Clinical trial NCT04629339
Conditions: Non Small Cell Lung Cancer Urothelial Cancer Renal Cell Carcinoma Hepatocellular Carcinoma Melanoma
Keywords: checkpoint inhibitor naive Metastatic PD-L1
Sponsor: Incyte Corporation
Start date: 2021-09-02; Completion date: 2024-03-26
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
An open-label, nonrandomized study to evaluate the efficacy and safety of INCB086550, a first-in-class oral inhibitor of PD-L1, as initial immune checkpoint inhibitor therapy in participants with select solid tumors

Detailed description:

Arms: arm 1: INCB086550 will be administered orally twice a day.
Interventions: intervention 1: INCB086550
Intervention descriptions: intervention 1: INCB086550 will be administered orally twice a day.

Protocol documents:
Prot_000.pdf: 
Official Title: 
NCT Number: 
Document Date: 
A Phase 2 Study of INCB086550 (Oral PD-L1 Inhibitor) in 
Participants Who Are Immune Checkpoint Inhibitor–Naïve With 
Selected Solid Tumors
NCT04629339
Protocol Amendment 1, Version 2: 08-March-2021


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Clinical Study Protocol 
INCB 86550-203 
A Phase 2 Study of INCB086550 (Oral PD-L1 Inhibitor) in Participants 
Who Are Immune Checkpoint Inhibitor–Naïve With Selected Solid 
Tumors 
Product: 
INCB086550 
IND Number: 
139,900 
EudraCT Number: 
2020-000157-27 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 1): 
01 APR 2020 
Amendment 1 (Version 2): 
08 MAR 2021 
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, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
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 prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 86550-203 Protocol Amendment 1 (Version 2 dated 08 MAR 2021) 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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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................9
1.
PROTOCOL SUMMARY ..........................................................................................12
2.
INTRODUCTION ......................................................................................................43
2.1.
Background .................................................................................................................43
2.2.
Study Rationale ...........................................................................................................43
2.2.1.
Scientific Rationale for Study Design ........................................................................43
2.2.2.
Justification for Dose ..................................................................................................43
2.3.
Benefit/Risk Assessment ............................................................................................44
2.3.1.
INCB086550 Preclinical Background ........................................................................45
2.3.2.
INCB086550 Nonclinical Safety Summary ...............................................................46
3.
OBJECTIVES AND ENDPOINTS ............................................................................47
4.
STUDY DESIGN .......................................................................................................48
4.1.
Overall Design ............................................................................................................48
4.2.
Overall Study Duration ...............................................................................................49
4.3.
Study Termination ......................................................................................................49
5.
STUDY POPULATION .............................................................................................49
5.1.
Inclusion Criteria ........................................................................................................49
5.2.
Exclusion Criteria .......................................................................................................51
5.3.
Lifestyle Considerations .............................................................................................54
5.3.1.
Meals and Dietary Restrictions ...................................................................................54
5.4.
Screen Failures ............................................................................................................54
5.5.
Replacement of Participants .......................................................................................55
5.6.
Data Monitoring Committee .......................................................................................55
6.
STUDY TREATMENT ..............................................................................................56
6.1.
Study Treatment Administered ...................................................................................56
6.2.
Preparation, Handling, and Accountability ................................................................56
6.3.
Measures to Minimize Bias:  Randomization and Blinding .......................................57
6.4.
Study Treatment Compliance .....................................................................................57
6.5.
Dose Modifications .....................................................................................................58
6.5.1.
Management of Immune-Related Adverse Events .....................................................58
6.5.2.
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................64


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6.5.3. 
Criteria for Permanent Discontinuation of Study Drug ..............................................66 
6.5.4. 
Treatment After Initial Evidence of Radiologic Evidence of Disease 
Progression .................................................................................................................67 
6.6. 
Concomitant Medications and Procedures .................................................................68 
6.6.1. 
Permitted Medications and Procedures ......................................................................68 
6.6.2. 
Restricted Medications and Procedures ......................................................................69 
6.6.2.1. 
P-glycoprotein Substrates ...........................................................................................69 
6.6.2.2. 
Metformin ...................................................................................................................69 
6.6.2.3. 
Stomach Acid–Reducing Medications .......................................................................69 
6.6.2.4. 
Systemic Steroids ........................................................................................................69 
6.6.3. 
Prohibited Medications and Procedures .....................................................................69 
6.6.4. 
COVID-19 ..................................................................................................................70 
6.7. 
Treatment After the End of the Study .........................................................................70 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................71 
7.1. 
Discontinuation of Study Treatment ...........................................................................71 
7.1.1. 
Reasons for Discontinuation .......................................................................................71 
7.1.2. 
Discontinuation Procedures ........................................................................................71 
7.2. 
Participant Withdrawal From the Study .....................................................................72 
7.3. 
Lost to Follow-Up.......................................................................................................72 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................73 
8.1. 
Administrative and General Procedures .....................................................................73 
8.1.1. 
Informed Consent Process ..........................................................................................73 
8.1.2. 
Screening Procedures ..................................................................................................74 
8.1.3. 
Interactive Response Technology Procedure ..............................................................74 
8.1.4. 
Distribution of Dosing Diary and Patient Information Cards .....................................74 
8.1.5. 
Demography and Medical History ..............................................................................75 
8.1.5.1. 
Demographics and General Medical History .............................................................75 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................75 
8.1.5.3. 
Baseline Biomarker Documentation ...........................................................................75 
8.2. 
Efficacy Assessments .................................................................................................75 
8.2.1. 
Tumor Imaging by RECIST v1.1 ...............................................................................75 
8.2.1.1. 
Baseline Assessment During Screening .....................................................................76 




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9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................87 
9.1. 
Definition of Adverse Event .......................................................................................87 
9.2. 
Definition of Serious Adverse Event ..........................................................................88 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........89 
9.4. 
Reporting of Serious Adverse Events .........................................................................91 
9.5. 
Emergency Unblinding of Treatment Assignment .....................................................92 
9.6. 
Pregnancy ...................................................................................................................93 
9.7. 
Warnings and Precautions ..........................................................................................93 
9.8. 
Product Complaints ....................................................................................................93 
9.9. 
Treatment of Overdose ...............................................................................................94 
10. 
STATISTICS ..............................................................................................................95 
10.1. 
Sample Size Determination ........................................................................................95 
10.2. 
Populations for Analysis .............................................................................................95 
10.3. 
Level of Significance ..................................................................................................96 
10.4. 
Statistical Analyses .....................................................................................................96 
10.4.1. 
Primary Efficacy Analysis ..........................................................................................96 
10.4.1.1. 
Overall Response Rate ................................................................................................96 
10.4.2. 
Secondary Efficacy Analysis ......................................................................................97 
10.4.2.1. 
Duration of Response .................................................................................................97 
10.4.2.2. 
Disease Control Rate ..................................................................................................97 
 
97 
 
97 
 
97 
10.4.4. 
Safety Analyses ..........................................................................................................97 
10.4.4.1. 
Adverse Events ...........................................................................................................98 
10.4.4.2. 
Clinical Laboratory Tests ...........................................................................................98 
10.4.4.3. 
Vital Signs ..................................................................................................................98 
10.4.4.4. 
Electrocardiograms .....................................................................................................99 
10.4.4.5. 
Dose Intensity .............................................................................................................99 
 
99 
 
100 
10.5. 
Interim Analysis ........................................................................................................100 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................101 
11.1. 
Investigator Responsibilities .....................................................................................101 
11.1.1. 
Identification of the Coordinating Principal Investigator .........................................102 
11.2. 
Data Management .....................................................................................................102 
11.3. 
Data Privacy and Confidentiality of Study Records .................................................103 
11.4. 
Financial Disclosure .................................................................................................104 
11.5. 
Publication Policy .....................................................................................................104 
11.6. 
Study and Site Closure..............................................................................................105 
12. 
REFERENCES .........................................................................................................106 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS .............................................................................108 
110 
APPENDIX C. INSTRUCTION TO PARTICIPANTS FOR HANDLING STUDY 
DRUG (INCB086550) ..............................................................................................111 
APPENDIX D. MANAGEMENT OF POTENTIAL HY'S LAW CASES ..............................112 
APPENDIX E. CYTOCHROME P450 INHIBITORS/INDUCERS ........................................116 
APPENDIX F. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .....................................................................................................117 
APPENDIX G. PROTOCOL AMENDMENT SUMMARY OF CHANGES .........................119 
 
LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................12 
Table 2: 
Key Study Design Elements .......................................................................................13 
Table 3: 
Schedule of Activities for Schedule A (Continuous, 2-Week and 3-Week 
Intermittent, or 2-Week and 3-Week Step-Down Treatment Schedules in a 
28-Day Cycle) .............................................................................................................15 
Table 4: 
Schedule of Activities for Schedule B (1-Week Intermittent or Step-Down 
Treatment Schedules in a 28-Day Cycle) ...................................................................22 
Table 5: 
Schedule of Activities for Schedule C (2-Week Intermittent or Step-Down 
Treatment Schedules in a 21-Day Cycle) ...................................................................28 
Table 6: 
Schedule of Activities for Schedule D (1-Week Intermittent or Step-Down 
Treatment Schedules in a 21-Day Cycle) ...................................................................35 
Table 7: 
Objectives and Endpoints ...........................................................................................47 
Table 8: 
Exclusionary Laboratory Values ................................................................................52 
Table 9: 
Study Treatment Information .....................................................................................56 




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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
AJCC 
American Joint Committee on Cancer 
ALK 
anaplastic lymphoma kinase 
ALT 
alanine transaminase 
anti-HBc 
anti–hepatitis B core 
anti-HCV 
hepatitis C virus antibody 
aPTT 
activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate transaminase 
BCG 
Bacillus Calmette–Guérin 
BID 
twice daily 
CAR-T 
chimeric antigen receptor T-cell therapy 
CBC 
complete blood cell count 
cfDNA 
cell-free DNA 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CNS 
central nervous system 
COVID-19 
coronavirus disease 2019 
CPS 
composite performance score 
CR 
complete response 
CrCl 
creatinine clearance 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
DCR 
disease control rate 
DMC 
Data Monitoring Committee 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EDTA 
ethylenediaminetetraacetic acid 


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Abbreviations and 
Special Terms 
Definition 
EGFR 
epidermal growth factor receptor 
EOT 
end of treatment 
ER/PR 
estrogen and progesterone receptors 
ESMO 
European Society for Medical Oncology 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HAV 
hepatitis A virus 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCC 
hepatocellular carcinoma 
HCV 
hepatitis C virus 
HER2 
human epidermal growth factor receptor 2 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HPV 
human papillomavirus 
IB 
Investigator's Brochure 
IC50 
concentration that results in 50% inhibition 
ICF 
informed consent form  
ICH 
International Council on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IHC 
immunohistochemistry 
IFNγ 
interferon gamma 
INR 
international normalized ratio 
irAE 
immune-related adverse events 
IRB 
institutional review board 
IRT 
interactive response technology  
IV 
intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MSI-H 
microsatellite instability – high  
mTOR 
mammalian target of rapamycin 
NSCLC 
non–small cell lung cancer 


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Abbreviations and 
Special Terms 
Definition 
ORR 
objective response rate 
 
 
 
 
PD 
progressive disease 
PD-1 
programmed death 1 
PD-L1 
programmed death-ligand 1 
 
 
P-gp 
P-glycoprotein 
PHL 
potential Hy's law 
 
 
PR 
partial response 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QD 
once daily 
QTc 
QT interval corrected 
QTcF 
QT interval corrected using Fridericia's formula 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
stable disease 
SoA 
schedule of activities 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TGI 
tumor growth inhibition 
TPS 
tumor proportion score 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
VEGF 
vascular endothelial growth factor 
WBC 
white blood cell 


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1. 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 2 Study of INCB086550 (Oral PD-L1 Inhibitor) in Participants Who Are Immune 
Checkpoint Inhibitor–Naïve With Selected Solid Tumors 
Protocol Number:  INCB 86550-203 
Objectives and Endpoints: 
Table 1 presents the primary and major/key secondary endpoints and objectives. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpointsa 
Primary 
To determine the ORR of participants treated with 
INCB086550. 
ORR, defined as the percentage of participants 
with a best overall response of CR or PR 
confirmed by at least 1 repeat assessment 
≥ 28 days later according to RECIST v1.1 as 
determined by the investigator. 
Secondary 
To determine the efficacy of INCB086550 in 
participants with advanced solid tumors in respect 
to DCR. 
DCR, defined as the percentage of participants 
with a best overall response of CR or PR 
confirmed by at least 1 repeat assessment 
≥ 28 days later, or SD for ≥ 12 weeks, by 
investigator assessment per RECIST v1.1. 
To determine the efficacy of INCB086550 in 
participants with advanced solid tumors in respect 
to DOR. 
DOR, defined as the time from the earliest date of 
CR or PR confirmed by at least 1 repeat 
assessment ≥ 28 days later until the earliest date 
of disease progression by investigator assessment 
per RECIST v1.1, or death due to any cause, if 
occurring sooner than progression. 
To evaluate the safety of INCB086550 in 
participants with advanced solid tumors. 
Safety is determined by monitoring the frequency 
and severity of AEs, including the evaluation of 
laboratory tests, vital signs, and ECGs 
a The primary and secondary endpoints will be analyzed after all participants are considered evaluable for response 
according to the RECIST evaluable population. 
Overall Design: 
Table 2 presents the key study design elements.  Further study details are presented after the 
table.  Figure 1 presents the study design schema.  Adherence to the study design requirements, 
including those specified in the SoA (see Table 3, Table 4, Table 5, and Table 6), is essential and 
required for study conduct. 


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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indications 
Treatment of participants with recurrent or metastatic solid tumors who are 
immunotherapy naïve and may or may not have been treated with prior therapy 
for their disease. 
Population 
Male and female participants at least 18 years of age with 1 of the following 
solid tumors: 
 Participants with treatment-naïve, stage IV NSCLC (AJCC v8) whose tumors 
express PD-L1 TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay and who 
have no known activating genomic tumor aberrations that require targeted 
therapy (eg, EGFR, ALK, ROS, BRAF). 
 Participants with locally advanced, and unresectable or metastatic UC of the 
renal pelvis, ureter, bladder, or urethra (including transitional cell and mixed 
transitional or nontransitional cell histologies) who are cisplatin-ineligible, 
who are immune checkpoint inhibitor–naïve, and whose tumors express high 
PD-L1 (CPS ≥ 10) using the Dako PD-L1 IHC 22C3 assay. 
 Participants with advanced HCC that is not amenable to curative surgery or 
local treatment who have received at least 1 previous line of systemic therapy 
(ie, sorafenib or lenvatinib) or who were intolerant of sorafenib or lenvatinib 
treatment.  Participants must be immune checkpoint inhibitor–naïve. 
 Participants with advanced or metastatic RCC with a clear cell component 
with or without sarcomatoid features who have received prior systemic 
therapy for their disease (up to 2 previous regimens of a VEGF or mTOR 
inhibitor) and who are immune checkpoint inhibitor–naïve. 
 Participants with unresectable stage III or IV melanoma (excluding 
ocular/uveal melanoma) who are immune checkpoint inhibitor–naïve and 
have known BRAF V600 mutational status. 
Number of 
Participants 
Up to approximately 304 participants will receive INCB086550 and be 
enrolled into disease-specific cohorts of 23-42 participants. 
Study Design 
This is a Phase 2, open-label, nonrandomized, multicohort, global, multicenter 
study. 
Estimated Duration 
of Study 
Participation 
The study consists of 3 periods:  screening, study drug treatment, and 
follow-up.  Up to 28 days for screening, treatment for up to 2 years as long as 
participants are receiving benefit and have not met any criteria for study 
withdrawal, and 30 (± 7) days and 90 (± 14) days for safety follow-up, 
 
 every 12 weeks (± 14) days for up to 2 years from EOT. 
DMC 
Yes 
Treatment Groups and Duration: 
Disease-specific cohorts receiving single-agent INCB086550 (up to 2 years of treatment). 




























































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2. 
INTRODUCTION 
This open-label, global, nonrandomized multicohort trial is designed to provide a benchmark of 
efficacy for INCB086550 in key indications in which other PD-(L)1 inhibitors have already 
demonstrated efficacy. 
2.1. 
Background 
INCB086550 is a small molecule inhibitor of PD-L1 (also known as CD274).  PD-1, also known 
as CD279, is a cell surface receptor expressed on activated T cells, natural killer T cells, B cells, 
and macrophages (Greenwald et al 2005, Okazaki and Honjo 2006).  PD-1 functions as an 
intrinsic negative feedback system to prevent the activation of T cells, which in turn reduces 
autoimmunity and promotes self-tolerance.  In addition, PD-1 is also known to play a critical role 
in the suppression of antigen-specific T-cell response in diseases such as cancer and viral 
infection (Postow et al 2015, Sharpe et al 2007).  PD-1 binds to PD-L1, which is highly 
upregulated on many types of tumor cells as well as immune cells; therefore, targeting PD-L1 is 
an alternate approach for the treatment of some types of cancer. 
In the clinical setting, therapeutic use of blocking antibodies to either PD-L1 or PD-1 has been 
validated as an effective cancer treatment.  Durable clinical responses in a wide variety of solid 
and hematologic malignancies has led to marketing approvals of the anti–PD-1 antibodies 
pembrolizumab, cemiplimab, and nivolumab, as well as the anti–PD-L1 antibodies atezolizumab, 
durvalumab, and avelumab. 
2.2. 
Study Rationale 
2.2.1. 
Scientific Rationale for Study Design 
This open-label, nonrandomized study will evaluate the efficacy and safety of INCB086550, a 
first-in-class oral inhibitor of PD-L1, as initial immune checkpoint inhibitor therapy in 
participants with select solid tumors (ie, HCC, melanoma, NSCLC, RCC, and urothelial 
carcinoma) in which the efficacy of PD-(L)1 inhibitors has previously been established.  
INCB086550 selectively binds to PD-L1 with high affinity, thereby inhibiting the interaction of 
PD-L1 with PD-1.  INCB086550 also reduces surface PD-L1 expression by inducing PD-L1 
dimerization and subsequent internalization.  Treatment with INCB086550 results in immune 
activation as evidenced in preclinical and/or clinical studies by increased nuclear factor of 
activated T cells activity and cytokine production.  The primary endpoint of this study is ORR 
assessed by RECIST v1.1 as determined by the investigator.  Secondary 
 
endpoints include safety and tolerability, 
 changes observed with 
INCB086550 treatment. 
2.2.2. 
Justification for Dose 
INCB086550 will be administered orally in 21-day or 28-day cycles at a dose of 400 mg BID or 
lower.  
The dose was selected based on clinical and safety data from the Phase 1 first in human dose 
escalation trial (INCB 86550-102).  As of 30 OCT 2020, INCB086550 has been evaluated in 


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48 participants with advanced cancer in the Phase 1 study.  Participants have been treated at 
100 mg QD (n = 6), 200 mg QD (n = 3), 200 mg BID (n = 10), 400 mg QD (n = 4), 400 mg BID 
(n = 18), 800 mg QD (n = 1), and 800 mg BID (n = 6).  INCB086550 has been generally 
well-tolerated, and no dose-limiting toxicities have been observed to date.  The most frequently 
occurring TEAEs regardless of causality were decreased appetite (22.9%), fatigue (22.9%), 
nausea (22.9%), increased blood creatinine (20.8%), constipation (18.8%), diarrhea (18.8%), and 
increased lipase (16.7%).  The most frequently occurring TEAEs assessed as related to 
INCB086550 by the investigator were nausea (16.7% each) and increased lipase (10.4%).  Most 
TEAEs were Grade 1 or 2 in severity.  Serious TEAEs occurred in 16 participants (33.3%).  
Serious TEAEs that occurred in more than 1 participant were asthenia (n = 2, 4.2%), 
immune-related peripheral neuropathy (n = 2, 4.2%), and pneumonia (n = 2, 4.2%).  Serious 
TEAEs with a fatal outcome were dyspnea, intracranial hemorrhage, and cerebrovascular 
accident, each in 1 participant (2.1%).  All serious TEAEs with a fatal outcome were assessed as 
not related to INCB086550 by the investigator.  Refer to the INCB086550 IB for more detailed 
information. 
Immune activation has been observed in participants who received doses of INCB086550 at 
200 mg QD and higher.  Participants whose drug exposure correlated with ≥ 80% inhibition of 
PD-L1 in an ex vivo whole blood assay had increases in immune markers of T-cell activation or 
exhaustion (Ki-67, PD-1, ICOS, and/or TIM3) and interferon-related cytokines in plasma 
(CXCL9, CXCL10, IFNγ).  These findings align with those seen with anti–PD-(L)1 monoclonal 
antibodies. 
As of 01 MAR 2021, 6 participants in Study INCB 86550-102 have had investigator-assessed 
objective responses per RECIST v1.1.  The following responses have been observed:  confirmed 
CR in a participant with squamous cell anal carcinoma (400 mg BID), unconfirmed PR in a 
participant with squamous cell anal carcinoma (800 mg BID), confirmed PR in a participant with 
MSI-H colorectal carcinoma (400 mg BID), confirmed PR in a participant with ovarian cancer 
(400 mg BID), unconfirmed PR in a participant with MSI-H colorectal carcinoma with 
neuroendocrine histology (400 mg BID), and confirmed PR in a participant with MSI-H 
colorectal carcinoma (400 mg BID). 
The short half-life of INCB086550 (t½ = 8.62 hours) facilitates the investigation of alternative 
study dosing schedules to optimize benefit/risk.  Therefore, intermittent and/or step-down dosing 
schedules of INCB086550 may be investigated in specified cohorts.  These alternative schedules 
will consist of INCB086550 administered at or below 400 mg BID daily, followed by a period of 
either no treatment (intermittent dosing) or lower dosing (step-down dosing).  These cycles will 
then be repeated. 
2.3. 
Benefit/Risk Assessment 
Antibodies against PD-L1 or PD-1 can enhance or restore T-cell effector function, including 
cytokine production and cytolytic activity against tumor cells, as well as increase proliferation 
and/or infiltration of tumor-reactive CD8 T cells into established tumors.  To date, immune 
checkpoint inhibitors have shown that they are generally well-tolerated in patients with many 
different types of solid tumors.  Common treatment-related AEs that are related to the 
mechanism of action have occurred in several organ systems.  Although many different types of 
serious irAEs have uniformly occurred with different immune checkpoint inhibitors, most irAEs 


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are successfully managed by following irAE management guidelines (Brahmer et al 2018, 
Haanen et al 2017), an adapted version of which is incorporated in the current study. 
INCB086550 has a short half-life (8.62 hours after a single 100-mg dose) in comparison to 
monoclonal antibodies such as nivolumab, which has a terminal half-life of 26 days and receptor 
occupancy of 72% after 57 days (Fessas et al 2017).  Thus, blockage of PD-(L)1 signaling is 
maintained for extended periods after interruption of monoclonal antibodies for irAEs.  In this 
regard, the ability to more rapidly interrupt immune checkpoint blockade with INCB086550 
along with the option to utilize standard therapy such as corticosteroids may improve irAE 
management options compared with immune checkpoint monoclonal antibodies. 
Treatment with PD-(L)1 therapies causes irAEs in all organ systems evaluated.  In fact, 
development of irAEs predicts clinical benefit for patients, and appropriate management of 
irAEs may provide maximum clinical benefit (Ricciuti et al 2019, Toi et al 2018, Xing 
et al 2019).  Therefore, the assessment of outcomes for participants who experience AEs 
including the frequency and overall CTCAE grade will be key safety objectives in INCB086550 
studies. 
2.3.1. 
INCB086550 Preclinical Background 
INCB086550 binds to, and reduces the cellular surface expression of PD-L1 with high affinity.  
For example, PD-L1 expression was decreased following treatment with INCB086550 in 
MDA-MB-231 breast cancer cells (which express high levels of PD-L1) with an IC50 of 2 nM.  
Similarly, INCB086550 reduced PD-L1 expression on IFNγ-stimulated human peripheral blood 
monocytes with an IC50 value of 12.2 nM (see Figure 2). 
Figure 2: 
INCB086550 Reduces Tumor PD-L1 Expression 
 
INCB086550 also appears as efficacious as atezolizumab in preclinical humanized mouse model 
studies.  Figure 3 shows that INCB086550 and atezolizumab produce a similar reduction of 
tumor volume in humanized mice bearing MDA-MB-231 tumors. 


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Figure 3: 
MDA-MB-231 Humanized Mouse Model 
 
More detailed information about the preclinical activity of INCB086550 may be found in the IB. 
2.3.2. 
INCB086550 Nonclinical Safety Summary 
In vitro studies were conducted to characterize the potential risks of inhibiting the PD-(L)1 
interaction with INCB086550.  These studies demonstrated that INCB086550 binds to human 
PD-L1 and disrupts the PD-L1/PD-1 interaction at nanomolar concentrations.  Clinical studies 
with blocking antibodies to either PD-1 or PD-L1 have shown an induction of autoimmune 
responses.  Given the mechanism of action of INCB086550, autoimmune AEs may be seen upon 
administration.  Nonclinical pharmacology and toxicology studies have shown no adverse effects 
or target organ toxicity. 
In the pivotal 28-day studies, INCB086550 was well tolerated at all tested doses up to 
1000 mg/kg in rats and 715 mg/kg per day in monkeys.  Findings associated with INCB086550 
in rats were observed only at 1000 mg/kg per day and included decreased red blood cell mass 
(red blood cells, hemoglobin, and hematocrit), higher reticulocyte counts and red cell 
distribution, higher neutrophil and monocyte counts, and histiocytic infiltrates in the duodenum, 
jejunum, and/or ileum, and increased apoptosis/necrosis in the ileum in both males and females.  
The severity of these findings was limited to minimal to mild, and they were thus considered 
nonadverse.  Treatment-related findings in monkeys were limited to emesis at doses ≥ 200 mg/kg 
per day with no evidence of target organ toxicity. 
Consistent with pharmacodynamic data, INCB086550 reduced the growth of MDA-MB-231 in 
humanized NSG mice and increased the number of CD4 T cells after 28 days of treatment.  
INCB086550 induced statistically significant TGI compared to vehicle control.  The dose levels 
of INCB086550 0.2, 2, and 20 mg/kg induced TGI of 40%, 49%, and 52%, respectively.  A 
similar study was conducted using immunocompromised Balb/C nu/nu mice as the host, and no 
TGI was found.  These results indicate that an intact immune system is required for the efficacy 
of INCB086550.  Similar data were obtained using MC38 tumor cells that genetically 
overexpressed human PD-L1.  INCB086550 induced statistically significant TGI compared with 
the vehicle control.  The dose levels of INCB086550 2, 20, and 200 mg/kg induced TGI of 37%, 
60%, and 71%, respectively.  Consistent with the MDA-MB-231 xenograft data, INCB086550 
did not inhibit MC38-hPD-L1 tumor growth in immunocompromised NSG mice.  This indicates 
that an intact immune system is required for the efficacy of INCB086550.  Dose-dependent 
tumor growth inhibition and PD-L1 reduction were observed.  Accordingly, increasing numbers 


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of infiltrating CD8 T cells were observed after INCB086550 administration.  Antitumor activity 
was abolished in immunocompromised animals for both preclinical mouse models, suggesting an 
immune-mediated mode of action. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of INCB086550 may be found in the IB. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 7 presents the objectives and endpoints. 
Table 7: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the ORR of participants treated with 
INCB086550. 
ORR, defined as the percentage of participants with a 
best overall response of CR or PR confirmed by at least 
1 repeat assessment ≥ 28 days later according to 
RECIST v1.1 as determined by the investigator. 
Secondary 
To determine the efficacy of INCB086550 in 
participants with advanced solid tumors in respect to 
DCR. 
DCR, defined as the percentage of participants with a 
best overall response of CR or PR confirmed by at least 
1 repeat assessment ≥ 28 days later, or SD for 
≥ 12 weeks, by investigator assessment per 
RECIST v1.1. 
To determine the efficacy of INCB086550 in 
participants with advanced solid tumors in respect to 
DOR. 
DOR, defined as the time from the earliest date of CR 
or PR confirmed by at least 1 repeat assessment 
≥ 28 days later until the earliest date of disease 
progression by investigator assessment per 
RECIST v1.1, or death due to any cause, if occurring 
sooner than progression. 
To evaluate the safety of INCB086550 in participants 
with advanced solid tumors. 
Safety is determined by monitoring the frequency and 
severity of AEs, including the evaluation of laboratory 
tests, vital signs, and ECGs 




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4.2. 
Overall Study Duration 
The study begins when the first participant signs the ICF.  The end of the study is defined as the 
date of the last visit of the last participant in the study.  Participants completing treatment or 
prematurely discontinuing the study drug will be followed 
 
A participant is considered to have completed the study if he/she has completed all periods of the 
study 
 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract.  The investigator is to notify the IRB/IEC in writing of the 
study's completion or early termination, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, if, for example, required by regulatory decision 
or upon advice of the DMC.  If the study is terminated prematurely, the sponsor will notify the 
investigators, the IRBs and IECs, and regulatory bodies of the decision and reason for 
termination of the study.  The DMC will recommend termination of the study if warranted, as 
described in Section 5.6. 
5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential.  Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign a written ICF for the study. 
2. Men and women 18 years of age or older. 
3. Measurable disease per RECIST v1.1. 
4. ECOG performance status of 0 to 1 for all tumor types.  Urothelial carcinoma allows 
ECOG of 0 to 2. 
5. Histologically or cytologically confirmed disease-specific diagnosis as follows: 
a. Treatment-naïve, stage IV NSCLC (AJCC v8) in participants whose tumors express 
PD-L1 TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay and who have no known 
activating genomic aberrations that require targeted therapy (eg, EGFR, ALK, ROS, 
BRAF). 


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b. Locally advanced, and unresectable or metastatic UC of the renal pelvis, ureter, 
bladder, or urethra (including transitional cell and mixed transitional or 
nontransitional cell histologies) in participants who are cisplatin-ineligible, who are 
immune checkpoint inhibitor–naïve, and whose tumors express high PD-L1 
(CPS ≥ 10) using the Dako PD-L1 IHC 22C3 assay. 
Exception for UC:  Previous systemic therapy for locally advanced and unresectable 
or metastatic UC is not allowed except for neoadjuvant or adjuvant chemotherapy if 
more than 12 months before disease recurrence. 
c. Advanced HCC that is not amenable to curative surgery or local treatment in 
participants who have received at least 1 previous line of systemic therapy 
(ie, sorafenib or lenvatinib) or who were intolerant of sorafenib/lenvatinib treatment, 
have a Child-Pugh score of ≤ 6 (Child-Pugh A), and who are immune checkpoint 
inhibitor–naïve.  Participants with HBV infection are required to be receiving 
effective antiviral therapy and have a viral load < 100 IU/mL at screening; 
participants with HCV must have no detectable HCV RNA after curative therapy.  
Participants with fibrolamellar and mixed hepatocellular/cholangiocarcinoma 
subtypes are not eligible. 
Exception for HCC:  Participants without access to prior systemic therapy 
(ie, sorafenib or lenvatinib). 
d. Advanced or metastatic RCC with a clear cell component with or without 
sarcomatoid features in participants who have received prior systemic therapy for 
their disease (up to 2 previous regimens of a VEGF or mTOR inhibitor) and who are 
immune checkpoint inhibitor–naïve. 
Exception for RCC:  Participants without access to prior systemic therapy (ie, VEGF 
or mTOR inhibitors). 
e. Unresectable stage III or IV melanoma (excluding ocular/uveal melanoma) in 
participants who are immune checkpoint inhibitor–naïve.  BRAF V600 mutation 
status must be known. 
Exception for melanoma:  Participants may have received 1 prior line of therapy.  
This therapy could include previous treatment with BRAF/MEK inhibitors in 
participants with known BRAF V600 mutation or chemotherapy.   
6. Willingness to avoid pregnancy or fathering children based on the criteria below (CTFG 
2020). 
a. Men must agree to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening through 190 days after the last dose of study drug 
(or longer as appropriate based on country-specific requirements) and must refrain 
from donating sperm during this period.  Permitted methods that are at least 
99% effective in preventing pregnancy (see Appendix A) should be communicated to 
the participants and their understanding confirmed. 


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b. Women of childbearing potential must:  
− have a negative serum pregnancy test at screening and must agree to take 
appropriate precautions to avoid pregnancy (with at least 99% certainty) from 
screening through 190 days after the last dose of study treatment.  Additionally, 
monthly telephone visits should take place to check pregnancy status (which may 
include home pregnancy tests) during the period when contraception is mandatory 
(190 days after the last dose of study drug).  Permitted methods that are at least 
99% effective in preventing pregnancy (see Appendix A) should be 
communicated to the participants and their understanding confirmed. 
− refrain from donating oocytes from 30 days before the first dose of study drug 
until 190 days after the last dose. 
c. Women of nonchildbearing potential (as defined in Appendix A) are eligible. 
7. Participants must have radiologic documentation of disease progression after treatment 
with available therapies except for participants with NSCLC, who are required to be 
treatment-naïve.   
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Prior receipt of an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent, or treatment with an 
immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL2, 4-1BB, 
CAR-T). 
2. Receipt of any anticancer therapy or participation in another interventional clinical study.  
Note:  For RCC and HCC, the participant must not have received treatment within 
21 days or 5 half-lives (whichever is longer) before the first administration of study drug. 
3. Radiotherapy within 14 days of first dose of study treatment (28 days for pelvic 
radiotherapy or 6 months for thoracic region radiotherapy that is > 30 Gy). 
4. Concomitant treatment with moderate and potent CYP3A4/CYP3A5 inhibitors or 
inducers (see Appendix E).   
Note:  A washout period ≥ 5 half-lives before the first dose of INCB086550 is required 
for enrollment into the study for prior treatment with CYP3A4/CYP3A5 
inhibitors/inducers. 
5. Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with the 
exception of anemia not requiring transfusion support and any grade of alopecia).  
Endocrinopathy, if well-managed, is not exclusionary and should be discussed with the 
medical monitor. 
6. Participant has not recovered adequately from toxicities and/or complications from 
surgical intervention before starting study drug. 
7. Participants with laboratory values at screening defined in Table 8. 


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Table 8: 
Exclusionary Laboratory Values 
Laboratory Parameter 
Exclusion Criterion 
Hematology 
a 
Platelets 
≤ 100 × 109/L 
b 
Hemoglobin 
≤ 9 g/dL or 
< 5.6 mmol/L (transfusion is acceptable to meet this criterion) 
c 
ANC 
≤ 1.5 × 109/L 
Hepatic 
d 
ALT 
> 2.5 × institutional ULN 
For participants with HCC or liver metastases:  > 5 × ULN 
e 
AST 
> 2.5 × institutional ULN 
For participants with HCC or liver metastases:  > 5 × ULN 
f 
Total bilirubin 
≥ 1.5 × institutional ULN unless conjugated bilirubin ≤ ULN (conjugated bilirubin 
only needs to be tested if total bilirubin exceeds ULN).  If there is no institutional 
ULN, then direct bilirubin must be < 40% of total bilirubin. 
g 
Alkaline 
phosphatase 
≥ 2.5 × ULN. 
Note:  Participants with 1) bone metastases and 2) no hepatic parenchymal 
metastases on screening radiographic examinations may enroll if the alkaline 
phosphatase is < 5 × ULN.  Participants with 1) bone metastases and 2) hepatic 
parenchymal metastases on screening radiographic examinations may enroll if the 
alkaline phosphatase is < 5 × ULN only with medical monitor approval. 
Renal 
h 
Serum creatinine; or 
calculated CrCla 
Serum creatinine > 1.5 × institutional ULN; or 
CrCl < 50 mL/min for participants with creatinine levels < 1.5 × institutional ULN. 
For participants with UC or RCC, CrCl < 40 mL/min with creatinine levels 
< 1.5 × institutional ULN. 
Coagulation 
i 
INR or PT 
> 1.5 × institutional ULN for participants not receiving anticoagulant therapy. 
For participants with HCC:  > 2.3 × institutional ULN. 
j 
aPTT or PTT 
> 1.5 × institutional ULN for participants not receiving anticoagulant therapy 
k 
Albumin 
< 3 g/dL 
For participants with HCC or liver metastases:  < 2.5 g/dL 
a The Cockcroft and Gault equation (1976):  CrCl = {([140–age] × weight in kg) / (72 × serum creatinine)} × 0.85 (if female). 
8. Active malignancy of a type not included in the study population requiring treatment. 
Note:  Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of 
the skin that has undergone potentially curative therapy, in situ cervical cancer, or 
early-stage endometrial cancer. 
9. Active autoimmune disease requiring systemic immunosuppression in excess of 
physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent). 
10. Evidence of interstitial lung disease or active, noninfectious pneumonitis. 


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11. Untreated or known active CNS metastases and/or carcinomatous meningitis. 
Note:  Participants with previously treated brain metastases may participate provided they 
are stable (without evidence of progression by imaging for at least 28 days before the first 
dose of study drug and any neurologic symptoms have returned to baseline), have no 
evidence of new or enlarging brain metastases or CNS edema, and have not required 
steroids for at least 7 days before the first dose of study drug. 
12. With the exception of participants with HCC, known active HAV, HBV, or HCV 
infection, as defined by elevated transaminases with the following serology:  positivity 
for HAV IgM antibody, anti-HCV, anti-HBc IgG or IgM, or HBsAg (in the absence of 
prior immunization). 
Note:  For participants with cleared prior HBV infection:  HBV prophylaxis should be 
considered per investigator discretion.  Monitor for HBV reactivation every 3 cycles by 
performing HBV viral load and HBsAg serology test.  Additional viral serologic testing 
may be performed at the investigator's discretion. 
Note:  Participants with no prior history of HBV infection who have been vaccinated 
against HBV and who have a positive antibody against HBsAg as the only evidence of 
prior exposure may participate in the study. 
Note:  Hepatitis C antibody–positive participants who received and completed treatment 
for hepatitis C that was intended to eradicate the virus may participate if HCV RNA 
levels are undetectable. 
13. Active infection requiring systemic therapy. 
14. Receipt of systemic antibiotics within 28 days of first dose of study treatment. 
15. Probiotic usage during screening and throughout the study treatment period. 
16. Participants who are known to be HIV-positive. 
17. Participants with impaired cardiac function or clinically significant cardiac disease: 
a. New York Heart Association Class III or IV cardiac disease, including preexisting 
clinically significant ventricular arrhythmia, congestive heart failure, or 
cardiomyopathy. 
b. Unstable angina pectoris ≤ 6 months before study participation. 
c. Acute myocardial infarction ≤ 6 months before study participation. 
d. Other clinically significant heart disease (ie, ≥ Grade 3 hypertension, history of labile 
hypertension, or poor compliance with an antihypertensive regimen) must have 
recovered (to baseline or ≤ Grade 1) from toxicity associated with prior treatment. 
18. History or presence of an ECG finding that, in the investigator's opinion, is clinically 
meaningful.  Screening QTcF interval > 450 milliseconds is excluded; in the event that a 
single QTc is > 450 milliseconds, the participant may enroll if the average QTc for the 
3 ECGs is  ≤ 450 milliseconds.  For participants with an intraventricular conduction delay 
(QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with 
sponsor approval.  The JTc must be ≤ 340 milliseconds if JTc is used in place of the QTc.  
Participants with left bundle branch block are excluded. 


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Note:  Participants with QTc prolongation due to pacemaker may enroll if the JTc is 
normal (≤ 340 milliseconds) and medical monitor approval is granted. 
19. Female participant is pregnant or breastfeeding within the projected duration of the study, 
starting with the screening visit through the 90-day safety follow-up, or male participant 
is expecting to conceive or father children within the projected duration of the study, 
starting with the screening visit through 100 days after the last dose of study treatment. 
20. Has received a live vaccine within 90 days of the planned start of study drug. 
Note:  Examples of live vaccines include, but are not limited to, the following:  measles, 
mumps, rubella, chicken pox, some zoster, yellow fever, rabies, BCG, and typhoid 
vaccines.  Seasonal influenza vaccines for injection are generally killed virus vaccines 
and are allowed; however, intranasal influenza vaccines are live-attenuated vaccines and 
are not allowed. 
21. Current use of a prohibited medication as described in Section 6.6.3. 
22. Life expectancy < 3 months. 
23. Known hypersensitivity or severe reaction to any component of study drug or formulation 
components. 
24. History of organ transplant, including allogeneic stem cell transplantation. 
25. Presence of a gastrointestinal condition that may affect drug absorption.   
26. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug and attending required study visits; 
pose a significant risk to the participant; or interfere with interpretation of study data. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Participants will refrain from consuming Seville oranges, pomegranates, grapefruit, pomelos, 
exotic citrus fruits, grapefruit hybrids, and juice containing these restricted fruits from 72 hours 
before the first dose of study drug and throughout the study. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study.  This could be because the participant does not meet the 
eligibility criteria as described in Section 5.1 and Section 5.2 or for any other reason.  At a 
minimum, the following information must be collected and entered into the eCRF:  demography, 
screen failure details, and eligibility criteria.  Information on SAEs that occur after consent 
should be submitted to the sponsor. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened 1 time. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error.  Additionally, a participant who fails screening may 


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repeat the screening process 1 time if the investigator believes that there has been a change in 
eligibility status.  Participants who rescreen must reconsent and be assigned a new participant 
number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. 
5.6. 
Data Monitoring Committee 
This study will use a DMC to monitor safety at the planned analyses.  The DMC will make 
recommendations to the Sponsor clinical team regarding steps to ensure both participant safety 
and the continued ethical integrity of the trial.  Also, the DMC may review interim trial results 
(see Section 10.5), consider the overall risk and benefit to trial participants, and recommend if 
the trial should continue in accordance with the Protocol.  Specific details regarding 
composition, responsibilities, and governance, including the roles and responsibilities of the 
members are described in the DMC charter.  Requirements for and proper documentation of 
DMC reports, minutes, and recommendations are also described in the DMC charter.  The DMC 
charter will be reviewed and approved by all the DMC members. 




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The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records).  Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities.  The 
investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug including tablet counts from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the participants were provided the 
specified study drug.  These records should include dates, quantities, and any available batch or 
serial numbers or unique code numbers assigned to the investigational product and study 
participants. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional SOPs.  
If local procedures mandate on-site destruction of investigational supply, the site should (where 
local procedures allow) maintain the investigational supply until the study monitor inspects the 
accountability records in order to evaluate compliance and accuracy of accountability by the 
investigative site.  At sites where the study drug is destroyed before monitor inspection, the 
monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the Study Reference Manual. 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
All participants will be centrally assigned to open-label study treatment using IRT.  Full details 
will be provided in the IRT Study Reference Manual.  Study drug will be dispensed at the study 
visits summarized in the SoA (see Table 3, Table 4, Table 5, and Table 6).  Returned study drug 
should not be redispensed to the participants. 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with INCB086550 will be calculated by the sponsor based on the drug 
accountability (eg, tablet counts) documented by the site staff and monitored by the 
sponsor/designee.  Participants will be instructed to bring all unused study drug with them to the 
study visits in order for site personnel to conduct tablet counts to assess study drug 
accountability.  The drug accountability documentation will be used by the sponsor to calculate 
treatment compliance. 


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6.5. 
Dose Modifications 
Interruptions and modifications to the study treatment regimen are allowed per Protocol.  The 
occurrence of toxicities (related or unrelated to study drug) will guide decisions for treatment 
interruptions, modifications, or discontinuation for individual participants.   
Investigators should contact and discuss dose modifications with the medical monitor. 
Intraparticipant dose escalations will not be permitted during the course of the study. 
6.5.1. 
Management of Immune-Related Adverse Events 
An AE of a potential immunologic etiology or an irAE may be defined as an AE consistent with 
an immune phenomenon associated with drug exposure after all other etiologies have been 
eliminated.  Immune-related AEs may be expected based on the nature of INCB086550, its 
mechanism of action, and reported experience with other immunotherapies.  If an irAE is 
suspected, efforts should be made to rule out neoplastic, infectious, metabolic, autoimmune, 
toxic, or other etiologic causes before categorizing an AE as an irAE.  The investigator should 
promptly notify the sponsor (or designee) about participants who develop an irAE ≥ Grade 2. 
Participants, who have irAEs that resolve to ≤ Grade 1 within 14 days, may be rechallenged at 
the starting dose or with a dose reduction.  Continuation, withholding, dose modification, or 
discontinuation of INCB086550 will depend on severity of the irAE and affected organ/organ 
system and should be discussed with the medical monitor.  Any irAEs ≥ Grade 3 that require 
permanent discontinuation of INCB086550 per Table 10 may only be rechallenged with approval 
of the medical monitor.  Elevations in amylase or lipase that are ≥ Grade 3 do not require dose 
interruption or reduction if the participant is asymptomatic or if the elevation is clinically 
insignificant and has been discussed with the medical monitor. 
Participants should receive appropriate supportive care measures as deemed necessary by the 
treating investigator.  Suggested measures for the management of irAEs are outlined in Table 10.  
For each AE, attempts should be made to rule out other causes, including but not limited to 
metastatic disease, bacterial infection, or viral infection that might require specific supportive 
care. 
Management guidance for irAEs not detailed elsewhere in the Protocol should follow the ASCO 
Clinical Practice Guideline or ESMO Clinical Practice Guidelines (Brahmer et al 2018, Haanen 
et al 2017). 


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Table 10: 
Immune-Related Adverse Events Management Guidelines for INCB086550 
irAE 
CTCAE v5 
Grade 
Guidance for Restarting 
INCB086550 
Monitoring and/or Supportive Care 
Pneumonitis  
Grade 1 
Continue INCB086550 if 
asymptomatic. 
 
Withhold INCB086550 
given radiographic evidence 
of pneumonitis progression.  
May resume with 
radiographic evidence of 
improvement or resolution. 
• Monitor as appropriate (CT, 
spirometry/DLCO, history and physical 
examination, pulse oximetry, chest 
x-ray). 
• If no improvement, treat as Grade 2. 
Grade 2 
Withhold INCB086550 until 
resolution to ≤ Grade 1. 
• Administer systemic corticosteroid 
(prednisone 1-2 mg/kg or equivalent) 
with taper. 
• May consider empiric antibiotics. 
• Consider bronchoscopy with 
bronchoalveolar lavage. 
• Monitor as appropriate (history and 
physical examination, pulse oximetry, 
chest x-ray). 
• If no improvement within 2-3 days, treat 
as Grade 3. 
Grade 3, 
Grade 4, or 
recurrent 
Grade 2 
Permanently discontinue 
INCB086550. 
• Administer IV methylprednisolone 
1-2 mg/kg or equivalent with taper. 
• Administer empiric antibiotics. 
• If no improvement after 2 days, may add 
infliximab 5 mg/kg, mycophenolate 
mofetil IV 1 g twice daily, IV 
immunoglobulin for 5 days, or 
cyclophosphamide. 
• Pulmonary and infectious disease 
consults, if necessary. 
• Bronchoscopy with bronchoalveolar 
lavage ± transbronchial biopsy. 
Note:  If clinical presentation is 
consistent with pneumonitis, 
transbronchial biopsy is not needed. 


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Table 10: 
Immune-Related Adverse Events Management Guidelines for INCB086550 
(Continued) 
irAE 
CTCAE v5 
Grade 
Guidance for Restarting 
INCB086550 
Monitoring and/or Supportive Care 
Diarrhea/colitis 
Grade 1 
Continue INCB086550. 
• Monitor as appropriate. 
• Provide supportive care (hydration, 
electrolyte replacement, dietary 
changes). 
• Consider gastroenterology consult for 
prolonged event. 
Grade 2 or 
Grade 3 
Withhold INCB086550 until 
resolution to ≤ Grade 1. 
Grade 2:  
• If clinically indicated, administer 
systemic corticosteroids (prednisone 
1 mg/kg or equivalent) with taper. 
• Consider symptomatic treatment with 
antidiarrheal if infection has been ruled 
out. 
Grade 3:  
• Administer systemic corticosteroids 
(prednisone 1-2 mg/kg or equivalent) 
with taper. 
• If no improvement after 3-5 days, IV 
corticosteroid with taper or infliximab.  
• Gastroenterology consult for additional 
workup as appropriate. 
Grade 4 
Permanently discontinue 
INCB086550. 
• Administer IV methylprednisolone 
1-2 mg/kg or equivalent with taper.  
• If no improvement after 2-3 days, 
consider infliximab 5-10 mg/kg. 
• Gastroenterology consult for additional 
workup as appropriate. 


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Table 10: 
Immune-Related Adverse Events Management Guidelines for INCB086550 
(Continued) 
irAE 
CTCAE v5 
Grade 
Guidance for Restarting 
INCB086550 
Monitoring and/or Supportive Care 
Hepatitis 
(AST/ALT 
increased and/or 
total bilirubin 
increased) 
Grade 1 
Continue INCB086550. 
• Repeat laboratory measurements
1-2 times/week until return to baseline.
• Provide supportive care for symptoms.
Grade 2 or 
Grade 3 
lasting 
≤ 10 days 
Withhold INCB086550 until 
resolution to ≤ Grade 1. 
• Repeat laboratory measurements every
3 days until return to baseline.
• If elevations persist after 3 days or
symptomatic, administer systemic
corticosteroids (prednisone 0.5-1 mg/kg
or equivalent) with taper.
• Infliximab should NOT be used.
Grade 3 
lasting 
> 10 days or
Grade 4
Permanently discontinue 
INCB086550. 
• Repeat laboratory measurements every
1-2 days until return to baseline.
• Administer IV methylprednisolone
1-2 mg/kg or equivalent with taper.
• If corticosteroid refractory or elevations
persist after 3 days, consider
mycophenolate mofetil or azathioprine.
• Infliximab should NOT be used.
• Hepatology consult for additional
workup, as appropriate.
Dermatitis 
Grade 1 or 
Grade 2 
Continue INCB086550. 
• Consider dermatology consult.
• Supportive care with topical emollients,
oral antihistamines.
• Administer topical corticosteroid as
needed.
• If no improvement with topical
corticosteroid, consider systemic (oral)
corticosteroid.
Grade 3 
Withhold INCB086550 until 
resolution to ≤ Grade 1. 
• Dermatology consult.
• Administer IV methylprednisolone
1-2 mg/kg or equivalent with taper.
• Monitor for progression to severe
cutaneous adverse reaction (eg,
Stevens-Johnson syndrome, toxic
epidermal necrolysis, drug reaction with
eosinophilia and system
symptoms/drug-induced hypersensitivity
syndrome).
Grade 4 
Permanently discontinue 
INCB086550. 
Nephritis or renal 
dysfunction 
(creatinine 
increased) 
See Table 12 for immune-related nephritis and renal dysfunction AE 
management guidelines. 


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Table 10: 
Immune-Related Adverse Events Management Guidelines for INCB086550 
(Continued) 
irAE 
CTCAE v5 
Grade 
Guidance for Restarting 
INCB086550 
Monitoring and/or Supportive Care 
Diabetes mellitus 
Grade 1 or 
Grade 2 
Continue INCB086550. 
• Endocrine consult, especially for Type 1 
diabetes mellitus. 
• Oral antihyperglycemic therapy ± insulin 
for new onset Type 2 diabetes mellitus, 
as appropriate. 
• Insulin for Type 1 diabetes mellitus. 
• Titrate therapy to achieve glucose 
control. 
Grade 3 or 
Grade 4 
Withhold INCB086550 until 
glucose control is achieved 
and ≤ Grade 1. 
Hypothyroidism 
Grade 1 
Continue INCB086550. 
• Monitor TSH, FT4 as appropriate. 
Grade 2 
Consider withholding until 
resolution to ≤ Grade 1. 
• Endocrine consult for Grade 3 or 
Grade 4, consider for Grade 2. 
• Thyroid hormone replacement as 
appropriate. 
• Monitor TSH, FT4 while titrating 
hormone replacement and once 
adequately resolved. 
Grade 3 or 
Grade 4 
Withhold INCB086550 until 
resolution to ≤ Grade 1 with 
appropriate thyroid hormone 
supplementation. 
Hyperthyroidism 
Grade 1 
Continue INCB086550. 
• Monitor TSH, FT4 as appropriate. 
Grade 2 
Consider withholding until 
resolution to ≤ Grade 1. 
• Consider endocrine consult. 
• Beta-blocker (eg, atenolol, propranolol) 
for symptomatic relief. 
Grade 3 or 
Grade 4 
Withhold INCB086550 until 
resolution to ≤ Grade 1 with 
appropriate therapy. 
• Endocrine consult. 
• Prednisone 1-2 mg/kg or equivalent with 
taper only for severe symptoms of 
concern for thyroid storm. 
• Beta-blocker (eg, atenolol, propranolol) 
for symptomatic relief. 
• Consider potassium iodide or thionamide 
(methimazole or propylthiouracil). 
Myocarditis 
Any Grade 
Permanently discontinue 
INCB086550. 
• Administer high-dose corticosteroids 
initiated rapidly (oral or IV depending on 
symptoms). 
• Manage cardiac symptoms according to 
American College of 
Cardiology/American Heart Association. 
• Cardiology consult. 
• May offer immediate transfer to a 
coronary care unit for participants with 
elevated troponin or conduction 
abnormalities. 
• In participants without an immediate 
response to high-dose corticosteroids, 
may offer early institution of cardiac 
transplant rejection doses of 
corticosteroids (eg, methylprednisolone 
1 g every day) and the addition of either 
mycophenolate, infliximab, or 
antithymocyte globulin. 


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Table 10: 
Immune-Related Adverse Events Management Guidelines for INCB086550 
(Continued) 
irAE 
CTCAE v5 
Grade 
Guidance for Restarting 
INCB086550 
Monitoring and/or Supportive Care 
Hypophysitis or 
adrenal 
insufficiency 
Grade 1 or 
Grade 2 
Consider withholding until 
resolution to ≤ Grade 1. 
 Endocrine consult. 
 Administer systemic corticosteroids 
(with taper) and hormone replacement as 
clinically indicated. 
Grade 3 or 
Grade 4 
Withhold INCB086550 until 
resolution to ≤ Grade 1. 
Nervous system 
disorders 
Grade 1 
Continue INCB086550. 
 Neurologic consult 
 Monitor closely for any symptom 
progression. 
Grade 2 
Withhold INCB086550 until 
resolution to ≤ Grade 1. 
 Neurologic consult and workup 
including MRI.  Consider EMG, lumbar 
puncture, and CSF analysis. 
 Administer supportive care and 
corticosteroids. 
 Monitor closely for any symptom 
progression. 
Grade 3  
Withhold INCB086550 until 
resolution to ≤ Grade 1 OR  
Permanently discontinue 
INCB086550. 
 Neurologic consult and workup 
including MRI.  Consider EMG, lumbar 
puncture, and CSF analysis. 
 Administer supportive care and 
corticosteroids. 
 Continuation, withholding, or 
discontinuation of INCB086550 will 
depend on severity of irAE and affected 
organ/organ system.  Restarting 
participants after Grade 3 nervous system 
AEs requires medical monitor approval. 
Grade 4 
Permanently discontinue 
INCB086550. 
 Neurologic consult and workup 
including MRI.  Consider EMG, lumbar 
puncture, and CSF analysis. 
 Administer supportive care and/or 
corticosteroids. 
Other irAEs 
Grade 1 
Continue INCB086550. 
 Administer supportive care and/or 
corticosteroid for symptoms. 
 Continuation, withholding, or 
discontinuation of INCB086550 will 
depend on severity of irAE and affected 
organ/organ system.  Investigator must 
discuss with medical monitor. 
 Consider relevant consults, as 
appropriate. 
Grade 2 
Continue INCB086550 OR 
withhold INCB086550 until 
resolution to ≤ Grade 1  
Grade 3 
Withhold INCB086550 until 
resolution to ≤ Grade 1  
Grade 4  
Permanently discontinue 
INCB086550. 
CSF = cerebrospinal fluid; EMG = electromyography; FT4 = free thyroxine; TSH = thyroid-stimulating hormone. 


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6.5.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Dose interruptions and modifications of INCB086550 may occur for participants during the 
study treatment period.  The short half-life of INCB086550 (8.62 hours after a single 100 mg 
dose) may improve management options for participants who experience irAEs, unobtainable 
with immune checkpoint monoclonal antibodies, which possess long half-lives.  Management 
guidelines for AEs requiring dose modifications are described for general hematologic and 
nonhematologic toxicities that are not thought to be immune-related in Table 11.  Decisions 
regarding dose interruptions of INCB086550 should be made using clinical judgment of the 
investigator, taking into account the possible relatedness of the AE to the study drug and the 
participant's underlying condition.  Adverse events that have a clear alternative explanation or 
transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs 
or symptoms may be exempt from dose-interruption/discontinuation rules.  Participants may 
resume treatment as per management guidelines if no medical condition or other circumstance 
exists that, in the opinion of the investigator, would make the participant unsuitable for further 
treatment and participation in the study.  Treatment with INCB086550 may be delayed for up to 
28 days to allow for resolution of toxicity.  The treating investigator should contact the medical 
monitor to discuss the case of any participant whose treatment has been interrupted for more than 
28 days before restarting treatment with INCB086550.  
Dose interruptions are permitted in the case of medical/surgical events or logistical reasons not 
related to study therapy (eg, elective surgery, unrelated medical events, subject vacation, 
holidays).  Participants should be placed back on study therapy within 4 weeks (ie, 28 days) of 
the scheduled interruption, unless otherwise discussed with the medical monitor.  The reason for 
interruption should be documented accordingly. 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment.  Additional 
unscheduled visits with CBC may be performed.   


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Table 11: 
Non–Immune-Related Adverse Events Dose Modification Guidelines 
CTCAE Severity 
Suggested Modification 
Hematological toxicities 
CTCAE Grade 1 or Grade 2 
Continue INCB086550 treatment at the discretion of the investigator. 
CTCAE Grade 3 
• Restart when toxicity resolves to baseline or ≤ Grade 1. 
• First occurrence:  Restart at same dose or reduce dose by 1 dose level at 
the discretion of the investigator after discussion with the medical monitor. 
• Second occurrence:  Restart at reduced dose (if not already). 
CTCAE Grade 4 
Permanently discontinue study drug or discuss with medical monitor if 
treatment algorithm for CTCAE Grade 3 events (above) is appropriate. 
Nonhematological toxicities 
All Grades 
• For irAEs, follow the guidelines in Table 10. 
Permanently discontinue treatment for: 
• Any liver function abnormalities that meet the definition of Hy's law.  
• Encephalopathy of any grade. 
CTCAE Grade 1 or 2 
Continue treatment and initiate supportive care at the discretion of the 
investigator EXCEPT: 
• Permanently discontinue treatment for ≥ Grade 2 ocular toxicity. 
CTCAE ≥ Grade 3 
Permanently discontinue study treatment for any ≥ Grade 3 nonhematologic 
toxicity EXCEPT: 
• Transient (≤ 72 hours) abnormal laboratory values without associated 
clinically significant signs or symptoms. 
• Laboratory abnormalities ≥ Grade 3 without associated clinically 
significant signs or symptoms. 
• Nondesquamating rash ≥ Grade 3 that resolves within 48 hours with 
standard treatment. 
Grade 3 rash in the absence of desquamation, without mucosal involvement, 
and not requiring systemic steroids that resolves to ≤ Grade 1 in ≤ 14 days. 
• Grade 3 fatigue < 1 week. 
• Nausea, vomiting, and diarrhea adequately controlled with medical 
therapy within 48 hours. 
− For ≥ Grade 3 events that do not require permanent discontinuation, the 
following guidelines should be used: 
• Restart when toxicity resolves to baseline or ≤ Grade 1. 
• First occurrence:  Restart at same dose or reduce dose by 1 dose level at 
the discretion of the investigator after discussion with the medical monitor. 
• Second occurrence:  Restart at reduced dose (if not already). 
• Third occurrence:  Permanently discontinue study drug. 
INCB086550 is an inhibitor of the creatinine transporter OCT2 (in vitro IC50 of 2.6 µM).  
Creatinine increases observed during treatment with INCB086550 may be due to 
immune-mediated nephritis, inhibition of the OCT2 transporter, or may be unrelated to drug 
administration.  Work-up should begin early and a nephrology consult considered.  Assessment 
and management of INCB086550 should consider the relative increase in creatinine from 
baseline, and timing of the increase.  Guidelines for continuing or withholding INCB086550 
treatment and the timing for repeat chemistry laboratory studies are presented in Table 12. 


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Table 12: 
Management and Evaluation of Increased Creatinine 
CTCAE v5.0 Grade 
Guidance for Restarting 
INCB086550 
Monitoring and/or Supportive Care 
Relative increase of 
1 CTCAE Grade in Cycle 1 
(If baseline was within 
normal range, a change to 
Grade 1, or if Grade 1 at 
baseline, a change to 
Grade 2). 
Continue INCB086550 and recheck 
chemistry labs in 48 hours. 
If creatinine is stable and there is no 
further increase in 48 hours, 
INCB086550 may be continued and 
labs checked in 48-72 hours. 
If creatinine increases within 48 hours, 
withhold INCB086550 and recheck 
chemistry labs in 48 hours.  
INCB086550 treatment may resume 
when creatinine returns to Grade 1 or 
baseline. 
• Evaluate for alternative etiologies 
(eg, IV contrast, fluid status) and 
recheck labs in 48 hours. 
Grade 1  
(> ULN ‒ 1.5 × ULN) 
Continue INCB086550. 
• Evaluate for alternative etiologies 
(eg, IV contrast, fluid status). 
Grade 2  
(> 1.5 × ULN ‒ 3.0 × ULN) 
If creatinine was Grade 1 at baseline, 
INCB086550 may be continued and 
labs checked in 48 hours.  If creatinine 
is stable and there is no further increase 
in 48 hours, INCB086550 may be 
continued and labs checked in 
48-72 hours.  If creatinine increases 
within 48 hours, withhold INCB086550 
and recheck chemistry labs in 48 hours.  
INCB086550 treatment may resume 
when creatinine returns to Grade 1 or 
baseline. 
If creatinine was within normal range 
at baseline, withhold INCB086550 
until resolution to ≤ Grade 1. 
• Consult nephrology. 
• Evaluate for alternative etiologies 
(eg, IV contrast, fluid status). 
• Administer prednisone 0.5-1 mg/kg 
or equivalent with appropriate taper. 
Grade 3 
(> 3.0 × ULN ‒ 6.0 × ULN), 
Grade 4 (> 6.0 × ULN), or 
persistent Grade 2 
Permanently discontinue INCB086550. 
• Consult nephrology. 
• Evaluate for alternative etiologies 
(eg, IV contrast, fluid status). 
• Administer prednisone 1-2 mg/kg or 
equivalent with appropriate taper. 
• If elevations persist for > 3 days, 
consider mycophenolate. 
6.5.3. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study drug be permanently discontinued.  Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to study drug that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the participant's ability to 
continue study-specific procedures or is considered to not be in the participant's best 
interest. 


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− Adverse events requiring treatment discontinuation are found in Table 10 and 
Table 11. 
• A persistent AE requiring a delay of therapy for more than 4 weeks (ie, 28 days) 
unless a greater delay has been approved by the sponsor. 
See Section 7 for discontinuation procedures. 
6.5.4. 
Treatment After Initial Evidence of Radiologic Evidence of Disease Progression 
Immunotherapeutic agents such as INCB086550 may produce antitumor effects by potentiating 
endogenous cancer-specific immune responses.  The response patterns seen with such an 
approach may extend beyond the typical time course of responses seen with cytotoxic agents and 
can manifest as a clinical response after an initial increase in tumor burden or even the 
appearance of new lesions. 
If radiologic imaging shows PD, tumor assessment should be repeated ≥ 4 weeks later to confirm 
PD, with the option of continuing treatment as described in the following text while awaiting 
radiologic confirmation of progression.  If repeat imaging shows a reduction in the tumor burden 
compared with the initial scan demonstrating PD, treatment may be continued according to the 
treatment calendar.  If repeat imaging confirms PD, participants will be discontinued from study 
treatment.  In determining whether the tumor burden has increased or decreased, investigators 
should consider all target lesions as well as nontarget lesions. 
When feasible, participants should not be discontinued until progression is confirmed; however, 
the decision to continue study treatment after the first evidence of disease progression is at the 
investigator's discretion based on the clinical status of the participant as described in Table 13. 
Participants may receive study treatment while waiting for confirmation of PD if they are 
clinically stable as defined by the following criteria: 
• Absence of signs and symptoms (including worsening of laboratory values) indicating 
disease progression. 
• No decline in ECOG performance status. 
• Absence of rapid PD. 
• Absence of progressive tumor at critical anatomical sites (eg, cord compression) 
requiring urgent alternative medical intervention. 


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Table 13: 
Imaging and Treatment After First Radiologic Evidence of Progressive 
Disease 
 
Clinically Stable 
Clinically Unstable 
Imaging 
Treatment 
Imaging 
Treatment 
First radiologic 
evidence of PD 
Repeat imaging at 
≥ 4 weeks to 
confirm PD 
May continue study 
treatment at the 
investigator's 
discretion while 
awaiting 
confirmatory scan 
Repeat imaging at 
≥ 4 weeks to 
confirm PD if 
possible 
Discontinue 
treatment 
Repeat scan 
confirms PD 
No additional 
imaging required 
Discontinue 
treatment 
No additional 
imaging required 
N/A 
Repeat scan shows 
SD, PR, or CR 
Continue regularly 
scheduled imaging 
assessments every 
8 weeks 
Continue study 
treatment at the 
investigator's 
discretion 
Continue regularly 
scheduled imaging 
assessments every 
8 weeks 
May restart study 
treatment if 
condition has 
improved and/or is 
clinically stable per 
investigator's 
discretion 
6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any 
prior medication received up to 28 days before the first dose of study drug and 30 days after the 
last dose of study drug, or until the participant begins a new anticancer therapy, whichever 
occurs first, will be recorded in the eCRF.  Any addition, deletion, or change in the dose of these 
medications will also be recorded.  Concomitant medications administered more than 30 days 
after the last dose of study drug should be recorded for SAEs as defined in Section 9.3.  
Concomitant treatments/procedures that are required to manage a participant's medical condition 
during the study will also be recorded in the eCRF.  The medical monitor should be contacted if 
there are any questions regarding concomitant or prior therapy. 
6.6.1. 
Permitted Medications and Procedures 
All treatments that the investigator considers necessary for a participant's welfare may be 
administered at the discretion of the investigator, in keeping with the community standards of 
medical care, except those specifically defined as prohibited (see Section 6.6.3).  All 
concomitant medications will be recorded in the eCRF, including all prescription and 
over-the-counter medications, herbal supplements, and IV medications and fluids.  If changes 
occur during the study, documentation of drug regimen, frequency, route, and date may also be 
included in the eCRF. 
Use of prophylactic growth factors should be based on ASCO or ESMO guidelines for the use of 
WBC growth factors (Crawford et al 2010, Smith et al 2015) and the investigator's clinical 
judgment.  Bisphosphonates are allowed while participants are receiving study treatment. 


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6.6.2. 
Restricted Medications and Procedures 
6.6.2.1. 
P-glycoprotein Substrates 
INCB086550 is an inhibitor of P-gp and BCRP.  Concomitant medications that are P-gp 
substrates with a narrow therapeutic index (eg, apixaban, colchicine, cyclosporine, dabigatran, 
digoxin, edoxaban, rivaroxaban, and tacrolimus) should be administered with caution and 
INCB086550 administration should be separated by a least 6 hours before or after the 
administration of the P-gp substrate. 
6.6.2.2. 
Metformin 
INCB086550 is an inhibitor of the creatinine transporter OCT2.  Metformin is an OCT2 
substrate and should be administered with caution.  Careful monitoring of blood glucose levels 
should be performed when metformin is administered as a concomitant medication.   
6.6.2.3. 
Stomach Acid–Reducing Medications 
Since the impact on INCB086550 absorption is unknown, stomach acid–reducing medications 
such as proton pump inhibitors and H2-receptor blockers should be used with caution.  For 
participants who have a requirement for stomach acid–reducing medication, H2-receptor blockers 
should be considered rather than proton pump inhibitors.  H2-receptor blockers should be 
administered > 2 hours after INCB086550 administration.   
6.6.2.4. 
Systemic Steroids 
Systemic steroids may be used at doses ≤ 10 mg/day prednisone or equivalent with medical 
monitor approval.  The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.6.3. 
Prohibited Medications and Procedures 
Medications or vaccinations specifically prohibited in the exclusion criteria (see Section 5.2) are 
not allowed during the study.  If there is a clinical indication for one of these medications or 
vaccinations specifically prohibited during the study, discontinuation from study treatment may 
be required.  The investigator should discuss any questions regarding this with the medical 
monitor.  The final decision on any supportive therapy or vaccination rests with the investigator 
and/or the participant's primary physician.  However, the decision to continue the participant on 
study treatment requires the mutual agreement of the investigator, the sponsor, and the 
participant. 
Participants are prohibited from receiving the following therapies during the screening and 
treatment periods of this study, unless otherwise indicated: 
• Any anticancer medications, including chemotherapy or biologic therapy other than 
study treatment. 
• Moderate and potent CYP3A4/CYP3A5 inducers and inhibitors. 
− A washout period ≥ 5 half-lives before the first dose of INCB086550 is required 
for enrollment into the study for prior treatment with CYP3A4/CYP3A5 
inhibitors/inducers. 


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• Any immunological-based treatment for any reason from screening through the 
30-day follow-up visit. 
Note:  Completed adjuvant therapy (eg, vaccines) with medical monitor approval, 
inhaled or topical steroids, systemic steroids (eg, prednisone or equivalents) at doses 
≤ 10 mg/day, and immunosuppressants are allowed for the treatment of irAEs as 
described in Table 10 or as prophylaxis for contrast allergy for imaging procedures. 
Note:  Allergy shots may be permitted after consultation with the medical monitor. 
• Investigational agents other than study treatment.  Use of such medications from 
screening through the follow-up period is strictly prohibited. 
• Concomitant radiation therapy.  A washout period of 14 days is required before the 
first dose of INCB086550. 
Note:  Radiation therapy to a symptomatic solitary lesion or to the brain may be 
considered on an exceptional case-by-case basis after consultation with the medical 
monitor.  The participant must have clear measurable disease outside the radiated 
field.  Administration of palliative radiation therapy will be considered clinical 
progression.   
• Live vaccines within 90 days of the first dose of study treatment and while 
participating in the study through 90 days after the last dose of study drug.  Examples 
of live vaccines include, but are not limited to, the following:  measles, mumps, 
rubella, chicken pox, some zoster, yellow fever, rabies, Bacillus Calmette–Guérin, 
and typhoid (oral) vaccine.  Seasonal influenza vaccines for injection are generally 
killed virus vaccines and are allowed.   
• A 28-day washout period before the first dose of INCB086550 is required for 
systemic antibiotics. 
• Probiotic usage during screening and while receiving study treatment. 
• Participants may receive other medications that the investigator deems to be 
medically necessary. 
6.6.4. 
COVID-19 
Information on COVID-19 pandemic mitigation strategies and instructions can be found in 
Appendix F. 
6.7. 
Treatment After the End of the Study 
Following treatment discontinuation, participants will not be eligible to receive further study 
drug treatment as part of this study.  Participants should remain on the study and continue in 
follow-up accordingly, as outlined in Sections 8.8 and 8.9. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• The participant becomes pregnant. 
• Disease progression (see Section 8.2). 
• Consent is withdrawn.   
Note:  Consent withdrawn means that the participant has explicitly indicated that they 
do not want to be followed any longer; in this case no further data, except data in 
public domain, may be solicited from or collected on the participant.  Participants 
may choose to discontinue study treatment and remain in the study 
 
. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 
• Unacceptable toxicity as noted in Section 6.5.3. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC.  
• If, during the course of the study, a participant is found not to have met eligibility 
criteria. 
A participant may be discontinued from study treatment as follows: 
• If a participant is noncompliant with study procedures or study drug/treatment 
administration in the investigator's opinion, the sponsor should be consulted for 
instruction on handling the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted.  Reasonable efforts should be made to have the participant return for a 
follow-up visit.  These visits are described in Table 3, Table 4, Table 5, and Table 6.  The last 
date of the last dose of study drug and the reason for discontinuation of study drug will be 
recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The EOT visit should be performed. 


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• The status of the participant should be updated to EOT in the IRT. 
• After the EOT visit, participants will remain in the study 
 
 and will be followed for safety and AEs per Sections 8.9 
and 9. 
Discontinuation from study drug does not mean withdrawal from the study, and remaining study 
procedures should be completed as indicated by the study Protocol. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety/efficacy assessments 
according to Table 3, Table 4, Table 5, and Table 6. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
See Table 3, Table 4, Table 5, and Table 6 for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods).  These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the countries in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that his/her personal study-related data will be used 
by the sponsor in accordance with local data protection laws.  The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained.  The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative. 
Participants who are rescreened are required to sign a new ICF. 


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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is enrolled in the 
study (Cycle 1 Day 1).  Screening may not exceed 28 days.  Assessments that are required to 
demonstrate eligibility may be performed over the course of 1 or more days during the screening 
process. 
Procedures conducted as part of the participant's routine clinical management (eg, blood count, 
imaging study) and obtained before signing of the ICF may be used for screening or baseline 
purposes provided the procedure meets the Protocol-defined criteria and has been performed in 
the timeframe of the study (ie, within 28 days of Cycle 1 Day 1).  For participants who are 
enrolled in the study, information associated with eligibility requirements must be entered into 
the appropriate eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
enrollment or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results to be 
in error.  For screening assessments that are repeated, the most recent available result before 
enrollment into the study will be used to determine eligibility.  Treatment should start as soon as 
possible but within 7 days after the date of enrollment registration. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number.  Site staff should contact the IRT to obtain the 
participant ID number during screening.  Upon determining that the participant is eligible to 
participate in the study, the IRT will be contacted to obtain the treatment assignment.  
Additionally, the IRT will be contacted on Day 1 of each cycle to update the study drug supply.  
Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Dosing Diary and Patient Information Cards 
Participants will be provided with a reminder card and dosing diary at each visit, as specified in 
Table 3, Table 4, Table 5, and Table 6.  The reminder card and dosing diary will indicate the 
date/time of the next visit and will also remind the participants when they should not take their 
morning dose of study drug and when they should arrive for their visit on days of blood draws 
for 
 safety evaluation.  The dosing diary will have an area on which the date and 
time of the last dose taken (from the previous evening) and the time and contents of their last 
meal before the visit should be recorded.  Participants will receive a participant information card 
that lists common irAE symptoms and reminds them to report any symptoms to their study 
physician immediately. 


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8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 
history, and current illnesses.  Medical history will include relevant medical or surgical treatment 
within the last 5 years that are considered to be clinically significant by the investigator. 
8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history will be collected at screening.  Details 
regarding the participant's malignancy under study, including date of diagnosis, initial and 
current cancer stage, tumor histology, relevant disease characteristics, and prior treatments, 
including systemic treatments, radiation, and surgical procedures, will be recorded. 
8.1.5.3. 
Baseline Biomarker Documentation 
Information regarding microsatellite instability and/or DNA mismatch repair deficiency, PD-L1 
expression, HPV status, KRAS, NRAS, ALK, EBV, EGFR, ER/PR, HER2, ROS1, BRAF, and 
other tumor markers should be recorded in the eCRF. 
8.2. 
Efficacy Assessments 
Objective assessment of disease status is required, using the evaluations by RECIST v1.1 
(Eisenhauer et al 2009).  The investigator's assessment will be used to determine responses and 
will be recorded in the eCRF.   
Efficacy baseline assessments will be performed at screening, and further efficacy assessments 
will be performed throughout the study at the intervals defined in Table 3, Table 4, Table 5, and 
Table 6.  Cycle delays should not interrupt the 8-week scan interval; thus, tumor assessments and 
cycles may become out of sync.  Participants who discontinue treatment for reasons other than 
disease progression should continue to have disease assessments performed and recorded every 8 
weeks until they have experienced disease progression or started a subsequent anticancer 
treatment. 
8.2.1. 
Tumor Imaging by RECIST v1.1 
A local reading (investigator assessment with site radiology reading) will be used to determine 
eligibility and for participant management; radiological and clinical assessments (including 
photographs) will be collected for retrospective analysis by a central vendor.  The same imaging 
technique should be used for a participant throughout the study.  The baseline scan must be a 
contrast CT or MRI, except in circumstances in which there is a contrast allergy or with medical 
monitor approval.  The CT component of a positron emission tomography/CT scan may use 
higher energy and thinner slices.  This allowance must recorded accordingly in the eCRF and the 
same method must be used for all subsequent scans.  Images of the chest, abdomen, and pelvis 
are required for all participants.  Additional imaging of anatomical sites (eg, head, neck, brain) 
should be performed as applicable for the malignancy under study.  Based on the methods of 
assessment guidelines from the RECIST Working Group, participants with skin lesions should 
have documentation of their skin lesions by color photography, which would include a ruler to 


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estimate the size of the lesion.  Therefore, per RECIST guidance, participants with target lesions 
in the skin that cannot be followed by standard imaging (CT/MRI) should have a photograph 
taken (with caliper measurement) to follow their disease.  If a participant does not have other 
target lesions that can be followed by CT/MRI, photography is required. 
A CT or MRI scan of the brain will be performed at screening if there are signs or symptoms 
suggesting that the participant has disease involvement in the CNS. 
Bone scans will be performed at baseline for all participants.  Participants with positive bone 
scans at baseline will be followed with additional scans performed at the same schedule and 
interval as CT/MRI.  For participants with new symptoms suggestive of osseous metastasis, a 
bone scan should be obtained.  Additionally, a plain x-ray evaluation should be obtained for 
symptomatic sites with negative bone scan evaluations. 
8.2.1.1. 
Baseline Assessment During Screening 
Initial tumor imaging must be performed within 28 days before the first dose of study treatment.  
The site study team must review prestudy reports and images to confirm that the participant has 
measurable disease per RECIST v1.1.  Participants with a single target lesion that has been 
previously irradiated or subjected to other local-regional therapy may be enrolled if the target 
lesion is considered measureable per RECIST v1.1 and has demonstrated at least a 10-mm 
increase in the shortest diameter of the lesion.  Additionally, it is recommended that tumor 
lesions selected for biopsy not be selected as target lesions. 
Scans performed as part of routine clinical management are acceptable for use as the screening 
scan if they are of diagnostic quality and performed within 28 days before the first dose of study 
treatment. 
8.2.1.2. 
Assessment of Disease Response During Treatment 
The first imaging assessment should be performed 8 weeks (56 ± 7 days) after the first dose of 
INCB086550 and then every 8 weeks (56 ± 7 days) for the first 6 months.  After 6 months of 
study treatment, imaging frequency may be reduced to every 12 weeks (84 ± 14 days).  
Participants who discontinue study treatment for a reason other than disease progression should 
continue to have efficacy assessments performed according to the original schedule following 
their final on-study treatment scan until disease progression as determined by RECIST, new 
anticancer therapy is started, death, withdrawal of consent, or end of study.  Imaging assessments 
may be performed more frequently if clinically indicated. 
Complete response or PR should be confirmed by imaging at least 4 weeks after the initial 
documentation. 
Imaging should follow calendar days and should not be delayed for delays in cycle starts. 
8.2.1.3. 
Assessment of Disease Response After Treatment 
If the participant discontinues study treatment for reasons other than disease progression, 
imaging assessments should continue at the Protocol-specified interval until documented disease 
progression, the start of new anticancer treatment, withdrawal of consent, death, or the end of the 
study, whichever occurs first. 




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8.3.2. 
Physical Examinations 
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.  Abnormalities identified after the first dose of study drug constitute an AE if they are 
considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study drug.  Investigators should pay special attention to clinical 
signs related to previous serious illnesses. 
At the screening visit, a comprehensive physical examination should be conducted.  The 
comprehensive physical examination will include height and body weight, and assessment(s) of 
the following organ or body systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a 
thorough neurological examination. 
During the study, a targeted examination of the participants will be conducted by the investigator 
or medically qualified designee per institutional standard of care.  These assessments should be 
an evaluation as indicated by participant symptoms, AEs, or other findings and documented on 
the AE eCRF. 
8.3.2.1. 
Neurologic Examination 
At baseline and throughout the study, including the 30-day safety follow-up visit, neurologic 
examinations should be performed as part of the physical examination.  The neurologic 
examination should include assessment of motor system, muscle reflexes, sensory system, 
coordination, and gait and stance. 
8.3.3. 
Vital Signs 
Vital sign measurements (to be taken before blood collection for laboratory tests), include blood 
pressure, pulse, respiratory rate, and body temperature.  If vital signs cannot be taken before 
blood collection for laboratory tests, there must be a minimum of 30 minutes from the 
completion of the blood collection procedures to the beginning of the vital signs collection.  
Blood pressure and pulse will be taken with the participant in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest.  Abnormal vital sign results identified after the first dose 
of study treatment constitute an AE if they are considered clinically meaningful, induce clinical 
signs or symptoms, require concomitant therapy, or require changes in study drug. 
8.3.4. 
Eastern Cooperative Group Performance Status 
The ECOG performance status score will be assessed according to the criteria in Table 14. 


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Table 14: 
Eastern Cooperative Group Performance Status Scoring 
Grade 
ECOG 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. 
8.3.5. 
Electrocardiograms 
Twelve-lead ECGs will be obtained as outlined in the SoA (see Table 3, Table 4, Table 5, and 
Table 6), Table 15, and Table 16 using an ECG machine that automatically calculates the heart 
rate and measures PR, QRS, QT, and QTc intervals.  On days of timed blood collections, ECGs 
are to be collected before any blood draws.  All 12-lead ECGs will be performed with the 
participant in a recumbent or semirecumbent position after 5 minutes of rest.  The 12-lead ECGs 
(screening and during study treatment period) will be collected from a single measurement.  In 
the event that a single QTc is > 450 milliseconds, 2 additional ECGs will be measured and the 
average ECG from the triplicates will be reported for the occasion (ie, visit and/or timepoint if 
applicable).  For participants with an intraventricular conduction delay (QRS interval 
> 120 milliseconds) at screening, the JTc interval may be used in place of the QTc.  The JTc 
must be ≤ 340 milliseconds if JTc is used in place of the QTc.  In addition, the JTc interval 
should be used for all subsequent assessments. 
The 12-lead ECGs will be interpreted by the investigator at the site to be used for immediate 
participant management.  Additional 12-lead ECGs may be performed as clinically indicated to 
manage participant safety.  The decision to include or exclude a participant or discontinue study 
treatment based on an ECG flagged as "Abnormal, Clinically Significant" is the responsibility of 
the investigator, in consultation with the sponsor's medical monitor, as appropriate.  Clinically 
notable abnormalities that are considered clinically significant in the judgment of the investigator 
are to be reported as AEs. 


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Table 15: 
Electrocardiogram Collection Schedule (≥ 2-Week Treatment Schedules) 
Visit 
Any Time 
Before the Morning 
Dose of INCB086550a 
2 and 4 Hours 
After the Morning Dose 
of INCB086550a,b 
Screening 
X 
 
 
Cycle 1 Day 1 
 
X 
X 
Cycle 1 Day 14 
 
X 
X 
Every 2 cycles thereafter 
(eg, C3, C5, C7) 
 
X 
 
EOT 
X 
 
 
a INCB086550 is administered in the clinic on days of timed ECGs. 
b To be collected within 15 minutes before blood draws. 
The ECG schedule in Table 15 applies to participants who are assigned to continuous, 2-week 
and 3-week intermittent, or 2-week and 3-week step-down treatment schedules in a 21-day or 
28-day cycle. 
Table 16: 
Electrocardiogram Collection Schedule (1 Week Intermittent/Step-Down 
Treatment Schedule) 
Visit 
Any Time 
Before the Morning 
Dose of INCB086550a 
2 and 4 Hours 
After the Morning Dose 
of INCB086550a,b 
Screening 
X 
 
 
Cycle 1 Day 1 
 
X 
X 
Cycle 1 Day 7 
 
X 
X 
Every 2 cycles thereafter 
(eg, C3, C5, C7) 
 
X 
 
EOT 
X 
 
 
a INCB086550 is administered in the clinic on days of timed ECGs. 
b To be collected within 15 minutes before blood draws. 
The ECG schedule in Table 16 applies to participants who are assigned to 1-week intermittent 
step-down treatment schedules in a 21-day or 28-day cycle. 
8.3.6. 
Laboratory Assessments 
See Table 17 for the list of clinical laboratory tests to be performed and the SoA (see Table 3, 
Table 4, Table 5, and Table 6) for the timing and frequency.  A certified laboratory local to the 
investigative site will perform all clinical laboratory assessments for safety (eg, blood 
chemistries, hematology assessments, coagulation tests, endocrine function, and urinalysis).  The 
investigative site will enter the laboratory results and laboratory normal ranges into the eCRF.  
Additional testing may be required by the sponsor based on emerging safety data.  Additional 
tests may also be performed if clinically indicated. 


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Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.  All laboratory tests with values considered clinically significantly 
abnormal during participation in the study or within 30 days after the last dose of study treatment 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
Screening laboratory assessments must be performed within the 28-day screening window and 
the tests must be repeated and eligibility confirmed before the first dose of study treatment is 
administered on Cycle 1 Day 1.  A 48-hour window before first dose is permitted for safety 
laboratory assessments before Cycle 1 Day 1.  After Cycle 1, predose laboratory procedures can 
be conducted up to 72 hours before study treatment administration (within the 3-day study 
window), and results should be reviewed by the investigator or qualified designee and found to 
be acceptable before a new cycle of treatment is initiated. 


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Table 17: 
Required Laboratory Analytes 
Blood Chemistries 
Hematology 
Urinalysis With 
Microscopic Examination 
Serology 
Coagulation 
Albumin (screening only) 
Alkaline phosphatase 
ALT 
AST 
Amylase 
Bicarbonate or CO2a 
Blood urea nitrogen or ureaa 
Calcium 
Chloride 
Creatinine 
C reactive protein (low sensitivity 
assay) 
Glucose 
Lactate dehydrogenase 
Lipase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total bilirubin 
is elevated above ULN) 
Total protein 
Uric acid 
Complete blood count, 
including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell count 
• WBC count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
 
Absolute values must be 
provided for: 
• WBC differential 
laboratory results 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
HBsAg 
HBsAg antibody 
Hepatitis B core antibody 
HAV-IgM 
HBV-DNA 
HCV antibody 
HCV-RNA 
HIV 
PT 
PTT or aPTT 
INR 
Lipid Panel 
Endocrine Function 
Pregnancy Testing 
Total cholesterol 
Triglycerides 
LDL 
HDL 
Thyroid-stimulating 
hormone 
Free T4 
Total T3 (free T3 only if 
total T3 is not performed 
locally) 
Women of childbearing 
potential require a serum 
test at screening and 
EOT. 
Urine or serum 
pregnancy tests may be 
used for other scheduled 
assessments. 
Additionally, monthly 
telephone visits should 
take place to check 
pregnancy status (via 
testing, including home 
pregnancy tests) during 
the period when 
contraception is 
mandatory (190 days 
after the last dose of 
study drug).   
Note:  Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data. 
a If considered standard by the region. 








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8.8. 
End of Treatment and/or Early Termination 
When the participant permanently discontinues study drug, whether the participant is terminating 
the study early or the participant has completed the study, the EOT visit should be conducted.  If 
the EOT visit coincides with a regular study visit, the EOT evaluations will supersede those of 
that scheduled visit, and the data should be entered in the EOT visit in the eCRF.  The participant 
should be encouraged to return for the follow-up visit. 
8.9. 
Follow-Up 
Participants who discontinue study treatment are to continue in the follow-up period for up to 
90 days (± 14 days) for collection of post-treatment evaluations.  The assessment schedule 
following treatment discontinuation is described in Table 3, Table 4, Table 5, and Table 6. 
8.9.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 30 and 90 days after the EOT visit (or after the last dose of study drug 
if the EOT visit was not performed).  Adverse events and SAEs must be reported up until 1) at 
least 90 days after the last dose of study drug, or the start of a new anticancer therapy or 2) until 
toxicities resolve, return to baseline, or are deemed irreversible, whichever is longer.  Reasonable 
efforts should be made to have the participant return for the follow-up visit and report any AEs 
that may occur during this period.  If the participant cannot return to the site for the safety 
follow-up visit (eg, lives far away), the participant should be contacted by telephone for 
assessment of AEs and SAEs, which should be appropriately documented in the source 
documents and eCRF. 
If a participant is scheduled to begin a new anticancer therapy before the end of the 90-day safety 
follow-up period, the safety follow-up visit should be performed before a new anticancer therapy 
is started.  Once a new anticancer therapy has been initiated, the participant will move into the 
. 
8.9.2. 
Post-Treatment 
 Follow-Up 
Participants who discontinue study treatment for a reason other than disease progression will 
move into the 
 follow-up period and should be assessed as follows to monitor 
: 
• If before 6 months from first dose of study treatment - every 8 weeks (56 ± 7 days). 
• If after 6 months from first dose of study treatment - every 12 weeks (84 ± 14 days). 
Every effort should be made to collect information 
 until: 
• The start of new anticancer therapy. 
• Disease progression. 
• Death. 
• The end of the study. 




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Events NOT Meeting the Adverse Event Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety assessments that are 
associated with the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant's condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant's condition or 
considered to be treatment-related by the investigator. 
• Efficacy endpoints as outlined in Section 3 will not be reported as AE/SAEs, specifically, any event 
that is related to disease progression of the cancer under study.  Unblinded aggregated efficacy 
endpoint events and safety data will be monitored to ensure the safety of the participants in the study.  
Any suspected endpoint that upon review is not progression of the cancer under study will be 
forwarded to Incyte Pharmacovigilance as a SAE within 24 hours of determination that the event is 
not progression of the cancer under study. 
• Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that leads to the 
procedure is the AE if it occurred after signing informed consent.  If present before entering the 
study, the condition should be captured as medical history. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A Serious Adverse Event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an adverse drug experience that places 
the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurred.  This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether "hospitalization" occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 


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d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person's ability to conduct normal life 
functions. 
• This definition is not intended to include experiences of relatively minor medical significance, such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, 
sprained ankle), that may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations (Important Medical Event) 
An event that may not result in death, be immediately life-threatening, or require hospitalization, but 
may be considered serious when, based on appropriate medical judgment, the event may jeopardize the 
participant and may require medical or surgical intervention to prevent one of the outcomes listed in 
the above definition.  Examples of such events include invasive or malignant cancers (excluding the 
disease[s] under study), intensive treatment in an emergency department or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.  Secondary malignancies should always be considered SAEs. 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Event Form in the eCRF.  Conditions that were present at the time informed consent was 
given should be recorded on the Medical History Form in the eCRF. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records in 
lieu of completing the AE eCRF page. 
• There may be instances when copies of medical records for certain cases are requested.  In this case, 
all participant identifiers, with the exception of the participant number, will be redacted on the copies 
of the medical records before submission. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information.  Whenever possible, the diagnosis (not the individual signs/symptoms) 
will be documented as the AE/SAE.  When a clear diagnosis cannot be identified, each sign or 
symptom should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine: 
• The severity grade (CTCAE v5 Grade 1 to 5).  See below for further instructions on the assessment 
of intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study treatment:  
suspected (yes) or not suspected (no).  See below for further instructions on the assessment of 
causality. 
• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 


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• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication 
or nondrug therapy, this action should be recorded on the Adverse Event Form and the treatment 
should be specified on the appropriate eCRF (eg, Prior/Concomitant Medications, Procedures and 
Non-Drug Therapy). 
Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5 Grades 1 through 5.  If an event is not classified 
by CTCAE, the severity of the AE will be graded according to the scale below to estimate the grade of 
severity: 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate 
activities of daily living. 
• Grade 3:  Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study treatment and each occurrence 
of each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or arguments 
to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• The investigator will also consult the Reference Safety Information in the IB and/or Product 
Information, for marketed products, in his/her assessment. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well 
as the temporal relationship of the event to study treatment administration, will be considered and 
investigated. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report.  However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements.  Therefore, it is very important that 
the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE. 
− The investigator may change his/her opinion of causality in light of follow-up information and 
send a follow-up SAE report with the updated causality assessment. 


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Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible.  This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings including 
histopathology. 
• New or updated information will be recorded in the originally completed eCRF. 
• Any updated SAE data will be submitted to the sponsor (or designee) within 24 hours of receipt of 
the information. 
• Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any changes 
in severity, the suspected relationship to the study drug, the interventions required to treat the event, 
and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves. 
See Appendix D for the management of potential Hy's law cases. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedure[s]), all SAEs 
occurring after the participant has signed the ICF through 90 days after the last dose of study 
treatment or until the participant starts a new anticancer therapy, whichever occurs earlier) must 
be reported to the sponsor (or designee) within 24 hours of learning of its occurrence, unless 
otherwise specified by the Protocol.  The investigator will submit any updated SAE data to the 
sponsor (or designee) within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE information after conclusion of the 
study participation.  However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study treatment or study participation, the investigator must notify the 
sponsor (or designee) within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification to inform all investigators involved in any study 
with the same drug that this SAE has been reported.  Suspected Unexpected Serious Adverse 


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Reactions 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. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the Investigator's Brochure and will notify the IRB/IEC, if appropriate according to 
local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must also complete the Incyte Serious Adverse Event Report Form, in English.  
Refer to the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• Facsimile or email transmission of the Serious Adverse Event Report Form is the preferred method 
to transmit this information to Incyte Pharmacovigilance/designee.  The contact information of the 
sponsor's study-specific representatives is listed in the Study Reference Manual provided to each site.  
The original copy of the Serious Adverse Event Report Form and the confirmation sheet must be 
kept at the study site. 
• Follow-up information is recorded on an amended or new Serious Adverse Event Report Form, with 
an indication that it is follow-up to the previously reported SAE and the date of the original report.  
The follow-up report should include information that was not provided on the previous Serious 
Adverse Event Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or participant disposition (eg, continued or withdrew from study participation).  Each 
recurrence, complication, or progression of the original event should be reported as follow-up to that 
event, regardless of when it occurs. 
• In rare circumstances and in the absence of facsimile or computer equipment, notification by 
telephone is acceptable with a copy of the Incyte Serious Adverse Event Report Form sent by 
overnight mail or courier service.  Initial notification via telephone does not replace the need for the 
investigator to complete and sign the Serious Adverse Event Report Form within the designated 
reporting time frames. 
• Contacts for SAE reporting can be found in Study Reference Manual. 
9.5. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 


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9.6. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study treatment must be interrupted immediately (female participants only). 
• If the female participant is no longer pregnant and meets the treatment continuation 
criteria within 28 days of the scheduled start of a cycle, study treatment may be 
resumed after approval has been received from the sponsor medical monitor.  
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluation.  
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee.  Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later.  Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy of a study participant must be recorded on the 
Serious Adverse Event Report Form and submitted to the sponsor or designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.7. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study, as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.8. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 




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10. 
STATISTICS 
10.1. 
Sample Size Determination 
The number of participants has been determined independently for each disease-specific cohort 
(irrespective of dose level) and can be found in Table 20.  The target ORR (p1) for each cohort is 
based on published clinical experience with a reference PD-1 inhibitor (El-Khoueiry et al 2017, 
Keytruda 2018, Mok et al 2019, Motzer et al 2015, Reck et al 2016, Robert et al 2015).  The 
target ORR (p1) for the NSCLC cohort was calculated by combining 2 different studies (Mok 
et al 2019, Reck et al 2016).  The null ORR (p0) for the melanoma and RCC cohorts is based on 
the control arm ORRs in the reference studies.  For the NSCLC, UC, and HCC cohorts, the null 
ORR (p0) was selected to be the p0 that creates a test with a rejection region that begins with the 
lower CI bound of the reference PD-1 inhibitors.  The sample size for each cohort provides 
approximately 80% power and 5% 1-sided Type I error. 
Table 20: 
Sample Size per Cohort 
Tumor Type (Cohort) 
ORR 
Sample Size 
p0 
p1 
NSCLC 
18.0% 
41.1% 
32 
UC 
20.0% 
47.0% 
25 
HCC 
6.0% 
20.0% 
42 
RCC 
5.0% 
25.0% 
23 
Melanoma 
11.9% 
32.9% 
30 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 21. 






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10.4.4.1. Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first dose of study drug up to 90 days after the last dose of study drug.  Analysis of AEs will be 
limited to TEAEs, but data listings will include all AEs regardless of their timing to study drug 
administration.  Adverse events will be tabulated by MedDRA system organ class and preferred 
term.  Severity of AEs will be based on the NCI CTCAE v5 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, the AE will be considered treatment-related. 
Number (%) of participants reporting any TEAEs, any SAEs, any Grade 3 or higher TEAEs, 
irAEs, any treatment-related TEAEs, any treatment-related serious TEAEs, any treatment-related 
Grade 3 or higher TEAEs, any fatal TEAEs, and any TEAEs leading to treatment 
interruption/discontinuation will be tabulated by MedDRA system organ class and preferred 
term. 
10.4.4.2. Clinical Laboratory Tests 
Laboratory data will be classified into Grades 1 through 4 using CTCAE v5 when applicable.  
The following summaries will be produced for the laboratory data: 
• Descriptive statistics of the value and change from baseline at each assessment time 
will be provided. 
• For laboratory parameters that have CTC grading, shift tables will be provided 
showing change in CTC grade from baseline to the worst postbaseline grade. 
Categorical laboratory data will be tabulated by visit at baseline and postbaseline visits when 
necessary.  Possible Hy's law events will be listed.  The criteria for determining possible Hy's 
law events will be provided in the Statistical Analysis Plan. 
10.4.4.3. Vital Signs 
Descriptive statistics for the value at each assessment and change from baseline will be provided 
for vital signs (ie, blood pressure, pulse, respiratory rate, and body temperature).  Vital sign 
results will be reviewed for clinically notable abnormalities (see Table 22), and the abnormal 
values for participants exhibiting clinically notable vital sign abnormalities will be listed.  Alert 
vital sign values are defined as an absolute value outside the defined range and an absolute 
percentage change of > 25% from baseline.  The abnormal values for participants exhibiting alert 
vital sign abnormalities will be listed. 
Table 22: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 160 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 120 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35°C 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 






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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both Health Authorities 
and IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 


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− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the Sponsor Medical Monitor before 
the end of the study.  As part of his or her responsibilities, the coordinating principal investigator 
will review the final CSR.  Agreement with the final CSR will be documented by the dated 
signature of the coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system.  The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF.  The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements.  Other data outside the EDC system required in the study conduct 
of the protocol such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors, and as designated by the sponsor, will have their own data flow 
management plans, or study charters, 
, as applicable. 
The sponsor (or designee) will be responsible for: 
• Managing the integrity of the data and the quality of the conduct of the study, such as  
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated, and/or collected including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 
The investigator will be responsible for: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
, photographs, diary data), 
or as otherwise specified in the Protocol. 
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 


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• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at the 
investigator's site. 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained.  
The investigator may need to request previous medical records or transfer records, 
depending on the study.  Also, current applicable medical records must be 
available. 
• May have responsibility for sending participants' data, either as unique samples, or 
copies, or photographs, to be evaluated centrally or analyzed centrally, or both, by a 
qualified vendor designated by the sponsor. 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 


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Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number will be recorded in the eCRF; if the participant's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee.  Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 10 years after study completion unless local regulations require 
otherwise.  No records may be destroyed during the retention period without the written approval 
of the sponsor.  No records may be transferred to another location or party without written 
notification to the sponsor. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply.  For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator.  These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 
The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.  
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 


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multicenter studies only in their entirety and not as individual site data.  In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
11.6. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
REFERENCES 
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patients treated with immune checkpoint inhibitor therapy: American Society of Clinical 
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and pregnancy testing in clinical trials. 2014. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
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Crawford J, Caserta C, Roila F. Hematopoietic growth factors: ESMO clinical practice 
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Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
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El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular 
carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and 
expansion trial. Lancet 2017;389:2492-2502. 
Fessas P, Lee H, Ikemizu S, Janowitz T. A molecular and preclinical comparison of the PD-1–
targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol 
2017;44:136-140. 
Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 
2005;23:515-548. 
Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: 
ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 
2017;28:iv119-iv142. 
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of Type I error 
probability spending functions. Stat Med 1990;9:1439-1445. 
INCB086550 Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Keytruda (pembrolizumab) [prescribing information]. Merck & Co, Inc; June 2018. 
Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously 
untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer 
(KEYNOTE-042): a randomized, open-label, controlled, phase 3 trial. Lancet 
2019;393:1819-1830. 
Motzer R, Escudier B, McDermott D, et al. Nivolumab versus everolimus in advanced renal-cell 
carcinoma. N Engl J Med 2015;373:1803-1813. 
Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol 
2006;27:195-201. 


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Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol 1982;5;649-655. 
Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin 
Oncol 2015;33:1974-1982. 
Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for 
PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-1833. 
Ricciuti B, Genova C, De Giglio A, et al. Impact of immune-related adverse events on survival 
in patients with advanced non-small cell lung cancer treated with nivolumab: long-term 
outcomes from a multi-institutional analysis. J Cancer Res Clin Oncol 2019;145:479-485. 
Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced 
melanoma. N Engl J Med 2015;372:2521-2532. 
Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its 
ligands in regulating autoimmunity and infection. Nat Immunol 2007;8:239-245. 
Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: 
American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 
2015;33:3199-3212. 
Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with 
clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. 
Oncologist 2018;23:1358-1365. 
Xing P, Zhang F, Wang G, et al. Incidence rates of immune-related adverse events and their 
correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a 
systematic review and meta-analysis. J Immunother Cancer 2019;7:341. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
Definitions 
WOCBP 
A woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile 
(see below). 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel's review of the participant's medical records, medical 
examination, or medical history interview. 
• Postmenopausal 
− A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 
o A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or HRT.  However, in the absence of 12 months of 
amenorrhea, confirmation with 2 FSH measurements in the postmenopausal range is required.   
− Female participants on HRT and whose menopausal status is in doubt will be required to use 1 of the 
nonhormonal, highly effective contraception methods if they wish to continue their HRT during the study.  
Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
For male participants of reproductive potentiala 
The following methods during the Protocol-defined timeframe in Section 5.1 are highly effective: 
• 
Use of a male condom plus partner use of an additional contraceptive method when having 
penile-vaginal intercourse with a WOCBP who is not currently pregnant. 
• 
Vasectomy with medical assessment of the surgical success (verified by site personnel's review of the 
participant's medical records) 
• 
Sexual abstinenceb  
• 
Abstinence from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a 
long-term and persistent basis) and agreement to remain abstinent. 
Note:  Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration.   


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For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 that can achieve a failure rate of 
< 1% per year when used consistently and correctly are considered as highly effective birth control methods: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation. 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation 
− oral 
− injectable 
− implantable 
• Intrauterine devicec 
• Intrauterine hormone-releasing systemc 
• Bilateral tubal occlusionc 
• Vasectomized partnerd 
• Sexual abstinenceb 
FSH = follicle-stimulating hormone; HRT = hormone replacement therapy; WOCBP = woman of childbearing potential. 
a If the male participant has a partner with childbearing potential, the partner should also use contraceptives. 
b 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 study and the preferred and usual lifestyle of the 
participant.  
c Contraception methods that in the context of this guidance are considered to have low user dependency. 
d Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success. 
Source:  Clinical Trials Facilitation and Coordination Group 2014 and Clinical Trials Facilitation and Coordination Group 2020. 
 


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APPENDIX D. MANAGEMENT OF POTENTIAL HY'S LAW CASES 
INTRODUCTION 
During the course of the study, the investigator will remain vigilant for increases in liver 
biochemistry.  The investigator is responsible for determining whether a participant meets PHL 
criteria at any point during the study. 
The investigator participates, in conjunction with Incyte clinical project and pharmacovigilance 
representatives, in the review and assessment of cases fulfilling PHL criteria to ascertain whether 
there is an alternative explanation for the elevations in liver biochemistry other than 
drug-induced liver injury caused by the study drug. 
The investigator fulfils requirements for the recording of data pertaining to PHL or Hy's law 
cases and AE/SAE reporting according to the outcome of the review and assessment in line with 
standard safety reporting processes. 
DEFINITIONS 
For the purpose of this process definitions are as follows 
Potential Hy's Law 
An increase in AST or ALT > 3 × ULN and total bilirubin > 2 × ULN at any point during the 
study.  The elevations do not have to be at the same time or within a specified timeframe. 
Hy's Law 
An increase in AST or ALT ≥ 3 × ULN and total bilirubin > 2 × ULN, where no other reason can 
be found to explain the combination of increases (eg, elevated serum ALP indicating cholestasis, 
viral hepatitis, another drug). 
ACTIONS REQUIRED IN CASES OF AST OR ALT > 3 × ULN OR TOTAL BILIRUBIN 
≥ 2 × ULN 
Identification and Determination of Potential Hy's Law 
To identify cases of AST or ALT > 3 × ULN or total bilirubin > 2 × ULN and consequently 
determine whether the participant meets PHL criteria, please follow the instructions below: 
• Review the laboratory report and if a participant has AST or ALT > 3 × ULN OR 
total bilirubin > 2 × ULN at any visit: 
− Determine without delay whether the participant meets PHL criteria by reviewing 
laboratory reports from all previous visits. 
− Enter the laboratory data into the laboratory eCRF as soon as possible. 
Potential Hy's Law Criteria Not Met 
If the participant has NOT had AST or ALT ≥ 3 × ULN AND total bilirubin > 2 × ULN at any 
point in the study (the elevations do not have to be at the same time or within a specified 
timeframe), irrespective of ALP, please follow the instruction below: 


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• Perform follow-up on subsequent laboratory results according to the guidance 
provided in Section 8.3.6. 
Potential Hy's Law Criteria Met 
If the participant has had AST or ALT ≥ 3 × ULN AND total bilirubin > 2 × ULN at any point in 
the study (the elevations do not have to be at the same time or within a specified timeframe), 
irrespective of ALP, please follow the instruction below: 
• Have participant interrupt study drug. 
• Notify Incyte study team without delay. 
− The investigator, or designee, should contact the medical monitor to discuss and 
agree upon an approach for the study participant's follow-up and the continuous 
review of data. 
• Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as medically indicated. 
• Investigate the etiology of the event and perform any relevant diagnostic 
investigations as discussed with the medical monitor. 
• Enter the laboratory data into the laboratory CRF as soon as possible. 
• If at any time (in consultation with the medical monitor) the PHL case meets serious 
criteria, report it as an SAE using standard reporting procedures. 
REVIEW AND ASSESSMENT 
No later than 3 weeks after the biochemistry abnormality is initially detected and the criteria for 
PHL is met, the medical monitor, Incyte pharmacovigilance physician, and investigator will 
discuss and review available data and agree on whether there is an alternative explanation for the 
elevations in liver biochemistry other than drug-induced liver injury caused by the study drug.  
Participant matter experts will be included in the review as appropriate. 
Evaluation of Alternative Causes 
In order to gather additional clinical information to seek other possible causes of the observed 
liver test abnormalities, the following alternative etiologies should be considered, including but 
not limited to, 
• Active viral hepatitis 
• Alcoholic and autoimmune hepatitis 
• Hepatobiliary disorders 
− Biliary tract disease, such as migration of gallstones or intrahepatic lesions, more 
often causes cholestatic injury initially and should be investigated with gall 
bladder and ductal imaging studies, especially if alkaline phosphatase is 
increased.  Malignant interruption of the biliary tract also should be considered. 
• Concomitant treatment 


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• Other causes such as systemic infections (bacterial, fungal, viral), nonalcoholic 
steatohepatitis, and cardiovascular diseases 
Actions After Review and Assessment 
According to outcome of the review and assessment, please follow the instructions below: 
If there is an agreed alternative explanation for the AST or ALT and total bilirubin elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for a SAE. 
• If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate CRF if possible. 
• If the alternative explanation is an AE/SAE, record the AE/SAE in the eCRF 
accordingly and follow the standard study processes. 
• Have participant resume study drug as per Protocol guidelines. 
If it is agreed that there is no explanation that would explain the AST or ALT and total bilirubin 
elevations: 
• Have participant permanently discontinue study drug and perform end-of-treatment 
procedures. 
• Report an SAE (report term "Hy's Law"). 
− The 'medically important' serious criterion should be used if no other serious 
criteria apply. 
− As there is no alternative explanation for the Hy's law case, a causality assessment 
of related should be assigned. 
• If there is an unavoidable delay of over 3 weeks in obtaining the information 
necessary to assess whether or not the case meets the criteria for a Hy's law case, then 
it is assumed that there is no alternative explanation until such time as an informed 
decision can be made.  Report an SAE (report term "Potential Hy's Law") applying 
serious criteria and causality assessment as per above. 
ACTIONS REQUIRED FOR REPEAT EPISODES OF AST OR ALT > 3 × ULN AND/OR 
TOTAL BILIRUBIN > 2 × ULN 
The requirement to conduct follow-up, review, and assessment of a repeat occurrence(s) of PHL 
is based on the nature of the alternative cause identified for the previous occurrence. 
If the alternative cause for the previous occurrence of PHL was not chronic or progressing 
malignant disease, please follow the process for PHL review and assessment as described in this 
appendix. 
If the alternative cause for the previous occurrence of PHL was chronic or progressing malignant 
disease, please follow the instructions below: 
• Determine whether there has been a significant change* in the participant's condition. 
− If there is no significant change, no action is required. 


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− If there is a significant change, follow the process described for PHL review and 
assessment as described in this appendix. 
* A 'significant' change in the participant's condition refers to a clinically relevant change in ALT, AST, or total 
bilirubin, or associated symptoms.  The determination of whether there has been a significant change will be at the 
discretion of the investigator; this may be in consultation with the medical monitor if there is any uncertainty. 


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APPENDIX E. CYTOCHROME P450 INHIBITORS/INDUCERS 
Concomitant treatment with moderate and potent CYP3A4/CYP3A5 inhibitors or inducers are 
prohibited in this study. 
Below is a list of potent and moderate inhibitors and inducers.  This list is not exhaustive.  For a 
comprehensive list, please check with your pharmacy personnel for the most current list of 
potent CYP3A4/CYP3A5 inhibitors or inducers. 
Additional references include: 
• Food and Drug Administration.  Drug Development and Drug Interactions:  Table of 
Substrates, Inhibitors and Inducers. 
• EMA (2013) Guideline on the Investigation of Drug Interactions. 
• NPS Australia. 
Potent and Moderate CYP3A4/CYP3A5 Inhibitors 
Aprepitant 
Grapefruit 
Posaconazole 
Atazanavir 
Grapefruit juice 
Ritonavir 
Cannabidiol (CBD) 
Indinavir 
Saquinavir 
Casopitant 
Itraconazole 
Telithromycin 
Clarithromycin 
Ketoconazolea 
Troleandomycin 
Diltiazem 
Mibefradil 
Verapamil 
Erythromycin 
Nefazodone 
Voriconazole 
Fluconazole 
Nelfinavir 
 
a Note topical use of 2% ketoconazole cream is allowed. 
Potent CYP3A4/CYP3A5 Inducers 
Apalutamide 
Enzalutamide 
Phenytoin 
Bosentan 
Etravirine 
Primidone 
Carbamazepine 
Mitotane 
Rifampicin 
Efavirenz 
Phenobarbital 
St. John's wort 


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APPENDIX F. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic presents challenges to the ongoing conduct of clinical trials.  In 
line with regulatory guidance regarding clinical trial execution during the pandemic, the sponsor 
has issued the following Protocol considerations to ensure participant safety is maintained and 
adequate benefit/risk analyses are applied relative to the completion of study procedures and 
maintaining the investigational product supply chain.  Recognizing the dynamic nature and 
flexibility required to manage the impact of the pandemic on this clinical trial, additional details 
will be incorporated into respective study manuals and site-specific monitoring plans as 
applicable, with institutional requirements as warranted, and communicated to the investigative 
sites as needed.  Relevant test results will be documented in the eCRF, and applicable changes to 
the ICF will be made and monitored. 
Study Site Visits 
If local travel restrictions, isolation requirements, or the investigator's benefit/risk assessment 
determines it to be unsafe for participants to attend study visits at the investigational site, the site 
staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video) or as per site institutional guidelines.  At a minimum, a 
review of AEs and concomitant medications must be completed.  On-site visits 
should be conducted whenever feasible and are required for administration of study 
treatment. The participant may also be asked to undergo additional safety laboratory 
assessments. 
• In order to support investigator oversight of participant safety and disease 
management, the participant may be asked to undergo some laboratory tests or study 
procedures at a local laboratory or facility closer to the participant's residence rather 
than at the investigational site.  In this case, the study physician will provide the 
participant with the list of parameters to be checked.  These tests should be performed 
in certified laboratories. 
• Some tests, such as ECG or CT scan assessments, may require longer windows due to 
the COVID-19 pandemic and may be performed outside the regularly scheduled visit 
window or may be conducted at the next scheduled visit.  It is the investigator's 
responsibility to check with the facility (if performed at a different facility) that the 
data will be obtained and available for evaluation. General procedures performed 
outside of protocol parameters will be captured as protocol deviations due to 
COVID-19 in the eCRF. 
Participant SARS-CoV-2 Infection and Study Treatment 
An event of active SARS-CoV-2 infection by a participant in the study should be reported as an 
AE or SAE and appropriate medical intervention provided.  For participants with active 
SARS-CoV-2 infection, study treatment should be delayed until the resolution of symptoms and 
until it is allowable for the participant to return to the clinic per institutional guidelines.  Prior to 
restarting treatment, the participant should be afebrile for 72 hours and the treating physician 
should determine that the participant's condition is stable enough to resume study treatment.  The 


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study physician should also consider if the participant is SARS-CoV-2 negative (by test) before 
restarting study treatment if COVID-19 was diagnosed during the trial.  The study team should 
be notified when the study treatment is restarted.  Safety monitoring following COVID-19 
should be implemented as per institutional guidance or clinical judgment (eg, coagulation 
factors). 
COVID-19 Vaccination 
Participants may receive the COVID-19 vaccine as long as it is not a live vaccine, which is 
prohibited per the Protocol (see Section 5.2).  COVID-19 vaccination will be captured in the 
eCRF as a concomitant medication.  Administration of study treatment may be delayed to ensure 
vaccination is completed.  The medical monitor may be consulted if needed. 
Clinical Trial Monitoring 
Study monitoring visits could be postponed; however, the site monitor and sponsor will continue 
to employ off-site monitoring practices such as routine communication methods (eg, phone calls, 
emails, video visits) with the sites to get information on trial progress, participant status, and 
information on issue resolution.  The study monitor may remotely review data entered into the 
EDC for accuracy and completeness if allowed by the national regulatory body, investigational 
site, and/or in compliance with local authorities. 
Reimbursement of Additional Expenses 
The sponsor will reimburse for any extraordinary expenses, keeping appropriate documentation 
as evidence (eg, travel expenses for the local laboratory visit[s], the costs of local [proximate] 
laboratory tests). 


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APPENDIX G. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 (Version 2): 
08 MAR 2021 
Amendment 1 (08 MAR 2021) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to incorporate additional dose levels to evaluate the 
safety and preliminary activity of INCB086550 with intermittent and/or step-down dose 
administration schedules.  The changes are summarized below. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements; Figure 1:  
Study Design Schema; Table 3:  Schedule of Activities for 28-Day Cycle [Schedule 
A]; Table 4:  Schedule of Activities for 28-Day Cycle [Schedule B]; Table 5:  
Schedule of Activities for 21-Day Cycle [Schedule C]; Table 6:  Schedule of 
Activities for 21-Day Cycle [Schedule D]); Section 2.2.1, Scientific Rationale for 
Study Design; Section 2.2.2, Justification for Dose; Section 4.1, Overall Design; 
Section 6.1, Study Treatment Administered (Table 9:  Study Treatment 
Administered) 
Description of change:  Removed initial treatment regimen of 400 mg BID as the 
pharmacologically active dose that will be used initially and provided updated safety 
language from the Phase 1 study.  Updated INCB086550 treatment administration to 
incorporate evaluation of intermittent and/or step-down dose administration regimens.  
Added a 21-day schedule of assessments as an option and added new SoA to 
accommodate the additional schedules (Tables 4-6). 
Rationale for change:  To enable the evaluation of safety and tolerability and 
preliminary efficacy of intermittent and/or step-down dose administration in 21-day or 
28-day treatment cycles. 
2. Section 1, Protocol Summary (Table 2:  Key Study Design Elements) 
Description of change:  The number of participants planned to receive INCB086550 has 
been clarified as up to approximately 304 participants, rather than 152 participants, given 
that more than 1 level may be tested. 
Rationale for change:  Ability to add dose levels. 
3. Section 1, Protocol Summary (Figure 1:  Study Design Schema); Section 4.1, Overall 
Design; Section 10.5, Interim Analysis 
Description of change:  Added nonbinding safety and efficacy run-in analysis in up to 
15 participants in select disease-specific cohorts. 
Rationale for change:  To enable the early evaluation of safety and efficacy. 


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4. Section 1, Protocol Summary (Table 3:  Schedule of Activities for 28-Day Cycle 
[Schedule A]; Table 4:  Schedule of Activities for 28-Day Cycle [Schedule B]; 
Table 5:  Schedule of Activities for 21-Day Cycle [Schedule C]; Table 6:  Schedule of 
Activities for 21-Day Cycle [Schedule D]); Section 8.5.1, Serum and Plasma for 
Correlative Assessments 
Description of change:  Added note to hematology panel that additional unscheduled 
CBCs may be performed.  Added note to endocrine panel, plasma and serum for 
correlative studies, 
 that additional assessments may be 
performed if a participant has an irAE.  Added a new collection of serum for correlative 
studies.   
Rationale for change:  To further evaluate immune activation and irAEs. 
5. Section 1, Protocol Summary (Table 3:  Schedule of Activities for 28-Day Cycle 
[Schedule A]; Table 4:  Schedule of Activities for 28-Day Cycle [Schedule B]; 
Table 5:  Schedule of Activities for 21-Day Cycle [Schedule C]; Table 6:  Schedule of 
Activities for 21-Day Cycle [Schedule D]); Section 5.1, Inclusion Criteria (Inclusion 
Criterion 6); Section 8.3.6, Laboratory Assessments (Table 17:  Required 
Laboratory Analytes); Section 8.3.6.1, Pregnancy Testing; Appendix A, Information 
Regarding Effectiveness of Contraceptive Methods 
Description of change:  Modified requirements for pregnancy testing and contraception 
based on Clinical Trials Facilitation and Coordination Group 2014 and 2020 guidance. 
Rationale for change:  Updated guidance. 
6. Section 3, Objectives and Endpoints (Table 7:  Objectives and Endpoints); 
Section 8.2, Efficacy Assessments; Section 8.2.1.2, Assessment of Disease Response 
During Treatment; Section 10.4, Statistical Analyses 
Description of change:  Removed evaluation of efficacy per iRECIST and option for 
treatment beyond progression.   
Rationale for change:  Not required. 
7. Section 5.1, Inclusion Criteria 
Description of change:  Modified Inclusion Criterion 5.e to include chemotherapy as an 
allowable line of prior therapy and added Inclusion Criterion 7 to clarify that participants 
(except those with NSCLC) must have documented disease progression after treatment 
with available therapies. 
Rationale for change:  Clarification. 


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8. Section 6.1, Study Treatment Administered (Table 7:  Study Treatment 
Information); Appendix C, Instruction to Participants for Handling Study Drug 
(INCB086550) 
Description of change:  Added INCB086550 400 mg tablet strength.  Specified that 
INCB086550 tablets may be crushed and administered with water, apple juice, 
applesauce, or yogurt.  Clarified language pertaining to doses for QD and BID dose 
schedules. 
Rationale for change:  Addition of new tablet strength and treatment administration 
method and clarification of QD and BID dose schedules.  
9. Section 6.6.2, Restricted Medications and Procedures 
Description of change:  Added examples of P-gp inhibitors with a narrow therapeutic 
window as well as information pertaining to INCB086550 as an inhibitor of the 
creatinine transporter OCT2 and use of stomach acid–reducing medications such as 
proton pump inhibitors and H2-receptor blockers.   
Rationale for change:  To provide examples of P-gp inhibitors and clarification on use 
of metformin (an OCT2 substrate) and stomach acid–reducing medications.  
 
  
10. Section 6.6.4, COVID-19; Appendix F, COVID-19 Pandemic Mitigation Strategies 
and Instructions 
Description of change:  Added information related to management of the study and 
participants during the COVID-19 pandemic. 
Rationale for change: New information. 
11. Section 1, Protocol Summary (Table 3:  Schedule of Activities for 28-Day Cycle 
[Schedule A]; Table 4:  Schedule of Activities for 28-Day Cycle [Schedule B]; 
Table 5:  Schedule of Activities for 21-Day Cycle [Schedule C]; Table 6:  Schedule of 
Activities for 21-Day Cycle [Schedule D]); Section 8.1.4, Distribution of Dosing 
Diary and Patient Information Cards 
Description of change:  Dosing diaries will also be provided for each patient at each 
visit. 
Rationale for change:  Clarification. 
12. Section 8.2.1, Tumor Imaging by RECIST v1.1; Section 10.2, Populations for 
Analysis (Table 21:  Populations for Analysis) 
Description of change:  Updated information for assessment of skin lesions according to 
RECIST v1.1 and the evaluable populations. 
Rationale for change:  Clarification. 
13. Section 8.3.5, Electrocardiograms 
Description of change:  Revised Table 15 and added Table 16 to clarify the ECG 
collection schedule based on treatment schedule. 
Rationale for change:  Clarification. 




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SAP_001.pdf: 
Official Title: 
NCT Number: 
Document Date: 
A Phase 2 Study of INCB086550 (Oral PD-L1 Inhibitor) in 
Participants Who Are Immune Checkpoint Inhibitor–Naïve With 
Selected Solid Tumors
NCT04629339
Statistical Analysis Plan Amendment 1, Version 1: 01 
December-2023


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Statistical Analysis Plan 
INCB 86550-203 
A Phase 2 Study of INCB086550 (Oral PD-L1 Inhibitor) in Participants 
Who Are Immune Checkpoint Inhibitor–Naïve With Selected Solid 
Tumors 
 
 
IND Number: 
139,900 (NCT04629339) 
EudraCT Number: 
2020-000157-27 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol Amendment 1 dated 08 MAR 2021 
CRF Approval Date: 
30 MAR 2022 
SAP Version: 
Amendment 1 
SAP Author: 
, PhD 
, Biostatistics 
Date of Plan: 
01 DEC 2023 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1.
INTRODUCTION ........................................................................................................7 
2.
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives and Endpoints ...................................................................................8 
3.
STUDY DESIGN .........................................................................................................9 
3.1. 
Randomization ..............................................................................................................9 
3.2. 
Control of Type I Error ...............................................................................................10 
3.3. 
Sample Size Considerations .......................................................................................10 
3.4. 
Schedule of Assessments ............................................................................................10 
4.
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................11 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................11 
4.1.1. 
Day 1 ...........................................................................................................................11 
4.1.2. 
Study Day ...................................................................................................................11 
4.1.3. 
Baseline Value ............................................................................................................11 
4.1.4. 
Handling of Missing and Incomplete Dates ...............................................................11 
4.1.5. 
Cycle Length and Duration .........................................................................................12 
4.2. 
Variable Definitions ....................................................................................................12 
4.2.1. 
Prior and Concomitant Medication .............................................................................12 
5.
STATISTICAL METHODOLOGY ...........................................................................13 
5.1. 
General Methodology .................................................................................................13 
5.2. 
Treatment Groups .......................................................................................................13 
5.3. 
Analysis Populations ..................................................................................................13 
6.
BASELINE, EXPOSURE, AND DISPOSITION ......................................................15 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................15 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................15 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................15 
6.1.3. 
Prior Anticancer Therapy ...........................................................................................15 
6.1.4. 
Medical History ..........................................................................................................15 


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6.2. 
Disposition of Participants ..........................................................................................15 
6.3. 
Protocol Deviations ....................................................................................................15 
6.4. 
Exposure .....................................................................................................................15 
6.5. 
Study Drug Compliance .............................................................................................16 
6.6. 
Prior and Concomitant Medications ...........................................................................16 
7. 
EFFICACY .................................................................................................................17 
7.1. 
Efficacy Hypotheses ...................................................................................................17 
7.2. 
Analysis of the Primary Efficacy Parameters .............................................................17 
7.2.1. 
Response Criteria ........................................................................................................17 
7.2.2. 
Best Overall Response ................................................................................................17 
7.2.3. 
Objective Response Rate ............................................................................................19 
7.3. 
Analysis of the Secondary Efficacy Parameters .........................................................19 
7.3.1. 
Duration of Response .................................................................................................19 
7.3.2. 
Disease Control Rate ..................................................................................................19 
 
19 
 
19 
 
19 
 
19 
9. 
SAFETY AND TOLERABILITY ..............................................................................20 
9.1. 
General Considerations ...............................................................................................20 
9.2. 
Adverse Events ...........................................................................................................20 
9.2.1. 
Adverse Event Definitions ..........................................................................................20 
9.2.2. 
Immune-Related Adverse Events ...............................................................................20 
9.2.3. 
Adverse Event Summaries ..........................................................................................20 
9.3. 
Clinical Laboratory Tests ...........................................................................................21 
9.3.1. 
Laboratory Value Definitions .....................................................................................21 
9.3.2. 
Laboratory Value Summaries .....................................................................................21 
9.3.3. 
Potential Drug-Induced Liver Injuries ........................................................................22 
10. 
INTERIM ANALYSES ..............................................................................................22 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................22 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................22 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................22 
11.2.1. 
Original to Amendment 1 ...........................................................................................22 


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12. 
REFERENCES ...........................................................................................................23 
APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................24 
 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Sample Size per Cohort ..............................................................................................10 
Table 3: 
Populations for Analysis .............................................................................................13 
Table 4: 
Analysis Populations by Endpoint ..............................................................................14 
Table 5: 
Confirmed Response Based on Subsequent Assessments ..........................................18 
Table 6: 
Statistical Analysis Plan Versions ..............................................................................22 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema ...................................................................................................9 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ALK 
anaplastic lymphoma kinase 
BID 
twice daily 
CI 
confidence interval 
CNS 
central nervous system 
COVID-19 
coronavirus disease 2019 
CPS 
composite performance score 
CR 
complete response 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
disease control rate 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EGFR 
epidermal growth factor receptor 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
HCC 
hepatocellular carcinoma 
irAE 
immune-related adverse event 
KM 
Kaplan Meier 
MedDRA 
Medical Dictionary for Regulatory Activities  
NE 
not evaluable 
NSCLC 
non–small cell lung cancer 
ORR 
objective response rate 
PI


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Abbreviation 
Term 
PD 
progressive disease 
PD-1 
programmed death 1 
PD-L1 
programmed death-ligand 1 
PR 
partial response 
PS 
performance score 
PT 
preferred term 
QT 
QT interval in electrocardiogram tracings 
QTc 
corrected QT interval 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RCC 
renal cell carcinoma 
ROS 
reactive oxygen species 
SAP 
Statistical Analysis Plan 
SD 
stable disease 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TPS 
tumor proportion score 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
PI


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1. 
INTRODUCTION 
This open-label, global, nonrandomized, multicohort trial is designed to provide a benchmark of 
efficacy for INCB086550 in key indications in which other PD-(L)1 inhibitors have already 
demonstrated efficacy. 
Section 2 of the Protocol provides a detailed description of the investigational product, rationale 
for doses to be examined, and potential risks and benefits of treatment with INCB086550. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
INCB 86550-203 Protocol Amendment 1. The scope of this plan includes the analyses that are 
planned and will be executed by the Department of Biostatistics or designee. Pharmacokinetic 
analysis will not be performed for this study. This study was terminated early. 
 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 86550-203 Protocol Amendment 1 dated 08 MAR 2021 and CRFs 
approved 30 MAR 2022. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the ORR of participants treated with 
INCB086550. 
ORR, defined as the percentage of participants with a 
best overall response of CR or PR confirmed by at least 
1 repeat assessment ≥ 28 days later according to 
RECIST v1.1 as determined by the investigator. 
Secondary 
To determine the efficacy of INCB086550 in 
participants with advanced solid tumors in respect to 
DCR. 
DCR, defined as the percentage of participants with a 
best overall response of CR or PR confirmed by at least 
1 repeat assessment ≥ 28 days later, or SD for 
≥ 12 weeks, by investigator assessment per 
RECIST v1.1. 
To determine the efficacy of INCB086550 in 
participants with advanced solid tumors in respect to 
DOR. 
DOR, defined as the time from the earliest date of CR 
or PR confirmed by at least 1 repeat assessment 
≥ 28 days later until the earliest date of disease 
progression by investigator assessment per 
RECIST v1.1, or death due to any cause, if occurring 
sooner than progression. 
To evaluate the safety of INCB086550 in participants 
with advanced solid tumors. 
Safety is determined by monitoring the frequency and 
severity of AEs, including the evaluation of laboratory 
tests, vital signs, and ECGs. 




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3.2. 
Control of Type I Error 
Not applicable. 
3.3. 
Sample Size Considerations 
The number of participants based on a group sequential design with 1 interim per cohort at 
approximately 50% information using a Hwang-Shih-DeCani (1990) spending function has been 
determined independently for each disease-specific cohort (irrespective of dose level) and can be 
found in Table 2. The target ORR (p1) for each cohort is based on published clinical experience 
with a reference PD-1 inhibitor (El-Khoueiry et al 2017, Keytruda 2018, Mok et al 2019, Motzer 
et al 2015, Reck et al 2016, Robert et al 2015). The target ORR (p1) for the NSCLC cohort was 
calculated by combining 2 different studies (Mok et al 2019, Reck et al 2016). The null ORR (p0) 
for the melanoma and RCC cohorts is based on the control arm ORRs in the reference studies. 
For the NSCLC, UC, and HCC cohorts, the null ORR (p0) was selected to be the p0 that creates a 
test with a rejection region that begins with the lower CI bound of the reference PD-1 inhibitors. 
The sample size for each cohort provides approximately 80% power and 5% 1-sided Type I 
error. 
Table 2: 
Sample Size per Cohort 
Tumor Type (Cohort) 
ORR 
Sample Size 
p0 
p1 
NSCLC 
18.0% 
41.1% 
32 
UC 
20.0% 
47.0% 
25 
HCC 
6.0% 
20.0% 
42 
RCC 
5.0% 
25.0% 
23 
Melanoma 
11.9% 
32.9% 
30 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 1 dated 08 MAR 2021 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 
Day 1 is the date that the first dose of study drug (INCB086550) is administered to the 
participants. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date). 
A study day of –1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of 
INCB086550. 
When scheduled assessments and unscheduled assessments occur on the same day and the time 
of the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Handling of Missing and Incomplete Dates 
In general, values for missing dates will not be handled unless methods for handling missing 
dates are specified in this section or relevant sections. The original reported dates collected on 
the eCRF should be used in all relevant listings. The following rules will be used for handling 
partial dates for analyses requiring dates. 
When calculating the time since diagnosis of cancer, a partial cancer diagnosis date will be 
handled as follows in the calculation: 
• If only the day is missing, then the first day of the month will be used. 
• If both the month and day are missing, then 01 JAN of the year will be used. 
• If the diagnosis date is completely missing, then the time since diagnosis will not be 
calculated. 


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When the date of the last dose is used in deriving variables such as duration of treatment or 
TEAE flag, a missing or partial date of the last dose will be handled as follows: 
• If only the day is missing, then the earlier date of the last day of the month or the date 
that the participant discontinued treatment will be used. 
• If both the month and day are missing, then the earlier date of 31 DEC of the year or 
the date that the participant discontinued treatment will be used.  
• Otherwise, the date that the participant discontinued treatment will be used as the date 
of the last dose. 
For DOR, 
, a partial date of the death date will be handled as 
follows in the calculation: 
• 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 
Cycle 1 Day 1 is the day that the first dose of study drug is administered. The scheduled cycle 
length is either 21 or 28 days (Protocol Tables 3-6). The actual Day 1 of subsequent cycles will 
correspond with the first day of administration of INCB086550 in that cycle; thus, treatment 
cycles may become out of sync with the originally planned schedule, and the cycle length may 
be different from 21 or 28 days. The date of the Day 1 of subsequent cycles recorded on the 
eCRF will be used as the Day 1 of the subsequent cycles. 
4.2. 
Variable Definitions 
4.2.1. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB086550. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first administration of INCB086550 and is ongoing throughout the 
study or ends on/after the date of first study drug administration. 
• On/after the date of first administration of INCB086550 and is ongoing or ends 
during the course of the study. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after the first dose of INCB086550. In the listing, it will be indicated whether a 
medication is only prior, only concomitant, 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. 
PI


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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 participants in each category. 
Interim analyses are planned for this study as defined in Section 10; however, the study was 
terminated early, and no interim analyses will be performed. 
5.2. 
Treatment Groups 
Participants will be enrolled at 1 or more dose levels into disease-specific cohorts, with a 
safety/efficacy run-in analysis in up to 15 participants. The study was terminated prior to 
completion of the safety/efficacy run-in analysis. Data will be summarized separately for each 
cohort and dose level and may be summarized in total, as appropriate depending on enrollment. 
5.3. 
Analysis Populations 
Table 3 presents the populations for analysis. Table 4 presents the analysis populations by 
endpoint.  
Table 3: 
Populations for Analysis 
Population 
Description 
FAS 
The FAS includes all study participants who received at least 1 dose of study drug. 
The FAS will be used for the summary of demographics, baseline characteristics, 
participant disposition, and all efficacy analyses. Participants will be analyzed 
according to the treatment group/dose to which they have been assigned. 
Safety evaluable 
The safety evaluable population includes all participants who received at least 1 dose 
of study drug. All safety analyses will be conducted using the safety evaluable 
population. Treatment groups for this population will be determined according to the 
actual treatment group/dose the participant received regardless of assigned study drug 
treatment. 


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Table 4: 
Analysis Populations by Endpoint 
Endpoint 
Analysis Population 
ORR, defined as the percentage of participants with a best 
overall response of CR or PR confirmed by at least 1 repeat 
assessment ≥ 28 days later according to RECIST v1.1 as 
determined by the investigator. 
FAS 
DCR, defined as the percentage of participants with a best 
overall response of CR or PR confirmed by at least 1 repeat 
assessment ≥ 28 days later, or SD for ≥ 12 weeks, by 
investigator assessment per RECIST v1.1. 
FAS 
DOR, defined as the time from the earliest date of CR or 
PR confirmed by at least 1 repeat assessment ≥ 28 days 
later until the earliest date of disease progression by 
investigator assessment per RECIST v1.1, or death due to 
any cause, if occurring sooner than progression. 
FAS 
Safety is determined by monitoring the frequency and 
severity of AEs, including the evaluation of laboratory 
tests, vital signs, and ECGs. 
Safety evaluable 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics and baseline characteristics will be summarized for the FAS: age, 
sex, race, ethnicity, weight, and height. 
6.1.2. 
Baseline Disease Characteristics and Disease History 
The following baseline disease characteristics and disease history will be summarized for the 
FAS: ECOG PS, cancer type, current stage, current sites of metastatic disease, and PD-L1 TPS 
for participants with NSCLC and participants with UC. Relevant 
 
 
6.1.3. 
Prior Anticancer Therapy     
Prior anticancer therapy will be listed. 
6.1.4. 
Medical History 
Medical history will be listed. 
6.2. 
Disposition of Participants 
The number and percentage of participants who were treated, who were ongoing with study 
treatment, who completed study treatment, who discontinued study treatment with a primary 
reason for discontinuation, who were still in the study, who completed the study, and who 
withdrew from the study with a primary reason for withdrawal will be summarized for the FAS. 
The number of participants enrolled by country and/or site will also be provided by cohort and 
dose level. 
6.3. 
Protocol Deviations 
Important Protocol deviations will be summarized and listed for the FAS. 
6.4. 
Exposure 
For participants in the safety evaluable population, exposure will be summarized as follows: 
• Duration of treatment with INCB086550 days: (date of last dose of INCB086550 – 
date of first dose of INCB086550 + 1) (including scheduled dose holds [days] for 
intermittent schedule). 
• Average daily dose of INCB086550 (mg/day): total actual INCB086550 dose taken 
(mg) / duration of treatment with INCB086550 (days). 


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Total actual dose taken will be calculated based on the information entered on the Dosing 
eCRF. 
6.5. 
Study Drug Compliance 
For participants in the safety evaluable population, overall compliance (%) for INCB086550 will 
be calculated for all participants as follows: 
compliance (%) = 100  [total dose actually taken] / [total prescribed dose]. 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 
The total actual dose taken will be calculated based on information entered on the Dosing eCRF. 
6.6. 
Prior and Concomitant Medications 
Prior medications and concomitant medications will be listed. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
7.1. 
Efficacy Hypotheses 
Not applicable. 
7.2. 
Analysis of the Primary Efficacy Parameters 
7.2.1. 
Response Criteria 
Overall disease status will be categorized using RECIST v1.1 (Eisenhauer et al 2009). 
Participants will have their overall response evaluated as CR, PR, SD, PD, or NE at each 
postbaseline radiologic assessment based on changes in target lesions, nontarget lesions, and 
appearance of new lesions. 
7.2.2. 
Best Overall Response 
In general, under RECIST v1.1, best overall response is the best response recorded postbaseline 
prior to and including the first PD, in the order of CR, PR, SD, PD, and NE. The best overall 
response will be determined from response assessments prior to or on the same day as new 
anticancer therapy. If any alternative cancer therapy is taken while on study, any subsequent 
assessments will be excluded from the best overall response determination. 
In the case of SD, measurements must meet the SD criteria at least once after the date of first 
dose at a minimum interval of 12 weeks. Participants who fail to meet this criterion will have 
best overall response of PD if the next available assessment indicates PD or NE if there is no 
additional assessment available. 
The participant's best overall response assessment will depend on the achievement of both 
measurement and confirmation criteria in Table 5, with confirmation assessment occurring after 
a gap of ≥ 28 days. 


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Table 5: 
Confirmed Response Based on Subsequent Assessments 
First Timepoint Response 
Second Timepoint Response 
Confirmed Response 
CR 
CR 
CR or SD or NEa 
CR 
PRb 
SD or NEc 
CR 
PRb 
SD or NEc 
CR 
PD 
SD or NEc 
CR 
NE 
SD or NEc 
CR 
No further evaluation 
SD or NEc 
PR 
CR 
PR or SD or NEd 
PR 
PR 
PR or SD or NEe 
PR 
SD 
SD or NEc 
PR 
NE 
SD or NEc 
PR 
PD 
SD or NEc 
PR 
No further evaluation 
SD or NEc 
SD 
CR 
SD or NEc 
SD 
PR 
SD or NEc 
SD 
SD 
SD or NEc 
SD 
PD 
SD or NEc 
SD 
NE 
SD or NEc 
SD 
No further evaluation 
SD or NEc 
PD 
No further evaluation 
PD 
NE 
CR 
NE 
NE 
PR 
NE 
NE 
SD 
NE 
NE 
PD 
NE 
NE 
NE 
NE 
NE 
No further evaluation 
NE 
Note: A confirmed response of SD can only be made after the participant is on study for a minimum of 12 weeks according to the 
study Protocol or SAP. If the participant is on study less than 12 weeks, any tumor assessment indicating SD before this time 
period will have a confirmed response of NE. NE is not required to be confirmed according to the table. 
Note: Subsequent documentation of CR may provide confirmation of a previously identified CR for participants where the 
second integrated response was NE. Subsequent documentation of PR may provide confirmation of a previously identified PR 
for participants where the second integrated response was NE or SD. If the third tumor assessment confirms the CR (or PR), 
then the confirmed response will be CR (or PR). Only 1 intervening NE is allowed between CRs/PRs. For example: CR NE CR 
= CR; PR NE PR/CR = PR. Additionally, 1 SD (≥ 25% reduction in target lesions comparing with baseline) is allowed between 
PRs (eg, PR SD PR/CR = PR). Note: in the scenario of PR SD NE PR, this is not a confirmed PR. 
a Confirmed response is CR if 28-day gap is met. Otherwise, confirmed response is SD if at least 12 weeks on study or NE if 
within 12 weeks on study. 
b Special case programming: assign PR or SD following CR as PD in confirmed response. 
c Confirmed response will be SD if the first tumor assessment is at least 12 weeks on study. Otherwise, the confirmed response 
will be NE. 
d Confirmed response is PR if 28-day gap is met. Otherwise, confirmed response is SD if at least 12 weeks on study or NE if 
within 12 weeks on study. 


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7.2.3. 
Objective Response Rate  
A participant is considered an objective responder if they have a best overall response of CR or 
PR confirmed by at least 1 repeat assessment ≥ 28 days later according to RECIST v1.1 as 
determined by the investigator. The ORR will be calculated separately for each cohort and dose 
level.  
7.3. 
Analysis of the Secondary Efficacy Parameters 
7.3.1. 
Duration of Response 
Duration of response is defined as the time from the earliest date of CR or PR confirmed by at 
least 1 repeat assessment ≥ 28 days later until the earliest date of disease progression by 
investigator assessment per RECIST v1.1, or death due to any cause, if occurring sooner than 
progression. Partial death dates will be handled using the rules described in Section 4.1.4. 
For participants who have not had disease progression and are still alive at the time of the 
analysis, DOR will be censored on the day of last evaluable disease assessment. For participants 
who have discontinued the study or have started other anticancer treatment, DOR will be 
censored on the day of last evaluable disease assessment documenting absence of PD before the 
discontinuation or the start of the new anticancer treatment. The KM estimate of median DOR 
and its 95% CI will be calculated using the KM method if the number of responders is ≥ 5. 
Duration of response will be listed for each responder. 
7.3.2. 
Disease Control Rate 
Disease control rate is defined as the percentage of participants with a best overall response of 
CR or PR confirmed by at least 1 repeat assessment ≥ 28 days later, or SD for ≥ 12 weeks, by 
investigator assessment per RECIST v1.1. The DCR will be summarized separately for each 
cohort and dose level. 
 
 
 
 
 
 
 
. 
 
 
 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
9.1. 
General Considerations 
The clinical safety data (ie, routine laboratory tests and AEs) will be summarized using 
descriptive statistics (eg, mean, frequency) using the safety evaluable population. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first dose of study drug up to 90 days after the last dose of study drug or until the start of new 
anticancer therapy, whichever occurs first. Analysis of AEs (as discussed below) will be limited 
to TEAEs, but data listings will include all AEs regardless of their timing in relation to study 
drug administration. For purposes of analysis, all AEs will be considered TEAEs unless the AE 
can unequivocally be defined as not treatment-emergent. 
Adverse events will be tabulated by MedDRA SOC and PT. Severity of AEs will be graded 
using the National Cancer Institute CTCAE v5 using Grades 1 through 5. The CTCAE reporting 
guidelines and grading details are available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. 
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. 
9.2.2. 
Immune-Related Adverse Events 
Number (%) of participants reporting any irAEs will be tabulated by immune-related category 
and PT. Potential irAEs will be identified according to a sponsor-defined list of terms. Final 
clinical irAE review details will be outlined in the CSR. 
9.2.3. 
Adverse Event Summaries 
Overall summaries of AEs and irAEs by cohort, dose, and total will include the following: 
• Participants who had a TEAE/irAE 
• Participants who had a serious TEAE/irAE 
• Participants who had a Grade 3 or higher TEAE/irAE 
• Participants who had a treatment-related TEAE 


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• Participants who had a serious treatment-related TEAE 
• Participants who had a Grade 3 or higher treatment-related TEAE 
• Participants who had a fatal TEAE/irAE 
• Participants who had a TEAE/irAE leading to dose reduction 
• Participants who had a TEAE/irAE leading to dose interruption 
• Participants who had a TEAE/irAE leading to discontinuation of INCB086550 
• Participants who had a TEAE/irAE leading to dose reduction, interruption, or 
discontinuation of INCB086550 
The following summaries will be produced by MedDRA SOC and/or PT or irAE category: 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of serious TEAEs by SOC and PT 
• Summary of serious treatment-related TEAEs by PT in decreasing order of frequency 
• Summary of TEAEs with a fatal outcome by SOC and PT 
• Summary of TEAEs leading to dose modification of INCB086550 by SOC and PT 
• Summary of TEAEs leading to discontinuation of INCB086550 by SOC and PT 
• Summary of sponsor-defined irAEs by category and PT 
9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
Laboratory values and change from baseline values will be summarized descriptively by visit. 
Baseline will be determined according to Section 4.1.3. If there are multiple values that meet the 
criteria for baseline, 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 using Grades 1 through 4 using CTCAE v5 when applicable. 
9.3.2. 
Laboratory Value Summaries 
A certified laboratory local to the investigative site will perform all clinical laboratory 
assessments for safety (ie, blood chemistries, hematology assessments, coagulation tests, 
endocrine function, and urinalysis). 
Any laboratory test results and associated normal ranges from local laboratories will be 
converted to SI units.  
Shift tables will be presented showing change in CTCAE grade from baseline to worst grade 
postbaseline for hematology and chemistry laboratory assessments. Separate summaries for 
abnormally high and abnormally low laboratory values will be provided when the laboratory 


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parameter has both high and low grading criteria. The denominator for the percentage calculation 
will be the number of participants in the baseline category. 
9.3.3. 
Potential Drug-Induced Liver Injuries 
Participants with elevated alanine aminotransferase or aspartate aminotransferase ≥ 3 × ULN and 
alkaline phosphatase < 2 × ULN accompanied by total bilirubin ≥ 2 × ULN within ± 7 days will 
be listed by cohort and dose. 
10. 
 INTERIM ANALYSES 
An interim analysis was planned per Protocol Section 10.5, but due to early study termination, 
the interim analysis was not conducted. 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 6. 
Table 6: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
09 FEB 2022 
Amendment 1 
01 DEC 2023 
11.1. 
Changes to Protocol-Defined Analyses 
The analysis of potential Hy's law events has been changed from the Protocol version to a newly 
created company standard of assessing potential drug-induced liver injuries.  
 
The ECG variable QTcF was updated to QTc to correct a typo in the statistics section of the 
Protocol. RR was also removed since it was not mentioned in Protocol Section 8.3.5. 
The number of responses needed at the final analysis was increased by 1 for the HCC and RCC 
cohorts in order to make the number higher than the number required for the interim. 
 
11.2. 
Changes to the Statistical Analysis Plan 
11.2.1. 
Original to Amendment 1 
Modifications were made to the original SAP to streamline analyses for a synoptic CSR, as this 
study was terminated early with minimal enrollment. 
PI
PI


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12. 
REFERENCES 
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. 
El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular 
carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and 
expansion trial. Lancet 2017;389:2492-2502. 
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of Type I error 
probability spending functions. Stat Med 1990;9:1439-1445. 
Keytruda (pembrolizumab) [prescribing information]. Merck & Co, Inc; June 2018. 
Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously 
untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer 
(KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 
2019;393:1819-1830. 
Motzer R, Escudier B, McDermott D, et al. Nivolumab versus everolimus in advanced renal-cell 
carcinoma. N Engl J Med 2015;373:1803-1813. 
Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for 
PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-1833. 
Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced 
melanoma. N Engl J Med 2015;372:2521-2532. 


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APPENDIX A. PLANNED TABLES AND LISTINGS 
This appendix provides a list of the planned tables and listings for the CSR. Standard tables will 
follow the conventions in the standard safety tables. Shells are provided for nonstandard tables in 
a separate document. In-text tables are identical in structure and content as appendix tables but 
follow a rich text format. 
The list of tables and listings and the shells are to be used as guidelines. Modifications of the list 
or shells that do not otherwise affect the nature of the analysis will not warrant an amendment to 
the SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
Baseline and Demographic Characteristics 
1.1.1 
Analysis Populations 
FAS 
X 
1.1.2 
Summary of Participant Disposition 
FAS 
X 
1.1.3 
Summary of Number of Participants Enrolled by Country and Site 
FAS 
X 
1.1.4 
Summary of Important Protocol Deviations 
FAS 
X 
1.2.1 
Summary of Demographics and Baseline Characteristics 
FAS 
X 
1.3.1 
Summary of Baseline Disease Characteristics 
FAS 
X 
Efficacy 
2.3.1 
Summary of Best Overall Response per RECIST v1.1  
FAS 
 
Safety 
3.1.1 
Summary of Exposure and Duration of Exposure to INCB086550 
Safety 
X 
3.1.2 
Summary of Study Drug Compliance 
Safety 
X 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
X 
3.2.1.1 
Overall Summary of Sponsor-Defined Immune-Related Adverse Events 
Safety 
X 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term 
Safety 
X 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.4 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
X 
3.2.5 
Summary of Serious Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.6 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.7 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of INCB086550 by MedDRA System Organ Class and 
Preferred Term 
Safety 
X 
3.2.8 
Summary of Sponsor-Defined Immune-Related Adverse Events by 
Category and MedDRA Preferred Term 
Safety 
X 
3.2.9 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Modification of INCB086550 by MedDRA System Organ Class and 
Preferred Term 
Safety 
  
3.3.3.1 
Shift Summary of Hematology Laboratory Values in CTCAE Grade – 
to the Worst Abnormal Value  
Safety 
X 
3.3.3.2 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade – to 
the Worst Abnormal Value 
Safety 
X 


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Listings 
Listing No. 
Title 
2.1.1 
Participant Enrollment and Disposition Status 
2.1.1.1 
Deaths 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.2.1 
Important Protocol Deviations  
2.3.1 
Analysis Populations 
2.4.1 
Demographic and Baseline Characteristics 
2.4.2 
Disease History  
2.4.3 
Prior Anticancer Radiation Treatment 
2.4.4 
Prior Systemic Anticancer Therapy 
2.4.5 
Prior Anticancer Surgery or Surgical Procedure 
2.4.6 
Medical History 
2.4.7 
Prior and Concomitant Medication 
2.4.8 
ECOG Performance Status 
2.5.1 
Study Drug Compliance 
2.5.2 
Study Drug Administration 
2.6.1 
Investigator-Reported Response Assessment per RECIST v1.1 
2.6.2 
Duration of Response per RECIST v1.1  
2.6.3 
Response Assessment: Target Lesions 
2.6.4 
Response Assessment: Nontarget Lesions  
2.6.5 
Response Assessment: New Lesions  
2.6.6 
Bone Scan Results 
2.7.1 
Adverse Events  
2.7.2 
Serious Adverse Events 
2.7.3 
Fatal Adverse Events 
2.7.4 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of INCB086550 
2.7.5 
Sponsor-Defined Immune-Related Adverse Events 
2.8.1.1 
Clinical Laboratory Values – Hematology 
2.8.1.2 
Clinical Laboratory Values – Chemistry 
2.8.1.3 
Clinical Laboratory Values – Endocrine Function 
2.8.1.4 
Potential Drug-Induced Liver Injuries