. 
3.3.3. 
Sample Size in Phase 2 
Phase 2 will include 2 treatment cohorts:  Cohort I and Cohort J.  A Simon 2-stage design (1989) 
will be used to evaluate the efficacy of combination regimens in these cohorts.  Let p0 denote the 
historical response rate, and p1 denote the target response rate.  Using a 1-sided Type I error of 
0.10 and power of 80%, with the assumption that p0 = 26% and p1=46%, each cohort will enroll 
an initial number of subjects (n1 = 9) at Stage 1.  If ≤ 2 subjects have responses among these 
9 subjects, it will be concluded that the true response rate is unlikely to be greater than or equal 
to the target rate, and no more subjects will be enrolled in that cohort.  Otherwise, if at least 
3 subjects have responses, 24 additional subjects will be treated in Stage 2 to estimate the 
response rate.  At the end of Stage 2, if ≤ 11 subjects have responded among the total of 
33 subjects, the efficacy improvement of the combination regimen will not be statistically 
significant.  
Up to 66 subjects will be enrolled for Cohort I and Cohort J in Phase 2. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 9 dated 02 MAY 2017 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 monotherapy (Phase 1a), Day 1 is the date that the first dose of INCB052793 is administered 
to the subjects. 
For combination therapy (Phase 1b and Phase 2), Day 1 is the date that the first dose of study 
treatment (INCB052793, dexamethasone, azacitidine, or itacitinib) 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 
For monotherapy (Phase 1a), baseline is the last nonmissing measurement obtained before the 
first administration of INCB052793, unless otherwise defined. 
For combination therapy (Phase 1b and Phase 2), baseline is the last nonmissing measurement 
obtained before the first administration of INCB052793 and dexamethasone for Cohort B; 
INCB052793 and azacitidine for Cohort F and Cohort I; or itacitinib and azacitidine for Cohort J. 
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. 


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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. 
When calculating time since diagnosis of cancer, partial cancer diagnosis date will be handled as 
follows: 
 If only the day is missing, then the imputed day will be the first 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. 
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 last 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 date of death will be imputed as follows:  
 If mmyyyy for the last known alive date = mmyyyy for the death date, then the death 
date will be set to the day after the last known alive date. 
 If mmyyyy for the last known alive 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. 
4.1.5. 
Cycle Length and Duration 
Dexamethasone will be administered as open-label commercial product at a starting dose of 
40 mg administered orally weekly on Days 1, 8, 15, and 22 of each 28-day cycle. 
Azacitidine will be administered as an open-label commercial product at a starting dose of 
75 mg/m2 subcutaneously for 5 days, followed by 2 days of no treatment, then 75 mg/m2 for 
2 days of each 28-day treatment cycle.  Intravenous administration is permitted if subcutaneous 
administration is not tolerated. 
Itacitinib will be administered at a starting dose of 300 mg administered orally QD. 
For monotherapy (Phase 1a), Cycle 1 Day 1 is the day that the first dose of INCB052793 is 
administered.  Scheduled cycle length is 21 days.  Actual Day 1 of subsequent cycles will 
correspond with the first day of administration of INCB052793 in that cycle. 
For combination therapy (Phase 1b and Phase 2), Cycle 1 Day 1 is the day that first dose of 
INCB052793 and dexamethasone is administered for Cohort B; INCB052793 and azacitidine is 
administered for Cohort F and Cohort I; or itacitinib and azacitidine is administered for Cohort J.  
Scheduled cycle length is 28 days.  Actual Day 1 of subsequent cycles will correspond with the 
first day of administration of dexamethasone or azacitidine in that cycle. 


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In the event that treatment cycles become out of sync with the originally planned schedule and 
cycle length is different from scheduled cycle length, the date of the Day 1 of subsequent cycles 
recorded on the eCRF will be used as the Day 1 of the subsequent cycles. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2. 
4.2.2. 
Body Surface Area 
Body surface area will be calculated based on the Mosteller (1987) formula as follows: 
BSA (m2) = {[weight (kg)  height (cm)] / 3600}½. 
4.2.3. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB052793 (Phase 1a); INCB052793 and dexamethasone for Cohort B; INCB052793 and 
azacitidine for Cohort F and Cohort I; or itacitinib and azacitidine for Cohort J. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
 Before the date of first administration of INCB052793 (Phase 1a); INCB052793 and 
dexamethasone for Cohort B; INCB052793 and azacitidine for Cohort F and Cohort 
I; or itacitinib and azacitidine for Cohort J and is ongoing throughout the study or 
ends on/after the date of first study medication administration. 
 On/after the date of first administration of INCB052793 (Phase 1a); INCB052793 and 
dexamethasone for Cohort B; INCB052793 and azacitidine for Cohort F and Cohort 
I; or itacitinib and azacitidine for Cohort J and is ongoing or ends during the course of 
study medication administration. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of study treatment (ie, INCB052793, dexamethasone, azacitidine, or 
itacitinib).  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. 
Interim analyses are planned for this study as defined in Section 9. 
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 
characteristics, 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/Safety Evaluable Population 
The efficacy/safety evaluable population includes all subjects enrolled in the study who received 
at least 1 dose of study treatment.  All efficacy analyses will be conducted using the efficacy 
evaluable population.  All demographics, baseline characteristics, disease history, subject 
disposition, and safety analyses will be conducted using the safety evaluable population. 
Specific analysis populations to be used for analysis by cancer type may include the following 
subgroups: 
 Solid tumor efficacy/safety evaluable population 
 Lymphoma efficacy/safety evaluable population 
 AML efficacy/safety evaluable population 
 MDS efficacy/safety evaluable population 
 MDS/MPN efficacy/safety evaluable population 
 MM efficacy/safety evaluable population 
5.3.2. 
Dose Escalation Tolerability Evaluable Populations 
The dose escalation tolerability evaluable population includes all subjects enrolled in the dose 
escalation part of Phase 1a who received at least 17 of 21 days of study medication or who 
discontinued treatment due to an adverse event in the DLT monitoring period and all subjects 
enrolled in the dose escalation part of Phase 1b who received at least 75% of planned study 
medication or who discontinued treatment due to an adverse event in the DLT monitoring period. 


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5.3.3. 
Pharmacokinetic Evaluable Populations 
The PK evaluable population includes all subjects who received at least 1 dose of study 
treatment 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. 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of planned tables, figures, and listings.  Sample data displays are 
included in a separate document. 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
6.1.1. 
Demographics 
The following demographics will be summarized and listed for the safety evaluable population:  
age, sex, race, ethnicity, height, weight, BMI, and BSA. 
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 evaluable population. 
For all subjects, baseline ECOG performance status will be summarized and listed. 
For subjects with solid tumors, time since initial diagnosis and solid tumor cancer type will be 
summarized and listed. 
For subjects with lymphoma, time since initial diagnosis, disease subtype, results from 
cytogenetic testing, Ann Arbor staging, presence of B-symptoms at baseline, and International 
Prognostic Index results will be summarized and listed. 
For subjects with AML, time since initial diagnosis, AML disease category, WHO classification, 
ELN risk classification, and FLT3 status will be summarized and listed. 
For subjects with MDS, time since initial diagnosis, WHO classification, IPSS-R group, and 
IPSS-R prognostic variables will be summarized and listed. 
For subjects with MDS/MPN, time since initial diagnosis, MDS/MPN disease type, and presence 
of extramedullary disease will be summarized and listed.  
For subjects with MM, time since initial diagnosis, initial DSS, initial ISS stage, current DSS, 
current ISS stage, myeloma type, light chain, and light chain type will be summarized and listed. 
Time since diagnosis will be calculated as: 
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25. 


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6.1.3. 
Prior Therapy 
Prior therapy will be summarized and listed for all subjects in the safety evaluable population. 
Number of subjects who received prior systemic cancer therapy and the number of prior systemic 
cancer therapy regimens for each subject will be summarized.  In addition, the number of 
subjects with each prior systemic cancer therapy will be summarized by drug class and preferred 
term.  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.  The date 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 of cells, 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 evaluable 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, were receiving ongoing treatment, 
discontinued study treatment with a primary reason for discontinuation, and withdrew from the 
study with a primary reason for withdrawal will be summarized and listed for the safety 
evaluable population. 
6.3. 
Protocol Deviations  
Protocol deviations recorded on the eCRF will be summarized by deviation category and 
presented in the subject data listings. 
6.4. 
Exposure 
For subjects in the safety evaluable population, exposure to INCB052793, dexamethasone, 
azacitidine, and itacitinib will be summarized descriptively as indicated in the following sections. 
6.4.1. 
Exposure for INCB052793 
 Duration of treatment (days):  Date of last dose of INCB052793 – date of first dose 
of INCB052793 + 1. 
 Average reported daily dose of INCB052793 (mg/day):  Total reported 
INCB052793 dose (mg) / duration of treatment with INCB052793 (days). 
 Dose modifications for INCB052793:  Number of subjects who had INCB052793 
dose reduction and interruption will be summarized. 


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6.4.2. 
Exposure for Itacitinib 
 Duration of treatment (days):  Date of last dose of itacitinib – date of first dose of 
itacitinib + 1. 
 Average reported daily dose of itacitinib (mg/day):  Total reported itacitinib dose 
(mg) / duration of treatment with itacitinib (days). 
 Dose modifications for itacitinib:  Number of subjects who had itacitinib dose 
reduction and interruption will be summarized. 
6.4.3. 
Exposure for Dexamethasone 
 Duration of treatment (days):  Date of last dose of dexamethasone – date of first 
dose of dexamethasone + 1. 
 Average reported daily dose of dexamethasone (mg/day):  Total reported 
dexamethasone dose (mg) / duration of treatment with dexamethasone (days). 
 Dose modifications for dexamethasone:  Number of subjects who had 
dexamethasone dose reduction and interruption will be summarized. 
6.4.4. 
Exposure for Azacitidine 
 Number of cycles:  Number of cycles with a nonzero dose of azacitidine. 
 Relative dose intensity of azacitidine (%):  100 × [total actual dose] / [total 
assigned dose]. 
Total actual dose (mg/m2) administered is the sum of the BSA-adjusted cumulative 
dose of azacitidine that has been administered to the subject. 
Total assigned dose (mg/m2) is the total dose expected if the subject had taken all 
doses as initially assigned.  Let S be the study day of the last date that the subject is 
exposed to azacitidine.  Let D be the assigned dose level of 75 mg/m2.  The total 
assigned dose is defined as: 
Total assigned dose (mg/m2) = D  (S / 28 + (S – 1) / 28 + (S – 2) / 28 + (S – 3) 
/ 28 + (S – 4) / 28 + (S – 7)/ 28 + (S – 8) / 28) 
where . assigns the smallest integer not less than the argument. 
 Azacitidine dose modifications:  Number of subjects who had azacitidine dose 
reduction and interruption will be summarized. 
6.5. 
Study Drug Compliance 
For subjects in the safety evaluable population, overall compliance (%) for INCB052793 or 
itacitinib will be calculated for all subjects as: 
Compliance (%) = 100  [total dose actually taken] / [total prescribed dose]. 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 


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The total actual dose taken will be calculated based on information entered on the Drug 
Accountability eCRF.  If there are dispensed drugs that have not been returned yet, the actual 
dose taken starting from the dispense date of the unreturned drugs will be imputed by the dose 
taken as reported on the Dosing eCRF. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary.  
Number and percentage of subjects in the safety evaluable population with each prior and 
concomitant mediations will be summarized by WHO drug class and WHO drug preferred term. 
7. 
EFFICACY 
Appendix A provides a list of planned tables, figures, and listings.  Sample data displays are 
included in a separate document. 
7.1. 
General Considerations 
All efficacy analyses will be performed using the efficacy evaluable population.  If there are 
fewer than 5 subjects for a disease subtype, efficacy data may be presented in data listings only. 
Due to study termination, only the primary and secondary efficacy endpoints will be analyzed. 
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 the 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 before 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. 


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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. 
7.3.2. 
Lymphoma 
7.3.2.1. 
Response Assessment 
Disease assessment for subjects with lymphoma 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 CT/MRI and/or PET for lymphoma will be 
recorded at each response assessment visit as Complete Radiologic Response/Complete 
Metabolic Response, Partial Remission/Partial Metabolic Response, SD/No Metabolic Response, 
PD/Progressive Metabolic Disease, NE, or ND. 
7.3.2.2. 
Best Overall Response and Objective Response Rate 
Best overall response for subjects with lymphoma is the best response recorded before and 
including the first PD/Progressive Metabolic Disease, in the order of Complete Radiologic 
Response/Complete Metabolic Response, Partial Remission/Partial Metabolic Response, SD/No 
Metabolic Response, PD/Progressive Metabolic Disease, and NE.  In the case of SD/No 
Metabolic Response, measurements must meet the SD/No Metabolic Response criterion at least 
once on or after Day 42.  Subjects who fail to meet this criterion will have a BOR of 
PD/Progressive Metabolic Disease if the next available assessment after the initial assessment 
indicates PD/Progressive Metabolic Disease 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 Complete Radiologic 
Response/Complete Metabolic Response or Partial Remission/Partial Metabolic Response. 
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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7.3.3. 
Acute Myeloid Leukemia 
7.3.3.1. 
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 at each response 
assessment as complete remission, CRi, partial remission, MLFS, SD, or treatment failure. 
7.3.3.2. 
Best Overall Response and Objective Response Rate 
For subjects with AML, BOR is the best response recorded before and including the first 
treatment failure, in the order of complete remission, CRi, partial remission, MLFS, SD, and 
treatment failure. 
A subject is considered a responder if the subject has a BOR of complete remission, CRi, or 
partial remission. 
Objective response rate is defined as 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. 
7.3.4. 
Myelodysplastic Syndrome 
7.3.4.1. 
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. 
Response status per investigator's assessment for MDS will be recorded at each response 
assessment as complete remission, partial remission, marrow complete remission, SD, treatment 
failure, disease progression, disease transformation, or relapse after complete remission or partial 
remission. 
7.3.4.2. 
Best Overall Response and Objective Response Rate 
For subjects with MDS, BOR is the best response recorded before and including the first 
progression, which consists of treatment failure, disease progression, disease transformation, and 
relapse after complete remission or partial remission, in the order of complete remission, partial 
remission, marrow complete remission, SD, and progression. 
A subject is considered a responder if the subject has a BOR of complete remission, partial 
remission, or marrow complete remission. 


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Objective response rate is defined as 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. 
7.3.5. 
Myelodysplastic Syndrome/Myeloproliferative Neoplasms 
7.3.5.1. 
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 will be recorded at each response assessment visit as complete remission, partial 
remission, marrow response, clinical benefit, SD, and disease progression. 
7.3.5.2. 
Best Overall Response and Objective Response Rate 
For subjects with MDS/MPN, BOR is the best response recorded before and including the first 
PD in the order of complete remission, partial remission, marrow response, clinical benefit, SD, 
and disease progression. 
A subject is considered a responder if the subject has a BOR of complete remission, partial 
remission, or marrow response. 
Objective response rate is defined as 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. 
7.3.6. 
Multiple Myeloma 
7.3.6.1. 
Response Assessment 
Disease assessment for subjects with MM will be performed following the International Uniform 
Response Criteria for Multiple Myeloma (Durie et al 2006) and 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), which is for assessing MR only.  
The investigator's assessment will be used to determine responses and will be logged into the 
eCRF. 
Response status per investigator's assessment for MM will be recorded at each response 
assessment visit as sCR, CR, VGPR, PR, MR, SD, PD, or relapse. 


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7.3.6.2. 
Best Overall Response and Objective Response Rate 
Best overall response for MM is the best response recorded before and including the first 
progression, which consists of PD and relapse, 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. 
7.4. 
Analysis of Other Efficacy Variables 
7.4.1. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group Performance status will be listed. 
7.5. 
Pharmacokinetic Analyses 
Pharmacokinetic analysis of INCB052793, including Cmax, Tmax, Cmin, AUC0-t, AUC0-τ and Cl/F, 
will be performed on samples collected at the specified timepoints.  The parameters will be 
calculated from the blood plasma concentrations of INCB052793 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. 


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8. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of planned tables, figures, and listings.  Sample data displays are 
included in a separate document. 
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 preferred terms reported on 
relatively few subjects. 
Unless otherwise stated, table summaries will be limited to AEs occurring within 30 days of the 
last administration of study drug. 
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 treatment (until 30 days after the last dose of study treatment).  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 treatment administration. 
Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be graded 
using the NCI CTCAE v4.03 (2010).  The CTCAE reporting guidelines and grading details are 
available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study treatment will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study treatment, the AE will be considered to be treatment-related.  The incidence of 
AEs and treatment-related AEs will be tabulated.  In addition, serious TEAEs will also be 
tabulated. 
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.  
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not 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 
The MTD will be defined as 1 dose level below that at which one-third or more of subjects in a 
particular cohort experience DLTs. 


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8.2.4. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include: 
 Number (%) of subjects reporting any TEAEs 
 Number (%) of subjects reporting any serious TEAEs 
 Number (%) of subjects reporting any Grade 3 or 4 TEAEs 
 Number (%) of subjects reporting any TEAEs related to INCB052793/itacitinib 
 Number (%) of subjects reporting any TEAEs related to dexamethasone/azacitidine 
 Number (%) of subjects who temporarily interrupted INCB052793/itacitinib because 
of TEAEs 
 Number (%) of subjects who temporarily interrupted dexamethasone/azacitidine 
because of TEAEs 
 Number (%) of subjects who permanently discontinued INCB052793/itacitinib 
because of TEAEs 
 Number (%) of subjects who permanently discontinued dexamethasone/azacitidine 
because of TEAEs 
 Number (%) of subjects with INCB052793/itacitinib dose reductions because of 
TEAEs 
 Number (%) of subjects with dexamethasone/azacitidine 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 Grade 3 or 4 TEAEs by PT in decreasing order of frequency 
 Summary of INCB052793 treatment-related TEAEs by SOC and PT 
 Summary of INCB052793 treatment-related TEAEs by PT in decreasing order of 
frequency 
 Summary of Grade 3 or 4 INCB052793 treatment-related TEAEs by SOC and PT 
 Summary of itacitinib treatment-related TEAEs by SOC and PT 
 Summary of itacitinib treatment-related TEAEs by PT in decreasing order of 
frequency 


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 Summary of Grade 3 or 4 itacitinib treatment-related TEAEs by SOC and PT 
 Summary of dexamethasone/azacitidine treatment-related TEAEs by SOC and PT 
 Summary of dexamethasone/azacitidine treatment-related TEAEs by PT in decreasing 
order of frequency 
 Summary of Grade 3 or 4 dexamethasone/azacitidine treatment-related TEAEs by 
SOC and PT 
 Summary of TEAEs with a fatal outcome 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 INCB052793 treatment-related serious TEAEs by SOC and PT 
 Summary of Itacitinib treatment-related serious TEAEs by SOC and PT 
 Summary of dexamethasone/azacitidine treatment-related serious TEAEs by SOC and 
PT 
 Summary of TEAEs leading to INCB052793 dose reduction by SOC and PT 
 Summary of TEAEs leading to itacitinib dose reduction by SOC and PT 
 Summary of TEAEs leading to dexamethasone/azacitidine dose reduction by SOC 
and PT 
 Summary of TEAEs leading to INCB052793 dose interruption by SOC and PT 
 Summary of TEAEs leading to itacitinib dose interruption by SOC and PT 
 Summary of TEAEs leading to dexamethasone/azacitidine dose interruption by SOC 
and PT 
 Summary of TEAEs leading to discontinuation of INCB052793 by SOC and PT 
 Summary of TEAEs leading to discontinuation of itacitinib by SOC and PT 
 Summary of TEAEs leading to discontinuation of dexamethasone/azacitidine by SOC 
and PT 
 Summary of Grade 3 or 4 TEAEs during the DLT monitoring period 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 will be assessed for severity based on the numerical component of 
CTCAE v4.03. 


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8.3.2. 
Laboratory Value Summaries 
Any laboratory test results and associated normal ranges from local laboratories will be 
converted to SI units.  When there are multiple laboratory nonmissing values for a subject's 
particular test at a scheduled visit, the laboratory value with the smallest laboratory sequence 
number will be used in by-visit summaries. 
Numeric laboratory values will be summarized descriptively in SI units, and non-numeric test 
values will be tabulated when necessary.  In addition, line graphs will be provided for 
hemoglobin, platelet counts, white blood cell counts, neutrophils, and lymphocytes. 
Shift tables will be presented showing change in CTCAE grade from baseline to worst grade 
postbaseline.  Separate summaries for abnormally high and abnormally low laboratory values 
will be provided when the laboratory parameter has both high and low grading criteria.  The 
denominator for the percentage calculation will be the number of subjects in the baseline 
category. 
8.4. 
Vital Signs 
Values at each scheduled timepoint, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, body 
temperature, and body weight will be summarized descriptively. 
Normal ranges for vital sign values are defined in Table 2.  The abnormal values for subjects 
exhibiting vital sign abnormalities will be listed along with their assigned dose level.  Alert vital 
signs are defined as an absolute value outside the defined normal range and percentage change 
from baseline greater than 25%.  The values for subjects exhibiting alert vital sign abnormalities 
will be listed. 
Table 2: 
Normal Ranges for Vital Sign Values 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35.5°C 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 
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 timepoint, 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 study treatment. 


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Normal ranges for ECG values are defined in Table 3.  Electrocardiogram values will also be 
considered abnormal if the absolute percentage change from baseline is more than 25% (30% for 
QRS interval).  Subjects exhibiting ECG abnormalities will be listed with study visit and 
assigned dose level.  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 3: 
Normal Ranges for Electrocardiogram Values 
Parameter 
High Threshold 
Low Threshold 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
QTcF, QTcB 
> 460 ms 
< 295 ms 
RR 
> 1330 ms 
< 600 ms 
QTcB = Bazett's correction; QTcF = Fridericia's correction. 
9. 
INTERIM ANALYSES 
9.1. 
Overview of Interim Analyses 
For Cohort I and Cohort J, a stopping rule for futility is planned for each cohort when 9 subjects 
have been treated and evaluated for response or have permanently discontinued study treatment 
because of disease progression, withdrawal of consent, or death.  Further enrollment in that 
cohort will be terminated for futility if ≤ 2 of the 9 subjects responded based on assessments 
provided by investigator. 


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10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 4. 
Table 4: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
28 MAY 2019 
10.1. 
Changes to Protocol-Defined Analyses 
Due to study termination, only primary and secondary efficacy endpoints will be analyzed.  
Cohorts A, C, D, E, G, and H were never opened to enrollment. 
Interim analyses of the primary efficacy endpoint are planned for Stage 1 subjects in Cohorts I 
and J. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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11. 
REFERENCES 
Bladé 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, 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 tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. 
Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987;317:1098. 
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 May 24, 2019. 
Savona MR, Malcovati 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. 
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1-10. 


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APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the Clinical Study 
Report.  Standard tables will follow the conventions in the Standard Safety Tables v1.3.  Shells 
are provided for nonstandard tables in a separate document. 
The lists of tables, figures, and listings are to be used as guidelines.  Modifications of the lists 
that do not otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
1.1.1 
Analysis Populations 
Safety Evaluable 
1.1.2 
Summary of Subject Disposition 
Safety Evaluable 
1.1.4 
Summary of Protocol Deviations 
Safety Evaluable 
1.2.1 
Summary of Demographic and Baseline Characteristics 
Safety Evaluable 
1.3.1.1 
Summary of Baseline Disease Characteristics and Disease History for Subjects 
with Solid Tumors 
Safety Evaluable 
1.3.1.2 
Summary of Baseline Disease Characteristics and Disease History for Subjects 
With Lymphoma 
Safety Evaluable 
1.3.1.3 
Summary of Baseline Disease Characteristics and Disease History for Subjects 
With AML 
Safety Evaluable 
1.3.1.4 
Summary of Baseline Disease Characteristics and Disease History for Subjects 
With MDS 
Safety Evaluable 
1.3.1.5 
Summary of Baseline Disease Characteristics and Disease History for Subjects 
With MDS/MPN 
Safety Evaluable 
1.3.1.6 
Summary of Baseline Disease Characteristics and Disease History for Subjects 
With MM 
Safety Evaluable 
1.3.2 
Summary of Prior Cancer Therapy 
Safety Evaluable 
1.3.3 
Summary of Prior Cancer Medication by Drug Class and Preferred Term 
Safety Evaluable 
1.4.1 
Summary of Prior Medications 
Safety Evaluable 
1.4.2 
Summary of Concomitant Medications 
Safety Evaluable 
1.5.1 
Summary of General Medical History 
Safety Evaluable 
2.1.1 
Summary of Best Overall Response for Subjects With Solid Tumors 
Efficacy Evaluable 
2.1.2 
Summary of Best Overall Response for Subjects With Lymphoma  
Efficacy Evaluable 
2.1.3 
Summary of Best Overall Response by IWG Response Criteria for Subjects 
With AML 
Efficacy Evaluable 
2.1.4 
Summary of Best Overall Response by IWG Response Criteria for Subjects 
With MDS 
Efficacy Evaluable 
2.1.5 
Summary of Best Overall Response for Subjects with MDS/MPN 
Efficacy Evaluable 
2.1.6 
Summary of Best Overall Response by International Uniform Response 
Criteria for Subjects With MM 
Efficacy Evaluable 
3.1 
Summary of Exposure and Compliance 
Safety Evaluable 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety Evaluable 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term 
Safety Evaluable 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred 
Term in Decreasing Order of Frequency 
Safety Evaluable 
3.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term, and Maximum Severity 
Safety Evaluable 
3.2.5 
Summary of Grade 3 or 4 Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety Evaluable 


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Table No. 
Title 
Population 
3.2.6 
Summary of Grade 3 or 4 Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency 
Safety Evaluable 
3.2.7 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety Evaluable 
3.2.8 
Summary of Serious Treatment-Emergent Adverse Events by Preferred Term 
in Decreasing Order of Frequency 
Safety Evaluable 
3.2.9.1 
Summary of INCB052793 Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.9.2 
Summary of Itacitinib Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.9.3 
Summary of Dexamethasone or Azacitidine Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.10.1 
Summary of INCB052793 Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety Evaluable 
3.2.10.2 
Summary of Itacitinib Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety Evaluable 
3.2.10.3 
Summary of Dexamethasone or Azacitidine Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety Evaluable 
3.2.11.1 
Summary of Grade 3 or 4 INCB052793 Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.11.2 
Summary of Grade 3 or 4 Itacitinib Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.11.3 
Summary of Grade 3 or 4 Dexamethasone or Azacitidine Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.12.1 
Summary of INCB052793 Treatment-Related Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.12.2 
Summary of Itacitinib Treatment-Related Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.12.3 
Summary of Dexamethasone or Azacitidine Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.13 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.14.1 
Summary of Treatment-Emergent Adverse Events Leading to INCB052793 
Dose Reduction by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.14.2 
Summary of Treatment-Emergent Adverse Events Leading to Itacitinib Dose 
Reduction by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.14.3 
Summary of Treatment-Emergent Adverse Events Leading to Dexamethasone 
or Azacitidine Dose Reduction by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.15.1 
Summary of Treatment-Emergent Adverse Events Leading to INCB052793 
Dose Interruption by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.15.2 
Summary of Treatment-Emergent Adverse Events Leading to Itacitinib Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.15.3 
Summary of Treatment-Emergent Adverse Events Leading to Dexamethasone 
or Azacitidine Dose Interruption by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.16.1 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of INCB052793 by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 


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Table No. 
Title 
Population 
3.2.16.2 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of Itacitinib by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.2.16.3 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of Dexamethasone or Azacitidine by MedDRA System Organ Class and 
Preferred Term 
Safety Evaluable 
3.2.17 
Summary of Grade 3 or 4 Treatment-Emergent Adverse Events During the 
DLT Monitoring Period by MedDRA System Organ Class and Preferred Term 
Safety Evaluable 
3.3.1 
Summary of Laboratory Values – Hematology 
Safety Evaluable 
3.3.2 
Shift Summary of Hematology Laboratory Values in CTC Grade – to the 
Worst Abnormal Value 
Safety Evaluable 
3.3.3 
Summary of Laboratory Values – Chemistry 
Safety Evaluable 
3.3.4 
Shift Summary of Chemistry Laboratory Values in CTC Grade – to the Worst 
Abnormal Value 
Safety Evaluable 
3.3.5 
Summary of Laboratory Values – Coagulation 
Safety Evaluable 
3.3.6 
Shift Summary of Coagulation Laboratory Values in CTC Grade – to the 
Worst Abnormal Value 
Safety Evaluable 
3.4.1 
Summary of Systolic Blood Pressure 
Safety Evaluable 
3.4.2 
Summary of Diastolic Blood Pressure 
Safety Evaluable 
3.4.3 
Summary of Pulse 
Safety Evaluable 
3.4.4 
Summary of Respiratory Rate 
Safety Evaluable 
3.4.5 
Summary of Body Temperature 
Safety Evaluable 
3.4.6 
Summary of Body Weight 
Safety Evaluable 
3.5.1 
Summary of PR Interval (ms) From 12-Lead ECG 
Safety Evaluable 
3.5.2 
Summary of QRS Interval (ms) From 12-Lead ECG 
Safety Evaluable 
3.5.3 
Summary of QT Interval (ms) From 12-Lead ECG 
Safety Evaluable 
3.5.4 
Summary of QTcB Interval (ms) From 12-Lead ECG 
Safety Evaluable 
3.5.5 
Summary of QTcF Interval (ms) From 12-Lead ECG 
Safety Evaluable 
3.5.6 
Summary of RR Interval (ms) From 12-Lead ECG 
Safety Evaluable 
3.5.7 
Summary of Outliers of QT and QTcB/QTcF Interval Values From 12-Lead 
ECG 
Safety Evaluable 
Figures 
Figure No. 
Title 
4.4.1  
Line Graph 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  
2.3.1 
Analysis Populations 
2.4.1 
Demographic and Baseline 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 Compliance 
2.5.2 
Study Drug Administration 
2.6.1 
Deaths 
2.6.2 
Best Overall Response 
2.6.3 
Overall Response Assessment by Visit 
2.6.4 
ECOG Status 
2.7.2 
Adverse Events 
2.7.3 
Dose-Limiting Toxicities 
2.7.4 
Serious Adverse Events 
2.7.5 
Fatal Adverse Events 
2.7.6 
Grade 3 or 4 Adverse Events During the DLT Monitoring Period 
2.7.7.1 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of INCB052793 
2.7.7.2 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of Itacitinib 
2.7.7.3 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of Dexamethasone and 
Azacitidine 
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 
2.11.1 
Body Weight 
 


Signature Manifest
Document Number: IC-STS-SAP-0150
Revision: 0
Title: 52793-101 SAP Original
All dates and times are in Eastern Standard Time.
APPROVAL: INCB 52793-101 SAP
Approval and Release
Name/Signature
Title
Date
Meaning/Reason
28 May 2019, 02:44:19 PM
Approved
29 May 2019, 03:41:21 PM
Approved
29 May 2019, 04:22:01 PM
Approved
30 May 2019, 12:35:32 PM
Approved