Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: Arginase inhibitor multiple myeloma Daratumumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 15
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and antitumor activity of INCB001158 in combination with daratumumab SC, compared with daratumumab SC alone, in participants with relapsed or refractory multiple myeloma.

Detailed description:

Arms:
arm 1: INCB001158 + daratumumab arm 2: Daratumumab will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy. arm 3: INCB001158 will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.

Interventions: intervention 1: INCB001158 intervention 2: Daratumumab SC
Intervention descriptions: intervention 1: Phase 1: INCB001158 administered orally twice daily at the protocol-defined starting dose, with dose escalation/de-escalation based on protocol-defined toxicity criteria to determine the maximum tolerated dose. INCB001158 is administered in combination with daratumumab SC. Phase 2: INCB001158 administered orally at the recommended dose from Phase 1 either as a monotherapy or in combination with daratumumab SC. intervention 2: Daratumumab 1800 mg co-formulated with rHuPH20 (2000 U/mL) and administered subcutaneously once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and then once every 4 weeks. Daratumumab will be administered either as monotherapy or in combination with INCB001158.

Protocol document:
Prot_000.pdf: 
Official Title: 
NCT Number: 
Document Date: 
A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined 
With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, 
in Participants With Relapsed or Refractory Multiple Myeloma
NCT03837509 
Clinical Study Protocol Amendment 2: 01 December 2021


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Protocol INCB 01158-206 Am 3 
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CONFIDENTIAL 
Clinical Study Protocol 
INCB 01158-206 
A Randomized Open-Label Phase 1/2 Study of INCB001158 
Combined With Subcutaneous (SC) Daratumumab, Compared to 
Daratumumab SC, in Participants With Relapsed or Refractory 
Multiple Myeloma 
 
 
Product: 
INCB001158 
IND Number: 
 
EudraCT Number: 
2018‐004076‐35 
Phase of Study: 
1/2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
25 JAN 2019 
Amendment (Version) 1: 
11 MAR 2019 
Amendment (Version) 1-EU: 
18 MAR 2019 
Amendment (Version) 1-DE: 
16 JUL 2019 
Amendment (Version) 2: 
12 OCT 2020 
Amendment (Version) 3: 
01 DEC 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 01158-206 Protocol Amendment 3 (dated 01 DEC 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 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................10 
1.
PROTOCOL SUMMARY ..........................................................................................15 
2.
INTRODUCTION ......................................................................................................29
2.1. 
Background .................................................................................................................29 
2.1.1. 
Multiple Myeloma and Progressive Disease ..............................................................29 
2.1.2. 
Targeting Myeloid-Derived Suppressor Cells and Arginase in Multiple 
Myeloma .....................................................................................................................29 
2.1.3. 
INCB001158 ...............................................................................................................29 
2.1.4. 
Daratumumab .............................................................................................................30 
2.2. 
Study Rationale ...........................................................................................................31 
2.2.1. 
Rationale for Study Design .........................................................................................31 
2.2.2. 
Combination of INCB001158 and Daratumumab ......................................................32 
2.2.3. 
Justification for the Dose ............................................................................................32 
2.3. 
Benefit/Risk Assessment ............................................................................................32 
3.
OBJECTIVES AND ENDPOINTS ............................................................................33 
4.
STUDY DESIGN .......................................................................................................35 
4.1. 
Overall Design ............................................................................................................35 
4.1.1. 
Phase 1:  Dose Escalation of INCB001158 + Daratumumab SC ...............................35 
4.1.2. 
Phase 2:  Expansion ....................................................................................................37 
4.2. 
Overall Study Duration ...............................................................................................39 
4.3. 
Study Termination ......................................................................................................39 
5.
STUDY POPULATION .............................................................................................40 
5.1. 
Inclusion Criteria ........................................................................................................40 
5.2. 
Exclusion Criteria .......................................................................................................41 
5.3. 
Lifestyle Considerations .............................................................................................43 
5.4. 
Screen Failures ............................................................................................................43 
5.5. 
Replacement of Participants .......................................................................................44 
6.
STUDY TREATMENT ..............................................................................................44 
6.1. 
Study Treatment(s) Administered ...............................................................................44 
6.2. 
Preparation, Handling, and Accountability ................................................................45 


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6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................45 
6.4. 
Study Treatment Compliance .....................................................................................46 
6.5. 
Guidelines for Prevention and Management of Injection-Related Reactions ............46 
6.5.1. 
Prevention of Injection-Related Reactions Due to Daratumumab SC ........................46 
6.5.1.1. 
Pre-Administration Medication ..................................................................................46 
6.5.1.2. 
Post-Administration Medication .................................................................................47 
6.5.2. 
Management of Injection-Related Reactions ..............................................................47 
6.5.2.1. 
Local Injection Site Reactions ....................................................................................47 
6.5.2.2. 
Systemic Injection-Related Reactions ........................................................................47 
6.6. 
Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose 
and/or Pharmacologically Active Dose of INCB001158 ...........................................48 
6.6.1. 
Definition of a Dose-Limiting Toxicity ......................................................................48 
6.6.2. 
Management of Dose-Limiting Toxicities or Other Urgent Situations ......................49 
6.6.3. 
Follow-Up of Dose-Limiting Toxicities .....................................................................49 
6.6.4. 
Procedures for Dose Level Review and Dose Escalation ...........................................50 
6.7. 
Dose Modifications .....................................................................................................50 
6.7.1. 
Dose Modifications of INCB001158 ..........................................................................50 
6.7.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................50 
6.7.3. 
Management of Hyperammonemia ............................................................................55 
6.7.4. 
Dose Delays and Dose Modification of Daratumumab SC ........................................55 
6.7.5. 
Daratumumab SC Interruption or Missed Doses ........................................................56 
6.8. 
Concomitant Medications and Procedures .................................................................56 
6.8.1. 
Permitted Medications and Procedures ......................................................................57 
6.8.1.1. 
Bisphosphonate Therapy ............................................................................................57 
6.8.1.2. 
Therapy for Tumor Lysis Syndrome ..........................................................................57 
6.8.1.3. 
Management of Hepatitis B Virus Reactivation .........................................................57 
6.8.2. 
Prohibited Medications and Procedures .....................................................................58 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................59 
7.1. 
Discontinuation of Study Treatment ...........................................................................59 
7.1.1. 
Reasons for Discontinuation .......................................................................................59 
7.1.2. 
Discontinuation Procedures ........................................................................................59 


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7.2. 
Participant Withdrawal From the Study .....................................................................60 
7.3. 
Lost to Follow-Up.......................................................................................................60 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................61 
8.1. 
Administrative and General Procedures .....................................................................61 
8.1.1. 
Informed Consent Process ..........................................................................................61 
8.1.2. 
Screening Procedures ..................................................................................................62 
8.1.3. 
Interactive Response Technology Procedure ..............................................................62 
8.1.4. 
Distribution of Reminder Cards and Diaries ..............................................................63 
8.1.5. 
Demography and Medical History ..............................................................................63 
8.1.5.1. 
Demographics and General Medical History .............................................................63 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................63 
8.2. 
Efficacy Assessments .................................................................................................63 
8.2.1. 
Evaluations .................................................................................................................63 
8.2.1.1. 
Responses Categories .................................................................................................63 
8.2.1.2. 
Myeloma Protein Measurements in Serum and Urine ................................................65 
8.2.1.3. 
Serum Calcium Corrected for Albumin ......................................................................66 
8.2.1.4. 
β2-microglobulin and Albumin ..................................................................................67 
8.2.1.5. 
Bone Marrow Examination .........................................................................................67 
8.2.1.6. 
Minimal Residual Disease Assessment ......................................................................68 
8.2.1.7. 
Assessment of Lytic Disease ......................................................................................68 
8.2.1.8. 
Assessment of Extramedullary Plasmacytomas .........................................................68 
8.2.2. 
Health Economics .......................................................................................................69 
8.3. 
Safety Assessments .....................................................................................................69 
8.3.1. 
Adverse Events ...........................................................................................................69 
8.3.2. 
Forced Expiratory Volume Test .................................................................................70 
8.3.3. 
Physical Examinations ................................................................................................70 
8.3.3.1. 
Comprehensive Physical Examination .......................................................................70 
8.3.3.2. 
Targeted Physical Examination ..................................................................................70 
8.3.4. 
Vital Signs ..................................................................................................................70 
8.3.5. 
Electrocardiograms .....................................................................................................70 
8.3.6. 
Eastern Cooperative Oncology Group Performance Status ........................................71 
8.3.7. 
Laboratory Assessments .............................................................................................71 
8.3.7.1. 
Blood Type Assessment .............................................................................................74 


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8.3.7.2. 
Chemistries .................................................................................................................74 
8.3.7.3. 
Urinalysis ....................................................................................................................74 
8.3.7.4. 
Plasma Ammonia ........................................................................................................74 
8.3.7.5. 
Pregnancy Testing ......................................................................................................75 
8.3.7.6. 
Serology ......................................................................................................................75 
 
75 
 
75 
 
76 
 
76 
 
76 
 
76 
 
77 
 
 
77 
 
77 
 
77 
 
77 
 
78 
 
78 
8.6. 
Unscheduled Visits .....................................................................................................78 
8.7. 
End of Treatment and/or Early Termination ..............................................................78 
8.8. 
Follow-Up ...................................................................................................................78 
8.8.1. 
Safety Follow-Up ........................................................................................................78 
8.8.2. 
Disease Status Follow-Up ...........................................................................................79 
8.8.3. 
Survival Follow-Up ....................................................................................................79 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................80 
9.1. 
Definition of Adverse Event .......................................................................................80 
9.2. 
Definition of Serious Adverse Event ..........................................................................81 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........82 
9.4. 
Reporting of Serious Adverse Events .........................................................................84 
9.5. 
Adverse Events of Special Interest .............................................................................85 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................85 


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9.7. 
Pregnancy ...................................................................................................................86 
9.8. 
Warnings and Precautions ..........................................................................................86 
9.9. 
Product Complaints ....................................................................................................86 
9.10. 
Treatment of Overdose ...............................................................................................87 
10. 
STATISTICS ..............................................................................................................87 
10.1. 
Sample Size Determination ........................................................................................87 
10.1.1. 
Sample Size for Phase 1 .............................................................................................87 
10.1.2. 
Sample Size for Phase 2 .............................................................................................87 
10.2. 
Populations for Analysis .............................................................................................88 
10.3. 
Level of Significance ..................................................................................................89 
10.4. 
Statistical Analyses .....................................................................................................89 
10.4.1. 
Efficacy Analyses .......................................................................................................89 
10.4.1.1. 
Primary Efficacy Analyses .........................................................................................89 
10.4.1.2. 
Secondary Efficacy Analyses .....................................................................................90 
10.4.2. 
Safety Analyses ..........................................................................................................90 
10.4.2.1. 
Adverse Events ...........................................................................................................90 
10.4.2.2. 
Clinical Laboratory Tests ...........................................................................................91 
10.4.2.3. 
Vital Signs ..................................................................................................................91 
10.4.2.4. 
Electrocardiograms .....................................................................................................91 
10.4.2.5. 
Adverse Events of Special Interest .............................................................................92 
 
92 
 
92 
10.5. 
Interim Analysis ..........................................................................................................92 
10.5.1. 
Interim Analysis for Phase 1 .......................................................................................92 
10.5.2. 
Interim Analysis for Phase 2 .......................................................................................93 
10.5.2.1. 
Efficacy Interim Analysis for Phase 2 ........................................................................93 
10.5.2.2. 
Safety Interim Analysis for Phase 2 ...........................................................................93 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................94 
11.1. 
Investigator Responsibilities .......................................................................................94 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................95 
11.2. 
Data Management .......................................................................................................95 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................97 


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11.4. 
Financial Disclosure ...................................................................................................97 
11.5. 
Publication Policy .......................................................................................................98 
11.6. 
Study and Site Closure................................................................................................98 
12. 
REFERENCES ...........................................................................................................99 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS .............................................................................102 
APPENDIX B. INSTRUCTION TO PARTICIPANTS FOR HANDLING STUDY 
DRUG (INCB001158) ..............................................................................................103 
APPENDIX C. DARATUMUMAB SC DRUG INFORMATION ..........................................104 
APPENDIX D. ANTIHISTAMINES THAT MAY BE USED PREDOSE .............................106 
APPENDIX E. INTERPRETATION OF DARATUMUMAB INTERFERENCE 
REFLEX ASSAY .....................................................................................................107 
APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................108 
 
LIST OF TABLES 
Table 1: 
Primary Objectives and Endpoints .............................................................................15 
Table 2: 
Key Study Design Elements .......................................................................................16 
Table 3: 
Schedule of Activities for Participants in Phase 1, Phase 2, Treatment Group 
A, Treatment Group B – Part 1 (Prior to Crossover), and Treatment Group C 
– Part 1 (Prior to Crossover) .......................................................................................18 
Table 4: 
Schedule of Activities for Participants in Phase 2, Treatment Group B – Part 
2 and Treatment Group C – Part 2 (Who Cross Over) ...............................................21 
Table 5: 
Schedule of Laboratory Assessments for Participants in Phase 1, Phase 2, 
Treatment Group A, Treatment Group B – Part 1 (Prior to Crossover), and 
Treatment Group C – Part 1 (Prior to Crossover) .......................................................24 
Table 6: 
Schedule of Laboratory Assessments for Participants in Phase 2, Treatment 
Group B – Part 2 and Treatment Group C – Part 2 (Who Cross Over) ......................27 
Table 7: 
Schedule of Activities for All Participants (as of Protocol Amendment 3) ...............28 
Table 8: 
Objectives and Endpoints ...........................................................................................33 
Table 9: 
Study Treatment for Participants in Phase 1 Dose Escalation ....................................35 
Table 10: INCB001158 Dose Levels ..........................................................................................36 
Table 11: Dose Escalation, De-Escalation, and Elimination Boundaries for Target DLT 
Rate of 33% in Phase 1 ...............................................................................................36 
Table 12: Treatments for Treatment Groups A, B, and C ..........................................................38 
Table 13: Exclusionary Laboratory Values ................................................................................42 


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Table 14: Study Treatment Information .....................................................................................44 
Table 15: Recommendations for the Management of Systemic Injection-Related 
Reactions .....................................................................................................................48 
Table 16: Definition of a Dose-Limiting Toxicity ......................................................................49 
Table 17: Guidelines for Interruption and Restarting of Study Drug .........................................51 
Table 18: Daratumumab SC–Related Toxicity Management .....................................................56 
Table 19: International Uniform Response Criteria Consensus Recommendations ...................64 
Table 20: Bone Marrow Testing .................................................................................................67 
Table 21: ECOG Performance Status .........................................................................................71 
Table 22: Required Laboratory Analytes ....................................................................................73 
Table 23: Sample Collection Times for Assessments of Urinary Orotic Acid ...........................74 
 
 
76 
 
 
 
76 
Table 26: Estimates of Operating Characteristics for Response Adaptive Design .....................88 
Table 27: Populations for Analysis .............................................................................................88 
Table 28: Criteria for Clinically Notable Vital Sign Abnormalities ...........................................91 
Table 29: Criteria for Clinically Notable Electrocardiogram Abnormalities .............................92 
Table 30: Pocock-Like Boundaries for Treatment Group A (INCB001158 + 
Daratumumab) ............................................................................................................94 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................16 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
 
 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
ADCP 
antibody-dependent cellular phagocytosis 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
anti-HBc 
antibodies to hepatitis B core antigen 
anti-HBs 
antibodies to hepatitis B surface antigen 
AST 
aspartate aminotransferase 
BID 
twice daily 
BOIN 
Bayesian Optimal Interval 
Bregs 
regulatory B cells 
BUN 
blood urea nitrogen 
CDC 
complement-dependent cytotoxicity 
CFR 
Code of Federal Regulations 
 
 
Cmin 
minimum observed plasma or serum concentration over the dose interval 
COPD 
chronic obstructive pulmonary disease 
CR 
complete response 
CSR 
Clinical Study Report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
 
 
Dara 
daratumumab 
DIRA 
daratumumab interference reflex assay 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 


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Abbreviations and 
Special Terms 
Definition 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EOT 
end of treatment 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second 
FFPE 
formalin-fixed, paraffin embedded 
FLC 
free light chain 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
GM-CSF 
granulocyte macrophage colony-stimulating factor 
 
 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDL 
high-density lipoprotein 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
IB 
Investigator's Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IFE 
immunofixation 
IFN-γ 
interferon gamma 
Ig 
immunoglobulin 
IHC 
immunohistochemistry 
IMiD 
immunomodulatory drug 
IMWG 
International Myeloma Working Group 
IPPI 
Investigational Product Preparation Instructions 


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Abbreviations and 
Special Terms 
Definition 
irAE 
immune-related adverse event 
IRB 
institutional review board 
IRR 
systemic injection-related reaction for SC daratumumab; infusion-related 
reaction for IV daratumumab 
IRT 
interactive response technology 
IV 
intravenous 
LDL 
low-density lipoprotein 
MDSC 
myeloid-derived suppressor cells 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFOLFOX6 
modified FOLFOX6 (leucovorin, 5-fluorouracil, and oxaliplatin) 
MM 
multiple myeloma 
M-protein 
monoclonal protein 
MR 
minimal response 
MRD 
minimal residual disease 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NGS 
next generation sequencing 
NK 
natural killer 
ORR 
objective response rate  
OS 
overall survival 
PAD 
pharmacologically active dose 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PD-1 
programmed death-1 receptor 
PFS 
progression-free survival 
PI 
proteasome inhibitor 
 
 
PMN 
polymorphonuclear neutrophils 
PO 
per os 


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Abbreviations and 
Special Terms 
Definition 
POEMS 
polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin 
changes 
PPoS 
posterior probability of success 
PR 
partial response 
QW 
once every week 
QXW 
once every X weeks  
RAR 
response adaptive randomization 
RBC 
red blood cell 
rHuPH20 
recombinant human hyaluronidase 
RNA 
ribonucleic acid 
RNA-seq 
ribonucleic acid sequencing 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SC 
subcutaneous 
sCR 
stringent complete response 
SD 
stable disease 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SIPPM 
Site Investigational Product and Procedures Manual 
SmPC 
summary of product characteristics 
 
 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SPD 
sum of the products of the maximal perpendicular diameters of measured 
lesions 
SPEP 
serum M-protein quantitation by electrophoresis 
study drug 
INCB001158 
study treatment 
This term refers to all medications that the participant is required to receive as 
part of this study. 
T1DM 
Type 1 diabetes mellitus 
TAM 
tumor-associated macrophages 
TCR 
T-cell receptor 


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Abbreviations and 
Special Terms 
Definition 
TEAE 
treatment-emergent adverse event, AEs reported for the first time or worsening 
of a pre-existing event after first dose of study treatment 
 
 
TSH 
thyroid-stimulating hormone 
TTR 
time to response 
ULN 
upper limit of normal 
UPEP  
urine M-protein quantitation by electrophoresis 
VGPR 
very good partial response 
WBC 
white blood cell 


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1.
PROTOCOL SUMMARY
Protocol Title:  A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined With 
Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Participants With 
Relapsed or Refractory Multiple Myeloma 
Protocol Number:  INCB 001158-206 
Objectives and Endpoints: 
Table 1 presents the primary objectives and endpoints. 
Table 1: 
Primary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Phase 1:  To determine the safety, tolerability, 
and RP2D of INCB001158 in combination with 
daratumumab SC. 
Safety and tolerability determined by monitoring 
the frequency, duration, and severity of AEs. 
Phase 2:  To compare the ORR of the RP2D of 
INCB001158 in combination with daratumumab 
SC to daratumumab SC monotherapy. 
ORR, defined as the proportion of participants with 
a documented response PR or better, as per IMWG 
criteria. 
Overall Design: 
This study will evaluate the safety and efficacy of INCB001158 in combination with 
daratumumab SC in participants with relapsed or refractory MM, based on the hypothesis that 
INCB001158 in combination with daratumumab SC will improve response rates compared with 
daratumumab SC alone. 
Table 2 presents the key study design elements.  Further details are presented after the table in 
the study design schema (see Figure 1). 


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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 1/2 
Clinical Indication 
Multiple myeloma  
Population 
Male and female participants ≥ 18 years of age who have relapsed or refractory 
MM. 
Number of 
Participants 
Phase 1:  Approximately up to 18 evaluable participants will be enrolled. 
Phase 2:  Approximately up to 80 evaluable participants will be enrolled. 
Study Design 
Open-label, dose-escalation Phase 1 and randomized Phase 2 study.  
Estimated Duration 
of Study 
Participation 
Up to 28 days for screening, continuous treatment in consecutive 28-day 
cycles as long as participants are receiving benefit and have not met any 
criteria for study withdrawal, and every 8 to 12 weeks for follow-up. 
NOTE:  As of Protocol Amendment 3, no further disease status and survival 
follow-up assessments will be required beyond the last safety follow-up visit. 
Coordinating 
Principal 
Investigator 
, MD 
Figure 1: 
Study Design Schema 
 
Treatment Groups and Duration: 
The study consists of 2 parts:  1) a Phase 1 dose escalation to define the RP2D of INCB001158 
in combination with daratumumab SC, and 2) a Phase 2 expansion to assess the clinical benefit 
of the RP2D of INCB001158 in combination with daratumumab SC compared with 
daratumumab SC alone, or as monotherapy. 


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In Phase 1 eligible participants will receive continuous treatment of INCB001158 at escalating 
dose levels in combination with daratumumab SC, as long as participants are receiving benefit 
and have not met any criteria for study withdrawal.  Daratumumab SC treatment will consist of 
subcutaneous injections of 1800 mg once weekly for Cycles 1 and 2, once every 2 weeks for 
Cycles 3 to 6, and once every 4 weeks thereafter (28-day treatment cycle).  At the discretion of 
the sponsor, up to 6 additional "backfill" participants may be enrolled at any tolerable dose level 
to further investigate safety, efficacy 
. 
In Phase 2 eligible participants will be initially equally randomized (1:1:1) into 3 treatment 
groups of 10 participants per group: 
• Treatment Group A:  continuous treatment of the RP2D of INCB001158 in 
combination with daratumumab SC, as long as participants are receiving benefit and 
have not met any criteria for study withdrawal. 
• Treatment Group B:  daratumumab SC alone (Treatment Group B – Part 1), as long 
as participants are receiving benefit and have not met any criteria for study 
withdrawal.  At the time of confirmed disease progression participants will cross over 
to INCB001158 + daratumumab SC (Treatment Group B – Part 2) and continue 
treatment until PD, or unacceptable toxicity, or any criteria for study withdrawal. 
• Treatment Group C:  continuous treatment of INCB001158 alone at the RP2D 
determined in Phase 1, for at least 2 cycles if the participants are not progressing, and 
beyond Cycle 2 only if they are receiving clinical benefit and have not met any 
criteria for study withdrawal (Treatment Group C – Part 1).  At the time of confirmed 
disease progression participants will then cross over to INCB001158 + daratumumab 
SC (Treatment Group C – Part 2) and continue treatment until PD, or unacceptable 
toxicity, or any criteria for study withdrawal. 
After the equal randomization period, an RAR design will be used to compare the ORR of 
Treatment Groups A and B with adjustments to the randomization rate based on the observed 
ORR.  Evaluation of the safety and tolerability of the 3 treatment groups will be performed 
periodically throughout the study.  Details of the randomization method and model for response 
are provided in the Statistical Methods section.  Participants will be analyzed for efficacy based 
on the treatment group in which they were randomized. 
Table 3 and Table 4 present the SoA for study site visit assessments prior and post-crossover 
respectively.  Table 5 and Table 6 present the schedule of laboratory assessments prior and 
post-crossover respectively.  As of Protocol Amendment 3, only the SoA presented in Table 7 
will be used. Table 22 presents the safety laboratory analytes to be evaluated.  Adherence to the 
study design requirements, including those specified in the SoA, is essential and required for 
study conduct. 
NOTE:  As of Protocol Amendment 3, no further disease status and survival follow-up 
assessments will be required beyond the last safety follow-up visit.


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Table 3: 
Schedule of Activities for Participants in Phase 1, Phase 2, Treatment Group A, Treatment Group B – Part 1 
(Prior to Crossover), and Treatment Group C – Part 1 (Prior to Crossover) 
Visit Day (Range) 
Screening 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Days 
-28 to -1 
Cycles 1 and 2 
Cycles 3 to 6 
Cycles 
7+ 
Safety 
Disease 
Status 
Survival 
D1 
D8 
(± 2d) 
D15 
(± 2d) 
D22 
(± 2d) 
D1 
(± 3d) 
D15 
(± 3d) 
D1 
(± 3d) + 7d 
28-35d 
After 
EOT 
Q8W 
After 
EOT  
± 7d 
Q12W 
After 
EOT  
± 7d 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.1. 
Contact IRT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
See Section 8.1.3. 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
See Section 5. 
General and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.5. 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 6.8. 
Distribute reminder cards  
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
See Section 8.1.4. 
Assess study treatment 
compliance 
 
X* 
 
 
 
X 
 
X 
X 
 
 
 
* C2D1 only. 
See Section 6.4. 
Study treatment 
Dispense/administer 
INCB001158 (participants 
receiving INCB001158 
monotherapy or in 
combination with 
daratumumab SC) 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
In clinic, should be given just before 
administration of daratumumab SC (if 
applicable). 
See Section 6.1, Appendix B, and 
refer to the Pharmacy Manual. 
Administer daratumumab 
SC (participants receiving 
daratumumab SC 
monotherapy or in 
combination with 
INCB001158) 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
In clinic, should be administered after 
INCB001158 (if applicable). 
See Section 6.1, Appendix C, and 
refer to the Pharmacy Manual. 


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Table 3: 
Schedule of Activities for Participants in Phase 1, Phase 2, Treatment Group A, Treatment Group B – Part 1 
(Prior to Crossover), and Treatment Group C – Part 1 (Prior to Crossover) (Continued) 
Visit Day (Range) 
Screening 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Days 
-28 to -1 
Cycles 1 and 2 
Cycles 3 to 6 
Cycles 
7+ 
Safety 
Disease 
Status 
Survival 
D1 
D8 
(± 2d) 
D15 
(± 2d) 
D22 
(± 2d) 
D1 
(± 3d) 
D15 
(± 3d) 
D1 
(± 3d) + 7d 
28-35d 
After 
EOT 
Q8W 
After 
EOT  
± 7d 
Q12W 
After 
EOT  
± 7d 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 8.3.1. 
Forced expiratory volume 
test (participants with COPD 
or asthma) 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.2. 
Physical examination, 
weight, height 
X* 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
*Comprehensive examination and 
height at screening only, targeted 
physical examination thereafter. 
See Section 8.3.3. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 8.3.4. 
Electrocardiogram 
X 
X* 
 
 
 
X** 
 
 
 
X 
 
 
* Predose and 2-4 h after morning 
dose. 
** Predose on C3D1 and C6D1 only. 
See Section 8.3.5. 
ECOG performance status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 8.3.6. 
Subsequent therapy status 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
See Section 8.8.2. 
Survival status 
 
 
 
 
 
 
 
 
 
 
 
X 
See Section 8.8.3. 
Efficacy/disease assessments (blood/urine) – samples to be sent to central laboratory 
Serum 2-microglobulin 
X 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.4. 
Quantitative Ig (IgA, IgM, 
IgG, IgD, IgE) 
X 
 
 
 
 
X* 
 
X* 
X 
 
 
 
* Every 3 months during treatment 
(window of ± 1 month). 
See Section 8.2.1.2. 
SPEP 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
SPEP and UPEP are to be performed 
within 14 days before Cycle 1 Day 1 
and on the scheduled assessment days 
(± 3 d). 
See Section 8.2.1.2. 
UPEP (24 h urine sample) 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
 


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Table 3: 
Schedule of Activities for Participants in Phase 1, Phase 2, Treatment Group A, Treatment Group B – Part 1 
(Prior to Crossover), and Treatment Group C – Part 1 (Prior to Crossover) (Continued) 
Visit Day (Range) 
Screening 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Days 
-28 to -1 
Cycles 1 and 2 
Cycles 3 to 6 
Cycles 
7+ 
Safety 
Disease 
Status 
Survival 
D1 
D8 
(± 2d) 
D15 
(± 2d) 
D22 
(± 2d) 
D1 
(± 3d) 
D15 
(± 3d) 
D1 
(± 3d) + 7d 
28-35d 
After 
EOT 
Q8W 
After 
EOT  
± 7d 
Q12W 
After 
EOT  
± 7d 
Serum calcium corrected for 
albumin 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
See Section 8.2.1.3. 
Serum FLC & serum/urine 
immunofixation 
X 
X* 
 
 
 
X* 
 
X* 
X* 
X* 
X* 
 
To be performed when CR is 
suspected or maintained. 
* For participants with light chain 
only disease, serum FLC to be 
performed on Day 1 of each cycle, at 
EOT, and at safety and disease status 
follow-up. 
See Section 8.2.1.2. 
 
Efficacy/disease assessments (other) 
Bone marrow 
aspirate/biopsy for 
assessment of MRD 
 
 
X* 
Samples are requested at the time of suspected CR to 
confirm CR/sCR and to evaluate MRD.  
 
 
 
X** 
 
 
 
Bone marrow samples to be collected 
at screening (up to 42 d before C1D1). 
*In the event a fresh screening biopsy 
will not be collected, use 
non-decalcified diagnostic tissue (ie, 
bone marrow aspirate slides or FFPE 
tissue).  ** If feasible, collect at 
disease progression for participants 
who achieved PR/CR. 
See Sections 8.5.8 and 8.2.1.6. 
Skeletal survey 
X* 
As clinically indicated 
 
*For screening, up to 42 d before 
C1D1.   
See Section 8.2.1.7. 
Assess extramedullary 
plasmacytomas 
X* 
Measurable sites every 4 weeks (if applicable; for physical examination) and every 
12 weeks** (for radiologic examination) for participants with a history of 
plasmacytomas, or as clinically indicated for others. 
 
*For screening, up to 42 d before 
C1D1. 
** At 18 months after the participant's 
first dose, the timing of radiologic 
assessment of extramedullary 
plasmacytomas should follow the 
standard of care. 
See Section 8.2.1.8. 


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Table 4: 
Schedule of Activities for Participants in Phase 2, Treatment Group B – Part 2 and Treatment Group C – Part 2 
(Who Cross Over) 
Visit Day (Range) 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Cycles 1 and 2 
Cycles 3 to 6 
Cycles 
7+ 
Safety 
Disease 
Status 
Survival 
D1 
D8 
(± 2d) 
D15 
(± 2d) 
D22 
(± 2d) 
D1 
(± 3d) 
D15 
(± 3d) 
D1 
(± 3d) + 7d 
28-35d 
After 
EOT 
Q8W 
After 
EOT  
± 7d 
Q12W 
After 
EOT  
± 7d 
Administrative procedures 
Review criteria for crossover 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 6.8. 
Distribute reminder cards  
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
See Section 8.1.4. 
Assess study treatment compliance X* 
 
 
 
X 
 
X 
X 
 
 
 
* C2D1 only. 
See Section 6.4. 
Study treatment 
Dispense/administer INCB001158  
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
In clinic, should be given just before 
administration of daratumumab SC. 
See Section 6.1, Appendix B, and refer to 
the Pharmacy Manual. 
Administer daratumumab SC  
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
In clinic, should be administered after 
INCB001158. 
See Section 6.1, Appendix C, and refer to 
the Pharmacy Manual. 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 8.3.1. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 8.3.4. 
Electrocardiogram 
X* 
 
 
 
X** 
 
 
 
X 
 
 
* Predose and 2-4 h after morning dose. 
** Predose on C3D1 and C6D1 only. 
See Section 8.3.5. 
ECOG performance status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
See Section 8.3.6. 
Subsequent therapy status 
 
 
 
 
 
 
 
X 
X 
X 
X 
See Section 8.8.2. 
Survival status 
 
 
 
 
 
 
 
 
 
 
X 
See Section 8.8.3. 


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Table 4: 
Schedule of Activities for Participants in Phase 2, Treatment Group B - Part 2 and Treatment Group C - Part 2 
(Who Cross Over) (Continued) 
Visit Day (Range) 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Cycles 1 and 2 
Cycles 3 to 6 
Cycles 
7+ 
Safety 
Disease 
Status 
Survival 
D1 
D8 
(± 2d) 
D15 
(± 2d) 
D22 
(± 2d) 
D1 
(± 3d) 
D15 
(± 3d) 
D1 
(± 3d) + 7d 
28-35d 
After 
EOT 
Q8W 
After 
EOT  
± 7d 
Q12W 
After 
EOT  
± 7d 
Efficacy/disease assessments (blood/urine) – samples to be sent to central laboratory 
Quantitative Ig (IgA, IgM, IgG, 
IgD, IgE) 
X* 
 
 
 
X** 
 
X** 
X 
 
 
 
* Does not need to be repeated if collected 
at EOT prior to crossover  
** Every 3 months during treatment 
(window of ± 1 month). 
See Section 8.2.1.2. 
SPEP 
X* 
 
 
 
X 
 
X 
X 
X 
X 
 
SPEP and UPEP are to be performed 
within 14 days before Cycle 1 Day 1 and 
on the scheduled assessment days (± 3 d). 
* Does not need to be repeated if collected 
at EOT prior to crossover 
See Section 8.2.1.2. 
UPEP (24 h urine sample) 
X* 
 
 
 
X 
 
X 
X 
X 
X 
 
Serum calcium corrected for 
albumin 
X* 
 
 
 
X 
 
X 
X 
X 
X 
 
* Does not need to be repeated if collected 
at EOT prior to crossover  
See Section 8.2.1.3. 
Serum FLC & serum/urine 
immunofixation 
X* 
 
 
 
X** 
 
X** 
X** 
X** 
X** 
 
To be performed when CR is suspected or 
maintained. 
* Does not need to be repeated if collected 
at EOT prior to crossover  
** For participants with light chain only 
disease, serum FLC to be performed on 
Day 1 of each cycle, at EOT, and at safety 
and disease status follow-up. 
See Section 8.2.1.2. 


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Table 4: 
Schedule of Activities for Participants in Phase 2, Treatment Group B - Part 2 and Treatment Group C - Part 2 
(Who Cross Over) (Continued) 
Visit Day (Range) 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Cycles 1 and 2 
Cycles 3 to 6 
Cycles 
7+ 
Safety 
Disease 
Status 
Survival 
D1 
D8 
(± 2d) 
D15 
(± 2d) 
D22 
(± 2d) 
D1 
(± 3d) 
D15 
(± 3d) 
D1 
(± 3d) + 7d 
28-35d 
After 
EOT 
Q8W 
After 
EOT  
± 7d 
Q12W 
After 
EOT  
± 7d 
Efficacy/disease assessments (other) 
Skeletal survey 
As clinically indicated 
 
See Section 8.2.1.7. 
Assess extramedullary 
plasmacytomas 
Measurable sites every 4 weeks (if applicable; for physical examination) and every 
12 weeks** (for radiologic examination) for participants with a history of 
plasmacytomas, or as clinically indicated for others. 
 
** At 18 months after the participant's 
first dose, the timing of radiologic 
assessment of extramedullary 
plasmacytomas should follow the standard 
of care. 
See Section 8.2.1.8. 


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Table 5: 
Schedule of Laboratory Assessments for Participants in Phase 1, Phase 2, Treatment Group A, Treatment 
Group B – Part 1 (Prior to Crossover), and Treatment Group C – Part 1 (Prior to Crossover) 
Visit Day (Range) 
Screening 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Days 
-28 to -1 
Cycles 1 and 2 
Cycles 3+ 
28-35d 
After EOT 
D1 
D8  
(± 2d) 
D15  
(± 2d) 
D22  
(± 2d) 
D1  
(± 3d) 
+ 7d 
Local laboratory assessments 
Blood type assessment 
X 
 
 
 
 
 
 
 
Record on participant's identification wallet card. 
See Section 8.3.7.1. 
Chemistries 
X 
X* 
X 
X 
X 
X 
X 
X 
* Does not need to be repeated if the screening assessment was 
performed within 7 days before C1D1, unless a clinically 
significant change is suspected. 
See Section 8.3.7. 
Hematology 
X 
X* 
X 
X 
X 
X 
X 
X 
Lipid panel 
X 
X* 
 
 
 
X 
X 
X 
Urinalysis 
X 
X* 
 
 
 
X 
 
 
Thyroid panel 
X 
X* 
 
 
 
X 
 
 
Pregnancy testing 
X 
X 
 
 
 
X 
X 
 
All female participants of childbearing potential.  Serum at 
screening and urine at Day 1 of each cycle, at EOT, and as 
medically indicated or per country or institutional 
requirements. 
See Section 8.3.7.5. 
Serology 
X/X* 
X* 
* For participants positive for anti-HBs or anti-HBc, HBV 
DNA testing must be performed at screening, every 12 weeks 
during treatment, at EOT, and Q12W for up to 6 months after 
the last dose of study treatment. 
See Section 8.3.7.6. 
Blood sample for plasma 
ammonia levels 
X 
X* 
X* 
X* 
 
X* 
 
 
Collect during screening.  If plasma ammonia is above ULN, 
repeat screening sample to confirm value. 
* Additional samples may be collected as clinically indicated 
according to urine orotic acid elevations. 
See Section 8.3.7.4. 
Central laboratory assessments 
Urine sample for orotic acid 
 
X 
X*/** 
X* 
 
X 
 
 
See Table 23 for sample collection times.  
* Cycle 1 only. 
** C1D8 only for participants enrolled in Phase 1. 
Additional samples may be collected as clinically indicated.  
See Section 8.3.7.3. 


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Table 5: 
Schedule of Laboratory Assessments for Participants in Phase 1, Phase 2, Treatment Group A, Treatment 
Group B – Part 1 (Prior to Crossover), and Treatment Group C – Part 1 (Prior to Crossover) (Continued) 
Visit Day (Range) 
Screening 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Days 
-28 to -1 
Cycles 1 and 2 
Cycles 3+ 
28-35d 
After EOT 
D1 
D8  
(± 2d) 
D15  
(± 2d) 
D22  
(± 2d) 
D1  
(± 3d) 
+ 7d 
Central laboratory assessments (continued) 


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Table 5: 
Schedule of Laboratory Assessments for Participants in Phase 1, Phase 2, Treatment Group A, Treatment 
Group B – Part 1 (Prior to Crossover), and Treatment Group C – Part 1 (Prior to Crossover) (Continued) 
Visit Day (Range) 
Screening 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Days 
-28 to -1 
Cycles 1 and 2 
Cycles 3+ 
28-35d 
After EOT 
D1 
D8  
(± 2d) 
D15  
(± 2d) 
D22  
(± 2d) 
D1  
(± 3d) 
+ 7d 


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Table 6: 
Schedule of Laboratory Assessments for Participants in Phase 2, Treatment Group B – Part 2 and Treatment 
Group C – Part 2 (Who Cross Over) 
Visit Day (Range) 
Treatment (28-day Cycles) 
EOT 
Follow-Up 
Notes 
Cycles 1 and 2 
Cycles 3+ 
28-35d 
After EOT 
D1 
D8  
(± 2d) 
D15  
(± 2d) 
D22  
(± 2d) 
D1  
(± 3d) 
+ 7d 
Local laboratory assessments 
Chemistries 
X* 
X 
X 
X 
X 
X 
X 
* Does not need to be repeated if the EOT assessment prior to 
crossover was performed within 7 days before C1D1, unless a 
clinically significant change is suspected. 
See Section 8.3.7. 
Hematology 
X* 
X 
X 
X 
X 
X 
X 
Lipid panel 
X* 
 
 
 
X 
X 
X 
Urinalysis 
X* 
 
 
 
X 
 
 
Thyroid panel 
X* 
 
 
 
X 
 
 
Pregnancy testing 
X 
 
 
 
X 
X 
 
All female participants of childbearing potential.  Urine at 
Day 1 of each cycle, at EOT, and as medically indicated or per 
country or institutional requirements. 
See Section 8.3.7.5. 
Serology 
X* 
* For participants positive for anti-HBs or anti-HBc, HBV 
DNA testing must be performed every 12 weeks during 
treatment, at EOT, and Q12W for up to 6 months after the last 
dose of study treatment. 
See Section 8.3.7.6. 
Blood sample for plasma ammonia levels 
X* 
X* 
X* 
 
X* 
 
 
* Additional samples may be collected as clinically indicated 
according to urine orotic acid elevations. 
See Section 8.3.7.4. 
Urine sample for orotic acid 
X 
X* 
X* 
 
X 
 
 
See Table 23 for sample collection times.  
* Cycle 1 only. 
Additional samples may be collected as clinically indicated.  
See Section 8.3.7.3. 
 


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Table 7: 
Schedule of Activities for All Participants (as of Protocol Amendment 3) 
Procedure 
Protocol 
Section 
Treatment  
EOT 
Safety  
Follow-Up 
Notes 
(28-Day 
Cycle) 
+ 7 d 
28-35 d After 
EOT 
Informed consent 
8.1.1 
X 
 
 
Participants will sign a new ICF as per Protocol Amendment 3. 
Contact IRT 
8.1.3 
X 
X 
 
 
Concomitant medications 
6.8 
X 
X 
X 
Review to ensure no prohibited medications are being used. 
Provide data to sponsor about medications used for SAEs and 
AESIs only. 
Distribute reminder cards 
8.1.4 
X* 
X 
 
*On the clinic days for the next visit. 
Assess study treatment compliance 
6.4 
X* 
X 
 
*Day 1 of each cycle. 
Dispense/administer INCB001158 
(participants receiving INCB001158 
monotherapy or in combination with 
daratumumab SC) 
6.1 
X 
 
 
On clinic day, INCB001158 should be given just before 
administration of daratumumab SC (if applicable). See 
Appendix B and Pharmacy Manual. 
Administer daratumumab SC at site 
(participants receiving daratumumab 
SC monotherapy or in combination 
with INCB001158) 
6.1 
X 
 
 
In clinic, daratumumab SC should be administered after 
INCB001158. See Appendix C and Pharmacy Manual. 
AE assessments 
8.3.1 
X 
X 
X 
All SAEs and AESIs must be recorded in the eCRFs, 
regardless of the causal relationship. 
Efficacy/disease assessments 
(blood/urine/other) 
8.2.1 
X 
X 
 
As of Protocol Amendment 3, the disease assessments are only 
required to be performed as per standard of care guidelines for 
the participant's condition and monitoring. 
Pregnancy testing 
8.3.7.5 
X* 
X 
 
All female participants of childbearing potential. 
*Urine at Day 1 of each cycle, at EOT, and as medically 
indicated or per country or institutional requirements. 
Post-treatment anticancer therapy 
status 
8.8.2 
 
 
X 
If a participant is scheduled to begin a post-treatment 
anticancer therapy before the end of the safety follow-up 
period, then the safety follow-up visit should be performed 
before post-treatment anticancer therapy is started. 
 


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2. 
INTRODUCTION 
2.1. 
Background 
2.1.1. 
Multiple Myeloma and Progressive Disease  
Multiple myeloma is the second most common type of blood cancer (Siegel et al 2012).  Despite 
recent developments with PIs, IMiDs, and novel therapeutic agents, management of MM remains 
challenging, as relapses and disease progression occur even after complete remission (Palumbo 
and Anderson 2011).  Relapsed and PD associated with genetic alterations and resistances are 
frequently observed, causing gradually shorter DOR and leading to relapsed/refractory MM 
(Chim et al 2018).  The bone marrow microenvironment plays a critical role in MM pathogenesis 
and progressive immune dysfunction (Kawano et al 2015).   
2.1.2. 
Targeting Myeloid-Derived Suppressor Cells and Arginase in Multiple Myeloma 
The inflammatory milieu in the bone marrow of MM patients support the growth of 
immunosuppressive cells such as MDSCs, TAMs, and Tregs (Kumar et al 2016).  These immune 
suppressor cells correlate with clinical outcomes and are involved in the "immune escape" that 
favors myeloma progression.  MDSCs have been shown to promote MM progression via a 
number of different mechanisms, including promotion of angiogenesis, chemoresistance, and 
immunosuppression in the bone marrow microenvironment (Herlihy et al 2017).  MDSCs and 
neutrophils accumulate in the blood and bone marrow and promote tumor growth while inducing 
T cell immunosuppression (Görgün et al 2013, Ramachandran et al 2013).  In MM, MDSCs and 
neutrophils secrete high levels of arginase, and disease progression is associated with increased 
levels of circulating MDSCs (Romano et al 2018). 
2.1.3. 
INCB001158 
INCB001158 is an orally bioavailable small molecule shown to be a potent and selective 
inhibitor of arginase and developed for cancer indications.  Upon stimulation by factors within 
the tumor microenvironment (eg, proinflammatory cytokines, such as interleukin-8 and tumor 
necrosis factor-alpha), arginase is released into the tumor microenvironment via degranulation, 
resulting in substantial local depletion of the amino acid arginine.  Arginine is a key factor for 
T cell and NK cell proliferation and increases the survival of effector T cells as well as their 
antitumor activity (Steggerda et al 2017, Geiger et al 2016).  Arginine depletion prevents the 
activity of effector T cells in tumors by decreasing the production of IFN-γ, as well as the 
expression of TCR ζ-chain and T cell proliferation (Timosenko et al 2017).  In the tumor 
microenvironment, arginase 1 is expressed and released extracellularly by immunosuppressive 
myeloid cells, including MDSCs and neutrophils. 
INCB001158 inhibits arginase activity and restores arginine levels in the tumor 
microenvironment, resulting in antitumor effects in immunocompetent mice implanted with 
mouse tumors.  INCB001158 has additive activity when administered in combination with PD-1 
checkpoint inhibitors, IDO1 inhibitor, or chemotherapy agents in mouse tumor models (refer to 
the INCB001158 IB).   


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As of 21 JUL 2018, INCB001158 is being investigated in participants with advanced or 
metastatic solid tumors, as monotherapy and in combination with the anti–PD-1 monoclonal 
antibody pembrolizumab (Study INCB 01158-101), or in combination with chemotherapy 
(mFOLFOX6, gemcitabine/cisplatin, and paclitaxel) in Study INCB 01158-203.  Preliminary 
data obtained in participants receiving INCB001158 monotherapy and in combination with 
pembrolizumab indicate that INCB001158 inhibits arginase activity and increases arginine levels 
in participant plasma (refer to the INCB001158 IB). 
Among the 164 participants with advanced cancer exposed to INCB001158, the most frequently 
(≥ 10%) reported TEAEs overall were fatigue, nausea, anemia, constipation, hyperglycemia, 
decreased appetite, hyponatremia, abdominal pain, and diarrhea.  Among the 83 participants 
receiving INCB001158 monotherapy, TEAEs occurred in 72 participants (86.7%), with the most 
frequent TEAEs being anemia (n = 17, 20.5%) and constipation and fatigue (n = 15 each, 
18.1%).  There has been no pattern of clinically significant urea cycle inhibition, hemodynamic 
effects, or immune-related AEs, which are potential on-target safety concerns associated with 
INCB001158 administration. 
For the most comprehensive nonclinical and clinical information regarding INCB001158, refer 
to the latest version of the INCB001158 IB. 
2.1.4. 
Daratumumab 
Daratumumab (JNJ-54767414) is a recombinant human IgG monoclonal antibody 
immunotherapy that binds with high affinity to CD38, a transmembrane glycoprotein, expressed 
on tumor cells, and induces tumor cell death through multiple mechanisms of action, including 
CDC, ADCC, ADCP, and direct cytotoxicity by induction of apoptosis by FcR-mediated 
crosslinking of the tumor cells bound by the monoclonal antibodies.  Daratumumab treatment 
decreases CD38+ Tregs, CD38+ MDSCs, and CD38+ Bregs (Krejcik et al 2016).  The elimination 
of these immunosuppressive cells, modulation of CD38 enzymatic activity, and destruction of 
the malignant myeloma cells is thought to lead to the clonal expansion of CD8+ and CD4+ T cells 
(Chiu et al 2016). 
Daratumumab by IV infusion, and by SC injection, has been approved in the United States and 
the European Union in different settings as monotherapy and in combination with standards of 
care therapies (such as PIs and immunomodulatory agents), for the treatment of patients with 
MM (Darzalex® and Darzalex FASPRO™ Prescribing Information and Darzalex® SmPC). 
Daratumumab SC is composed of daratumumab co-formulated with a recombinant human 
hyaluronidase (rHuPH20), which enables manual SC injection in a few minutes.  For the most 
comprehensive nonclinical and clinical information regarding daratumumab SC, refer to the 
latest version of the daratumumab IB. 
Recombinant human hyaluronidase (rHuPH20) is the active ingredient of Hylenex® recombinant 
(hyaluronidase human injection), which was approved in the United States in DEC 2005 as an 
adjuvant to increase the dispersion and absorption of other injected drugs (Hylenex® Prescribing 
Information).  rHuPH20 is also approved in combination with protein therapeutics for SC 
administration, such as HyQvia (immune globulin infusion 10% [human] with rHuPH20) in the 
United States and EU, as well as anticancer medications such as trastuzumab (Herceptin® SC in 


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the EU) and rituximab (MabThera® SC in the European Union, Rituxan Hycela® SC in the 
United States).  
2.2. 
Study Rationale 
2.2.1. 
Rationale for Study Design 
Arginase is expressed by bone marrow myeloid and granulocytic MDSCs in relapsed and 
refractory MM patients (Görgün et al 2013, Giallongo et al 2016).  INCB001158 is an oral small 
molecule that inhibits arginase and increases arginine levels and promotes antitumor immune 
function of NK and T cells (refer to the INCB001158 IB).  Daratumumab is an anti-CD38 
immunotherapy for MM approved as monotherapy or in combination with standards of care for 
the treatment of MM, such as immunomodulatory agents or PIs.  Daratumumab has direct 
antitumor activity as well as immunomodulatory action by decreasing regulatory T and B cells 
(Krejcik et al 2016).  
INCB001158 in vitro studies show that T cells from patients receiving daratumumab treatment 
or who are daratumumab-naïve, and cocultured with autologous PMNs and MDSCs, do not 
respond to anti-CD3/CD28 stimulation, demonstrating pronounced arginase-mediated anergy 
(M. Munder et al, unpublished data).  Upon treatment with INCB001158, this anergic state is 
reversed, and T cells show a hyper-response in proliferation in cocultures from both 
daratumumab-naïve and daratumumab-exposed patients, providing evidence to support the 
evaluation of INCB001158 as a potential single agent and in combination with daratumumab for 
the treatment of multiple myeloma. 
The study will investigate whether the combination of the anti-CD38 immunotherapy 
daratumumab with the arginase inhibitor INCB001158 will result in improved clinical benefit in 
participants with relapsing or refractory MM after at least 3 prior treatment lines (including 
IMiD, PI, and anti-CD38 therapies) but not more than 5 prior treatment lines. 
This is an open-label, dose-escalation Phase 1 and randomized Phase 2 study in participants with 
relapsed or refractory MM.  The objective of the study is to evaluate the safety and efficacy of 
INCB001158 given in combination with daratumumab SC and to compare the RP2D of 
INCB001158 in combination with daratumumab SC to daratumumab SC monotherapy, using a 
RAR design.  At the time of confirmed disease progression participants treated with 
daratumumab SC monotherapy (Treatment Group B – Part 1) will cross over to 
INCB001158 + daratumumab SC (Treatment Group B – Part 2).  The safety, efficacy, 
 
 effects of INCB001158 monotherapy will be also evaluated for 2 cycles, 
provided that the participants are not progressing.  This selected timeframe is based on the 
mechanism of action and preliminary clinical data obtained in other cancer indications (refer to 
the INCB001158 IB), to allow safe clinical and translational assessments.  Beyond Cycle 2, 
participants will continue treatment with INCB001158 monotherapy only if they are receiving 
clinical benefit and have not met any criteria for study withdrawal, followed by a crossover to 
INCB001158 in combination with daratumumab SC at the time of confirmed disease 
progression.  


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2.2.2. 
Combination of INCB001158 and Daratumumab 
In patients with MM, efficacy of the CD38-targeting antibody daratumumab can be improved by 
adding a partner drug with a different mode of action, such as an IMiD.  Further improvement 
may be achieved by combining daratumumab with an agent that is able to enhance or 
complement the immunomodulatory effect of daratumumab and/or host–antitumor T-cell 
immunity, and re-challenge can be used (Orlowski and Lonial 2016, van de Donk and Usmani 
2018). 
Therefore, combining the anti-CD38 immunotherapy daratumumab with the arginase inhibitor 
INCB001158 to reduce immunosuppression and restore antitumor activity may improve 
treatment efficacy for relapsing and refractory MM patients. 
2.2.3. 
Justification for the Dose 
In the Phase 1 dose escalation, the starting dose of INCB001158 will be 75 mg BID, which is 
1 dose level below the RP2D and 2 dose levels below the highest dose of INCB001158 that was 
shown to be tolerable as a monotherapy in Study INCB 01158-101 (refer to the INCB001158 
IB).  The second dose level that will be tested is 100 mg BID, which was well-tolerated as 
monotherapy and in combination with pembrolizumab or with chemotherapy and was selected as 
the RP2D in INCB 01158-101 (for both monotherapy and combination with pembrolizumab) and 
INCB 01158-203 (combination with chemotherapy) studies in advanced cancer (refer to the 
INCB001158 IB).  In case of INCB001158-related toxicity, the dose may be reduced by 1 dose 
level, from 75 mg to 50 mg BID and from 100 mg to 75 mg BID (see Sections 4.1.1 and 6.7.1). 
Daratumumab SC is a co-formulated product of daratumumab and rHuPH20, which allows for 
the SC administration of daratumumab in 3 to 5 minutes compared with 4 to 7 hours for an IV 
infusion of daratumumab.  Daratumumab SC has similar efficacy and safety with fewer 
infusion-related reactions compared with the IV formulation.  Daratumumab SC has been  
approved in US and Europe for the treatment of patients with multiple myeloma (refer to the 
daratumumab IB, Darzalex and Darzalex FASPRO Prescribing Information and SmPC). The 
approved 1800 mg dose of daratumumab SC will be used in this study. 
2.3. 
Benefit/Risk Assessment 
Immunomodulatory agents and PIs among others are established treatments of MM.  
Daratumumab and new immune therapies inducing direct tumor cell killing and/or blocking 
immunosuppression have been approved or are in clinical development (Kumar et al 2016).  
INCB001158 is in early phase development and although the safety profile has not been fully 
evaluated, INCB001158 has been generally well-tolerated in 164 advanced or metastatic solid 
tumor participants.  The main toxicity risks of arginase inhibition by INCB001158 are linked to 
potential urea cycle inhibition, hemodynamic effects, and immune-related AEs (refer to the 
INCB001158 IB). 
Daratumumab SC was well-tolerated in relapsed/refractory MM patients with low rates of IRRs 
and no new safety signals compared with daratumumab IV.  Daratumumab SC enabled dosing in 
3 to 5 minutes and improves patient convenience.  The most commonly reported AEs from 
rHuPH20 in combination with protein therapeutics for SC administration have been mild 


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injection site reactions.  Pre- and post-administration medications are administrated with 
daratumumab SC (co-formulated with rHuPH20) to reduce the risk of IRRs. 
Combining therapies with different mechanism of actions is an effective approach for the 
treatment of MM.  Inhibition of arginase may decrease the immunosuppressive 
microenvironment driven by myeloid suppressive cells.  Combining the arginase inhibitor 
INCB001158 with the anti-CD38 antibody daratumumab (SC formulation) may improve 
treatment efficacy with a manageable safety profile in participants with relapsed or refractory 
MM.   
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of INCB001158 and daratumumab SC may be found in their respective IBs, 
Darzalex and Darzalex FASPRO Prescribing Information and SmPC.  For rHuPH20, refer to the 
Hylenex® Prescribing Information. 
3. 
OBJECTIVES AND ENDPOINTS 
The study objectives and endpoints are presented in Table 8. 
Table 8: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Phase 1:  To determine the safety, tolerability, 
and RP2D of INCB001158 in combination with 
daratumumab SC. 
Safety and tolerability determined by monitoring 
the frequency, duration, and severity of AEs. 
Phase 2:  To compare the ORR of the RP2D of 
INCB001158 in combination with daratumumab 
SC to daratumumab SC monotherapy. 
ORR, defined as the proportion of participants with 
a documented response PR or better, as per IMWG 
criteria. 
Secondary 
Phase 1:  To determine the efficacy of 
INCB001158 in combination with daratumumab 
SC. 
ORR, defined as the proportion of participants with 
a documented response PR or better, as per IMWG 
criteria. 
Phase 2:  To determine the safety and 
tolerability of INCB001158 monotherapy at 
RP2D, and to compare the safety and tolerability 
and RP2D of INCB001158 in combination with 
daratumumab SC to daratumumab SC 
monotherapy. 
Safety and tolerability determined by monitoring 
the frequency, duration, and severity of AEs. 


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Table 8: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Secondary (continued) 
Phase 1:   To determine the efficacy of 
INCB001158 in combination with daratumumab 
SC. 
Phase 2:  To estimate the efficacy of 
INCB001158 monotherapy, and to compare the 
efficacy of INCB001158 in combination with 
daratumumab SC to daratumumab SC 
monotherapy. 
• TTR, defined as the time from the first dose of 
study drug to the first documented response PR 
or better, as per IMWG criteria. 
• DOR, defined as time from first documented 
response PR or better, as per IMWG criteria, 
until date of disease progression or death, 
whichever occurs first. 
• PFS, defined as the duration from the date of first 
dose of study drug until either PD, as per IMWG 
criteria, or death, whichever occurs first. 
• MRD, defined as the percentage of 
MRD-negative participants. 
• OS, defined as the time from the first dose of 
study drug to death from any cause. 
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is an open-label, dose-escalation Phase 1 and randomized Phase 2 study, to evaluate the 
safety and antitumor activity of INCB001158 in combination with daratumumab SC, compared 
with daratumumab SC alone, in participants with relapsed or refractory MM who have received 
at least 3 prior lines (including IMiD, PI, and anti-CD38 therapies) but not more than 5 prior 
lines of therapy. 
Phase 1 will consist of dose-escalation using a BOIN design and will determine the RP2D of 
INCB001158 in combination with daratumumab SC; efficacy will also be explored. 
Phase 2 will consist of a randomized expansion phase to compare the RP2D of INCB001158 in 
combination with daratumumab SC to daratumumab SC alone using a RAR design.  
INCB001158 monotherapy will also be explored. 
The study design schema is presented in Figure 1, and the SoA in Table 3 and Table 4 for study 
visit assessments prior to and post-crossover, respectively.  
NOTE:  As of Protocol Amendment 3, see only Table 7 for the SoA for all participants. 
4.1.1. 
Phase 1:  Dose Escalation of INCB001158 + Daratumumab SC 
In Phase 1, INCB001158 in combination with daratumumab SC will be administrated in 28-day 
treatment cycles, and study treatment is summarized in Table 9.  
Table 9: 
Study Treatment for Participants in Phase 1 Dose Escalation 
Study 
Treatment 
INCB001158 
Daratumumab SC 
50-100 mg PO BID continuous 
dosing until disease progression, 
unacceptable toxicity, or 
discontinuation from study 
treatment for any other reason. 
1800 mg SC co-formulated with rHuPH20 
(2000 U/mL).  Administration is once weekly for 
Cycles 1 and 2, once every 2 weeks for Cycles 3 to 
6, and then once every 4 weeks until disease 
progression, unacceptable toxicity, or 
discontinuation from study treatment for any other 
reason. 
BID = twice daily; IV = intravenous; PO = orally; SC = subcutaneous. 
Dose escalation of INCB001158 will begin at a starting dose 75 mg BID, which is 1 dose level 
below the RP2D for both monotherapy and combination with PD-1 inhibitor (per study 
INCB 01158-101) and for combination with chemotherapy (per study INCB 01158-203) in 
participants with advanced/metastatic solid tumors.  The starting dose of 75 mg BID is also 
2 dose levels below the highest dose (150 mg BID) tested in the INCB 01158-101 study, while 
the MTD has not been reached (see Section 2.2.3). 
The doses of INCB001158 to be evaluated and scenarios for dose escalation and de-escalation 
are summarized in Table 10. 


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Table 10: 
INCB001158 Dose Levels 
INCB001158 Dose Level 
INCB001158 Dose 
-1 
50 mg BID 
1 (starting dose) 
75 mg BIDa 
2 
100 mg BID 
BID = twice daily. 
a If INCB001158 75 mg BID is not tolerated, INCB001158 50 mg BID may be evaluated. 
Dose escalation and de-escalation in Phase 1 will follow the BOIN design algorithm (Yuan and 
Liu 2016).  Given the target DLT rate of 33% for INCB001158 in combination with 
daratumumab SC, the dose escalation and de-escalation rules are shown in Table 11.  The BOIN 
design also includes an elimination rule.  When  3 participants have been treated, if the 
probability that the estimated toxicity rate that is above the target DLT rate is > 95% at a certain 
dose level, then this dose level and higher dose levels are assumed to be too toxic and will be 
eliminated.  If the lowest dose level is eliminated, then the whole dose escalation will be 
terminated.  Table 11 (in the bottom row) provides the elimination rules.  Based on this 
algorithm, a minimum of 3 evaluable participants and a maximum of 9 evaluable participants 
will be enrolled at each tested dose level.  The dose escalation will continue, based on the rules 
in Table 11, until at least 1 of the following occurs: 
• Enrollment of additional participants at a dose level that already has 9 evaluable 
participants. 
• Dose escalation to a dose level that has already been eliminated. 
• Dose escalation above 100 mg BID. 
At that point, the dose escalation will be stopped. 
Table 11: 
Dose Escalation, De-Escalation, and Elimination Boundaries for Target DLT 
Rate of 33% in Phase 1 
Action 
Number of Evaluable Participants Treated at the Current Dose 
1 
2 
3 
4 
5 
6 
7 
8 
9a 
Escalate if # of 
DLTs ≤ 
0 
0 
0 
1 
1 
1 
1 
2 
2 
De-escalate if # of 
DLTs ≥ 
1 
1 
2 
2 
2 
3 
3 
4 
4 
Elimination if # of 
DLTs ≥ 
N/A 
N/A 
3 
3 
4 
4 
5 
5 
6 
DLT = dose-limiting toxicity; N/A = not applicable. 
a If 9 evaluable participants are enrolled at a dose level, and 3 of those participants experience a DLT, then the 
medical monitor and the investigators will review the entirety of the data and decide whether to escalate the dose 
level, de-escalate the dose level, or stop at that dose level. 
The INCB001158 dose will be escalated using an open-label BOIN design and a PAD or the 
MTD will be determined, or the maximum dose of INCB001158 (100 mg BID) will be reached.  


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A PAD of INCB001158 is defined as a dose that achieves a Cmin of INCB001158 at steady state 
of ≥ 1 μM that is equivalent to the IC90 for arginase 1.  The MTD is the maximum tolerated or 
tested dose of INCB001158, such that fewer than 33% of the participants receiving the 
combination experience a DLT during the first 28 days on study drug.  After the dose escalation 
is completed, one of the INCB001158 dose levels that is pharmacologically active and tolerable 
in combination with daratumumab SC (ie, MTD or lower), will be selected as the RP2D. 
Dose interruptions and/or modifications may be implemented based on toxicity.  Dose 
modifications should not be made during the DLT observation period without discussion with 
the medical monitor.  Intraparticipant dose escalation is not permitted.  At the discretion of the 
sponsor, up to 6 additional "backfill" participants may be enrolled at any tolerable dose level to 
further investigate safety, efficacy 
. 
4.1.2. 
Phase 2:  Expansion 
An initial 1:1:1 randomization of 30 participants between the RP2D of INCB001158 in 
combination with daratumumab SC (Treatment Group A), daratumumab SC monotherapy 
(Treatment Group B – Part 1), and INCB001158 monotherapy at the RP2D determined in 
Phase 1 (Treatment Group C – Part 1) will be conducted.  Participants in Treatment Groups A 
and B will receive continuous treatment until disease progression or unacceptable toxicity, or 
discontinuation from study treatment for any other reason.  At the time of confirmed disease 
progression, participants in Treatment Group B (Part 1) will cross over to 
INCB001158 + daratumumab SC (Treatment Group B – Part 2) and continue combination 
treatment as long as they are receiving clinical benefit and have not met any criteria for study 
withdrawal. Participants in Treatment Group C will receive continuous treatment with 
INCB001158 for at least 2 cycles if they are not progressing, and beyond Cycle 2 only if they are 
receiving clinical benefit and have not met any criteria for study withdrawal (Treatment Group C 
– Part 1), and then they will cross over to INCB001158 + daratumumab SC at the time of 
confirmed disease progression (Treatment Group C – Part 2).  Stopping rules for unacceptable 
toxicity based on Grade 4 or higher treatment-related AEs will be used as indicated in 
Section 10.5.2.  
After the equal randomization period, an RAR design will be used to compare the ORR of 
Treatment Groups A and B with adjustments to the randomization rate based on the observed 
ORR.  Evaluation of the safety and tolerability of the 3 treatment groups will be performed 
periodically throughout the study.  Participants will be analyzed for efficacy based on the 
treatment group in which they were randomized.  Details of the randomization method and 
model for response are provided in the statistical methods Section 10.4. 
Participants will be assigned to the randomization Treatment Groups A, B, or C: 
• Treatment Group A:  INCB001158 + daratumumab SC 
• Treatment Group B:  daratumumab SC monotherapy (Part 1), then crossover to  
INCB001158 + daratumumab SC (Part 2) 
• Treatment Group C:  INCB001158 monotherapy (Part 1), then crossover to 
INCB001158 + daratumumab SC (Part 2) 


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Treatments will be administrated in 28-day cycles for Treatment Groups A, B and C and are 
summarized in Table 12. 
Table 12: 
Treatments for Treatment Groups A, B, and C 
Treatment 
Group A 
INCB001158 
Daratumumab SC 
RP2D PO continuous dosing until 
disease progression, unacceptable 
toxicity, or discontinuation from study 
treatment for any other reason. 
1800 mg SC co-formulated with rHuPH20 
(2000 U/mL).  Administration is once weekly 
for Cycles 1 and 2, once every 2 weeks for 
Cycles 3 to 6, and then once every 4 weeks 
until disease progression, unacceptable toxicity, 
or discontinuation from study treatment for any 
other reason. 
Treatment 
Group B 
Part 1 
Daratumumab SC monotherapy 
 
1800 mg SC co-formulated with rHuPH20 (2000 U/mL).  Administration is once weekly 
for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and then once every 4 weeks 
until disease progression, unacceptable toxicity, or discontinuation from study treatment 
for any other reason.  At the time of confirmed disease progression, participants will 
cross over to Treatment Group B - Part 2, and continue with combination treatment as 
indicated below 
Treatment 
Group B 
Part 2 
INCB001158 
Daratumumab SC 
RP2D PO continuous dosing until 
disease progression, unacceptable 
toxicity, or discontinuation from study 
treatment for any other reason. 
1800 mg SC co-formulated with rHuPH20 
(2000 U/mL).  Administration is once weekly 
for Cycles 1 and 2, every 2 weeks for Cycles 3 
to 6, and then every 4 weeks until disease 
progression, unacceptable toxicity, or 
discontinuation from study treatment for any 
other reason. 
Treatment 
Group C 
Part 1 
INCB001158 monotherapy 
RP2D PO continuous dosing for at least 2 cycles if participants are not progressing, and 
beyond Cycle 2 only if they are receiving clinical benefit and have not met any criteria 
for study withdrawal.  The participants will then cross over to Treatment Group C - Part 
2 at the time of confirmed disease progression, and continue with combination treatment 
as indicated below. 
Treatment 
Group C 
Part 2 
INCB001158 
Daratumumab SC 
RP2D PO continuous dosing until 
disease progression, unacceptable 
toxicity, or discontinuation from study 
treatment for any other reason. 
1800 mg SC co-formulated with rHuPH20 
(2000 U/mL).  Administration is once weekly 
for Cycles 1 and 2, every 2 weeks for Cycles 3 
to 6, and then every 4 weeks until disease 
progression, unacceptable toxicity, or 
discontinuation from study treatment for any 
other reason. 
BID = twice daily; IV = intravenous; PO = orally; RP2D = recommended Phase 2 dose; SC = subcutaneous. 




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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 or women aged 18 years or older. 
3. Prior diagnosis of MM according to IMWG diagnostic criteria (Rajkumar et al 2014). 
4. Has measurable disease at screening, as defined by the following: 
• Serum M-protein level ≥ 1.0 g/dL, or 
• Urine M-protein level ≥ 200 mg/24 hours, or 
• Serum Ig FLC ≥ 10 mg/dL and abnormal serum Ig kappa to lambda FLC ratio. 
5. Has received at least 3 prior lines (including PI, IMiD, and anti-CD38 therapies) but not 
more than 5 prior lines of MM treatment. 
a. Has received last dose of prior anti-CD38 therapy at least 3 months before initiation 
of study treatment. 
b. Has achieved a response (MR or better), based on investigator's evaluation of 
response by IMWG criteria, to prior anti-CD38 therapy. 
c. Has documented evidence of PD as defined by the IMWG criteria on or after their 
last regimen. 
6. ECOG performance status of 0 or 1.  
7. Willing to avoid pregnancy or fathering children based on the criteria below: 
a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or 
bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 51 years of age). 
b. Woman of childbearing potential who has a negative serum pregnancy test at 
screening and before the first dose on Day 1 and who agrees to take appropriate 
precautions to avoid pregnancy (with at least 99% certainty) from screening until 
3 months after the last dose of the last component of study treatment and must refrain 
from donating eggs (ova, oocytes).  Permitted methods that are at least 99% effective 
in preventing pregnancy (see Appendix A) should be communicated to the participant 
and their understanding confirmed. 


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c. Man who agrees to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening until 3 months after the last dose of the last 
component of study treatment 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 participant and their understanding 
confirmed. 
8. Willing to provide fresh and archival bone marrow aspiration and biopsy tissue during 
screening and on study. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Receipt of any of the following treatment within the indicated interval before the first 
administration of study drug: 
a. Anti-myeloma treatment within 2 weeks or 5 half-lives (whichever is longer). 
− Exception:  Washout of immune checkpoint inhibitor therapy is NOT required. 
b. Investigational drug (including investigational vaccines) or invasive investigational 
medical device within 4 weeks.  
c. Autologous stem cell transplant within 12 weeks, or allogeneic stem cell transplant at 
any time. 
d. Plasmapheresis within 4 weeks. 
e. Radiation therapy within 2 weeks.  
f. Major surgery within 2 weeks, or inadequate recovery from an earlier surgery, or 
surgery planned during the time the participant is expected to participate in the study 
or within 2 weeks after the last dose of study treatment. 
2. Toxicity ≥ Grade 2 from previous anti-myeloma therapy except for stable chronic 
toxicities (≤ Grade 2) not expected to resolve, such as stable Grade 2 peripheral 
neuropathy.  
3. Known additional malignancy (other than MM) that is progressing or requires active 
treatment, or history of other malignancy within 2 years of study entry with the exception 
of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, 
prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or 
indolent malignancy, or cancers from which the participant has been disease-free for 
> 1 year, after treatment with curative intent. 
4. Known meningeal involvement of MM. 
5. Participants with laboratory values at screening defined in Table 13. 


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Table 13: 
Exclusionary Laboratory Values 
Laboratory Parameter 
Exclusion Criterion 
Hematology 
a 
Platelets 
< 75 × 109/L for participants in whom < 50% of bone marrow nucleated 
cells are plasma cells; otherwise < 50 × 109/L (transfusions are not 
permitted to reach this level) 
b 
Hemoglobin 
< 7.5 g/dL (transfusions are not permitted to reach this level) 
c 
ANC 
< 1.0 × 109/L (prior growth factor support is not permitted within 
10 days before initiation of therapy) 
d 
Corrected serum 
calcium 
> 14.0 mg/dL (3.5 mmol/L) 
Hepatic 
e 
ALT 
> 2.5 × ULN 
f 
AST 
> 2.5 × ULN 
g 
Total bilirubin 
> 1.5 × ULN OR > 3.0 mg/dL for participants with documented 
Gilbert's syndrome. 
Renal 
h 
Measured or calculated 
creatinine clearance 
< 40 mL/minute  
6. Significant concurrent, uncontrolled medical condition, including but not limited to the 
following: 
a. Known COPD (defined as a FEV1 < 50% of predicted normal), persistent asthma, or 
history of asthma within the past 2 years.  Participants with known or suspected 
COPD or asthma must have a FEV1 test during screening. 
b. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, 
or antiviral treatment. 
c. Acute diffuse infiltrative pulmonary disease. 
d. Clinically significant or uncontrolled cardiac disease, including the following: 
− Unstable angina, acute myocardial infarction within 6 months from Day 1 of 
study drug administration, New York Heart Association Class III or IV congestive 
heart failure, and arrhythmia requiring therapy unless approved by medical 
monitor. 
− History or presence of an abnormal ECG that, in the investigator's opinion, is 
clinically meaningful.  A screening QTcF interval > 470 ms is excluded. 
e. Inability of the participant to swallow and retain oral medication. 


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7. Any of the following: 
a. Known to be seropositive for hepatitis B (defined by a positive test for HBsAg).  
Participants with resolved infection (ie, participants who are HBsAg-negative but 
positive for antibodies to anti-HBc and/or anti-HBs) must be screened using real-time 
PCR measurement of HBV DNA levels.  Those who are PCR-positive will be 
excluded. 
− Exception:  Participants with serologic findings suggestive of HBV vaccination 
(anti-HBs positivity as the only serologic marker) AND a known history of prior 
HBV vaccination do not need to be tested for HBV DNA by PCR. 
b. Known to be seropositive for hepatitis C.  Participants who have had definitive 
treatment for HCV are permitted if HCV RNA is undetectable at screening visit.  
c. Known to be seropositive for HIV.  HIV testing is not required unless mandated by 
the local health authority. 
8. Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or 
amyloidosis. 
9. Prior treatment with an arginase inhibitor for any indication. 
10. Known or suspected defect in the function of the urea cycle, including a known 
deficiency of carbamoyl phosphate synthetase I, ornithine transcarbamylase, 
argininosuccinate synthetase, argininosuccinate lyase, N-acetyl glutamate synthetase, or 
arginase. 
11. Current use of any prohibited medication as described in Section 6.8.2. 
12. Known hypersensitivity or severe reaction to INCB001158, daratumumab, hyaluronidase, 
monoclonal antibodies, human proteins, or their excipients (refer to the INCB001158 IB, 
daratumumab IB, Prescribing Information and SmPC, and Hylenex® Prescribing 
Information). 
13. Women who are pregnant or breastfeeding. 
14. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study treatment and attending required study 
visits; pose a significant risk to the participant; or interfere with interpretation of study 
data. 
15. Candidates for autologous or allogenic transplantation (for participants enrolled at sites in 
Germany only). 
5.3. 
Lifestyle Considerations 
Not applicable. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently assigned to study treatment in the study. 


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Tests with results that fail eligibility requirements may be repeated during screening.  
Additionally, a participant who fails screening may 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 
In Phase 1, any participant who withdraws from study treatment before the completion of the 
DLT observation period for any reason other than a DLT (eg, not evaluable for DLT) may be 
replaced to ensure a minimum number of evaluable participants. 
In Phase 2, any participant who withdraws consent before the first administration of study 
treatment may be replaced to ensure a minimum number of evaluable participants. 
6. 
STUDY TREATMENT 
6.1. 
Study Treatment(s) Administered 
In this Protocol, the term "study drug" refers to INCB001158 only, and "study treatment" refers 
to INCB001158, daratumumab SC, or the combination of INCB001158 and daratumumab SC. 
Table 14 presents the study treatment information. 
Table 14: 
Study Treatment Information 
Study treatment 
name: 
INCB001158 
Daratumumab SC 
Dosage formulation: 
25 mg and 100 mg tablets 
120 mg/mL daratumumab + 20 μg/mL rHuPH20 
solution 
Unit dose 
strength(s) 
/dosage level(s): 
50 mg BID 
75 mg BID 
100 mg BID 
1800 mg 
Route of 
administration: 
PO 
SC 
Administration 
instructions: 
Administrated PO BID, in the morning and 
evening, approximately 12 hours apart, 
without respect to food (see Appendix B). 
Administered SC by manual push over 3-5 minutes 
(see Appendix C and daratumumab IPPI). 
Packaging and 
labeling: 
INCB001158 will be provided as 25 mg and 
100 mg tablets packaged in bottles, 
respectively.  No preparation is required. 
Each bottle will be labeled as required per 
country requirement. 
Daratumumab SC will be provided in glass vials 
containing daratumumab at a concentration of 
120 mg/mL and rHuPH20 at a concentration of 
2000 U/mL (~20 μg/mL). 
It will be supplied to the site/pharmacy as open-
label supply. 
Each vial will be labeled as required per country 
requirement. 
Storage: 
Ambient conditions 15°C to 30°C (59°F to 
86°F). 
Under refrigeration 2°C-8°C (36°F-46°F).  Protect 
from light. 


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6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study treatment must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff. 
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(s) to the study site. 
• Inventory of study drug(s) at the site. 
• Participant use of the study drug(s) including tablets counts from each supply 
dispensed. 
• Return of study drug(s) 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 Pharmacy Manual. 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
This is a randomized, open-label, Phase 1/2 study.  In Phase 2, all participants will be centrally 
assigned to study treatment using an IRT system.  The first 30 participants will be randomized 
1:1:1 between the Treatment Groups A (RP2D of INCB001158 in combination with 
daratumumab SC), B (daratumumab SC monotherapy followed by crossover to 


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INCB001158 + daratumumab SC at the time of confirmed disease progression), or C (RP2D of 
INCB001158 as monotherapy with crossover to INCB001158 + daratumumab SC at the time of 
confirmed disease progression).  After the initial equal randomization period, a RAR design will 
be used to randomize participants between Treatment Groups A and B.  The system will update 
the randomization rates in Treatment Groups A or B based on the observed ORR by investigator 
assessment at the time each participant is enrolled.  See Section 10.5.2 for details regarding the 
algorithm used for RAR design. 
The IRT system will track participant visits, randomize according to the defined parameters, and 
manage study drug inventory.  Periodic reconciliation of responses between the IRT system and 
the clinical database will be performed.  Study treatment will be dispensed at the study visits 
summarized in the SoA (see Table 3 and Table 4 for study site visit assessments prior to and 
post-crossover, respectively, and Table 7 for the SoA for all participants as of Protocol 
Amendment 3). 
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 INCB001158 will be calculated by the sponsor based on the drug 
accountability documented by the site staff and monitored by the sponsor/designee (tablet 
counts).  Participants will be instructed to bring all unused INCB001158 tablets 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. 
Compliance with daratumumab SC administration will be calculated by the sponsor based on 
drug accountability and administration records documented by the site staff and monitored by the 
sponsor/designee.  The details of each administration will be recorded in the eCRF. 
6.5. 
Guidelines for Prevention and Management of Injection-Related 
Reactions 
6.5.1. 
Prevention of Injection-Related Reactions Due to Daratumumab SC 
6.5.1.1. 
Pre-Administration Medication 
In an effort to prevent IRRs, all participants will receive the following medications 1 to 3 hours 
before each daratumumab SC administration: 
• An antipyretic:  paracetamol (acetaminophen) 650 to 1000 mg PO. 
• An antihistamine:  diphenhydramine 25 to 50 mg PO, or equivalent.  Avoid IV use of 
promethazine (see Appendix D for a list of antihistamines that may be used). 
• Administer 20 mg dexamethasone or equivalent before every administration. 
If necessary, all mandatory PO pre-administration medications may be administered outside of 
the clinic on the day of the injection, provided they are taken within 1 to 3 hours before the 
injection. 


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Predose administration of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) is 
optional on Cycle 1 Day 1 and can be administered up to 24 hours before the injection according 
to investigator discretion. 
6.5.1.2. 
Post-Administration Medication 
For participants at higher risk of respiratory complications (eg, participants with mild asthma or 
participants with COPD developing FEV1 < 80% during the study without any medical history), 
the following post-administration medications should be considered: 
• Antihistamine (diphenhydramine or equivalent) 
• Leukotriene inhibitor (montelukast or equivalent) 
• A short-acting β2 adrenergic receptor agonist such as salbutamol aerosol  
• Control medications for lung disease (eg, inhaled corticosteroids ± long-acting β2 
adrenergic receptor agonists for participants with asthma; long-acting bronchodilators 
such as tiotropium or salbutamol ± inhaled corticosteroids for participants with 
COPD) 
In addition, these at-risk participants may be hospitalized for monitoring for up to 2 nights after 
daratumumab SC administration.  If participants are hospitalized, then an improvement in FEV1 
should be documented before discharge.  If these participants are not hospitalized, then a 
follow-up telephone call should be made to monitor their condition within 48 hours after all 
daratumumab SC administrations.  If the participant has not experienced a significant medical 
event but is hospitalized overnight only for observation, then the hospitalization should not be 
reported as an SAE.  Investigators may prescribe bronchodilators, H1-antihistamines, and 
corticosteroids that are deemed necessary to provide adequate supportive care in the event that a 
bronchospasm occurs after participants are released from the hospital/clinic.  If an at-risk 
participant experiences no major IRRs, then these post-administration medications may be 
waived after 4 doses at the investigator's discretion.  Any post-administration medication will be 
administered after the administration has completed. 
6.5.2. 
Management of Injection-Related Reactions 
6.5.2.1. 
Local Injection Site Reactions 
In Study MMY1004, SC administration of daratumumab in abdominal subcutaneous tissue was 
associated with local injection site reactions such as induration and erythema in some 
participants.  The reactions usually resolved within 60 minutes.  Local injection site reactions 
should be managed according to institutional standards. 
6.5.2.2. 
Systemic Injection-Related Reactions 
Participants should be observed carefully during daratumumab SC administration.  Trained study 
staff at the clinic should be prepared to intervene in case of any IRRs, and resources necessary 
for resuscitation (eg, agents such as epinephrine and aerosolized bronchodilator, also medical 
equipment such as oxygen tanks, tracheostomy equipment, and a defibrillator) must be available.  


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If an IRR develops, then daratumumab SC administration should be temporarily interrupted, as 
indicated in Table 15.  Please refer to the daratumumab IPPI for further details.  Participants who 
experience AEs during daratumumab SC administration must be treated for their symptoms.  
Participants should be treated with acetaminophen, antihistamine, or corticosteroids, as needed.  
Intravenous saline may be indicated.  For bronchospasm, urticaria, or dyspnea, participants may 
require antihistamines, oxygen, corticosteroids, or bronchodilators.  For hypotension, participants 
may require vasopressors.  In the event of a life-threatening IRR (which may include pulmonary 
or cardiac events) or anaphylactic reaction, daratumumab SC should be discontinued, and no 
additional daratumumab SC should be administered to the participant. 
Table 15: 
Recommendations for the Management of Systemic Injection-Related 
Reactions 
IRR 
Action  
Grade 1 or 2 
Daratumumab SC administration should be 
interrupted.  When the participant's condition 
is stable, daratumumab SC administration 
may be restarted at the investigator's 
discretion. 
For instructions for restarting administration, 
refer to the daratumumab IPPI. 
≥ Grade 2 laryngeal edema, or  
≥ Grade 2 bronchospasm that does not respond to 
systemic therapy and resolve with 6 hours from onset 
Participant must be discontinued from 
daratumumab SC treatment. 
≥ Grade 3 (other than laryngeal edema or 
bronchospasm) 
Daratumumab SC administration must be 
interrupted.  Monitor participants carefully 
until resolution or return to Grade 1.  
Daratumumab SC administration may be 
restarted at the investigator's discretion. 
If the intensity of the IRRs returns to ≥ Grade 3 after 
restart of the daratumumab SC administration 
Participant must be discontinued from 
daratumumab SC treatment. 
Grade 4 
Daratumumab SC administration must be 
stopped and the participant discontinued from 
daratumumab SC treatment. 
Grade 3 (or ≥ Grade 2 laryngeal edema or 
bronchospasm) recurrence during or within 24 hours 
after a subsequent daratumumab SC administration  
Participant must be discontinued from 
daratumumab SC treatment. 
6.6. 
Dose-Limiting Toxicity and Determination of Maximum Tolerated 
Dose and/or Pharmacologically Active Dose of INCB001158 
6.6.1. 
Definition of a Dose-Limiting Toxicity 
A DLT will be defined as the occurrence of any of the toxicities in Table 16 occurring from the 
start of study treatment up to and including Day 28, except those with a clear alternative 
explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values 


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without associated clinically significant signs or symptoms based on investigator determination.  
All DLTs will be assessed for severity by the investigator using CTCAE v5 criteria.  Participants 
who receive at least 42 of 56 (≥ 75%) doses of study drug at the level assigned or have a DLT 
will be considered evaluable for determining tolerability of the dose.  Participants who do not 
meet these criteria may be replaced to obtain sufficient evaluable participants to be able to assess 
that dose level using the BOIN design, as outlined in Table 11. 
Clear evidence of urea cycle inhibition (eg, an increase in fasting urinary orotic acid to 
> 10 × ULN or any orotic acid value of > 40 × ULN, accompanied by plasma ammonia elevation 
≥ 2 × ULN and ≥ 2 × baseline, or symptomatic hyperammonemia) would be considered a 
dose-limiting event and will be treated the same as a DLT with regard to the dose-escalation 
rules and definition of the MTD described in Section 4.1.1.  Refer to the INCB001158 IB for an 
explanation of the orotic acid thresholds. 
Individual participant dose reductions may be made based on events observed at any time during 
treatment with study drug; however, for the purposes of dose level escalation/de-escalation, 
expanding a dose level, and for determining the MTD of INCB001158, decisions will be made 
based on events that are observed from the first day of study drug administration through and 
including the final day of Cycle 1 (Day 28).  A lower MTD may subsequently be determined 
based on relevant toxicities that become evident after Day 28. 
Table 16: 
Definition of a Dose-Limiting Toxicity 
Toxicity 
Definition 
Nonhematologic 
• Any ≥ Grade 3 nonhematologic toxicity EXCEPT the following: 
− Transient (≤ 72 hours) abnormal laboratory values without associated clinically 
significant signs or symptoms. 
− Nausea, vomiting, and diarrhea adequately controlled with medical therapy within 
72 hours. 
− Fatigue or asthenia that was present at baseline or that lasts for < 7 days. 
− An event clearly associated with the underlying disease, disease progression, a 
concomitant medication, or comorbidity. 
Hematologic 
• Grade 3 thrombocytopenia with clinically significant bleeding (requires hospitalization, 
transfusion of blood products, or other urgent medical intervention). 
• Grade 4 hematologic toxicity, except for Grade 4 lymphopenia. 
• Febrile neutropenia (ANC < 1.0 × 109/L and fever > 101°F/38.5°C). 
6.6.2. 
Management of Dose-Limiting Toxicities or Other Urgent Situations 
Investigators may employ any measures or concomitant medications necessary to optimally treat 
the participant after discussion with the sponsor (whenever possible). 
6.6.3. 
Follow-Up of Dose-Limiting Toxicities 
Any DLT should be monitored until it resolves to baseline or appears to have stabilized for a 
minimum of 4 weeks, unless the participant discontinues study treatment, in which case, the 
participant will be followed for 28 days after last dose of study treatment or 90 days for irAEs 
(see Section 9).  During follow-up, participants should be seen as often as medically indicated to 
assure safety. 


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6.6.4. 
Procedures for Dose Level Review and Dose Escalation 
Telephone conferences with study investigators will be scheduled by the sponsor in order to 
review dose level–specific data and overall safety data, to agree on dose escalation, to adjudicate 
individual high-grade AEs as potentially dose-limiting, and to guide other major study decisions. 
6.7. 
Dose Modifications 
Selections and modifications to the study treatment regimen are planned for dose-escalation.  
Dose interruptions and modifications also may occur for individual study participants.  The 
identification of DLTs will define the doses used in planned dose levels (see Section 4.1.1).  
Further, the occurrence of DLTs and other toxicities (related or unrelated to study drug) will 
guide decisions for treatment interruptions and discontinuation for individual participants.  
Intraparticipant dose escalation for any study drug is not permitted. 
6.7.1. 
Dose Modifications of INCB001158 
For participants in Phase 1, dose reductions of INCB001158 will be permitted during the first 
28 days only if a participant experiences a DLT or a toxicity that may herald a DLT.  If a 
participant experiences a DLT, treatment continuation at a lower dose of INCB001158 will be 
permitted as long as the toxicity has returned to ≤ Grade 1 or baseline within 28 days.  When 
INCB001158 is held or discontinued, daratumumab SC may be continued, at the investigator's 
discretion.  Upon recovery, participants may restart at 1 INCB001158 dose level lower.  
Participants who do not recover within 28 days will not be eligible for resumption of study 
treatment without approval from the medical monitor.  See also Table 17.  
6.7.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment. 
As described in Section 2.3, INCB001158 has the potential to cause toxicity related to the 
inhibition of arginase 1 in the hepatic urea cycle.  Table 17 provides guidance for INCB001158 
dose modifications and participant management if there is evidence of urea cycle inhibition. 
Dose modification and toxicity management for potential irAEs associated with INCB001158 
should be managed as follows. 
Adverse events (both nonserious and serious) associated with INCB001158 exposure may 
represent an immunologic etiology.  These irAEs may occur shortly after the first dose or several 
months after the last dose of treatment and may affect more than 1 body system simultaneously.  
Therefore, early recognition and initiation of treatment is critical to reduce complications.  For 
suspected irAEs, ensure adequate evaluation to confirm etiology or exclude other causes.  
Additional procedures or tests such as bronchoscopy, endoscopy, or skin biopsy may be included 
as part of the evaluation.  Based on the severity of irAEs, withhold or permanently discontinue 
INCB001158 and administer corticosteroids. 
Table 17 summarizes the AE dose modification actions for INCB001158.  Of note, when 
indicated by Table 17 to mitigate irAEs, the dose of INCB001158 must be reduced using the 
dosing levels outlined in Table 11.  Once reduced, re-escalation of INCB001158 is not permitted. 


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Table 17: 
Guidelines for Interruption and Restarting of Study Drug 
Adverse Event 
Toxicity Grade or 
Conditions (CTCAE v5) 
Action Taken 
AE Management With 
Corticosteroid and/or Other 
Therapies 
Monitor and Follow-Up 
Evidence of urea 
cycle inhibition 
• Fasting urinary orotic acid 
> 2 × and ≤ 10 × ULN 
• Any urinary orotic acid 
> 2 × and ≤ 40 × ULN 
• Continue. 
• None. 
• Retest 1 week later.  If still 
abnormal, withhold INCB001158 
and retest every week until orotic 
acid returns to normal level, then 
consider restarting (at a lower 
dose) in consultation with medical 
monitor. 
• Ammonia 2 × ULN and 
2 × baseline (repeated 
measurements or with 
symptoms) 
• Fasting urinary orotic acid 
> 10 × ULN 
• Any urinary orotic acid 
> 40 × ULN 
• BUN < 50% LLN 
• Withhold. 
• Consider restarting (at a lower 
dose) in consultation with medical 
monitor. 
• See Section 6.7.3 for management 
of hyperammonemia. 
 
 
Pneumonitis 
Grade 2 
• Withhold until Grade 0-1.  Restart 
at full dose. 
• Administer corticosteroids (initial 
dose of 1-2 mg/kg/day prednisone 
or equivalent) followed by taper. 
• Monitor participants for signs and 
symptoms of pneumonitis. 
• Evaluate participants with 
suspected pneumonitis with 
radiographic imaging and initiate 
corticosteroid treatment. 
• Add prophylactic antibiotics for 
opportunistic infections. 
Grade 3 or 4, or recurrent 
Grade 2 
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 


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Table 17: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
Adverse Event 
Toxicity Grade or 
Conditions (CTCAE v5) 
Action Taken 
AE Management With 
Corticosteroid and/or Other 
Therapies 
Monitor and Follow-Up 
Diarrhea/colitis 
Grade 2 or 3 
• Withhold until Grade 0-1. 
• Grade 2:  Restart at same dose 
level. 
• Grade 3:  Restart at next dose 
level lower. 
• Administer corticosteroids (initial 
dose of 1-2 mg/kg/day prednisone 
or equivalent) followed by taper. 
• Monitor participants for signs and 
symptoms of enterocolitis (ie, 
diarrhea, abdominal pain, blood or 
mucus in stool with or without 
fever) and of bowel perforation (ie, 
peritoneal signs and ileus). 
• Participants with ≥ Grade 2 
diarrhea suspecting colitis should 
consider GI consultation and 
performing endoscopy to rule out 
colitis.  
• Participants with diarrhea/colitis 
should be advised to drink liberal 
quantities of clear fluids.  If 
sufficient oral fluid intake is not 
feasible, fluid and electrolytes 
should be substituted via IV 
infusion. 
Grade 4 
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 
AST/ALT elevation 
or increased bilirubina 
Grade 2 
• Withhold until Grade 0-1.  Restart 
at same dose level. 
• Administer corticosteroids (initial 
dose of 0.5-1 mg/kg prednisone or 
equivalent) followed by taper. 
• Monitor with liver function tests 
(consider weekly or more 
frequently until liver enzyme value 
returns to baseline or is stable). 
Grade 3 or 4  
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 
• Administer corticosteroids (initial 
dose of 1-2 mg/kg prednisone or 
equivalent) followed by taper. 
T1DM or 
hyperglycemiab 
Newly onset T1DM or 
Grade 3 or 4 hyperglycemia 
associated with evidence of 
-cell failure 
• Withhold until Grade 0-1. 
• Grade 2:  Restart at same dose 
level. 
• Grade 3:  Restart at next dose 
level lower. 
• Initiate insulin replacement therapy 
for participants with T1DM. 
• Administer antihyperglycemic in 
participants with hyperglycemia. 
• Monitor participants for 
hyperglycemia or other signs and 
symptoms of diabetes. 
Hypophysitis 
Grade 2 
• Withhold until Grade 0-1.  Restart 
at same dose level. 
• Administer corticosteroids and 
initiate hormonal replacements as 
clinically indicated. 
• Monitor for signs and symptoms of 
hypophysitis (including 
hypopituitarism and adrenal 
insufficiency). 
Grade 3 or 4 
• Withhold until Grade 0-1. 
• Grade 3:  Restart at same dose 
level. 
• Grade 4:  Consider rechallenge at 
next dose level lower. 


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Table 17: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
Adverse Event 
Toxicity Grade or 
Conditions (CTCAE v5) 
Action Taken 
AE Management With 
Corticosteroid and/or Other 
Therapies 
Monitor and Follow-Up 
Hyperthyroidismb 
Grade 2 
• Continue. 
• Treat with nonselective β-blockers 
(eg, propranolol) or thionamides as 
appropriate. 
• Monitor for signs and symptoms of 
thyroid disorders. 
Grade 3 or 4 
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 
Hypothyroidismb 
Grade 2-4 
• Continue. 
• Initiate thyroid replacement 
hormones (eg, levothyroxine or 
liothyronine) per standard of care. 
• Monitor for signs and symptoms of 
thyroid disorders. 
Nephritis and renal 
dysfunction 
Grade 2 
• Withhold until Grade 0-1.  Restart 
at same dose level. 
• Administer corticosteroids 
(prednisone 1-2 mg/kg or 
equivalent) followed by taper. 
• Monitor changes of renal function. 
Grade 3 or 4  
• Withhold until Grade 0-1. 
• Grade 3:  Restart at same dose 
level. 
• Grade 4:  Consider rechallenge at 
next dose level lower. 
Rash 
Grade 1 or 2 
• Continue. 
• Manage with topical steroids with 
or without drug interruption. 
 
Grade 3c 
• Withhold until Grade 0-1. 
• Restart at same dose level. 
• Consider dermatology consultation 
and biopsy for confirmation of 
diagnosis. 
• Administer corticosteroids (initial 
dose of 1-2 mg/kg prednisone or 
equivalent) followed by taper. 
• If toxicity does not resolve within 
12 weeks of last dose, or cannot 
taper below 10 mg or less of 
prednisone or equivalent within 
12 weeks, must permanently 
discontinue. 
Grade 4 
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 
• Dermatology consultation and 
consideration of biopsy and clinical 
dermatology photograph. 
• Administer corticosteroids (initial 
dose of 1-2 mg/kg prednisone or 
equivalent) followed by taper. 
 


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Table 17: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
Adverse Event 
Toxicity Grade or 
Conditions (CTCAE v5) 
Action Taken 
AE Management With 
Corticosteroid and/or Other 
Therapies 
Monitor and Follow-Up 
Asymptomaticd 
amylase or lipase 
increased 
Grade 3 
• May continue treatment with 
medical monitor approval. 
 
• Permanently discontinue if clinical 
signs and symptoms of pancreatitis 
develop (abdominal pain, nausea, 
vomiting). 
• If toxicity does not resolve within 
12 weeks of last dose after an 
interruption, must permanently 
discontinue unless approved by the 
medical monitor to continue. 
• If Grade 4 lipase/amylase elevation 
is asymptomatic and abdominal 
imaging suggests no pathology, 
study drug administration dosing 
may continue with medical monitor 
approval. 
Grade 4 
• Withhold until Grade 0-1.  Restart 
at same dose level. 
 
All other irAEs 
Grade 3, or 
intolerable/persistent 
Grade 2 
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 
• Based on severity of AE, 
administer corticosteroids. 
• Ensure adequate evaluation to 
confirm etiology or exclude other 
causes 
Grade 4 or recurrent Grade 3  
• Withhold until Grade 0-1.  
Consider rechallenge at next dose 
level lower. 
General Instructions: 
1. Corticosteroid taper should be initiated upon AE improving to Grade 1 or less and should be continued over at least 4 weeks. 
2. For situations where INCB001158 has been withheld, INCB001158 can be resumed after AE has been reduced to Grade 1 or 0 and corticosteroid has been tapered.  
INCB001158 should be permanently discontinued if AE does not resolve within 12 weeks of last dose or if corticosteroids cannot be reduced to ≤ 10 mg prednisone or 
equivalent per day within 12 weeks.  
3. For severe and life-threatening irAEs, IV corticosteroid should be initiated first followed by oral steroid.  Other immunosuppressive treatment should be initiated if irAEs 
cannot be controlled by corticosteroids. 
AE = adverse event; ALT (SGPT) = alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT) = aspartate aminotransferase (serum glutamic oxaloacetic 
transaminase); BUN = blood urea nitrogen; CTCAE = Common Terminology Criteria for Adverse Events; IV = intravenous; irAE = immune-related adverse events; 
LLN = lower limit of normal; T1DM = Type 1 diabetes mellitus; ULN = upper limit of normal. 
a Participants with radiographically documented liver metastases should withhold at > 5 × ULN. 
b For participants with Grade 3 or 4 immune-related endocrinopathy where withholding of INCB001158 is required, INCB001158 may be resumed when AE resolves to ≤ Grade 2 
and is controlled with hormonal replacement therapy or achieved metabolic control (in case of T1DM). 
c Participants with Grade 3 rash in the absence of desquamation, with no mucosal involvement, that does not require systemic steroids, and that resolves to Grade 1 within 14 days 
do not have to hold study medication and may be treated similar as Grade 1 events. 
d If Grade 4 lipase/amylase elevation is asymptomatic and abdominal imaging suggests no pathology, then study drug administration dosing may continue (with or without dose 
reduction) with medical monitor approval. 


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6.7.3. 
Management of Hyperammonemia 
Participants receiving INCB001158 as monotherapy or in combination with daratumumab SC 
should be monitored for elevated venous plasma ammonia.  Asymptomatic clinically significant 
drug-related elevations in ammonia (eg, a repeatable elevation in ammonia > 2 × ULN AND 
> 2 × baseline) should be managed by interrupting INCB001158 and monitoring to resolution.  
For symptomatic elevations (ie, significant ammonia elevation associated with nausea, vomiting, 
severe anorexia, mental status changes, seizure, or other symptoms associated with 
hyperammonemia), participants should be admitted for management according to the local 
institutional protocol for hyperammonemia, including 1) sending appropriate laboratory samples 
(ammonia [on ice, measured immediately], plasma amino acid profile, liver function tests, 
electrolytes, bicarbonate, BUN or urea, creatinine, glucose, and urine orotic acid), 2) IV 
hydration with dextrose-containing fluids, 3) discontinuation of protein intake, 4) implementing 
therapy to reduce ammonia levels (oral lactulose/lactitol, IV Ammonul®), and 5) identifying and 
treating any potential triggers (eg, discontinue corticosteroids, treat infections). 
6.7.4. 
Dose Delays and Dose Modification of Daratumumab SC 
Dose modification of daratumumab SC is not permitted.  Dose delay is the primary method for 
managing toxicities related to daratumumab SC. 
On the first day of each new treatment cycle and before each daratumumab SC administration, 
the participant will be evaluated by the treating physician for possible toxicities that may have 
occurred after the previous dose(s).  Toxicities are to be assessed according to CTCAE v5.  Dose 
delays will be made based on the toxicity experienced during the previous cycle of therapy or 
newly encountered on Day 1 of a cycle. 
For all daratumumab SC doses in a treatment cycle except the first dose, if daratumumab SC 
administration does not commence within the prespecified window (see Table 3 and Table 4 for 
study site visit assessments prior to and post-crossover, respectively, and Table 7 for all 
participants as of Protocol Amendment 3) of the scheduled administration date, then the dose 
will be considered a missed dose.  Administration may resume at the next planned dosing date.  
A missed dose will not be made up.  The minimal time interval between daratumumab SC doses 
should be 4 days. 
Daratumumab SC treatment must be held if any of the following criteria below are met, to allow 
for recovery from toxicity, regardless of relationship to INCB001158 or daratumumab SC.  
• Grade 4 hematologic toxicity, except for Grade 4 lymphopenia 
• Grade 3 thrombocytopenia with bleeding 
• Febrile neutropenia 
• Neutropenia with infection, of any grade 
• Grade 3 or higher nonhematologic toxicities, with the following exceptions:  
− Grade 3 nausea or Grade 3 vomiting that responds to antiemetic treatment within 
7 days 
− Grade 3 diarrhea that responds to antidiarrheal treatment within 7 days 


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− Grade 3 fatigue that was present at baseline or that lasts for < 7 days after the last 
administration of daratumumab SC 
− Grade 3 asthenia that was present at baseline or that lasts for < 7 days after the 
last administration of daratumumab SC. 
Administration of daratumumab SC may be restarted (as indicated in Table 18) upon recovery 
from toxicity to Grade 2 or baseline, with the exception that Grade 2 laryngeal edema or Grade 2 
bronchospasm must be fully recovered. 
Table 18: 
Daratumumab SC–Related Toxicity Management 
Cycles 
Frequency 
Dose Held 
Dosing Re-Start at 
1 and 2 
QW 
> 3 days 
Next planned QW dosing date 
3 to 6 
Q2W 
> 7 days 
Next planned Q2W dosing date 
7+ 
Q4W 
> 14 days 
Next planned Q4W dosing date 
The cycles may be delayed up to 4 weeks (Cycle 1 to Cycle 6) or up to 6 weeks (Cycle 7 and 
beyond).  If Day 1 of a cycle is delayed, Day 1 of subsequent cycles should be adjusted 
accordingly to maintain the 28-day cycle duration.  However, if a within-cycle dose is delayed, 
then the dates of the subsequent within-cycle doses should not be adjusted.  
 
 
 
When daratumumab SC is held, INCB001158 may be continued, at the investigator's discretion 
with approval of the medical monitor.   
6.7.5. 
Daratumumab SC Interruption or Missed Doses 
A daratumumab SC dose that is held for more than the permitted time (see Table 18) from the 
per-Protocol administration date for any reason other than toxicities suspected to be related to 
daratumumab SC should be brought to the attention of the sponsor at the earliest possible time.  
Participants whose dose was delayed for more than 4 weeks (Cycle 1 to Cycle 9) or 
2 consecutive planned doses (after Cycle 9) should have daratumumab SC discontinued, unless, 
upon consultation with the sponsor and the review of safety and efficacy, continuation is agreed 
upon. 
6.8. 
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 30 days before the first dose of study treatment and 30 days after 
the last dose of the last study treatment, 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 after 
30 days after the last dose of study treatment should be recorded for SAEs as defined in 
Section 9.4.  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. 


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NOTE:  As of Protocol Amendment 3, use of concomitant medications should be monitored for 
participants to verify that they are not taking any concomitant medication prohibited per 
Protocol; however, concomitant medications no longer need to be collected in the eCRF, except 
for concomitant medications in relation with SAEs or AESIs. 
6.8.1. 
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.  All concomitant medication will be recorded on the eCRF including all 
prescription, over-the-counter, herbal supplements, and IV medications and fluids.  If changes 
occur during the study period, documentation of drug dosage frequency, route, and date will also 
be included on the eCRF. 
6.8.1.1. 
Bisphosphonate Therapy 
Bisphosphonate therapy is strongly recommended for all participants with evidence of lytic 
destruction of bone or with osteopenia.  Bisphosphonate therapy is recommended to be continued 
according to treatment guidelines (NCCN 2014).  Commercially available IV bisphosphonates 
(pamidronate and zoledronic acid) are preferred when available and should be used according to 
the manufacturer's recommendations, as described in the prescribing information, for participants 
with osteolytic or osteopenic myelomatous bone disease.  Oral bisphosphonates may be used as 
alternatives if IV bisphosphonates are not available at the study site.  It is preferred that 
investigators use the same route of bisphosphonate therapy for all participants at their sites.  
Participants who are using bisphosphonate therapy when they enter the study should continue the 
same treatment.  Participants with evidence of lytic destruction of bone or with osteopenia who 
are not using a bisphosphonate at the time of administration of study treatment should start a 
bisphosphonate as soon as possible during Cycle 1 or 2 of treatment.  Investigators should not 
start bisphosphonate therapy during the study, unless it has been agreed with the sponsor that 
there is no sign of disease progression.  
6.8.1.2. 
Therapy for Tumor Lysis Syndrome 
Participants should be monitored for symptoms of tumor lysis syndrome.  Management of tumor 
lysis syndrome, including dehydration and abnormal laboratory test results such as 
hyperkalemia, hyperuricemia, and hypocalcemia, are highly recommended.  It is also 
recommended that high-risk participants (ie, those with a high tumor burden) should be treated 
prophylactically in accordance with local standards (eg, rehydration, diuretics).  Xanthine 
oxidase inhibitors (eg, allopurinol) are not allowed (see Section 6.8.2), as they cause an 
accumulation of orotic acid in the urine, which would confound assessment of safety in these 
participants.  Participants will receive prophylactic therapy to prevent IRRs during the treatment 
period, as described in Section 6.5.1. 
6.8.1.3. 
Management of Hepatitis B Virus Reactivation 
For participants who are diagnosed with HBV reactivation while on treatment, daratumumab SC 
should be interrupted until the infection is adequately controlled.  If the benefits outweigh the 
risks, daratumumab SC may be resumed with concomitant antiviral prophylaxis as per local 
standard of care and in consultation with the medical monitor. 


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6.8.2. 
Prohibited Medications and Procedures 
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing study.  If there is a clinical indication for any medication or vaccination 
specifically prohibited during the study, discontinuation from study therapy 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 medical monitor, and the 
participant. 
Participants are prohibited from receiving the following therapies during the screening and 
treatment of this study: 
• Investigational treatments or commercially available agents with activity against or 
under investigation for MM. 
• Live vaccines within 30 days before the first dose of study treatment, while 
participating in the study, and until 3 months after the last dose of study treatment. 
− Examples of live vaccines include, but are not limited to, the following:  measles, 
mumps, rubella, chickenpox, yellow fever, nasal seasonal flu, nasal H1N1 flu, 
rabies, Bacillus Calmette-Guérin, and typhoid. 
• Except for erythropoietin or darbepoetin alpha (Aranesp®), use of growth factors 
(G-CSF, GM-CSF, etc) is not permitted in the first treatment cycle unless the 
participant experiences a hematologic DLT. 
• Typically, IV contrast is not used in CT scanning of participants with secretory MM 
because of the risk to the kidney.  If administration of IV contrast is necessary, then 
adequate precautions including hydration are indicated. 
• Concomitant treatment with valproic acid/valproate-containing therapies is not 
permitted, as hyperammonemia is a well-described toxicity of valproic acid, 
particularly at high exposures, potentially through inhibition of the urea cycle 
(Verrotti et al 2002, Wadzinski et al 2007). 
• Concomitant treatment with allopurinol or other xanthine oxidase inhibitors is not 
allowed.  Xanthine oxidase inhibitors (eg, allopurinol) cause an accumulation of 
orotic acid in the urine, which would confound the assessment of safety in these 
participants. 
• Prolonged therapy with systemic glucocorticoids (> 7 days) for any purpose other 
than to modulate symptoms from an AE, SAE, or event of clinical interest, or for use 
as pre- and post-administration medications.  Brief, limited use of systemic 
corticosteroids (≤ 7 days) are permitted where such use is considered standard of care.  
− Replacement doses of steroids (for example, prednisone 5 to 7.5 mg daily) are 
permitted while on study, as is the use of local steroids. 


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Participants who, in the assessment by the investigator, require the use of any of the 
aforementioned treatments for clinical management should be removed from treatment but 
should continue in the study for assessment of disease status and survival. 
There are no prohibited therapies during the post-treatment follow-up period. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• 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 to be followed for 
progression and survival. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 
• The participant has an unacceptable toxicity or a toxicity that does not recover in 
6 weeks.  Investigators who wish to continue treatment after a treatment delay of 
4 weeks should consult with the sponsor's medical monitor for approval. 
• An AE requiring more than 2 dose reductions of INCB001158. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study 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 and Table 4 (SoA prior and post-crossover 
respectively), and Table 5 and Table 6 (for laboratory assessments prior and post-crossover 
respectively).  As of Protocol Amendment 3, see only Table 7 for the SoA for all participants. 


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The last date of the last dose of study treatment and the reason for discontinuation of study 
treatment 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 withdrawal must be documented in the participant's medical record 
and the primary reason for withdrawal must be included in the eCRF. 
• The EOT visit should be performed. 
• The date of the EOT visit should be recorded in the IRT. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety or disease status follow-up), 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. 
NOTE:  As of Protocol Amendment 3, no further disease status and survival follow-up 
assessments will be required beyond the last safety follow-up visit. 
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 and Table 4 (SoA prior and post-crossover respectively), and Table 5 and Table 6 
(laboratory assessments prior and post-crossover respectively) for data to be collected at the time 
of study discontinuation and follow-up and for any further evaluations that need to be completed. 
NOTE:  As of Protocol Amendment 3, see only Table 7 for the SoA and laboratory assessments 
for all participants. 
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. 


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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. 
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. 


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• 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(s) 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. 
 
  Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period. 
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 informed consent 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 
treatment assignment will be used to determine eligibility.  Additionally, a participant who fails 
screening may repeat the screening process 1 time if the investigator believes there has been a 
change in eligibility status (eg, after recovery from an infection). 
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 system to 
obtain the participant ID number during screening.  Upon determining that the participant is 


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eligible for study entry, the IRT will be contacted to obtain the treatment assignment.  
Additionally, the IRT system will be contacted at each regular study visit to update the study 
drug supply.  Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and Diaries 
Participants will be provided with a reminder card at each visit.  The reminder card will indicate 
the date/time of the next visit and will also remind the participant that they should not take their 
morning dose of INCB001158 before visiting the clinic on those days, as they will take them 
after blood draws for safety evaluation have been completed. 
Participants will also be provided with diaries to record dates, times, and doses of INCB001158 
that they take between clinic visits. 
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 10 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, and relevant disease characteristics, and prior treatments, 
including systemic treatments, radiation, and surgical procedures, will be recorded. 
8.2. 
Efficacy Assessments 
NOTE:  As of Protocol Amendment 3, the disease assessments are only required to be performed 
as per the site standard of care guidelines for the participant's condition and monitoring.  
Participants must be withdrawn from the study if, in the opinion of the investigator, the disease 
has progressed and the participant is no longer having clinical benefit from the study treatment. 
8.2.1. 
Evaluations 
8.2.1.1. 
Responses Categories 
Assessment of tumor response and disease progression will be conducted in accordance with the 
IMWG response criteria.  Disease evaluations will include measurements of myeloma proteins, 
bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and 
measurements of serum calcium corrected for albumin. 
Efficacy/disease evaluations must be performed at each treatment cycle as specified in the SoA 
(see Table 3 and Table 4; as of Protocol Amendment 3, see Table 7 for all participants).  The 
sponsor may request that the disease assessments be sent for central independent review.  
Disease evaluations scheduled for treatment days should be collected before study treatment is 
administered.  Disease evaluations will be performed by a central laboratory (unless otherwise 


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specified) until disease progression or the EOT.  This study will use the IMWG consensus 
recommendations for MM treatment response criteria (Durie et al 2006, Kumar et al 2016, 
Rajkumar et al 2011) presented in Table 19.  Per IMWG uniform response criteria, all response 
categories and PD require 2 consecutive assessments except for radiographic or bone marrow 
assessments.  For quantitative Ig at baseline, M-protein, IFE, and FLC measurements in serum 
and 24-hour urine, the investigator will use results provided by the central laboratory.  For 
participants with suspected daratumumab interference on SPEP and IFE, a reflex assay will be 
performed (see Appendix E).  Participants with confirmed daratumumab interference who meet 
all other clinical criteria for CR or sCR will be considered CR/sCR. 
Table 19: 
International Uniform Response Criteria Consensus Recommendations 
Response 
Response Criteria 
Stringent 
complete 
response (sCR) 
• CR as defined below, plus 
• Normal FLC ratio, and 
• Absence of clonal PCs by immunohistochemistry, immunofluorescence,a or 2- to 
4-color flow cytometry. 
Complete 
response (CR)b 
• Negative immunofixation on the serum and urine, and 
• Disappearance of any soft tissue plasmacytomas, and 
• < 5% PCs in bone marrow. 
Very good 
partial response 
(VGPR)b 
• Serum and urine M-component detectable by immunofixation but not on 
electrophoresis, or 
•  90% reduction in serum M-protein plus urine M-protein < 100 mg/24 hours. 
Partial response 
(PR) 
•  50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 
 90% or to < 200 mg/24 hours. 
• If the serum and urine M-protein are not measurable, a decrease of  50% in the 
difference between involved and uninvolved FLC levels is required in place of the 
M-protein criteria. 
• If serum and urine M-protein are not measurable, and serum free light assay is also 
not measurable,  50% reduction in bone marrow PCs is required in place of 
M-protein, provided baseline bone marrow plasma cell percentage was  30%. 
• In addition to the above criteria, if present at baseline, a  50% reduction in the size 
(SPD) of soft tissue plasmacytomas is also required. 
Minimal 
response (MR) 
•  25% but  49% reduction of serum M-protein and reduction in 24-hour urine 
M-protein by 50% to 89%. 
• In addition to the above criteria, if present at baseline, 25% to 49% reduction in the 
size of soft tissue plasmacytomas is also required. 
• No increase in size or number of lytic bone lesions (development of compression 
fracture does not exclude response). 
Stable disease 
(SD) 
• Not meeting criteria for CR, VGPR, PR, MR, or PD. 


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Table 19: 
International Uniform Response Criteria Consensus Recommendations 
(Continued) 
Response 
Response Criteria 
Progressive 
disease (PD)c 
Increase of 25% from lowest response value in any one of the following: 
• Serum M-component (absolute increase must be  0.5 g/dL),  
• Urine M-component (absolute increase must be  200 mg/24 hours),  
• Only in participants without measurable serum and urine M-protein levels:  the 
difference between involved and uninvolved FLC levels (absolute increase must 
be > 10 mg/dL). 
• Only in participants without measurable serum and urine M-protein levels and 
without measurable disease by FLC levels, bone marrow PC percentage (absolute 
percentage must be  10%). 
• Bone marrow plasma cell percentage:  the absolute percentage must be > 10%. 
• Definite development of new bone lesions or soft tissue plasmacytomas or definite 
increase in the size of existing bone lesions or soft tissue plasmacytomas (SPD).  
• Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be 
attributed solely to the PC proliferative disorder. 
FLC = free light chain; PC = plasma cell; SPD = sum of the products of the maximal perpendicular diameters of 
measured lesions. 
Note:  All response categories (CR, sCR, VGPR, PR, and PD) require 2 consecutive assessments made at any time 
before the institution of any new therapy; CR, sCR, VGPR, PR, and SD categories also require no known evidence 
of progressive or new bone lesions if radiographic studies were performed.  VGPR and CR categories require 
serum and urine studies regardless of whether disease at baseline was measurable on serum, urine, both, or neither. 
Note:  Radiographic studies are not required to satisfy these response requirements.  Bone marrow assessments need 
not be confirmed.  For PD, serum M-component increases of more than or equal to 1 g/dL are sufficient to define 
relapse if starting M-component is  5 g/dL. 
a Presence/absence of clonal cells is based upon the kappa/lambda ratio.  An abnormal kappa/lambda ratio by 
immunohistochemistry or immunofluorescence requires a minimum of 100 plasma cells for analysis.  An 
abnormal ratio reflecting presence of an abnormal clone is kappa/lambda of > 4:1 or < 1:2. 
b Clarifications to IMWG criteria for coding CR and VGPR in participants in whom the only measurable disease is 
by serum FLC levels:  CR in such participants indicates a normal FLC ratio of 0.26 to 1.65 in addition to CR 
criteria listed above.  VGPR in such participants requires a > 90% decrease in the difference between involved and 
uninvolved FLC levels. 
c Clarifications to IMWG criteria for coding PD:  Bone marrow criteria for PD are to be used only in participants 
without measurable disease by M-protein and by FLC levels; "25% increase" refers to M-protein, FLC, and bone 
marrow results, and does not refer to bone lesions, soft tissue plasmacytomas, or hypercalcemia, and the "lowest 
response value" does not need to be a confirmed value. 
8.2.1.2. 
Myeloma Protein Measurements in Serum and Urine 
Blood and 24-hour urine samples for M-protein measurements will be sent to and analyzed by a 
central laboratory.  Only 1 serum and one 24-hour urine sample at each timepoint are required by 
the central laboratory to perform the following tests: 
• Serum quantitative Igs 
− All participants will be evaluated for IgG, IgA, IgM, IgE, and IgD as indicated in 
Table 3 and Table 4.  
• SPEP 


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• Serum IFE at screening and thereafter when M-protein is nonquantifiable  
• Serum FLC assay 
• 24-hour UPEP 
• Urine IFE at screening and thereafter when a M-protein is nonquantifiable 
Blood and 24-hour urine samples will be collected as specified in the SoA (see Table 3 and 
Table 4; see Table 7 for the SoA for all participants as of Protocol Amendment 3) until the 
development of confirmed disease progression.  If the 24-hour urine collection (UPEP) began 
before informed consent was obtained as part of routine patient care, the sample can be used in 
this study as long as it was sent to the central laboratory for analysis after the informed consent 
was obtained.  Disease progression based on one of the laboratory tests alone must be confirmed 
by at least 1 repeat investigation performed 1 to 3 weeks later.  Disease evaluations will continue 
beyond relapse from CR until disease progression is confirmed.  Serum and urine IFE and serum 
FLC assay will be performed at screening and thereafter when a CR is suspected or maintained 
(when serum or 24-hour urine M-protein electrophoresis [by SPEP or UPEP] are 0 or 
nonquantifiable).  For participants with light chain MM, both serum and urine IFE test will be 
performed routinely. 
Serum IFE assay samples will be split into 2 aliquots, with 1 reserved for potential follow-on 
testing if daratumumab interference with IFE is suspected.  As daratumumab is a monoclonal 
IgG antibody, additional serum samples may be used to monitor for potential daratumumab 
interference with the IFE. 
Previous studies have demonstrated potential interference of therapeutic monoclonal antibodies 
with detection of endogenous myeloma M-protein on serum IFE (McCudden et al 2015).  For 
participants with suspected daratumumab interference on SPEP, serum IFE, or both, a follow-up 
test will be run using anti-idiotype antibodies against daratumumab to remove antibody 
interference. 
Participants who meet all other IMWG criteria for CR or sCR, and whose positive IFE is 
confirmed to be daratumumab, will be considered as having a CR or sCR. 
8.2.1.3. 
Serum Calcium Corrected for Albumin 
Blood samples for calculating serum calcium corrected for albumin will be collected and 
analyzed centrally (as specified in Table 3 and Table 4; see Table 7 for the SoA for all 
participants as of Protocol Amendment 3).  During the treatment period, development of 
hypercalcemia (corrected serum calcium > 11.5 mg/dL or > 2.8 mmol/L) can indicate disease 
progression or relapse if it is not attributable to any other cause (see disease response criteria, 
Table 19).  Calcium binds to albumin, and only the unbound (free) calcium is biologically active; 
therefore, the serum calcium level must be adjusted for abnormal albumin levels ("corrected 
serum calcium").  Measurement of free ionized calcium is an acceptable alternative to corrected 
serum calcium for determining hypercalcemia.  Free ionized calcium levels greater than the ULN 
(local laboratory reference ranges) are considered as having achieve a CR or sCR. 


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8.2.1.4. 
β2-microglobulin and Albumin 
Blood samples for β2 microglobulin and albumin are to be collected at screening and will be 
analyzed by the central laboratory.  The central laboratory values will be used for the 
International Staging System calculation. 
8.2.1.5. 
Bone Marrow Examination 
Bone marrow assessments to be performed locally and centrally are summarized in Table 20. 
Table 20: 
Bone Marrow Testing 
 
Local Testing 
Central Testing 
Screening Disease characterization (morphology 
and either immunohistochemistry or 
immunofluorescence or flow cytometry).  
Cytogenetics by conventional karyotype 
or FISH. 
MRD assessment:  a portion of the bone 
marrow aspirate collected at screening will be 
sent to the central laboratory (see 
Section 8.2.1.6). 
A fresh bone marrow aspirate is preferred, but 
if a fresh bone marrow aspirate is not 
performed at screening because a sample is 
available within 42 days before administration 
of study treatment, obtain non-decalcified 
slides (bone marrow aspirate, touch 
preparation, or clot selection) or FFPE block 
(clot section only, no bone marrow biopsy). 
CR, sCR 
For response confirmation, additional 
bone marrow aspirates or biopsies (or 
both) will be performed locally to 
confirm sCR or CR.  Response 
characterization (morphology by 
immunohistochemistry or 
immunofluorescence or flow cytometry). 
For sCR:  Detection of kappa/lambda 
ratio by 2-4 color flow cytometry is 
strongly preferred.  If flow cytometry is 
not available at site, either 
immunohistochemistry or 
immunofluorescence can be done; 
however, kappa/lambda ratio from 
analysis of  100 plasma cells is required 
to confirm sCR. 
If sCR is not met, repeat local testing for 
sCR with subsequent bone marrow 
examinations will be performed. 
MRD assessment:  a portion of the bone 
marrow aspirate collected for confirmation of 
CR/sCR will be sent to the central laboratory 
for MRD assessment.  For participants who 
achieve CR and remain on study, an 
additional bone marrow aspirate will be 
obtained as indicated in Table 3. 
CR = complete response; FFPE = formalin-fixed, paraffin-embedded; FISH = fluorescence in situ hybridization; 
MRD = minimal residual disease; sCR = stringent complete response. 


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8.2.1.6. 
Minimal Residual Disease Assessment 
Bone marrow aspirate will be collected for MRD analysis, when bone marrow samples are 
obtained at screening, confirmation of CR/sCR, and subsequent timepoints after the first dose 
(see Table 20).  Baseline bone marrow aspirate samples will be subjected to DNA sequencing to 
establish a MM clone for MRD monitoring.  A fresh bone marrow aspirate at screening is 
required, if possible.  By exception, non-decalcified diagnostic tissue slides (bone marrow 
aspirate, touch preparation or clot selection) or FFPE block (clot selection only, no bone marrow 
biopsy) may be supplied for MRD assessment.  For participants who achieve a CR, bone marrow 
aspirates will be used for assessment of MRD by NGS of Ig heavy and light chains.  If this 
methodology is unavailable, or determined to be scientifically inferior, then alternative methods 
for MRD assessment may be used. 
8.2.1.7. 
Assessment of Lytic Disease 
A complete skeletal survey (including skull, entire vertebral column, pelvis, chest, humeri, 
femora, and any other bones for which the investigator suspects involvement by disease) is to be 
performed and evaluated by the local laboratory by roentgenography (or the local standard of 
care imaging, eg, low-dose whole body CT) during the screening period.  Please note that the 
same methodology used at screening should be used throughout the study for comparison 
purposes.  During the treatment period and before disease progression is confirmed, imaging 
should be performed whenever clinically indicated based on symptoms or to document response 
or progression.  Magnetic resonance imaging is an acceptable method for evaluation of bone 
disease and may be included as an additional assessment at the discretion of the investigator (see 
the disease response criteria in Table 19). 
Participants may show disease progression manifested by symptoms of pain due to bone 
changes.  Therefore, disease progression may be documented, in these cases, by skeletal survey 
or other radiographs, depending on the symptoms that the participant experiences.  If the 
diagnosis of disease progression is obvious by radiographic investigations, then no repeat 
confirmatory imaging is necessary.  In instances where changes may be subtler, repeat imaging 
may be performed in 1 to 3 weeks according to investigator discretion. 
8.2.1.8. 
Assessment of Extramedullary Plasmacytomas 
Sites of known extramedullary plasmacytomas must be documented during the screening period.  
Clinical examination or MRI may be used to document extramedullary sites of disease.  
Computed tomography scan evaluations are an acceptable alternative if there is no 
contraindication to the use of IV contrast.  Positron emission tomography scan alone (ie, without 
a CT) or ultrasound tests are not acceptable to document the size of extramedullary 
plasmacytomas. 
Extramedullary plasmacytomas should be assessed for all participants with a history of 
plasmacytomas or if clinically indicated at screening, by clinical examination or radiologic 
imaging.  For participants with a history of plasmacytomas assessed by physical examination, 
physical examination should be repeated on Cycle 1 Day 1 if not done within 14 days before 
administration of study treatment.  Assessment of measurable sites of extramedullary disease 
will be performed and evaluated locally approximately every 4 weeks by physical examination 
or approximately every 12 weeks by imaging (if required) for participants with a history of 


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plasmacytomas or as clinically indicated during treatment for other participants, until 
development of confirmed CR or confirmed disease progression.  For every participant, the 
methodology used for evaluation of each disease site should be consistent across all visits.  
Irradiated or excised lesions will be considered not measurable and will be monitored only for 
disease progression. 
To qualify for PR, the sum of products of the perpendicular diameters of the existing 
extramedullary plasmacytomas must have decreased by at least 50%, and new plasmacytomas 
must not have developed (see the disease response criteria in Table 19).  To qualify for disease 
progression, either the sum of products of the perpendicular diameters of the existing 
extramedullary plasmacytomas must have increased by at least 50% or a new plasmacytoma 
must have developed.  In the cases where not all existing extramedullary plasmacytomas are 
reported, but the sum of products of the perpendicular diameters of the reported plasmacytomas 
have increased by at least 50%, this will also qualify as disease progression. 
8.2.2. 
Health Economics 
Not applicable. 
8.3. 
Safety Assessments 
See Section 6.7 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
NOTE:  As of Protocol Amendment 3, safety assessments are only required to be performed as 
per the site standard of care guidelines for the participant's condition and monitoring.  Only 
SAEs, AESIs, and pregnancy will be collected in the eCRF. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
28 days after the last dose of study drug.  Immune-related AEs will be collected until 90 days after 
the last dose of study drug.  Adverse events that begin or worsen after informed consent should be 
recorded on the Adverse Events Form in the eCRF regardless of the assumption of a causal 
relationship with the study drug.  Conditions that were already present at the time of informed 
consent should be recorded on the Medical History Form in the eCRF.  Adverse events 
(including laboratory abnormalities that constitute AEs) should be described using a diagnosis 
whenever possible rather than by individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following-up on AEs that are serious, 
considered related to the study treatment/procedures, or that caused the participant to discontinue 
the study treatment.  Care will be taken not to introduce bias when detecting AEs and/or SAEs.  
Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?" is the preferred method to inquire about AE occurrences.  Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits, or through physical examinations, laboratory tests, or other assessments.  The definition, 
reporting, and recording requirements for AEs are described in Section 9. 


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All SAEs will be recorded and reported to the sponsor or designee within 24 hours.  The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs, and nonserious AESIs (as defined in Section 9.5), 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). 
8.3.2. 
Forced Expiratory Volume Test 
Participants with known or suspected COPD or asthma must have an FEV1 test during 
screening.  See Section 6.5.1.2 for details on participants with higher risk of respiratory 
complications. 
8.3.3. 
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. 
8.3.3.1. 
Comprehensive Physical Examination 
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 brief 
neurological examination. 
8.3.3.2. 
Targeted Physical Examination 
The targeted physical examination will be a symptom-directed evaluation.  The targeted physical 
examination will include body weight and assessment(s) of the body systems or organs, as 
indicated by participant symptoms, AEs, or other findings. 
8.3.4. 
Vital Signs 
Vital sign measurements (to be taken before blood collection for laboratory tests), include blood 
pressure, pulse, respiratory rate, body temperature.  Blood pressure and pulse will be taken with 
the participant in the recumbent, semirecumbent, or sitting position after 5 minutes of rest.  
Weight will also be assessed at each study visit.  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. 
8.3.5. 
Electrocardiograms 
Electrocardiograms (triplicate 12-lead ECGs) will be obtained using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.  All 


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12-lead ECGs will be performed in triplicate (within approximately 15 minutes) with the 
participant in a recumbent or semirecumbent position after 5 minutes of rest.  Whenever 
possible, ECGs should be performed immediately before chemistry 
 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 withdraw a 
participant from the 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.   
8.3.6. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group performance status will be used to evaluate the effect of 
the disease status on the activities of daily living according to the criteria in Table 21.  When 
scheduled, ECOG performance status assessments should be obtained before any other study 
procedures planned for the same day whenever possible. 
Table 21: 
ECOG Performance Status 
Grade  
Performance Status  
0  
Fully active, able to carry on all pre-disease performance without restriction. 
1  
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work. 
2  
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up and 
about more than 50% of waking hours. 
3  
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4  
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5  
Dead. 
Source:  Oken et al 1982. 
8.3.7. 
Laboratory Assessments 
See Table 22 for the list of clinical laboratory tests to be performed and the Schedule of 
Laboratory Assessments (see Table 5 and Table 6) for the timing and frequency.  A certified 
laboratory local to the investigative site will perform most of the clinical laboratory assessments 
for safety (ie, blood chemistries, hematology assessments, lipid panel, thyroid panel, and 
urinalysis).  All local laboratory assessments should be performed using standard procedures on 
the days indicated in Table 5 and Table 6.  Table 22 lists the specific laboratory analytes required 
for each test.  Some additional tests (ie, 
 urinary orotic acid; 
see Table 23) will be conducted by 1 or more central laboratories, on the days indicated in 
Table 5 and Table 6.  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 
(or until start if a new anticancer therapy) 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 7 days of Cycle 1 Day 1.  If 
performed more than 7 days before Cycle 1 Day 1, then the tests must be repeated and eligibility 
confirmed before study treatment administration on Cycle 1 Day 1.  Laboratory samples 
collected on study Day 1 must be performed before study treatment administration.  After 
Cycle 1, predose laboratory procedures can be conducted up to 72 hours before study treatment 
administration (within the study windows indicated in Table 3 and Table 4; Table 5 and Table 6; 
see Table 7 for the SoA for all participants as of Protocol Amendment 3), and results should be 
reviewed by the investigator or qualified designee and found to be acceptable before a new cycle 
of treatment is initiated. 
NOTE:  As of Protocol Amendment 3, laboratory assessments should be performed in 
accordance with the standard of care of the investigational site for the participant's condition.  
Laboratory results do not need to be reported in the eCRF, but all laboratory results 
corresponding with an SAE or an AESI will be reported on the SAE form.  In addition, 
pregnancy testing will continue to be performed for all participants as per the SoA in Table 7.


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Table 22: 
Required Laboratory Analytes 
Chemistries 
Hematology 
Urinalysis With Microscopic 
Examination 
Serologya 
Albumin 
Alkaline phosphatase 
ALT 
Ammonia 
Amylase 
 
AST 
Bicarbonate or CO2  
BUN or urea  
Calcium 
Chloride 
Creatinine 
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 
• White blood cell count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
 
Absolute values must be provided 
for: 
• WBC differential laboratory 
results 
 
• Blood type testc 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Orotic acidb 
Protein 
Hepatitis B surface antigen 
Hepatitis B surface antigen antibody 
Hepatitis B core antibody 
HBV DNA 
HCV antibody 
HCV RNA 
HIV RNA (if required by local 
regulations) 
Lipid Panel 
Pregnancy Testing 
Total cholesterol 
Triglycerides 
LDL 
HDL 
Female participants of childbearing 
potential require a serum pregnancy 
test at screening and a urine 
pregnancy test on Day 1 of every 
cycle, at EOT, and as medically 
indicated or per country or 
institutional requirements.   
Pregnancy tests (serum or urine) 
should be repeated if required by local 
regulations. 
Thyroid panel 
TSH 
FT4 
FT3/T3 
Note:  Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data. 
a Hepatitis B and C viral loads by PCR assay only need to be assessed when respective serology results are positive.  Hepatitis B virus DNA does not need to be performed if the 
surface antibody is the only positive result. 
 
 
 
c For participants receiving daratumumab SC (monotherapy or in combination with INCB001158) only. 


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8.3.7.1. 
Blood Type Assessment 
A blood type test will be performed as outlined in Table 22.  CD38 is expressed on erythrocytes 
to a minor extent.  Hemolysis could occur after the administration of daratumumab SC, which 
would confound the blood type assessment.  To be cautious and in case of urgent need for blood 
transfusion, the participant's blood type will be assessed before administration of daratumumab 
SC, and it is recommended that the participants carries a card with the blood type during the 
study at all times. 
8.3.7.2. 
Chemistries 
 
 
  
See Table 5 and Table 6 for sampling time points and the Laboratory Manual for details of how 
to process, store, and ship the samples to the certified central laboratory or laboratories for 
sample analysis. 
8.3.7.3. 
Urinalysis 
Standard urinalysis will be performed as outlined in Table 22, and urinary orotic acid, which is a 
marker of urea cycle inhibition that is a potential side effect of INCB001158 (refer to the IB), 
will be assessed as outlined in Table 23.  Participants must fast at least 8 hours before each clinic 
visit and void their bladder in the morning before providing the predose urine sample at the 
clinic. 
Table 23: 
Sample Collection Times for Assessments of Urinary Orotic Acid 
Study Visit 
Time 
C1D1 
Predose and 6 h (± 1 h) postdose 
C1D8a 
Predose 
C1D15 
Predose and 6 h (± 1 h) postdose 
C2D1 and D1 of all subsequent cycles 
Predose 
Note:  Additional samples may be collected as clinically indicated.  
a The C1D8 sample will be collected only for participants enrolled in Phase 1. 
8.3.7.4. 
Plasma Ammonia 
Plasma ammonia levels are to be tested during screening (see Table 5 and Table 6).  If above the 
ULN, repeat the sample to confirm the value.  If the participant experiences an elevation in urine 
orotic acid (> 10 × ULN fasted or > 40 × ULN of any value) while on study treatment or during 
the follow-up period, monitor plasma ammonia levels each time the urine orotic acid is tested, at 
least until orotic acid levels have returned to normal, at the investigator's and medical monitor's 
discretion. 


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8.3.7.5. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential during 
screening.  Urine pregnancy tests will be performed locally as outlined in Table 5 and Table 6, as 
medically indicated (eg, in case of loss of menstrual cycle, when pregnancy is suspected), or per 
country-specific requirement (note that country-required urine pregnancy testing will be outlined 
and communicated to investigational sites under separate cover).  If a urine pregnancy test is 
positive, the results should be confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study treatment and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.7 for reporting 
requirements. 
8.3.7.6. 
Serology 
Hepatitis and HIV screening assessments will be performed at the screening visit (see Table 5) to 
rule out hepatitis and HIV infection, respectively; required analytes are shown in Table 22. 
Participants who are positive for anti-HBs or anti-HBc will undergo testing for HBV DNA by 
PCR as specified in Table 5 and Table 6.  Participants with serologic findings suggestive of HBV 
vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior 
HBV vaccination do not need to be tested for HBV DNA by PCR. 
Generally, hepatitis and HIV tests should be performed early in the screening process due to the 
length of time needed to obtain the results.  Additional tests may be performed if clinically 
indicated. 


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8.6. 
Unscheduled Visits 
Unscheduled study visits may occur at any time if medically warranted.  Any assessments 
performed at those visits should be recorded in the eCRF. 
8.7. 
End of Treatment and/or Early Termination 
When the participant permanently discontinues all study treatment, 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. 
8.8. 
Follow-Up 
8.8.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 28 to 35 days after the EOT visit (or after the last dose of study 
treatment if the EOT visit was not performed).  Adverse events and SAEs must be reported up 


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until 1) at least 28 days after the last dose of study treatment and 90 days for irAEs 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, the participant should be 
contacted by telephone for assessment of AEs and SAEs, and this contact should be documented 
in the source. 
If a participant is scheduled to begin a new anticancer therapy before the end of the 28- to 35-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 survival follow-up period. 
NOTE:  As of Protocol Amendment 3, data will only be collected for SAEs, AESIs, and 
pregnancy.  Once a new anticancer therapy has been initiated, the participant will no longer be 
followed for survival follow-up beyond the last safety follow-up visit. 
8.8.2. 
Disease Status Follow-Up 
Participants who discontinue study treatment for a reason other than disease progression will 
move into the disease status follow-up period and should be assessed every 8 weeks ± 7 days 
after EOT to monitor disease status.  Every effort should be made to collect information 
regarding disease status until: 
• The start of new anticancer therapy. 
• Disease progression. 
• Death. 
• The end of the study. 
NOTE:  As of Protocol Amendment 3, disease status follow-up visits for participants who 
discontinue study treatment for a reason other than disease progression are no longer required 
beyond the safety follow-up visit.  The last disease status follow-up data will be recorded in the 
eCRF at the time of the safety follow-up visit.  The last study visit will be the safety follow-up 
visit. 
8.8.3. 
Survival Follow-Up 
Once a participant has received the last dose of study drug, has confirmed disease progression, or 
starts a new anticancer therapy, the participant moves into the survival follow-up period and 
should be contacted by telephone, email, or visit at least every 12 weeks following EOT to assess 
for survival status until death, withdrawal of consent, or the end of the study, whichever occurs 
first. 
For participants having entered the survival follow-up period of the study, the site will use 
continuing participant records to supply data on subsequent treatment regimens, disease 
assessments (if discontinued treatment for a reason other than progression), and OS in the eCRF.  
For participants who do not intend to return to the study investigator for their ongoing care, 
follow-up should be maintained by phone contact, patient records, and public records/databases 
at intervals of no longer than 12 weeks. 


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NOTE:  As of Protocol Amendment 3, the survival follow-up visits for participants who 
discontinue study treatment for a reason other than disease progression are no longer required 
beyond the safety follow-up visit.  The last survival follow-up data will be recorded in the eCRF 
at the time of the safety follow-up visit.  The last study visit will be the safety follow-up visit. 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
NOTE:  As of Protocol Amendment 3, the only safety data that will be collected will be related 
to SAEs, AESIs, and pregnancy.  The safety follow-up visits may be completed remotely (such 
as by televisit). 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug-related. 
• An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 
treatment. 
Additional Guidance for Events Meeting the Adverse Event Definition  
• Any safety assessments (eg, ECG, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study treatment.  Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded 
in the eCRF rather than the abnormal lab result (eg, low hemoglobin, platelet count decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after study treatment administration are to be reported as an 
AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dosing errors of a study treatment (eg, overdose) or a concomitant 
medication are to be reported as an AE. 
• "Lack of efficacy," "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy assessments. 
• A condition that leads to a medical or surgical procedure (eg, endoscopy, appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent, and the procedure is to be 
documented as well.  If the condition is present before entering the study, then it should be captured 
as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 


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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 or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) are not considered SAEs. 
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. Is an important medical event (Important Medical Event) 
An important medical event is 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 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, or suspected transmission of an 
infectious agent via a medicinal product.  Secondary malignancies should always be considered SAEs. 
Suspected transmission of an infectious agent via a medicinal product is also to be considered an SAE. 


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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 rare 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.  These records can be submitted to Incyte 
Pharmacovigilance by email/fax per the contact information listed in the Study Reference Manual or 
as per SAE completing guidelines. 
• 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 v5.0 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 
(including INCB001158 and/or daratumumab SC):  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 safety follow-up visit. 
• The action taken with regard to INCB001158 and/or daratumumab SC as a result of the AE/SAE(s). 
• 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 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 v5.0 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. 


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• 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.  If appropriate, the relationship to the combination may be assessed as well. 
• 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 respective INCB001158 
and daratumumab IBs, or Darzalex/Darzalex FASPRO Product Information, in making 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 based on the available information 
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. 
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. 
• Once an AE is detected, it should be followed in the AE eCRFs 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 treatment, the interventions required 
to treat the event, and the outcome. 
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance (either via email/fax if paper SAE form is used or in the SAE EDC CRF) until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 


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9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study treatment, or study procedure[s]), all 
SAEs occurring after the participant has signed the ICF through 28 days after the last dose of 
study drug 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.  Serious AEs that are irAEs must be reported until 90 days 
after the last dose of study drug.  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.  If the investigator learns of any SAE, including death, at any time during 
this period, 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, and nonserious AESIs (as defined in Section 9.5), 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 a 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 Reference Safety Information in the respective INCB001158 
and daratumumab IBs, or Darzalex/Darzalex FASPRO Product Information (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 expedited 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 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 IB and will notify the IRB/IEC, if appropriate according to local requirements. 
NOTE:  As of Protocol Amendment 3, all SAEs regardless of causality relationship will continue 
to be reported in the eCRF. 


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Serious Adverse Event Reporting 
 Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF.   
 The investigator must report within 24 hours of learning of its occurrence any SAE via the EDC 
system (primary method) or by completing the Serious Adverse Event Report Form in English (only 
if the EDC system is not available.  The contact information for Incyte Pharmacovigilance by 
email/fax is listed in the Study Reference Manual or as per the Incyte Reference Guide for 
Completing the Serious Adverse Event Report Form). 
 In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Report Form.  Once the EDC system is functional, the 
SAE report should be retrospectively added to the EDC system and follow-up should be completed 
through the EDC.  The original copy of the Serious Adverse Event Report Form and the email or 
facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference Guide for 
Completing the Serious Adverse Report Form or Study Reference Manual for details and for the 
email address or fax number). 
 Follow-up information is recorded in the eCRF and transmitted to Incyte Pharmacovigilance via the 
EDC system.  The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study treatment 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. 
9.5. 
Adverse Events of Special Interest 
Adverse events that are potentially immune-related or related to urea cycle inhibition will be 
assessed as AESIs that must rapidly be communicated to Incyte for further evaluation. Adverse 
events of special interest may be laboratory abnormalities or clinical AEs. 
The description of the AESI should generally include the following: 
 The definition of the event 
 Whether it is a measurable quantity.  If so, how will the measurement be done? 
 Whether it is a clinical event.  If so, how will it be confirmed? 
Adverse events of special interest should be captured in the eCRF, and/or be provided as 
expedited reporting from investigators to Incyte's Pharmacovigilance department. 
NOTE:  As of Protocol Amendment 3, all AESIs will continue to be reported in the eCRF. 
9.6. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 


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9.7. 
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 or Study Reference Manual. 
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. 
NOTE:  As of Protocol Amendment 3, pregnancy will continue to be reported in the eCRF. 
9.8. 
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. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 


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All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9.10. 
Treatment of Overdose 
Overdose, as defined for this study, refers to the use of study treatment in doses exceeding those 
specified in the protocol.  
Incyte does not recommend specific treatment of overdose.  Treatment of overdose should 
consist of general supportive measures.  In the event of an overdose with INCB001158, the 
participant should be observed closely for signs of toxicity. 
Daratumumab SC is provided as a single vial for administration by a health care professional. 
Thus, the risk of overdose with daratumumab SC is negligible.  There is no known specific 
antidote for daratumumab overdose. In the event of an overdose of daratumumab SC, the 
participant should be monitored for any signs or symptoms of adverse effects and appropriate 
symptomatic treatment should be instituted immediately.  
10. 
STATISTICS 
10.1. 
Sample Size Determination 
10.1.1. 
Sample Size for Phase 1 
In Phase 1, the BOIN design will be used to determine the RP2D of INCB001158 given in 
combination with daratumumab SC, in participants with relapsed or refractory MM.  Dose 
escalation and de-escalation will follow the BOIN design algorithm.  Based on this algorithm, a 
minimum of 3 evaluable participants and a maximum of 9 evaluable participants will be enrolled 
at each tested dose level, so up to 18 evaluable participants will be enrolled in Phase 1.  The 
details of the dose escalation, de-escalation, and elimination rules according to the BOIN design 
are provided in Section 4.1.1. 
10.1.2. 
Sample Size for Phase 2 
In Phase 2, the sample size will be guided by the RAR design based on a Bayesian beta-binomial 
model, which will include within individual treatment groups early termination rules for efficacy 
and early stopping rules for safety.  The proposed RAR design has an expected frequentist 
1-sided Type I error of approximately 10% and power of 78% to detect an improvement in 
response from 20% to 45%.  The response rates for each treatment group will be estimated with 
90% Bayesian credible intervals.   


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The expected number of participants accrued each month is 4, and the expected number of 
months between treatment and assessment of response is 3.  The simulation results for various 
Treatment Group A response rates are presented in Table 26. 
Table 26: 
Estimates of Operating Characteristics for Response Adaptive Design 
True Response 
Rate: 
Treatment Group A 
True Response 
Rate: 
Treatment Group B 
Probability to Reject 
Null Hypothesis 
(Early Termination) 
Expected Sample Size 
in Treatment 
Groups A, B, and C 
(Treatment Group A) 
Average Study 
Duration in 
Months 
20% 
20% 
9.8% (1.2%) 
79.7 (34.7) 
22.9 
35% 
20% 
50.1% (12.1%) 
76.6 (41.4) 
21.8 
40% 
20% 
65.7% (19.8%) 
74.5 (41.5) 
21.0 
45% 
20% 
78.7% (30.0%) 
71.7 (40.6) 
20.0 
Note:  For each simulated study replication, the first 30 participants were equally randomized among Treatment Groups A, B, and 
C, and the next 50 participants were randomized among Treatment Groups A and B using RAR.  Sample size and study 
duration estimates were based on projected enrollment of 4 participants per month and the time to response of 3 months.  
Estimates were based on simulation of 300,000 study replications.  
Descriptive statistics for the ORR, DOR, and other efficacy parameters for Treatment Group C 
will be provided. 
10.2. 
Populations for Analysis 
Table 27 presents the populations for analysis. 
Table 27: 
Populations for Analysis 
Population 
Description 
Enrolled 
All participants who sign the ICF. 
FAS 
All participants enrolled in the study who received at least 1 dose of study treatment 
(INCB001158 or daratumumab SC).  Participants will be analyzed according to the 
treatment that they were assigned to. 
The FAS will be used for the summary of demographics, baseline characteristics, and 
disposition. 
IMWG response 
evaluable 
All participants enrolled in the study who have received at least 1 dose of study 
treatment (INCB001158 or daratumumab SC), completed a baseline disease 
assessment, and meet at least 1 of the following criteria: 
• ≥ 1 postbaseline disease assessment 
• Been on the study for a minimum of 35 days of follow-up 
• Discontinued from treatment 
DLT evaluable 
All participants who receive at least 42 of 56 doses for the 28-day cycle regimen 
(representing ≥ 75% of the dose planned) of INCB001158 at the level assigned or 
who have a DLT. 
 
 
 
 
 
 
 


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10.3. 
Level of Significance 
The test for the primary efficacy analysis in Phase 2 has approximately a 1-sided 10% Type I 
error level.  Other secondary 
 endpoints will be compared using a 2-sided, 
5% significance level but are not considered alpha-controlled hypotheses. 
10.4. 
Statistical Analyses 
10.4.1. 
Efficacy Analyses 
10.4.1.1. Primary Efficacy Analyses 
The primary endpoint of the Phase 2 portion of the Protocol is ORR, defined as the proportion of 
participants with CR, VGPR, or PR, according to IMWG Criteria in the randomized IMWG 
response evaluable population.  Participants will be summarized by treatment group assignment 
in Phase 2. 
The primary analysis of ORR in Phase 2 will compare Treatment Groups A and B modeling the 
ORR of each treatment group with a Beta (0.5,0.5) prior, calculating the probability that the 
posterior distribution of the ORR for Treatment Group A exceeds that of the posterior 
distribution the ORR for Treatment Group B.  If x1 (n1) is the number of responders (evaluable 
participants) in Treatment Group A and x2 (n2) correspond to the same for Treatment Group B, 
the resulting posterior distribution will be  
 
𝑓𝑖(𝛾𝑖|𝑥𝑖, 𝑛𝑖) =
Γ(𝑛𝑖+ 1)
Γ(𝑥𝑖+ 0.5)Γ(𝑛𝑖+ 0.5 −𝑥𝑖) 𝛾𝑖
𝑥𝑖+0.5(1 −𝛾𝑖) 𝑛𝑖+0.5−𝑥𝑖 
The resulting probability that the ORR for Treatment Group A exceeds that of Treatment 
Group B, that is, the PPoS, is the quantity 
PPoS = Pr(𝑂𝑅𝑅𝐴> 𝑂𝑅𝑅𝐵|𝑥1, 𝑛1, 𝑥2, 𝑛2) = ∫∫𝑓1(𝛾1|𝑥1, 𝑛1)𝑓2(𝛾2|𝑥2, 𝑛2)𝑑𝛾1𝑑𝛾2
1
𝛾2
1
0
 
Objective response rate and its 90% Bayesian credible intervals for each treatment group will be 
presented. 
Interim analyses will be conducted after the 31st participant is randomized and after each 
subsequent participant is to be randomized to adjust the randomization rate between 
Treatment Groups A and B and to determine whether the study should be terminated for positive 
efficacy.  See Section 10.5.2.1 for details on the conduct of these interim analyses. 
If the study does not terminate for early efficacy, the final analysis will take place once all 
participants have been randomized and monitored for response for 3 months OR once all 
participants have discontinued the study.  If PPoS > 0.915, then the null hypothesis will be 
rejected, and Treatment Group A will be considered to be superior (with respect to ORR) to 
Treatment Group B. 


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10.4.1.2. Secondary Efficacy Analyses 
Objective response rate will be summarized descriptively for Phase 1 IMWG response evaluable 
participants. 
Time to response is defined as the number of days from the randomization in Phase 2 (or first 
dose of study drug in Phase 1) to the first documented response of PR, VGPR, or CR (as per 
IMWG criteria).  Time to response will be summarized descriptively by assigned treatment 
group in Phase 2 and by dose level in Phase 1. 
Duration of response is defined as the number of days from earliest date of PR, VGPR, or CR (as 
per IMWG criteria) until the earliest date of disease progression, relapse, or death due to any 
cause.  Duration of response will be summarized descriptively by assigned treatment group in 
Phase 2 and by dose level in Phase 1. 
Progression-free survival is defined as the duration from the date of first dose of study drug until 
either progressive disease, as per IMWG criteria, or death, whichever occurs first.  
Progression-free survival will be summarized descriptively by assigned treatment group in 
Phase 2 and by dose level in Phase 1. 
Minimal residual disease rate is defined as the percentage of participants who are considered 
MRD negative by IMWG criteria at any time after randomization in Phase 2 or first dose of 
study drug in Phase 1.  The MRD rate will be estimated with 95% binomial confidence intervals 
provided. 
Overall survival is defined as the number of days from randomization in Phase 2 (or first dose of 
study drug in Phase 2) to death due to any cause.  Overall survival will be summarized 
descriptively by assigned treatment group in Phase 2 and by dose level in Phase 1. 
10.4.2. 
Safety Analyses 
10.4.2.1. Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug.  Analysis of AEs will be limited to TEAEs, but data listings will include 
all AEs regardless of their timing to study drug administration.  Adverse events will be tabulated 
by the MedDRA preferred term and system organ class for all events and AESIs, including irAEs 
and potential inhibition of the urea cycle (based on urinary orotic acid, plasma ammonia and 
urea/BUN assessments).  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, then the AE will be considered treatment-related.  The incidence of AEs 
and treatment-related AEs will be tabulated. 
Periodic safety stopping rules will be applied in the Phase 2 portion of the study.  See 
Section 10.5.2.2 for details regarding these interim safety analyses. 


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10.4.2.2. Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory.  The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. 
Laboratory data will be classified into Grades 1 through 5 using CTCAE v5.  The following 
summaries will be produced for the laboratory data: 
• Number and percentage of participants with worst postbaseline CTCAE grade 
(regardless of baseline value).  Each participant will be counted only for the worst 
grade observed postbaseline. 
• Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
For laboratory parameters where CTCAE grades are not defined, shift tables to the worst 
postbaseline value using the low/normal/high classifications based on laboratory reference 
ranges. 
10.4.2.3. Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature) at each assessment time.  Vital sign 
results will be reviewed for clinically notable abnormalities (see Table 28), and participants 
exhibiting clinically notable vital sign abnormalities will be listed.  A value will be considered an 
"alert" value if it is outside the established range and shows a > 25% change from baseline. 
Table 28: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter  
High Threshold 
Low Threshold 
Systolic blood pressure  
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure  
> 100 mmHg 
< 40 mmHg 
Pulse  
> 100 beats/min 
< 45 beats/min 
Temperature  
> 38ºC 
< 35.5ºC 
Respiratory rate  
> 24 breaths/min 
< 8 breaths/min 
10.4.2.4. Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Electrocardiogram results will be reviewed for clinically notable 
abnormalities according to predefined criteria (see Table 29).  Participants exhibiting clinically 
notable ECG abnormalities will be listed. 


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Table 29: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 470 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 
QTcF = Fridericia correction. 
10.4.2.5. Adverse Events of Special Interest 
Adverse events of special interest include irAEs that are seen with immunotherapy and potential 
inhibition of the urea cycle (based on urinary orotic acid, plasma ammonia, and BUN/urea 
assessments). 
An overall summary of irAEs will include number (%) of participants reporting any irAEs, any 
Grade 3 or higher irAEs, any treatment-related irAEs, any fatal irAEs, and any irAEs leading to 
treatment interruption/dose reduction/discontinuation. 
10.5. 
Interim Analysis 
The Statistical Analysis Plan will describe the planned interim analyses in greater detail. 
10.5.1. 
Interim Analysis for Phase 1 
In Phase 1, the BOIN design will be used to determine the RP2D of INCB001158 in combination 
with daratumumab SC.  For the design parameters, let 𝜙 denote the target DLT rate.  Let 𝜙1 
(= 0.6𝜙) denote the highest toxicity probability below the MTD so that dose escalation is 


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required, and 𝜙2 (= 1.4𝜙) denote the lowest toxicity probability deemed overly toxic so that dose 
de-escalation is required. 
A dose elimination rule is also applied to avoid assigning participants to an overly toxic dose.  
Let 𝑝𝑗 represent the DLT rate, 𝑛𝑗 the participants in the treatment group treated at dose level j, 
and 𝑚𝑗 the participants with a DLT at dose level 𝑗.  If 𝑃𝑟(𝑝𝑗> 𝜙|𝑚𝑗, 𝑛𝑗) > 0.95 and 𝑛𝑗≥3, 
then dose levels 𝑗 and higher are eliminated from the dose escalation for the treatment group, and 
the dose level is terminated if the first dose level is eliminated. 
Table 11 (in the bottom row) provides the elimination boundaries for the target DLT rate of 33%, 
respectively.  For example, for the target DLT rate 33%, when the number of participants treated 
at the current dose 𝑛𝑗= 4, we will eliminate that dose and higher doses if 3 or more participants 
experience toxicity. 
Based on the algorithm of the BOIN design, a minimum of 3 evaluable participants will be 
enrolled in each dose level with a maximum of 9 evaluable participants in each dose level. 
10.5.2. 
Interim Analysis for Phase 2 
10.5.2.1. Efficacy Interim Analysis for Phase 2  
In Phase 2, a RAR design will be used to adjust randomization between Treatment Groups A and 
B and to determine if the study should be terminated for superior efficacy.  The first 
30 participants will be equally randomized (1:1:1) between Treatment Groups A, B and C.  From 
the 31st participant, adaptive randomization will begin based on the PPoS (as defined in 
Section 10.4.1.1), comparing Treatment Group A to B ORR using posterior probabilities with the 
probability of assignment to Treatment Group A being  
Randomization Probability = {
0.2
𝑖𝑓 𝑃𝑃𝑜𝑆< 0.2
0.8
𝑖𝑓 𝑃𝑃𝑜𝑆> 0.8
𝑃𝑃𝑜𝑆
𝑜𝑡ℎ𝑒𝑟𝑤𝑖𝑠𝑒
 
If during randomization PPoS > 0.9975, then the study will be terminated for superior efficacy.  
Properties of the design parameters, including likelihood of early termination for efficacy and 
expected sample sizes, are provided in Section 10.1.2, Table 26.  Stopping rules will also be 
applied in the event of unacceptable toxicity and are provided in Section 10.5.2.2.  Up to 
50 participants will be adaptively randomized to expansion Treatment Groups A and B.  
10.5.2.2. Safety Interim Analysis for Phase 2  
Stopping rules will be applied using the historical rate of Grade 4 or higher AEs for 
daratumumab monotherapy as the endpoint in question for potential early stopping for safety.  
The expected proportion of participants experiencing such AEs is approximately 19.2% (30/156) 
in participants receiving daratumumab monotherapy (see Appendix 3 of the daratumumab IB).  
Table 30 provides the resulting stopping boundaries for various numbers of evaluable 
participants and will use the Pocock-type boundary (Ivanova et al 2005). 
The boundary was selected using a 10% Type 1 error for stopping when the true rate of Grade 4 
or higher AEs is 19.2% assuming a maximum sample size of 55 participants.  If 55 participants 
are to be treated in the INCB001158 + daratumumab treatment group and the treatment group 
has a true Grade 4 or higher AE rate of 40%, the resulting rule has a 96% probability to halt 


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enrollment to the study with a probability of approximately 12% if the AE rate is only 20%.  If 
only 40 participants are randomized and treated with INCB001158 + daratumumab, then the rule 
has an 89% probability to halt enrollment to the study and a probability of approximately 10% if 
the AE rate is only 20%. 
Table 30: 
Pocock-Like Boundaries for Treatment Group A (INCB001158 + 
Daratumumab) 
Boundaries 
No. of Participants 
Number of evaluable  
participants 
3-4 
5-6 
7-9 
10-13 
14-16 
17-20 
21-23 
24-27 
28-31 
Halt enrollment if 
Grade 4 and 5 AEs 
observed in ≥ 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Number of evaluable  
participants 
32-35 
36-39 
40-43 
44-47 
48-51 
52-55 
 
 
 
Halt enrollment if 
Grade 4 and 5 AEs 
observed in ≥ 
12 
13 
14 
15 
16 
17 
 
 
 
 
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 IRB/IEC approval 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. 


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− 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. 
− 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 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 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. 


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The sponsor (or designee) will be responsible for: 
• The data management of this study including quality checking of the data. 
• 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. 
The investigator will be responsible for: 
• Ensuring participant data relating to the study is recorded in the eCRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data, diary data) 
or as otherwise specified in the Protocol.  The investigator is responsible for verifying 
that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF. 
− 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 reported on the CRF or 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 medical records 
must be available. 
• 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. 


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− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
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).  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. 
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. 


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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 (Incyte), for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 
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 
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 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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2017;5:101. 
Timosenko E, Hadjinicolaou AV, Cerundolo V. Modulation of cancer-specific immune 
responses by amino acid degrading enzymes. Immunotherapy 2017;9:83-97. 
Usmani SZ, Nahi H, Mateos M-V, et al. Open-label, multicenter, dose escalation Phase 1b study 
to assess the subcutaneous delivery of daratumumab in patients (pts) with relapsed or refractory 
multiple myeloma (PAVO). Blood 2016;128:1149. 


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van de Donk NWCJ, Usmani SZ. CD38 antibodies in multiple myeloma: mechanisms of action 
and modes of resistance. Front Immunol 2018;9:2134. 
Verrotti A, Trotta D, Morgese G, Chiarelli F. Valproate-induced hyperammonemic 
encephalopathy. Metab Brain Dis 2002;17:367-373. 
Wadzinski J, Franks R, Roane D, Bayard M. Valproate-associated hyperammonemic 
encephalopathy. J Am Board Fam Med 2007;20:499-502. 
Yuan Y, Liu S. BOIN: Bayesian Optimal INterval (BOIN) Design for Single-Agent and 
Drug-Combination Phase I Clinical Trials. R Package Version 2.6.4. 2016. http://CRAN.R-
project.org/package=BOIN. Accessed March 13, 2018. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For male participants in the study: 
Male participants should use a condom from screening through 90 days after the end of systemic 
exposure.  If the male participant has a partner that is of child-bearing potential, the partner should also 
use contraception through 90 days after the end of relevant systemic exposure.  In addition, male 
participants must refrain from donating sperm from screening through 90 days after the end of relevant 
systemic exposure.  Males who have had a vasectomy qualify as having met the requirement for a 
highly effective birth control method. 
For female participants in the study: 
The following methods that can achieve a failure rate of less than 1% per year when used consistently 
and correctly are considered as highly effective birth control methods: 
• 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulationa 
− 
oral 
− 
intravaginal 
− 
transdermal 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulationa 
− 
oral 
− 
injectable 
− 
implantableb 
• 
Intrauterine deviceb 
• 
Intrauterine hormone-releasing systemb 
• 
Bilateral tubal occlusionb 
• 
Vasectomized partnerbc 
• 
Sexual abstinenced 
Acceptable birth control methods that result in a failure rate of more than 1% per year include: 
• 
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary 
mode of action 
• 
Male or female condom with or without spermicidee 
• 
Cap, diaphragm, or sponge with spermicidee 
• 
Tubal ligation 
a Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may 
reduce the efficacy of the contraception method. 
b Contraception methods that in the context of this guidance are considered to have low user dependency. 
c Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual 
partner of the woman of childbearing potential study participant and that the vasectomized partner has received 
medical assessment of the surgical success. 
d 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. 
e A combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) 
are also considered acceptable, but not highly effective, birth control methods. 
Source:  Clinical Trial Facilitation Group 2014. 


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APPENDIX B. INSTRUCTION TO PARTICIPANTS FOR HANDLING 
STUDY DRUG (INCB001158) 
The participant must be instructed in the handling of study drug as follows: 
• To store the study drug at room temperature. 
• To only remove from the study drug bottle the number of tablets needed at the time of 
administration. 
• Not to remove doses in advance of the next scheduled administration. 
• To make every effort to take doses on schedule. 
• To report any missed doses. 
• To take study drug at approximately the same times each day, without respect to food 
(except on Protocol-defined clinic days when the participant should fast for at least 
8 hours before taking study drug) with a full glass of water.  The second dose on any 
given day should be taken approximately 12 hours after the first dose. 
• If the participant vomits after taking study drug, the participant should not take 
another dose.  The participants should report the frequency of vomiting occurrences 
associated with study drug administration to the site.  
 
 
 
• To keep study drug in a safe place and out of reach of children. 
• To bring all used and unused study drug containers to the site at each visit. 
• Missed doses of INCB001158 should be skipped.  If a participant forgets to take a 
dose of study drug and he/she is outside of the allotted window period (± 6 h), he/she 
should be instructed to skip that dose and NOT take extra study drug at their next 
administration. 
On Protocol-defined clinic days (see Table 3 and Table 4; Table 5 and Table 6; see Table 7 
for the SoA for all participants as of Protocol Amendment 3) participants should be 
instructed NOT to take their morning dose of INCB001158 at home.  The morning dose must 
be administered at the clinical site after all predose procedures have been performed.  The 
time of dose administration will be recorded in the clinic.  The evening doses will be 
self-administered by the participant after all postdose activities have been completed. 


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APPENDIX C. DARATUMUMAB SC DRUG INFORMATION 
Detailed information on the composition of the daratumumab SC is in the SIPPM and the 
daratumumab IPPI. 
Physical Description of Daratumumab SC  
The daratumumab supplied for SC injection (daratumumab SC) in this study is a colorless to 
yellow liquid and sterile concentrate of 120 mg/mL daratumumab + 2000 U/mL rHuPH20 as a 
liquid in vial.  The study agent should be essentially free of visible particulate matter at the time 
of syringe preparation and drug product administration.  Refer to the daratumumab IB for a list 
of excipients. 
Packaging 
Daratumumab SC is supplied in glass vials containing daratumumab at a concentration of 
120 mg/mL and rHuPH20 at a concentration of 2000 U/mL (~20 g/mL).  It will be supplied to 
the site/pharmacy as open-label supply. 
Labelling 
Daratumumab SC labels will contain information to meet the applicable regulatory requirements.  
Each vial will contain a study-specific label with a unique identification number. 
Preparation, Handling, and Storage 
Daratumumab SC Formulation 
Daratumumab SC must be stored in the original carton in a refrigerator at controlled 
temperatures ranging from 2°C to 8°C until it is removed for dose preparation.  Daratumumab 
SC must not be used after the expiry date printed on the label.  Daratumumab SC must be 
protected from light and must not be frozen.  The product does not contain preservatives; 
therefore, any unused portion remaining in the vial must be discarded.  Refer to the IPPI for 
additional guidance on daratumumab SC preparation, handling, and storage. 
Daratumumab SC Preparation 
Daratumumab SC is a fixed combination drug product containing rHuPH20 drug substance 
(2000 U/mL) and daratumumab drug substance (120 mg/mL) in a single vial.  Detailed 
instructions for preparation of SC daratumumab will be supplied in the SIPPM and IPPI.  
Daratumumab SC Delivery 
Daratumumab SC will be delivered by SC injection given through a syringe and needle by a 
manual push over approximately 3 to 5 minutes.  Each dose will be administered at alternating 
locations on the abdomen.  The volume of the SC solution will be 15 mL for the 1800 mg dose.  
Refer to the IPPI for additional guidance on SC administration of daratumumab SC.  All 
participants will be observed for at least 6 hours after the end of the SC injection during Cycle 1 
Day 1 and, if deemed necessary by the investigator, after consecutive injections.  


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Participants will receive pre-administration and post-administration medications as detailed in 
Section 6.5.1.  All participants should have vital signs monitored as specified in Table 3 and 
Table 4.  If a participant experiences a significant medical event, then the investigator should 
assess whether the participant should stay overnight for observation.  If the participant has not 
experienced a significant medical event but is hospitalized overnight only for observation, then 
the hospitalization should not be reported as an SAE. 


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APPENDIX D. ANTIHISTAMINES THAT MAY BE USED PREDOSE 
The following antihistamines may be used pre-dose, before daratumumab SC injection 
(including, but not limited to): 
• Diphenhydramine 
• Cetirizine 
• Fexofenadine 
• Loratadine 
• Clemastine 
• Dexchlorpheniramine 
• Promethazine* 
* The IV use of promethazine should be avoided.  


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APPENDIX E. INTERPRETATION OF DARATUMUMAB 
INTERFERENCE REFLEX ASSAY 
Background:  Clinical response assessment in myeloma relies on SPEP and IFE.  As 
daratumumab is a monoclonal IgG kappa antibody, the SPEP and IFE can be positive for 
daratumumab at the serum levels anticipated during this protocol.  
Implementation:  To mitigate this interference, the sponsor has developed the DIRA to 
distinguish a positive SPEP/IFE due to the presence of daratumumab versus the presence of the 
underlying (endogenous) monoclonal protein (McCudden et al 2015).  The DIRA test will be 
sent automatically to the central laboratory if a participant with IgG kappa multiple myeloma has 
an SPEP at or below 0.2 g/dL on 2 or more consecutive cycles.  In addition, the DIRA test will 
be sent automatically to the central laboratory if a participant has an SPEP of 0 but persistently 
positive IFE for IgG kappa on 2 or more occasions. 
Interpretation of Results:  The results will be available to the investigator by the central 
laboratory interface and will be reported as either "POSITIVE" or "NEGATIVE." 
• POSITIVE:  indicates that the sample is still positive for underlying (endogenous) 
monoclonal myeloma protein.  Therefore, this participant is not in a CR, because the 
CR response criteria require a negative SPEP and serum IFE. 
• NEGATIVE:  indicates that the sample is negative for underlying (endogenous) 
monoclonal myeloma protein.  This participant may be in a CR if the other criteria for 
CR (including negative bone marrow aspiration/biopsy) are achieved. 
Source:  McCudden et al 2015. 


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APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1-EU: 
18 MAR 2019 
Amendment (Version) 1-DE: 
16 JUL 2019 
Amendment (Version) 2: 
12 OCT 2020 
Amendment (Version) 3: 
01 DEC 2021 
Amendment 3 (01 DEC 2021) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to provide 
guidance for the management of ongoing participants, as enrollment has been terminated and 
sufficient data have been collected for safety analysis. 
1. Protocol Summary (Table 2:  Key Study Design Elements; Table 7:  Schedule of 
Activities for All Participants [as of Protocol Amendment 3]; Section 4.1, Overall 
Design; Section 4.2, Overall Study Duration; Section 6.3, Measures to Minimize 
Bias:  Randomization and Blinding; Section 6.7.4, Dose Delays and Dose 
Modification of Daratumumab SC; Section 6.8, Concomitant Medications and 
Procedures; Section 7.1.2, Discontinuation Procedures; Section 7.2, Participant 
Withdrawal From the Study; Section 8.2, Efficacy Assessments; Section 8.2.1.1, 
Responses Categories; Section 8.2.1.2, Myeloma Protein Measurements in Serum 
and Urine; Section 8.2.1.3, Serum Calcium Corrected for Albumin; Section 8.3, 
Safety Assessments; Section 8.3.7, Laboratory Assessments; Section 8.8.1, Safety 
Follow-Up; Section 8.8.2, Disease Status Follow-Up; Section 8.8.3, Survival 
Follow-Up; Section 9, Adverse Events:  Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting; Section 9.4, Reporting of Serious Adverse 
Events; Section 9.5, Adverse Events of Special Interest; Section 9.7, Pregnancy; 
Appendix B, Instruction to Participants For Handling Study Drug (INCB001158) 
Description of change:  Study assessments for all participants remaining on study 
treatment have been limited to standard of care for the participant's condition.  Safety 
data will only be collected for SAEs and AESIs, and disease status and survival 
follow-up data will only be collected until the last safety follow-up visit. 
Rationale for change:  To update the study assessments for all ongoing participants.   
2. Protocol Summary (Table 2:  Key Study Design Elements); Section 11.1.1, 
Identification of the Coordinating Principal Investigator 
Description of change:  Included the process for identification of the coordinating 
principal investigator. 
Rationale for change:  To update applicable sections as per current protocol template. 
3. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 
 
 


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Amendment 2 (12 OCT 2020) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to 
introduce a crossover to INCB001158+Daratumumab after Daratumumab monotherapy.  
1. Section 1, Protocol Summary, Figure 1, Study Design Schema, SoA (Tables 3 and 4), 
Schedule of Laboratory Assessments (Tables 5 and 6); Section 2.2.1, Rationale for 
Study Design; Section 4.1, Overall Design; Section 4.1.2, Phase 2:  Expansion and 
Table 11, Treatments for Treatment Groups A, B, and C; Section 6.3, Measures to 
Minimize Bias:  Randomization and Blinding; Section 6.7.4, Dose Delays and Dose 
Modification of Daratumumab SC; Section 7.1.1, Reasons for Discontinuation; 
Section 7.1.2, Discontinuation Procedures; Section 7.2, Participant Withdrawal 
From the Study; Section 8.2.1.1, Responses Categories; Section 8.2.1.2, Myeloma 
Protein Measurements in Serum and Urine; Section 8.2.1.3, Serum Calcium 
Corrected for Albumin; Section 8.3.7, Laboratory Assessments; Section 8.3.7.2, 
Chemistries; Section 8.3.7.4, Plasma Ammonia; Section 8.3.7.5, Pregnancy Testing; 
Section 8.3.7.6, Serology 
Description of change:  Added a crossover to INCB001158+Daratumumab (Treatment 
Group B - Part 2) for participants enrolled in Treatment Group B – Part 1.  
(Daratumumab SC monotherapy) at confirmed PD.  Updated SoA and Laboratory 
Assessments Tables. 
Rationale for change:  Introduce a crossover to combination treatment for patient 
progressing under daratumumab monotherapy, and update the SoA and Schedule of 
Laboratory Assessments prior to and post-crossover. 
2. Section 9.1 Definition of Adverse Event; Section 9.2 Definition of Serious Adverse 
Event; Section 9.3, Recording and Follow-Up of Adverse Events and/or Serious 
Adverse Events; Section 9.4 Reporting of Serious Adverse Events; Section 9.5, 
Adverse Events of Special Interest; Section 9.7, Pregnancy; Section 9.10 Treatment 
of Overdose; Appendix B, Instruction to Participants for Handling Study Drug 
(INCB00158); Appendix C, Daratumumab SC Drug Information 
Description of change: Updated AE definitions, overdose, and SAE reporting via EDC. 
Rationale for change:  Sponsor Pharmacovigilance updated guidance 
3. Section 2.1.4, Daratumumab; Section 2.2.3, Justification for the Dose; Section 2.3, 
Benefit/Risk Assessment; Section 12, References 
Description of change:  Updated background information in relation to the approval of 
the daratumumab subcutaneous formulation in United States of America and European 
Union. 
Rationale for change:  To align with FDA and EMA approvals of Daratumumab SC. 


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4. Section 1, Protocol Summary, Table 2, Key Study Design Elements; Table 3, 
Schedule of Activities for Participants in Phase 1, Phase 2, Treatment Group A, 
Treatment Group B - Part 1 (Prior to Crossover), and Treatment Group C - Part 1 
(Prior to Crossover); Table 5, Schedule of Laboratory Assessments for Participants 
in Phase 1, Phase 2, Treatment Group A, Treatment Group B - Part 1 (Prior to 
Crossover), and Treatment Group C - Part 1 (Prior to Crossover); Section 8.1.2, 
Screening Procedures 
Description of change:  Updated the screening period of time from 21 days to up to 
28 days. 
Rationale for change:  To provide a longer period of time for the screening assessments. 
5. Section 5.5, Replacement of Participants 
Description of change:  Clarified that the participants in Phase 2 may be replaced in case 
of withdrawal before first administration of study treatment.   
Rationale for change:  Clarification on the condition for Phase 2 participant 
replacement. 
6. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 1-DE (16 JUL 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to address 
change requested by the Federal Institute for Drugs and Medical Devices (BfArM) in Germany. 
1. Section 5.2, Exclusion Criteria 
Description of change:  Added new exclusion criterion #15 to exclude participants who 
are candidates for autologous or allogenic transplantation. 
Rationale for change:  Requested by BfArM. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 1-EU (18 MAR 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to update 
the study drug formulation with tablets and to incorporate changes from global 
Amendment 1 requested by the FDA in the United States of America. 
1. Section 6.1, Study Treatment(s) Administrated (Table 11, Study Treatment 
Information); Section 6.2, Preparation, Handling, and Accountability; Section 6.4, 
Study Treatment Compliance; Appendix B, Instruction to Participants for Handling 
Study Drug (INCB001158) 
Description of change:  Clarified that INCB001158 tablet formulation and bottle 
packaging will be used. 
Rationale for change:  Clarification. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 
Changes incorporated from global Amendment 1 (11 MAR 2019): 
1. Section 2.2.1, Rationale for Study Design 
Description of change:  A summary of experimental studies was added to provide 
evidence to support the biologic rationale for the combination.  
2. Section 1, Protocol Summary; Section 2.2.1, Rationale for Study Design; Section 4.1, 
Overall Design; Section 4.1.2, Phase 2: Expansion; Section 5.1, Inclusion Criteria  
Description of change:  Updated to allow for 2 cycles of INCB001158 monotherapy 
instead of 3 cycles in Treatment Group C – Part 1, and to require all participants to have 
had at least 3 prior treatments (including IMiD, PI, and anti-CD38 therapies). 
3. Section 4.1.2, Phase 2 Expansion; Section 10.1.2, Sample Size for Phase 2; 
Section 10.4.2.1, Adverse Events; Section 10.5.2, Interim Analysis for Phase 2 
Description of change: Stopping rules were added for safety in Phase 2. 
4. List of Abbreviations; Section 6.5.2.2, Systemic Injection-Related Reaction  
Description of change:  A revision was made to clarify the definition of injection-related 
reactions and management of IRRs. 


Signature Page for VV-CLIN-000653 v5.0
Signature Page for VV-CLIN-000653 v5.0
Approval
Approver
01-Dec-2021 17:18:45 GMT+0000
Approval
Approver
01-Dec-2021 17:28:01 GMT+0000
Approval
Approver
Clinical Trial Head
02-Dec-2021 17:23:02 GMT+0000
Approval
Biostatistician
02-Dec-2021 20:45:11 GMT+0000

SAP_001.pdf: 
Official Title: 
NCT Number: 
Document Date: 
A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined 
With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, 
in Participants With Relapsed or Refractory Multiple Myeloma
NCT03837509 
Statistical Analysis Plan: 19 April 2022


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Statistical Analysis Plan 
 
 
INCB 01158-206 
A Randomized Open-Label Phase 1/2 Study of INCB001158 
Combined With Subcutaneous (SC) Daratumumab, Compared to 
Daratumumab SC, in Participants With Relapsed or Refractory 
Multiple Myeloma 
Product: 
INCB001158 
IND Number: 
 
EudraCT Number: 
2018-004076-35 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol Amendment 3 dated 01 DEC 2021 
CRF Approval Date: 
09 JUL 2021 
SAP Version: 
Original 
SAP Author: 
 
, Biostatistics 
Date of Plan: 
19 APR 2022 
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 .......................................................................................................10 
3.1. 
Randomization ............................................................................................................10 
3.2. 
Control of Type I Error ...............................................................................................10 
3.3. 
Sample Size Considerations .......................................................................................10 
3.4. 
Schedule of Assessments ............................................................................................11 
4.
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................11 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................11 
4.1.1. 
Day 1 ...........................................................................................................................11 
4.1.2. 
Study Day ...................................................................................................................11 
4.1.3. 
Baseline Value ............................................................................................................11 
4.1.4. 
Handling of Missing and Incomplete 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 ...........................................................................14 
5.1. 
General Methodology .................................................................................................14 
5.2. 
Study Phases and Treatment Groups ..........................................................................14 
5.2.1. 
Phase 1: Dose Escalation ............................................................................................14 
5.2.2. 
Phase 2: Expansion .....................................................................................................14 
5.3. 
Analysis Populations ..................................................................................................14 
5.3.1. 
Enrolled .......................................................................................................................14 
5.3.2. 
Full Analysis Set .........................................................................................................14 
5.3.3. 
DLT Evaluable Population for Phase 1 ......................................................................15 
6.
BASELINE, EXPOSURE, AND DISPOSITION ......................................................15 


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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 Therapy ..............................................................................................................15 
6.1.4. 
Medical History ..........................................................................................................16 
6.2. 
Disposition of Participants ..........................................................................................16 
6.3. 
Protocol Deviations ....................................................................................................16 
6.4. 
Exposure .....................................................................................................................16 
6.4.1. 
Exposure to INCB001158 ...........................................................................................16 
6.4.2. 
Exposure to Daratumumab SC ...................................................................................16 
6.5. 
Study Drug Compliance .............................................................................................17 
6.6. 
Prior and Concomitant Medication .............................................................................17 
7. 
EFFICACY .................................................................................................................18 
7.1. 
General Considerations ...............................................................................................18 
7.2. 
Efficacy Hypotheses ...................................................................................................18 
7.3. 
Analysis of the Efficacy Parameters ...........................................................................18 
7.3.1. 
Primary Efficacy Analysis ..........................................................................................18 
7.3.2. 
Secondary Efficacy Analyses .....................................................................................20 
7.3.2.1. 
Best Overall Response ................................................................................................20 
7.3.2.2. 
Time to Response .......................................................................................................20 
7.3.2.3. 
Duration of Response .................................................................................................20 
7.3.2.4. 
Progression-Free Survival ..........................................................................................20 
7.3.2.5. 
Overall Survival ..........................................................................................................21 
8. 
SAFETY AND TOLERABILITY ..............................................................................21 
8.1. 
General Consideration ................................................................................................21 
8.2. 
Adverse Events ...........................................................................................................21 
8.2.1. 
Adverse Event Definitions ..........................................................................................21 
8.2.2. 
Dose-Limiting Toxicities ............................................................................................22 
8.2.3. 
Adverse Events of Special Interest .............................................................................22 
8.2.4. 
Adverse Event Summaries ..........................................................................................22 
8.3. 
Clinical Laboratory Tests ...........................................................................................23 
8.3.1. 
Laboratory Value Definitions .....................................................................................23 
8.3.2. 
Laboratory Value Summaries .....................................................................................24 


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8.4. 
Vital Signs ..................................................................................................................25 
8.5. 
Electrocardiograms .....................................................................................................25 
9.
INTERIM ANALYSES ..............................................................................................26 
10.
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................26 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................26 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................26 
APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................27 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
International Uniform Response Criteria Consensus Recommendations ...................18 
Table 3: 
Evaluation and Censoring of Progression-Free Survival ............................................20 
Table 4: 
Identification of Baseline Record ...............................................................................24 
Table 5: 
Identification of Records for Postbaseline By-Visit Summaries ................................24 
Table 6: 
Normal Vital Sign Values ...........................................................................................25 
Table 7: 
Statistical Analysis Plan Versions ..............................................................................26 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................10 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
BID 
twice daily 
BOIN 
Bayesian optimal interval 
 
 
CR 
complete response 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
 
 
DLT 
dose-limiting toxicity 
 
 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
FAS 
full analysis set 
FLC 
free light chain 
 
IMiD 
immunomodulatory drug 
IMWG 
International Myeloma Working Group 
irAE 
immune-related adverse event 
IV 
intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities  
MM 
multiple myeloma 
MR 
minimal response 
MRD 
minimal residual disease 
NCI 
National Cancer Institute 
NE 
not evaluable 
 
 
ORR 
objective response rate 
OS 
overall survival 
PC 
plasma cell 
PD 
progressive disease 
PFS 
progression-free survival 
PI 
proteasome inhibitor 


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Abbreviation 
Term 
 
 
PO 
orally 
PR 
partial response 
PT 
preferred term 
QTcF 
QT interval corrected using Fridericia's formula 
RAR 
response adaptive randomization 
R-ISS 
Revised International Staging System 
RP2D 
recommended Phase 2 dose 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
sCR 
stringent complete response 
SD 
stable disease 
SI 
Standard International 
 
 
SOC 
system organ class 
SPD 
sum of the products of the maximal perpendicular diameters of measured lesions 
TEAE 
treatment-emergent adverse event 
 
 
TTR 
time to response 
 
 
VGPR 
very good partial response 
WHO 
World Health Organization  


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1. 
INTRODUCTION 
This is an open-label, dose-escalation Phase 1 and randomized Phase 2 study to evaluate the 
safety and antitumor activity of INCB001158 in combination with daratumumab SC, compared 
with daratumumab SC alone, in participants with relapsed or refractory MM who have received 
at least 3 prior lines (including IMiD, PI, and anti-CD38 therapies) but not more than 5 prior 
lines of therapy. 
Phase 1 will consist of dose-escalation using a BOIN design and will determine the RP2D of 
INCB001158 in combination with daratumumab SC; efficacy will also be explored. 
Phase 2 will consist of a randomized expansion phase to compare the RP2D of INCB001158 in 
combination with daratumumab SC to daratumumab SC alone using an RAR design. 
INCB001158 monotherapy will also be explored. 
Section 2 of the Protocol provides a detailed description of the investigational products 
INCB001158 and daratumumab SC, target patient population, rationale for doses to be 
examined, and potential risks and benefits of treatment with INCB001158 and daratumumab SC. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the INCB 01158-206 Protocol. 
 
 
 
 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 01158-206 Protocol Amendment 3 dated 01 DEC 2021 and CRFs 
approved 09 JUL 2021. 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. 
Due to early termination decision following recruitment challenge (no safety-related concerns), 
primary safety analyses but no efficacy analyses will be performed due to insufficient number of 
participant enrolled in Phase 2. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Phase 1: To determine the safety, tolerability, and 
RP2D of INCB001158 in combination with 
daratumumab SC. 
Safety and tolerability determined by monitoring 
the frequency, duration, and severity of AEs. 
Phase 2: To compare the ORR of the RP2D of 
INCB001158 in combination with daratumumab 
SC to daratumumab SC monotherapy. 
ORR, defined as the proportion of participants 
with a documented response PR or better, as per 
IMWG criteria. 
Secondary 
Phase 1: To determine the efficacy of 
INCB001158 in combination with daratumumab 
SC. 
ORR, defined as the proportion of participants 
with a documented response PR or better, as per 
IMWG criteria. 
Phase 2: To determine the safety and tolerability 
of INCB001158 monotherapy at RP2D, and to 
compare the safety and tolerability and RP2D of 
INCB001158 in combination with daratumumab 
SC to daratumumab SC monotherapy 
Safety and tolerability determined by monitoring 
the frequency, duration, and severity of AEs. 
Phase 1: To determine the efficacy of 
INCB001158 in combination with daratumumab 
SC. 
Phase 2: To estimate the efficacy of INCB001158 
monotherapy, and to compare the efficacy of 
INCB001158 in combination with daratumumab 
SC to daratumumab SC monotherapy. 
• TTR, defined as the time from the first dose of 
study drug to the first documented response PR 
or better, as per IMWG criteria. 
• DOR, defined as time from first documented 
response PR or better, as per IMWG criteria, 
until date of disease progression or death, 
whichever occurs first. 
• PFS, defined as the duration from the date of 
first dose of study drug until either PD, as per 
IMWG criteria, or death, whichever occurs first. 
• MRD, defined as the percentage of 
MRD-negative participants. 
• OS, defined as the time from the first dose of 
study drug to death from any cause. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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3.
STUDY DESIGN
This is an open-label, dose-escalation Phase 1 and randomized Phase 2 study to evaluate the 
safety and antitumor activity of INCB001158 in combination with daratumumab SC, compared 
with daratumumab SC alone, in participants with relapsed or refractory MM who have received 
at least 3 prior lines (including IMiD, PI, and anti-CD38 therapies) but not more than 5 prior 
lines of therapy. 
Phase 1 will consist of dose-escalation using a BOIN design and will determine the RP2D of 
INCB001158 in combination with daratumumab SC; efficacy will also be explored. 
Phase 2 will consist of a randomized expansion phase to compare the RP2D of INCB001158 in 
combination with daratumumab SC to daratumumab SC alone using an RAR design. 
INCB001158 monotherapy will also be explored. 
As a result of an early-termination decision following a recruitment challenge (no safety-related 
concerns), primary safety analyses but no efficacy analyses will be performed due to an 
insufficient number of participants enrolled in Phase 2. 
The study design schema is presented in Figure 1. 
Figure 1: 
Study Design Schema 
3.1. 
Randomization 
 Refer to Protocol Amendment 3 dated 01 DEC 2021 for a full description of randomization. 
3.2. 
Control of Type I Error 
Refer to Protocol Amendment 3 dated 01 DEC 2021 for a full description of control of Type I 
error. 
3.3. 
Sample Size Considerations 
Refer to Protocol Amendment 3 dated 01 DEC 2021 for a full description of the sample size 
considerations. 


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3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 3 dated 01 DEC 2021 for a full description of all study procedures 
and assessment schedules for this study. 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
The term "study drug" refers to INCB001158 only, and "study treatment" refers to INCB001158, 
daratumumab SC, or the combination of INCB001158 and daratumumab SC. 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study treatment (INCB001158 or daratumumab SC) 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 study 
treatment (INCB001158 or daratumumab SC), unless otherwise defined. 
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 imputed 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. 


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A partial disease diagnosis date will be handled as follows in calculations: 
• 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 no imputation will be done. 
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 relevant efficacy endpoints, 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 treatment is administered. The scheduled 
cycle length is 28 days. INCB001158 will be administered on a continuous dose schedule.  
Daratumumab SC administration will be once weekly for Cycles 1 and 2, once every 2 weeks for 
Cycles 3 to 6, and once every 4 weeks thereafter. 
The estimated duration of study participation contains up to 28 days for screening, continuous 
treatment in consecutive 28-day cycles as long as participants are receiving benefit and have not 
met any criteria for study withdrawal, and every 8 to 12 weeks for follow-up. 
4.2. 
Variable Definitions 
The following variables will only be calculated if not reported on the eCRF. 
4.2.1. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB001158 or daratumumab SC. 


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Concomitant medication is defined as any nonstudy medication that is started accordingly: 
•
Before the date of first administration of INCB001158 or daratumumab SC 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 INCB001158 or daratumumab SC and is
ongoing or ends during the course of study.
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCB001158 or daratumumab SC. 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. 
Additional rules that will be applied for the analysis and classification of prior and concomitant 
medications are given below: 
•
Consider the following cases as prior medication.
−
The end date is before the first dose date.
−
If the day of end date is missing, and the last day of the month is before the first
dose date.
−
If the month of end date is missing, and the last day of the year is before the first
dose date.
•
Consider the following cases as concomitant medication.
−
The start date is after the first dose date.
−
If the day of start date is missing, and the first day of the month is on or after the
first dose date.
−
If the month of start date is missing, and the first day of the year is on or after the
first dose date.
•
All other cases will be considered as both prior and concomitant medication.


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9 or later) will be used 
for the generation of all tables, graphs, and statistical analyses. Descriptive summaries for 
continuous variables will include but not be limited to the number of observations, mean, 
standard deviation, median, minimum, and maximum. Descriptive summaries for categorical 
variables will include the number and percentage of participants in each category. 
Interim analyses are planned for this study as defined in Section 9. 
5.2. 
Study Phases and Treatment Groups 
All summaries will be presented by dose level for Phase 1 and by treatment group for Phase 2. 
Note that separate listings will be provided for Phase 1 and Phase 2. 
5.2.1. 
Phase 1: Dose Escalation 
In Phase 1, INCB001158 (50-100 mg PO BID) in combination with daratumumab SC will be 
administrated in 28-day treatment cycles. 
5.2.2. 
Phase 2: Expansion 
Participants will be randomized 1:1:1 to Treatment Groups A, B, or C as follows: 
 Treatment Group A: INCB001158 + daratumumab SC 
 Treatment Group B: daratumumab SC monotherapy (Part 1), then crossover to 
INCB001158 + daratumumab SC (Part 2) 
 Treatment Group C: INCB001158 monotherapy (Part 1), then crossover to 
INCB001158 + daratumumab SC (Part 2) 
Treatments will be administrated in 28-day cycles for Treatment Groups A, B, and C. 
5.3. 
Analysis Populations 
5.3.1. 
Enrolled 
This population will include all participants who sign the ICF. 
5.3.2. 
Full Analysis Set 
The FAS will include all participants who received at least 1 dose of INCB001158 or 
daratumumab SC. Participants will be analyzed according to the treatment to which they have 
been initially assigned. 
This population will be used for summaries of demographics, baseline characteristics, participant 
disposition, safety, and exposure. 


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5.3.3. 
DLT Evaluable Population for Phase 1 
The DLT evaluable population includes participants who have received at least 42 of 56 doses 
for the 28-day cycle regimen (representing ≥ 75% of the dose planned) of INCB001158 or who 
have a DLT. 
Note that the DLT evaluable population will exclude participants in the randomized part 
(Phase 2) of the study. 
6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
All summaries will be presented by dose level for Phase 1 and by treatment group for Phase 2. 
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 performance status, time since diagnosis, Durie Salmon stage of initial diagnosis, 
R-ISS stage at initial diagnosis, Durie Salmon stage of current diagnosis, R-ISS stage at current 
diagnosis, and current myeloma type. 
Time since diagnosis will be calculated as follows: 
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25. 
6.1.3. 
Prior Therapy 
The number of prior therapy regimens for the disease under study will be summarized for all 
participants in the FAS. The component drugs of prior therapy regimens will be coded using the 
WHO Drug Dictionary. The number and percentage of participants who received each drug will 
be summarized by WHO drug class and WHO drug preferred term. The regimen name, 
component drugs, start and stop dates, purpose of the regimen, best response, reason for 
discontinuation, and date of relapse/progression will be listed. 
The number of participants who received prior radiation will be summarized for the FAS. The 
radiotherapy type, body site, and start and stop dates will be listed. 
The number of participants who had prior surgery or surgical procedure for the malignancies 
under study will be summarized for the FAS. The date and description of the surgery/procedure 
will be listed. 


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6.1.4. 
Medical History 
For participants in the FAS, medical history will be summarized. This summary will include the 
number and percentage of participants with medical history events for each body system/organ 
class as documented on the eCRF. 
6.2. 
Disposition of Participants 
The number and percentage of participants who were screened, who failed screening, who were 
enrolled, 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 site will also be provided. 
6.3. 
Protocol Deviations 
Protocol deviations recorded on the eCRF will be listed. 
6.4. 
Exposure 
6.4.1. 
Exposure to INCB001158 
For participants in the Phase 1 and Phase 2 combined FAS, exposure to INCB001158 will be 
summarized descriptively as the following using information entered on the Dose INCB001158 
eCRF: 
• Total actual dose (mg): total actual dose taken of INCB001158. 
• Duration of treatment (days): date of last dose of INCB001158 – date of first dose 
of INCB001158 + 1. 
• Average daily dose (mg): total actual INCB001158 dose taken (mg) divided by the 
duration of treatment with INCB001158 (days). 
6.4.2. 
Exposure to Daratumumab SC 
For participants in the Phase 1 and Phase 2 combined FAS, exposure to daratumumab SC will be 
summarized descriptively as the following using information entered on the Daratumumab 
Dosing eCRF: 
• Number of infusions: number of administered, nonzero infusions of daratumumab. 
• Average dose (mg): total actual daratumumab dose (mg) divided by the number of 
infusions of daratumumab. 
• Dose administered per cycle (mg): the actual dose of daratumumab administered 
(mg) per cycle. 


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6.5. 
Study Drug Compliance 
For participants in the FAS, overall compliance (%) for INCB001158 will be calculated as 
follows: 
overall compliance (%) = 100  [total dose actually taken] / [total prescribed dose]. 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator, 
accounting for dose modifications. 
The total actual dose taken will be calculated based on information entered on the Drug 
Accountability eCRF. If there are dispensed drugs that have not been returned yet, the actual 
dose taken starting from the dispense date of the unreturned drugs will be imputed by the dose 
taken as reported on the Dose INCB001158 eCRF. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
The number and percentage of participants in the FAS for each prior and concomitant medication 
will be summarized by WHO drug class and PT. 
A listing of post-treatment anticancer treatments will also be provided. 


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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. 
General Considerations 
The primary endpoint of the Phase 2 portion of the Protocol is ORR, defined as the proportion of 
participants with CR, VGPR, or PR, according to IMWG criteria in the randomized FAS. Due to 
the small sample size of participants enrolled in Phase 2 at the time of study termination, only 
listings of the efficacy data will be provided. 
7.2. 
Efficacy Hypotheses 
As a result of an early-termination decision following a recruitment challenge (no safety-related 
concerns), efficacy analyses will not be performed due to an insufficient number of participants 
enrolled in Phase 2. Listings of the efficacy data will be provided for participants in Phase 1 and 
Phase 2. Details of the efficacy hypotheses may be found in the Protocol. 
7.3. 
Analysis of the Efficacy Parameters 
7.3.1. 
Primary Efficacy Analysis 
Objective response rate is defined as the proportion of participants with at least 1 confirmed 
response of CR, VGPR, or PR, according to IMWG criteria. 
Objective response rate in Phase 2 was the planned primary endpoint. Due to the small number 
of participants in Phase 2, only listings of the response assessment data will be provided. 
Therefore, ORR will not be calculated and will not be presented in the CSR. 
The IMWG criteria are presented in Table 2. Per IMWG uniform response criteria, all response 
categories and PD require 2 consecutive assessments except for radiographic or bone marrow 
assessments. If a participant discontinues treatment without a PD, receives a subsequent 
anticancer therapy and then responds, this will not be included as a responder for ORR. 
Table 2: 
International Uniform Response Criteria Consensus Recommendations 
Response 
Response Criteria 
sCR 
• CR as defined below, plus 
• Normal FLC ratio, and 
• Absence of clonal PCs by immunohistochemistry, immunofluorescence,a or 2- to 4-color flow 
cytometry 
CRb 
• Negative immunofixation on the serum and urine, and 
• Disappearance of any soft tissue plasmacytomas, and 
• < 5% PCs in bone marrow 
VGPRb 
• Serum and urine M-component detectable by immunofixation but not on electrophoresis, or 
• ≥ 90% reduction in serum M-protein plus urine M-protein < 100 mg/24 hours 


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Table 2: 
International Uniform Response Criteria Consensus Recommendations 
(Continued) 
Response 
Response Criteria 
PR 
•  50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by  90% or to 
< 200 mg/24 hours 
• If the serum and urine M-protein are not measurable, a decrease of  50% in the difference 
between involved and uninvolved FLC levels is required in place of the M-protein criteria 
• If serum and urine M-protein are not measurable, and serum free light assay is also not 
measurable,  50% reduction in bone marrow PCs is required in place of M-protein, provided 
baseline bone marrow PC percentage was  30% 
• In addition to the above criteria, if present at baseline, a  50% reduction in the size (SPD) of soft 
tissue plasmacytomas is also required 
MR 
•  25% but  49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% 
to 89% 
• In addition to the above criteria, if present at baseline, 25% to 49% reduction in the size of soft 
tissue plasmacytomas is also required 
• No increase in size or number of lytic bone lesions (development of compression fracture does not 
exclude response) 
SD 
• Not meeting criteria for CR, VGPR, PR, MR, or PD 
PDc 
Increase of 25% from lowest response value in any one of the following: 
• Serum M-component (absolute increase must be  0.5 g/dL) 
• Urine M-component (absolute increase must be  200 mg/24 hours) 
• Only in participants without measurable serum and urine M-protein levels: the difference between 
involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL) 
• Only in participants without measurable serum and urine M-protein levels and without measurable 
disease by FLC levels, bone marrow PC percentage (absolute percentage must be  10%) 
• Bone marrow PC percentage: the absolute percentage must be > 10% 
• Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the 
size of existing bone lesions or soft tissue plasmacytomas (SPD) 
• Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be attributed 
solely to the PC proliferative disorder 
Note: All response categories (CR, sCR, VGPR, PR, and PD) require 2 consecutive assessments made at any time before the 
institution of any new therapy; CR, sCR, VGPR, PR, and SD categories also require no known evidence of progressive or new 
bone lesions if radiographic studies were performed. VGPR and CR categories require serum and urine studies regardless of 
whether disease at baseline was measurable on serum, urine, both, or neither. 
Note: Radiographic studies are not required to satisfy these response requirements. Bone marrow assessments need not be 
confirmed. For PD, serum M-component increases of more than or equal to 1 g/dL are sufficient to define relapse if starting 
M-component is  5 g/dL. 
a Presence/absence of clonal cells is based upon the kappa/lambda ratio. An abnormal kappa/lambda ratio by 
immunohistochemistry or immunofluorescence requires a minimum of 100 PCs for analysis. An abnormal ratio reflecting 
presence of an abnormal clone is kappa/lambda of > 4:1 or < 1:2. 
b Clarifications to IMWG criteria for coding CR and VGPR in participants in whom the only measurable disease is by serum 
FLC levels: CR in such participants indicates a normal FLC ratio of 0.26 to 1.65 in addition to CR criteria listed above. VGPR 
in such participants requires a > 90% decrease in the difference between involved and uninvolved FLC levels. 
c Clarifications to IMWG criteria for coding PD: Bone marrow criteria for PD are to be used only in participants without 
measurable disease by M-protein and by FLC levels; "25% increase" refers to M-protein, FLC, and bone marrow results, and 
does not refer to bone lesions, soft tissue plasmacytomas, or hypercalcemia, and the "lowest response value" does not need to 
be a confirmed value. 


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7.3.2. 
Secondary Efficacy Analyses 
7.3.2.1. 
Best Overall Response 
The best overall response, according to IMWG criteria, will be listed for each participant in the 
FAS. 
7.3.2.2. 
Time to Response 
Time to response is defined as the number of days from the randomization in Phase 2 (or first 
dose of study drug in Phase 1) to the first documented response of PR, VGPR, or CR (as per 
IMWG criteria). Time to response will be listed for the FAS. 
7.3.2.3. 
Duration of Response 
Duration of response is defined as the number of days from earliest date of PR, VGPR, or CR (as 
per IMWG criteria) until the earliest date of disease progression, relapse, or death due to any 
cause. Duration of response will be listed for the FAS. 
7.3.2.4. 
Progression-Free Survival 
Progression-free survival is defined as the number of days from the date of first dose of study 
drug in Phase 1 (or from randomization date in Phase 2) until either PD, as per IMWG criteria, or 
death, whichever occurs first. 
Censoring rules for PFS are described in Table 3. 
Table 3: 
Evaluation and Censoring of Progression-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline tumor assessments 
Censored 
Date of randomization or Day 1 (for Phase 1) 
No valid postbaseline response 
assessments 
Censored 
Date of randomization or Day 1 (for Phase 1) 
Progression documented between 
scheduled response assessments 
Progressed Date of first overall response of PD 
No progression 
Censored 
Date of last valid efficacy/disease assessment 
(not NE and not missing) 
Study withdrawal for 
undocumented progression 
Censored 
Date of last valid efficacy/disease assessment 
(not NE and not missing) 
Study withdrawal for toxicity or 
other reason 
Censored 
Date of last valid radiologic assessment (not NE and 
not missing) 
New anticancer treatment started 
Censored 
Date of last valid efficacy/disease assessment 
(not NE and not missing) on/before starting a new 
anticancer treatment 
Death before first progressive 
response assessment 
Progressed Date of death 
Death between adequate response 
assessments 
Progressed Date of death 
Death or progression after 2 or 
more missed assessments 
Censored 
Date of last valid efficacy/disease assessment 
(not NE and not missing) 


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7.3.2.5. 
Overall Survival 
Overall survival will be listed for the FAS and is defined as the number of days from 
randomization in Phase 2 (or first dose of study drug in Phase 1) to death due to any cause. Date 
of death will be determined using the Death Report, the Survival Follow-Up, and the Participant 
Status eCRFs. Participants who are lost to follow-up or still alive at the time of analysis will be 
right-censored at the earlier of the date the participant was last known alive and the clinical data 
cutoff date for the analysis. The last known alive date is defined as the later of the last study visit 
and the date the participant was last known alive from the Survival Follow-Up and Participant 
Status eCRFs. 
8. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
8.1. 
General Consideration 
Summary tables may be replaced with listings when appropriate. For instance, an AE frequency 
table may be replaced with a listing if it only contains a few unique PTs reported on relatively 
few participants. 
Unless otherwise stated, table summaries will be limited to TEAEs. 
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first dose of study drug. Analysis of AEs (as discussed below) will be limited to TEAEs, but data 
listings will include all AEs regardless of their timing in relation to study drug administration. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be graded 
using the NCI CTCAE v5. The CTCAE reporting guidelines and grading details are available on 
the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. In addition, serious TEAEs will also be tabulated. 
A grading (severity) scale is provided for each AE term. If the toxicity is not included in the 
CTCAE v5 criteria, it will be rated on a scale of 1 to 5 as follows: 1 = mild, 2 = moderate, 
3 = severe, 4 = life threatening, and 5 = death related to AE. All toxicities will be graded based 
on the worst level reached, not the level they may have reached if they had not been treated. 
When the intensity of an AE changes over time for a reporting period (eg, between visits), each 
change in intensity will be collected as an AE until the event resolves. Only the worst grade will 
be reported in AE summaries. Also, Grade 3 or higher AEs will be summarized. 


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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. 
8.2.2. 
Dose-Limiting Toxicities 
Participants in the DLT evaluable population with DLTs and the type of DLT will be listed by 
dose level and treatment group. An AE for a participant will be identified as a DLT if the event is 
recorded as a Protocol-defined DLT on the Adverse Event eCRF. 
8.2.3. 
Adverse Events of Special Interest 
Adverse events of special interest include irAEs that are seen with immunotherapy and potential 
inhibition of the urea cycle (based on urinary orotic acid, plasma ammonia, and BUN/urea 
assessments). 
An overall summary of irAEs will include number (%) of participants reporting any irAEs. 
8.2.4. 
Adverse Event Summaries 
An overall summary of AEs by dose level for Phase 1 and by treatment group for Phase 2 using 
the FAS population as applicable will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants who had a fatal TEAE 
• Number (% ) of participants who had a TEAE related to INCB001158 
• Number (%) of participants who had a TEAE related to daratumumab SC 
• Number (%) of participants who had a TEAE related to INCB001158 and/or 
daratumumab SC 
• Number (%) of participants who had a Grade 3 or higher TEAE related to 
INCB001158 
• Number (%) of participants who had a Grade 3 or higher TEAE related to 
daratumumab SC 
• Number (%) of participants who had a Grade 3 or higher TEAE related to 
INCB001158 and/or daratumumab SC 
• Number (%) of participants who had a serious TEAE related to INCB001158 
• Number (%) of participants who had a serious TEAE related to daratumumab SC 
• Number (%) of participants who had a serious TEAE related to INCB001158 and/or 
daratumumab SC 


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• Number (%) of participants who had a TEAE leading to temporary interruption of 
INCB001158 
• Number (%) of participants who had a TEAE leading to INCB00158 dose reduction 
• Number (%) of participants who had a TEAE leading to permanent discontinuation of 
INCB001158 
• Number (%) of participants who had an irAE 
The following summaries will be produced by MedDRA term for the Phase 1 and Phase 2 FAS 
population (if 10 or fewer participants appear in a table, a listing may be appropriate): 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of Grade 3 or higher TEAEs by PT in decreasing order of frequency 
• Summary of serious TEAEs by PT in decreasing order of frequency 
• Summary of INCB001158 treatment-related TEAEs by PT in decreasing order of 
frequency 
• Summary of Grade 3 or higher INCB001158 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 INCB001158 dose reduction by PT in decreasing 
order of frequency 
• Summary of TEAEs leading to INCB001158 dose interruption by PT in decreasing 
order of frequency 
• Summary of TEAEs leading to discontinuation of INCB001158 by PT in decreasing 
order of frequency 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
Laboratory values and change from baseline values will be summarized descriptively by visit. 
The baseline value will be determined using the nonmissing values collected before the first dose 
using the priority defined in Table 4. The last record before administration in the highest priority 
will be considered the baseline record. For baseline laboratory candidates with the same date and 
time in the same priority category, additional rules may be provided after consultation with the 
medical monitor to delineate which value will be defined as baseline. 


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Table 4: 
Identification of Baseline Record 
Priority 
Laboratory Visit 
Central or Local Laboratory 
1 
Scheduled 
Central 
2 
Scheduled 
Local 
3 
Unscheduled 
Central 
4 
Unscheduled 
Local 
Laboratory test values will be assessed for severity based on the numerical component of 
CTCAE v5. 
8.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from central laboratories will be reported in SI 
units. Any laboratory test results and associated normal ranges from local laboratories will be 
converted to SI units. 
When there are multiple nonmissing laboratory values for a participant's particular test within a 
visit window, the convention described in Table 5 will be used to determine the record used for 
by-visit tabulations and summaries. 
Table 5: 
Identification of Records for Postbaseline By-Visit Summaries 
Priority 
Laboratory Visit 
Central or Local 
Laboratory 
Proximity to Visit 
Window 
Tiebreaker 
1 
Scheduled 
Central 
In-window 
Use smallest 
laboratory sequence 
number 
2 
Scheduled 
Local 
In-window 
3 
Unscheduled 
Central 
In-window 
4 
Unscheduled 
Local 
In-window 
5 
Scheduled 
Central 
Out-of-window 
6 
Scheduled 
Local 
Out-of-window 
For coagulation and urinalysis laboratory values, listings will be provided. 
Numeric chemistry and hematology laboratory values will be summarized descriptively in SI 
units, and non-numeric test values will be tabulated when necessary. 
Severity grades will be assigned to laboratory test values based on the numerical component of 
CTCAE v5. The number of participants who experienced worsening of laboratory abnormalities 
will be summarized by maximum severity. 
In cases where differentials of hematology parameters are obtained without corresponding 
absolute count data, efforts will be made to investigate if the conversion to an absolute value will 
lead to additional abnormalities. This will be discussed with the clinical team regarding 
appropriate documentation and action. 


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8.4. 
Vital Signs 
Values at each scheduled visit, change, and percent change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, temperature, respiratory rate, 
and weight, will be summarized descriptively. 
Normal ranges for vital sign values are defined in Table 6. For participants exhibiting vital sign 
abnormalities, the abnormal values will be listed along with their assigned treatment group. Alert 
vital signs are defined as an absolute value outside the defined normal range and percentage 
change greater than 25%. Note that the definition of alert vital signs does not apply for body 
temperature and weight. The abnormal values for participants exhibiting alert vital sign 
abnormalities will be listed. 
Table 6: 
Normal Vital Sign Values 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
≤ 155 mmHg 
≥ 85 mmHg 
Diastolic blood pressure 
≤ 100 mmHg 
≥ 40 mmHg 
Pulse 
≤ 100 bpm 
≥ 45 bpm 
Temperature 
≤ 38ºC 
≥ 35.5ºC 
Respiratory rate 
≤ 24 breaths/min 
≥ 8 breaths/min 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, RR, QT, QRS, and QTcF intervals will be obtained for each 
participant during the study. Values at each scheduled visit, change, and percentage change from 
baseline will be summarized for each ECG parameter. Baseline will be determined as the 
average of all nonmissing values before the first administration of INCB001158 or 
daratumumab SC. 
Electrocardiogram results will be reviewed for clinically notable abnormalities according to the 
investigator. Electrocardiogram values will also be considered abnormal if the absolute 
percentage change from baseline is more than 25% (30% for QRS interval). Participants 
exhibiting ECG abnormalities will be listed with study visit and assigned treatment group. 
Outliers of QT and QTcF values, defined as absolute values > 450 milliseconds, 
> 500 milliseconds, or change from baseline > 30 milliseconds, will be summarized.


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9.
INTERIM ANALYSES
As a result of an early-termination decision following a recruitment challenge (no safety-related 
concerns), primary safety analyses but no efficacy analyses will be performed due to an 
insufficient number of participants enrolled in Phase 2. No formal interim analysis will be 
performed. 
10.
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN
All versions of the SAP are listed in Table 7. 
Table 7: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
19 APR 2022 
10.1. 
Changes to Protocol-Defined Analyses 
As a result of an early-termination decision following a recruitment challenge (no safety-related 
concerns), primary safety analyses but no efficacy analyses will be performed due to an 
insufficient number of participants enrolled in Phase 2. Listings of efficacy data will be provided. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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APPENDIX A. PLANNED TABLES AND LISTINGS 
This appendix provides a list of the planned tables and listings for the Clinical Study Report. 
Shells are provided in a separate document for tables that are not in the Standard Safety 
Tables v1.11. 
The lists of tables and listings are to be used as guidelines. Modifications of the lists that do not 
otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Note that separate listings will be provided for the Phase 1 FAS and the Phase 2 FAS and will 
include ".1" and ".2", respectively, at the end of the listing number. 
Tables 
Table No. 
Title 
Population 
Standard 
Baseline and Demographic Characteristics 
1.1.1 
Summary of Participants Screened and Screen Failures 
Enrolled 
1.1.2 
Analysis Populations 
FAS 
X 
1.1.3 
Summary of Participant Disposition 
FAS 
X 
1.1.4 
Summary of Number of Participants Enrolled by Country and Site 
FAS 
X 
1.2.1 
Summary of Demographics and Baseline Characteristics 
FAS 
X 
1.3.1 
Summary of Baseline Disease Characteristics 
FAS 
X 
1.4.1 
Summary of Prior Therapy for Disease Under Study 
FAS 
1.4.2 
Summary of Prior Radiation Therapy 
FAS 
1.4.3 
Summary of Prior Surgical Procedures 
FAS 
1.4.4 
Summary of Prior Medications 
FAS 
X 
1.4.5 
Summary of Concomitant Medications 
FAS 
X 
1.5.1 
Summary of General Medical History 
FAS 
X 
Exposure and Safety 
3.1.1 
Summary of Exposure and Duration of Exposure to INCB001158 
FAS 
X 
3.1.2 
Summary of Exposure and Duration of Exposure to Daratumumab 
SC 
FAS 
X 
3.1.3 
Summary of Study Drug Compliance to INCB001158 
FAS 
X 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
FAS 
X 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
FAS 
X 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency 
FAS 
X 
3.2.4 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency 
FAS 
X 
3.2.5 
Summary of INCB001158 Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA Preferred Term in Decreasing Order of 
Frequency 
FAS 
X 
3.2.6 
Summary of Grade 3 or Higher INCB001158 Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
3.2.7 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term 
FAS 
X 


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Table No. 
Title 
Population 
Standard 
3.2.8 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB001158 Dose Reduction by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
 
3.2.9 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB001158 Dose Interruption by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
 
3.2.10 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of INCB001158 by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
 
3.3.1.1 
Summary of Laboratory Values - Hematology 
FAS 
X 
3.3.1.2 
Summary of Laboratory Values - Chemistry 
FAS 
X 
3.3.3.4 
Treatment-Emergent Worsening of Laboratory Abnormalities - 
Hematology 
FAS 
X 
3.3.3.5 
Treatment-Emergent Worsening of Laboratory Abnormalities - 
Chemistry 
FAS 
X 
3.4.1 
Summary of Systolic Blood Pressure 
FAS 
X 
3.4.2 
Summary of Diastolic Blood Pressure 
FAS 
X 
3.4.3 
Summary of Pulse 
FAS 
X 
3.4.4 
Summary of Respiratory Rate 
FAS 
X 
3.4.5 
Summary of Body Temperature 
FAS 
X 
3.4.6 
Summary of Body Weight 
FAS 
X 
3.5.1 
Summary of PR Interval (ms) From 12-Lead ECG 
FAS 
X 
3.5.2 
Summary of QRS Interval (ms) From 12-Lead ECG 
FAS 
X 
3.5.3 
Summary of QT Interval (ms) From 12-Lead ECG 
FAS 
X 
3.5.4 
Summary of QTcF Interval (ms) From 12-Lead ECG 
FAS 
X 
3.5.5 
Summary of RR Interval (ms) From 12-Lead ECG 
FAS 
X 
3.5.6 
Summary of Heart Rate (bpm) From 12-Lead ECG 
FAS 
X 
3.5.7 
Summary of Outliers of QT and QTcF Interval Values (ms) From 
12-Lead ECG 
FAS 
X 


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Listings 
Listing No. 
Title 
2.1.2.x 
Participant Enrollment and Disposition Status 
2.2.1.x 
Participant Inclusion and Exclusion Criteria Violations 
2.2.2.x 
Protocol Deviations 
2.3.1.x 
Analysis Populations 
2.4.1.x 
Demographics and Baseline Characteristics 
2.4.2.x 
Baseline Disease Characteristics 
2.4.3.x 
Prior Radiation Treatment 
2.4.4.x 
Prior Therapy for Disease Under Study 
2.4.5.x 
Prior Surgery or Surgical Procedure 
2.4.6.x 
Medical History 
2.4.7.x 
Prior and Concomitant Medications 
2.4.8.x 
Post-Treatment Anticancer Therapy 
2.5.1.x 
Study Drug Administration for INCB001158 
2.5.2.x 
Study Drug Compliance for INCB001158 
2.5.3.x 
Study Drug Administration for Daratumumab SC 
2.6.1.x 
Overall Response Assessments and Best Overall Response Under IMWG Criteria 
2.6.2.x 
Efficacy Endpoints (TTR, DoR, PFS, and OS) 
2.6.3.x 
ECOG Status 
2.6.4.x 
Clinical Laboratory Values – Chemistry, SPEP 
2.6.5.x 
Clinical Laboratory Values – Immunology 
2.6.6.x 
Clinical Laboratory Values – Immunology, Free Light Chains 
2.6.7.x 
Clinical Laboratory Values – Immunology, Immunofixation 
2.6.8.x 
Clinical Laboratory Values – Immunology, SPEP 
2.6.9.x 
Clinical Laboratory Values – Urinalysis, UPEP 
2.7.1.x 
Adverse Events 
2.7.2.1 
Dose-Limiting Toxicities 
2.7.3.x 
Serious Adverse Events 
2.7.4.x 
Fatal Adverse Events 
2.7.5.x 
Adverse Events Leading to Discontinuation of INCB001158 
2.7.6.x 
Investigator-Identified Immune-Related Adverse Events 
2.8.1.1.x 
Clinical Laboratory Values – Hematology 
2.8.1.2.x 
Clinical Laboratory Values – Chemistry 
2.8.1.3.x 
Clinical Laboratory Values – Coagulation and Urinalysis 
2.8.1.4.x 
Clinical Laboratory Values – Orotic Acid 
2.8.1.5.x 
Abnormal Clinical Laboratory Values – Hematology 
2.8.1.6.x 
Abnormal Clinical Laboratory Values – Chemistry 
2.8.1.7.x 
Clinical Laboratory Values – Endocrine 
2.8.2.1.x 
Vital Signs 
2.8.2.2.x 
Abnormal Vital Sign Values 
2.8.3.1.x 
12-Lead ECG Values