Phase 1 Study to Identify the Immunomodulatory Activity of LY3022855 (IMC-CS4) in Patients With Advanced, Refractory Breast or Prostate Cancer
Phase: PHASE1
Conditions: Neoplasms, Neoplasm Metastasis
Sponsor: Eli Lilly and Company

 
 
Protocol I5F-MC-JSCB(d) 
 
 
Phase 1 Study to Identify the Immunomodulatory Activity of LY3022855 (IMC-CS4) in Patients 
With Advanced, Refractory Breast or Prostate Cancer 
 
 
NCT02265536 
 
 
Approval Date: 10-Nov-2016 

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LY3022855 (IMC-CS4)
1.
Protocol I5F-MC-JSCB(d)
Phase 1 Study to Identify the Immunomodulatory Activity 
of LY3022855 (IMC-CS4) in Patients with Advanced, 
Refractory Breast or Prostate Cancer
Confidential Information
The information contained in this protocol is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
LY3022855 (IMC-CS4), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.  This document and its associated attachments 
are subject to United States Freedom of Information Act (FOIA) Exemption 4.
LY3022855 (IMC-CS4)
This Phase 1 study is a single-center, open-label, nonrandomized, noncontrolled study of 
intravenous LY3022855 (IMC-CS4) in patients with advanced, refractory breast or prostate 
cancer.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly: 09 April 2014.
Amendment (a) Electronically Signed and Approved by Lilly on 05 September 2014.
Amendment (b) Electronically Signed and Approved by Lilly on 18 March 2015.
Amendment (c) Electronically Signed and Approved by Lilly on 25 September 2015.
Amendment (d) Electronically Signed and Approved by Lilly on approval date provided 
below.
Approval Date: 10-Nov-2016 GMT

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2.
Synopsis
This Phase 1 study is a single-center, open-label, nonrandomized, noncontrolled study of
intravenous LY3022855 (IMC-CS4) in patients with advanced, refractory breast or prostate
cancer.

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3.
Table of Contents
Phase 1 Study to Identify the Immunomodulatory Activity of 
LY3022855 (IMC-CS4) in Patients with Advanced, Refractory
Breast or Prostate Cancer
Section
Page
1.
Protocol I5F-MC-JSCB(d)  Phase 1 Study to Identify the 
Immunomodulatory Activity of LY3022855 (IMC-CS4) in Patients 
with Advanced, Refractory Breast or Prostate Cancer .........................................................1
2.
Synopsis .............................................................................................................................2
3.
Table of Contents................................................................................................................3
4.
Abbreviations and Definitions.............................................................................................9
5.
Introduction ......................................................................................................................15
5.1.
Rationale and Justification for the Study ......................................................................15
5.2.
Objectives ....................................................................................................................16
5.2.1.
Primary Objective ................................................................................................16
5.2.2.
Secondary Objectives...........................................................................................17
5.2.3.
Exploratory Objectives.........................................................................................17
5.3.
General Introduction to LY3022855.............................................................................17
5.3.1.
Definition of Immunomodulatory Change ............................................................18
5.4.
LY3022855 – Nonclinical and Clinical Experience ......................................................18
5.4.1.
Nonclinical Pharmacokinetics ..............................................................................18
5.4.2.
Nonclinical Pharmacokinetic/Pharmacodynamic Model.......................................19
5.4.3.
Clinical Pharmacokinetics....................................................................................19
5.4.4.
Nonclinical Toxicology........................................................................................21
5.4.4.1.
Single-Dose Toxicity......................................................................................22
5.4.4.2.
Repeat-Dose Toxicity.....................................................................................23
5.4.5.
Clinical Experience..............................................................................................25
5.5.
Rationale for Selection of Dose....................................................................................28
6.
Investigational Plan...........................................................................................................30
6.1.
Study Population..........................................................................................................30
6.1.1.
Inclusion Criteria .................................................................................................30
6.1.2.
Exclusion Criteria ................................................................................................33
6.2.
Summary of Study Design............................................................................................34
6.2.1.
Study Completion and End of Trial......................................................................37
6.2.2.
Continued Access Period......................................................................................37
6.3.
Discontinuations ..........................................................................................................38

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6.3.1.
Discontinuation of Patients...................................................................................38
6.3.2.
Discontinuation of Study Sites .............................................................................39
6.3.3.
Discontinuation of the Study................................................................................39
7.
Treatment..........................................................................................................................40
7.1.
Materials and Supplies .................................................................................................40
7.2.
Study Drug Administration ..........................................................................................40
7.2.1.
Dose Adjustments and Delays..............................................................................41
7.2.1.1.
Infusion-Related Reactions.............................................................................42
7.2.1.2.
Other Adverse Events.....................................................................................43
7.2.1.2.1.
Immune-Related Adverse Events (irAEs)..................................................43
7.3.
Method of Assignment to Treatment ............................................................................43
7.4.
Blinding .......................................................................................................................43
7.5.
Concomitant Therapy...................................................................................................44
7.6.
Treatment Compliance .................................................................................................44
7.6.1.
Evaluable Patients................................................................................................44
8.
Safety, Pharmacokinetic, Pharmacodynamic, and Efficacy Data 
Collection .........................................................................................................................46
8.1.
Safety Evaluations........................................................................................................46
8.1.1.
Safety Data Collection and Review ......................................................................46
8.1.2.
Adverse Events ....................................................................................................46
8.1.2.1.
Serious Adverse Events ..................................................................................48
8.1.2.2.
Adverse Event and Serious Adverse Event Reporting .....................................49
8.1.2.2.1.
Prior to Administration of Study Drug(s) ..................................................49
8.1.2.2.2.
On Therapy...............................................................................................49
8.1.2.2.3.
30-Day Follow-Up Visit ...........................................................................49
8.1.2.3.
Suspected Unexpected Serious Adverse Reactions..........................................50
8.1.2.4.
Summary of AE/SAE Reporting Guidelines ...................................................50
8.1.3.
Other Safety Measures .........................................................................................51
8.1.3.1.
Electrocardiograms.........................................................................................51
8.1.4.
Safety Monitoring ................................................................................................52
8.1.5.
Complaint Handling.............................................................................................52
8.2.
Sample Collection and Testing.....................................................................................53
8.2.1.
Samples for Study Qualification and Health Monitoring.......................................53
8.2.2.
Samples for Drug Concentration Measurements 
Pharmacokinetics/Pharmacodynamics..................................................................54
8.2.2.1.
Pharmacokinetic Samples...............................................................................54
8.2.2.2.
Pharmacodynamic Samples ............................................................................54
8.2.3.
Samples for Tailoring Biomarkers........................................................................55

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8.2.4.
Samples for Immunogenicity Research.................................................................56
8.3.
Efficacy Evaluation......................................................................................................56
8.4.
Procedure/Sampling Compliance..................................................................................58
9.
Data Management Methods...............................................................................................59
9.1.
Data Quality Assurance................................................................................................59
9.2.
Data Capture Systems ..................................................................................................59
9.2.1.
Case Report Form ................................................................................................59
9.2.2.
Ancillary Data......................................................................................................59
10.
Data Analyses...................................................................................................................61
10.1. General Considerations ................................................................................................61
10.2. Patient Disposition .......................................................................................................62
10.3. Patient Characteristics ..................................................................................................62
10.4. Safety Analyses............................................................................................................62
10.5. Pharmacokinetic Analyses............................................................................................63
10.6. Pharmacodynamic Analyses.........................................................................................63
10.7. Pharmacokinetic/Pharmacodynamic Analyses..............................................................63
10.8. Efficacy Analyses ........................................................................................................64
10.9. Interim Analyses ..........................................................................................................64
11.
Informed Consent, Ethical Review, and Regulatory Considerations ..................................65
11.1. Informed Consent.........................................................................................................65
11.2. Ethical Review.............................................................................................................65
11.3. Regulatory Considerations ...........................................................................................66
11.3.1.
Investigator Information.......................................................................................66
11.3.2.
Protocol Signatures ..............................................................................................66
11.3.3.
Final Report Signature .........................................................................................66
12.
References ........................................................................................................................67

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List of Tables
Table
Page
Table JSCB.1.
Summary of LY3022855 Dosages in Study JSCB..........................................28
Table JSCB.2.
General Dose Reduction Guidelines...............................................................41
Table JSCB.3.
Toxicities for Which Dose Adjustments and Delays Apply............................42
Table JSCB.4.
Adverse Event and Serious Adverse Reporting Guidelines for 
Study JSCB ...................................................................................................51

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List of Figures
Figure
Page
Figure JSCB.1.
Individual observed clearance versus patient body weight (upper panel) 
and LY3022855 dose (lower panel) for Studies JSCA and JSCB. ..................21
Figure JSCB.2.
CD14dimCD16bright (relative percentage of CD45+ HLA-DR+ CD14+) in 
the blood of patients from Study JSCA. .........................................................27
Figure JSCB.3.
Study JSCB study design...............................................................................35

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List of Attachments
List of Protocol Attachments
Attachment
Page
Attachment 1.
Protocol JSCB Study Schedules.....................................................................70
Attachment 2.
Protocol JSCB Clinical Laboratory Tests.......................................................81
Attachment 3.
Protocol JSCB Hepatic Monitoring Tests for Treatment-Emergent 
Abnormality ..................................................................................................82
Attachment 4.
Protocol JSCB Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Sampling Schedule for Dosages A and B Only....................83
Attachment 5.
Protocol JSCB Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Sampling Schedule for Dosage C Only................................94
Attachment 6.
Protocol JSCB Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Sampling Schedule for Dosage D Only................................97
Attachment 7.
Protocol JSCB Recommendations for Reporting 
Serious Adverse Events ...............................................................................101
Attachment 8.
Protocol JSCB ECOG Performance Status...................................................102
Attachment 9.
Protocol JSCB RECIST Criteria 1.1.............................................................103
Attachment 10.
Protocol JSCB Guidelines for the Management of Immune-Related 
Adverse Events............................................................................................110
Attachment 11.
Protocol JSCB Protocol Amendment I5F-MC-JSCB(d) Summary Phase 
1 Study to Identify the Immunomodulatory Activity of LY3022855 
(IMC-CS4) in Patients with Advanced, Refractory Breast or Prostate 
Cancer .........................................................................................................115

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4.
Abbreviations and Definitions
Term
Definition
ADA
anti-drug antibody
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event (AE) can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of medicinal (investigational) product, whether or not 
related to the medicinal (investigational) product.
ALT
alanine aminotransferase (also known as alanine transaminase)
AP
alkaline phosphatase
ASCO
American Society of Clinical Oncology
assent
Agreement from a minor or other individual who is not legally capable of providing 
consent, but who can understand the circumstances and potential risks involved in 
participating in a study (required by some institutional review boards [IRBs]/ethical 
review boards [ERBs]).
AST
aspartate aminotransferase (also known as aspartate transaminase)
AUC(0-168hr)
area under the plasma concentration-time curve from time zero to 168 hours
AUC0-∞
area under the plasma concentration-time curve from time zero to infinity
audit
A systematic and independent examination of the study-related activities and documents 
to determine whether the evaluated study-related activities were conducted, and the data 
were recorded, analyzed, and accurately reported according to the protocol, applicable 
standard operating procedures (SOPs), good clinical practice (GCP), and the applicable 
regulatory requirement(s).
BLQ
below the quantifiable lower limit of the assay
CnWn
Cycle and Week numbers
C168hr
concentration at 168 hours
Ctrough
trough concentration (predose concentration)
CA 15-3
cancer antigen 15-3
CBC
complete blood count
CEA
carcinoembryonic antigen
CK
creatine kinase (also known as creatine phosphokinase)

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CL
total body clearance
Cmax
maximum plasma concentration
CNS
central nervous system
collection database
A computer database where clinical trial data are entered and validated.
companion 
diagnostic
An in vitro diagnostic device (assay or test) that provides information that is essential for 
the safe and effective use of a corresponding therapeutic product.
complaint
Any written, electronic, or oral communication that alleges deficiencies related to the 
identity, quality, purity, durability, reliability, safety, effectiveness, or performance of a 
drug or drug delivery system.
compliance
Adherence to all the study-related requirements, good clinical practice (GCP) 
requirements, and the applicable regulatory requirements.
confirmation
A process used to confirm that laboratory test results meet the quality requirements 
defined by the laboratory generating the data and that Lilly is confident that results are 
accurate.  Confirmation will either occur immediately after initial testing or will require 
that samples be held to be retested at some defined time point, depending on the steps 
required to obtain confirmed results.
continued access 
period
The period between study completion and end of trial during which patients on study 
treatment who continue to experience clinical benefit and no undue risks may continue to 
receive study treatment until one of the criteria for discontinuation is met.
CR
complete response
CRF/eCRF
case report form/electronic case report form:  Sometimes referred to as clinical report 
form, a printed or electronic form for recording study participants’ data during a clinical 
study, as required by the protocol.
CRP
clinical research physician
CRPC
castrate-resistant prostate cancer
CRS
clinical research scientist
CS7
A recombinant rat IgG1 antibody specific for murine CSF-1R, used as a surrogate 
antibody to evaluate the effects of targeting CSF-1R on macrophages in murine models of 
cancer.
CSF
colony-stimulating factor
CSF-1
colony-stimulating factor-1
CSF-1R
colony-stimulating factor-1 receptor
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events

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DCR
disease control rate
DLT
dose-limiting toxicity
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
ELISA
enzyme-linked immunosorbent assay
end of trial
End of trial is the date of the last visit or last scheduled procedure for the last patient.
enroll
Patients who are enrolled in the trial are those who have been assigned to a treatment and 
have received at least one dose of study treatment.
enter
Patients who are entered in the trial are those who have signed the informed consent form 
directly or through their legally acceptable representatives.
ERB/IRB
ethical review board/institutional review board: A board or committee (institutional, 
regional, or national) composed of medical and nonmedical members whose 
responsibility is to verify that the safety, welfare, and human rights of the patients 
participating in a clinical study are protected.
FACS
fluorescence-activated cell sorting (a type of flow cytometry)
FOIA
United States Freedom of Information Act
GCP
good clinical practice
GERD
gastroesophageal reflux disease
GnRH
gonadotropin-releasing hormone
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
IC50
half maximal inhibitory concentration
ICF
informed consent form
ICH
International Conference on Harmonisation
IgG1
immunoglobulin G, subclass 1
IL
interleukin
IMC-CS4
sponsor code name for recombinant human immunoglobulin G, subclass 1 (IgG1) 
monoclonal antibody targeted to the colony-stimulating factor-1 receptor (CSF-1R); also 
known as LY3022855
INF
interferon

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informed consent
A process by which a patient voluntarily confirms his or her willingness to participate in a 
particular trial, after having been informed of all aspects of the trial that are relevant to the 
patient’s decision to participate.  Informed consent is documented by means of a written, 
signed and dated informed consent form (ICF).
interim analysis
An analysis of clinical study data that is conducted before the final reporting database is 
authorized for data lock.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial.
investigator
A person responsible for the conduct of the clinical study at a study site.  If a study is 
conducted by a team of individuals at a study site, the investigator is the responsible 
leader of the team and may be called the principal investigator.
irAE
immune-related adverse event
irRECIST
immune-related RECIST (Response Evaluation Criteria in Solid Tumors)
I.V.
intravenous(ly)
Kd
dissociation constant
legal representative
An individual, judicial, or other body authorized under applicable law to consent on 
behalf of a prospective patient, to the patient’s participation in the clinical study.
Lilly Safety System
Global safety database that tracks and reports serious adverse and spontaneous events 
occurring while using a drug/drug delivery system.
LDH
lactate dehydrogenase
LY3022855
Lilly code name for recombinant human immunoglobulin G, subclass 1 (IgG1) 
monoclonal antibody targeted to the colony-stimulating factor-1 receptor (CSF-1R); also 
known as IMC-CS4
LVEF
left ventricular ejection fraction
monitor
A person responsible for ensuring the investigator site complies with the monitoring plan, 
applicable local standard operating procedures (SOPs), if any, and global Medical SOPs.  
Monitors are trained on the investigational product(s), the protocol, informed consent 
form (ICF), any other written information provided to subjects, relevant SOPs, 
International Conference on Harmonisation Good Clinical Practice guidelines (ICH-
GCP), and all applicable laws (for example, privacy and data protection) and regulations. 
MRI
magnetic resonance imaging
MSD
Meso Scale Discovery
NCI
National Cancer Institute
NK
natural killer (cells)
NOAEL
no-observed-adverse-effect level

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NYHA
New York Heart Association
open-label
A study in which there are no restrictions on knowledge of treatment allocation; therefore,
the investigator and the study participants are aware of the drug therapy received during 
the study.
ORR
overall response rate
OS
overall survival
patient
A subject with a defined disease.
PCWG2
Prostate Cancer Clinical Trials Working Group
PD
pharmacodynamic or progressive disease
Note - “Pharmacodynamic” and “progressive disease” are spelled out throughout this 
protocol, except as follows:  The abbreviation “PD” appears only in the study design 
figure and in tables in the protocol attachments. In these locations, the abbreviation is 
clearly defined.
PET
positron emission tomography
PFS
progression-free survival
PK
pharmacokinetic(s)
PR
partial response
Q2W
once every 2 weeks
QW
once weekly
RECIST
Response Evaluation Criteria in Solid Tumors
reporting database
A point-in-time copy of the collection database.  The final reporting database is used to 
produce the analyses and output reports for interim or final analyses of data.
re-screen
To screen a patient who was previously declared a screen failure for the same study
RP2D
recommended Phase 2 dose
SAE
serious adverse event
screen
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical trial. In this study, screening 
involves invasive or diagnostic procedures and/or tests (for example, x-rays, blood 
draws).  For this type of screening, informed consent for these screening procedures 
and/or tests shall be obtained; this consent may be separate from obtaining consent for the 
study.
screen failure
A patient who does not meet one or more criteria required for participation in a trial.
sponsor
The party who takes responsibility for the initiation, management and/or financing of a 
clinical study.

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study completion
This study will be considered complete when 16 evaluable patients are attained.
SUSAR
suspected unexpected serious adverse reactions
t1/2
half-life
TEAE
treatment-emergent adverse event
TK
toxicokinetic
TNF
tumor necrosis factor
TPO
third-party organization
ULN
upper limit of normal
Vss
volume of distribution at steady state
WOCBP
women of childbearing potential

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Phase 1 Study to Identifythe Immunomodulatory Activity of 
LY3022855 (IMC-CS4) in Patients with Advanced, Refractory
Breast or Prostate Cancer
5. Introduction
5.1. Rationale and Justification for the Study
CCI
Colony-stimulating factor-1 receptor (CSF-1R) is a tyrosine kinase receptor expressed 
selectively on macrophage and granulocyte cell lineages in normal individuals and on some
tumor cells in cancer (Kacinski 1995; Sasmono et al. 2003).  Upon colony-stimulating factor-1 
(CSF-1) or interleukin-34 (IL-34) binding to CSF-1R, CSF-1R and downstream signaling 
molecules are phosphorylated and activated, resulting in the regulation of proliferation, 
differentiation, survival,and migration of monocytes/macrophages (Bourette and Rohrschneider 
2000; Pixley and Stanley 2004; Lin et al. 2008).  In cancer, increased infiltration of macrophages 
within and surrounding the tumor mass correlates with increased tumor invasiveness and growth 
(Nowicki et al. 1996; Lewis and Pollard 2006), and depleting these tumor-associated 
macrophages results in decreased growth of experimental tumors in mice (Lin et al. 2001,2006).  
While CSF-1R levels are infrequently increased in tumors compared with analogous normal 
tissues, increased CSF-1 in sera of cancer patients is more frequently observed and is associated 
with poor prognosis and severity of disease in multiple cancers, in particular prostate and breast 
cancers (Lawicki et al. 2006; Mroczko et al. 2007; Ide et al. 2008; Zhu et al. 2008).  These data 
suggest that targeting CSF-1R has potential to limit cancer progression.
LY3022855 (also knownasIMC-CS4)is a recombinant human monoclonal antibody of the 
immunoglobulin G, subclass 1 (IgG1) targeting CSF-1R.  LY3022855prevents the ligands CSF-1 
and IL-34 from binding to CSF-1R 
 
, and in this way inhibits CSF-1R activation.  CSF-1R 
activation is required for proper functioning and survival of tumor-associated macrophages.  
Thus, by blocking CSF-1R activation, 
 
 
 
 
 
 
 
 
 
Interactions between the innate and adaptive immune systems are critical for normal immune 
function and also in the tumor microenvironment.  Forexample, high numbers of 
tumor-associated macrophages inversely correlate with infiltration by CD8+ T cells. 
CCI

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Anti-CSF-1R treatment that limits tumor-associated macrophages enhances CD8+ T-cell
infiltration, leading to decreases in tumor burden (DeNardo et al. 2011).  Moreover, in a 
syngeneic breast cancer model, depletion of CD8+ T cells rendered treatment with CS7 less 
efficacious, indicating interplaybetween macrophage activity and T-cellinfiltration.  Thus, 
knowledge not only of the macrophage subpopulation but also of the T-cellsubset may affect the 
efficacy of LY3022855treatment in patients.
 
 
In addition,pharmacodynamic results from the ongoing Phase 1 
dose-escalation study of LY3022855, Study I5F-IE-JSCA (also known as IMCL CP24-1001; 
hereafter referred to as JSCA), have suggested target engagement and biologic activity at a 
dosageof 1.25mg/kg once weekly.  
 
The sponsor, monitor, and investigators will perform this study in compliance with the protocol, 
good clinical practice (GCP) and InternationalConference on Harmonisation (ICH) guidelines, 
and applicable regulatory requirements.
5.2. Objectives
5.2.1. Primary Objective
The primary objective of this study is to document the immunomodulatory activityof 
LY3022855treatment in patients with advanced, refractorybreast orprostate cancers, according 
tothe following measures:
Changes from baseline over time inperipheral blood immune cell subsets,as determined
by flow cytometric analysis using an antibody panel,and that may include butnot be 
limited to the following markers: Live-Dead, CD3, CD4, CD8, CD14, CD16, FoxP3, 
PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS.

CCI
Changes from baseline over timein serum cytokines, as determined by Meso Scale 
Discovery (MSD) multiplex cytokine immunoassay technologyor enzyme-linked 
immunosorbent assay (ELISA),and thatmay includebutnot be limited tothe following:  
CSF-1, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-34, and tumor 
necrosis factoralpha (TNF-α).
CCI

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LY3022855(IMC-CS4)
5.2.2. Secondary Objectives
The secondary objectives of this study are:
To evaluatethe safety and toxicity profile of LY3022855,as assessed bythe Common 
Terminology Criteria for Adverse Events, version 4.0(CTCAE v4.0)
To assessthe pharmacokinetic (PK) serum concentrationsof LY3022855
To document antitumor activity, per ResponseEvaluation Criteria in Solid Tumors, 
version 1.1 (RECIST 1.1)(Eisenhauer et al. 2009)and immune-related RECIST 
(irRECIST)(Nishino et al. 2013)(Note:  If a patient has confirmed progressive disease 
per RECIST 1.1 but not per irRECIST, the patient will be considered to have not 
progressed.)
Toassess the development of antibodies against LY3022855(immunogenicity), as 
assessed bya validated immunogenicity assay
5.2.3. ExploratoryObjectives
The exploratoryobjectives of this study are:
To explore serum biomarkersthat may be relevant to the mechanism of action of 
LY3022855,
 
To explore the pharmacodynamic effects of LY3022855on tissue biomarkers, using
flash-frozen baseline and posttreatment tumor biopsies
To assess antitumor activity in bone,per the ProstateCancer Clinical Trials Working 
Group (PCWG2) (Scher et al. 2008)criteria
5.3. General Introduction to LY3022855
LY3022855is a recombinant human monoclonal antibody of IgG1 that targetsCSF-1R, a 
tyrosine kinase receptor expressed selectively on macrophage and granulocyte cell lineages in 
normal individuals and on tumor cells in cancer (Kacinski 1995; Sasmono et al. 2003). 
The presenttrial will look specifically at the immunomodulatory activity of LY3022855in 
patients with advanced breast orprostate cancerrefractory or intolerant to at least one prior 
therapy for their cancer.
Refer to Section 5.1for a review of the literature relevant to this study.  Refer to Section5.4.5
CCI
for a summary of prior clinical findings relevant to the present trial.
CCI

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5.3.1. Definition of Immunomodulatory Change
Immunomodulatory change is the capacity to modify, regulate, or potentiate one or more 
immune functions by changes in immune cell activity or ratios or changes in immune or 
inflammatory cytokine levels. Data from the sponsor’s preclinical animal studies and the 
literature (DeNardo et al. 2011) highlight the importance of T cells in anti-CSF-1R responses, 
illustrating the necessity of studying this interaction further.
The present study will evaluate changes in immune function in patients with advanced, refractory 
breast or prostate cancer by assessing changes in subset distribution and activation marker 
phenotypes in CD4, CD8, regulatory T cells, and myeloid cells in the peripheral blood.  In 
addition, immune function will be evaluated through assessments of specific immune cytokines 
in peripheral blood, such as IL-2 and TNF-α, which modulate immune function.
5.4.
LY3022855 – Nonclinical and Clinical Experience
5.4.1. Nonclinical Pharmacokinetics
The pharmacokinetics of LY3022855 were evaluated in mice administered 20 mg/kg and in
cynomolgus monkeys at dose levels that ranged from 10 to 180 mg/kg. The PK of LY3022855
in cynomolgus monkeys was characterized by a relatively long serum half-life (t1/2) after single
(183-275 hours) or multiple doses (158-470 hours); these half-lives were substantially longer
than that observed in CD-1 mice (110 hours). Accumulation (approximately 2-fold) of 
LY3022855 was evident after repeated once-weekly dosing in monkeys, suggesting that 
accumulation may similarly occur in humans, depending on the frequency of dosing. The 
estimated volume of distribution of LY3022855 in monkeys (approximately 29-64 mL/kg) 
indicated that LY3022855 was not substantially distributed beyond the vasculature. In the 
cynomolgus monkey studies, LY3022855 serum exposures were generally proportional to the 
increases in dose from 10 to 180 mg/kg and no sex differences were observed.
The concentration of serum CSF-1 increased in cynomolgus monkeys that were treated with
LY3022855, suggesting that CSF-1 is a pharmacodynamic marker of LY3022855 exposure.  
However, in contrast to the LY3022855 levels, CSF-1 levels did not increase proportionally with
the increase in LY3022855 dose. The concentration of CSF-1 reached apparent maximal level in
all dose groups after the first dose, typically between 24 and 168 hours following administration
of LY3022855. This observation suggests that the pharmacodynamic effect of LY3022855 on
circulating CSF-1 reached saturation at the lowest dose levels (10 or 20 mg/kg). CSF-1 levels
were generally sustained throughout the sampling period. However, in the repeat-dose
cynomolgus monkey study, the concentration of CSF-1 began to decrease in some animals from
the low- (20 mg/kg) and middle- (60 mg/kg) dose groups during the recovery period.
Formal studies to characterize the metabolism and disposition of LY3022855 have not been
conducted. As a monoclonal antibody, LY3022855 will be largely confined to the extracellular
space, which is supported by data from numerous investigations and is consistent with the PK
evaluation of LY3022855. No formal metabolism studies of LY3022855 have been performed 

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LY3022855 (IMC-CS4)
because the catabolism of antibodies by mammalian systems is largely understood and formal 
studies of the metabolic degradation of these molecules are not warranted.
For details on the nonclinical PK of LY3022855, refer to Section 5 of the current Investigator’s 
Brochure (IB).
5.4.2. Nonclinical Pharmacokinetic/Pharmacodynamic Model
One of the main pharmacological effects of LY3022855 proposed to underlie the inhibition of 
cancer progression is the depletion of tumor-associated macrophages.  To model this effect and 
estimate the minimum effective blood level required to achieve significant antitumor effects, 
cancer models established in mice were utilized.  However, since LY3022855 does not bind to 
murine CSF-1R, a surrogate antibody, CS7, was developed and utilized in order to examine 
PK/pharmacodynamic relationships.  The binding affinity of CS7 to murine CSF-1R 
(dissociation constant [Kd] = 0.13nM) is 6-fold greater than that of LY3022855 to human CSF-
1R (Kd = 0.8nM).  However, comparable potencies of the antibodies were observed in cell-based 
assays of inhibition of CSF-1-induced phosphorylation (IC50 = 0.3nM for both antibodies), 
monocyte differentiation (IC50 = 0.3nM vs 0.25nM for CS7 and LY3022855, respectively), and 
inhibition of monocyte proliferation (IC50 = 0.13nM or 0.1nM for CS7 and LY3022855, 
respectively).  Therefore, CS7 and LY3022855 were anticipated to have similar pharmacological 
effects in vivo at similar concentrations.  Hence, CS7 was utilized in animal models to directly 
predict the trough serum LY3022855 levels necessary to achieve relevant efficacy in human 
subjects.
Based on these assumptions, to estimate target serum concentrations for efficacy in initial 
clinical investigations, trough concentrations associated with efficacy were determined in human 
breast cancer HCC-1954 and human leukemia NKM-1 models established in mice.  LY3022855
was evaluated in the leukemia model established following intravenous (I.V.) injection of 
CSF-1R-expressing NKM-1 cells.  The rat surrogate, CS7, was used in the breast cancer model 
established following subcutaneous injection of CSF-1R-negative HCC-1954 cells.  The results 
from the 2 studies identified markedly different efficacious concentrations for the antibodies in 
the different models.  The human NKM-1 model appeared very sensitive to the antitumor effect 
of LY3022855, as efficacy was achieved at mean trough concentrations down to 0.2 µg/mL. For 
CS7, notably higher doses and concentrations were required to inhibit human HCC-1954 breast 
cancer tumor growth, as a mean trough concentration of 425 µg/mL was associated with 
efficacy.
5.4.3. Clinical Pharmacokinetics
As of 28 January 2016, the clinical experience of LY3022855 PK comprised 27 patients enrolled 
in Study JSCA (0.3 mg/kg once weekly [QW] [n=4], 0.6 mg/kg QW [n=3], 1.25 mg/kg QW 
[n=5], 1.25 mg/kg once every 2 weeks [Q2W] [n=9], and 2.5 mg/kg QW [n=6]), and 14 patients 
enrolled in Study JSCB (1.25 mg/kg Q2W [n=9] and 1 mg/kg on Weeks 1, 2, 4, and 5 of every 
6-week cycle [n=5]).

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LY3022855 (IMC-CS4)
LY3022855 in cancer patients exhibited moderate total body clearance (CL) (mean values on 
Day 1 ranged from 0.0378 to 0.0651 L/h), low volume of distribution at steady state (Vss) (mean 
values on Day 1 ranged from 2.85 to 4.93 L), and moderate t1/2 (mean values on Day 1 ranged 
from 30.8 to 92.2 hours).
LY3022855 CL appeared to be nonlinear with respect to LY3022855 concentration, where
higher doses of LY3022855 tended to exhibit lower CL values. However, this apparent 
nonlinearity was confounded by the high incidence of concentrations reported as below the 
quantifiable lower limit of the assay (BLQ), which could artificially inflate the calculated CL at 
lower doses.
An apparent lack of relationship between patient body weight and LY3022855 CL 
(Figure JSCB.1, upper panel) resulted in an amended dose-escalation plan for Study JSCA, to 
evaluate the safety, PK, and immunogenicity of LY3022855 using a fixed-dosing approach (that 
is, mg as opposed to mg/kg).
The clinical PK of LY3022855 are described in greater detail in Section 6.1 of the IB.

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Abbreviations:  N = number of patients treated; QW = once weekly; Q2W = once every 
2 weeks.
Figure JSCB.1.
Individual observed clearance versus patient body weight (upper 
panel) and LY3022855 dose (lower panel) for Studies JSCA and 
JSCB.
5.4.4. Nonclinical Toxicology
A standard nonclinical toxicology program for advancement of a monoclonal antibody into
clinical trials in oncology indications was conducted to assess the safety and toxicity of
LY3022855. The nonclinical safety assessment of LY3022855 was conducted in cynomolgus
monkeys. This species was considered a relevant model for the nonclinical safety evaluation of
LY3022855, based on a preliminary cross-species evaluation of tissue/receptor binding and/or
functional in vitro pharmacological activity in human and cynomolgus monkey test systems and
in a subsequent comprehensive tissue cross-reactivity study using full panels of monkey and
human tissues. The toxicology studies conducted with LY3022855 included an exploratory
single-dose toxicity and toxicokinetic (TK) dose range-finding study and a pivotal 4-week
repeat-dose good laboratory practice toxicity, TK, and immunogenicity study with a 6-week
recovery period. Animals were administered LY3022855 by I.V. infusion, the intended clinical
method of administration, using the dosing schedule (once weekly) in the planned initial clinical
investigations of LY3022855. The pivotal study included evaluations of relevant safety

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LY3022855(IMC-CS4)
pharmacology parameters. Because of an anticipated effect of LY3022855on circulating levels 
ofthe target ligand, CSF-1, the levels of CSF-1 were also measured in the study animals as a
potential marker of the pharmacodynamic activity of the antibody. A thorough assessment of
peripheral blood and spleen mononuclear cell subsets and an immunohistochemical analysis of
CD68+ cells (cellular marker of monocytes/macrophages) in liver and spleen were also included
to determine the effects that blockade of the CSF-1 receptor might have on these endpoints.
Assessment of the genotoxicity potential of monoclonal antibodies is not relevant and was,
therefore,not studied. Based on the early stage of clinical development and the oncology
indication, reproductive toxicity studies of LY3022855have not been conducted.
5.4.4.1.
Single-Dose Toxicity
CCI
Single-dose administration of LY3022855at dose levels of 10, 40, and 140 mg/kg administered 
byI.V. infusion over a 15-minute period was well tolerated in cynomolgus monkeys 
(2monkeys/sex/group) during the 14-day observation period. Sustained dose-proportional 
exposure to LY3022855was generally observedthroughout the 14-day observation period at all 
dose levels following administration, with noapparent sex differences. 
 
 
 
 
 
 
 
 
 
Similar 
elevations in serumenzyme levels have also been observed when treating with other 
pharmacological agentstargeting CSF-1R (Wang et al. 2011) or CSF-1 (Radi et al. 2011).
No other adverse clinical signs or effects on food consumption, body weight, hematology, and
organ weights were associated with administration of LY3022855.
CSF-1 serum levels increased relatively quickly after LY3022855administration and remained
sustained throughout the 14-day observation period. CSF-1 was not detected in any control
animals at any time. The maximum levels of CSF-1 reached were comparable across dose
groups, suggesting that a maximal pharmacodynamic effect of LY3022855on this parameter 
wasachieved at even the lowestdose level in the study.
The no-observed-adverse-effect level (NOAEL) in this study was considered to be 
 This dose corresponded to a dosing Day 1 
 
CCI
CCI
CCI

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LY3022855(IMC-CS4)
5.4.4.2.
Repeat-Dose Toxicity
CCI
In the pivotal repeat-dose toxicity, TK, and immunogenicity study of LY3022855, doses of 0, 20,
60, and 180 mg/kg/dose LY3022855were administered by I.V. infusion once weekly to
cynomolgus monkeys (5/sex/group) for 4 weeks, followed by a 6-week recovery period. 
Standard toxicological and relevant safety pharmacology(cardiovascular, central nervous[CNS], 
and respiratory systems)endpoints were assessed. As in thesingle-dose study, circulating levels 
of CSF-1 were measured. A thorough assessment ofperipheral blood and spleen mononuclear 
cell subsets and an immunohistochemical analysis ofCD68+ mononuclear cells in liver and 
spleen were also conducted.
Intravenous infusion of LY3022855was generally well tolerated at all dose levels. Sustained 
dose-proportionalto slightly-greater-than-dose-proportional increases in exposure to LY3022855
weregenerally observed, and no sex differences in exposure were apparent. Moderate 
accumulation(approximately 2-fold) of LY3022855occurred after repeated administration. 
Anti-drug antibodies (ADA)
 
 
As noted in the single-dose exploratory study, circulating concentrations of CSF-1 increased
shortly after LY3022855administration. CSF-1 was not detected in any control animals. In
contrast to LY3022855, the concentration of CSF-1 did not vary with dose, as comparable
maximum levels were reached in all 3 dose groups. Towards the end of the recovery period,
CSF-1 levels generally decreased in the 20-and 60-mg/kg dose groups, but remained elevated in
the 180-mg/kg dose group.
The key toxicological findings attributed to LY3022855administration in this studywere 
periorbital swelling, increases in serum transaminases as noted in the exploratory
 study,changes 
in leukocyte populations (monocytes, neutrophils, CD68+ mononuclear cells, naturalkiller [NK] 
cells), and target organ effects in liver (Kupffer cell hypertrophy/hyperplasia), spleen(follicular 
hypertrophy/dendritic cell hyperplasia), and bone marrow (hypercellularity). The
immunomodulatory effects on leukocytes, Kupffer cells, spleen, and bone marrow likely reflect
an exaggerated pharmacological response to LY3022855, possibly associated with elevations in
circulating CSF-1 levels noted during the study.
Elevations in ALT after the last dosing of LY3022855were generally minimal in the lowest dose
group (20 mg/kg) and minimal to moderate at the 60-and 180-mg/kg dose levels. AST levels
were minimally to moderately increased at all dose levels. ALT and AST returned to baseline in
the 20-mg/kg group and trended towards baseline in the 60-and 180-mg/kg groups during the
recovery period, but remained increased in some individual animals compared with baseline. No
histological changes in the liver were noted to correlate with the transaminase increases, nor
were any changes noted in liver functional parameters (that is, AP, bilirubin,and coagulation). 
Therefore, based on the small magnitude of the elevations and the absence ofhistological or 
functional changes, the increases in ALT and AST were not considered adverse.

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LY3022855 (IMC-CS4)
Increases in circulating white blood cells due to increases in neutrophils and monocytes were
observed in both sexes at 60 and 180 mg/kg. Flow cytometry analysis of spleen and peripheral
blood revealed increases in monocytes in spleen and blood at 60 and 180 mg/kg and reductions
in splenic NK cells in all LY3022855-treated groups. Variability in NK cell numbers in the
peripheral blood of animals in all dose groups (including control) precluded assigning a
definitive relationship with LY3022855 treatment. These changes in white blood cell counts, in
conjunction with minimal reversible increases in serum globulin concentrations with a
corresponding decrease in albumin to globulin ratio, are consistent with the presence of an
inflammatory response. However, no histopathologic evidence of inflammation was observed.
The monocyte, neutrophil, and globulin changes were reversible by the end of the recovery
period, while the splenic NK cell reductions were still apparent in some animals. These changes
were not considered adverse because of their small magnitude.
Anatomic pathology changes attributed to the administration of LY3022855 at the end of the
dosing period included increased spleen weights in females (all dose groups), which generally
correlated with splenic follicular hypertrophy (males at 60 and 180 mg/kg; females at 20 and
180 mg/kg), bone marrow hypercellularity (all female dose groups, one male at 60 mg/kg), bone
marrow lymphoid aggregates (one male, one female at 180 mg/kg), and Kupffer cell
hypertrophy/hyperplasia (primarily minimal, all male dose groups, one female at 60 mg/kg).
Immunohistochemical analyses confirmed the presence of increased size or number of CD68+
Kupffer cells in the liver and increased numbers of CD68+ mononuclear cells in the spleen at all
dose levels. The CD68+ cells in the spleen were likely follicular dendritic cells. The
immunohistochemical findings in liver and spleen generally correlated with the histopathologic
diagnoses of Kupffer cell hypertrophy/hyperplasia and splenic follicular hypertrophy. Similar
anatomic pathology findings in spleen, liver, and bone marrow were observed after the recovery
period. These changes were not considered adverse because of their small magnitude.
Slight to moderate periorbital swelling was observed primarily during the recovery phase in all
LY3022855-treated groups (20, 60, and 180 mg/kg/dose). This clinical sign has been reported to
occur in humans with another antibody to CSF-1 (Sadis et al. 2009) and may thus represent a
delayed response to LY3022855 in the treated monkeys. Watery feces was observed only in the
60-mg/kg/dose animals, but is considered possibly related to the administration of LY3022855.
These clinical signs were not considered adverse based on their limited impact to the overall
health of the animal. No adverse effects were noted in assessments of the central nervous
(neurological behavioral examination), respiratory (rate), or cardiovascular (heart rate, blood
pressure, electrocardiogram [ECG]) systems. In addition, no evidence of an adverse reaction or
intolerance attributable to LY3022855 was apparent at the injection sites after I.V. infusion in the
cynomolgus monkey repeat-dose toxicity studies.
Based on the absence of any definitive LY3022855-related adverse findings, the NOAEL for
LY3022855 administered via 15-minute I.V. infusion weekly on 4 occasions was considered to 
be 180 mg/kg/dose. The dose corresponded to a dosing Day 22 mean Cmax of 7985 µg/mL, C168hr
of 2945 µg/mL, and mean AUC(0-168hr) of 711340 µg·hr/mL.

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5.4.5. Clinical Experience
Clinical experience with LY3022855 comprises 43 patients (as of 28 January 2016) who 
received the following doses I.V. in 2 ongoing Lilly-sponsored Phase 1 studies (I5F-IE-JSCA 
[JSCA] and I5F-MC-JSCB [JSCB]): 2.5 mg/kg QW (n=6), 0.3 mg/kg QW (n=4), 0.6 mg/kg 
QW (n=3), 1.25 mg/kg Q2W (n=20), 1.25 mg/kg QW (n=5), and 1 mg/kg on Weeks 1, 2, 4, and 
5 of every 6-week cycle (n=5). At the first human dose studied, 2.5 mg/kg QW (Study JSCA), 
which was also the highest dose administered, laboratory abnormalities, including Grade 2-3 
creatine kinase (CK) and Grade 2-3 AST elevations, were noted in 5 patients but were not 
classified as dose-limiting toxicities (DLTs) due to the lack of clinical signs or symptoms of 
organ toxicity.  Because of these laboratory abnormalities, the protocol for Study JSCA was 
amended and dose escalation was restarted at a lower dose, 0.3 mg/kg QW.
Elevated levels of CK and AST, in the absence of clinical signs or symptoms or other laboratory 
abnormalities suggestive of end-organ damage are, in retrospect, believed to be
pharmacodynamic indicators of target engagement, rather than markers of drug-related toxicity.  
This belief is strengthened by findings of Radi et al. (2011), in which preclinical models support 
the hypothesis that increases in the levels of serum enzymes can be the result of decreases in 
Kupffer cells, in the apparent absence of hepatic or skeletal muscle injury.  In all cases where 
elevated enzymes were observed following LY3022855 administration in Study JSCA, the levels 
decreased to Grade <2 upon discontinuation of LY3022855, indicating that these effects were 
reversible.
As of 12 October 2016, four DLTs have been observed in Study JSCA:  an event of left 
ventricular dysfunction (Cohort 4, 1.25 mg/kg Q2W), an event of pancreatitis (a patient in 
Cohort 5, 1.25 mg/kg QW), an event of rhabdomyolysis (another patient in Cohort 5), and an 
event of Grade 3 CK elevation (Cohort 7a, 150 mg QW).  The patient with the DLT of left 
ventricular dysfunction had a baseline left ventricular ejection fraction (LVEF) of 35%, which 
obfuscated the relationship between LY3022855 and the DLT event; therefore, the patient was 
considered to be a suboptimal candidate for study participation.  The patient in Cohort 5 who 
experienced pancreatitis had a medical history significant for irritable bowel syndrome and 
gastroesophageal reflux disease (GERD), rendering the patient prone to nausea and abdominal 
pain.  During the course of treatment in Study JSCA, this patient’s serum levels of lipase 
gradually increased, from 21 U/L (baseline) to 138 U/L (Cycle 1, Week 6 [C1W6]) (C1W2 = 79 
U/L, C1W3 = 90 U/L, C1W4 = 121 U/L, C1W5 = 149 U/L).  Following the C1W3 
administration of LY3022855, the patient’s treatment with study drug was held due to rising 
lipase levels.  Steroids were not initiated until the patient presented for medical attention with 
complaints of nausea, vomiting, and abdominal pain on C1W6, at which time the patient was 
diagnosed with Grade 3 pancreatitis.  The symptoms improved with hospitalization, supportive 
therapy, and systemic steroids.  Although this particular case resulted in a DLT, the relationship 
between elevated lipase and gastrointestinal symptoms is not clear, given the patient’s history of 
irritable bowel syndrome and GERD.
Following the occurrence of the 2 DLTs in Cohort 5 of Study JSCA, dose escalation was 
temporarily halted.  Subsequent PK and pharmacodynamic analyses revealed the following:

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LY3022855 (IMC-CS4)

A lack of correlation between body weight and LY3022855 clearance (Figure JSCB.1)

Intermittent inhibition of CSF-1R signaling with Q2W dosing of LY3022855, as 
evidenced by levels of both circulating CSF-1 and peripheral CD14dimCD16bright cells by 
fluorescence-activated cell sorting (FACS) (Figure JSCB.2)

Sustained inhibition of CSF-1R signaling with 2.5 mg/kg QW and 1.25 mg/kg QW 
dosing (Study JSCA Cohorts 1 and 5, respectively) of LY3022855, as evidenced by 
levels of both circulating CSF-1 and peripheral CD14dimCD16bright cells by FACS (Figure 
JSCB.2)
Based on these observations, the protocol for Study JSCA was amended to:  (1) examine fixed 
(non-weight-based) dosing of LY3022855 on weekly administration schedules to optimize the 
biological effects of LY3022855 on CSF-1R inhibition, (2) redefine a DLT as any LY3022855-
related AE that occurs during Cycle 1 and does not improve to Grade ≤2, unless stated otherwise, 
despite medical management, including steroids (if applicable) within 7 days of documented 
occurrence, and (3) incorporate management guidelines for immune-related AEs.  Dosing in 
Study JSCA resumed at a fixed dose of 100 mg QW, which is comparable to 1.33 mg/kg in a 75-
kg person and within the coefficient of variation in exposure (34% to 49%).  As of 12 October
2016, 3 patients in Study JSCA have received 100 mg QW for 6 weeks (Cycle 1, DLT 
assessment period) without experiencing a DLT. Of the 3 patients treated at the next higher dose 
level of 150 mg QW, 1 patient experienced a DLT of Grade 3 CK elevation associated with 
elevated serum and urine myoglobin.

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LY3022855 (IMC-CS4)
Abbreviation:  C = cohort.
Figure JSCB.2.
CD14dimCD16bright (relative percentage of CD45+ HLA-DR+ CD14+) in 
the blood of patients from Study JSCA.
More information about the known and expected benefits, risks, and reasonably anticipated AEs 
may be found in the IB.  Information on AEs expected to be related to the investigational product 
may be found in Section 7 (Development Core Safety Information) of the IB.  Information on 
SAEs expected in the study population independent of drug exposure and that will be assessed 
by the sponsor in aggregate, periodically during the course of the study, may be found in Section 
6 (Effects in Humans) of the IB.

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5.5.
Rationale for Selection of Dose
The optimal dose and schedule of LY3022855 in humans are not known.  The protocol will 
utilize 4 dosages of LY3022855,where Dosages A and B are weight based, while Dosages C and 
D are non-weight based (that is, fixed), as prior data suggest that weight-based dosing does not 
affect exposure (Section 5.4.3).  Refer to Table JSCB.1 for a summary of the LY3022855 
dosages to be used in this study.
Table JSCB.1.
Summary of LY3022855 Dosages in Study JSCB
Dosage
Dose
Schedule (based on a 6-week cycle)
Dosage A (weight based dose)
1.25 mg/kg
Q2W
Dosage B (weight based dose)
1 mg/kg
Weeks 1, 2, 4, and 5 of a 6-week cycle
Dosage C (non-weight based/fixed dose)
100 mg
QW
Dosage D (non-weight based/fixed dose)
100 mg
Q2W
Abbreviations:  QW = weekly; Q2W = every 2 weeks (Weeks 1, 3, and 5).
The rationale for each dosage is presented as follows.
Dosage A is based on the following observations from Study JSCA:

A dosage of 1.25 mg/kg every 2 weeks was the lowest dosage tested in Study JSCA that 
demonstrated a significant increase in the 2 ligands of CSF-1R (CSF-1, IL-34).

Results demonstrated an acceptable clinical safety profile of LY3022855 at a dose of 
1.25 mg/kg every 2 weeks.
Dosage B rationale:

PK parameters from Study JSCA revealed a 34% to 49% coefficient of variation in 
exposure (AUC0-∞) for patients administered LY3022855 at 1.25 mg/kg every 2 weeks or 
1.25 mg/kg weekly.  Dosage B at 1 mg/kg on Weeks 1, 2, 4, and 5 of a 6-week cycle will 
result in a cumulative dose of 4 mg/kg every 6 weeks, which is 0.25 mg/kg (6.7%) 
greater than the cumulative dose per (6-week) cycle of Dosage A (1.25 mg/kg every 
2 weeks).  However, a 6.7% increase in exposure is within the variation of exposure 
documented in Cohorts 4 and 5.  Thus, Dosage B is a reasonable dose and schedule in 
terms of safety.  Additionally, dosing 2 consecutive weeks is expected to enhance 
inhibition of CSF-1R, based upon preliminary pharmacodynamic data (CSF-1 and IL-34) 
from Cohorts 4 and 5.  Furthermore, interruption of dosing every 3 weeks provides an 
opportunity for LY3022855-associated laboratory abnormalities to normalize prior to 
resumption of dosing, as has been observed in the Phase 1 dose-escalation Study JSCA.

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LY3022855 (IMC-CS4)
Dosage C rationale:

Pharmacodynamic data (Section 5.4.5) suggest that weekly administration of LY3022855 
results in enhanced target engagement.  Thus, Dosage C will be implemented to examine 
weekly administration of LY3022855.
Dosage D rationale:

It has been observed that all patients who were treated with LY3022855 and experienced
antitumor activity (as evidenced by tumor shrinkage or stability) as of 24 August 2016
were treated on a Q2W schedule.  Thus, Dosage D will be implemented to continue 
exploring Q2W dosing, but at a fixed (non-weight-based) dose.  Furthermore, the Q2W 
schedule may be preferable for quality of life, because the patient will require fewer 
clinic visits.

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6.
Investigational Plan
6.1.
Study Population
Individuals with advanced, refractory breast or prostate cancer are eligible. Specifically, to be 
enrolled in the trial, patients must have a biopsy-proven breast or prostate cancer diagnosis with 
clinical evidence of advanced-stage disease and must be willing to undergo 2 separate core 
needle or surgical biopsy procedures (1 at baseline [predose] and 1 prior to Cycle 2), optimally 
from the same lesion. Patients are considered evaluable if they complete 1 cycle of treatment 
(at least Cycle 1, Day 43, based on a 6-week cycle), undergo 1 baseline and 1 posttreatment 
tumor biopsy procedure (ie, attempted, whether the biopsy is successful or not), and complete 
immune blood studies for 1 cycle.
Individuals who do not meet the criteria for participation in this study (screen failure) may be re-
screened if agreed upon by the sponsor. If a patient discontinues prior to the second biopsy, the 
patient will be replaced.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.1. Inclusion Criteria
Patients may be included in the study if they meet all of the following criteria during screening 
prior to first dose of study drug.
[1]
Have a confirmed diagnosis of advanced, refractory breast or prostate cancer
that is evaluable by radiologic testing.  Patients must have experienced tumor 
progression on or treatment intolerance to at least one prior therapy for their 
cancer and have declined or are ineligible for a standard treatment.
[2a] For patients with metastatic castrate-resistant prostate cancer (CRPC) only:
a) must continue ongoing androgen deprivation therapy (gonadotropin-
releasing hormone [GnRH] agonist or antagonist) with castrate levels of 
serum testosterone <50 ng/dL determined within 4 weeks prior to starting 
treatment;
b) if receiving an antiandrogen as part of first-line hormonal therapy, must 
have shown progression of disease off the antiandrogen prior to 
enrollment;
c) must be willing to continue androgen deprivation therapy while on study, 
if no prior orchiectomy;

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LY3022855 (IMC-CS4)
d) must meet at least 1 of the following 3 criteria for progressive metastatic 
disease, according to PCWG2 criteria:
i. a rise in prostate-specific antigen (minimal value 2 ng/mL; 
≥3 consecutive rising values), or
ii. ≥2 new metastases on transaxial imaging or radionuclide bone scan, or
iii. soft tissue progression;
e) replacement hormone therapy (including prednisone or equivalent up to 
10 mg/day) initiated before study entry is permitted per Section 7.5.
[2b] For patients with breast cancer only:
a) may continue ongoing antiestrogen therapy (for example, an aromatase 
inhibitor), 
b) replacement hormone therapy initiated before study entry is permitted per 
Section 7.5, and
c) may continue ongoing trastuzumab therapy.
[3]
Are 18 years of age.
[4]
Have given written informed consent prior to any study-specific procedures.
[5]
Have adequate organ and hematologic function, including:

Hepatic:  Bilirubin 1.5 × the upper limit of normal (ULN), and ALT and 
AST 3.0 × ULN.  For patients with tumor involvement of the liver, AST 
and ALT ≤5.0 × ULN are acceptable.  For patients with tumor 
involvement of the bone, alkaline phosphatase ≤5.0 × ULN is acceptable.

Renal:  Serum creatinine 2.0 × ULN.

Absolute neutrophil count (ANC) ≥1.0 × 109/L.

Hemoglobin ≥9 g/dL (5.58 mmol/L).

Platelets ≥90 × 109/L.
[6]
Have a performance status of ≤2 on the Eastern Cooperative Oncology Group 
(ECOG) scale.  See Attachment 8.
[7]
Except as addressed in Inclusion Criterion [2], have discontinued all 
disease-modifying therapy for the primary cancer >28 days prior to initiation 
of study treatment.  In addition, clinically significant toxicities associated with 
any prior therapy for the primary cancer, including investigational treatments,
have resolved or stabilized to Grade ≤1 toxicity >28 days prior to initiation of 
study treatment with the exception of neuropathy, which must have resolved 
to Grade ≤2.  Continuation of a stable dose (minimum of 28 days prior to 
study entry) of denosumab or bisphosphonate is permitted on study.

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LY3022855 (IMC-CS4)
[8]
Are reliable and willing to make themselves available for the duration of the 
study and are willing and able to comply with study procedures (includes 
1 baseline and 1 posttreatment tumor biopsy procedure) and instructions.  
Patients enrolled in this trial must receive the study treatment at the study 
center.
[9a]
Male patients:
agree to use a reliable method of birth control and to not donate sperm during 
the study and for at least 12 weeks following last dose of study drug or 
country requirements, whichever is longer.
[9b] Female patients:
are women of childbearing potential who test negative for pregnancy within 
7 days prior to enrollment based on a urine or serum pregnancy test and agree 
to use a reliable method of birth control during the study and for 12 weeks 
following the last dose of the study drug and also must not be breastfeeding,
OR
are postmenopausal women.  Postmenopausal women include women with:
1) at least 6 weeks postsurgical bilateral oophorectomy with or without 
hysterectomy, confirmed by medical history
or
2) spontaneous amenorrhea for at least 12 months, not induced by a 
medical condition such as anorexia nervosa and not taking medications 
during the amenorrhea that induced the amenorrhea (for example, oral 
contraceptives, hormones, gonadotropin releasing hormone, 
antiestrogens, selective estrogen receptor modulators, or chemotherapy)
or
3) spontaneous amenorrhea 6 to 12 months and a follicle-stimulating 
hormone level greater than 40 mIU/mL.
[10] Have an estimated life expectancy that, in the judgment of the investigator, 
will permit the patient to complete 1 cycle of treatment.
[11] May have received treatment with an investigational product or non-approved 
use of a drug (other than the study drug used in this study) or device for 
non-cancer indications; however, not within 28 days prior to the initial dose of 
study drug (see also Exclusion Criterion [12]).
Refer to Section 7.5 for additional details regarding concomitant therapy.

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LY3022855 (IMC-CS4)
6.1.2. Exclusion Criteria
Potential study patients may not be included in the study if any of the following apply during 
screening.
[12] Have received treatment within 28 days prior to the initial dose of study drug 
with an investigational product or non-approved use of a drug or device (other 
than the study drug/device used in this study) for non-cancer indications or are 
concurrently enrolled in any other type of medical research judged not to be 
scientifically or medically compatible with this study (see also Inclusion 
Criterion [11]).
[13] Have serious preexisting medical conditions (left to the discretion of the 
investigator).
[14] Have symptomatic CNS malignancy or metastasis (screening not required).
Patients with treated CNS metastases are eligible for this study if they are not 
currently receiving corticosteroids (to control CNS edema), and their disease 
is asymptomatic for at least 28 days prior to enrollment.  Magnetic resonance 
imaging (MRI) documenting disease stability within 60 days prior to 
enrollment is also required.
[15] Have an active fungal, bacterial, and/or known viral infection, including 
human immunodeficiency virus (HIV) or viral (B or C) hepatitis (screening 
required for HIV and viral hepatitis B and C within 60 days prior to 
enrollment).
[16] Have any of the following cardiovascular conditions:
a) symptomatic coronary artery disease currently or within the past 6 months,
b) confirmed left ventricular ejection fraction ≤50% or any cardiac 
insufficiency > New York Heart Association (NYHA) class II* currently 
or within the past 6 months,
c) uncontrolled hypertension (>170/100 mm Hg) currently or within the past 
7 days, or
d) serious cardiac arrhythmia (well-controlled atrial fibrillation is permitted)
currently or within the past 6 months.
[17] Have a second active primary malignancy that, in the judgment of the 
investigator or sponsor, may affect the interpretation of the results.
[18] Are unwilling or unable to participate in tumor biopsies.
[19] Have corrected QT interval of >500 msec on screening ECG.
[20] Have received treatment with agents specifically targeting CSF-1 or CSF-1R,
including imatinib, nilotinib, and sunitinib.

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LY3022855 (IMC-CS4)
*NYHA Congestive Heart Failure Classification (NYHA 1994):
Class I – Patients with no limitation of activities; they suffer no symptoms from ordinary activities.
Class II – Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion.
Class III – Patients with marked limitation of activity; they are comfortable only at rest.
Class IV – Patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and 
symptoms occur at rest.
Refer to Section 7.5 for additional details regarding concomitant therapy.
6.2.
Summary of Study Design
Study I5F-MC-JSCB (JSCB) is a single-center, open-label, nonrandomized, noncontrolled
Phase 1 study of I.V. LY3022855 in patients with advanced, refractory breast or prostate cancer.  
Eligible patients will receive LY3022855 as an infusion, suggested to be administered over 
approximately 90 minutes for the first infusion, decreasing by 30 minutes for subsequent 
infusions, until administered over 30 minutes (refer to Section 7.2 for further details of study 
drug administration).  Study JSCB is intended to explore clinical response and immunological
activity of single-agent LY3022855 in approximately 40 patients (enrolled, of whom 36 will be
evaluable), by assessment of biomarkers, cytokines, and immune cells.  The study schema is 
shown in Figure JSCB.3.

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LY3022855 (IMC-CS4)
Abbreviations:  LY = LY3022855 (IMC-CS4); PD = progressive disease.
Figure JSCB.3.
Study JSCB study design.
Enrollment will be sequential, starting with the assignment of patients to Dosage A (LY3022855, 
1.25 mg/kg every 2 weeks [Q2W] of a 6-week cycle), then the assignment of patients to Dosage 
B (LY3022855, 1.0 mg/kg on Weeks 1, 2, 4, and 5 of a 6-week cycle) once the Dosage A cohort 
is fully enrolled.  Once the Dosage B breast cancer cohort is fully enrolled, patients with breast 
cancer will be assigned by the sponsor to Dosage C (LY3022855, 100 mg QW of a 6-week 
cycle) or D (LY3022855, 100 mg Q2W of a 6-week cycle) on an alternating basis until 5 patients 
are enrolled to each of Dosages C and D.  Once 5 patients are enrolled to each of Dosages C and 
D, the sponsor and the investigators will review clinical data to determine if enrollment of an
additional 5 patients to each of Dosages C and D is warranted (refer to Section 10 for details 
regarding sample size).

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LY3022855 (IMC-CS4)
Patients will receive Dosage A, B, C, or D for one 6-week cycle or until the patient meets one or 
more criteria for study discontinuation.  After 1 cycle, patients who are benefitting from study 
treatment (that is, no disease progression or unacceptable toxicity) may continue to receive study 
treatment at the same dose and schedule until there is clear (confirmed) evidence of disease 
progression or other withdrawal criteria are met.  At the time of study completion, if a patient 
continues to benefit from study treatment, that patient may enter the continued access period.
Immune studies will include evaluations of changes in baseline over time in:  (1) peripheral 
blood immune cell subsets, as determined by flow cytometric analysis using an antibody panel, 
and that may include but not be limited to the following markers: Live-Dead, CD3, CD4, CD8, 
CD14, CD16, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS, as well as (2) serum 
cytokines, as determined by MSD multiplex cytokine immunoassay technology or ELISA, and 
that may include but not be limited to CSF-1, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, IL-34, and TNF-α.  Blood samples for the immunomodulatory studies will be 
taken as described in Attachment 4, Attachment 5, and Attachment 6.
In addition, for all patients, 2 separate tumor biopsy procedures will be performed (attempted):  
the first will be performed at baseline (predose), within 14 days prior to dosing on Cycle 1, Day 
1, and the second will be performed within 14 days prior to dosing on Cycle 2, Day 1.  Biopsy 
samples will be flash frozen, for exploratory biomarker research, to be used in understanding the 
pharmacodynamic effects of LY3022855.  To ensure adequate enrollment for the immune 
studies, additional patients will be enrolled as needed to replace a patient who either:  (1)
discontinues from the study prior to the second biopsy procedure, or (2) does not have sufficient 
tumor tissue for the second biopsy procedure and in the opinion of the investigator is benefitting 
from study treatment (in which case, the patient will be allowed to remain on study treatment).  
In addition to the required blood and tumor samples previously noted, optional tumor biopsies 
and/or blood samples for biomarker research may be obtained at the investigator’s discretion in 
discussion with the patient, such as at the time of radiographic response or treatment progression.
For patients with measurable disease per RECIST, clinical endpoints for response will be 
standard tumor response as determined by RECIST 1.1 and irRECIST criteria. For the prostate 
cancer cohort only, progression in bone will be determined by using the PCWG2 criteria, which 
defines progression as the point at which at least 2 new lesions are observed on bone scan
(compared with baseline), and are then confirmed on a follow-up bone scan performed at least 
6 weeks later. However, if the point when the new lesions are observed is the first interval bone 
scan (that is, Week 6), then the confirmatory bone scan must demonstrate at least 2 additional 
new lesions (that is, a total of at least 4 new lesions from baseline).  Further details of the 
PCWG2 criteria are provided in Section 8.3.

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LY3022855 (IMC-CS4)
To document the immunomodulatory activity of LY3022855 treatment in patients with
advanced, refractory breast or prostate cancers, an adequate sample size is required (refer to 
Section 10).
The planned duration of treatment is not fixed; patients will remain on study until they fulfill one 
of the criteria for study discontinuation (Section 6.3).
Refer to Attachment 1 for the Study Schedule.
6.2.1. Study Completion and End of Trial
This study will be considered complete (that is, the scientific evaluation will be complete [study
completion]) when 36 evaluable patients* are attained.  “End of trial” refers to the date of the last 
visit or last scheduled procedure for the last patient.
* Patients are considered evaluable if they complete 1 cycle of treatment (at least Cycle 1, 
Day 43, based on a 6-week cycle), undergo 1 baseline and 1 posttreatment tumor biopsy 
procedure (ie, attempted, whether the biopsy is successful or not), and complete immune blood 
studies for 1 cycle.
6.2.2. Continued Access Period
All patients remaining on study treatment without disease progression following the final 
analysis of the primary and secondary endpoints will be able to enter the continued access period
of the study.  The continued access period begins after study completion and ends at the end of 
trial.  During the continued access period, patients on study treatment who continue to 
experience clinical benefit may continue to receive study treatment until disease progression, 
death, unacceptable toxicity, or start of new anticancer treatment.  The continued access period 
includes a follow-up visit.  The follow-up visit begins after the last dose of study drug and lasts 
approximately 30 days.  If it is deemed to be in the best interest of the patient to start a new 
anticancer treatment prior to the scheduled end of the follow-up visit, the follow-up visit duration 
may be shortened. In this case, the follow-up assessments should be completed prior to the 
initiation of the new therapy.
Lilly will notify investigators when the continued access period begins.
During the continued access period, all AEs, SAEs, study drug dosing, and dose reduction of 
treatment will be collected on the electronic case report form (eCRF).
Serious adverse events will also be reported to Lilly Global Patient Safety and collected in the 
pharmacovigilance system.  In the event that an SAE occurs, additional information (such as 
local laboratory results, concomitant medications, and hospitalizations) may be requested by 
Lilly in order to evaluate the reported SAE.
Investigators may perform other standard procedures and tests needed to treat and evaluate 
patients; however, Lilly will not routinely collect the results of these assessments.

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6.3.
Discontinuations
6.3.1. Discontinuation of Patients
The criteria for enrollment must be followed explicitly.  If the investigator site identifies a patient 
who did not meet enrollment criteria and who was inadvertently enrolled, the sponsor must be 
notified.  If the sponsor identifies a patient who did not meet enrollment criteria and who was 
inadvertently enrolled, the investigator site will be notified. A discussion must occur between 
the sponsor clinical research physician (CRP) and the investigator to determine whether the 
patient may continue in the study, with or without investigational product.  Inadvertently 
enrolled patients may be maintained in the study and on investigational product when the Lilly 
CRP agrees with the investigator that it is medically appropriate for that patient. The patient 
may not continue in the study with or without investigational product if the Lilly CRP does not 
agree with the investigator’s determination that it is medically appropriate for the patient to 
continue. The investigator must obtain documented approval from the Lilly CRP to allow the 
inadvertently enrolled patient to continue in the study with or without investigational product.
In addition, patients will be discontinued from the study drug in the following circumstances:

Enrollment in any other clinical trial involving an investigational product or enrollment in 
any other type of medical research judged not to be scientifically or medically compatible 
with this study.

Investigator/Physician Decision
o
the investigator/physician decides that the patient should be discontinued from the 
study or study drug(s)
o
if the patient, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study drug(s) occurs prior to introduction of the other 
agent

Patient Decision
o
the patient or the patient’s designee (for example, parents or legal guardian) 
requests to be discontinued from the study or study drug

Sponsor Decision
o
Lilly stops the study or stops the patient’s participation in the study for medical, 
safety, regulatory, or other reasons consistent with applicable laws, regulations, 
and GCP

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LY3022855 (IMC-CS4)

The patient has confirmed evidence of progressive disease.
o
Exceptions for continuing with study treatment beyond confirmed radiographic 
progression may be made on a case-by-case basis for patients who are believed to 
be clinically benefiting from protocol therapy and both the investigator and 
sponsor (the CRP/clinical research scientist [CRS]) agree that continuing protocol 
therapy is in the patient’s best interest.

The patient experiences unacceptable toxicity.

The patient experiences a Grade 3 or 4 infusion-related reaction (IRR) to LY3022855.

The patient experiences Grade ≥2 AST or ALT elevation and Grade ≥2 bilirubin 
elevation (cases confirmed by Hy’s Law).

The patient is noncompliant with study procedures and/or treatment (Section 7.6).
The reason for and date of discontinuation will be collected for all patients.  The Date of 
Discontinuation (for any of the above reasons) from study treatment is to be reported on the 
eCRF.  Patients who discontinue will have follow-up procedures performed as shown in the 
Study Schedule (Attachment 1).
6.3.2. Discontinuation of Study Sites
Study site participation may be discontinued if Lilly, the investigator, or the ethical review board 
(ERB) of the study site judges it necessary for any scientific, medical, safety, regulatory, ethical, 
or other reasons consistent with applicable laws, regulations, and GCP.
6.3.3. Discontinuation of the Study
The study will be discontinued if Lilly, while considering the rights, safety, and well-being of the 
patient(s), judges it necessary for any scientific, medical, safety, regulatory, ethical, or other 
reasons consistent with applicable laws, regulations, and GCP.

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7.
Treatment
7.1.
Materials and Supplies
LY3022855 for Injection is supplied at 5 mg/mL strength as a solution dosage, packaged in glass 
vials with an elastomeric closure.  Each vial of LY3022855 for Injection contains 20 mL of the 
drug product (100 mg/20-mL vial).  Vials of LY3022855 for Injection should be stored 
refrigerated at 2°C to 8°C.  The drug product is formulated to contain the active LY3022855 in 
10mM histidine, 100mM glycine, 100mM arginine, and 0.01% polysorbate 80 at pH 6.0.  
LY3022855 is a clear or slightly opalescent and colorless or slightly yellow liquid without 
visible particles.
LY3022855 will be administered as an I.V. infusion.  The dose is prepared and infused at room 
temperature (23°C-27°C).  LY3022855 will be diluted in normal saline to a final volume of 
250 mL.  Lilly instructions regarding dilution requirements should be followed.
Clinical study materials will be labeled according to the country’s regulatory requirements.
7.2.
Study Drug Administration
Four dosages of LY3022855 will be administered in this study.  Refer to Table JSCB.1 for a 
summary of the LY3022855 dosages to be used.  Eligible patients will receive LY3022855 as an 
I.V. infusion administered over a minimum duration of 30 minutes and a maximum duration of 4 
hours, based on the known safety and stability of the prepared drug.  The infusion rate should not 
exceed 25 mg/minute.
Suggested infusion times are as follows:

90 minutes for the first infusion; if no IRR is observed, decrease the infusion time to 
60 minutes

60 minutes for the second infusion; if no IRR is observed, decrease the infusion time to 
30 minutes

30 minutes for the third and subsequent infusions
If, at any time, a patient experiences an IRR, the infusion time should not be decreased.
For Dosages A and B, the first dose of LY3022855 is dependent upon the patient’s baseline body 
weight in kilograms.  Subsequent doses of LY3022855 must be recalculated if there is a ≥10% 
change (increase or decrease) in body weight from baseline; subsequent doses may be 
recalculated if there is a <10% change (increase or decrease) in body weight from baseline.
For patients with fluid retention, the estimated dry weight, instead of the actual body weight, 
should be used for dose calculation or recalculation (in the setting of substantial fluid retention, 
the Lilly CRP or designee should be consulted regarding optimal assessment of dry weight).
Dosages C and D are to be non-weight based (fixed dosing).

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LY3022855 (IMC-CS4)
The investigator or designee is responsible for:

explaining the correct use of the investigational agent(s) to the site personnel,

verifying that instructions are followed properly,

maintaining accurate records of study drug dispensation, destruction, and collection, and

returning or destroying all unused medication to Lilly or its designee at the end of the 
study.
Patients will be instructed to contact the investigator as soon as possible if they have a complaint 
or problem with the study drug(s) so that the situation can be assessed.
7.2.1. Dose Adjustments and Delays
Dose reductions are not permitted within a cycle, only between cycles.
If benefitting from treatment (that is, no disease progression or other withdrawal criteria), a 
patient who experiences a toxicity may continue to receive LY3022855 upon agreement of the 
sponsor and according to the dose reduction guidelines for this study (Table JSCB.2).  For any 
given patient in the study, their dose may be reduced up to a maximum of 3 times.
Table JSCB.2.
General Dose Reduction Guidelines
Dosage
Starting Dose and Schedule
First Reduction
Second Reduction
Third Reduction
A
1.0 mg/kg (Weeks 1, 2, 4, and 5)
0.6 mg/kg (QW)
0.3 mg/kg (QW)
0.3 mg/kg (Q2W)
B
1.25 mg/kg (Q2W)
0.6 mg/kg (QW)
0.3 mg/kg (QW)
0.3 mg/kg (Q2W)
C
100 mg (QW)
75 mg (QW)
50 mg (QW)
40 mg (QW)
D
100 mg (Q2W)
75 mg (Q2W)
50 mg (Q2W)
40 mg (Q2W)
Abbreviations:  QW = weekly; Q2W = every 2 weeks (Weeks 1, 3, and 5).
In the case of the toxicities listed in Table JSCB.3, study treatment may be held (if appropriate, 
in the opinion of the investigator and upon agreement with the sponsor) for a maximum of 
4 weeks, until resolution to baseline or improvement to Grade <2.  Upon resolution to baseline or 
improvement to Grade <2, study treatment may be administered at a reduced dose (according to 
Table JSCB.2), beginning with the next cycle, if appropriate, in the opinion of the investigator 
and upon agreement with the sponsor.  If toxicity does not resolve to baseline or improve to 
Grade <2 within 4 weeks following the last administered dose, study treatment should be 
permanently discontinued and the patient should be discontinued from the trial.
Once a patient has had a dose reduction (has started a new cycle at the reduced dose), all 
subsequent infusions will be at the reduced dose level; there will be no resumption to prior dose 
level(s).  Any patient experiencing toxicity that would necessitate more than 3 dose reductions 
must discontinue treatment.  Dose reductions must be confirmed by the sponsor.

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Table JSCB.3.
Toxicities for Which Dose Adjustments and Delays Apply

Grade 4 hematologic toxicity

Grade 3 hematologic toxicity lasting >7 days

Grade 3 or 4 nonhematologic toxicity.  Exceptions maybe be made for the following, if agreed upon by the 
sponsor AND the investigator:
o
Grade ≥3 liver function test (LFT) abnormality, such as alkaline phosphatase, gamma glutamyl 
transferase (GGT), AST, and ALT, not suspected to be drug related
o
Transient Grade ≥2 bilirubin elevation in the presence of known liver metastases lasting ≤7 days
o
Laboratory abnormalities that improve to Grade <2 or baseline levels within 7 days after initial 
documentation
o
Laboratory abnormalities ≥Grade 3 that are deemed not clinically significant 
o
Grade ≥3 asymptomatic elevation of CK WITHOUT elevation in serum and urine myoglobin
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CK = creatine kinase; 
CRP = clinical research physician.
Refer to Section 7.2.1.1 (Infusion-Related Reactions) regarding dose adjustment, delay, and 
discontinuation of study treatment due to LY3022855 IRRs.
7.2.1.1.
Infusion-Related Reactions
If a patient experiences Grade 1 IRR/allergic reaction, the infusion rate should be decreased by 
50% for the duration of the infusion.  In case of a Grade 2 IRR/allergic reaction, the infusion 
must be stopped until resolution to Grade ≤1; the infusion may then be resumed at 50% of the 
prior infusion rate (the duration of the infusion should not exceed 3 hours).  Once the infusion 
rate has been reduced for a Grade 1 or 2 IRR, it is recommended to maintain the lower infusion 
rate for all subsequent infusions (premedication must be provided prior to any subsequent doses 
of LY3022855 if the patient has experienced a Grade 1 or 2 IRR).  Occurrence of a Grade 3 or 4
IRR requires immediate and permanent discontinuation of LY3022855.
During Cycles 1 and 2 only, patients are to be observed closely for any potential AEs, from the 
start of the infusion until at least 1 hour after the end of the infusion of LY3022855.  This 
observation is to be done in an area with resuscitation equipment and medications necessary for 
advanced life support and cardiopulmonary resuscitation, such as bronchodilators, vasopressor 
agents (for example, epinephrine), oxygen, glucocorticoids, antihistamines, and I.V. fluids, etc.
CAUTION:  Infusion-related reactions may occur during or following LY3022855
administration.
Premedication is not recommended to be administered prior to the first infusion of LY3022855.  
However, if the patient experiences a Grade 1 or 2 IRR, premedication must be provided prior to 
any subsequent doses of LY3022855.  The choice of premedication is to be made after 
discussion and agreement between the investigator and the Lilly CRP.  In such cases (Grade 1 or 
2 IRRs), administration of steroids should be avoided, if possible.  Any premedication 
administered should be documented in the eCRF, including dose and route of administration.

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If at any time a patient experiences an IRR to LY3022855, all attempts will be made to obtain a 
blood sample for immunogenicity analysis as close to the onset of the event as possible, at the 
resolution of the event, and 30 days following the event. A portion of the sample taken for 
immunogenicity testing may be used for PK analysis, in the setting of IRRs.
For further details regarding IRRs, including characterization according to CTCAE v4.0 and 
treatment guidelines, refer to the LY3022855 IB.
7.2.1.2.
Other Adverse Events
Based on observations in nonclinical toxicological studies with LY3022855 and/or observations 
in one clinical trial with another monoclonal antibody targeting CSF-1 (Sadis et al. 2009), 
patients receiving LY3022855 should be closely monitored for signs indicative of hepatic 
function impairment (for example, increases in transaminases, LDH, bilirubin, coagulation 
disorders), inflammation (for example, leukocyte alterations, C-reactive protein), CK increases, 
and periorbital swelling.  For details, refer to the LY3022855 IB.
7.2.1.2.1.
Immune-Related Adverse Events (irAEs)
Symptoms occurring during or following infusion of investigational therapy will be defined 
according to the NCI-CTCAE, Version 4.0.
In the setting of symptoms consistent with irAEs occurring following infusion of investigational 
therapy, investigators are encouraged to refer to Attachment 10 as a guideline for the 
management of potential toxicities encountered with immuno-oncology agents.  Due to the 
potential of rapid and serious sequelae associated with irAEs, early intervention with 
immunomodulatory agents as indicated is encouraged, concurrent with further diagnostic 
medical evaluations for possible non-immune-related causes of AEs.  Attachment 10 is a 
guideline for the management of irAEs; local standards may supersede recommendations when 
deemed appropriate by the investigator.
7.3.
Method of Assignment to Treatment
Patients who meet all criteria for enrollment will be assigned to receive LY3022855 in this study.  
Before each patient’s enrollment into the study, an eligibility check must be conducted between 
the investigational site and the Lilly clinical research personnel to confirm that each patient 
meets all enrollment criteria.  Upon confirmation of eligibility, the sponsor will confirm the dose 
and identification number assignment for each patient.
7.4.
Blinding
This is an open-label study.

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7.5.
Concomitant Therapy
No other chemotherapy, immunotherapy, or experimental drugs will be permitted while the 
patients are on this study (refer to Sections 6.1.1 and 6.1.2 for entry criteria). Exceptions will be 
made for:

Prostate cancer patients continuing GnRH agonist/antagonist therapy (refer to Inclusion 
Criterion [2] in Section 6.1.1)

Prostate cancer patients receiving prednisone up to 10 mg/day (or an equivalent dose of 
another glucocorticoid agent)

Breast cancer patients continuing antiestrogen therapy (for example, an aromatase 
inhibitor) or trastuzumab
Palliative radiotherapy will be allowed provided patients do not have overt signs of progression.  
Any disease progression requiring other forms of specific antitumor therapy will also necessitate 
early discontinuation from the study.  Appropriate documentation for all forms of premedication, 
supportive care, and concomitant medication must be captured on the eCRF. Replacement 
hormonal therapy initiated before study entry will be allowed.
Patients should receive full supportive care with the exception that the routine use of granulocyte 
colony-stimulating factors is not permitted during this study. Should the use of hematopoietic 
colony-stimulating factors (CSFs) be necessary, the American Society of Clinical Oncology 
(ASCO) recommendations for the use of CSFs (Smith et al. 2006) should be followed.  If 
clinically indicated at any time during the study, erythropoietin and packed red blood cell 
transfusions may be used according to ASCO guidelines (Rizzo et al. 2010).
All concomitant medications should be recorded throughout the patient’s participation in the 
study.
7.6.
Treatment Compliance
LY3022855 will be administered I.V. at the investigational site, under the direction of the 
investigator.  As a result, a patient’s compliance with study drug administration is ensured.  
Patients should attend scheduled clinic visits and must comply with study criteria under their 
control. Deviation(s) from the prescribed dosage regimen should be recorded on the eCRF.
7.6.1. Evaluable Patients
Patients who withdraw from the study before receiving study drug(s) will be replaced and will 
not be included in the safety or efficacy assessments.  Safety analyses will be conducted on all 
patients who have received at least one dose of study drug, regardless of whether they are 
deemed evaluable for the assessment of a dose level.
Any patient who does not complete 1 cycle of LY3022855 treatment, undergo 1 baseline and 
1 posttreatment tumor biopsy procedure (ie, attempted, whether the biopsy is successful or not), 
and complete immune blood studies for 1 cycle will be deemed nonevaluable for assessment of a 
dose level.

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Patients who complete 1 cycle of LY3022855 treatment, undergo 1 baseline and 1 posttreatment 
tumor biopsy procedure (ie, attempted, whether the biopsy is successful or not), and complete 
immune blood studies for 1 cycle will be considered evaluable for the assessment of a dose level.  
Nonevaluable patients may be replaced to ensure that 36 evaluable patients are attained.
Patients who complete 1 cycle of therapy but, for whatever reason, are not evaluable for PK may 
be replaced upon consultation with the investigator(s) and the Lilly CRP or CRS to ensure 
adequate PK data.

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8.
Safety, Pharmacokinetic, Pharmacodynamic, and 
Efficacy Data Collection
8.1.
Safety Evaluations
The safety and tolerability of LY3022855 have been assessed in nonclinical toxicology studies 
and the results from these studies are detailed in the IB.  This Phase 1 study contains detailed 
safety monitoring that will permit further characterization of the safety profile of LY3022855 in 
patients, beyond that initially characterized in Phase 1 study JSCA.  Study procedures and their 
timing, including collection of blood and urine samples, are described in the Study Schedule 
(Attachment 1).
Standard laboratory tests, including chemistry, hematology, coagulation, and urinalysis panels, 
will be performed.  A urine or serum pregnancy test (based on institutional standards) will be 
administered if applicable.  Other clinical laboratory tests will also be collected.  Attachment 2
lists the specific tests that will be performed for this study.
8.1.1. Safety Data Collection and Review
Investigators are responsible for monitoring the safety of patients who have entered into this 
study and for alerting Lilly or its designee to any event that seems unusual, even if this event 
may be considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of the patient during the study.
The investigator remains responsible for following, through an appropriate health care option,
AEs that are serious, considered related to study treatment or the study, or that caused the patient 
to discontinue before completing the study.  The patient should be followed until the event is 
resolved, the event is no longer considered to be drug-related, the event becomes stable or 
returns to baseline, a new treatment is initiated for the patient, or the patient dies or is lost to 
follow-up.  Frequency of AE and SAE follow-up evaluation is left to the discretion of the 
investigator.
The timing of all safety evaluations is shown in the Study Schedule (Attachment 1).  
Table JSCB.4 presents a summary of AE and SAE reporting guidelines.  Table JSCB.4 also 
shows which database or system is used to store AE and SAE data.
8.1.2. Adverse Events
Lilly has standards for reporting AEs that are to be followed regardless of applicable regulatory 
requirements that may be less stringent.  A clinical study AE is any untoward medical occurrence 
in a patient or clinical investigation subject administered a pharmaceutical product and which 
does not necessarily have a causal relationship with this treatment.  An adverse event (AE) can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of medicinal (investigational) product, 
whether or not related to the medicinal (investigational) product.  Any clinically significant 
findings from labs, vital sign measurements, and so on that occur should also be reported to Lilly

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or its designee as an AE.  Lack of drug effect is not an AE in clinical studies because the purpose 
of the clinical study is to establish drug effect.
The investigator, monitor, and sponsor will review the collected data regularly for evidence of 
AEs. All patients will be assessed routinely for AEs as outlined in the study schedule.  All AEs 
observed will be graded using CTCAE v4.0.
The National Cancer Institute (NCI)-CTCAE v4.0 will serve as the reference document for 
choosing appropriate terminology for, and grading the severity of, all AEs and other symptoms. 
All AEs observed will be graded using CTCAE v4.0.  Any minor version of CTCAE v4.0 (for 
example, version 4.0X) may be used for this study.  Minor CTCAE v4.0 updates from the NCI 
will not necessitate a protocol amendment.  For AEs without matching terminology within the 
CTCAE v4.0 criteria, the investigator will be responsible for selecting the appropriate system 
organ class and assessing severity grade based on the intensity of the event.  Note that both 
CTCAE term (actual or coded) and severity grade must be selected by study site personnel and 
collected on the eCRF.  This collection is in addition to verbatim text used to describe the AE.
In addition to collecting the AE verbatim, the CTCAE term, and the CTCAE severity grade, AE 
verbatim text will also be mapped by the sponsor or designee to corresponding terminology 
within the Medical Dictionary for Regulatory Activities dictionary.
Cases of pregnancy that occur during maternal or paternal exposures to study drug should be 
reported.  Data on fetal outcome and breastfeeding should be collected, if feasible, for regulatory 
reporting and drug safety evaluation.
Upon documentation of pregnancy, the patient must be removed from the study and treatment 
with study drug(s) must be stopped immediately.
For all enrolled patients, study site personnel will record the occurrence and nature of each 
patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  While the patient is on study, site personnel will record any 
change in these preexisting condition(s) and the occurrence and nature of any AEs.  In addition,
all AEs related to protocol procedures are reported to Lilly or designee.
If a patient's dosage is reduced or treatment is discontinued as a result of an AE, study site 
personnel must clearly report to Lilly or its designee via eCRF the circumstances and data 
leading to any such dosage reduction or discontinuation of treatment.
Investigators will be instructed to report to Lilly or its designee their assessment of the potential 
relatedness of each AE to protocol procedure or study drug via eCRF.

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The investigator decides whether he or she interprets the observed AEs as either related to 
disease, to the study medication, study procedure, or other concomitant treatment or pathologies.  
To assess the relationship of the AE to the study drug, the following terminologies are defined:

Related:  A direct cause and effect relationship between the study treatment and 
the AE is likely.

Possibly related:  A cause and effect relationship between the study treatment 
and the AE has not been demonstrated at this time and is not probable, but is also 
not impossible.

Unrelated:  Without question, the AE is definitely not associated with the study 
treatment.
As per Lilly’s standard operating procedures, all “related” and “possibly related” AEs and SAEs 
will be defined as related to study drug.
8.1.2.1.
Serious Adverse Events
Planned surgeries should not be reported as SAEs unless the underlying medical condition has 
worsened during the course of the study.
Planned hospitalizations or elective procedures for underlying preexisting conditions that are 
already recorded in the patient’s medical history at the time of study enrollment should not be 
considered SAEs.  Hospitalization or prolongation of hospitalization without a precipitating 
clinical AE (for example, for the administration of study therapy or other protocol-required 
procedure) should not be considered SAEs.
An SAE is any adverse event during this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization (except for study drug 
administration)

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

considered significant by the investigator for any other reason
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.
Serious adverse events due to disease progression, including death, should not be reported unless 
the investigator deems them to be possibly related to the study drug.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they

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are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.
If an investigator becomes aware of SAEs occurring after the patient’s participation in the trial 
has ended, and the investigator believes that the SAE is related to a protocol procedure or study 
drug, the investigator should report the SAEs to the sponsor, and the SAEs will be entered in the
Lilly Safety System.
Information on SAEs expected in the study population independent of drug exposure and that 
will be assessed by the sponsor in aggregate periodically during the course of the trial may be 
found in the IB.
8.1.2.2.
Adverse Event and Serious Adverse Event Reporting
Data on SAEs that occur before the end of trial will be stored in the collection database and the 
Lilly Safety System (see Attachment 7 for reporting recommendations).
8.1.2.2.1.
Prior to Administration of Study Drug(s)
During screening, all AEs and SAEs (regardless of relatedness to protocol procedures) are 
collected after the patient has signed the informed consent form (ICF).  For patients who do not 
enroll in the trial (that is, have not received at least one dose of LY3022855), only AEs and 
SAEs related to protocol procedures are required to be collected.
8.1.2.2.2.
On Therapy
All AEs and SAEs, regardless of relatedness to study drug(s) or protocol procedures, occurring 
while the patient is receiving study drug must be reported to Lilly or its designee.  A patient is 
considered to be receiving study drug from the time he/she receives the first dose of study drug
until the time he/she receives the last dose of study drug.
8.1.2.2.3.
30-Day Follow-Up Visit
All AEs and SAEs, regardless of relatedness to study drug(s) or protocol procedures, occurring 
during the 30-Day Follow-up visit must be reported to Lilly or its designee.  The 30-Day
Follow-up visit starts following the last dose of study drug and lasts approximately 30 days.  At 
the end of the 30-Day Follow-up visit, the patient will be required to have specific safety
assessments (Attachment 1).  The timing of these safety assessments is to occur 30 days ±7 days 
after the last dose of study drug.
Following the safety assessments that mark the end of the 30-Day Follow-up visit, the patient 
will be discontinued from the study, unless there is an ongoing AE or SAE that is at least 
possibly related to study drug.  In this instance, the patient should be followed in subsequent 
follow-up visits (every 30 days) until the event is resolved, the event is no longer considered to 
be drug-related, the event becomes stable or returns to baseline, a new treatment is initiated for 
the patient, or the patient dies or is lost to follow-up.
If it is deemed to be in the best interest of the patient to start a new anticancer treatment prior to 
the scheduled end of the 30-Day Follow-up visit, the duration for this visit may be shortened. In 

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this case, the follow-up assessments should be completed prior to the initiation of the new 
therapy.
After the 30-Day Follow-up visit, AEs are not required to be reported unless the investigator 
feels the AEs were related to either study drug, drug delivery system, or a protocol procedure. If 
an investigator becomes aware of an SAE believed to be related to protocol procedures or study 
drug, the investigator should report the SAE to the sponsor, and the SAE will be entered in the
Lilly Safety System.
8.1.2.3.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious adverse events that are 
not listed in the Development Core Safety Information  in the IB and that the investigator 
identifies as related to study drug or procedure.  The United States 21 CFR 312.32, the European 
Union Clinical Trial Directive 2001/20/EC, and the associated detailed guidances or national 
regulatory requirements in participating countries require the reporting of SUSARs.  Lilly has 
procedures that will be followed for the recording and expedited reporting of SUSARs that are 
consistent with global regulatory regulations and the associated detailed guidances.
8.1.2.4.
Summary of AE/SAE Reporting Guidelines
The AE and SAE reporting guidelines are summarized in Table JSCB.4.

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Table JSCB.4.
Adverse Event and Serious Adverse Reporting Guidelines for 
Study JSCB
Timing
Types of AEs/SAEs Reported
Collection 
Database
Lilly Safety 
System
Prestudy (baseline assessments)
(starts at the signing of informed consent and 
ends immediately before the first dose of study 
drug)
Preexisting conditions
All AEs
All SAEs, regardless of 
relatedness
x
x
x
x
On therapy
(starts at first dose of study drug and ends at 
last dose of study drug)
All AEs
All SAEs, regardless of 
relatedness
x
x
x
30-Day Follow-up visit
(starts just after the last dose of study drug and 
ends when end-of-study safety assessments are 
completed [30 days ± 7 days after last dose of 
study drug])
All AEs
All SAEs, regardless of 
relatedness
x
x
x
Subsequent follow-up visits, if necessary for 
patient monitoring
Ongoing AEs possibly related to 
study drug(s) or protocol 
procedures
All SAEs related to protocol 
procedures or study drug
x
x
x
Continued access period (starts after study 
completion and ends at the end of the trial)
All AEs
All SAEs, regardless of 
relatedness
x
x
x
Continued access period follow-up
(starts just after the last dose of study drug and 
ends when end-of-study safety assessments are 
completed [30 days ± 7 days after last dose of 
study drug])
All AEs
All SAEs, regardless of 
relatedness
x
x
x
Patient no longer on study
All SAEs related to protocol 
procedures or study drug that the 
investigator becomes aware of
x
Abbreviations:  AEs = adverse events; SAEs = serious adverse events.
8.1.3. Other Safety Measures
8.1.3.1.
Electrocardiograms
For each patient, a local 12-lead digital ECG will be collected (normal vs clinically significantly 
abnormal) according to the Study Schedule (Attachment 1).  Patients must be supine for 
approximately 5 to 10 minutes before ECG collection and remain supine but awake during ECG 
collection.
Electrocardiograms may be obtained at additional times, when deemed clinically necessary.  
Collection of more ECGs (more replicates) than expected at a particular time point is allowed to 
ensure high-quality records.

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Electrocardiograms will be interpreted by a qualified physician (the investigator or qualified 
designee) at the site as soon after the time of ECG collection as possible, and ideally while the 
patient is still present, to determine whether the patient meets entry criteria at the relevant visit(s) 
and for immediate patient management, should any clinically relevant findings be identified.
If a clinically significant quantitative or qualitative change from baseline is identified after 
enrollment, the investigator will assess the patient for symptoms (for example, palpitations, near 
syncope, syncope) to determine whether the patient can continue in the study.  The investigator 
or qualified designee is responsible for determining if any change in patient management is 
needed and must document his/her review of the ECG printed at the time of evaluation from at 
least one of the replicate ECGs from each time point.
8.1.4. Safety Monitoring
The Lilly CRP or CRS will monitor safety data throughout the course of the study.
Representatives from Lilly Global Patient Safety will specifically monitor SAEs.  Lilly will 
review SAEs within time frames mandated by company standard operating procedures.  The 
Lilly CRP/CRS will, as is appropriate, consult with the functionally independent Global Patient 
Safety therapeutic area physician or clinical research scientist, and periodically review:

Trends in safety data.

Laboratory analytes, including AP, ALT, AST, CK, LDH, and C-reactive protein.

Adverse events, including monitoring of hepatotoxicity and muscle damage.

If a study patient experiences elevated ALT ≥5 × ULN and elevated total bilirubin ≥2 ×
ULN, clinical and laboratory monitoring should be initiated by the investigator.

For patients entering the study with ALT ≥3 × ULN, monitoring should be triggered at 
ALT ≥2 × baseline.
Details for hepatic monitoring depend upon the severity and persistence of observed laboratory 
test abnormalities.  To ensure patient safety and to comply with regulatory guidance, the 
investigator is to consult with the Lilly CRP/CRS regarding collection of specific recommended 
clinical information and follow-up laboratory tests (see Attachment 3).
8.1.5. Complaint Handling
Lilly collects complaints on study drugs used in clinical studies in order to ensure the safety of 
study participants, monitor quality, and facilitate process and product improvements.
Complaints related to concomitant drugs are reported directly to the manufacturers of those 
drugs in accordance with the package insert.

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The investigator or his/her designee is responsible for handling the following aspects of the 
complaint process in accordance with the instructions provided for this study:

recording a complete description of the complaint reported and any associated 
AEs using the study-specific complaint forms provided for this purpose

faxing the completed complaint form within 24 hours to Lilly or its designee
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint form with the product.
8.2.
Sample Collection and Testing
Attachment 1 lists the schedule for sample collections in this study.
Attachment 2 lists the specific clinical laboratory tests that will be performed for this study.
Attachment 4, Attachment 5, and Attachment 6 list the detailed schedules for sample collections 
specifically for PK, pharmacodynamics, and immunogenicity in this study.
8.2.1. Samples for Study Qualification and Health Monitoring
Blood, urine, and tissue samples will be collected to determine whether patients meet 
inclusion/exclusion criteria and to monitor patient health.
C-reactive protein will be assessed as a serum marker of inflammation.  Total CK will be 
monitored via the chemistry panel, and serum and urine myoglobin will be measured in the event 
that serum CK ≥2.5 × ULN.  Coagulation parameters will be assessed prior to biopsy procedures.  
Refer to Attachment 1 for details about the timing of all assessments.
Tissue biopsy will be taken by core needle or surgical biopsy.  For each core needle biopsy, an
attempt should be made to collect 6 core needle samples; however, if it is not medically feasible 
to collect 6 samples, the investigator or designee should attempt to collect as much tumor tissue 
as is deemed medically feasible. Fine-needle aspiration should not be used as a method of tissue 
acquisition, unless first discussed with and agreed upon by the Lilly CRP.  Due diligence should 
be used to ensure that tumor specimen (not normal adjacent or tumor margins) is provided.
Investigators must document their review of each laboratory safety report.  Investigators must 
also document their determination of clinical significance of all abnormal laboratory values.
Samples collected for specified laboratory tests will be destroyed within 60 days of receipt of 
confirmed test results.  Tests are run and confirmed promptly whenever scientifically 
appropriate.  When scientific circumstances warrant, however, it is acceptable to retain samples 
to batch the tests run, or to retain the samples until the end of the study to confirm that the results 
are valid.  Certain samples may be retained for a longer period, if necessary, to comply with 
applicable laws, regulations, or laboratory certification standards.

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8.2.2. Samples for Drug Concentration Measurements 
Pharmacokinetics/Pharmacodynamics
Pharmacokinetic and pharmacodynamic samples will be collected as specified in Attachment 1.
8.2.2.1.
Pharmacokinetic Samples
At the visits and times specified in the sampling schedule (Attachment 4, Attachment 5, and 
Attachment 6), venous blood samples of approximately 3 to 6 mL each will be collected to 
determine the serum concentrations of LY3022855. If a patient remains on study until Cycle 3, 
additional samples will be drawn at that time.  Additional samples may be drawn at additional 
time points during the study, if warranted and agreed upon by the investigator, Lilly, and the 
patient.  Instructions for the collection and handling of blood samples will be provided by the 
sponsor.  The actual date and time of each sampling must be clearly and accurately recorded.
These samples will be analyzed at a laboratory designated by the sponsor.  Serum concentrations 
of LY3022855 will be assayed using a validated ELISA method.
The PK samples will be stored at a facility (in the United States) designated by the sponsor.
The remaining serum from the samples collected for PK may be pooled and used for exploratory 
metabolism work as deemed appropriate.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.
8.2.2.2.
Pharmacodynamic Samples
The following pharmacodynamic assessments are based on the primary study objective and are, 
therefore, required assessments.  Samples will be tested for changes from baseline over time in 
peripheral blood immune cell subsets and in serum cytokines to document the 
immunomodulatory activity of LY3022855 treatment in patients with advanced, refractory breast 
or prostate cancers.  Flow cytometric analysis using an antibody panel that may include, but not 
be limited to markers Live-Dead, CD3, CD4, CD8, CD14, CD16, FoxP3, PD-1, Ki-67, CTLA-4, 
TIM-3, LAG-3, and ICOS will be used to evaluate T-cell and monocyte subsets from peripheral 
blood. In addition, serum cytokine levels will be determined by MSD multiplex cytokine 
immunoassay technology or ELISA, and may include, but not be limited to CSF-1, IFN-γ, IL-1β, 
IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-34, and TNF-α.
Collection of samples for other biomarker research is also part of this study.

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Required samples for biomarker research to be collected from all patients in this study are the 
following:
blood (for exploratory analysis of serum biomarkers that may be relevant to the
mechanism of action of LY3022855,
tumor tissue (for exploratory analysis of the immunomodulatory effects of LY3022855
administration, including the understanding of the pharmacodynamic effectsof
LY3022855)
Tissuebiopsy will be taken by core needle biopsy or surgical biopsy.  Fine-needle aspiration
should not be used as a method of tissue acquisition, unless first discussed with the Lilly CRP.  
Due diligence should be used to ensure that tumor specimen (not normal adjacent or tumor 
margins) is provided.  Pathology notes accompanying the tissue may also be requested.  Tissue 
and blood samples will be kept with the intention to perform tests as new techniques, research 
tools, and biomarkers become available.
Optional tissue(core needle or surgical biopsy)and/orblood samples(in addition to the required 
samples previously described)for biomarker research maybe obtained at the investigator’s
discretion in discussion with the patient, such as at the time of radiographic response or treatment 
progression.
The samples will be coded with the patient number and stored at a facility selected by the 
sponsor for up to a maximum of 15years after the last patient visit for the study.  The samples 
and any data generated from them can only belinked back to the patient by investigator site 
personnel.  The duration allows the sponsor to respond to regulatory requests related to the study 
drug.
Samples will be destroyed according to a process consistent with local regulation.  Patients may 
request to have their samples destroyed at any time.
8.2.3. Samples for Tailoring Biomarkers
CCI
There is growing evidence that genetic variation may impact a patient’s response to therapy.  
Variable response to therapy may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion, the mechanism of action of the drug, the disease 
etiology and/or the molecular subtype of the disease being treated.  Therefore, where local 
regulations and ERBs allow, a blood sample will be collected for pharmacogenetic analysis.
In the event of an unexpected AE or the observation of unusual response, the pharmacogenetic 
biomarker samples may be genotyped and analysis may be performed to evaluate a genetic 
association with response to LY3022855.  These investigations may be limited to a focused 
candidate gene study or, if appropriate, genome-wide analysis may be performed to identify 
regions of the genome associated with the variability observed in drug response.  The 
pharmacogenetic biomarker samples will only be used for investigations related to disease and 
drug or class of drugs under study in the context of this clinical program.  They will not be used 
for broad exploratory unspecified disease or population genetic analysis.

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The samples will be coded with the patient number and stored for up to a maximum of 15 years 
after the last patient visit for the study, at a facility selected by the sponsor.  The samples and any 
data generated from them can only be linked back to the patient by investigator site personnel.  
The duration allows the sponsor to respond to regulatory requests related to the study drug.
Samples will be destroyed according to a process consistent with local regulation.
Refer to Section 8.2.2.2, Pharmacodynamic Samples, for details of samples collected for other 
biomarker research that is part of this study.  These other samples may be used for research to 
develop methods, assays, prognostics and/or companion diagnostics related to CSF-1, CSF-1R,
and/or the mechanism of action of study drugs (LY3022855).
8.2.4. Samples for Immunogenicity Research
Blood samples for immunogenicity testing will be collected to determine antibody production 
against LY3022855.  Immunogenicity will be assessed by a validated assay designed to detect 
ADA in the presence of LY3022855.  Antibodies may be further characterized and/or evaluated 
for their ability to neutralize the activity of LY3022855.
In addition to planned sampling for immunogenicity testing, if at any time a patient experiences 
an IRR to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity 
analysis as close to the onset of the event as possible, at the resolution of the event, and 30 days
following the event. A portion of the sample taken for immunogenicity testing may be used for 
PK analysis, in the setting of IRRs.
Samples may be stored for a maximum of 15 years following last patient visit for the trial at a 
facility selected by the sponsor to enable further analysis of immune responses to LY3022855.  
The duration allows the sponsor to respond to regulatory requests related to LY3022855.
8.3.
Efficacy Evaluation
One of the secondary objectives of the study is to measure any antitumor activity.  Refer to 
Attachment 1 for details regarding the timing of specific efficacy measures.
Each patient will be assessed by one or more of the following radiologic tests for tumor 
measurement:

Computed tomography (CT) scan

Magnetic resonance imaging (MRI)

Chest x-ray, as clinically indicated

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Each patient’s full extent of disease will also be assessed as follows:

For patients with measurable disease defined by RECIST, tumor measurements 
are to be assessed by RECIST 1.1 (Eisenhauer et al. 2009; Attachment 9) and 
irRECIST (Nishino et al. 2013).

For patients with prostate cancer, bone metastatic disease is to be evaluated by PCWG2 
criteria (Scher et al. 2008).  A CRPC patient will be considered to have progressed by 
bone scan when at least 2 new lesions are observed on bone scan (compared with 
baseline), and are then confirmed on a follow-up bone scan performed at least 6 weeks 
later.  However, if the point when the new lesions are observed is the first interval scan 
(Week 6), then the confirmatory bone scan must demonstrate at least 2 additional new 
lesions (that is, a total of at least 4 new lesions, compared with baseline). This 
confirmatory bone scan is required, given the prevalence of pseudoprogression, often 
referred to as “bone scan flare.” For this trial, bone scans will be performed at baseline, 
Week 6 (first interval), and every 6 weeks thereafter, or as clinically indicated.
The following are further details of the PCWG2 criteria for progression in bone:
o
For the first interval assessment bone scan performed following Cycle 1, Day 1, at 
least 2 new lesions, compared with baseline, must be visualized, and a 
confirmatory bone scan at least 6 weeks later should be performed and 
demonstrate at least 2 new lesions (that is, a total of at least 4 new lesions from 
baseline).
o
For all other interval assessment bone scans (that is, after the first posttreatment 
scan), at least 2 new lesions, compared with baseline, must be visualized, and a 
confirmatory bone scan should be performed and demonstrate confirmation of 
these 2 (or more) new lesions (that is, a total of at least 2 new lesions from 
baseline) to be considered progression.
o
The date of progression is considered the date of the first scan that demonstrates
at least 2 new lesions.
o
Changes in intensity of bone lesions or the extent of existing bone lesions on bone 
scintigraphy are not considered in the assessment of bone disease progression per 
PCWG2 criteria.
o
Ambiguous results on bone scintigraphy may be clarified with other imaging 
modalities (CT/MRI), per investigator discretion.
Within 4 weeks prior to first dose of study drug (that is, baseline), each patient will be assessed 
by a radiologic imaging study for tumor measurement.  Ultrasound will not be permitted as a 
method of tumor measurement.
Tumor assessment should be repeated every 6 weeks, using the same radiologic method that was 
used at baseline.

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8.4.
Procedure/Sampling Compliance
Every attempt will be made to enroll patients who have the ability to understand and comply 
with instructions.  Noncompliant patients may be discontinued from the study.
The collection times of safety assessments, PK samples, pharmacodynamic samples, and efficacy 
measurements are given as targets, to be achieved within reasonable limits.  The scheduled time 
points may be subject to minor alterations; however, the actual collection time must be correctly 
recorded on the eCRF or lab requisition form.
The scheduled collection times may be modified by the sponsor based on analysis of the safety 
and PK information obtained during the study.  Any major modifications that might affect the 
conduct of the study, patient safety, and/or data integrity will be detailed in a protocol 
amendment.

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9.
Data Management Methods
9.1.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

Provide instructional material to the study sites, as appropriate.

Sponsor start-up training to instruct the investigators and study coordinators.  This 
session will give instruction on the protocol, the completion of the eCRFs, and study 
procedures.

Make periodic visits to the study site.

Be available for consultation and stay in contact with the study site personnel by e-mail, 
telephone, and/or fax.

Review and evaluate eCRF data and/or use standard system edit checks and manual 
listing reviews to detect errors in data collection.

Conduct a quality review of the eCRF database.
In addition, Lilly or its representatives may periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives and/or regulatory agencies at any time. Investigators will be given notice before 
an audit occurs.
To ensure the safety of participants in the study, and to ensure accurate, complete, and reliable 
data, the investigator will keep records of laboratory tests, clinical notes, and patient medical 
records in the patient files as original source documents for the study.  If requested, the 
investigator will provide the sponsor, applicable regulatory agencies, and applicable IRBs/ERBs 
with direct access to the original source documents.
9.2.
Data Capture Systems
9.2.1. Case Report Form
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site into the sponsor-provided electronic data capture system.
For data handled by a data management third-party organization (TPO), eCRF data and some or 
all data that are related will be managed and stored electronically in the TPO system.  
Subsequent to the final database lock, validated data will be transferred to the Lilly data 
warehouse, using standard Lilly file transfer processes.
For data handled by the sponsor internally, eCRF data and some or all data that are related will 
be managed by the sponsor and stored electronically in the sponsor’s system.
9.2.2. Ancillary Data
Data managed by a central vendor will be stored electronically in the central laboratory’s 
database system.  Data will subsequently be transferred from the central vendor to the Lilly 
generic labs system.

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Bioanalytical data will be stored electronically in the bioanalytical laboratory’s database.  Data 
will subsequently be transferred from the bioanalytical laboratory to the Lilly generic labs 
system.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

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10. Data Analyses
For this study, approximately 40 patients will be enrolled. Patients with prostate cancer will be 
treated at 1 of 2 dosages of LY3022855, and patients with breast cancer will be treated at 1 of 4
dosages of LY3022855.  Of those enrolled patients, approximately 36 patients will be evaluable:  
30 patients with advanced, refractory breast cancer and 6 patients with advanced, refractory 
prostate cancer.  Refer to Section 6.1 for the definition of an evaluable patient.
CSF-1 is the primary pharmacodynamic biomarker documented in Study JSCA. Serum CSF-1 
was quantified for 17 patients over time; that is, at baseline and 8 hours after the first infusion. 
All those patients had increased levels of CSF-1 at 8 hours, compared with the baseline level.
The effect size (or Cohen’s d) is 5.81. Consequently, the power of observing any change 
between the eighth hour and baseline is close to 1 as long as the number of samples is ≥3.
However, when the effect size is as small as 1 for the pharmacodynamic markers other than
CSF-1, the power is approximately 0.159 if only 3 patients are sampled.
For Dosages C and D (patients with breast cancer), the sample size of 10 for each dosage 
provides a reasonable power to explore preliminary signals of efficacy. Assuming that a true 
best overall response rate (ORR) less than 20% indicates inadequate antitumor activity, then at a 
one-sided type 1 error rate of 5%, the total sample size of 10 will provide 80% power if the true 
best ORR is 60% or higher, using a 2-stage design method as follows. During the first stage, 5 
patients will be enrolled and treated on each of Dosages C and D. If 2 or more of the 5 patients 
on either dosage (C or D) are observed to be responders by the end of the first stage, an 
additional 5 patients will be enrolled at the applicable dosage. Then, if 5 or more of the total of 
10 patients at that dosage are observed to be responders by the end of the second stage, further 
exploration of drug efficacy is warranted for that dosage.
All data collected will be summarized using descriptive statistics or graphics, if appropriate, and 
will also be listed.
10.1. General Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company.
The interpretation of the study results will be the responsibility of the investigator with the Lilly
CRP, pharmacokineticist, and statistician.  The CRP and statistician will also be responsible for 
the appropriate conduct of an internal review for both the final study report and any study-related 
material to be authorized by Lilly for publication.

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10.2. Patient Disposition
All patient discontinuations will be documented, and the extent of each patient’s participation in 
the study will be reported.  If known, a reason for their discontinuation will be given.
A summary of the number and percentage of patients entered into the study, enrolled in the 
study, and treated, as well as number and percentage of patients discontinuing (overall and by 
reason for discontinuation), will be provided.
A summary of all important protocol deviations will be provided.
10.3. Patient Characteristics
Patient characteristics will include the following:

Patient demographics

Baseline disease characteristics

ECOG performance status

Preexisting conditions

Historical illnesses

Prior disease-related therapies (including information on best response and 
time to progressive disease)

Concomitant medications
Other patient characteristics will be summarized as deemed appropriate.
10.4. Safety Analyses
All patients who receive at least one dose of LY3022855 will be evaluated for safety and 
toxicity.  Adverse event terms and severity grades will be assigned by the investigator using 
CTCAE v4.0.
All safety summaries and analyses will be based upon the Safety Population, defined as all 
enrolled patients who have received at least one dose of study drug.
Overall exposure to study drug, the numbers of patients completing each cycle, and the dose 
intensity will be summarized using descriptive statistics.
An overall summary will be provided for AEs deemed by the investigator to be possibly related 
to study medication, and repeated for events regardless of study drug causality.
The number of evaluable patients who experienced a TEAE, an SAE, or an AE related to study 
drug, or who died or discontinued from the study due to an AE will be summarized.
Reasons for death will be summarized separately for on-therapy and within 30 days after last 
dose of study drug.

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Laboratory results will be classified according to CTCAE v4.0.  Laboratory results not 
corresponding to a CTCAE v4.0 grade will not be graded.
10.5. Pharmacokinetic Analyses
Pharmacokinetic analyses will be conducted on patients who have received at least one dose of 
the study drug and have had samples collected, and PK serum concentrations of LY3022855 will 
be determined.
The parameters for analysis will include but not be limited to maximum concentration (Cmax) 
and trough concentration (Ctrough) of LY3022855.  Additional analyses will be performed if 
warranted by data, and other validated PK software programs (for example, NONMEM) may be 
used if appropriate and approved by Global Pharmacokinetic management.  The version of any 
software used for the analysis will be documented and the program will meet the Lilly 
requirements of software validation.
10.6. Pharmacodynamic Analyses
Pharmacodynamic data from all patients undergoing pharmacodynamic assessments will be 
analyzed.
To study the impact of the study drug and the dose levels on the patients, the changes from 
baseline over time in peripheral blood immune cell subsets will be documented. The
immunomodulatory activity of LY3022855 will be documented by examining markers that 
include, but are not limited to: Live-Dead, CD3, CD4, CD8, CD14, CD16, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS. The expression of those markers will be quantified by flow 
cytometric analysis with an antibody panel.
In addition, changes from baseline over time in serum cytokines will be determined by MSD
multiplex cytokine immunoassay or ELISA. The markers to be measured using these
technologies include, but are not limited to: CSF-1, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, IL-34, and TNF-α.
Biomarker measures of protein expression, based on flow cytometry, MSD, and ELISA, will be 
summarized by tumor type and/or dosage, based on enrolled patients.  Summary statistics may
include means, medians, corresponding standard errors, quartiles, and ranges.  Graphics, 
including profile plots of markers over time, will be generated to explore potential patterns 
between patients.  Correlation analyses between biomarkers and relative laboratory tests may be 
performed to further explore the activity of LY3022855.
10.7. Pharmacokinetic/Pharmacodynamic Analyses
An exploratory correlative analysis of LY3022855 PK and pharmacodynamics may be 
conducted.

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10.8. Efficacy Analyses
Tumor response data will be reported using listings and descriptive statistics. The ORR is 
estimated by the proportion of enrolled patients who have a best overall response of complete 
response (CR) or partial response (PR). The disease control rate (DCR) is estimated by the 
proportion of enrolled patients who have a best overall response of CR, PR, or stable disease. A 
95% exact confidence interval will be constructed to determine the level of precision of the ORR 
and DCR if appropriate. Time-to-event variables such as progression-free survival (PFS), 
duration of response, and overall survival (OS) will be tabulated if appropriate. The Kaplan-
Meier method (Kaplan and Meier 1958) will be used to estimate the survival curves, medians, 
and survival rates at specified time points, if applicable.
10.9. Interim Analyses
Since this is a Phase 1 study, safety data will be reviewed on an ongoing basis.
For Dosages C and D (patients with breast cancer), interim analyses will be conducted in each 
dosage to review available safety, efficacy, PK, and pharmacodynamic data after 5 patients in 
that particular dosage have either completed approximately 3 cycles of therapy or discontinued 
from the treatment. If 2 or more responders are observed, an additional 5 patients will be 
enrolled. Further interim analysis may be considered if deemed appropriate by the sponsor.
If it is deemed that enough data are obtained to assess the primary objective and the secondary 
objectives, a clinical study report might be created before the last patient visit.  In this case, all 
data until the data cutoff date will be used for the analysis of safety, efficacy, PK, and 
pharmacodynamic biomarkers.  All data defined in the protocol will continue to be collected 
from patients on treatment after the data cutoff date.  These data may be reported separately, and 
the analyses on all patients including these data may not be performed.

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11. Informed Consent, Ethical Review, and 
Regulatory Considerations
11.1. Informed Consent
The investigator is responsible for ensuring that the patient understands the potential risks and 
benefits of participating in the study, including answering any questions the patient may have in 
regard to the study procedures and patient requirements throughout the study and sharing in a 
timely manner any new information that may be relevant to the patient’s willingness to continue 
his or her participation in the study in a timely manner.
The ICF will be used to explain the potential risks and benefits of study participation to the 
patient in simple terms before the patient is entered into the study and to document that the 
patient is satisfied with his or her understanding of the potential risks and benefits of 
participating in the study and desires to participate in the study.
The investigator is ultimately responsible for ensuring that informed consent is given by each 
patient or legal representative before the study is started.  This includes obtaining the appropriate 
signatures and dates on the ICF prior to the performance of any protocol screening procedures 
and prior to the administration of study drug.
In this protocol, the term “informed consent” includes all consent and assent given by patients or 
their legal representatives.
11.2. Ethical Review
Lilly or its representatives must approve all ICFs before they are used at investigative sites(s).  
All ICFs must be compliant with the ICH guideline on GCP.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  The ERB(s) will review the protocol as required.
The study site’s ERB(s) should be provided with the following prior to any study activities and 
during the course of the trial for any amendments/addendums or administrative notifications:

the current IB

ICF

relevant curricula vitae

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11.3. Regulatory Considerations
This study will be conducted in accordance with:
1) consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences
International Ethical Guidelines 
2) ICH GCP Guideline [E6]
3) applicable laws and regulations
The investigator or designee will promptly submit the protocol to applicable ERB(s).
Some of the obligations of the sponsor will be assigned to a TPO.
An identification code assigned by the sponsor to each patient will be used in lieu of the patient’s 
name to protect the patient’s identity when reporting AEs and/or other study-related data.
11.3.1. Investigator Information
Site-specific contact information may be provided in a separate document.
11.3.2. Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative along with the IB acknowledgement 
form.
11.3.3. Final Report Signature
The investigator or designee will sign the clinical study report for this study, indicating 
agreement with the analyses, results, and conclusions of the report.
The sponsor’s responsible medical officer and statistician will approve the final clinical study 
report for this study, confirming that, to the best of his or her knowledge, the report accurately 
describes the conduct and results of the study.

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12. References
Bourette RP, Rohrschneider LR. Early events in M-CSF receptor signaling. Growth Factors.
2000;17(3):155-166.
Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, 
Version 4.0, DCTD, NCI, NIH, DHHS. 2009. Publish date: 29 May 2009.
DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, 
Wadhwani N, Keil SD, Junaid SA, Rugo HS, Hwang ES, Jirström K, West BL, Coussens LM. 
Leukocyte complexity predicts breast cancer survival and functionally regulates response to 
chemotherapy. Cancer Discov. 2011;1(1):54-67.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, 
Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. 
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
Eur J Cancer. 2009;45(2):228-247.
Ide H, Hatake K, Terado Y, Tsukino H, Okegawa T, Nutahara K, Higashihara E, Horie S. Serum 
level of macrophage colony-stimulating factor is increased in prostate cancer patients with 
bone metastasis. Hum Cell. 2008;21(1):1-6.
Kacinski BM. CSF-1 and its receptor in ovarian, endometrial and breast cancer. Ann Med.
1995;27(1):79-85.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Amer Stat
Assoc. 1958;53(282):457-481.
Lawicki S, Szmitkowski M, Wojtukiewicz M. The pretreatment plasma level and diagnostic 
utility of M-CSF in benign breast tumor and breast cancer patients. Clin Chim Acta.
2006;371(1-2):112-116.
Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. 
Cancer Res. 2006;66(2):605-612.
Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D, 
Hollenbaugh D, Linnemann T, Qin M, Wong J, Chu K, Doberstein SK, Williams LT. 
Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. 
Science. 2008;320(5877):807-811.
Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW. 
Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res.
2006;66(23):11238-11246.
Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression 
of mammary tumors to malignancy. J Exp Med. 2001;193(6):727-740.
Mroczko B, Groblewska M, Wereszczynska-Siemiatkowska U, Okulczyk B, Kedra B, 
Laszewicz W, Dabrowski A, Szmitkowski M. Serum macrophage-colony stimulating factor 
levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis. 
Clin Chim Acta. 2007;380(1-2):208-212.

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Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a 
common language for tumor response to immunotherapy: immune-related response criteria 
using unidimensional measurements. Clin Cancer Res. 2013;19(14):3936-3943.
Nowicki A, Szenajch J, Ostrowska G, Wojtowicz A, Wojtowicz K, Kruszewski AA, 
Maruszynski M, Aukerman SL, Wiktor-Jedrzejczak W. Impaired tumor growth in colony-
stimulating factor 1 (CSF-1)-deficient, macrophage-deficient op/op mouse: evidence for a role 
of CSF-1-dependent macrophages in formation of tumor stroma. Int J Cancer.
1996;65(1):112-119.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5(6):649-655.
Pixley FJ, Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action. 
Trends Cell Biol. 2004;14(11):628-638.
Radi ZA, Koza-Taylor PH, Bell RR, Obert LA, Runnels HA, Beebe JS, Lawton MP, Sadis S. 
Increased serum enzyme levels associated with kupffer cell reduction with no signs of hepatic 
or skeletal muscle injury. Am J Pathol. 2011;179(1):240-247.
Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, Bennett CL, Bohlius J, 
Evanchuk D, Goode MJ, Jakubowski AA, Regan DH, Somerfield MR; American Society of 
Clinical Oncology; American Society of Hematology. American Society of Clinical 
Oncology/American Society of Hematology clinical practice guideline update on the use of 
epoetin and darbepoetin in adult patients with cancer. J Clin Oncol. 2010;28(33):4996-5010.
Sadis S, Mukherjee A, Olson S, Dokmanovich M, Maher R, Cai C-H, Le V. Safety, 
pharmacokinetics, and pharmacodynamics of PD-0360324, a human monoclonal antibody to 
monocyte/macrophage colony stimulating factor, in healthy volunteers. ACR/ARHP Annual 
Meeting Abstract (Poster 408), Philadelphia PA, 2009.
Sasmono RT, Oceandy D, Pollard JW, Tong W, Pavli P, Wainwright BJ, Ostrowski MC, 
Himes SR, Hume DA. A macrophage colony-stimulating factor receptor-green fluorescent 
protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. 
Blood. 2003;101(3):1155-1163.
Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, 
Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, 
Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials 
Working Group. Design and end points of clinical trials for patients with progressive prostate 
cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical 
Trials Working Group. J Clin Oncol. 2008;26(7):1148-1159.
Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, 
Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, 
Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, 
Wolff AC. 2006 update of recommendations for the use of white blood cell growth factors: an 
evidence-based clinical practice guideline. J Clin Oncol. 2006;24(19):3187-3205.

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Wang T, Papoutsi M, Wiesmann M, DeCristofaro M, Keselica MC, Skuba E, Spaet R, 
Markovits J, Wolf A, Moulin P, Pognan F, Vancutsem P, Petryk L, Sutton J, Chibout SD, 
Kluwe W. Investigation of correlation among safety biomarkers in serum, histopathological 
examination, and toxicogenomics. Int J Toxicol. 2011;30(3):300-312.
Zhu XD, Zhang JB, Zhuang PY, Zhu HG, Zhang W, Xiong YQ, Wu WZ, Wang L, Tang ZY, 
Sun HC. High expression of macrophage colony-stimulating factor in peritumoral liver tissue 
is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin 
Oncol. 2008;26(16):2707-2716.

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Attachment 1.
Protocol JSCB Study Schedules

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Baseline and Cycle 1 Assessments (for All Dosing Schedules)
Procedure
Baseline
Treatment Cycle 1 only
Comments
Relative Day Prior 
to Day 1 of Cycle 1
≤28
≤14
≤7
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Eligibility Assessments
Informed consent
X
ICF must be signed prior to performance of any protocol-specific tests/procedures.
Medical history
X
β-hCG Pregnancy test
X
At baseline, a urine or serum pregnancy test is required for WOCBP.  Thereafter,
every 12 weeks after the first dose or according to local regulations, whichever is 
more frequent.
ECG
X
X
X
Note that in cases where ECG and blood sample collection are scheduled at the 
same time, all blood sampling should be performed prior to ECG assessment.
ECOG PS assessment
X
X
X
X
X
X
X
Safety Assessments
Physical examination
X
X
X
X
Includes height (at baseline only), and thoracic, abdominal, and symptom-directed 
examination.
Vital signs and weight 
measurement
X
X
X
X
X
X
X
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.  
Vital signs will be checked and recorded prior to each infusion of LY3022855, 
midway through each infusion, at the end of each infusion, and every 15 minutes for 
the first hour following each infusion, including Cycle 1, Day 1 (also to be checked 
and recorded at nontreatment visits during Cycle 1).
Toxicity/AE assessment
X
X
X
X
X
X
X
Any preexisting toxicity should be documented, recorded, and graded (CTCAE v4.0 
grade) as a part of the baseline medical history.
AEs that are serious, considered related to study treatment or the study, or that 
caused the patient to discontinue before completing the study should be followed 
until the event is resolved, the event is no longer considered to be drug-related, the 
event becomes stable or returns to baseline, a new treatment is initiated for the 
patient, or the patient dies or is lost to follow-up.  Frequency of AE and SAE
follow-up evaluation is left to the discretion of the investigator.  Data on SAEs that 
occur before the end of the trial will be stored in the collection database and the 
Lilly Safety System.
Concomitant medication 
assessment
X
X
X
X
X
X
X
Including those medications taken within 28 days prior to the first dose of study 
therapy.

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Procedure
Baseline
Treatment Cycle 1 only
Comments
Relative Day Prior 
to Day 1 of Cycle 1
≤28
≤14
≤7
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Laboratory Tests
HIV and viral hepatitis B 
and C screening
X*
Includes HIV and hepatitis B and C, per institutional standards.
If done within 28 days prior to Cycle 1, Day 1 as part of standard of care, does not 
need to be repeated.
* Should be done within 60 days prior to enrollment.
Hematology
X
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
Coagulation
X
X*
Evaluations performed as part of the baseline assessment do not need to be repeated 
on Cycle 1, Day 1, unless required in the opinion of the investigator.
* Required within 14 days of planned posttreatment tumor biopsy.
Serum chemistry
X
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
CEA and CA 15-3
X
Applies only to breast cancer cohorts and if clinically applicable.
C-reactive protein
assessment
X
X
X
X
X
X
X
Every week for the first 12 weeks on therapy, and every 2 weeks thereafter.
Urinalysis
X
Evaluations performed as part of the baseline assessment do not need to be repeated 
on Cycle 1, Day 1, unless required in the opinion of the investigator.  Urinalysis 
evaluations will be performed at the beginning of each cycle (that is, approximately 
every 6 weeks following the first dose of study therapy).  If urine dipstick >1+ for 
protein, obtain 24-hour urine collection for protein analysis.
Serum and urine 
myoglobin
X*
X*
X*
X*
X*
X*
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Tailoring biomarkers
X
10 mL of blood to be drawn for future pharmacogenetic biomarker testing.
Blood sampling for PK, 
PD, IG
Refer to Attachment 4, Attachment 5, and Attachment 6.
All sampling indicated in Attachment 4, Attachment 5, and Attachment 6 is to be 
done only after study eligibility is met.
Efficacy Assessments
Imaging studies 
(CT/MRI)
X*
X
Radiographic assessment of tumor response should be performed prior to the start of 
a cycle so that results are available before the patient receives a new cycle of 
treatment.  If done within 28 days prior to Cycle 1, Day 1, as part of standard of 
care, does not need to be repeated prior to the start of Cycle 1.
* For patients with treated CNS metastases that are eligible for this study, a baseline 
MRI documenting disease stability within 60 days prior to enrollment is required.

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Procedure
Baseline
Treatment Cycle 1 only
Comments
Relative Day Prior 
to Day 1 of Cycle 1
≤28
≤14
≤7
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Bone scan
X
X*
Breast cancer cohort:  A baseline bone scan is required, except in the event that a 
PET scan is performed within 28 days prior to the first dose of study therapy that is 
negative for bone disease.  Routine bone scans during treatment are not required, 
except in the setting of bone-only disease (no lymph node, visceral, skin, or 
subcutaneous metastases), or as deemed appropriate by the investigator.
*Prostate cancer cohort:  Bone scans are required at baseline and (follow-up 
[posttreatment]) every 6 weeks thereafter, or as clinically indicated.
If done within 28 days prior to Cycle 1, Day 1, as part of standard of care, does not 
need to be repeated prior to the start of Cycle 1.
Tumor assessments
X
X
Radiographic assessment of tumor response should be performed prior to the start of 
a cycle so that results are available before the patient receives a new cycle of 
treatment.
If done within 28 days prior to Cycle 1, Day 1, as part of standard of care, does not 
need to be repeated prior to the start of Cycle 1.
Tumor core needle or 
surgical biopsy
X
X
Required:  The first tumor biopsy will be taken (attempted) at baseline (predose), 
within 14 days prior to dosing on Cycle 1, Day 1, and the second tumor biopsy will 
be taken (attempted) within 14 days prior to dosing on Cycle 2, Day 1.
Optional:  In cases of disease progression, if the patient’s condition allows it, an 
optional tumor biopsy will be performed, as clinically indicated (refer to 
Section 8.2.2.2).
Ad hoc tumor tissue and 
blood sampling
X
Optional:  Additional tumor tissue and/or blood samples for biomarker research 
may be obtained at the investigator’s discretion in discussion with the patient, such 
as at the time of radiographic response or treatment progression.  If, at any time 
during the study, tumor tissue is obtained through a core biopsy, surgical biopsy, or 
resection as routine clinical care, the sponsor requests a tissue block or unstained 
slides for analysis of potentially relevant surrogate biomarkers.
Study Therapy Administration
Administer LY3022855
Weekly (on Days 1, 8, 
15, 22, 29, and 36)
X
X
X
X
X
X
Administer LY3022855
Every 2 Weeks (on Days 
1, 15, and 29)
X
X
X
Administer LY3022855
on Weeks 1, 2, 4, and 5 
(on Days 1, 8, 22, and 
29)
X
X
X
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; CNS 
= central nervous system; CT = computed tomography; CTCAE v4.0 = Common Terminology Criteria for Adverse Events, version 4.0; ECG = electrocardiogram; ECOG PS= 
Eastern Cooperative Oncology Group performance status; HIV = human immunodeficiency virus; ICF = informed consent form; IG = immunogenicity; MRI = magnetic 
resonance imaging; PET = positron emission tomography; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse event; ULN = upper limit of normal; 
WOCBP = women of childbearing potential.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Cycle 2 Assessments (for All Dosing Schedules)
Procedure
Treatment Cycle 2 only
Comments
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated otherwise.
Safety Assessments
β-hCG Pregnancy test
Urine or serum pregnancy test is required for WOCBP every 12 weeks after the first dose or 
according to local regulations, whichever is more frequent.
ECG
Note that in cases where ECG and blood sample collection are scheduled at the same time, all blood 
sampling should be performed prior to ECG assessment.
ECOG PS assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol: Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
Physical examination
X
Includes thoracic, abdominal, and symptom-directed examination.
Vital signs and weight 
measurement
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.  Vital signs will be 
checked and recorded prior to each infusion of LY3022855, midway through each infusion, at the end 
of each infusion, and every 15 minutes for the first hour following each infusion.
Toxicity/AE assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
AEs that are serious, considered related to study treatment or the study, or that caused the patient to 
discontinue before completing the study should be followed until the event is resolved, the event is no 
longer considered to be drug-related, the event becomes stable or returns to baseline, a new treatment 
is initiated for the patient, or the patient dies or is lost to follow-up.  Frequency of AE and SAE 
follow-up evaluation is left to the discretion of the investigator.  Data on SAEs that occur before the 
end of the trial will be stored in the collection database and the Lilly Safety System.
Concomitant medication 
assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
Laboratory Tests
Hematology
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
Serum chemistry
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
CEA and CA 15-3
X
Applies only to breast cancer cohorts and if clinically applicable.
C-reactive protein
assessment
X
X
X
X
X
X
Every week for the first 12 weeks on therapy, and every 2 weeks thereafter.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 76
LY3022855 (IMC-CS4)
Procedure
Treatment Cycle 2 only
Comments
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated otherwise.
Urinalysis
X
Urinalysis evaluations will be performed at the beginning of each cycle (that is, approximately every 
6 weeks following the first dose of study therapy). If urine dipstick >1+ for protein, obtain 24-hour 
urine collection for protein analysis.
Serum and urine myoglobin
X*
X*
X*
X*
X*
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Blood sampling for PK, PD, 
IG
Refer to Attachment 4, Attachment 5, and 
Attachment 6.
Efficacy Assessments
Imaging studies (CT/MRI)
X
Radiographic assessment of tumor response should be performed prior to the start of a cycle so that 
results are available before the patient receives a new cycle of treatment.
Bone scan
X*
Breast cancer cohort:  Routine bone scans during treatment are not required, except in the setting of 
bone-only disease (no lymph node, visceral, skin, or subcutaneous metastases), or as deemed 
appropriate by the investigator.
*Prostate cancer cohort:  Follow-up (posttreatment) bone scans are required every 6 weeks, or as 
clinically indicated.
Tumor assessments
X
Radiographic assessment of tumor response should be performed prior to the start of a cycle so that 
results are available before the patient receives a new cycle of treatment.
Ad hoc tumor tissue and 
blood sampling
X
Optional:  Additional tumor tissue and/or blood samples for biomarker research may be obtained at 
the investigator’s discretion in discussion with the patient, such as at the time of radiographic 
response or treatment progression.  If, at any time during the study, tumor tissue is obtained through a 
core biopsy, surgical biopsy, or resection as routine clinical care, the sponsor requests a tissue block 
or unstained slides for analysis of potentially relevant surrogate biomarkers.
Study Therapy Administration
Administer LY3022855
Weekly (on Days 1, 8, 15, 
22, 29, and 36), 
X
X
X
X
X
X
Administer LY3022855
Every 2 Weeks (on Days 1, 
15, and 29
X
X
X
Administer LY3022855
Weeks 1, 2, 4, and 5 (on 
Days 1, 8, 22, and 29
X
X
X
X
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; CT = 
computed tomography; ECG = electrocardiogram; ECOG PS= Eastern Cooperative Oncology Group performance status; IG = immunogenicity; MRI = magnetic resonance 
imaging; PET = positron emission tomography; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse event; ULN = upper limit of normal; WOCBP = 
women of childbearing potential.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Cycle 3+ Assessments (for All Dosing Schedules)
Procedure
Treatment Cycle 3 and beyond
Comments
Day 1
Day 8
Day 15
Day 22
Day 29
Day 36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Safety Assessments
β-hCG Pregnancy test
X
Urine or serum pregnancy test is required for WOCBP 12 weeks after the first dose and 
every 12 weeks thereafter, or according to local regulations, whichever is more frequent.
ECG
X*
X*
Note that in cases where ECG and blood sample collection are scheduled at the same 
time, all blood sampling should be performed prior to ECG assessment.
* As clinically indicated, prior to last infusion of treatment cycle.
ECOG PS assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol: Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).
Physical examination
X
Includes thoracic, abdominal, and symptom-directed examination.
Vital signs and weight 
measurement
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.  Vital 
signs will be checked and recorded prior to each infusion of LY3022855, midway 
through each infusion, at the end of each infusion, and every 15 minutes for the first hour 
following each infusion.
Toxicity/AE assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).
AEs that are serious, considered related to study treatment or the study, or that caused the 
patient to discontinue before completing the study should be followed until the event is 
resolved, the event is no longer considered to be drug-related, the event becomes stable 
or returns to baseline, a new treatment is initiated for the patient, or the patient dies or is 
lost to follow-up.  Frequency of AE and SAE follow-up evaluation is left to the 
discretion of the investigator.  Data on SAEs that occur before the end of the trial will be 
stored in the collection database and the Lilly Safety System.
Concomitant medication 
assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Procedure
Treatment Cycle 3 and beyond
Comments
Day 1
Day 8
Day 15
Day 22
Day 29
Day 36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Laboratory Tests
Hematology:
For Weekly and 
Every-2-Week 
schedules
X
X
X
Cycle 3 and beyond:  Every 2 weeks for patients receiving treatment on the Weekly or 
Every-2-Week dosing schedule (on Days 1, 15, and 29).
For Weeks 1, 2, 4, 
and 5 schedule
X
X
Cycle 3 and beyond:  Every 3 weeks for patients receiving treatment Weeks 1, 2, 4, and 5 
(on Weeks 1 and 4 [that is, Days 1 and 22]).
Serum chemistry:
For Weekly and 
Every-2-Week 
schedules
X
X
X
Cycle 3 and beyond:  Every 2 weeks for patients receiving treatment on the Weekly or 
Every-2-Week dosing schedule (on Days 1, 15, and 29).
For Weeks 1, 2, 4, 
and 5 schedule
X
X
Cycle 3 and beyond:  Every 3 weeks for patients receiving treatment Weeks 1, 2, 4, and 5 
(that is, on Weeks 1 and 4 [that is, Days 1 and 22]).
CEA and CA 15-3
X
Applies only to breast cancer cohorts and if clinically applicable.
C-reactive protein
assessment
X
X
X
Cycle 3 and beyond:  Every 2 weeks.
Urinalysis
X
Urinalysis evaluations will be performed at the beginning of each cycle (that is, 
approximately every 6 weeks following the first dose of study therapy). If urine dipstick 
>1+ for protein, obtain 24-hour urine collection for protein analysis.
Serum and urine 
myoglobin
X*
X*
X*
X*
X*
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Blood sampling for PK, 
PD, IG
Refer to Attachment 4, Attachment 5, and Attachment 6.
Efficacy Assessments
Imaging studies (CT/MRI)
X
Radiographic assessment of tumor response should be performed prior to the start of a 
cycle so that results are available before the patient receives a new cycle of treatment.
Bone scan
X*
Breast cancer cohort:  Routine bone scans during treatment are not required, except in 
the setting of bone-only disease (no lymph node, visceral, skin, or subcutaneous 
metastases), or as deemed appropriate by the investigator.
*Prostate cancer cohort:  Follow-up (posttreatment) bone scans are required every 6 
weeks, or as clinically indicated.
Tumor assessments
X
Radiographic assessment of tumor response should be performed prior to the start of a 
cycle so that results are available before the patient receives a new cycle of treatment.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 79
LY3022855 (IMC-CS4)
Procedure
Treatment Cycle 3 and beyond
Comments
Day 1
Day 8
Day 15
Day 22
Day 29
Day 36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Ad hoc tumor tissue and 
blood sampling
X
Optional:  Additional tumor tissue and/or blood samples for biomarker research may be 
obtained at the investigator’s discretion in discussion with the patient, such as at the time 
of radiographic response or treatment progression.  If, at any time during the study, 
tumor tissue is obtained through a core biopsy, surgical biopsy, or resection as routine 
clinical care, the sponsor requests a tissue block or unstained slides for analysis of 
potentially relevant surrogate biomarkers.
Study Therapy Administration
Administer LY3022855
Weekly (on Days 1, 8, 15, 
22, 29, and 36)
X
X
X
X
X
X
For patients being treated on Dosage C and who are clinically benefitting, after the 
completion of Cycle 3, the dosing interval may be changed to once-every-2-week dosing 
after discussion with the sponsor.  If a patient’s dosage is changed from that of Dosage C 
(that is, weekly) to every-2-week dosing and then the patient develops progressive 
disease, the patient’s dosage may then be changed back to weekly dosing if agreed upon 
by the investigator and sponsor.
Administer LY3022855
Every 2 Weeks (on Days 
1, 15, and 29)
X
X
X
Administer LY3022855 on 
Weeks 1, 2, 4, and 5 (on 
Days 1, 8, 22, and 29)
X
X
X
X
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; CT = 
computed tomography; ECG = electrocardiogram; ECOG PS= Eastern Cooperative Oncology Group performance status; IG = immunogenicity; MRI = magnetic resonance 
imaging; PET = positron emission tomography; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse event; ULN = upper limit of normal; WOCBP = 
women of childbearing potential.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 80
LY3022855 (IMC-CS4)
Follow-up Assessments (for All Dosing Schedules)
Procedure
30-Day Follow-up
Comments
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated otherwise.
Safety Assessments
β-hCG Pregnancy test
X
Urine or serum pregnancy test is required for WOCBP.
ECG
X
In cases where ECG and blood sample collection are scheduled at the same time, all blood sampling should be 
performed prior to ECG assessment.
ECOG PS assessment
X
Physical examination
X
Includes thoracic, abdominal, and symptom-directed examination.
Vital signs and weight measurement
X
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.
Toxicity/AE assessment
X
All SAEs and LY3022855-related AEs will be followed until the event is resolved, stabilized, returned to 
baseline, deemed irreversible, or otherwise explained (frequency of follow-up evaluations is left to the 
discretion of the investigator).  Data on SAEs that occur before the end of the trial will be stored in the 
collection database and the Lilly Safety System.
Concomitant medication assessment
X
Laboratory Tests
Hematology
X
Serum chemistry
X
C-reactive protein assessment
X
Urinalysis
X
If urine dipstick > 1+ for protein, obtain 24-hour urine collection for protein analysis.
Serum and urine myoglobin
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Blood sampling for PK, PD, IG
Refer to Attachment 4,
Attachment 5, and 
Attachment 6.
Efficacy Assessments
Tumor core needle or surgical 
biopsy
X
Optional:  In cases of disease progression, if the patient’s condition allows it, an optional tumor biopsy will be 
performed, as clinically indicated (refer to Section 8.2.2.2).
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CK = creatine kinase; CRP = clinical research physician; ECG = electrocardiogram; 
ECOG PS= Eastern Cooperative Oncology Group performance status; IG = immunogenicity; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse 
event; ULN = upper limit of normal; WOCBP = women of childbearing potential.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Attachment 2.
Protocol JSCB Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologya

Hemoglobin

Hematocrit

Platelets

Leukocytes (WBC), including differential

Neutrophils – absolute and percentage

Lymphocytes – absolute and percentage

Monocytes – absolute and percentage

Eosinophils – absolute and percentage

Basophils – absolute and percentage
Clinical Chemistrya (Serum Concentrations)

Sodium

Potassium

Chloride

Bicarbonate

Magnesium

Calcium

Phosphorus

Total bilirubin

Direct bilirubin

Alkaline phosphatase

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Gamma glutamyl transpeptidase

Albumin

Total protein

Creatinine

Blood urea nitrogen (BUN)

Uric acid

Glucose (random)

Lipase

Amylase

Creatine kinase (CK)
Coagulationa

Partial thromboplastin time (PTT)

Prothrombin time (PT)/INR
Urinalysisa

Specific gravity

pH

Protein

Glucose

Ketones

Blood

Leukocyte esterase
Serum or Urine Pregnancy Testa
Cardiaca

Troponin I or T
Serologiesa

HIV screening

Viral hepatitis B and C screening
Isoenzymesb

Lactate dehydrogenase (LDH)

Creatine kinase (CK)

Alkaline phosphatase
Serum Markers of Bone Metabolismb

CTX-I
Serum Markers of Inflammationa

C-reactive protein
Additional tests to be performed, as clinically 
indicated, at a routine follow-up visita

Serum myoglobin – if CK ≥2.5 × ULN

Urine myoglobin – if CK ≥2.5 × ULN
Serum Tumor Markers - as clinically indicateda

CEA

CA 15-3
Abbreviations:  CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; HIV = 
human immunodeficiency virus; PT/INR = International Normalized Ratio of prothrombin time; ULN = upper 
limit of normal; WBC = white blood cells.
a
Local or investigator-designated laboratory.
b
Assayed by Lilly-designated laboratory.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Attachment 3.
Protocol JSCB Hepatic Monitoring Tests 
for Treatment-Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly clinical research physician
(CRP).
Hepatic Monitoring Tests (local laboratory)
Hepatic Hematology
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulation
RBC
Prothrombin time, INR
WBC
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B core antibody
Hepatic Chemistry
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibody
AST
GGT
Anti-smooth muscle antibody
CK
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CK = creatine kinase; GGT = gamma 
glutamyl transferase; Ig = immunoglobulin; INR = International Normalized Ratio; RBC = red blood cells; WBC = white 
blood cells.
a
As clinically indicated.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Attachment 4.
Protocol JSCB Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Sampling Schedule for Dosages A and B Only
Note:  All sampling indicated in Attachment 4 is to be done only after study eligibility is met.
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Weekly Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day 1 
(C1D1)
C1D2
Dosing 
Day
C1D8
Dosing 
Day
C1D15
Dosing 
Day
C1D22
Dosing 
Day
C1D29
Dosing 
Day
C1D36
Comments
(≤14 days 
of C1D1)
1 hr
(±6 
min)
EOI
4 hr
(±24 
min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all 
sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
X
PD #4=MSD assay for IFN-γ, IL-
1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
X
X
X
FC #2=Live-Dead, CD3, CD4, 
CD8, FoxP3, PD-1, Ki-67, CTLA-
4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
X
X
X
AP isoenzymes, total CK, CK 
isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
X
X
CTX-I
Troponin I or T - MSKCC lab
X
X
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 84
LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing 
Day
C2D1
Dosing Day
C3D1
C3D2
Dosing 
Day
C3D8
Dosing 
Day
C3D22
Comments
Predose
(±25 hr)
Predose
(±25 hr)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-
67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes
Bone marker - Central lab
X
CTX-I

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 85
LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±25 hr)
Pharmacokinetics
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity analysis as close to
the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be used for PK 
analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 86
LY3022855 (IMC-CS4)
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Every-2-Week Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day1 (C1D1)
C1D2
C1D8
Comments
(≤14 days 
of C1D1)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-
4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 87
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C1D15
Dosing Day
C1D29
C1D30
C1D36
Comments
Predose
(±50 hr)
Predose
(±50 hr)
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X*
X
PD #3=ALT, AST
* For this time point, a separate sample should not be collected 
for PD #3 assessment.  Use the serum chemistry sample 
(Attachment 1) taken at this time point for the PD #3 assessment.
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-
10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 88
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C2D1
Dosing Day
C3D1
C3D2
C3D8
Comments
Predose
Predose
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, 
IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 89
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C3D15
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±50 hr)
Predose
(±50 hr)
Pharmacokinetics
X
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, 
TNFα
Flow cytometry
FC #1 - Central lab
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, 
and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity analysis as close to 
the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be used for PK 
analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 90
LY3022855 (IMC-CS4)
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Weeks 1, 2, 4, and 5 Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day1 (C1D1)
C1D2
Dosing Day
C1D8
C1D15
Comments
(≤14 days 
of C1D1)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
1 hr
(±6 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be 
clearly and accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X*
PD #3=ALT, AST
* For this time point, a separate sample should not 
be collected for PD #3 assessment.  Use the serum 
chemistry sample (Attachment 1) taken at this 
time point for the PD #3 assessment.
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, 
IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-
1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total 
LDH, LDH isoenzymes
Bone marker - Central lab
X
X
CTX-I
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 91
LY3022855 (IMC-CS4)
Weeks 1, 2, 4, and 5 Schedule (continued)
Analyses
Dosing Day
C1D22
Dosing Day
C1D29
Dosing Day
C2D1
Dosing Day
C3D1
Comments
Predose
(±50 hr)
Predose
(±25 hr)
Predose
(±50 hr)
Predose
(±50 hr)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
PD #2=CBC with differential
PD #4 - MSKCC lab
X
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-
10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 92
LY3022855 (IMC-CS4)
Weeks 1, 2, 4, and 5 Schedule (continued)
Analyses
Dosing Day
C3D8
C3D15
Dosing Day
C3D22
Dosing Day
C5D1
Dosing Day
C5D29
Comments
Predose
(±25 hr)
1 hr
(±6 min)
EOI
168 hr
(±25 hr)
EOI
Predose
(±50 hr)
Predose
(±50 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X*
*To be done at this time point and every 12 weeks 
thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, 
IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, 
Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total 
LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 93
LY3022855 (IMC-CS4)
Weeks 1, 2, 4, and 5 Schedule (continued)
Analyses
Dosing Day
C6D29
30-Day Follow-up
(±7 days)
Comments
Predose
(±25 hr)
Pharmacokinetics
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and 
ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity analysis as close to
the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be used for PK 
analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 94
LY3022855 (IMC-CS4)
Attachment 5.
Protocol JSCB Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Sampling Schedule for Dosage C Only
Note: All sampling indicated in Attachment 5 is to be done only after study eligibility is met.
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Weekly Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day 1 
(C1D1)
C1D2
Dosing 
Day
C1D8
Dosing 
Day
C1D15
Dosing 
Day
C1D22
Dosing 
Day
C1D29
Dosing 
Day
C1D36
Comments
(≤14 days 
of C1D1)
1 hr
(±6 
min)
EOI
4 hr
(±24 
min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
X
The date and the time of all 
sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
X
PD #1=CSF-1, IL-34
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
X
PD #4=MSD assay for IFN-γ, IL-
1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
X
X
X
FC #2=Live-Dead, CD3, CD4, 
CD8, FoxP3, PD-1, Ki-67, CTLA-
4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
X
X
X
AP isoenzymes, total CK, CK 
isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 95
LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing 
Day
C2D1
Dosing Day
C3D1
C3D2
Dosing 
Day
C3D8
Dosing 
Day
C3D22
Comments
Predose
(±25 hr)
Predose
(±25 hr)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-
67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 96
LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±25 hr)
Pharmacokinetics
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity analysis as close to 
the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be used for PK 
analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 97
LY3022855 (IMC-CS4)
Attachment 6.
Protocol JSCB Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Sampling Schedule for Dosage D Only
Note:  All sampling indicated in Attachment 6 is to be done only after study eligibility is met.
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Every-2-Week Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day1 (C1D1)
C1D2
C1D8
Comments
(≤14 days 
of C1D1)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-
4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 98
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C1D15
Dosing Day
C1D29
C1D30
C1D36
Comments
Predose
(±50 hr)
Predose
(±50 hr)
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X*
X
PD #3=ALT, AST
* For this time point, a separate sample should not be collected 
for PD #3 assessment.  Use the serum chemistry sample 
(Attachment 1) taken at this time point for the PD #3 assessment.
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-
10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Troponin I or T - MSKCC lab
X

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Every-2-Week Schedule (continued)
Analyses
Dosing Day
C2D1
Dosing Day
C3D1
C3D2
C3D8
Comments
Predose
Predose
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, 
IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Troponin I or T - MSKCC lab
X

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Every-2-Week Schedule (continued)
Analyses
Dosing Day
C3D15
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±50 hr)
Predose
(±50 hr)
Pharmacokinetics
X
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, 
TNFα
Flow cytometry
FC #1 - Central lab
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, 
and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity analysis as close to 
the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be used for PK 
analysis, in the setting of infusion-related reactions.

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Attachment 7.
Protocol JSCB Recommendations for 
Reporting Serious Adverse Events
Recommendations for Reporting Serious Adverse Events
When contacting Lilly to report a SAE, please have the following information available:
Patient Demographics

patient identification (number), sex, date of birth, origin, height, and weight
Study Identification

full trial protocol number, investigator's name, and investigator’s number
Study Drug

drug code or drug name, unit dose, total daily dose, frequency, route, start dose, 
cycle details, start date, and last dose date (if applicable)
Adverse Event

description, date of onset, severity, treatment (including hospitalization), action 
taken with respect to study drug, clinical significance, and test and procedure 
results (if applicable)
Relationship to Study Drug and Protocol Procedures
Concomitant Drug Therapy

indication, total daily dose, duration of treatment, start date, and action taken
In Case of Death

cause, autopsy finding (if available), date, and relationship to study drug and 
protocol procedures

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Attachment 8.
Protocol JSCB ECOG Performance Status
ECOG Performance Status
Activity Status
Description
0
Fully active, able to carry on all predisease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours
4
Completely disabled.  Cannot carry on any self-care.  Totally confined to 
bed or chair
5
Dead
Abbreviation:  ECOG = Eastern Cooperative Oncology Group.
Source:  Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.

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Attachment 9.
Protocol JSCB RECIST Criteria 1.1
Response and progression will be evaluated in this study using the international criteria proposed 
by the new Response Evaluation Criteria in Solid Tumors (RECIST): Revised RECIST 
Guideline (version 1.1; Eisenhauer et al. 2009).
Measurability of Tumor at Baseline
Tumor lesions/lymph nodes will be categorized at baseline as measurable or nonmeasurable.  
Measurable disease is defined by the presence of at least 1 measurable lesion.
Measurable
Tumor lesions:  Measured in at least 1 dimension (longest diameter in the plane of measurement 
is to be recorded) with a minimum size of:

10 mm by computed tomography (CT) or magnetic resonance imaging (MRI) 
scan (slice thickness 5 mm)

10 mm caliper measurement by clinical exam (non-measurable lesions if cannot 
be accurately measured with calipers)

20 mm by chest X-ray.
Malignant lymph nodes:  To be considered pathologically enlarged and measurable, a lymph 
node must be 15 mm in short axis when assessed by CT scan (CT scan thickness recommended 
to be 5 mm).
Nonmeasurable
All other lesions, including small lesions (longest diameter <10 mm or pathological lymph nodes 
with 10 to <15 mm short axis) as well as truly nonmeasurable lesions.  Lesions considered truly 
non-measurable include:  leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pulmonis, inflammatory breast disease, lymphangitis involvement of skin or 
lung, abdominal masses/abdominal organomegaly identified by physical exam that is not 
measureable by reproducible imaging techniques.
Special Considerations for Lesion Measurability
Bone lesions:

Bone scan, positron emission tomography (PET) scan, or plain films are not 
considered adequate imaging techniques to measure bone lesions.

Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as 
CT or MRI, can be considered measurable lesions if the soft tissue component 
meets the definition of measurability.

Blastic bone lesions are non-measurable.

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Cystic lesions:

Simple cysts should not be considered as malignant lesions (neither measurable 
nor nonmeasurable).

Cystic lesions thought to represent cystic metastases can be considered as 
measurable lesions, if they meet the definition of measurability.  If noncystic 
lesions are presented in the same patients, these are preferred for selection as 
target lesions.
Lesions with Prior Local Treatment:

Tumor lesions situated at a previously irradiated area, or in an area subjected to 
other loco-regional therapy, are non-measurable unless there has been
demonstrated progression in the lesion.
Baseline Documentation of Target and Non-Target Lesion
Target Lesions
When more than 1 measurable lesion is present at baseline, all lesions up to a maximum of 
5 lesions total (and a maximum of 2 lesions per organ) representative of all involved organs 
should be identified as target lesions and will be recorded and measured at baseline. Non-nodal 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, and can be reproduced in repeated measurements.  
Measurable lymph nodes are target lesions if they meet the criteria of a short axis of 15 mm by 
CT scan.  All measurements are to be recorded in the eCRF in millimeters (or decimal fractions 
of centimeters [cm]).
Nontarget Lesions
All other lesions (or sites of disease) are identified as nontarget lesions (chosen based on their 
representativeness of involved organs and the ability to be reproduced in repeated measurements) 
and should be recorded at baseline.  Measurement of these lesions are not required but should be 
followed as ‘present,’ ‘absent,’ or in rare cases ‘unequivocal progression.’  In addition, it is 
possible to record multiple nontarget lesions involving the same organ as a single item on the 
eCRF (for example, multiple liver metastases recorded as one liver lesion).
Lymph nodes with short axis 10 mm but <15 mm should be considered nontarget lesions.  
Nodes that have a short axis <10 mm are considered nonpathological and are not recorded or 
followed.
Specifications by Methods of Measurement
All measurements should be recorded in metric notation, using a ruler or calipers if clinically 
assessed.  All baseline evaluations should be performed as closely as possible to the beginning of 
treatment and never more than 4 weeks before the beginning of the treatment.
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up.  Imaging-based evaluation is 

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should always be done rather than clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessed by clinical exam.
An adequate volume of a suitable contrast agent should be given so that the metastases are 
demonstrated to best effect and a consistent method is used on subsequent examinations for any 
given patient.  If prior to enrollment it is known a patient is not able to undergo CT scans with 
I.V. contrast due to allergy or renal insufficiency, the decision as to whether a non-contrast CT or 
MRI (with or without I.V. contrast) should be used to evaluate the patient at baseline and 
follow-up should be guided by the tumor type under investigation and the anatomic location of 
the disease.
Clinical Lesions:  Clinical lesions will only be considered measurable when they are superficial 
and 10 mm diameter as assessed using calipers (for example, skin nodules).  For the case of 
skin lesions, documentation by color photography, including a ruler to estimate the size of the 
lesion is recommended.  When lesions can be evaluated by both clinical exam and imaging, 
imaging evaluation should be undertaken since it is more objective and may be reviewed at the 
end of the study.
Chest X-ray:  Chest CT is preferred over chest X-ray when progression is an important endpoint.  
Lesions on chest X-ray may be considered measurable if they are clearly defined and surrounded 
by aerated lung.
CT and MRI:  CT scan is the best currently available and reproducible method to measure lesions 
selected for response assessment.  Measurability of lesions on CT scan is based on the 
assumption that CT slice thickness is 5 mm.  When CT scan have slice thickness >5 mm, the 
minimum size for a measurable lesion should be twice the slice thickness.  MRI is also 
acceptable in certain situations (for example, for body scans).  If there is concern about radiation 
exposure at CT, MRI may be used instead of CT in selected instances.
Ultrasound:  Ultrasound should not be used to measure lesion size.  Ultrasound examinations 
cannot be reproduced in their entirety for independent review at a later date and, because they are 
operator dependent, it cannot be guaranteed that the same technique and measurements will be 
taken from one assessment to the next.  If new lesions are identified by ultrasound in the course 
of the study, confirmation by CT or MRI is advised.
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor evaluation is 
not advised.  However, such techniques can be useful to confirm complete pathological response 
when biopsies are obtained or to determine relapse in trials where recurrence following complete 
response (CR) or surgical resection is an endpoint.
Tumor Markers:  Tumor markers alone cannot be used to assess tumor response.  If markers are 
initially above the upper normal limit, they must normalize for a patient to be considered in CR.  
Specific guidelines for both prostate-specific antigen response (in recurrent prostate cancer) and 
CA-125 response (in recurrent ovarian cancer) have been published.

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Cytology, Histology:  These techniques can be used to differentiate between partial response 
(PR) and CR in rare cases if required by protocol (for example, residual lesions in tumor types 
such as germ cell tumors, where known residual benign tumors can remain).  When effusions are 
known to be a potential adverse effect of treatment (for example, with certain taxane compounds 
or angiogenesis inhibitors), the cytological confirmation of the neoplastic origin of any effusion 
that appears or worsens during treatment can be considered if the measurable tumor has met 
criteria for response or stable disease (SD) in order to differentiate between response (or SD) and 
progressive disease.
PET Scan (FDG-PET, PET CT):  PET is not recommended for lesion assessment. If a new 
lesion is found by PET, another assessment must be done by CT, unless the PET CT is of 
diagnostic quality.  If CT is done to confirm the results of the earlier PET scan, the date of 
progression must be reported as the earlier date of the PET scan.
Bone Scan:  If lesions measured by bone scan are reported at baseline, it is necessary to repeat 
the bone scan when trying to identify a CR or PR in target disease or when progression in bone is 
suspected.
Response Criteria
Evaluation of Target Lesions
Complete Response (CR):  Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm.  Tumor marker 
results must have normalized.
Partial Response (PR):  At least a 30% decrease in the sum of diameter of target lesions, taking 
as reference the baseline sum diameters.
Progressive Disease:  At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (including the baseline sum if that is the smallest).  
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase 
of at least 5 mm.  The appearance of one or more new lesions is also considered progression.
For equivocal findings of progression (for example, very small and uncertain new lesions; cystic 
changes or necrosis in existing lesions), treatment may continue until the next scheduled 
assessment. If at the next scheduled assessment, progression is confirmed, the date of 
progression should be the earlier date when progression was suspected.
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for progressive disease, taking as reference the smallest sum diameters while on study.
Not Evaluable:  When an incomplete radiologic assessment of target lesions is performed or 
there is a change in the method of measurement from baseline that impacts the ability to make a 
reliable evaluation of response.
Evaluation of Nontarget Lesions
Complete Response:  Disappearance of all nontarget lesions and normalization of tumor marker 
level.  All lymph nodes must be non-pathological or normal in size (<10 mm short axis).

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Non-CR/ non-progressive disease:  Persistence of one or more nontarget lesions and/or 
maintenance of tumor marker level above the normal limits.
Progressive Disease:  Unequivocal progression of existing nontarget lesions.  The appearance of 
one or more new lesions is also considered progression.
Not Evaluable: When a change in method of measurement from baseline occurs and impacts the 
ability to make a reliable evaluation of response.
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
the earliest of objective progression or start of new anticancer therapy, taking into account any 
requirement for confirmation.  The patient’s best overall response assignment will depend on the 
findings of both target and nontarget disease and will also take into consideration the appearance 
of new lesions.  The Best Overall Response will be calculated via an algorithm using the 
assessment responses provided by the investigator over the course of the trial.
Time Point Response
It is assumed that at each protocol-specified time point, a response assessment occurs.  (When no 
imaging/measurement is done at all at a particular time point, the patient is not evaluable (NE) at 
that time point.)  Table 1 provides a summary of the overall response status calculation at each 
time point for patients who have measurable disease at baseline.
Table 1.
Time Point Response: Patients with Target (Nontarget) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Abbreviations:  CR = complete response; NE = inevaluable; PD = progressive disease; PR = partial response; SD = 
stable disease.

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Table 2 is to be used when patients have nonmeasurable disease only.
Table 2.
Time Point Response: Patients with Nontarget Disease Only
Nontarget Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
Abbreviations:  CR = complete response; NE = inevaluable; PD = progressive disease; SD = stable disease.
a
non-CR/non-PD is preferred over SD for nontarget disease. 
Frequency of Tumor Re-Evaluation
A baseline tumor evaluation must be performed within 4 weeks before patient begins study 
treatment. Frequency of tumor re-evaluation while on and adapted to treatment should be 
protocol-specific and adapted to the type and schedule of treatment.  In the context of Phase 2 
studies where the beneficial effect therapy is not known, follow-up every 6-8 weeks is 
reasonable.  Normally, all target and non-target sites are evaluated at each assessment using the 
same method.  However, bone scans may need to be repeated only when CR is identified in 
target disease or when progression in bone is suspected.
Confirmatory Measurement/Duration of Response
Confirmation:
The main goal of confirmation of objective response in clinical trials is to avoid overestimating 
the response rate observed. The confirmation of response is particularly important in 
nonrandomized trials where response (CR/PR) is the primary end point.  In this setting, to be 
assigned a status of PR/CR, changes in tumor measurements must be confirmed by repeat 
assessments that should be performed no less than 4 weeks after the criteria for response are first 
met.  To confirm a response of CR, a full assessment of all target and nontarget lesions that were 
present at baseline must occur, including those measured by bone scan.  To confirm a PR or SD, 
a full assessment of target lesions that were present at baseline must occur; assessment of 
nontarget lesions is not required.
However, in randomized trial (Phase 2 or 3) or studies where SD or progression is the primary 
endpoints, confirmation of response is not required.  But, elimination of the requirement may
increase the importance of central review to protect against bias, in particular of studies which 
are not blinded.
In the case of SD, follow-up measurements must have met the SD criteria at least once after start 
of treatment at a minimum interval not less than 6 weeks measured from first dose.
Duration of Overall Response
The duration of overall response is measured from the time measurement criteria are first met for 
CR or PR (whichever is first recorded) until the first date that disease is recurrent or objective 

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progression is observed (taking as reference for progressive disease the smallest measurements 
recorded on study).
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented.
Duration of Stable Disease
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for objective progression are met, taking as reference the 
smallest sum on study (if the baseline sum is the smallest, that is the reference for calculation of 
progressive disease).
Independent Review of Response and Progression
When objective response (CR + PR) is the primary end point, and when key drug development 
decisions are based on the observation of a minimum number of responders, it is recommended 
that all claimed responses be reviewed by an expert(s) independent of the study.  If the study is a 
randomized trial, ideally reviewers should be blinded to treatment assignment.

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Attachment 10.
Protocol JSCB Guidelines for the 
Management of Immune-Related Adverse Events

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Guidelines for the Management of Potential Toxicities Encountered with Immuno-Oncology Agents
System Organ Class
Adverse Event
CTCAE, Version 4.0 Grade (if 
applicable) and/or Symptomsa
Treatment Planb
Grade
Symptoms
Endocrine
Thyroid issues
Asymptomatic, with TSH 
<0.5 × LLN or >2 × ULN
Continue drug and include free T4 in subsequent cycles.
Symptomatic
Continue drug.  Administer thyroid replacement.
Hypotension, altered 
mental status, headache, 
fatigue
Endocrine issues aside from 
thyroid (for example,
hypophysitis, diabetes 
mellitus)
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).
Resume drug when symptoms resolve and are stable on hormone 
replacement.  In case of adrenal crisis, administer stress-dose steroids.
Permanently discontinue for Grade 3 or 4.
Gastrointestinal
Diarrhea, abdominal pain, 
blood in stool
2
Withhold drug for 1 wk.  Administer antidiarrheal medication and check 
etiology.
Resume drug when symptoms resolve to Grade 1.  If >5 days’ duration 
despite antidiarrheals, begin steroids (0.5 mg/kg/d prednisone); can resume 
drug during taper when symptoms resolve to Grade 1.
Diarrhea, ileus, perforation
≥3
Withhold drug and administer 1-2 mg/kg/day prednisone (no steroids if 
possible perforation); discontinue drug if Grade 3 persists or Grade 4.
If >3 days despite steroids, add nonsteroid immunosuppressive.
Symptomatic pancreatitis
1 or 2
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Can 
resume drug during taper.
≥3
Permanently discontinue drug.  Administer steroids (1-2 mg/kg/d 
prednisone).  Can resume drug during taper.

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System Organ Class
Adverse Event
CTCAE, Version 4.0 Grade (if 
applicable) and/or Symptomsa
Treatment Planb
Grade
Symptoms
Hepatobiliary
Liver abnormality
AST or ALT >5 × ULN but 
≤20 × ULN
AND
total bilirubin ≤ULN
Discuss with sponsor and consider continuing protocol treatment provided 
patient remains without other evidence of liver toxicity.
AST or ALT >20 × ULN
AND
total bilirubin ≤ULN
Discuss with sponsor and consider holding protocol treatment until 
AST/ALT becomes ≤20 × ULN.
AST or ALT >5 × ULN
AND
total bilirubin >ULN
Withhold drug. Administer steroids (1-2 mg/kg/d prednisone).  Consider 
resuming protocol treatment once total bilirubin ≤ULN.
Discontinue protocol therapy permanently if bilirubin does not return to 
below the ULN within 3 wk of holding drug.
3 or 4
GGT or alkaline phosphatase
Continue protocol treatment provided patient remains without other 
evidence of liver toxicity.
Musculoskeletal
Muscle abnormality
CK >2.5 × but ≤10 ULN
AND
Serum and urine myoglobin 
≤ULN
Discuss with sponsor and consider continuing protocol treatment provided 
patient remains without other evidence of muscle or renal toxicity.
CK ≥2.5 × ULN
AND
Serum and urine myoglobin 
>ULN
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Consider 
resuming protocol treatment once serum and urine myoglobin ≤ULN.
Discontinue protocol therapy permanently if serum and urine myoglobin 
does not return to below the ULN within 3 wk of holding drug.

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System Organ Class
Adverse Event
CTCAE, Version 4.0 Grade (if 
applicable) and/or Symptomsa
Treatment Planb
Grade
Symptoms
Nervous
Weakness, paresthesia (for 
example, Guillain-Barré 
syndrome, myasthenia 
gravis)
No impact on activities of 
daily living (ADL)
Withhold drug.  Resume drug when symptoms resolve.
Impact on ADL
Withhold drug.  Administer appropriate medical intervention and steroids 
(1-2 mg/kg/d prednisone).  Can resume drug during taper and after 
discussion with sponsor.
Respiratory
Dyspnea, hypoxia, 
pneumonitis
1
Consider to withhold drug.  Resume drug when stable.
2
Mild to moderate symptoms
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Can 
resume drug during taper.
≥3
Severe
Permanently discontinue drug.  Administer steroids (1-2 mg/kg/d 
prednisone).
If >2 days despite steroids, add nonsteroid immunosuppressive.
Renal and urinary
Elevated creatinine, 
decreased urine output, 
blood in urine, edema
1
<1.5 × baseline
Continue drug.
2 to 3
>1.5 × ULN but <6 × ULN
OR
>1.5 × baseline
Withhold drug.  Administer steroids (1- 2 mg/kg/d prednisone).If 
symptoms resolve to Grade ≤1, taper steroids over 1 month.  Can resume 
drug during taper.
If elevations persist >7 days or worsen treat with Grade 4
recommendations.
4
>6 × ULN
Permanently discontinue drug.  Administer steroids (1-2 mg/kg/d 
prednisone).
Skin
Rash, pruritus
≤50% skin affected
Withhold drug. Start supportive medications for pruritus, for example,
hydroxyzine/loratadine.  If symptoms persist or worsen after 1 wk, 
administer topical or systemic steroids. Resume drug if rash improves to 
mild (localized) and steroid dose <7.5 mg.
Stevens-Johnson syndrome, 
toxic epidermal necrolysis, 
necrosis, bullous or 
hemorrhagic lesions
Permanently discontinue drug.  Begin steroids (1-2 mg/kg/d prednisone).
Abbreviations:  ADL = activities of daily living; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria 
for Adverse Events; I.V. = intravenous(ly); LLN = lower limit of normal; TSH = thyroid-stimulating hormone; ULN = upper limit of normal.
a
If definition of grade not specified, use CTCAE, Version 4.0 definition.
b
Treatment plan should always include a thorough workup of the issue to rule out other potential etiologies.

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Note:  Other steroid options can be given at equivalent doses.  For severe cases, recommend using IV steroids.  For adrenal crisis, mineralocorticoid also needs to 
be added to stress-dose IV steroids.  Also, steroids should be tapered over 1 month once symptoms improve to grade 1, and drug should not be restarted 
until taper over at least 1 month complete.  During steroid use, add prophylactic antibiotics for opportunistic infections.  Immunosuppressive refers to 
infliximab or cyclophosphamide.

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Attachment 11.
Protocol JSCB Protocol Amendment I5F-
MC-JSCB(d) Summary Phase 1 Study to Identify the 
Immunomodulatory Activity of LY3022855 (IMC-CS4) in 
Patients with Advanced, Refractory Breast or Prostate 
Cancer
Overview
Protocol I5F-MC-JSCB Phase 1 Study to Identify the Immunomodulatory Activity of 
LY3022855 (IMC-CS4) in Patients with Advanced, Refractory Breast or Prostate Cancer has 
been amended.  The new protocol is indicated by Amendment (d) and will be used to conduct the 
study in place of any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are as follows:

Revised globally throughout the protocol to refer to the molecule primarily as 
LY3022855 (Lilly code), rather than as IMC-CS4 (ImClone code).

Updated the reference for irRECIST from Wolchok et al. 2009 to Nishino et al. 
2013.

Updated LY3022855 content on clinical pharmacokinetics (Section 5.4.3) and 
clinical experience (Section 5.4.5), based on updated information.

MAIN REASON FOR AMENDMENT:  Revised and/or added content on dose 
rationale (Section 5.5), study design (Section 6.2), study drug administration 
(Section 7.2), dose adjustments and delays (Section 7.2.1), data analyses (Section 
10), study schedules (Attachment 1), and sampling schedules (Attachments 5 and 
6) to account for the addition of 2 new dosages, Dosage C (100 mg QW) and 
Dosage D (100 mg Q2W), based on the RP2D from Study JSCA.  Clinical 
activity in terms of tumor reduction or disease stability was observed in patients 
with breast cancer enrolled to Study JSCA.  Based upon these results, additional
patients will be enrolled to this study for the purpose of collecting additional 
information to further delineate the immunomodulatory activity of LY3022855 in 
patients with breast cancer.

Revised language to permit re-screening of patients, if agreed upon by the 
sponsor.

Revised Exclusion Criterion [16] to exclude only those patients with current (but 
not historical) cardiovascular risks, to permit enrollment of patients with historical 
cardiovascular risks who have been treated and are now asymptomatic.

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LY3022855 (IMC-CS4)

Revised criteria for dose adjustments and delays in Section 7.2.1 for clarity.  
Extended the time permitted for holding study treatment and increased the 
number of dose reductions permitted to provide additional opportunity for
resolution of any toxicities occurring in patients benefitting from study treatment.

Added new Section 7.2.1.2.1 on immune-related AEs (irAEs) and a guideline for 
management of irAEs (Attachment 10), due to the immune modulation potential 
of LY3022855.

Added further details in Section 10.8 regarding data analyses for efficacy (tumor 
response data).

Added further details in Section 10.9 regarding interim analyses.

Deleted some assessments in Attachment 1 for physical examinations during 
Cycle 1, to minimize physician visits.

Added assessments in Attachment 1 for cancer markers CEA and CA 15-3, which 
apply to breast cancer cohorts.

Deleted some assessments in Attachment 1 for ECG to simplify study conduct.

Deleted some sampling time points in Attachment 4 for PK, pharmacodynamics, 
flow cytometry, and isoenzymes to simplify study conduct.

Deleted the sampling summary attachment, because it is not required in the 
protocol.
Additional minor clarifications/corrections were made, including but not limited to:

Deleted language in Section 10 stating a SAP will be provided.

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Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.
4. Abbreviations and Definitions
AUC0-∞
area under the plasma concentration-time curve from time zero to infinity
BLQ
below the quantifiable lower limit of the assay
CnWn
Cycle and Week numbers
CA 15-3
cancer antigen 15-3
CEA
carcinoembryonic antigen
CL
total body clearance
DCR
disease control rate
FACS
fluorescence-activated cell sorting (a type of flow cytometry)
GERD
gastroesophageal reflux disease
IMC-CS4
sSponsor code name for recombinant human immunoglobulin G, subclass 1 (IgG1) 
monoclonal antibody targeted to the colony-stimulating factor-1 receptor (CSF-1R); also 
known as LY3022855
irAE
immune-related adverse event
LVEF
left ventricular ejection fraction
ORR
overall response rate
OS
overall survival
PD
pharmacodynamic or progressive disease
Note - “Pharmacodynamic” and “progressive disease” are spelled out throughout this 
protocol, except as follows:  The abbreviation “PD” appears only in Figure JSCB.1the 
study design figure and in tables in the protocol attachments.  In these locations, the 
abbreviation is clearly defined.
PFS
progression-free survival
Q2Wq2w
once every 2 weeks
QWqw
once weekly
Vss
volume of distribution at steady state
WOCBP
women of child-bearing potential

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5.1. Rationale and Justification for the Study
LY3022855 (hereafter referred toalso knownas IMC-CS4)is a recombinant human monoclonal 
antibody of the immunoglobulin G, subclass 1 (IgG1) targeting CSF-1R.  LY3022855IMC-CS4 
prevents the ligands CSF-1 and IL-34 from binding to CSF-1R 
 
, and in this way inhibits CSF-1R 
activation.  CSF-1R activation is required for proper functioning and survival of tumor-
associated macrophages.  Thus, by blocking CSF-1R activation, 
 
 
 
 
 
 
 
 
 
 
Anti-CSF-1R treatment that limits tumor-associated macrophages enhances CD8+ T-cell
infiltration, leading to decreases in tumor burden (DeNardo et al. 2011).  Moreover, in a 
syngeneic breast cancer model, depletion of CD8+ T cells rendered treatment with CS7 less 
efficacious, indicating interplay between macrophage activity and T-cellinfiltration.  Thus, 
knowledge not only of the macrophage subpopulation but also of the T-cellsubset may affect the 
efficacy of LY3022855IMC-CS4treatment in patients.
 
 
 In addition, pharmacodynamic results from the ongoing Phase 1 
dose-escalation study ofLY3022855IMC-CS4, Study I5F-IE-JSCA (also known as IMCL CP24-
1001; hereafter referred to as JSCA), have suggested target engagement and biologic activity at a 
dosage of 1.25 mg/kg once weekly.  
 
5.2.1. Primary Objective
The primary objective of this study is to document the immunomodulatory activityof 
LY3022855IMC-CS4treatment in patients with advanced, refractory breast or prostate cancers, 
CCI
according to the following measures:
CCI
CCI
CCI

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5.2.2. Secondary Objectives
The secondary objectives of this study are:
To evaluatethe safety and toxicity profile of LY3022855IMC-CS4, as assessed by the 
Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0)
To assess the pharmacokinetic (PK) serum concentrationsof LY3022855IMC-CS4
To document antitumor activity, per ResponseEvaluation Criteria in Solid Tumors, 
version 1.1 (RECIST 1.1)(Eisenhauer et al. 2009)and immune-related RECIST 
(irRECIST)(Wolchok et al. 2009Nishino et al. 2013)(Note:  If a patient has confirmed 
progressive disease per RECIST 1.1 but not per irRECIST, the patient will be considered 
to have not progressed.)
To assess the development of antibodies against LY3022855IMC-CS4(immunogenicity), 
as assessed by a validated immunogenicity assay
5.2.3. Exploratory Objectives
The exploratoryobjectives of this study are:
To explore serum biomarkersthat may be relevant to the mechanism of action of 
LY3022855IMC-CS4, 
 
To explore the pharmacodynamic effects of LY3022855IMC-CS4on tissue biomarkers, 
usingflash-frozen baseline and posttreatment tumor biopsies
To assess antitumor activity in bone, per the Prostate Cancer Clinical Trials Working 
Group (PCWG2) (Scher et al. 2008)criteria
5.3. General Introduction to LY3022855IMC-CS4
LY3022855IMC-CS4is a recombinant human monoclonal antibody of IgG1 that targetsCSF-
1R, a tyrosine kinase receptor expressed selectively on macrophage and granulocyte cell lineages 
in normal individuals and on tumor cells in cancer (Kacinski 1995; Sasmono et al. 2003). 
The presenttrial will look specifically at the immunomodulatory activity of LY3022855IMC-
CS4in patients with advanced breast or prostate cancer refractory or intolerant to at least one 
CCI
prior therapy for their cancer.
CCI

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5.4. LY3022855 IMC-CS4 – Nonclinical and Clinical Experience
5.4.1. Nonclinical Pharmacokinetics of IMC-CS4
The pharmacokinetics of LY3022855IMC-CS4 were evaluated in mice administered 20 mg/kg 
and in cynomolgus monkeys at dose levels that ranged from 10 to 180 mg/kg. The PK of 
LY3022855IMC-CS4 in cynomolgus monkeys was characterized by a relatively long serum 
half-life (t1/2) after single (183-275 hours) or multiple doses (158-470 hours); these half-lives 
were substantially longer than that observed in CD-1 mice (110 hours). Accumulation 
(approximately 2-fold) of LY3022855IMC-CS4 was evident after repeated once-weekly dosing 
in monkeys, suggesting that accumulation may similarly occur in humans, depending on the 
frequency of dosing. The estimated volume of distribution of LY3022855IMC-CS4 in monkeys 
(approximately 29-64 mL/kg) indicated that LY3022855IMC-CS4 was not substantially 
distributed beyond the vasculature. In the cynomolgus monkey studies, LY3022855IMC-CS4
serum exposures were generally proportional to the increases in dose from 10 to 180 mg/kg and 
no sex differences were observed.
The concentration of serum CSF-1 increased in cynomolgus monkeys that were treated with
LY3022855IMC-CS4, suggesting that CSF-1 is a pharmacodynamic marker of LY3022855IMC-
CS4 exposure.  However, in contrast to the LY3022855IMC-CS4 levels, CSF-1 levels did not 
increase proportionally with the increase in LY3022855IMC-CS4 dose. The concentration of 
CSF-1 reached apparent maximal level in all dose groups after the first dose, typically between 
24 and 168 hours following administration of LY3022855IMC-CS4. This observation suggests 
that the pharmacodynamic effect of LY3022855IMC-CS4 on circulating CSF-1 reached 
saturation at the lowest dose levels (10 or 20 mg/kg). CSF-1 levels were generally sustained 
throughout the sampling period. However, in the repeat-dose cynomolgus monkey study, the 
concentration of CSF-1 began to decrease in some animals from the low- (20 mg/kg) and 
middle- (60 mg/kg) dose groups during the recovery period.
Formal studies to characterize the metabolism and disposition of LY3022855IMC-CS4 have not 
been conducted. As a monoclonal antibody, LY3022855IMC-CS4 will be largely confined to 
the extracellular space, which is supported by data from numerous investigations and is 
consistent with the PK evaluation of LY3022855IMC-CS4. No formal metabolism studies of 
LY3022855IMC-CS4 have been performed because the catabolism of antibodies by mammalian 
systems is largely understood and formal studies of the metabolic degradation of these molecules 
are not warranted.
For details on the nonclinical PK of LY3022855IMC-CS4, refer to Section 5 of the current 
Investigator’s Brochure (IB).
5.4.2. Nonclinical Pharmacokinetic/Pharmacodynamic Model
One of the main pharmacological effects of LY3022855IMC-CS4 proposed to underlie the 
inhibition of cancer progression is the depletion of tumor-associated macrophages.  To model 
this effect and estimate the minimum effective blood level required to achieve significant 
antitumor effects, cancer models established in mice were utilized.  However, since 

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LY3022855 (IMC-CS4)
LY3022855IMC-CS4 does not bind to murine CSF-1R, a surrogate antibody, CS7, was 
developed and utilized in order to examine PK/pharmacodynamic relationships.  The binding 
affinity of CS7 to murine CSF-1R (dissociation constant [Kd] = 0.13nM) is 6-fold greater than 
that of LY3022855IMC-CS4 to human CSF-1R (Kd = 0.8nM).  However, comparable potencies 
of the antibodies were observed in cell-based assays of inhibition of CSF-1-induced 
phosphorylation (IC50 = 0.3nM for both antibodies), monocyte differentiation (IC50 = 0.3nM vs 
0.25nM for CS7 and LY3022855IMC-CS4, respectively), and inhibition of monocyte 
proliferation (IC50 = 0.13nM or 0.1nM for CS7 and LY3022855IMC-CS4, respectively).  
Therefore, CS7 and LY3022855IMC-CS4 were anticipated to have similar pharmacological 
effects in vivo at similar concentrations.  Hence, CS7 was utilized in animal models to directly 
predict the trough serum LY3022855IMC-CS4 levels necessary to achieve relevant efficacy in 
human subjects.
Based on these assumptions, to estimate target serum concentrations for efficacy in initial 
clinical investigations, trough concentrations associated with efficacy were determined in human 
breast cancer HCC-1954 and human leukemia NKM-1 models established in mice.  
LY3022855IMC-CS4 was evaluated in the leukemia model established following intravenous 
(I.V.) injection of CSF-1R-expressing NKM-1 cells.  The rat surrogate, CS7, was used in the 
breast cancer model established following subcutaneous injection of CSF-1R-negative HCC-
1954 cells.  The results from the 2 studies identified markedly different efficacious 
concentrations for the antibodies in the different models.  The human NKM-1 model appeared 
very sensitive to the antitumor effect of LY3022855IMC-CS4, as efficacy was achieved at mean 
trough concentrations down to 0.2 µg/mL. For CS7, notably higher doses and concentrations 
were required to inhibit human HCC-1954 breast cancer tumor growth, as a mean trough 
concentration of 425 µg/mL was associated with efficacy.
5.4.3. Clinical Pharmacokinetics of IMC-CS4
As of 28 January 2016, the clinical experience of LY3022855 PK comprised 27 patients enrolled 
in Study JSCA (0.3 mg/kg once weekly [QW] [n=4], 0.6 mg/kg QW [n=3], 1.25 mg/kg QW 
[n=5], 1.25 mg/kg once every 2 weeks [Q2W] [n=9], and 2.5 mg/kg QW [n=6]), and 14 patients 
enrolled in Study JSCB (1.25 mg/kg Q2W [n=9] and 1 mg/kg on Weeks 1, 2, 4, and 5 of every 
6-week cycle [n=5]).
LY3022855 in cancer patients exhibited moderate total body clearance (CL) (mean values on 
Day 1 ranged from 0.0378 to 0.0651 L/h), low volume of distribution at steady state (Vss) (mean 
values on Day 1 ranged from 2.85 to 4.93 L), and moderate t1/2 (mean values on Day 1 ranged 
from 30.8 to 92.2 hours).
LY3022855 CL appeared to be nonlinear with respect to LY3022855 concentration, where 
higher doses of LY3022855 tended to exhibit lower CL values.  However, this apparent 
nonlinearity was confounded by the high incidence of concentrations reported as below the 
quantifiable lower limit of the assay (BLQ), which could artificially inflate the calculated CL at 
lower doses.

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An apparent lack of relationship between patient body weight and LY3022855 CL 
(Figure JSCB.1, upper panel) resulted in an amended dose-escalation plan for Study JSCA, to 
evaluate the safety, PK, and immunogenicity of LY3022855 using a fixed-dosing approach (that 
is, mg as opposed to mg/kg).
The clinical PK of LY3022855 are described in greater detail in Section 6.1 of the IB.

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LY3022855 (IMC-CS4)
Abbreviations:  N = number of patients treated; QW = once weekly; Q2W = once every 
2 weeks.
Figure JSCB.1.
Individual observed clearance versus patient body weight (upper 
panel) and LY3022855 dose (lower panel) for Studies JSCA and 
JSCB.
For the ongoing Phase 1 study of IMC-CS4, Study JSCA, PK data from 5 cohorts have been 
analyzed, wherein IMC-CS4 was administered in the following order:

Cohort 1 – 2.5 mg/kg once weekly

Cohort 2 – 0.3 mg/kg once weekly

Cohort 3 – 0.6 mg/kg once weekly

Cohort 4 – 1.25 mg/kg every 2 weeks

Cohort 5 – 1.25 mg/kg once weekly
PK samples were collected following the first dose for all 5 cohorts and again following 
subsequent doses at Cycle 1, Week 4 for Cohort 1, and at Cycle 1, Week 3 for Cohort 4.
Following single-dose administration of IMC-CS4, the area under the serum concentration-time 
curve serum exposure (AUC(0-∞)), the maximum serum concentration (Cmax), and the trough 

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LY3022855 (IMC-CS4)
concentrations (Ctrough) increased with increasing dose.  For the 1.25-mg/kg every-week dose, the 
trough concentrations following the first dose ranged from approximately 8 to 12 µg/mL, 
whereas for the 1.25-mg/kg every-2-week dose, the trough concentrations following the first 
dose ranged from approximately 3 to 7 µg/mL.
Following multiple dose (fourth dose [Cycle 1, Week 4]) of IMC-CS4 at the 2.5-mg/kg 
every-week dosing schedule (the highest dose tested), the geometric mean clearance (at steady 
state) and exposure (AUC(0-τ)) were 0.0189 L/hr and 11600 hr*µg/mL, respectively.  The 
terminal elimination half-life ranged from 7 to 12 days, and the accumulation ratios ranged from 
2.08 to 3.03.  The trough concentrations (Ctrough) ranged from 24.1 to 44.5 µg/mL.  However, 
these results were obtained from only 3 patients from one dose group (2.5 mg/kg every week).
5.4.4. Nonclinical Toxicology of IMC-CS4
A standard nonclinical toxicology program for advancement of a monoclonal antibody into
clinical trials in oncology indications was conducted to assess the safety and toxicity of
LY3022855IMC-CS4. The nonclinical safety assessment of LY3022855IMC-CS4 was 
conducted in cynomolgus monkeys. This species was considered a relevant model for the 
nonclinical safety evaluation of LY3022855IMC-CS4, based on a preliminary cross-species 
evaluation of tissue/receptor binding and/or functional in vitro pharmacological activity in 
human and cynomolgus monkey test systems and in a subsequent comprehensive tissue cross-
reactivity study using full panels of monkey and human tissues. The toxicology studies 
conducted with LY3022855IMC-CS4 included an exploratory single-dose toxicity and 
toxicokinetic (TK) dose range-finding study and a pivotal 4-week repeat-dose good laboratory 
practice toxicity, TK, and immunogenicity study with a 6-week recovery period. Animals were 
administered LY3022855IMC-CS4 by I.V. infusion, the intended clinical method of 
administration, using the dosing schedule (once weekly) in the planned initial clinical
investigations of LY3022855IMC-CS4. The pivotal study included evaluations of relevant 
safety pharmacology parameters. Because of an anticipated effect of LY3022855IMC-CS4 on 
circulating levels of the target ligand, CSF-1, the levels of CSF-1 were also measured in the 
study animals as a potential marker of the pharmacodynamic activity of the antibody. A 
thorough assessment of peripheral blood and spleen mononuclear cell subsets and an 
immunohistochemical analysis of CD68+ cells (cellular marker of monocytes/macrophages) in 
liver and spleen were also included to determine the effects that blockade of the CSF-1 receptor 
might have on these endpoints.
Assessment of the genotoxicity potential of monoclonal antibodies is not relevant and was, 
therefore, not studied. Based on the early stage of clinical development and the oncology
indication, reproductive toxicity studies of LY3022855IMC-CS4 have not been conducted.
5.4.4.1. Single-Dose Toxicity
Single-dose administration of LY3022855IMC-CS4 at dose levels of 10, 40, and 140 mg/kg 
administered by I.V. infusion over a 15-minute period was well tolerated in cynomolgus 
monkeys (2 monkeys/sex/group) during the 14-day observation period. Sustained dose-
proportional exposure to LY3022855IMC-CS4 was generally observed throughout the 14-day 

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LY3022855(IMC-CS4)
observation period at all dose levels following administration, with noapparent sex differences. 
 
 
 
 
 
 
 
 
 
Similar 
elevations in serumenzyme levels have also been observed when treating with other 
pharmacological agentstargeting CSF-1R (Wang et al. 2011) or CSF-1 (Radi et al. 2011).
No other adverse clinical signs or effects on food consumption, body weight, hematology, and
organ weights were associated with administration of LY3022855IMC-CS4.
CSF-1 serum levels increased relatively quickly after LY3022855IMC-CS4administration and 
remainedsustained throughout the 14-day observation period. CSF-1 was not detected in any 
controlanimals at any time. The maximum levels of CSF-1 reachedwere comparable across 
dosegroups, suggesting that a maximal pharmacodynamic effect of LY3022855IMC-CS4on this 
parameter wasachieved at even the lowest dose level in the study.
The no-observed-adverse-effect level (NOAEL) in this study was considered to be
 This dose corresponded to a dosing Day 1 
 
5.4.4.2. Repeat-Dose Toxicity
In the pivotal repeat-dose toxicity, TK, and immunogenicity study of LY3022855IMC-CS4, 
doses of 0, 20,60, and 180 mg/kg/dose LY3022855IMC-CS4were administered by I.V. infusion 
once weekly tocynomolgus monkeys (5/sex/group) for 4 weeks, followed by a 6-week recovery 
period. Standard toxicological and relevant safety pharmacology(cardiovascular, central 
nervous[CNS], and respiratory systems) endpoints were assessed. As in thesingle-dose study, 
circulating levels of CSF-1 were measured. A thorough assessment ofperipheral blood and 
spleen mononuclear cell subsets and an immunohistochemical analysis ofCD68+ mononuclear 
cells in liver and spleen were also conducted.
Intravenous infusion of LY3022855IMC-CS4was generally well tolerated at all dose levels. 
Sustained dose-proportionalto slightly-greater-than-dose-proportional increases in exposure to 
LY3022855IMC-CS4weregenerally observed, and no sex differences in exposure were 
CCI
CCI
CCI
CCI

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apparent. Moderate accumulation(approximately 2-fold) of LY3022855IMC-CS4occurred after 
repeated administration. 
 
 
 
  
As noted in the single-dose exploratory study, circulating concentrations of CSF-1 increased
shortly after LY3022855IMC-CS4administration. CSF-1 was not detected in any control 
animals. Incontrast to LY3022855IMC-CS4, the concentration of CSF-1 did not vary with dose, 
as comparablemaximum levels were reached in all 3 dose groups. Towards the end of the 
recovery period,CSF-1 levels generally decreased in the 20-and 60-mg/kg dose groups, but 
remained elevated inthe 180-mg/kg dose group.
The key toxicological findings attributed to LY3022855IMC-CS4administration in this study
were periorbital swelling, increases in serum transaminases as noted in the exploratory study,
changes in leukocyte populations (monocytes, neutrophils, CD68+ mononuclear cells, natural
killer [NK] cells), and target organ effects in liver (Kupffer cell hypertrophy/hyperplasia), spleen
(follicular hypertrophy/dendritic cell hyperplasia), and bone marrow (hypercellularity). The
immunomodulatoryeffects on leukocytes, Kupffer cells, spleen, and bone marrow likely reflect
an exaggerated pharmacological response to LY3022855IMC-CS4, possibly associated with 
elevations incirculating CSF-1 levels noted during the study.
Elevations in ALT after the last dosing of LY3022855IMC-CS4were generally minimal in the 
lowest dosegroup (20 mg/kg) and minimal to moderate at the 60-and 180-mg/kg dose levels. 
AST levelswere minimally to moderately increased at all dose levels. ALT and AST returned to 
baselineinthe 20-mg/kg group and trended towards baseline in the 60-and 180-mg/kg groups 
during therecovery period, but remained increased in some individual animals compared with 
baseline. Nohistological changes in the liver were noted to correlate with thetransaminase 
increases, norwere any changes noted in liver functional parameters (that is, AP, bilirubin,and 
coagulation). Therefore, based on the small magnitude of the elevations and the absence of
histological or functional changes, the increases inALT and AST were not considered adverse.
Increases in circulating white blood cells due to increases in neutrophils and monocytes were
observed in both sexes at 60 and 180 mg/kg. Flow cytometry analysis of spleen and peripheral
blood revealed increases in monocytes in spleen and blood at 60 and 180 mg/kg and reductions
in splenic NK cells in all LY3022855IMC-CS4-treated groups. Variability in NK cell numbers 
in theperipheral blood of animals in all dose groups (including control) precluded assigning a
definitive relationship with LY3022855IMC-CS4treatment. These changes in white blood cell 
CCI
counts, inconjunction with minimal reversible increases in serum globulin concentrations with a
corresponding decrease in albumin to globulin ratio, are consistent with the presence of an
inflammatory response. However, no histopathologic evidence of inflammation was observed.  
The monocyte, neutrophil, and globulin changes were reversible by the end of the recovery

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period, while the splenic NK cell reductions were still apparent in some animals. These changes
were not considered adverse because of their small magnitude.
Anatomic pathology changes attributed to the administration of LY3022855IMC-CS4 at the end 
of the dosing period included increased spleen weights in females (all dose groups), which 
generally correlated with splenic follicular hypertrophy (males at 60 and 180 mg/kg; females at 
20 and 180 mg/kg), bone marrow hypercellularity (all female dose groups, one male at 60 
mg/kg), bone marrow lymphoid aggregates (one male, one female at 180 mg/kg), and Kupffer 
cell hypertrophy/hyperplasia (primarily minimal, all male dose groups, one female at 60 mg/kg).  
Immunohistochemical analyses confirmed the presence of increased size or number of CD68+
Kupffer cells in the liver and increased numbers of CD68+ mononuclear cells in the spleen at all
dose levels. The CD68+ cells in the spleen were likely follicular dendritic cells. The
immunohistochemical findings in liver and spleen generally correlated with the histopathologic
diagnoses of Kupffer cell hypertrophy/hyperplasia and splenic follicular hypertrophy. Similar
anatomic pathology findings in spleen, liver, and bone marrow were observed after the recovery
period. These changes were not considered adverse because of their small magnitude.
Slight to moderate periorbital swelling was observed primarily during the recovery phase in all
LY3022855IMC-CS4-treated groups (20, 60, and 180 mg/kg/dose). This clinical sign has been 
reported to occur in humans with another antibody to CSF-1 (Sadis et al. 2009) and may thus 
represent a delayed response to LY3022855IMC-CS4 in the treated monkeys. Watery feces was 
observed only in the 60-mg/kg/dose animals, but is considered possibly related to the 
administration of LY3022855IMC-CS4.  These clinical signs were not considered adverse based 
on their limited impact to the overall health of the animal. No adverse effects were noted in 
assessments of the central nervous (neurological behavioral examination), respiratory (rate), or 
cardiovascular (heart rate, blood pressure, electrocardiogram [ECG]) systems. In addition, no 
evidence of an adverse reaction or intolerance attributable to LY3022855IMC-CS4 was apparent 
at the injection sites after I.V. infusion in the cynomolgus monkey repeat-dose toxicity studies.
Based on the absence of any definitive LY3022855IMC-CS4-related adverse findings, the 
NOAEL for LY3022855IMC-CS4 administered via 15-minute I.V. infusion weekly on 4 
occasions was considered to be 180 mg/kg/dose. The dose corresponded to a dosing Day 22 
mean Cmax of 7985 µg/mL, C168hr of 2945 µg/mL, and mean AUC(0-168hr) of 711340 µg·hr/mL.
5.4.5. Clinical Experience
Clinical experience with LY3022855 comprises 43 patients (as of 28 January 2016) who 
received the following doses I.V. in 2 ongoing Lilly-sponsored Phase 1 studies (I5F-IE-JSCA 
[JSCA] and I5F-MC-JSCB [JSCB]):  2.5 mg/kg QW (n=6), 0.3 mg/kg QW (n=4), 0.6 mg/kg 
QW (n=3), 1.25 mg/kg Q2W (n=20), 1.25 mg/kg QW (n=5), and 1 mg/kg on Weeks 1, 2, 4, and 
5 of every 6-week cycle (n=5).  At the first human dose studied, 2.5 mg/kg QW (Study JSCA), 
which was also the highest dose administered, laboratory abnormalities, including Grade 2-3 
creatine kinase (CK) and Grade 2-3 AST elevations, were noted in 5 patients but were not 
classified as dose-limiting toxicities (DLTs) due to the lack of clinical signs or symptoms of 

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organ toxicity.  Because of these laboratory abnormalities, the protocol for Study JSCA was 
amended and dose escalation was restarted at a lower dose, 0.3 mg/kg QW.
Elevated levels of CK and AST, in the absence of clinical signs or symptoms or other laboratory 
abnormalities suggestive of end-organ damage are, in retrospect, believed to be 
pharmacodynamic indicators of target engagement, rather than markers of drug-related toxicity.  
This belief is strengthened by findings of Radi et al. (2011), in which preclinical models support 
the hypothesis that increases in the levels of serum enzymes can be the result of decreases in 
Kupffer cells, in the apparent absence of hepatic or skeletal muscle injury.  In all cases where 
elevated enzymes were observed following LY3022855 administration in Study JSCA, the levels 
decreased to Grade <2 upon discontinuation of LY3022855, indicating that these effects were 
reversible.
As of 12 October 2016, four DLTs have been observed in Study JSCA:  an event of left 
ventricular dysfunction (Cohort 4, 1.25 mg/kg Q2W), an event of pancreatitis (a patient in 
Cohort 5, 1.25 mg/kg QW), an event of rhabdomyolysis (another patient in Cohort 5), and an 
event of Grade 3 CK elevation (Cohort 7a, 150 mg QW).  The patient with the DLT of left 
ventricular dysfunction had a baseline left ventricular ejection fraction (LVEF) of 35%, which 
obfuscated the relationship between LY3022855 and the DLT event; therefore, the patient was 
considered to be a suboptimal candidate for study participation.  The patient in Cohort 5 who 
experienced pancreatitis had a medical history significant for irritable bowel syndrome and 
gastroesophageal reflux disease (GERD), rendering the patient prone to nausea and abdominal 
pain.  During the course of treatment in Study JSCA, this patient’s serum levels of lipase 
gradually increased, from 21 U/L (baseline) to 138 U/L (Cycle 1, Week 6 [C1W6]) (C1W2 = 79 
U/L, C1W3 = 90 U/L, C1W4 = 121 U/L, C1W5 = 149 U/L).  Following the C1W3 
administration of LY3022855, the patient’s treatment with study drug was held due to rising 
lipase levels.  Steroids were not initiated until the patient presented for medical attention with 
complaints of nausea, vomiting, and abdominal pain on C1W6, at which time the patient was 
diagnosed with Grade 3 pancreatitis.  The symptoms improved with hospitalization, supportive 
therapy, and systemic steroids.  Although this particular case resulted in a DLT, the relationship 
between elevated lipase and gastrointestinal symptoms is not clear, given the patient’s history of 
irritable bowel syndrome and GERD.
Following the occurrence of the 2 DLTs in Cohort 5 of Study JSCA, dose escalation was 
temporarily halted.  Subsequent PK and pharmacodynamic analyses revealed the following:

A lack of correlation between body weight and LY3022855 clearance (Figure JSCB.1)

Intermittent inhibition of CSF-1R signaling with Q2W dosing of LY3022855, as 
evidenced by levels of both circulating CSF-1 and peripheral CD14dimCD16bright cells by 
fluorescence-activated cell sorting (FACS) (Figure JSCB.2)

Sustained inhibition of CSF-1R signaling with 2.5 mg/kg QW and 1.25 mg/kg QW 
dosing (Study JSCA Cohorts 1 and 5, respectively) of LY3022855, as evidenced by 
levels of both circulating CSF-1 and peripheral CD14dimCD16bright cells by FACS (Figure 
JSCB.2)

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Based on these observations, the protocol for Study JSCA was amended to:  (1) examine fixed 
(non-weight-based) dosing of LY3022855 on weekly administration schedules to optimize the 
biological effects of LY3022855 on CSF-1R inhibition, (2) redefine a DLT as any LY3022855-
related AE that occurs during Cycle 1 and does not improve to Grade ≤2, unless stated otherwise, 
despite medical management, including steroids (if applicable) within 7 days of documented 
occurrence, and (3) incorporate management guidelines for immune-related AEs.  Dosing in 
Study JSCA resumed at a fixed dose of 100 mg QW, which is comparable to 1.33 mg/kg in a 75-
kg person and within the coefficient of variation in exposure (34% to 49%).  As of 12 October 
2016, 3 patients in Study JSCA have received 100 mg QW for 6 weeks (Cycle 1, DLT 
assessment period) without experiencing a DLT.  Of the 3 patients treated at the next higher dose 
level of 150 mg QW, 1 patient experienced a DLT of Grade 3 CK elevation associated with 
elevated serum and urine myoglobin.

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Abbreviation:  C = cohort.
Figure JSCB.2.
CD14dimCD16bright (relative percentage of CD45+ HLA-DR+ CD14+) in 
the blood of patients from Study JSCA.
There is currently one IMC-CS4 study, Study JSCA, an ongoing Phase 1 dose-escalation study 
of single-agent therapy in advanced solid tumors that are refractory to standard therapy or for 
which no standard therapy is available.  As of 22 February 2015, IMC-CS4 has been 
administered by I.V. infusion over 6-week cycles to 26 patients in this study.  This includes:

6 patients dosed at the starting dose of 2.5 mg/kg weekly (Cohort 1),

4 patients dosed at 0.3 mg/kg weekly (Cohort 2),

3 patients dosed at 0.6 mg/kg weekly (Cohort 3),

6 patients dosed at 1.25 mg/kg every 2 weeks (Cohort 4),

5 patients dosed at 1.25 mg/kg weekly (Cohort 5), and

2 patients dosed at 1.25 mg/kg every 2 weeks (expansion cohort).
In Cohort 1 (2.5 mg/kg weekly), laboratory findings consistently reported for the 6 treated 
patients included serum elevations of creatine kinase (CK; also known as creatine 
phosphokinase), AST, and LDH.  None of these findings were considered to be dose-limiting 
toxicities (DLTs), due to the lack of clinical signs and symptoms of organ toxicity and because 
enzyme levels decreased upon discontinuation of IMC-CS4, indicating that this effect was 
temporary and reversible.  However, based on these findings, the planned dose-escalation 
scheme for Cohorts 2 and beyond was revised (via dose reductions and prolonged administration 
intervals) to better characterize the IMC-CS4 dose-response effect on the monocyte/macrophage 
system and on various serologic and hematologic parameters.
No DLTs were observed in Cohorts 2 and 3.  In Cohort 4, one patient with a history of cardiac 
dysfunction developed a Grade 3 left ventricular systolic dysfunction (verbatim) after one dose 
of IMC-CS4; the event was considered by the investigator to be related to IMC-CS4.  Because a 
DLT could not be ruled out for this event, 2 additional patients were enrolled into Cohort 4 and 
completed the cycle without experiencing a DLT.
Five patients were subsequently enrolled into Cohort 5, of whom 2 developed DLT events:

One patient developed rhabdomyolysis, complicated by acute renal failure, after one 
dose.  No clear contributing or inciting factors were identified other than possible 
dehydration caused by physical activity in hot humid weather 5 days after receiving 
IMC-CS4.

One patient was diagnosed with pancreatitis after 3 weekly doses.  No clear inciting 
factors could be identified other than study drug administration; however, the diagnosis 
of pancreatitis was obfuscated by concurrent medical issues, including irritable bowel 
syndrome and baseline Grade 1 nausea.
Due to these 2 DLTs, dose escalation was discontinued and enrollment to a 6-patient expansion 
cohort (to be dosed at 1.25 mg/kg every 2 weeks) was initiated.

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As of 28 January 2014 (the cutoff date for the 2014 IB for IMC-CS4), the most commonly 
reported treatment-emergent adverse events (TEAEs) (≥20% patients) regardless of grade or 
relationship to IMC-CS4 were:  fatigue (11 patients); hypoalbuminemia (8 patients); nausea, 
aspartate aminotransferase increased, and decreased appetite (6 patients each); cough and blood 
creatine phosphokinase increased (5 patients each); and lymphopenia, blood alkaline 
phosphatase increased, lymphocyte count decreased, weight decreased, hypocalcemia, 
hyponatremia, and hypertension (4 patients each).  Six patients who received at least 1 dose of 
IMC-CS4 in Study JSCA experienced the following Grade 3 or Grade ≥4 adverse events (AEs) 
regardless of relationship to IMC-CS4:  Grade 3 AEs of anemia, tachycardia, left ventricular 
dysfunction, ascites, fatigue, subcutaneous abscess, aspartate aminotransferase increased, blood 
creatine phosphokinase increased, blood alkaline phosphatase increased, lymphocyte count 
decreased, hypokalemia, pneumothorax, and hypotension; and Grade ≥4 sudden death.
Results from Study JSCA indicate that IMC-CS4 demonstrates a safety and toxicity profile that 
supports further testing of IMC-CS4 as single-agent therapy in advanced solid tumors that are 
refractory to standard therapy or for which no standard therapy is available.
For additional information, see the current IMC-CS4 IB.
More information about the known and expected benefits, risks, and reasonably anticipated AEs
may be found in the IB.  Information on AEs expected to be related to the investigational product 
may be found in Section 7 (Development Core Safety Information) of the IB.  Information on 
SAEs expected in the study population independent of drug exposure and that will be assessed 
by the sponsor in aggregate, periodically during the course of the study, may be found in Section 
6 (Effects in Humans) of the IB.
5.5. Rationale for Selection of Dose
The optimal dose and regimen schedule of LY3022855IMC-CS4 in humans are not known.  The 
protocol will utilize 42 dosages of LY3022855IMC-CS4, where Dosages A and B are weight 
based, while Dosages C and D are non-weight based (that is, fixed), as prior data suggest that 
weight-based dosing does not affect exposure (Section 5.4.3).  Dosage A will be 1.25 mg/kg 
administered every 2 weeks of a 6-week cycle, and Dosage B will be 1 mg/kg on Weeks 1, 2, 4, 
and 5 of a 6-week cycle.Refer to Table JSCB.1 for a summary of the LY3022855 dosages to be 
used in this study.
Table JSCB.1.
Summary of LY3022855 Dosages in Study JSCB
Dosage
Dose
Schedule (based on a 6-week cycle)
Dosage A (weight based dose)
1.25 mg/kg
Q2W
Dosage B (weight based dose)
1 mg/kg
Weeks 1, 2, 4, and 5 of a 6-week cycle
Dosage C (non-weight based/fixed dose)
100 mg
QW
Dosage D (non-weight based/fixed dose)
100 mg
Q2W
Abbreviations:  QW = weekly; Q2W = every 2 weeks (Weeks 1, 3, and 5).

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The rationale for each dosage is presented as follows.
Dosage A is based on the following observations from Study JSCA:

A dosage of 1.25 mg/kg every 2 weeks was the lowest dosage tested in Study JSCA that 
demonstrated a significant increase in the 2 ligands of CSF-1R (CSF-1, IL-34).

Results demonstrated an acceptable clinical safety profile of LY3022855IMC-CS4 at a 
dose of 1.25 mg/kg every 2 weeks.
Dosage B is based on the following rationale:

PK parameters from Study JSCA revealed a 34% to 49% coefficient of variation in 
exposure (AUC0-∞) for patients administered LY3022855IMC-CS4 at 1.25 mg/kg every 2 
weeks or 1.25 mg/kg weekly.  Dosage B at 1 mg/kg on Weeks 1, 2, 4, and 5 of a 6-week 
cycle will result in a cumulative dose of 4 mg/kg every 6 weeks, which is 0.25 mg/kg 
(6.7%) greater than the cumulative dose per (6-week) cycle of Dosage A (1.25 mg/kg 
every 2 weeks).  However, a 6.7% increase in exposure is within the variation of 
exposure documented in Cohorts 4 and 5.  Thus, Dosage B is a reasonable dose and 
schedule in terms of safety.  Additionally, dosing 2 consecutive weeks is expected to 
enhance inhibition of CSF-1R, based upon preliminary pharmacodynamic data (CSF-1 
and IL-34) from Cohorts 4 and 5.  Furthermore, interruption of dosing every 3 weeks 
provides an opportunity for LY3022855IMC-CS4-associated laboratory abnormalities to 
normalize prior to resumption of dosing, as has been observed in the Phase 1 dose-
escalation Study JSCA.
Dosage C rationale:

Pharmacodynamic data (Section 5.4.5) suggest that weekly administration of LY3022855 
results in enhanced target engagement.  Thus, Dosage C will be implemented to examine 
weekly administration of LY3022855.
Dosage D rationale:

It has been observed that all patients who were treated with LY3022855 and experienced 
antitumor activity (as evidenced by tumor shrinkage or stability) as of 24 August 2016 
were treated on a Q2W schedule.  Thus, Dosage D will be implemented to continue 
exploring Q2W dosing, but at a fixed (non-weight-based) dose.  Furthermore, the Q2W 
schedule may be preferable for quality of life, because the patient will require fewer 
clinic visits.
6.1. Study Population
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
re-screened if agreed upon by the sponsor.  If a patient discontinues prior to the second biopsy, 
the patient will be replaced.

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6.1.1. Inclusion Criteria
[6]
Have a performance status of ≤2 on the Eastern Cooperative Oncology Group 
(ECOG) scale.  See Attachment 8Attachment 6.
[9b] Female patients:
are women of child-bearing potential who test negative for pregnancy within 
7 days prior to enrollment based on a urine or serum pregnancy test and agree 
to use a reliable method of birth control during the study and for 12 weeks 
following the last dose of the study drug and also must not be breastfeeding,
10] Have an estimated life expectancy that, in the judgment of the investigator,
that will permit the patient to complete 1 cycle of treatment.
6.1.2. Exclusion Criteria
14] Have symptomatic CNS malignancy or metastasis (screening not required).
Patients with treated CNS metastases are eligible for this study if they are not 
currently receiving corticosteroids (to control CNS edema) and/or 
anticonvulsants, and their disease is asymptomatic for at least 28 days prior to 
enrollment.  Magnetic resonance imaging (MRI) documenting disease 
stability within 60 days prior to enrollment is also required.
[16] Have any of the following cardiovascular conditions a history of and/or 
current:
a) symptomatic coronary artery disease currently or within the past 6 months,
b) confirmed left ventricular ejection fraction ≤50% or any cardiac 
insufficiency > New York Heart Association (NYHA) class II,* currently 
or within the past 6 months,
c) uncontrolled hypertension (>170/100 mm Hg) currently or within the past 
7 days, or
d) serious cardiac arrhythmia (well-controlled atrial fibrillation is permitted)
currently or within the past 6 months.
6.2. Summary of Study Design
Study I5F-MC-JSCB (JSCB) is a single-center, open-label, nonrandomized, noncontrolled 
Phase 1 study of I.V. LY3022855IMC-CS4 in patients with advanced, refractory breast or 
prostate cancer.  Eligible patients will receive LY3022855IMC-CS4 as an infusion, suggested to 
be administered over approximately 90 minutes for the first infusion, decreasing by 30 minutes 
for subsequent infusions, until administered over 30 minutes (refer to Section 7.2 for further 
details of study drug administration).  Study JSCB is intended to explore clinical response and 
immunological activity of single-agent LY3022855IMC-CS4 in approximately 4020 patients 
(enrolled, of whom 3616 will be evaluable), by assessment of biomarkers, cytokines, and 
immune cells.  The study schema is shown in Figure JSCB.3.

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Abbreviations:  Ca = cancer; LY = LY3022855 (IMC-CS4); PD = progressive disease; 
Pts = patients.
Figure JSCB.3.
Study JSCB study design.
Enrollment will be sequential, starting with the assignment of patients to Dosage A 
(LY3022855IMC-CS4, 1.25 mg/kg every 2 weeks [Q2W] of a 6-week cycle), then the 
assignment of patients to Dosage B (LY3022855IMC-CS4, 1.0 mg/kg on Weeks 1, 2, 4, and 5 of 
a 6-week cycle) once the Dosage A cohort of the study is fully enrolled.  Once the Dosage B 
breast cancer cohort is fully enrolled, patients with breast cancer will be assigned by the sponsor 
to Dosage C (LY3022855, 100 mg QW of a 6-week cycle) or D (LY3022855, 100 mg Q2W of a 
6-week cycle) on an alternating basis until 5 patients are enrolled to each of Dosages C and D.  
Once 5 patients are enrolled to each of Dosages C and D, the sponsor and the investigators will 

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LY3022855 (IMC-CS4)
review clinical data to determine if enrollment of an additional 5 patients to each of Dosages C 
and D is warranted (refer to Section 10 for details regarding sample size).
Patients will receive Dosage A, or Dosage B, C, or D for one 6-week cycle or until the patient 
meets one or more criteria for study discontinuation.  After 1 cycle, patients who are benefitting 
from study treatment (that is, no disease progression or unacceptable toxicity) may continue to 
receive study treatment at the same dose and schedule until there is clear (confirmed) evidence of 
disease progression or other withdrawal criteria are met.  At the time of study completion, if a 
patient continues to benefit from study treatment, that patient may enter the continued access 
period.
Immune studies will include evaluations of changes in baseline over time in:  (1) peripheral 
blood immune cell subsets, as determined by flow cytometric analysis using an antibody panel, 
and that may include but not be limited to the following markers: Live-Dead, CD3, CD4, CD8, 
CD14, CD16, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS, as well as (2) serum 
cytokines, as determined by MSD multiplex cytokine immunoassay technology or ELISA, and 
that may include but not be limited to CSF-1, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, IL-34, and TNF-α.  Blood samples for the immunomodulatory studies will be 
taken as described in Attachment 4, Attachment 5, and Attachment 6.
In addition, for all patients, 2 separate tumor biopsy procedures will be performed (attempted):  
the first will be performed at baseline (predose), within 14 days prior to dosing on Cycle 1, Day 
1, and the second will be performed within 14 days prior to dosing on Cycle 2, Day 1.  Biopsy 
samples will be flash frozen, for exploratory biomarker research, to be used in understanding the 
pharmacodynamic effects of LY3022855IMC-CS4.  To ensure adequate enrollment for the 
immune studies, additional patients will be enrolled as needed to replace a patient who either:  
(1) discontinues from the study prior to the second biopsy procedure, or (2) does not have 
sufficient tumor tissue for the second biopsy procedure and in the opinion of the investigator is 
benefitting from study treatment (in which case, the patient will be allowed to remain on study 
treatment).  In addition to the required blood and tumor samples previously noted, optional tumor 
biopsies and/or blood samples for biomarker research may be obtained at the investigator’s 
discretion in discussion with the patient, such as at the time of radiographic response or treatment 
progression.
To document the immunomodulatory activity of LY3022855IMC-CS4 treatment in patients with 
advanced, refractory breast or prostate cancers, an adequate sample size is required (refer to 
Section 10).  A sufficient sample size will allow for 16 evaluable patients.  This sample size is 
estimated to be approximately 20 patients.  This assumes 20% of enrolled (treated) patients will 
be inevaluable.  The sample size is based on the observation that 14 of 17 patients evaluated in 
Study JSCA demonstrated a more-than-2-fold (>100%) increase in CSF-1 levels 8 hours after 
administration of IMC-CS4.

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6.2.1. Study Completion and End of Trial
This study will be considered complete (that is, the scientific evaluation will be complete [study
completion]) when 3616 evaluable patients* are attained.  “End of trial” refers to the date of the 
last visit or last scheduled procedure for the last patient.
6.3.1. Discontinuation of Patients

The patient has confirmed evidence of progressive disease.
o
Exceptions for continuing with study treatment beyond confirmed radiographic 
progression may be made on a case-by-case basis for patients who are believed to 
be clinically benefiting from protocol therapy and both the iInvestigator and 
sSponsor (the CRP/clinical research scientist [CRS]) agree that continuing 
protocol therapy is in the patient’s best interest.

The patient experiences unacceptable toxicity.

The patient experiences a Grade 3 or 4 infusion-related reaction (IRR) to 
LY3022855IMC-CS4.
7.1. Materials and Supplies
LY3022855IMC-CS4 for Injection is supplied at 5 mg/mL strength as a solution dosage, 
packaged in glass vials with an elastomeric closure.  Each vial of LY3022855IMC-CS4 for 
Injection contains 20 mL of the drug product (100 mg/20-mL vial).  Vials of LY3022855IMC-
CS4 for Injection should be stored refrigerated at 2°C to 8°C.  The drug product is formulated to 
contain the active LY3022855IMC-CS4 in 10mM histidine, 100mM glycine, 100mM arginine, 
and 0.01% polysorbate 80 at pH 6.0.  LY3022855IMC-CS4 is a clear or slightly opalescent and 
colorless or slightly yellow liquid without visible particles.
LY3022855IMC-CS4 will be administered as an I.V. infusion. The dose is prepared and infused 
at room temperature (23°C-27°C).  LY3022855IMC-CS4 will be diluted in normal saline to a 
final volume of 250 mL.  Lilly instructions regarding dilution requirements should be followed.
7.2. Study Drug Administration
TwoFour dosages of LY3022855IMC-CS4 will be administered in this study. Refer to 
Table JSCB.1 for a summary of the LY3022855 dosages to be used.:  Dosage A (1.25 mg/kg 
every 2 weeks of a 6-week cycle) and Dosage B* (1 mg/kg on Weeks 1, 2, 4, and 5 of every 6-
week cycle)  Eligible patients will receive LY3022855IMC-CS4 as an I.V. infusion administered 
over a minimum duration of 30 minutes and a maximum duration of 4 hours, based on the known 
safety and stability of the prepared drug.  The infusion rate should not exceed 25 mg/minute.
For Dosages A and B, tThe first dose of LY3022855IMC-CS4 is dependent upon the patient’s 
baseline body weight in kilograms.  Subsequent doses of LY3022855IMC-CS4 must be 
recalculated if there is a ≥10% change (increase or decrease) in body weight from baseline; 
subsequent doses may be recalculated if there is a <10% change (increase or decrease) in body 
weight from baseline.

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For patients with fluid retention, the estimated dry weight, instead of the actual body weight, 
should be used for dose calculation or recalculation (in the setting of substantial fluid retention, 
the Lilly CRP or designee should be consulted regarding optimal assessment of dry weight).
Dosages C and D are to be non-weight based (fixed dosing).
7.2.1. Dose Adjustments and Delays
If benefitting from treatment (that is, no disease progression or other withdrawal criteria), a 
patient who experiences a toxicity may continue to receive LY3022855IMC-CS4 upon 
agreement of the sponsor and according to the dose reduction guidelines for this study 
(Table JSCB.2Table JSCB.1).  For any given patient in the study, their dose may be reduced up 
to a maximum of 2 3 times.
Table JSCB.21.
General Dose Reduction Guidelines
Dosage
Starting Dose and Schedule
First Reduction
Second Reduction
Third Reduction
A
1.0 mg/kg (Weeks 1, 2, 4, and 5)
0.6 mg/kg (qwQW)
0.3 mg/kg (qwQW)
0.3 mg/kg (Q2W)
B
1.25 mg/kg (q2wQ2W)
0.6 mg/kg (qwQW)
0.3 mg/kg (qwQW)
0.3 mg/kg (Q2W)
C
100 mg (QW)
75 mg (QW)
50 mg (QW)
40 mg (QW)
D
100 mg (Q2W)
75 mg (Q2W)
50 mg (Q2W)
40 mg (Q2W)
Abbreviations:  QWqw = weekly; Q2Wq2w = every 2 weeks (Weeks 1, 3, and 5).
In the case of the toxicities listed in Table JSCB.3Table JSCB.2, study treatment may be held (if 
appropriate, in the opinion of the investigator and upon agreement with the sponsor) for a 
maximum of 34 weeks, until resolution to baseline or improvement to Grade <2.  Upon 
resolution to baseline or improvement to Grade <2, study treatment may be administered at a 
reduced dose (according to Table JSCB.2Table JSCB.1), beginning with the next cycle, if 
appropriate, in the opinion of the investigator and upon agreement with the sponsor.  If toxicity 
does not resolve to baseline or improve to Grade <2 within 3 4 weeks following the last 
administered dose, study treatment should be permanently discontinued and the patient should be 
discontinued from the trial.
Once a patient has had a dose reduction (has started a new cycle at the reduced dose), all 
subsequent infusions will be at the reduced dose level; there will be no resumption to prior dose 
level(s).  Any patient experiencing toxicity that would necessitate more than 32 dose reductions 
must discontinue treatment.  Dose reductions must be confirmed by the sponsor.

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Table JSCB.32.
Toxicities for Which Dose Adjustments and Delays Apply

Grade 4 hematologic toxicity

Grade 3 hematologic toxicity lasting >7 days

Grade 3 or 4 nonhematologic toxicity.  Exceptions maybe be made for the following, if agreed upon by the 
sSponsor AND the iInvestigator:
o
Grade ≥3 liver function test (LFT) abnormality, such as alkaline phosphatase, gamma glutamyl 
transferase (GGT), AST, and ALT, not suspected to be drug related
o
Transient Grade ≥2 bilirubin elevation in the presence of known liver metastases lasting ≤7 days,
o
Laboratory abnormalities that improve to Grade <2 or baseline levels within 7 days after initial 
documentation or that are deemed not clinically significant
o
{note that this bullet was promoted one level during this amendment} Laboratory abnormalities 
≥Grade 3 that are deemed not clinically significant do not require dose delay
o
Grade ≥3 asymptomatic elevation of CK WITHOUT elevation in serum and urine myoglobin 
does not require dose modification.
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CK = creatine kinase; 
CRP = clinical research physician.
Refer to Section 7.2.1.1 (Infusion-Related Reactions) regarding dose adjustment, delay, and 
discontinuation of study treatment due to LY3022855IMC-CS4 IRRs.
7.2.1.1. Infusion-Related Reactions
If a patient experiences Grade 1 IRR/allergic reaction, the infusion rate should be decreased by 
50% for the duration of the infusion.  In case of a Grade 2 IRR/allergic reaction, the infusion 
must be stopped until resolution to Grade ≤1; the infusion may then be resumed at 50% of the 
prior infusion rate (the duration of the infusion should not exceed 3 hours).  Once the infusion 
rate has been reduced for a Grade 1 or 2 IRR, it is recommended to maintain the lower infusion 
rate for all subsequent infusions (premedication must be provided prior to any subsequent doses 
of LY3022855IMC-CS4 if the patient has experienced a Grade 1 or 2 IRR).  Occurrence of a 
Grade 3 or 4 IRR requires immediate and permanent discontinuation of LY3022855IMC-CS4.
During Cycles 1 and 2 only, patients are to be observed closely for any potential AEs, from the 
start of the infusion until at least 1 hour after the end of the infusion of LY3022855IMC-CS4.  
This observation is to be done in an area with resuscitation equipment and medications necessary 
for advanced life support and cardiopulmonary resuscitation, such as bronchodilators, 
vasopressor agents (for example, epinephrine), oxygen, glucocorticoids, antihistamines, and I.V. 
fluids, etc.
CAUTION:  Infusion-related reactions may occur during or following LY3022855IMC-CS4
administration.
Premedication is not recommended to be administered prior to the first infusion of 
LY3022855IMC-CS4.  However, if the patient experiences a Grade 1 or 2 IRR, premedication 
must be provided prior to any subsequent doses of LY3022855IMC-CS4.  The choice of 
premedication is to be made after discussion and agreement between the investigator and the 

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Lilly CRP.  In such cases (Grade 1 or 2 IRRs), administration of steroids should be avoided, if 
possible.  Any premedication administered should be documented in the eCRF, including dose 
and route of administration.
If at any time a patient experiences an IRR to LY3022855IMC-CS4, all attempts will be made to 
obtain a blood sample for immunogenicity analysis as close to the onset of the event as possible, 
at the resolution of the event, and 30 days following the event. A portion of the sample taken for 
immunogenicity testing may be used for PK analysis, in the setting of IRRs.
For further details regarding IRRs, including characterization according to CTCAE v4.0 and 
treatment guidelines, refer to the LY3022855IMC-CS4 IB.
7.2.1.2. Other Adverse Events
Based on observations in nonclinical toxicological studies with LY3022855IMC-CS4 and/or 
observations in one clinical trial with another monoclonal antibody targeting CSF-1 (Sadis et al. 
2009), patients receiving LY3022855IMC-CS4 should be closely monitored for signs indicative
of hepatic function impairment (for example, increases in transaminases, LDH, bilirubin, 
coagulation disorders), inflammation (for example, leukocyte alterations, C-reactive protein), CK 
increases, and periorbital swelling.  For details, refer to the LY3022855IMC-CS4 IB.
7.2.1.2.1. Immune-Related Adverse Events (irAEs)
Symptoms occurring during or following infusion of investigational therapy will be defined 
according to the NCI-CTCAE, Version 4.0.
In the setting of symptoms consistent with irAEs occurring following infusion of investigational 
therapy, investigators are encouraged to refer to Attachment 10 as a guideline for the 
management of potential toxicities encountered with immuno-oncology agents.  Due to the 
potential of rapid and serious sequelae associated with irAEs, early intervention with
immunomodulatory agents as indicated is encouraged, concurrent with further diagnostic 
medical evaluations for possible non-immune-related causes of AEs.  Attachment 10 is a 
guideline for the management of irAEs; local standards may supersede recommendations when 
deemed appropriate by the investigator.
7.3. Method of Assignment to Treatment
Patients who meet all criteria for enrollment will be assigned to receive LY3022855IMC-CS4 in 
this study.  Before each patient’s enrollment into the study, an eligibility check must be 
conducted between the investigational site and the Lilly clinical research personnel to confirm 
that each patient meets all enrollment criteria.  Upon confirmation of eligibility, the sponsor will 
confirm the dose and identification number assignment for each patient.

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LY3022855 (IMC-CS4)
7.6. Treatment Compliance
LY3022855IMC-CS4 will be administered I.V. at the investigational site, under the direction of 
the investigator.  As a result, a patient’s compliance with study drug administration is ensured.  
Patients should attend scheduled clinic visits and must comply with study criteria under their 
control.  Deviation(s) from the prescribed dosage regimen should be recorded on the eCRF.
7.6.1. Evaluable Patients
Any patient who does not complete 1 cycle of LY3022855IMC-CS4 treatment, undergo 
1 baseline and 1 posttreatment tumor biopsy procedure (ie, attempted, whether the biopsy is 
successful or not), and complete immune blood studies for 1 cycle will be deemed nonevaluable 
for assessment of a dose level.
Patients who complete 1 cycle of LY3022855IMC-CS4 treatment, undergo 1 baseline and 
1 posttreatment tumor biopsy procedure (ie, attempted, whether the biopsy is successful or not), 
and complete immune blood studies for 1 cycle will be considered evaluable for the assessment 
of a dose level.  Nonevaluable patients may be replaced to ensure that 16 36 evaluable patients 
are attained.
8.1. Safety Evaluations
The safety and tolerability of LY3022855IMC-CS4 have been assessed in nonclinical toxicology 
studies and the results from these studies are detailed in the IB.  This Phase 1 study contains 
detailed safety monitoring that will permit further characterization of the safety profile of 
LY3022855IMC-CS4 in patients, beyond that initially characterized in Phase 1 study JSCA.  
Study procedures and their timing, including collection of blood and urine samples, are described 
in the Study Schedule (Attachment 1).
8.1.1. Safety Data Collection and Review
The timing of all safety evaluations is shown in the Study Schedule (Attachment 1).  
Table JSCB.4Table JSCB.3 presents a summary of AE and SAE reporting guidelines.  
Table JSCB.4Table JSCB.3 also shows which database or system is used to store AE and SAE 
data.
8.1.2.2. Adverse Event and Serious Adverse Event Reporting
Data on SAEs that occur before the end of trial will be stored in the collection database and the 
Lilly Safety System (see Attachment 7Attachment 5 for reporting recommendations).
8.1.2.2.1. Prior to Administration of Study Drug(s)
During screening, all AEs and SAEs (regardless of relatedness to protocol procedures) are 
collected after the patient has signed the informed consent form (ICF).  For patients who do not 
enroll in the trial (that is, have not received at least one dose of LY3022855IMC-CS4), only AEs 
and SAEs related to protocol procedures are required to be collected.

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LY3022855 (IMC-CS4)
8.1.2.4. Summary of AE/SAE Reporting Guidelines
The AE and SAE reporting guidelines are summarized in Table JSCB.4Table JSCB.3.
Table JSCB.43.
Adverse Event and Serious Adverse Reporting Guidelines for 
Study JSCB
8.2. Sample Collection and Testing
Attachment 4, Attachment 5, and Attachment 6 lists the detailed schedules for sample collections 
specifically for PK, pharmacodynamics, and immunogenicity in this study.
Attachment 7 provides a summary of the estimated maximum number and volume of invasive 
samples for all sampling during the study.
8.2.2. Samples for Drug Concentration Measurements 
Pharmacokinetics/Pharmacodynamics
Pharmacokinetic and pharmacodynamic samples will be collected as specified in the 
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule 
(Attachment 1).
8.2.2.1. Pharmacokinetic Samples
At the visits and times specified in the sampling schedule (Attachment 4, Attachment 5, and 
Attachment 6), venous blood samples of approximately 3 to 6 mL each will be collected to 
determine the serum concentrations of LY3022855IMC-CS4. If a patient remains on study until 
Cycle 3, additional samples will be drawn at that time.  Additional samples may be drawn at 
additional time points during the study, if warranted and agreed upon by the investigator, Lilly, 
and the patient.  Instructions for the collection and handling of blood samples will be provided 
by the sponsor.  The actual date and time of each sampling must be clearly and accurately 
recorded.
These samples will be analyzed at a laboratory designated by the sponsor.  Serum concentrations 
of LY3022855IMC-CS4 will be assayed using a validated ELISA method.
8.2.2.2. Pharmacodynamic Samples
The following pharmacodynamic assessments are based on the primary study objective and are, 
therefore, required assessments.  Samples will be tested for changes from baseline over time in 
peripheral blood immune cell subsets and in serum cytokines to document the 
immunomodulatory activity of LY3022855IMC-CS4 treatment in patients with advanced, 
refractory breast or prostate cancers.  Flow cytometric analysis using an antibody panel that may 
include, but not be limited to markers Live-Dead, CD3, CD4, CD8, CD14, CD16, FoxP3, PD-1, 
Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS will be used to evaluate T-cell and monocyte subsets 
from peripheral blood.  In addition, serum cytokine levels will be determined by MSD multiplex 
cytokine immunoassay technology or ELISA, and may include, but not be limited to CSF-1, 
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-34, and TNF-α.

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LY3022855(IMC-CS4)
Required samples for biomarker research to be collected from all patients in this study arethe 
following:
blood (for exploratory analysis of serum biomarkers that may be relevant to the 
mechanism of action of LY3022855IMC-CS4, 
 
tumor tissue (for exploratory analysis of the immunomodulatory effects of 
LY3022855IMC-CS4administration, including the understanding of the 
pharmacodynamic effects of LY3022855IMC-CS4)
8.2.3. Samples for Tailoring Biomarkers
In the event of an unexpected AE or the observation of unusual response, the pharmacogenetic 
biomarker samples may be genotyped and analysis may be performed to evaluate a genetic 
association with response to LY3022855IMC-CS4.  These investigations may be limited to a 
focused candidate gene study or, if appropriate, genome-wide analysis may be performed to 
identify regions of the genome associated with the variability observed in drug response.  The 
pharmacogenetic biomarker samples will only be used for investigations related to disease and 
drug or class of drugs under study in the context of this clinical program.  They will not be used 
for broad exploratory unspecified disease or population genetic analysis.
Refer to Section8.2.2.2, Pharmacodynamic Samples, for details of samples collected for other 
biomarker research that is part of this study.  These other samples may be used for research to 
develop methods, assays, prognostics and/or companion diagnostics related to CSF-1, CSF-1R,
and/or the mechanism of action of study drugs (LY3022855IMC-CS4).
8.2.4. Samples for Immunogenicity Research
Blood samples for immunogenicity testing will be collectedto determine antibody production 
against LY3022855IMC-CS4.  Immunogenicity will be assessed by a validated assay designed to 
detect ADAin the presence ofLY3022855IMC-CS4.  Antibodies may be further characterized 
and/or evaluated for their ability to neutralize the activity ofLY3022855IMC-CS4.
In addition to planned sampling for immunogenicity testing, ifat any time a patientexperiences 
an IRRto LY3022855IMC-CS4, all attempts will be made to obtain a bloodsample for 
immunogenicity analysis as close to the onset of the event as possible, at the resolution of the 
event, and 30 daysfollowing the event. A portion of the sample taken for immunogenicity 
testing may be used for PK analysis, in the setting ofIRRs.
Samples may be stored for a maximum of 15 years following last patient visit for the trial at a 
facility selected by the sponsor to enable further analysis of immune responses to 
LY3022855IMC-CS4.  The duration allows the sponsor to respond to regulatory requests related 
to LY3022855IMC-CS4.
CCI

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LY3022855 (IMC-CS4)
8.3. Efficacy Evaluation
Each patient’s full extent of disease will also be assessed as follows:

For patients with measurable disease defined by RECIST, tumor measurements 
are to be assessed by RECIST 1.1 (Eisenhauer et al. 2009; Attachment 
9Attachment 8) and irRECIST (Wolchok et al. 2009Nishino et al. 2013).
10. Data Analyses
For this study, approximately 4020 patients will be enrolled., eachPatients with prostate cancer
willto be treated at 1 of 2 dosages of LY3022855, and patients with breast cancer will be treated 
at 1 of 4 dosages of LY3022855IMC-CS4.  Of those enrolled patients, approximately 1636 
patients will be evaluable:  10 30 patients with advanced, refractory breast cancer and 6 patients 
with advanced, refractory prostate cancer.  Refer to Section 6.1 for the definition of an evaluable 
patient.
CSF-1 is the primary pharmacodynamic biomarker documented in Study JSCA.  Serum CSF-1 
was quantified for 17 patients over time; that is, at baseline and 8 hours after the first infusion.  
All those patients had increased levels of CSF-1 at 8 hours, compared with the baseline level.  
The effect size (or Cohen’s d) is 5.81.  Consequently, the power of observing any change 
between the eighth hour and baseline is close to 1 as long as the number of samples is ≥3.
On the other handHowever, when the effect size is as small as 1 for the other unknown
pharmacodynamic markers other than CSF-1, the power is approximately 0.159 if only 3 patients 
are sampled.
For Dosages C and D (patients with breast cancer), the sample size of 10 for each dosage 
provides a reasonable power to explore preliminary signals of efficacy.  Assuming that a true 
best overall response rate (ORR) less than 20% indicates inadequate antitumor activity, then at a 
one-sided type 1 error rate of 5%, the total sample size of 10 will provide 80% power if the true 
best ORR is 60% or higher, using a 2-stage design method as follows.  During the first stage, 5 
patients will be enrolled and treated on each of Dosages C and D.  If 2 or more of the 5 patients 
on either dosage (C or D) are observed to be responders by the end of the first stage, an 
additional 5 patients will be enrolled at the applicable dosage.  Then, if 5 or more of the total of 
10 patients at that dosage are observed to be responders by the end of the second stage, further 
exploration of drug efficacy is warranted for that dosage.
All data collected will be summarized using descriptive statistics or graphics, if appropriate, and 
will also be listed.  A detailed description of data analyses will be provided in separate statistical 
analysis plans for this study.
10.3. Patient Characteristics
Patient characteristics will include the following:

Patient demographics will be reported.

Baseline disease characteristics

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LY3022855 (IMC-CS4)
10.4. Safety Analyses
All patients who receive at least one dose of LY3022855IMC-CS4 will be evaluated for safety 
and toxicity.  Adverse event terms and severity grades will be assigned by the investigator using 
CTCAE v4.0.
10.5. Pharmacokinetic Analyses
Pharmacokinetic analyses will be conducted on patients who have received at least one dose of 
the study drug and have had samples collected, and PK serum concentrations of
LY3022855IMC-CS4 will be determined.
The parameters for analysis will include but not be limited to maximum concentration (Cmax) 
and trough concentration (Ctrough) of LY3022855IMC-CS4.  Additional analyses will be 
performed if warranted by data, and other validated PK software programs (for example, 
NONMEM) may be used if appropriate and approved by Global Pharmacokinetic management.  
The version of any software used for the analysis will be documented and the program will meet 
the Lilly requirements of software validation.
10.6. Pharmacodynamic Analyses
To study the impact of the study drug and the dose levels on the patients, the changes from 
baseline over time in peripheral blood immune cell subsets will be documented.  The
immunomodulatory activity of LY3022855IMC-CS4 will be documented by examining markers 
that include, but are not limited to: Live-Dead, CD3, CD4, CD8, CD14, CD16, FoxP3, PD-1, 
Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS.  The expression of those markers will be quantified 
by flow cytometric analysis with an antibody panel.
Biomarker measures of protein expression, based on flow cytometry, MSD, and ELISA, will be 
summarized by tumor type and/or dosage, based on enrolled patients.  Summary statistics may
include means, medians, corresponding standard errors, quartiles, and ranges.  Graphics, 
including profile plots of markers over time, will be generated to explore potential patterns 
between patients.  Correlation analyses between biomarkers and relative laboratory tests may be 
performed to further explore the activity of LY3022855IMC-CS4.
10.7. Pharmacokinetic/Pharmacodynamic Analyses
An exploratory correlative analysis of LY3022855IMC-CS4 PK and pharmacodynamics may be 
conducted.
10.8. Efficacy Analyses
Tumor response data will be reported using listings and descriptive statistics.  The ORR is 
estimated by the proportion of enrolled patients who have a best overall response of complete 
response (CR) or partial response (PR).  The disease control rate (DCR) is estimated by the 
proportion of enrolled patients who have a best overall response of CR, PR, or stable disease.  A 
95% exact confidence interval will be constructed to determine the level of precision of the ORR 
and DCR if appropriate.  Time-to-event variables such as progression-free survival (PFS), 

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LY3022855 (IMC-CS4)
duration of response, and overall survival (OS) will be tabulated if appropriate.  The Kaplan-
Meier method (Kaplan and Meier 1958) will be used to estimate the survival curves, medians, 
and survival rates at specified time points, if applicable.
10.9. Interim Analyses
Since this is a Phase 1 study, safety data will be analyzedreviewed on an ongoing basis.
For Dosages C and D (patients with breast cancer), interim analyses will be conducted in each 
dosage to review available safety, efficacy, PK, and pharmacodynamic data after 5 patients in 
that particular dosage have either completed approximately 3 cycles of therapy or discontinued 
from the treatment.  If 2 or more responders are observed, an additional 5 patients will be 
enrolled.  Further interim analysis may be considered if deemed appropriate by the sponsor.
If it is deemed that enough data are obtained to assess the primary objective and the secondary 
objectives, a clinical study report might be created before the last patient visit.  In this case, all 
data until the data cutoff date will be used for the analysis of safety, efficacy, PK, and 
pharmacodynamic biomarkers.  All data defined in the protocol will continue to be collected 
from patients on treatment after the data cutoff date.  These data may be reported separately, and 
the analyses on all patients including these data may not be performed.
12. References
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Amer Stat 
Assoc. 1958;53(282):457-481.
Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a 
common language for tumor response to immunotherapy: immune-related response criteria 
using unidimensional measurements. Clin Cancer Res. 2013;19(14):3936-3943.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Ggroup. Am J Clin Oncol. 
1982;5(6):649-655.
Radi ZA, Koza-Taylor PH, Bell RR, Obert LA, Runnels HA, Beebe JS, Lawton MP, Sadis S. 
Increased serum enzyme levels associated with kupffer cell reduction with no signs of hepatic 
or skeletal muscle injury. Am J Pathol. 2011;179(1):240-247.
Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, 
Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in 
solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-7420.

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LY3022855 (IMC-CS4)
Attachment 1. Protocol JSCB Study Schedules
Baseline and Cycle 1 Assessments (for All Dosing Schedules)
Procedure
Baseline
Treatment Cycle 1 only
Comments
Relative Day Prior 
to Day 1 of Cycle 1
≤28
≤14
≤7
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Eligibility Assessments
Informed consent
X
ICF must be signed prior to performance of any protocol-specific tests/procedures.
Medical history
X
β-hCG Pregnancy test
X
At baseline, a urine or serum pregnancy test is required for WOCBP.  Thereafter,
every 12 weeks after the first dose or according to local regulations, whichever is 
more frequent.
ECG
X
X
X
Note that in cases where ECG and blood sample collection are scheduled at the 
same time, all blood sampling should be performed prior to ECG assessment.
ECOG PS assessment
X
X
X
X
X
X
X
Safety Assessments
Physical examination
X
X
X
X
X
X
X
Includes height (at baseline only), and thoracic, abdominal, and symptom-directed 
examination.
Vital signs and weight 
measurement
X
X
X
X
X
X
X
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.  
Vital signs will be checked and recorded prior to each infusion of LY3022855IMC-
CS4, midway through each infusion, at the end of each infusion, and every 15 
minutes for the first hour following each infusion, including Cycle 1, Day 1 (also to 
be checked and recorded at nontreatment visits during Cycle 1).
Toxicity/AE assessment
X
X
X
X
X
X
X
Any preexisting toxicity should be documented, recorded, and graded (CTCAE v4.0 
grade) as a part of the baseline medical history.
AEs that are serious, considered related to study treatment or the study, or that 
caused the patient to discontinue before completing the study should be followed 
until the event is resolved, the event is no longer considered to be drug-related, the 
event becomes stable or returns to baseline, a new treatment is initiated for the 
patient, or the patient dies or is lost to follow-up.  Frequency of AE and SAE
follow-up evaluation is left to the discretion of the investigator.  Data on SAEs that 
occur before the end of the trial will be stored in the collection database and the 
Lilly Safety System.
Concomitant medication 
assessment
X
X
X
X
X
X
X
Including those medications taken within 28 days prior to the first dose of study 
therapy.

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LY3022855 (IMC-CS4)
Procedure
Baseline
Treatment Cycle 1 only
Comments
Relative Day Prior 
to Day 1 of Cycle 1
≤28
≤14
≤7
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Laboratory Tests
HIV and viral hepatitis B 
and C screening
X*
Includes HIV and hepatitis B and C, per institutional standards.
If done within 28 days prior to Cycle 1, Day 1 as part of standard of care, does not 
need to be repeated.
* Should be done within 60 days prior to enrollment.
Hematology
X
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
Coagulation
X
X*
Evaluations performed as part of the baseline assessment do not need to be repeated 
on Cycle 1, Day 1, unless required in the opinion of the investigator.
* Required within 14 days of planned posttreatment tumor biopsy.
Serum chemistry
X
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
CEA and CA 15-3
X
Applies only to breast cancer cohorts and if clinically applicable.
C-reactive protein
assessment
X
X
X
X
X
X
X
Every week for the first 12 weeks on therapy, and every 2 weeks thereafter.
Urinalysis
X
Evaluations performed as part of the baseline assessment do not need to be repeated 
on Cycle 1, Day 1, unless required in the opinion of the investigator.  Urinalysis 
evaluations will be performed at the beginning of each cycle (that is, approximately 
every 6 weeks following the first dose of study therapy).  If urine dipstick >1+ for 
protein, obtain 24-hour urine collection for protein analysis.
Serum and urine 
myoglobin
X*
X*
X*
X*
X*
X*
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Tailoring biomarkers
X
10 mL of blood to be drawn for future pharmacogenetic biomarker testing.
Blood sampling for PK, 
PD, IG
Refer to Attachment 4, Attachment 5, and Attachment 6.
All sampling indicated in Attachment 4, Attachment 5, and Attachment 6 is to be 
done only after study eligibility is met.
Efficacy Assessments
Imaging studies 
(CT/MRI)
X*
X
Radiographic assessment of tumor response should be performed prior to the start of 
a cycle so that results are available before the patient receives a new cycle of 
treatment.  If done within 28 days prior to Cycle 1, Day 1, as part of standard of 
care, does not need to be repeated prior to the start of Cycle 1.
* For patients with treated CNS metastases that are eligible for this study, a baseline 
MRI documenting disease stability within 60 days prior to enrollment is required.
Bone scan
X
X*
Breast cancer cohort:  A baseline bone scan is required, except in the event that a 
PET scan is performed within 28 days prior to the first dose of study therapy that is 
negative for bone disease.  Routine bone scans during treatment are not required, 
except in the setting of bone-only disease (no lymph node, visceral, skin, or 
subcutaneous metastases), or as deemed appropriate by the investigator.
*Prostate cancer cohort:  Bone scans are required at baseline and (follow-up 

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LY3022855 (IMC-CS4)
Procedure
Baseline
Treatment Cycle 1 only
Comments
Relative Day Prior 
to Day 1 of Cycle 1
≤28
≤14
≤7
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
[posttreatment]) every 6 weeks thereafter, or as clinically indicated.
If done within 28 days prior to Cycle 1, Day 1, as part of standard of care, does not 
need to be repeated prior to the start of Cycle 1.
Tumor assessments
X
X
Radiographic assessment of tumor response should be performed prior to the start of 
a cycle so that results are available before the patient receives a new cycle of 
treatment.
If done within 28 days prior to Cycle 1, Day 1, as part of standard of care, does not 
need to be repeated prior to the start of Cycle 1.
Tumor core needle or 
surgical biopsy
X
X {2 cells 
were merged 
in this 
amendment}
Required:  The first tumor biopsy will be taken (attempted) at baseline (predose), 
within 14 days prior to dosing on Cycle 1, Day 1, and the second tumor biopsy will 
be taken (attempted) within 14 days prior to dosing on Cycle 2, Day 1.
Optional:  In cases of disease progression, if the patient’s condition allows it, an 
optional tumor biopsy will be performed, as clinically indicated (refer to 
Section 8.2.2.2).
Ad hoc tumor tissue and 
blood sampling
X
Optional:  Additional tumor tissue and/or blood samples for biomarker research 
may be obtained at the investigator’s discretion in discussion with the patient, such 
as at the time of radiographic response or treatment progression.  If, at any time 
during the study, tumor tissue is obtained through a core biopsy, surgical biopsy, or 
resection as routine clinical care, the sponsor requests a tissue block or unstained 
slides for analysis of potentially relevant surrogate biomarkers.
Study Therapy Administration
Administer 
LY3022855IMC-CS4
Weekly (on Days 1, 8, 
15, 22, 29, and 36)
X
X
X
X
X
X
Administer 
LY3022855IMC-CS4
Every 2 Weeks (on Days 
1, 15, and 29)
X
X
X
Administer 
LY3022855IMC-CS4 on 
Weeks 1, 2, 4, and 5 (on 
Days 1, 8, 22, and 29)
X
X
X
X
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; CNS 
= central nervous system; CT = computed tomography; CTCAE v4.0 = Common Terminology Criteria for Adverse Events, version 4.0; ECG = electrocardiogram; ECOG PS= 
Eastern Cooperative Oncology Group performance status; HIV = human immunodeficiency virus; ICF = informed consent form; IG = immunogenicity; MRI = magnetic 

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
resonance imaging; PET = positron emission tomography; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse event; ULN = upper limit of normal; 
WOCBP = women of child-bearing potential.

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Cycle 2 Assessments (for All Dosing Schedules)
Procedure
Treatment Cycle 2 only
Comments
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated otherwise.
Safety Assessments
β-hCG Pregnancy test
Urine or serum pregnancy test is required for WOCBP every 12 weeks after the first dose or 
according to local regulations, whichever is more frequent.
ECG
X*
X*
Note that in cases where ECG and blood sample collection are scheduled at the same time, all blood 
sampling should be performed prior to ECG assessment.
* As clinically indicated, prior to last infusion of treatment cycle.
ECOG PS assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
Physical examination
X
Includes thoracic, abdominal, and symptom-directed examination.
Vital signs and weight 
measurement
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.  Vital signs will be 
checked and recorded prior to each infusion of LY3022855IMC-CS4, midway through each infusion, 
at the end of each infusion, and every 15 minutes for the first hour following each infusion.
Toxicity/AE assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
AEs that are serious, considered related to study treatment or the study, or that caused the patient to 
discontinue before completing the study should be followed until the event is resolved, the event is no 
longer considered to be drug-related, the event becomes stable or returns to baseline, a new treatment 
is initiated for the patient, or the patient dies or is lost to follow-up.  Frequency of AE and SAE 
follow-up evaluation is left to the discretion of the investigator.  Data on SAEs that occur before the 
end of the trial will be stored in the collection database and the Lilly Safety System.
Concomitant medication 
assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on Days 1, 8, 15, 
22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, and 5 (on Days 1, 8, 22, 
and 29).
Laboratory Tests
Hematology
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
Serum chemistry
X
X
X
X
X
X
Every week for the first 12 weeks on therapy.
CEA and CA 15-3
X
Applies only to breast cancer cohorts and if clinically applicable.
C-reactive protein
assessment
X
X
X
X
X
X
Every week for the first 12 weeks on therapy, and every 2 weeks thereafter.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Procedure
Treatment Cycle 2 only
Comments
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated otherwise.
Urinalysis
X
Urinalysis evaluations will be performed at the beginning of each cycle (that is, approximately every 
6 weeks following the first dose of study therapy). If urine dipstick >1+ for protein, obtain 24-hour 
urine collection for protein analysis.
Serum and urine myoglobin
X*
X*
X*
X*
X*
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Blood sampling for PK, PD, 
IG
Refer to Attachment 4, Attachment 5, and 
Attachment 6.
Efficacy Assessments
Imaging studies (CT/MRI)
X
Radiographic assessment of tumor response should be performed prior to the start of a cycle so that 
results are available before the patient receives a new cycle of treatment.
Bone scan
X*
Breast cancer cohort:  Routine bone scans during treatment are not required, except in the setting of 
bone-only disease (no lymph node, visceral, skin, or subcutaneous metastases), or as deemed 
appropriate by the investigator.
*Prostate cancer cohort:  Follow-up (posttreatment) bone scans are required every 6 weeks, or as 
clinically indicated.
Tumor assessments
X
Radiographic assessment of tumor response should be performed prior to the start of a cycle so that 
results are available before the patient receives a new cycle of treatment.
Ad hoc tumor tissue and 
blood sampling
X
Optional:  Additional tumor tissue and/or blood samples for biomarker research may be obtained at 
the investigator’s discretion in discussion with the patient, such as at the time of radiographic 
response or treatment progression.  If, at any time during the study, tumor tissue is obtained through a 
core biopsy, surgical biopsy, or resection as routine clinical care, the sponsor requests a tissue block 
or unstained slides for analysis of potentially relevant surrogate biomarkers.
Study Therapy Administration
Administer 
LY3022855IMC-CS4
Weekly (on Days 1, 8, 15, 
22, 29, and 36), 
X
X
X
X
X
X
Administer 
LY3022855IMC-CS4
Every 2 Weeks (on Days 1, 
15, and 29
X
X
X
Administer 
LY3022855IMC-CS4
Weeks 1, 2, 4, and 5 (on 
Days 1, 8, 22, and 29
X
X
X
X
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; CT = 
computed tomography; ECG = electrocardiogram; ECOG PS= Eastern Cooperative Oncology Group performance status; IG = immunogenicity; MRI = magnetic resonance 

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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imaging; PET = positron emission tomography; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse event; ULN = upper limit of normal; WOCBP = 
women of child-bearing potential.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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Cycle 3+ Assessments (for All Dosing Schedules)
Procedure
Treatment Cycle 3 and beyond
Comments
Day 1
Day 8
Day 15
Day 22
Day 29
Day 36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Safety Assessments
β-hCG Pregnancy test
X
Urine or serum pregnancy test is required for WOCBP 12 weeks after the first dose and 
every 12 weeks thereafter, or according to local regulations, whichever is more frequent.
ECG
X*
X*
Note that in cases where ECG and blood sample collection are scheduled at the same 
time, all blood sampling should be performed prior to ECG assessment.
* As clinically indicated, prior to last infusion of treatment cycle.
ECOG PS assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).
Physical examination
X
Includes thoracic, abdominal, and symptom-directed examination.
Vital signs and weight 
measurement
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.  Vital 
signs will be checked and recorded prior to each infusion of LY3022855IMC-CS4, 
midway through each infusion, at the end of each infusion, and every 15 minutes for the 
first hour following each infusion.
Toxicity/AE assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).
AEs that are serious, considered related to study treatment or the study, or that caused the 
patient to discontinue before completing the study should be followed until the event is 
resolved, the event is no longer considered to be drug-related, the event becomes stable 
or returns to baseline, a new treatment is initiated for the patient, or the patient dies or is 
lost to follow-up.  Frequency of AE and SAE follow-up evaluation is left to the 
discretion of the investigator.  Data on SAEs that occur before the end of the trial will be 
stored in the collection database and the Lilly Safety System.
Concomitant medication 
assessment
X
To be performed only on dosing days.  Dosing schedules, per protocol:  Weekly (on 
Days 1, 8, 15, 22, 29, and 36), Every 2 Weeks (on Days 1, 15, and 29), or Weeks 1, 2, 4, 
and 5 (on Days 1, 8, 22, and 29).

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Procedure
Treatment Cycle 3 and beyond
Comments
Day 1
Day 8
Day 15
Day 22
Day 29
Day 36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
Laboratory Tests
Hematology:
For Weekly and 
Every-2-Week 
schedules
X
X
X
Cycle 3 and beyond:  Every 2 weeks for patients receiving treatment on the Weekly or 
Every-2-Week dosing schedule (on Days 1, 15, and 29).
For Weeks 1, 2, 4, 
and 5 schedule
X
X
Cycle 3 and beyond:  Every 3 weeks for patients receiving treatment Weeks 1, 2, 4, and 5 
(on Weeks 1 and 4 [that is, Days 1 and 22]).
Serum chemistry:
For Weekly and 
Every-2-Week 
schedules
X
X
X
Cycle 3 and beyond:  Every 2 weeks for patients receiving treatment on the Weekly or 
Every-2-Week dosing schedule (on Days 1, 15, and 29).
For Weeks 1, 2, 4, 
and 5 schedule
X
X
Cycle 3 and beyond:  Every 3 weeks for patients receiving treatment Weeks 1, 2, 4, and 5 
(that is, on Weeks 1 and 4 [that is, Days 1 and 22]).
CEA and CA 15-3
X
Applies only to breast cancer cohorts and if clinically applicable.
C-reactive protein
assessment
X
X
X
Cycle 3 and beyond:  Every 2 weeks.
Urinalysis
X
Urinalysis evaluations will be performed at the beginning of each cycle (that is, 
approximately every 6 weeks following the first dose of study therapy). If urine dipstick 
>1+ for protein, obtain 24-hour urine collection for protein analysis.
Serum and urine 
myoglobin
X*
X*
X*
X*
X*
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Blood sampling for PK, 
PD, IG
Refer to Attachment 4, Attachment 5, and Attachment 6.
Efficacy Assessments
Imaging studies (CT/MRI)
X
Radiographic assessment of tumor response should be performed prior to the start of a 
cycle so that results are available before the patient receives a new cycle of treatment.
Bone scan
X*
Breast cancer cohort:  Routine bone scans during treatment are not required, except in 
the setting of bone-only disease (no lymph node, visceral, skin, or subcutaneous 
metastases), or as deemed appropriate by the investigator.
*Prostate cancer cohort:  Follow-up (posttreatment) bone scans are required every 6 
weeks, or as clinically indicated.
Tumor assessments
X
Radiographic assessment of tumor response should be performed prior to the start of a 
cycle so that results are available before the patient receives a new cycle of treatment.
Ad hoc tumor tissue and 
blood sampling
X
Optional:  Additional tumor tissue and/or blood samples for biomarker research may be 
obtained at the investigator’s discretion in discussion with the patient, such as at the time 
of radiographic response or treatment progression.  If, at any time during the study, 
tumor tissue is obtained through a core biopsy, surgical biopsy, or resection as routine 

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Procedure
Treatment Cycle 3 and beyond
Comments
Day 1
Day 8
Day 15
Day 22
Day 29
Day 36
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated 
otherwise.
clinical care, the sponsor requests a tissue block or unstained slides for analysis of 
potentially relevant surrogate biomarkers.
Study Therapy Administration
Administer 
LY3022855IMC-CS4
Weekly (on Days 1, 8, 15, 
22, 29, and 36)
X
X
X
X
X
X
For patients being treated on Dosage C and who are clinically benefitting, after the 
completion of Cycle 3, the dosing interval may be changed to once-every-2-week dosing 
after discussion with the sponsor.  If a patient’s dosage is changed from that of Dosage C 
(that is, weekly) to every-2-week dosing and then the patient develops progressive 
disease, the patient’s dosage may then be changed back to weekly dosing if agreed upon 
by the investigator and sponsor.
Administer 
LY3022855IMC-CS4 
Every 2 Weeks (on Days 
1, 15, and 29)
X
X
X
Administer 
LY3022855IMC-CS4 on 
Weeks 1, 2, 4, and 5 (on 
Days 1, 8, 22, and 29)
X
X
X
X
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; CT = 
computed tomography; ECG = electrocardiogram; ECOG PS= Eastern Cooperative Oncology Group performance status; IG = immunogenicity; MRI = magnetic resonance 
imaging; PET = positron emission tomography; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse event; ULN = upper limit of normal; WOCBP = 
women of child-bearing potential.

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Follow-up Assessments (for All Dosing Schedules)
Procedure
30-Day Follow-up
Comments
Except for the Cycle 1, Day 1 visit, allowable visit windows are ±3 days, unless indicated otherwise.
Safety Assessments
β-hCG Pregnancy test
X
Urine or serum pregnancy test is required for WOCBP.
ECG
X
In cases where ECG and blood sample collection are scheduled at the same time, all blood sampling should be 
performed prior to ECG assessment.
ECOG PS assessment
X
Physical examination
X
Includes thoracic, abdominal, and symptom-directed examination.
Vital signs and weight measurement
X
Vital signs include temperature, pulse rate, respiration rate, and blood pressure.
Toxicity/AE assessment
X
All SAEs and LY3022855IMC-CS4-related AEs will be followed until the event is resolved, stabilized, 
returned to baseline, deemed irreversible, or otherwise explained (frequency of follow-up evaluations is left to 
the discretion of the investigator).  Data on SAEs that occur before the end of the trial will be stored in the 
collection database and the Lilly Safety System.
Concomitant medication assessment
X
Laboratory Tests
Hematology
X
Serum chemistry
X
C-reactive protein assessment
X
Urinalysis
X
If urine dipstick > 1+ for protein, obtain 24-hour urine collection for protein analysis.
Serum and urine myoglobin
X*
*As clinically indicated, if serum CK ≥2.5 × ULN.
Blood sampling for PK, PD, IG
Refer to Attachment 4, 
Attachment 5, and 
Attachment 6.
Efficacy Assessments
Tumor core needle or surgical 
biopsy
X
Optional:  In cases of disease progression, if the patient’s condition allows it, an optional tumor biopsy will be 
performed, as clinically indicated (refer to Section 8.2.2.2).
Abbreviations:  β-hCG = beta human chorionic gonadotropin; AE = adverse event; CK = creatine kinase; CRP = clinical research physician; ECG = electrocardiogram; 
ECOG PS= Eastern Cooperative Oncology Group performance status; IG = immunogenicity; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAE = serious adverse 
event; ULN = upper limit of normal; WOCBP = women of child-bearing potential.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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Attachment 2. Protocol JSCB Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologya

Hemoglobin

Hematocrit

Platelets

Leukocytes (WBC), including differential

Neutrophils – absolute and percentage

Lymphocytes – absolute and percentage

Monocytes – absolute and percentage

Eosinophils – absolute and percentage

Basophils – absolute and percentage
Clinical Chemistrya (Serum Concentrations)

Sodium

Potassium

Chloride

Bicarbonate

Magnesium

Calcium

Phosphorus

Total bilirubin

Direct bilirubin

Alkaline phosphatase

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Gamma glutamyl transpeptidase

Albumin

Total protein

Creatinine

Blood urea nitrogen (BUN)

Uric acid

Glucose (random)

Lipase

Amylase

Creatine kinase (CK)
Coagulationa

Partial thromboplastin time (PTT)

Prothrombin time (PT)/INR
Urinalysisa

Specific gravity

pH

Protein

Glucose

Ketones

Blood

Leukocyte esterase
Serum or Urine Pregnancy Testa
Cardiaca

Troponin I or T
Serologiesa

HIV screening

Viral hepatitis B and C screening
Isoenzymesb

Lactate dehydrogenase (LDH)

Creatine kinase (CK)

Alkaline phosphatase
Serum Markers of Bone Metabolismb

CTX-I
Serum Markers of Inflammationa

C-reactive protein
Additional tests to be performed, as clinically 
indicated, at a routine follow-up visita

Serum myoglobin – if CK ≥2.5 × ULN

Urine myoglobin – if CK ≥2.5 × ULN
Serum Tumor Markers - as clinically indicateda

CEA

CA 15-3
Abbreviations:  CA 15-3 = cancer antigen 15-3; CEA = carcinoembryonic antigen; CK = creatine kinase; HIV = 
human immunodeficiency virus; PT/INR = International Normalized Ratio of prothrombin time; ULN = upper 
limit of normal; WBC = white blood cells.
a
Local or investigator-designated laboratory.
b
Assayed by Lilly-designated laboratory.

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Attachment 4. Protocol JSCB Pharmacokinetic, Pharmacodynamic, and Immunogenicity Sample Schedule for Dosages A 
and B Only
Note:  All sampling indicated in Attachment 4 is to be done only after study eligibility is met.
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Weekly Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day 1 
(C1D1)
C1D2
C1D3
Dosing 
Day
C1D8
Dosing 
Day
C1D15
Dosing 
Day
C1D22
Dosing 
Day
C1D29
Dosing 
Day
C1D36
Comments
(≤14 days 
of C1D1)
1 hr
(±6 
min)
EOI
4 hr
(±24 
min)
EOI
24 hr
(±2 hr
24 min)
EOI
48 hr
(±5 hr
45 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
X
The date and the time of all 
sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
X
PD #4=MSD assay for IFN-γ, 
IL-1β, IL-2, IL-4, IL-6, IL-8, 
IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
X
X
X
FC #2=Live-Dead, CD3, CD4, 
CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and 
ICOS
Isoenzymes - Central lab
X
X
X
X
X
X
X
AP isoenzymes, total CK, CK 
isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
X
X
CTX-I
Troponin I or T - MSKCC 
lab
X
X
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing 
Day
C2D1
Dosing Day
C3D1
C3D2
C3D3
Dosing 
Day
C3D8
Dosing 
Day
C3D22
Comments
Predose
(±25 hr)
Predose
(±25 hr)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
48 hr
(±5 hr
45 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
X
The date and the time of all sampling must be 
clearly and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, 
IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, 
Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
AP isoenzymes, total CK, CK isoenzymes, total 
LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±25 hr)
Pharmacokinetics
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855IMC-CS4, all attempts will be made to obtain a blood sample for immunogenicity analysis as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be 
used for PK analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Every-2-Week Dosing
Analyses
Prior to
the first 
infusion
Dosing Day
Cycle 1, Day1 (C1D1)
C1D2
C1D3
C1D4
C1D8
Comments
(≤14 days 
of C1D1)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
48 hr
(±5 hr
45 min)
EOI
72 hr
(±8 hr
64 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
X
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-
67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
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LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C1D15
Dosing Day
C1D29
C1D30
C1D31
C1D32
C1D36
Comments
Predose
(±50 hr)
Predose
(±50 hr)
24 hr
(±2 hr
24 min)
EOI
48 hr
(±5 hr
45 min)
EOI
72 hr
(±8 hr
64 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X*
X
X
X
PD #3=ALT, AST
* For this time point, a separate sample should not be 
collected for PD #3 assessment.  Use the serum 
chemistry sample (Attachment 1) taken at this time 
point for the PD #3 assessment.
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, 
Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 163
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C2D1
Dosing Day
C3D1
C3D2
C3D3
C3D8
Comments
Predose
Predose
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
48 hr
(±5 hr
45 min)
EOI 
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-
67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes
Troponin I or T - MSKCC 
lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 164
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C3D15
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±50 hr)
Predose
(±50 hr)
Pharmacokinetics
X
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, 
TNFα
Flow cytometry
FC #1 - Central lab
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, 
and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855IMC-CS4, all attempts will be made to obtain a blood sample for immunogenicity analysis as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be 
used for PK analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 165
LY3022855 (IMC-CS4)
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Weeks 1, 2, 4, and 5 Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day1 
(C1D1)
C1D2
C1D3
Dosing Day
C1D8
C1D15
Comments
(≤14 days 
of C1D1)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
48 hr
(± 5 hr
45 min)
EOI
Predose
(±25 hr)
1 hr
(±6 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
X
X
The date and the time of all sampling must be 
clearly and accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X*
PD #3=ALT, AST
* For this time point, a separate sample should 
not be collected for PD #3 assessment.  Use 
the serum chemistry sample (Attachment 1)
taken at this time point for the PD #3 
assessment.
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, 
IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, 
TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, 
PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and 
ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, 
total LDH, LDH isoenzymes
Bone marker - Central lab
X
X
CTX-I
Troponin I or T - MSKCC 
lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 166
LY3022855 (IMC-CS4)
Weeks 1, 2, 4, and 5 Schedule (continued)
Analyses
Dosing 
Day
C1D22
Dosing 
Day
C1D29
Dosing 
Day
C2D1
Dosing Day
C3D1
C3D3
Comments
Predose
(±50 hr)
Predose
(±25 hr)
Predose
(±50 hr)
Predose
(±50 hr)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
48 hr
(±5 hr
45 min)
EOI
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #4 - MSKCC lab
X
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, 
IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 167
LY3022855 (IMC-CS4)
Weeks 1, 2, 4, and 5 Schedule (continued)
Analyses
Dosing Day
C3D8
C3D15
Dosing Day
C3D22
Dosing Day
C5D1
Dosing Day
C5D29
Comments
Predose
(±25 hr)
1 hr
(±6 min)
EOI
168 hr
(±25 hr)
EOI
Predose
(±50 hr)
Predose
(±50 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X*
*To be done at this time point and every 12 weeks 
thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, 
IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, 
Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total 
LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 168
LY3022855 (IMC-CS4)
Weeks 1, 2, 4, and 5 Schedule (continued)
Analyses
Dosing Day
C6D29
30-Day Follow-up
(±7 days)
Comments
Predose
(±25 hr)
Pharmacokinetics
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and 
ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase; 
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855IMC-CS4, all attempts will be made to obtain a blood sample for immunogenicity analysis as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be 
used for PK analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 169
LY3022855 (IMC-CS4)
Attachment 5. Protocol JSCB Pharmacokinetic, Pharmacodynamic, and Immunogenicity Sampling Schedule for Dosage C 
Only
Note: All sampling indicated in Attachment 5 is to be done only after study eligibility is met.
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Weekly Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day 1 
(C1D1)
C1D2
Dosing 
Day
C1D8
Dosing 
Day
C1D15
Dosing 
Day
C1D22
Dosing 
Day
C1D29
Dosing 
Day
C1D36
Comments
(≤14 days 
of C1D1)
1 hr
(±6 
min)
EOI
4 hr
(±24 
min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
X
The date and the time of all 
sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
X
PD #1=CSF-1, IL-34
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
X
PD #4=MSD assay for IFN-γ, IL-
1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
X
X
X
FC #2=Live-Dead, CD3, CD4, 
CD8, FoxP3, PD-1, Ki-67, CTLA-
4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
X
X
X
AP isoenzymes, total CK, CK 
isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 170
LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing 
Day
C2D1
Dosing Day
C3D1
C3D2
Dosing 
Day
C3D8
Dosing 
Day
C3D22
Comments
Predose
(±25 hr)
Predose
(±25 hr)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
Predose
(±25 hr)
Predose
(±25 hr)
Pharmacokinetics
X
X
X
X
X
X
X
The date and the time of all sampling must be clearly 
and accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-
67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, 
LDH isoenzymes

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 171
LY3022855 (IMC-CS4)
Weekly Schedule (continued)
Analyses
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±25 hr)
Pharmacokinetics
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase;
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855IMC-CS4, all attempts will be made to obtain a blood sample for immunogenicity analysis as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be 
used for PK analysis, in the setting of infusion-related reactions.

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 172
LY3022855 (IMC-CS4)
Attachment 6. Protocol JSCB Pharmacokinetic, Pharmacodynamic, and Immunogenicity Sampling Schedule for Dosage D 
Only
Note:  All sampling indicated in Attachment 6 is to be done only after study eligibility is met.
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood Sampling Schedule for Every-2-Week Dosing
Analyses
Prior to 
the first 
infusion
Dosing Day
Cycle 1, Day1 (C1D1)
C1D2
C1D8
Comments
(≤14 days 
of C1D1)
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, 
IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-
4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 173
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C1D15
Dosing Day
C1D29
C1D30
C1D36
Comments
Predose
(±50 hr)
Predose
(±50 hr)
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X*
X
PD #3=ALT, AST
* For this time point, a separate sample should not be collected 
for PD #3 assessment.  Use the serum chemistry sample 
(Attachment 1) taken at this time point for the PD #3 assessment.
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-
10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 174
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C2D1
Dosing Day
C3D1
C3D2
C3D8
Comments
Predose
Predose
1 hr
(±6 min)
EOI
4 hr
(±24 min)
EOI
24 hr
(±2 hr
24 min)
EOI
168 hr
(±25 hr)
EOI
Pharmacokinetics
X
X
X
X
X
X
The date and the time of all sampling must be clearly and 
accurately recorded.
Immunogenicity
X
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
X
X
PD #1=CSF-1, IL-34
PD #2 - MSKCC lab
X
X
PD #2=CBC with differential
PD #3 - MSKCC lab
X
PD #3=ALT, AST
PD #4 - MSKCC lab
X
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, 
IL-10, IL-12p70, IL-13, TNFα
Flow cytometry
FC #1 - Central lab
X
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, 
CTLA-4, TIM-3, LAG-3, and ICOS
Isoenzymes - Central lab
X
X
X
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH 
isoenzymes
Troponin I or T - MSKCC lab
X

I5F-MC-JSCB(d) Phase 1 Oncology Protocol
Page 175
LY3022855 (IMC-CS4)
Every-2-Week Schedule (continued)
Analyses
Dosing Day
C3D15
Dosing Day
C5D1
30-Day Follow-up
(±7 days)
Comments
Predose
(±50 hr)
Predose
(±50 hr)
Pharmacokinetics
X
X
X
The date and the time of all sampling must be clearly and accurately recorded.
Immunogenicity
X*
X
*To be done at this time point and every 12 weeks thereafter, until last dose.
See Note at end of table.
Pharmacodynamics
PD #1 - Central lab
X
X
PD #1=CSF-1, IL-34
PD #4 - MSKCC lab
X
X
PD #4=MSD assay for IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, 
TNFα
Flow cytometry
FC #1 - Central lab
X
X
FC #1=CD14, CD16
FC #2 - MSKCC lab
X
X
FC #2=Live-Dead, CD3, CD4, CD8, FoxP3, PD-1, Ki-67, CTLA-4, TIM-3, LAG-3, 
and ICOS
Isoenzymes - Central lab
X
AP isoenzymes, total CK, CK isoenzymes, total LDH, LDH isoenzymes
Bone marker - Central lab
X
CTX-I
Troponin I or T - MSKCC 
lab
X*
*Only obtain for patients with cardiac symptoms.
Abbreviations:  ALT = alanine aminotransferase; AP = alkaline phosphatase; AST = aspartate aminotransferase; C = cycle; CBC = complete blood count; CK = creatine kinase; 
CSF-1 = colony-stimulating factor-1; D = day; EOI = post end of infusion; FC = flow cytometry; IFN = interferon; IL = interleukin; LDH = lactate dehydrogenase;
MSD = Meso Scale Discovery; MSKCC = Memorial Sloan Kettering Cancer Center; PD = pharmacodynamic(s); PK = pharmacokinetic(s); TNF = tumor necrosis factor.
Note:  If at any time a patient experiences an infusion-related reaction to LY3022855, all attempts will be made to obtain a blood sample for immunogenicity analysis as close to 
the onset of the event as possible, at the resolution of the event, and 30 days following the event.  A portion of the sample taken for immunogenicity testing may be used for PK 
analysis, in the setting of infusion-related reactions.

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Attachment 9. Protocol JSCB Sampling Summary
The following 3 tables summarize the maximum number of samples (venipunctures, tissue 
biopsies), volumes for all sampling, and tests (study qualification, health monitoring, 
pharmacodynamics, drug concentration, tailoring biomarkers, and immunogenicity) during the
study for each of the dosing schedules.  Estimates are provided; more samples could be required 
in the case of retests, additional health monitoring (if needed), or for patients continuing 
treatment beyond the protocol-specified number of cycles in the study.  Fewer samples may 
actually be taken (for example, patients who discontinue from the study).

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Protocol JSCB Sampling Summary - Weekly Dosing Schedule (includes samples for 
Cycle 1 [only] and 30-Day Follow-up)
Purpose
Sample 
Type
Maximum Amount 
per Sample
Maximum 
Number Samples
Maximum Total 
Amount
Study qualification, which 
includes the following:a
Blood
CBC
2 mL
1
2 mL
Chemistries
7.5 mL
1
7.5 mL
Coagulation
1.8 mL
1
1.8 mL
Health monitoring (may be more 
than 1 tube), which includes the 
following:b
Blood
CBC
2 mL
7
14 mL
Chemistries
7.5 mL
7
52.5 mL
Troponin
2 mL
4
8 mL
Coagulation
1.8 mL
1
1.8 mL
Pharmacodynamics
Tissue 
biopsy
Varies, 5-10 mm
Up to 12 cores
120 mm
Drug concentration (PK)
Blood
3 mL
9
27 mL
Tailoring biomarkers
Blood
10 mL
1
10 mL
Immunogenicity
Blood
10 mL
4
40 mL
Biomarkers, which includes the 
following:
Blood
Cytokine analysis
6 mL
11
66 mL
Flow cytometry
8 mL
12
96 mL
Bone markers of 
metabolism
3.5 mL
4
14 mL
Isoenzymes
5 mL + 3.5 mL
8 + 8
68 mL
AST/ALT – MSKCC 
lab
5 mL
1
5 mL
CBC – MSKCC lab
2 mL
3
6 mL
Total
[for each tissue sample type, 
rounded to nearest 10 mm]
Blood
Tissue
83
Up to 12 cores
422 mL
120 mm
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; 
MSKCC = Memorial Sloan Kettering Cancer Center; PK = pharmacokinetic(s).
a
Additional samples may be drawn if needed for safety purposes.
b
Based on laboratory safety values, unscheduled hepatic monitoring testing may be performed as part of patient 
follow-up, in consultation with the designated medical monitor.

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Protocol JSCB Sampling Summary – Every-2-Week Dosing Schedule (includes samples 
for Cycle 1 [only] and 30-Day Follow-up)
Purpose
Sample 
Type
Maximum Amount 
per Sample
Maximum 
Number Samples
Maximum Total 
Amount
Study qualification, which 
includes the following:a
Blood
CBC
2 mL
1
2 mL
Chemistries
7.5 mL
1
7.5 mL
Coagulation
1.8 mL
1
1.8 mL
Health Monitoring (may be 
more than 1 tube), which 
includes the following:b
Blood
CBC
2 mL
7
14 mL
Chemistries
7.5 mL
7
52.5 mL
Troponin
2 mL
3
6 mL
Coagulation
1.8 mL
1
1.8 mL
Pharmacodynamics
Tissue 
biopsy
Varies, 5-10 mm
Up to 12 cores
120 mm
Drug concentration (PK)
Blood
3 mL
14
42 mL
Tailoring biomarkers
Blood
10 mL
1
10 mL
Immunogenicity
10 mL
4
40 mL
Biomarkers, which includes the 
following:
Blood
Cytokine analysis
6 mL
12
72 mL
Flow cytometry
8 mL
13
104 mL
Bone markers of 
metabolism
3.5 mL
3
10.5 mL
Isoenzymes
5 mL + 3.5 mL
8 + 8
68 mL
AST/ALT – MSKCC 
lab
5 mL
7
35 mL
CBC – MSKCC lab
2 mL
8
16 mL
Total
[for each tissue sample type, 
rounded to nearest 10 mm]
Blood
Tissue
99
Up to 12 cores
482 mL
120 mm
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; 
MSKCC = Memorial Sloan Kettering Cancer Center; PK = pharmacokinetic(s).
a
Additional samples may be drawn if needed for safety purposes.
b
Based on laboratory safety values, unscheduled hepatic monitoring testing may be performed as part of patient 
follow-up, in consultation with the designated medical monitor.

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Protocol JSCB Sampling Summary - Weeks 1, 2, 4, and 5 Dosing Schedule (includes 
samples for Cycle 1 [only] and 30-Day Follow-up)
Purpose
Sample 
Type
Maximum Amount 
per Sample
Maximum 
Number Samples
Maximum Total 
Amount
Study qualification, which 
includes the following:a
Blood
CBC
2 mL
1
2 mL
Chemistries
7.5 mL
1
7.5 mL
Coagulation
1.8 mL
1
1.8 mL
Health Monitoring (may be 
more than 1 tube), which 
includes the following:b
Blood
CBC
2 mL
7
14 mL
Chemistries
7.5 mL
7
52.5 mL
Troponin
2 mL
3
6 mL
Coagulation
1.8 mL
1
1.8 mL
Pharmacodynamics
Tissue 
biopsy
Varies, 5-10 mm
Up to 12 cores
120 mm
Drug concentration (PK)
Blood
3 mL
11
33 mL
Tailoring biomarkers
Blood
10 mL
1
10 mL
Immunogenicity
10 mL
4
40 mL
Biomarkers, which includes the 
following:
Blood
Cytokine analysis
6 mL
12
72 mL
Flow cytometry
8 mL
12
96 mL
Bone markers of 
metabolism
3.5 mL
4
14 mL
Isoenzymes
3.5 mL + 5 mL
7 + 7
59.5 mL
CBC – MSKCC lab
2 mL
2
4 mL
Total
[for each tissue sample type, 
rounded to nearest 10 mm]
Blood
Tissue
81
Up to 12 cores
412 mL
120 mm
Abbreviations:  CBC = complete blood count; MSKCC = Memorial Sloan Kettering Cancer Center; PK = 
pharmacokinetic(s).
a
Additional samples may be drawn if needed for safety purposes.
b
Based on laboratory safety values, unscheduled hepatic monitoring testing may be performed as part of patient 
follow-up, in consultation with the designated medical monitor.

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Attachment 10. Protocol JSCB Guidelines for the Management of Immune-Related Adverse Events
Guidelines for the Management of Potential Toxicities Encountered with Immuno-Oncology Agents
System Organ Class
Adverse Event
CTCAE, Version 4.0 Grade (if 
applicable) and/or Symptomsa
Treatment Planb
Grade
Symptoms
Endocrine
Thyroid issues
Asymptomatic, with TSH 
<0.5 × LLN or >2 × ULN
Continue drug and include free T4 in subsequent cycles.
Symptomatic
Continue drug.  Administer thyroid replacement.
Hypotension, altered 
mental status, headache, 
fatigue
Endocrine issues aside from 
thyroid (for example, 
hypophysitis, diabetes 
mellitus)
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).
Resume drug when symptoms resolve and are stable on hormone 
replacement.  In case of adrenal crisis, administer stress-dose steroids.
Permanently discontinue for Grade 3 or 4.
Gastrointestinal
Diarrhea, abdominal pain, 
blood in stool
2
Withhold drug for 1 wk.  Administer antidiarrheal medication and check 
etiology.
Resume drug when symptoms resolve to Grade 1.  If >5 days’ duration 
despite antidiarrheals, begin steroids (0.5 mg/kg/d prednisone); can resume 
drug during taper when symptoms resolve to Grade 1.
Diarrhea, ileus, perforation
≥3
Withhold drug and administer 1-2 mg/kg/day prednisone (no steroids if 
possible perforation); discontinue drug if Grade 3 persists or Grade 4.
If >3 days despite steroids, add nonsteroid immunosuppressive.
Symptomatic pancreatitis
1 or 2
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Can 
resume drug during taper.
≥3
Permanently discontinue drug.  Administer steroids (1-2 mg/kg/d 
prednisone).  Can resume drug during taper.

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System Organ Class
Adverse Event
CTCAE, Version 4.0 Grade (if 
applicable) and/or Symptomsa
Treatment Planb
Grade
Symptoms
Hepatobiliary
Liver abnormality
AST or ALT >5 × ULN but 
≤20 × ULN
AND
total bilirubin ≤ULN
Discuss with sponsor and consider continuing protocol treatment provided 
patient remains without other evidence of liver toxicity.
AST or ALT >20 × ULN
AND
total bilirubin ≤ULN
Discuss with sponsor and consider holding protocol treatment until 
AST/ALT becomes ≤20 × ULN.
AST or ALT >5 × ULN
AND
total bilirubin >ULN
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Consider 
resuming protocol treatment once total bilirubin ≤ULN.
Discontinue protocol therapy permanently if bilirubin does not return to 
below the ULN within 3 wk of holding drug.
3 or 4
GGT or alkaline phosphatase
Continue protocol treatment provided patient remains without other 
evidence of liver toxicity.
Musculoskeletal
Muscle abnormality
CK >2.5 × but ≤10 ULN
AND
Serum and urine myoglobin 
≤ULN
Discuss with sponsor and consider continuing protocol treatment provided 
patient remains without other evidence of muscle or renal toxicity.
CK ≥2.5 × ULN
AND
Serum and urine myoglobin 
>ULN
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Consider 
resuming protocol treatment once serum and urine myoglobin ≤ULN.
Discontinue protocol therapy permanently if serum and urine myoglobin 
does not return to below the ULN within 3 wk of holding drug.

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System Organ Class
Adverse Event
CTCAE, Version 4.0 Grade (if 
applicable) and/or Symptomsa
Treatment Planb
Grade
Symptoms
Nervous
Weakness, paresthesia (for 
example, Guillain-Barré 
syndrome, myasthenia 
gravis)
No impact on activities of 
daily living (ADL)
Withhold drug.  Resume drug when symptoms resolve.
Impact on ADL
Withhold drug.  Administer appropriate medical intervention and steroids 
(1-2 mg/kg/d prednisone).  Can resume drug during taper and after 
discussion with ponsor.
Respiratory
Dyspnea, hypoxia, 
pneumonitis
1
Consider to withhold drug.  Resume drug when stable.
2
Mild to moderate symptoms
Withhold drug.  Administer steroids (1-2 mg/kg/d prednisone).  Can 
resume drug during taper.
≥3
Severe
Permanently discontinue drug.  Administer steroids (1-2 mg/kg/d 
prednisone).
If >2 days despite steroids, add nonsteroid immunosuppressive.
Renal and urinary
Elevated creatinine, 
decreased urine output, 
blood in urine, edema
1
<1.5 × baseline
Continue drug.
2 to 3
>1.5 × ULN but <6 × ULN
OR
>1.5 × baseline
Withhold drug.  Administer steroids (1- 2 mg/kg/d prednisone).If 
symptoms resolve to Grade ≤1, taper steroids over 1 month.  Can resume 
drug during taper.
If elevations persist >7 days or worsen treat with Grade 4 
recommendations.
4
>6 × ULN
Permanently discontinue drug.  Administer steroids (1-2 mg/kg/d 
prednisone).
Skin
Rash, pruritus
≤50% skin affected
Withhold drug. Start supportive medications for pruritus, for example, 
hydroxyzine/loratadine.  If symptoms persist or worsen after 1 wk, 
administer topical or systemic steroids. Resume drug if rash improves to 
mild (localized) and steroid dose <7.5 mg.
Stevens-Johnson syndrome, 
toxic epidermal necrolysis, 
necrosis, bullous or 
hemorrhagic lesions
Permanently discontinue drug.  Begin steroids (1-2 mg/kg/d prednisone).
Abbreviations:  ADL = activities of daily living; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria 
for Adverse Events; I.V. = intravenous(ly); LLN = lower limit of normal; TSH = thyroid-stimulating hormone; ULN = upper limit of normal.
a
If definition of grade not specified, use CTCAE, Version 4.0 definition.
b
Treatment plan should always include a thorough workup of the issue to rule out other potential etiologies.

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Note:  Other steroid options can be given at equivalent doses.  For severe cases, recommend using IV steroids.  For adrenal crisis, mineralocorticoid also needs to 
be added to stress-dose IV steroids.  Also, steroids should be tapered over 1 month once symptoms improve to grade 1, and drug should not be restarted 
until taper over at least 1 month complete.  During steroid use, add prophylactic antibiotics for opportunistic infections.  Immunosuppressive refers to 
infliximab or cyclophosphamide.

PPD
Leo Document ID = cd5adb38-4e12-4a02-8f9c-f35bbfa08c95
Approver:
Approval Date & Time: 09-Nov-2016 19:55:44 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 10-Nov-2016 15:51:11 GMT
Signature meaning: Approved
PPD