A Phase 1 Study of LY3009120 in Patients With Advanced or Metastatic Cancer
Phase: PHASE1
Conditions: Neoplasms, Neoplasm Metastasis, Melanoma, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms
Sponsor: Eli Lilly and Company

Protocol (d) I6X-MC-JBDA 
 
A Phase I Study of LY3009120 in Patients with Advanced or Metastatic Cancer 
 
NCT02014116 
 
Approval Date: 08-Jan-2016 
 

I6X-MC-JBDA(d)Phase 1 Oncology Protocol
Page 1
LY3009120
1. Protocol I6X-MC-JBDA(d)
A Phase 1 Study of LY3009120 in Patients with Advanced 
or Metastatic 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 
LY3009120, 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) Exemption4.
LY3009120
This Phase 1 study is a multicenter, nonrandomized, open-label, dose-escalation study 
followed by dose-confirmationof oral LY3009120in patients with advanced or metastatic 
cancer.
Approval Date: 08-Jan-2016 GMT
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol ElectronicallyS
igned and Approved by Lilly: 02 July 2013
Amendment (a) Electronically Signed and Approved by Lilly: 08 August 2013
Amendment (b) Electronically Signed and Approved by Lilly: 08 October 2013
Amendment (c) Electronically Signed and Approved by Lilly: 27 August 2015
Amendment (d) Electronically Signed and Approved by Lilly
on approval date provided below

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 2
LY3009120
2.
Synopsis
This Phase 1 study is a multicenter, nonrandomized, open-label, dose-escalation study followed
by dose-confirmation of oral LY3009120 in patients with advanced and/or metastatic cancer.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 3
LY3009120
3.
Table of Contents
A Phase 1 Study of LY3009120 in Patients with Advanced or 
Metastatic Cancer
Section
Page
1.
Protocol I6X-MC-JBDA(d) A Phase 1 Study of LY3009120 in 
Patients with Advanced or Metastatic Cancer......................................................................1
2.
Synopsis .............................................................................................................................2
3.
Table of Contents................................................................................................................3
4.
Abbreviations and Definitions.............................................................................................9
5.
Introduction ......................................................................................................................13
5.1.
Rationale and Justification for the Study ......................................................................13
5.2.
Objectives ....................................................................................................................14
5.2.1.
Primary Objective ................................................................................................14
5.2.2.
Secondary Objectives...........................................................................................14
5.2.3.
Exploratory Objectives.........................................................................................14
5.3.
General Introduction to LY3009120.............................................................................14
5.3.1.
Mechanism of Action and In Vitro/In Vivo Activity.............................................15
5.3.2.
Nonclinical Pharmacokinetics/Pharmacodynamics...............................................16
5.3.3.
Nonclinical Toxicology........................................................................................16
5.3.4.
Biomarkers...........................................................................................................19
5.3.4.1.
Pharmacodynamic Biomarkers in Part A.........................................................19
5.3.4.2.
Archived Sample Biomarkers for Stratification in Part B................................20
5.3.4.3.
Exploratory Analysis of Predictive Biomarkers...............................................20
5.4.
Rationale for Selection of Dose....................................................................................20
6.
Investigational Plan...........................................................................................................21
6.1.
Study Population..........................................................................................................21
6.1.1.
Inclusion Criteria .................................................................................................21
6.1.2.
Exclusion Criteria ................................................................................................23
6.2.
Summary of Study Design............................................................................................24
6.2.1.
Study Completion and End of Trial......................................................................26
6.3.
Discontinuations ..........................................................................................................26
6.3.1.
Discontinuation of Patients...................................................................................26
6.3.2.
Discontinuation of Study Sites .............................................................................27
6.3.3.
Discontinuation of the Study................................................................................27
7.
Treatment..........................................................................................................................28
7.1.
Materials and Supplies .................................................................................................28

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 4
LY3009120
7.2.
Study Drug Administration ..........................................................................................28
7.2.1.
Dosing Schedule ..................................................................................................28
7.2.2.
Dose Escalation Phase..........................................................................................29
7.2.2.1.
Dose-Limiting Toxicity Determination and Maximum 
Tolerated Dose Definition...............................................................................29
7.2.2.2.
Dose Escalation Method.................................................................................30
7.2.3.
Dose Confirmation Phase.....................................................................................31
7.2.4.
Dose Adjustments and Delays..............................................................................32
7.2.4.1.
Dose Adjustments within a Cycle ...................................................................32
7.2.4.2.
Dose Adjustment between Cycles...................................................................32
7.3.
Method of Assignment to Treatment ............................................................................33
7.4.
Blinding .......................................................................................................................33
7.5.
Concomitant Therapy...................................................................................................33
7.6.
Treatment Compliance .................................................................................................34
7.6.1.
Evaluable Patients................................................................................................34
8.
Safety, Pharmacokinetic, Pharmacodynamic, and Efficacy Data 
Collection .........................................................................................................................36
8.1.
Safety Evaluations........................................................................................................36
8.1.1.
Safety Data Collection and Review ......................................................................36
8.1.2.
Adverse Events ....................................................................................................36
8.1.2.1.
Serious Adverse Events ..................................................................................38
8.1.2.2.
Adverse Event and Serious Adverse Event Reporting .....................................38
8.1.2.2.1.
Prior to Administration of Study Drug(s) ..................................................38
8.1.2.2.2.
On Therapy...............................................................................................39
8.1.2.2.3.
Follow-Up Visit........................................................................................39
8.1.2.3.
Suspected Unexpected Serious Adverse Reactions..........................................39
8.1.2.4.
Summary of AE/SAE Reporting Guidelines ...................................................39
8.1.3.
Other Safety Measures .........................................................................................40
8.1.3.1.
Eye Safety Monitoring....................................................................................40
8.1.3.2.
Dermatological Safety Monitoring..................................................................40
8.1.3.3.
Electrocardiograms.........................................................................................41
8.1.4.
Safety Monitoring ................................................................................................42
8.1.5.
Complaint Handling.............................................................................................42
8.2.
Sample Collection and Testing.....................................................................................42
8.2.1.
Samples for Study Qualification and Health Monitoring.......................................42
8.2.2.
Samples for B-Raf Mutational Status Assessment ................................................43
8.2.3.
Samples for Drug Concentration Measurements...................................................43
8.2.3.1.
Pharmacokinetic Samples...............................................................................43

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 5
LY3009120
8.2.3.1.1.
Identification of LY3009120 Metabolites in Urine 
and Plasma................................................................................................44
8.2.4.
Pharmacodynamic and Tailoring Biomarker Tumor Samples ...............................44
8.2.4.1.
Tissue Collection for Pharmacodynamic Studies.............................................45
8.2.4.2.
Tissue Collection for Tailoring Biomarker Studies .........................................45
8.2.4.2.1.
Collection Procedures of Plasma Samples for 
Exploratory Biomarkers............................................................................46
8.2.5.
Pharmacogenetic Samples....................................................................................46
8.3.
Efficacy Evaluations ....................................................................................................46
8.4.
Procedure/Sampling Compliance..................................................................................47
9.
Data Management Methods...............................................................................................48
9.1.
Data Quality Assurance................................................................................................48
9.2.
Data Capture Systems ..................................................................................................48
9.2.1.
Case Report Form ................................................................................................48
9.2.2.
Ancillary Data......................................................................................................49
10.
Data Analyses ...................................................................................................................50
10.1. General Considerations ................................................................................................50
10.2. Patient Disposition .......................................................................................................50
10.3. Patient Characteristics ..................................................................................................50
10.4. Safety Analyses............................................................................................................50
10.5. Pharmacokinetic Analyses............................................................................................51
10.6. Pharmacodynamic Analyses.........................................................................................51
10.7. Pharmacokinetic/Pharmacodynamic Analyses..............................................................51
10.8. Efficacy........................................................................................................................52
10.9. Interim Analyses ..........................................................................................................52
11.
Informed Consent, Ethical Review, and Regulatory Considerations ..................................53
11.1. Informed Consent.........................................................................................................53
11.2. Ethical Review.............................................................................................................53
11.3. Regulatory Considerations ...........................................................................................53
11.3.1.
Investigator Information.......................................................................................54
11.3.2.
Protocol Signatures ..............................................................................................54
11.3.3.
Final Report Signature .........................................................................................54
12.
References ........................................................................................................................55

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 6
LY3009120
List of Tables
Table
Page
Table JBDA 5.1. Margin of Safety for Oral Administration of LY3009120 Based on 
Administered Dose and Predicted Exposure...................................................19
Table JBDA 7.1. Proposed Dose Escalation Scheme................................................................31
Table JBDA 8.1. Adverse Event and Serious Adverse Reporting Guidelines for Study 
JBDA ............................................................................................................40

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 7
LY3009120
List of Figures
Figure
Page
Figure JBDA 6.1.Study Design .................................................................................................25

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 8
LY3009120
List of Attachments
List of Protocol Attachments
Attachment
Page
Attachment 1.
Protocol JBDA Study Schedule .....................................................................58
Attachment 2.
Protocol JBDA Clinical Laboratory Tests ......................................................68
Attachment 3.
Protocol JBDA Hepatic Monitoring Tests for Treatment Emergent 
Abnormality ..................................................................................................69
Attachment 4.
Protocol JBDA Pharmacokinetic and Exploratory Blood Plasma 
Sampling Schedule ........................................................................................70
Attachment 5.
Protocol JBDA Recommendations for Reporting 
Serious Adverse Events .................................................................................72
Attachment 6.
Protocol JBDA ECOG Performance Status....................................................73
Attachment 7.
Protocol JBDA Creatinine Clearance Formula ...............................................74
Attachment 8.
Protocol JBDA Sampling Summary...............................................................75
Attachment 9.
Protocol JBDA RECIST Criteria 1.1..............................................................76
Attachment 10.
Protocol JBDA Toxicity Band Design ...........................................................83
Attachment 11.
Protocol JBDA Protocol Amendment I6X-MC-JBDA(d) Summary A 
Phase 1 Study of LY3009120 in Patients with Advanced or Metastatic 
Cancer ...........................................................................................................91

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 9
LY3009120
4.
Abbreviations and Definitions
Term
Definition
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
ANC
absolute neutrophil count
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
AUC(0-tlast)
area under the plasma concentration-time curve from time zero to last measurable 
plasma concentration
AUC(0-∞)
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).
Cmax
maximum plasma concentration
CL/F (or CL)
apparent systemic clearance
CNS
central nervous system
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.
CR
complete response

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 10
LY3009120
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.
CRC
colorectal cancer
CRM
continual reassessment method
CRP
clinical research physician
CRS
clinical research scientist
CSF
cerebrospinal fluid
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DLT
dose-limiting toxicity
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EDTA
ethylenediaminetetraacetic
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.
ERK
extracellular signal-regulated kinase
GCP
good clinical practice
G-CSF
granulocyte colony stimulating factors
GLP
good laboratory practices
HBSAg
hepatitis B surface antigen
HCAb
hepatitis C antibodies
HIV
human immunodeficiency virus
IB
Investigator’s Brochure

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 11
LY3009120
ICF
informed consent form
ICH
International Conference on Harmonisation
IND
Investigational New Drug
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.
interim analysis
An analysis of clinical study data that is conducted before the final reporting database is 
authorized for datalock.
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.
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.
monitor
A person responsible for ensuring the investigator site complies with the monitoring 
plan, applicable local SOPs (if any), and global Medical SOPs.  Monitors are trained on 
the investigational product(s), the protocol, informed consent document, 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
MTD
maximum tolerated dose
NCI
National Cancer Institute
NSCLC
non-small cell lung cancer
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.
patient
A subject with a defined disease.
PD
pharmacodynamic 
PDGFR
platelet-derived growth factor receptor
PK
Pharmacokinetic
PR
partial response
PSA
prostate-specific antigen

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 12
LY3009120
RECIST
Response Evaluation Criteria in Solid Tumors
re-screen
To screen a patient who was previously declared a screen failure for the same study
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, diagnostic 
psychological tests, 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.
study completion
This study will be considered complete (that is, the scientific evaluation will be 
complete [study completion]) after all patients have been discontinued from the 
treatment and have completed protocol defined follow-up period.
SUSAR
suspected unexpected serious adverse reactions
t1/2
half-life
tmax
time of maximal plasma concentration
TPO
third-party organization
ULN
upper limit of normal
US
United States
V/F (or V)
apparent volume of distribution

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 13
LY3009120
A Phase 1 Study of LY3009120 in Patients with Advanced or 
Metastatic Cancer
5.
Introduction
5.1.
Rationale and Justification for the Study
The Raf serine/threonine protein kinase family is comprised of three isoforms, A-Raf, B-Raf and 
C-Raf. They play a pivotal role in the mitogen-activated protein kinase (MAPK) pathway 
(Ras/Raf/MEK/ERK) in transducing extracellular signals to the nucleus (Madhunapantula and 
Robertson 2008; Beeram et al. 2005).  As part of the MAPK cascade, Raf protein kinases are 
involved in tumor cell proliferation, survival, invasion and angiogenesis (Friday and Adjei, 
2008).  B-Raf point mutations within the kinase domain of the protein occur in several human 
cancers, including melanoma and thyroid cancer, and to a lesser extent in colon cancer, ovarian 
cancer, and lung cancer (Flaherty and McArthur, 2010).  The majority of B-Raf mutations are 
substitutions of a single amino acid in the kinase domain (V600E) that results in significant 
increase in its kinase activity (Davies et al. 2002).  In melanoma, B-Raf mutations are found in 
40-50% of patients (Sullivan and Flaherty, 2013).  Therefore, B-Raf protein kinase is an 
attractive therapeutic target for improving outcomes of patients with these cancers.
Recently, two B-Raf specific kinase inhibitors, vemurafenib (also called PLX4032) and 
dabrafenib, were approved by the United States Food and Drug Administration (FDA) for 
treatment of melanoma patients with B-Raf V600E mutation. Trametinib, a Mek-kinase 
inhibitor, was also recently approved by the FDA for treatment of melanoma patients with B-Raf 
V600E and V600K mutations that have not received previous treatment with a B-Raf inhibitor.  
While vemurafenib has proven its effectiveness in this patient population, most patients 
eventually develop drug resistance which leads to disease relapse in an average of 7 months 
(Chapman et al. 2011). It is believed that the drug resistance could be due to reactivation of the 
MAPK pathway through Ras/Raf dependent mechanisms such as activating mutation in NRas or
MEK1 (Nazarian et al. 2010; Wagle et al. 2011), expression of truncated forms of B-Raf or
upregulation of C-Raf, or COT1 (Montagut et al. 2008, Corcoran et al. 2010; Johannessen et al. 
2010; Poulikakos et al. 2011). Moreover, the persistent expression of the receptor tyrosine 
kinases platelet-derived growth factor receptor- β (PDGFR-β) and IGF-1R conferred B-Raf
inhibitor resistance that may involve enhanced phosphatidylinositol 3-kinase (PI3K)/AKT 
pathway activation (Nazarian et al. 2010; Villanueva et al. 2010; Shi et al. 2011).  Therefore, 
similar to many other targeted therapies, the acquired resistance to B-Raf inhibition presents a 
significant therapeutic challenge for long-term survival benefit in this patient population.  
Additionally, vemurafenib is a B-Raf specific inhibitor, which promotes activation of 
extracellular signal-regulated kinase (ERK) phosphorylation, in B-Raf wild type cells.  
Therefore, vemurafenib is not indicated for patients with wild type B-Raf including patients with 
Ras mutations (Joseph et al. 2010).
LY3009120 is a pan-Raf kinase inhibitor with potent activities against A-, B-, and C-Raf 
isoforms and B-Raf V600E mutation, and induces minimal paradoxical MAPK pathway 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 14
LY3009120
activation due to pan Raf activities.  It possesses significant activity against several other 
receptor tyrosine kinases such as c-Kit and PDGFR-α and β. It is active against vemurafenib
resistant cells with different resistance mechanisms including NRas mutation, B-Raf splice 
variants, C-Raf elevation, and other MAPK reactivation mechanism. More importantly, 
LY3009120 is active against tumor cells with NRas or KRas mutation such as NRas mutant 
melanoma and acute myeloid leukemia (AML), and KRas mutant non-small cell lung cancer 
(NSCLC) and colorectal cancer (CRC).  In xenograft models, LY3009120 demonstrates 
inhibition of phospho-MEK and phospho-ERK, as well as tumor growth inhibition in melanoma 
or colon tumor models with B-Raf V600E mutation.  It also inhibits tumor growth in xenograft 
models with NRas or KRas mutations. This Phase 1 study (I6X-MC-JBDA [Study JBDA]) will 
evaluate the safety and tolerability of LY3009120 in patients with advanced cancer and will 
determine the dose and schedule for Phase 2 studies.
The sponsor, monitor, and investigators will perform this study in compliance with the protocol, 
good clinical practice (GCP) and International Conference on Harmonisation (ICH) guidelines, 
and applicable regulatory requirements.
5.2.
Objectives
5.2.1. Primary Objective
The primary objective of this study is to determine a recommended Phase 2 dose of LY3009120
that may be safely administered to patients with advanced and/or metastatic cancer.
5.2.2. Secondary Objectives
The secondary objectives of this study are:

to characterize the safety and toxicity profile of LY3009120.

to estimate the pharmacokinetic (PK) parameters of LY3009120.

to document any antitumor activity observed with LY3009120.
5.2.3. Exploratory Objectives

to explore pharmacodynamic (PD) biomarkers.

to explore biomarkers related to the safety and efficacy of LY3009120.
5.3.
General Introduction to LY3009120
More information about the known and expected benefits, risks and reasonably anticipated 
adverse events (AEs) may be found in the Investigator’s Brochure (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 serious adverse events (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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 15
LY3009120
5.3.1. Mechanism of Action and In Vitro/In Vivo Activity
Raf family of protein kinases are activated by Ras proteins in the signal transduction pathway or 
through raf mutations.  Mutated Raf protein, particularly B-Raf V600E, is found in many 
different cancers, with highest percent of this mutation reported in melanoma.  LY3009120 is a 
potent pan-Raf inhibitor with equal affinity in inhibiting A-, B-, and C-Raf, as well as B-Raf
V600E. Whole cell assay data show an IC50 of 44, 47 and 42 nM for A-, B- and C-Raf,
respectively. In an enzymatic assay, it inhibits wild type B-Raf, wild type C-Raf, and B-Raf 
V600E with IC50 values of 9.8, 15.47, and 5.77 nM, respectively.  In vitro, LY3009120 inhibits 
cellular phospho-ERK activity in melanoma A375 cells with B-Raf V600E mutation with IC50 
of 3 nM.  It also inhibits phospho-Mek and phospho-ERK activities in Ras mutant tumor cells 
with minimal paradoxical pathway activation.  It inhibits cell proliferation in vitro and tumor 
growth in vivo in a broad panel of tumor cells with different genetic background.

In melanoma B-Raf V600E mutant A375 cells, LY3009120 inhibits cell proliferation 
with IC50 of 9.2 nM in vitro, and exhibits significant tumor growth inhibition/regression 
at 5-15 mg/kg in vivo. LY3009120 is predicted to be active for melanoma patients with
the B-Raf V600E mutation.

In preclinical models, LY3009120 was demonstrated to be active against vemurafenib
resistant melanoma cells with MAPK reactivation. These resistant mechanisms include 
NRas mutation, B-Raf splice variants, C-Raf elevation, and FGFR3 activation.  
Therefore, LY3009120 may have activity in patients failing established B-Raf or MEK-
inhibitor treatment.

In preclinical models of NRas mutant melanoma, LY3009120 inhibits cell proliferation 
and induces tumor cell apoptosis, whereas vemurafenib is inactive. Similar activities are 
also observed for other NRas mutant tumor cells including AML cell lines, ie, HL-60 and 
THP-1cells. Therefore, LY3009120 may have activity in patients with NRas mutations.

In a panel of KRas mutant tumor cells including CRC, NSCLC, and pancreatic tumor 
cells, LY3009120 inhibits cell proliferation of many cell lines in vitro and tumor growth 
in vivo in multiple xenograft models.

In CRC tumor cells with B-Raf V600E mutation, LY3009120 is active with IC50 of 
7.3nM (HT-29) to 27 nM (Colo-205) in vitro, and inhibits tumor growth at 10-30 mg/kg 
in vivo.

In in vivo efficacy studies, LY3009120 demonstrated significant tumor growth inhibition 
and regression at 5-15 mg/kg twice daily dose schedule in melanoma A375 xenograft 
model. In multiple models with NRas or KRas mutation, LY3009120 showed significant 
tumor growth inhibition at 10-30 mg/kg twice daily dose schedule. In rat A375 xenograft 
PD model, LY3009120 demonstrated a dose and time-dependent inhibition of phospho-
ERK activities with absolute ED50 and ED80 of 4.36 and 16.37 mg/kg, and EC50 and 
EC80 of 68.9 and 365.5 ng/mL, respectively.  In mouse A375 PD model, LY3009120 
inhibited phospho-ERK with absolute ED50 and ED80 of 4.8 and 9.69 mg/kg, and EC50 
and EC80 of 127.9 and 428.1 ng/mL, respectively.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 16
LY3009120

Overall, these preclinical data support testing LY3009120 in unresectable/metastatic 
melanoma patients with B-Raf mutations, NRas mutations, and in advanced/metastatic 
non small cell lung cancer patients with KRas or B-Raf mutations.
5.3.2. Nonclinical Pharmacokinetics/Pharmacodynamics 
LY3009120 is a poorly soluble but highly permeable molecule with poor oral exposure when 
dosed in conventional suspension vehicles.  LY3009120 has improved oral bioavailability when 
formulated as a PVP-VA solid dispersion (rat, F = 55%; dog, F = 11% to 19%).  Metabolic 
profiling of rat and dog urine showed multiple oxidative metabolites.  These observations 
indicated that LY3009120 appeared to be cleared by oxidative metabolism.  LY3009120 was 
eliminated with a rapid intravenous T1/2 in rats (1.1 hr), dogs (1.8 and 2.1 hr), and monkeys 
(1.0 hr).  The plasma clearance after intravenous administration in rats and dogs was moderate 
and LY3009120 was well distributed into tissues; VD,SS = 1.08 L/kg (rat), 1.53 and 1.78 L/kg 
(dog) and 0.84 L/kg (monkey).
A PK/PD model was developed to relate plasma concentrations to the observed level of in vivo
pERK inhibition in a A375 xenograft model in the rat, with estimated maximal inhibition of 90% 
and IC50 of 63 ng/mL. A PK/PD model linking the pharmacokinetics of LY3009120 with tumor 
growth rate via pERK inhibition has also been developed. The results indicated that the 
minimum efficacious dose in rat could be as low as 1.8 mg/kg BID.
5.3.3. Nonclinical Toxicology 
The toxicity of LY3009120 was assessed after daily oral administration for one month in rats (0, 
10, 75, and 300 mg/kg) with one-month recovery groups (0 and 300 mg/kg) and similarly for 
one month in dogs (0, 10, 40, and 80 mg/kg) with one-month recovery groups (0, 40, and 
80 mg/kg).  Safety pharmacology parameters were evaluated in vitro and as part of the repeat 
dose study in dogs.  In dogs, the no-observed adverse-effect level (NOAEL) was 10 mg/kg and 
the highest non-severely toxic dose (HNSTD) was 40 mg/kg, due to preterminal euthanasia at 
80 mg/kg, and microscopic changes in lymphoid organs at ≥40 mg/kg/day.  Dogs administered 
80 mg/kg/day were euthanized early due to clinical signs including fecal changes (soft, watery, 
mucoid, and discolored), emesis, inappetence, decreased activity, and decreased food 
consumption and body weight.  Similar clinical signs were noted in some dogs at 40 mg/kg but 
were generally of reduced severity in comparison to the 80 mg/kg group.  In the one-month study 
in rats, no NOAEL was identified, and the HNSTD was 75 mg/kg due to loss of one toxicity 
animal at 300 mg/kg.  There were no clinical signs in rats associated with daily dosing.  
Common target organs in both species include the gastrointestinal tract, eyes, and lymphoid 
organs.  Additional target organs identified in the rat are liver, kidney, urinary bladder, thyroid, 
and ovary.
In dogs, important compound-related adverse effects were limited to lymphoid (decreased 
lymphocytes in lymphoid organs and decreased circulating lymphocytes at the high dose) and 
gastrointestinal inflammation with ulceration.  Clinical pathology changes (decreases in red cell 
mass, increases in neutrophils, monocytes, and platelets, and decreases in protein and electrolyte 
levels) correlated with reduced food consumption and inflammation in the GI tract.  Lymphoid 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 17
LY3009120
and gastrointestinal findings generally resolved or showed evidence of recovery in dogs taken 
through the one-month recovery period.
In rats, important LY3009120-related adverse findings at a low dose of 10 mg/kg/day included 
epithelial hyperplasia affecting the intestinal tract (males only), arterial degeneration and 
subacute portal inflammation in the liver (males only), degeneration/necrosis of tubules in the 
kidney in males, increased colloid in the thyroid in females, and lymphocyte necrosis in the 
thymus.  Additional adverse findings at the mid- and high-doses of 75 and 300 mg/kg/day 
included epithelial hyperplasia in the transitional epithelium of the kidney and urinary bladder, 
portal vein degeneration/proliferation, bile duct hypertrophy/hyperplasia, degeneration/necrosis 
of tubules in the kidney in males, decreased thickness of the physis in the femur, decreased 
acidophil granulation in the pituitary in males, increased colloid in the thyroid gland, corpus 
luteum cysts with hemorrhage and decreased corpora lutea and increased follicles in the ovary 
and effects secondary to the ovarian findings.  All clinical pathology changes reversed during the 
recovery period.  The only anatomic pathological change still present in the recovery group was 
minimal transitional cell hyperplasia in the bladder in one male.
Ocular effects were identified in both species in the nonclinical toxicology studies.  In rats, 
degeneration/atrophy of the outer retina occurred in all dose groups, including controls (2 control 
females in the main study and one recovery female).  There was an increased incidence (6/10) of 
retinal degeneration in female rats at the high dose (300 mg/kg).  This finding was considered 
consistent with an exacerbation of light-induced injury.  Among the animals in the recovery arm, 
only one animal demonstrated retinal degeneration, and this rat was in the control group.  
However, retinal degeneration is not considered reversible due to photoreceptor cell loss.
In LY3009120-treated dogs, ocular effects were identified in the clinical ophthalmology exam at 
the termination phase.  Subtle findings of irregular tapetal hyper-reflectivity, dullness, and 
occasional thin vasculature were observed in 4/5 of females at 40 mg/kg in ophthalmology 
exams just prior to terminal sacrifice.  In male dogs at 40 mg/kg, similar but more subtle changes 
were noted.  One affected female dog demonstrated a normal ophthalmology exam at the end of 
recovery period, indicating reversal of the changes.  There was no microscopic evidence of 
retinal degeneration/atrophy in dog eyes by routine histopathology, however, a more detailed 
histopathology assessment was pursued in an attempt to more fully characterize the test article-
related ophthalmic findings and evaluate the potential risk.
A focused histopathology assessment including morphometry was conducted on sections of eyes 
and optic nerves from terminal and recovery phase vehicle control and 40 mg/kg female dogs.  
Microscopic findings considered related to administration of LY3009120 were identified in two 
of three main study females given 40 mg/kg/day, were restricted to the tapetal portion of the 
retina, and included subtle findings related to vacuolation in the retinal pigmented epithelium 
(RPE) and minimal changes in the overlying outer segments.  These microscopic findings were 
not observed in the female recovery dogs given 40 mg/kg/day indicating they were likely 
reversible, consistent with the results of the clinical ophthalmoscopic examinations.  Based upon 
the indication of reversibility, the focal and minimal nature, and the lack of injury to the neuro-
retina, the microscopic findings were not considered adverse.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 18
LY3009120
In the dog study, decreases in blood pressure (6 to 34%) and increases in heart rate (16 to 83%) 
occurred at all doses on day 3 and at the terminal evaluation, with variable decreases in pulse 
pressure (6 to 18%) primarily observed on day 3.  At the terminal evaluation, changes in blood 
pressure and heart rate were decreased in magnitude, and these cardiovascular parameters 
returned to normal after the recovery period.  In an in vitro hERG (human ether á-go-go-related 
gene) assay, the half-maximal inhibitory concentration (IC50) was >10 M.  No physiologically 
significant changes in QTc were identified in vivo in dogs up to a concentration of 9.8 M 
(average Cmax in male and female dogs administered 80 mg/kg on day 1).  The concentration 
multiple between the IC50 in the hERG assay (>10 M) and cellular efficacy (5.8 nM, see 
Section 5.3.1) is greater than 1000-fold.  Thus the risk for QTc prolongation in humans is 
considered low.  There were no central nervous system or respiratory safety pharmacology 
findings.  An Ames test, an in vitro chromosomal aberration assay, and an in vivo micronucleus 
test in SD rats were all negative.  In addition, LY3009120 was a nonirritant in the Bovine 
Corneal Opacity and Permeability (BCOP) and dermal irritation tests.
In conclusion, nonclinical toxicology studies in rats and dogs dosed once daily for 1 month have 
characterized the target tissues for toxicity that may be clinically relevant.  The non-clinical 
safety findings described above are considered to be clinically monitorable through routine 
imaging and testing in the advanced cancer patient population.  Ophthalmological assessments 
are also incorporated during clinical testing, due to disparate ocular findings in both species as 
well as concern for potential target pathway-related ocular toxicity.  The planned clinical starting 
dose (50 mg BID/ 100 mg total) is approximately 7-fold lower than the rat HNSTD of 75 mg/kg 
and approximately 13-fold lower than the dog HNSTD of 40 mg/kg.  The predicted human area 
under the plasma drug concentration versus time curve (AUC) exposure at the starting dose of 
100 mg/day (2640 ng*hr/mL) is 16.9-fold and 4.7-fold lower than AUC at the HNSTD in rats 
and dogs, respectively.  Table JBDA 5.1. shows the dose and exposure multiples to the starting 
dose and highest anticipated clinical dose.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 19
LY3009120
Table JBDA 5.1.
Margin of Safety for Oral Administration of LY3009120 Based on 
Administered Dose and Predicted Exposure
Dose
(mg/kg/day)
Dose
(mg/m2/day)
Dose Multiplea
to starting dose
(to maximum dose)
AUC
(ng*hr/mL)
Exposure Multipleb
to starting dose
(to maximum dose)
Humanc
1.7 
61.7
2640
Humand
16.7
617
7560
Humane
23.3
863.3
7960
Rat STD10f
300
1800
29(2)
145538
55.1(18.3)
Rat HNSTDf
75
450
7.3(0.5)
44621
16.9(5.6)
Dog HNSTDg
40
800
13(0.9)
12500
4.7(1.6)
Abbreviations:  AUC = area under the plasma concentration x time curve; BID = twice daily; HNSTD = highest 
non-severely toxic dose; STD = severely toxic dose.
a
Dose multiple is the dose in animals/dose in humans based on mg/m2.
b
Exposure multiple is the calculated AUC in animals / predicted AUC in humans.  (See Table JBDA 7.1)
c
Proposed starting clinical dose.  Exposure is the median of the predicted AUC range at the starting dose.  As no 
accumulation is expected, AUC has been doubled to estimate daily exposure (BID dosing).
d
Predicted clinical efficacious dose.  Exposure is the median of the predicted AUC range at the efficacious dose.  
As no accumulation is expected, AUC has been doubled to estimate daily exposure (BID dosing).
e
Highest intended clinical dose.  Exposure is the median of the predicted AUC range at the highest intended dose 
and given that no accumulation is expected, AUC has been doubled to estimate daily exposure (BID dosing).
f
STD10 and HNSTD determined in a 1-month repeat-dose toxicity study (8271-636).  Exposure is the arithmetic 
mean of male and female exposure on Day 28 except for the exposure for the STD10 which is reported as the 
arithmetic mean of male and female exposure on Day 1 (female TK rats were euthanized on Day 9).
g
HNSTD determined in a 1-month repeat-dose toxicity study (130-284).  Exposure is the arithmetic mean of male 
and female exposure on Day 28.
5.3.4. Biomarkers
As part of an ongoing effort by Lilly to better understand how to predict which tumors are more 
likely to respond to LY3009120 treatment, the collection of samples for biomarker research is a 
mandatory part of this study. Additional details about sampling are summarized in 
Sections 8.2.4 and 8.2.5, Attachment 1, Attachment 4, and Attachment 8.
It is possible that biomarker data for patients in the study have already been generated from 
samples that were collected and analyzed before enrolling in this trial.  These may include data 
generated from genetic analyses.  If available, these data may be requested from medical records 
for use in the research described in Section 5.3.4.3.  
5.3.4.1.
Pharmacodynamic Biomarkers in Part A
In Part A, PD biomarkers will be used to assess target engagement for LY3009120 in tumor
tissue, and may include, but not be limited to, phospho-ERK, p27, and Ki67 protein expression 
in tumors.
Tumor tissue for PD evaluation will be collected via core needle or excisional biopsy 
pre-treatment (≤14 days pre-treatment) and after 4 weeks of treatment (C1 D28 ± 14 days) for 
patients added to any Part A cohort that will be expanded to determine MTD, and/or for patients 
added to any cohort expanded to explore a potential Phase 2 dose based on PK, safety, and 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 20
LY3009120
possibly early efficacy data.  Selection of patients for PD biopsies will be communicated to the 
sites by the sponsor.
5.3.4.2.
Archived Sample Biomarkers for Stratification in Part B
In Part B, patients will be stratified into cohorts based on existing local determination of 
molecular alterations, or lack thereof, in B-Raf, NRas, or KRas from archived tissue (see 
Section 6.1.1 for specific alterations).
5.3.4.3.
Exploratory Analysis of Predictive Biomarkers
Potential predictive biomarkers of efficacy to LY3009120 will be measured in archived tumor 
tissue, tumor tissue from core or excisional biopsies, and plasma.  Core or excisional biopsies for 
exploratory biomarker analysis will be performed on patients enrolled in all cohorts in Part B
(see Section 6.1.1 Inclusion Criterion [3]) before receiving the first dose of study drug, but this 
will not delay treatment.  Exploratory biomarker analysis may be performed on preexisting 
archival samples from patients in Part A and Part B.  The predictive biomarkers to be studied 
may include, but not limited to, somatic alterations in cancer-related genes such as B-Raf, NRas, 
KRas, and cKIT.  In plasma, analysis of biomarkers may include, but not limited to, potential 
nucleic acid predictive profiles to better understand the disease process and to develop predictive 
biomarkers.
5.4.
Rationale for Selection of Dose
A dose range from 100 to 1400 mg/day (50 mg BID to 700 mg BID orally) of LY3009120
administered is planned based on nonclinical toxicology and PK/PD modeling of nonclinical 
tumor growth and phospho-ERK (pERK) data.  Twice daily dosing is recommended due to the 
predicted human elimination half-life of 6 hours and to maintain maximum pERK inhibition, 
given the observed direct relationship of PK with pERK inhibition in preclinical species.
A daily dose of 100 mg is predicted to be safe in patients based on nonclinical toxicology data.  
The planned clinical starting human dose of 100 mg/day (equivalent to 61.7 mg/m2) is 7-fold and 
13.0-fold lower than the MTD/HNSTD dose level of 450 and 800 mg/m2 in rats and dogs, 
respectively. Table JBDA 5.1 shows dose multiples based on body surface area and exposure 
multiples based on predicted human AUC for the proposed clinical doses.
Tumor growth data from experiments with the A375 xenograft models in rats showed that
5 mg/kg BID dosing of LY3009120 was efficacious. The observed total drug exposure in 
plasma at this dose level was AUC0-12h = 2200 ng*h/mL, with a range of 1550 to 
3200 ng*h/mL. Due to interspecies differences of 1.6 fold in protein binding, the total AUC0-12h
in human will need to be 3520 (2480 to 5120) ng*h/mL to achieve the same unbound 
concentration in human as that observed in the rat efficacy model. Doses needed to achieve this 
in clinical conditions were predicted to be approximately 500 mg BID. At this dose, predicted 
peak pERK inhibition based on PK/PD modeling is predicted to be around 70%.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 21
LY3009120
6.
Investigational Plan
6.1.
Study Population
Individuals who do not meet the criteria for participation in this study (screen failure) may be re-
screened.  Individuals may be re-screened up to 1 time.  The interval between re-screenings 
should be at least 4 weeks (28 days).  Each time re-screening is performed, the individual must 
sign a new ICF and will be assigned a new identification number.
B-Raf mutational status should be documented for all patients enrolled in the study.  Results 
from previous testing or retesting of available archived tissue are acceptable.  Patients who do 
not have results from previous testing or adequate archived tissue available for B-Raf mutation 
retesting will have to undergo a biopsy prior to study drug administration (although results of 
B-Raf mutational status are not required before study drug administration).
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]
Part A:  Have histological or cytological diagnosis of cancer that is advanced 
and/or metastatic.  The patient must be, in the judgment of the investigator, an 
appropriate candidate for experimental therapy after available standard 
therapies have failed to provide clinical benefit for their disease or have a 
disease for which no proven effective therapy exists. 
Part B:  All patients must have histological or cytological evidence of cancer that is 
advanced and/or metastatic and have one of the alterations in the Ras/Raf pathway 
assessed by previous local somatic mutation testing (from archived tissue) listed 
below. Patients must have failed or be ineligible for available therapies for their 
disease, or have a disease for which no proven effective therapy exists.

Confirmation Cohort A: Advanced unresectable/metastatic melanoma carrying a 
B-Raf V600X (where X represents any amino acid) mutation that has relapsed 
after treatment with B-Raf inhibitors, MEK inhibitors, or the combination of B-
Raf/MEK inhibitors.

Confirmation Cohort B: Advanced unresectable/metastatic melanoma carrying a 
NRas mutation.

Confirmation Cohort C: Advanced unresectable/metastatic NSCLC carrying a 
KRas or B-Raf mutation.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 22
LY3009120
[2]
Part A:  Have the presence of measurable and/or nonmeasurable disease as 
defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
(Eisenhauer et al. 2009). Tumor lesions located in a previously irradiated area 
can be considered measurable only if they are new or if have shown 
unequivocal progression.
Part B:  Have the presence of measurable disease as defined by the Response 
Evaluation Criteria in Solid Tumors (RECIST 1.1) (Eisenhauer et al. 2009).
[3]
Part A and Part B:  Have a tumor that is safely amenable to core needle or 
excisional biopsies
[4]
Are 18 years of age.
[5]
Have given written informed consent prior to any study-specific procedures.
[6]
Have adequate organ function, including:

Hematologic:  Absolute neutrophil count (ANC) 1.5 x 109/L (without use 
of CSFs within the preceding 14 days), platelets 100 x 109/L (without 
platelet transfusion in the preceding 14 days), and hemoglobin 8 g/dL
(without transfusion in the preceding 14 days).

Hepatic:  Bilirubin 1.5 times upper limits of normal (ULN) (If the total 
bilirubin is >1.5 times ULN, and a subsequent direct bilirubin test is 
normal, the investigator and the Lilly Clinical Research Physician will 
determine patient eligibility.), alanine aminotransferase (ALT), and 
aspartate aminotransferase (AST) 2.5 times ULN.  If the liver has tumor 
involvement, AST and ALT equaling 5 times ULN are acceptable

Renal:  Serum creatinine 1.5 times ULN and calculated creatinine 
clearance ≥60 mL/min/1.73m2 (Creatinine Clearance Formula, Protocol 
Attachment 7)
[7]
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology 
Group (ECOG) scale (refer to Attachment 6).
[8]
Have discontinued all previous therapies for cancer (including chemotherapy, 
immunotherapy, corticosteroids, and radiotherapy) and recovered from the 
acute effects of therapy (treatment related toxicity resolved to Grade 1 or less) 
for at least 5 half-lives or a minimum of 4 weeks, (at least 42 days for 
mitomycin-C or nitrosoureas, 14 days for radiotherapy), prior to initiating 
study treatment.
At the discretion of the investigator, hormone-sensitive prostate cancer 
patients who are stable on gonadotropin-releasing hormone (GnRH) agonist 
therapy and breast cancer patients who are stable on anti-estrogen therapy (for 
example, an aromatase inhibitor) may have that treatment continued while 
they are enrolled in Study JBDA.
[9]
Are reliable and willing to make themselves available for the duration of the 
study and are willing to follow study procedures.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 23
LY3009120
[10] Males and females with reproductive potential must agree to use medically
approved contraceptive precautions during the trial and for 6 months
following the last dose of study drug.
[11]
Females with child bearing potential must have a negative serum pregnancy
test ≤3 days before the first dose of study drug.
[12] Have an estimated life expectancy, in the judgment of the investigator, of at 
least 12 weeks.
[13] Are able to swallow capsules.
6.1.2. Exclusion Criteria
Potential study patients may not be included in the study if any of the following apply during 
screening.
[14] Have received treatment within 5 half-lives or a minimum of 28 days of 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.
[15] Have serious preexisting medical conditions that in the opinion of the 
investigator would preclude participation in the study.
[16] Have active central nervous system (CNS) or leptomeningeal metastasis
(brain metastasis) at the time of study entry.  Patients with a history of a CNS
metastasis previously treated with curative intent (eg, stereotactic radiation or 
surgery) that have not progressed on follow-up imaging, have been 
asymptomatic for at least 28 days and are not receiving corticosteroids and 
or/anticonvulsants, are eligible.  Patients with signs or symptoms of 
neurological compromise should have appropriate radiographic imaging
performed before study entry to rule out brain metastasis.
[17] Have current hematologic malignancies.
[18] Have an active fungal, bacterial, and/or known viral infection including 
human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis 
(screening is not required).
[19] Part A: Have a second primary malignancy that in the judgment of the 
Investigator and of the sponsor may affect the interpretation of results.
Part B: Have a second primary malignancy treated within the previous 5 years

Exemptions will be permitted on a case-by-case basis after prior approval by the 
lead Lilly physician or designate, if in the judgment of the investigator the 
patient’s risk of recurrence and death is very low.

Exceptions: The following will be allowed

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 24
LY3009120
o
Adequately treated nonmelanoma skin cancer or in situ carcinoma of any 
origin regardless of the time of treatment
[20] Have QTcF (Fridericia corrected) interval of >470 msec on screening 
electrocardiogram (ECG).
[21] Have significant clinical/instrumental findings of:

Advanced dry age-related macular degeneration (AMD) or any wet-AMD.

Central or branch retinal artery or venous occlusion with significant vision loss

Moderate or worse non-proliferative diabetic retinopathy that is undergoing active 
treatment 

Active non-drug related uveitis, or evidence of any drug-related active ocular 
inflammation, including but not limited to, anterior chamber cell, vitreous cell, 
and active keratic precipitates

macular atrophy due to other cause or retinal thinning on Optical Coherence 
Tomography (OCT) examination.

Night vision impairment that is of recent onset (in the last year), sudden and 
progressive

Other retinal diseases that cause current visual impairment or would likely cause 
visual impairment over the time period of the study, as assessed by an 
ophthalmologist
6.2.
Summary of Study Design
Study JBDA is a multicenter, nonrandomized, open label, dose-escalation Phase 1 study of oral 
LY3009120 in patients with advanced or metastatic cancer.  Patients will receive LY3009120 
administered orally every 12 hours (BID) daily, in a 28-day cycle.  LY3009120 will be 
administered as a flat dose.  Study JBDA will consist of a dose-escalation phase in patients with 
advanced/metastatic cancer (Part A) followed by a dose-confirmation phase in advanced or 
metastatic melanoma carrying B-Raf or NRas mutations and NSCLC carrying KRas or B-Raf 
mutation (Part B).
The dose-escalation phase (Part A) (Figure JBDA 6.1), described in Section 7.2.2, will be guided
primarily by safety assessments from Days 1 through 28 of Cycle 1 for patients in all cohorts.  
Dose escalation will occur until the maximum tolerated dose (MTD, defined in Section 7.2.2.1)
is determined. Patients will be enrolled in cohorts starting with the first dose level at 50 mg BID; 
dose levels of LY3009120 ranging from 50 to 700 mg BID may be evaluated.  Table JBDA 7.1
outlines the proposed dose-escalation scheme. The maximum dose increase that will be allowed 
is 100%.  If the MTD has not yet been reached at the highest prespecified dose level, then 
additional dose levels may be investigated based on both safety and the available PK data. 
However, dose increments beyond 700 mg BID will never exceed a maximum increment of 
33%. Patients in all cohorts will not be enrolled in the next cohort until safety from the previous 
cohort has been assessed. In Part A, the sample size is estimated to be approximately 30 to 
35 patients depending on the relationship between exposure and toxicity as well as the 
relationship between exposure and pharmacodynamic effects.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 25
LY3009120
After the last patient on Part A has completed Cycle 1 and the recommended dose for the dose-
confirmation phase is determined, Part B will begin following an interim review of the data, as 
outlined in Section 10.9. The dose-confirmation phase will be opened in 3 cohorts of 
approximately 15 patients each, treated at a dose no greater than the MTD.
Cohort A:
Advanced unresectable/metastatic melanoma carrying a B-Raf V600X (where X represents any amino 
acid) mutation that has relapsed after treatment with B-Raf inhibitors, MEK inhibitors, or the 
combination of B-Raf/MEK inhibitors
Cohort B:
Advanced unresectable/metastatic melanoma carrying a NRas mutation
Cohort C:
Advanced unresectable/metastatic NSCLC carrying a KRas or B-Raf mutation
Figure JBDA 6.1.
Study Design
The total sample size for Parts A and B is estimated to be approximately 80 patients.  A total of 
approximately 45 patients has been selected in the dose-confirmation phase to ensure an 
adequate sample size for assessing the safety, PK, and preliminary efficacy signals.  The sample 
size of approximately 15 for each confirmation cohort provides a reasonable power to explore 
preliminary signals of efficacy.  If we assume that a true overall response (complete response 
[CR] + partial response [PR]) rate less than 10% indicates inadequate anti-tumor activity, then at 
a one-sided type 1 error rate of 5%, the sample size of 15 will provide 73% power if the true 
overall response rate is 30% or higher.
pERK will be investigated as one of the candidate biomarkers.  We are looking for 50% or 
higher pERK inhibition in treated patients.  If we assume less than 10% patients reach 50% or 
higher inhibition, then 100% biopsies in 15 patients will provide 73% power if more than 30% 
patients reach 50% or higher inhibition, at a one-sided type 1 error rate of 5%.
The planned duration of treatment is 2 cycles.  Patients may, however, remain on study for 
additional cycles if they are receiving clinical benefit (stable disease, partial response [PR], or 
complete response [CR]) until they fulfill one of the criteria for study discontinuation 
(Section 6.3).  Refer to Attachment 1 for the Study Schedule.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 26
LY3009120
6.2.1. Study Completion and End of Trial
This study will be considered complete (that is, the scientific evaluation will be complete) after 
all patients have been discontinued from the treatment and have completed protocol defined 
follow-up period.
“End of trial” refers to the date of the last visit or last scheduled procedure for the last patient.
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 and from the study 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.
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 occurs prior to introduction of the other agent

Patient Decision
o
the patient requests to be discontinued from the study

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 good clinical practice (GCP)

The patient has evidence of progressive disease.

The patient experiences unacceptable toxicity.

The patient is noncompliant with study procedures and/or treatment (Section 7.6).

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 27
LY3009120

The patient’s treatment is delayed for more than 14 days as the result of a drug-related
AE (refer to Section 7.2.4) upon discussion with Lilly CRP.
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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 28
LY3009120
7.
Treatment
7.1.
Materials and Supplies
LY3009120 will be supplied up to a maximum dose strength of 100 mg capsules for oral 
consumption.  LY3009120 capsules should be stored within the temperature range stated on the 
label.  Investigators should instruct patients to store the capsules at home in the original container 
and to keep out of the reach of children.  Capsules should not be opened, crushed, or dissolved.
Clinical study materials will be labeled according to the country’s regulatory requirements.
7.2.
Study Drug Administration
The investigator or designee is responsible for:

explaining the correct use of the investigational agent(s) and planned duration of each 
individual’s treatment to the patient and, if appropriate, to the patient’s designated legal 
representative,

verifying that instructions are followed properly,

maintaining accurate records of study drug dispensation, 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. Dosing Schedule
During both the dose-escalation phase (Part A) and the dose-confirmation phase (Part B)
LY3009120 will be administered orally BID daily in a 28-day cycle. In Part A only: on Cycle 1 
Day 1, the evening dose should be omitted to enable characterization of a full PK profile. The 
protocol may be amended to explore alternative schedules as a result of interim PK/PD data 
collection and analysis. During all cycles, study drug should be taken at approximately the same 
time.  Oral study drug will be taken at least 2 hours after and 2 hours before any food intake.
Patients should take study drug at least 2 hours after their last meal/snack and wait at least 
2 hours before eating again. Water consumption will be allowed at any time, while the same 
guidelines provided for food intake should be followed for any other liquid consumption.  Any 
deviations should be documented in the patient diary. If a patient misses or vomits a dose, that 
dose should be omitted.
During Cycle 1 and Cycle 2, patients will record the time of dosing and number of capsules 
taken in a diary. Clinic personnel will instruct patients to pay particularly close attention to 
record this information accurately on days of PK assessments (Attachment 4).
For Cycle 2 and beyond, a delay of ≤7 days in the start of a cycle (Dose 1) for justifiable reasons 
(for example, inclement weather, holidays, or weekends) other than toxicity will be permitted 
and does not constitute a protocol violation.  To allow for recovery from toxicity, a delay of 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 29
LY3009120
≤14 days in the start of a cycle (Dose 1) will be permitted for Cycle 2 and beyond and does not 
constitute a protocol violation.
7.2.2. Dose Escalation Phase
By nature of being a dose-escalation study, data will be evaluated on an ongoing basis until the 
maximum tolerated dose (MTD) is determined.
Safety data, in particular adverse events (AEs), will be the primary criteria for the dose 
escalation.  In addition, if available at the time of dose escalation decision, pharmacokinetics (eg,
Cmax, AUC, and CL) results will be used as secondary/supporting data for dose escalation.  No 
dose escalation can occur without prior discussion and agreement between the investigator and 
the Lilly study team; the decision will be documented in writing.
Based on the ongoing safety reviews, modifications to the dose escalation strategy or other 
design elements may be made via protocol amendment to ensure patient safety.
7.2.2.1.
Dose-Limiting Toxicity Determination and Maximum Tolerated Dose 
Definition
Dose-limiting toxicity (DLT) is defined as an adverse event (AE) during Cycle 1 for a patient 
enrolled in Part A that is possibly related to the study drug and fulfills any one of the following 
criterion using the National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) v4.0:

CTCAE Grade 3 non-hematological toxicity.  Exceptions will be made for:
o
Nausea, vomiting, diarrhea, or constipation that can be controlled with 
appropriate care. Grade 3 and Grade 4 nausea, vomiting, or diarrhea should be 
considered DLT if persisting more than 48 hours despite maximum supportive 
intervention.
o
Grade 3 elevations of ALT and/or AST lasting fewer than 8 days, without 
evidence of other hepatic injury, in the setting of preexisting hepatic metastasis 
and baseline elevation of these values, may not be considered a DLT if agreed by 
the study investigator and Lilly CRP.
o
Grade 3 rash that resolves or improves to a Grade 2 or less within 7 days and 
remains tolerable may not be considered a DLT if agreed by the study investigator 
and Lilly CRP/CRS.  

CTCAE Grade 4 hematological toxicity of >5 days duration.

Grade 4 thrombocytopenia of any duration

Grade 3 thrombocytopenia with bleeding

Grade 3 febrile neutropenia

Any other significant toxicity deemed by the primary investigator and Lilly clinical 
research personnel to be dose limiting (for example, any toxicity that is possibly related 
to the study medication that requires the withdrawal of the patient from the study during 
Cycle 1).

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 30
LY3009120
Investigators, together with the Lilly CRP, can declare a DLT if a patient is experiencing 
increasing toxicity during treatment, and it becomes clear that it is not going to be possible to 
complete the treatment without exposing the patient to excessive risk.
A DLT-equivalent toxicity is defined as an AE occurring between Day 1 and Day 28 of any 
cycle (other than Cycle 1) for a patient enrolled in Part A or in any cycle for a patient enrolled in 
Part B (including Cycle 1) that would have met the criteria for DLT if it had occurred during 
Cycle 1 for a patient enrolled in Part A.
For the purpose of this study, the MTD is defined as a safe dose that has the highest probability 
of DLT in the targeted toxicity interval (20 to 35%). A safe dose means that the probability of 
DLT larger than 35% is below 25%.
7.2.2.2.
Dose Escalation Method
Table JBDA 7.1. outlines the proposed dose-escalation scheme.  In this study, the escalation will 
start from the lowest planned dose, the maximum allowed dose increment is 100%, and each new 
dose level will have a minimum of 3 patients enrolled to it. The Bayesian model-based toxicity 
band method (Neuenschwander et al 2008) that incorporates prior expectations about the dose-
toxicity curve will be fitted to the data at the end of each cohort to recommend a dose for the 
next cohort. The toxicity band method is a Bayesian model-based design with built-in escalation 
with overdose control mechanism. After each cohort, the toxicity band model will utilize data 
from all available cohorts to make dose recommendation, based on the model based posterior 
probability of a DLT at each dose, and the overdose control criteria. The toxicity band method 
will stop if the pre-specified maximum number of subjects is reached or the recommended next 
dose has been taken by 9 patients.
During the escalation, the investigators and Lilly CRP will consider both the model 
recommendation and the observed DLT rate at each cohort to determine the next dose level and 
determine when to stop the escalation.  Dose levels for each cohort will not exceed those 
recommended by the toxicity band model.  Dose escalation will take into account PK and PD 
information when available. Additional patients may therefore be enrolled at a specific dose 
level to characterize PK/PD.
Intermediate or higher dose levels will be explored if deemed necessary after discussion between 
the sponsor and investigators. The JBDA toxicity band model has the ability to accommodate 
additional dose levels naturally.
Details regarding the JBDA toxicity band design are provided in Attachment 10.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 31
LY3009120
Table JBDA 7.1.
Proposed Dose Escalation Scheme
Dose 
level
LY3009120 
Dose (given 
BID) (mg)
Predicted Median 
AUC0-τ,ss 
(ng*h/mL)
Predicted 5th and 
95th percentiles 
AUC0-τ,ss (ng*h/mL)
Predicted 
Median 
Cmax,ss
(ng/mL)
Predicted 5th and 
95th percentiles 
Cmax,ss (ng*h/mL)
1
50
1320
571-2560
139
63-250
2
100
2250
989-4550
232
108-442
3
200
2620
1150-5050
272
125-499
4
300
2770
1220-5310
290
140-528
5
400
3230
1440-6250
339
160-618
6
500
3780
1670-7460
393
187-750
7
600
3840
1630-7690
407
182-773
8
700
3980
1770-7780
419
201-771
Abbreviation: AUC0-τ,ss = area under the plasma concentration versus time curve from time 0 to the end of the 
dosing interval (where τ=12h); Cmax,ss = maximum observed drug concentration during a dosing interval at 
steady state.
If, during dose escalation, a situation presents itself that is not described above, the investigator 
and Lilly CRP will determine the best method to select the appropriate dose for the patient(s) 
involved using all available information.  This decision will be documented in writing.  No dose 
escalations can occur without prior discussion and agreement between the site-specific 
investigator and the Lilly CRP.  Written notification will be sent to the site specifying the dose to 
be used for each patient at each dose level.
The first patient enrolled in Part A of the study (Cohort 1) must complete 28 days of dosing 
before enrolling subsequent patients at that dose level.  Once the first patient has completed 
28 days of dosing without significant toxicity, the second and third patients may be enrolled 
concurrently.  For cohort 2, the first patient must complete 15 days before enrolling subsequent 
patients.  For cohorts 3 and beyond patients may be enrolled concurrently.
7.2.3. Dose Confirmation Phase
Once the MTD has been defined, the dose-confirmation phase will be opened.  Enrollment will 
be expanded by approximately 45 additional evaluable patients with advanced
unresectable/metastatic melanoma and NSCLC.  The dose(s) to be studied in Part B will be 
defined at the end of dose escalation after a safety, PK, and PD review.  These dose(s) will not 
exceed the MTD.
If DLT-equivalent toxicities in the first cycle (that is, toxicities that would meet the DLT criteria 
in Section 7.2.2.1) occur in 33% or more of patients within this confirmation phase, then 
investigators and the Lilly CRP will assess the nature and severity of these toxicities.  No 
additional patients will be accrued until this safety review is completed and a decision is made 
either to continue at the current dose or to de-escalate the dose and define a new dose for the 
confirmation portion. If DLT-equivalent toxicity occurs in one third or more of patients during 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 32
LY3009120
Cycles 1 or 2 of Part B (with a minimum of 6 patients enrolled), the enrollment of new patients 
will cease until the Lilly CRP or CRS and study investigators assess the severity and nature of 
the toxicity.
The safety review and decision will be documented in writing.
7.2.4. Dose Adjustments and Delays
7.2.4.1.
Dose Adjustments within a Cycle
Part A: In the event that a patient experiences a DLT, DLT-equivalent or a Grade 3/4 toxicity 
that is not dose-limiting, treatment will be interrupted. Dosing can be resumed after resolution of 
the toxicity to baseline levels at the next lower dose level already deemed safe upon discussion 
with the Lilly CRP.
Part B: In the event that a patient experiences a DLT-equivalent toxicity that resolves with 
treatment interruption, at the investigator’s discretion and with the agreement of the Lilly 
physician or their designate, treatment may be resumed at a lower dose level than the one that 
was associated with the DLT event.
Part A and Part B: In the event that a patient experiences visual symptoms, or an abnormality is 
detected during in-treatment eye/vision assessment, treatment will be interrupted and appropriate 
therapeutic measures will be taken. After resolution of symptoms to baseline and/or 
normalization of eye tests, dosing can resume at the next lower dose level already deemed safe,
after discussion with the Lilly CRP.
7.2.4.2.
Dose Adjustment between Cycles
Before the start of each cycle, hematological toxicity except anemia must resolve to baseline and 
all nonhematological toxicities must resolve to CTCAE v4.0 Grade 0, 1, or baseline (except 
alopecia and fatigue).  The start of a cycle may be delayed up to 2 weeks to allow sufficient time 
for recovery.  Patients who do not recover from toxicity within 2 weeks should be discontinued.
If the patient has received granulocyte colony stimulating factors (G-CSFs) (see Section 7.5) 
and/or if the patient is in Cycle 3 or beyond and is continuing to receiving benefit from therapy, 
additional delays may be acceptable if agreed upon by both the investigator and sponsor.
The dose should be reduced to the previous dose level for the next cycle of therapy if a patient 
had at least 1 of the following events or if the investigator thinks it is in the best interest of the 
patient:

A DLT-equivalent toxicity (Part A patients in Cohort 2 and above; all patients enrolled in 
Part B)

Omission of more than 25% of doses in a single cycle due to toxicity (Part B only).
If a patient experiences a DLT-equivalent toxicity at the reduced dose, then he/she will be 
discontinued from treatment.  If the patient requires a dose reduction or omission in the absence 
of significant toxicity, then he/she may continue with treatment if the investigator determines 
that he/she is receiving benefit.  Re-escalation to the original dose is acceptable in the absence of 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 33
LY3009120
continuing toxicity, provided that this dose is not greater than the declared MTD.  If subsequent 
dose reduction is again required, the patient must be maintained at the reduced dose level for all 
remaining cycles.  If a patient in the first cohort experiences a DLT in the first cycle of treatment, 
he/she will be discontinued from the study.
7.3.
Method of Assignment to Treatment
Patients who meet all criteria for enrollment will be assigned to receive LY3009120 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, 
cohort, and identification number assignment for each patient.  No dose escalations (that is, to 
the next cohort) can occur without prior discussion and agreement with the responsible Lilly
CRP.
If investigators have eligible patients who have consented concurrently, up to 6 patients may be 
entered at a particular dose level provided that accrual has not ceased due to excessive toxicity.  
This enrollment procedure is allowed because of the advanced disease state of this patient 
population and the screening involved in defining eligibility.  This event should be approved by 
the sponsor following discussions with the investigators.
7.4.
Blinding
This is an open-label study.
7.5.
Concomitant Therapy
No other chemotherapy, radiotherapy, immunotherapy, cancer-related hormone therapy, or 
experimental drugs will be permitted while the patients are on this study. An exception will be 
made for prostate cancer patients continuing GnRH agonist therapy or breast cancer patients 
continuing antiestrogen therapy (for example, an aromatase inhibitor).  The need for any form of 
radiotherapy (including palliative) will be cause for early discontinuation from the study.  In 
addition, any disease progression requiring other forms of specific antitumor therapy will also 
necessitate early discontinuation from the study.  Appropriate documentation for all forms of 
premedications, supportive care, and concomitant medications must be captured on the case 
report form.
Patients should receive full supportive care with the exception that the routine use of G-CSF is 
not permitted during this study. Patients should not receive G-CSF prophylactically in any cycle.  
In Part A, no G-CSF use will be allowed in Cycle 1 unless hematological DLT is declared. In 
Cycle 2 and above and in Part B, patients may receive G-CSF or granulocyte-macrophage
colony-stimulating factor therapeutically for neutropenia or fever with neutropenia according to 
the most recent update of the American Society of Clinical Oncology (ASCO) guidelines for the 
use of white blood cell growth factors (Smith et al. 2006). During treatment with G-CSFs study 
drug administration will be discontinued.  G-CSFs must be discontinued at least 24 hours before 
resuming treatment with study drug treatment (pegylated colony-stimulating factors should be 
discontinued at least 14 days before resuming therapy with study drug).  If clinically indicated at 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 34
LY3009120
any time during the study, erythropoietin and packed red blood cell transfusions may be used 
according to ASCO guidelines (Rizzo et al. 2008).
Based on the available nonclinical data, there is a possible risk of clinical drug-drug interaction
when LY3009120 is administered with agents that are metabolized by CYP3A4. In the absence 
of more data to refine the risk of interaction, caution is warranted in the concomitant use of 
LY3009120 with CYP3A4 substrates with a narrow therapeutic margin (for example, alfentanil, 
cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and 
tacrolimus).
All concomitant medications should be recorded throughout the patient’s participation in the 
study.
7.6.
Treatment Compliance
Patient compliance with study drug will be assessed at each visit by direct questioning, patient’s 
diary examination and counting returned capsules.  Deviation(s) from the prescribed dosage 
regimen should be recorded on the case report form (CRF).
The patient must take 75% of the intended doses to be deemed compliant with study drug 
administration.  Similarly, a patient may be considered noncompliant if he or she is judged by the 
investigator to have intentionally or repeatedly taken more than the prescribed amount of 
medication.  Potential discontinuation of a patient due to study drug noncompliance will be 
discussed between the investigator and the Lilly CRP before making the final determination for 
discontinuation.
7.6.1. Evaluable Patients
Patients who withdraw from the study before receiving study drug 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 1 dose of study drug, regardless of whether they are deemed 
evaluable for the assessment of a dose level.
In Part A, patients who discontinue from the study before receiving at least 75% of planned 
doses of LY3009120 in Cycle 1 will be deemed non-evaluable for assessment of safety at that
dose level and may be replaced unless they experience a DLT or dose omission/reduction due to 
toxicity prior to withdrawal. 
Patients who receive at least 75% of the planned doses of LY3009120 but discontinue from 
study treatment before the end of Cycle 1 will be considered evaluable for the assessment of a 
dose level provided it can be documented whether the patient did or did not experience a DLT 
within 28 days of Day 1 in Cycle 1.
Part A: If the patient is noncompliant during Cycle 1 due to reasons other than drug-related 
toxicity he or she will be considered non-evaluable and may be replaced.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 35
LY3009120
Part B: If the patient is noncompliant during Cycle 1 or Cycle 2 due to reasons other than drug-
related toxicity or disease progression, he or she will be considered non-evaluable and may be 
replaced for the purpose of response assessment.
In Part A, nonevaluable patients may be replaced to ensure that no fewer than 3 patients receive 
at least 75% of planned doses of LY3009120 in Cycle 1 at each dose level, unless enrollment to 
that cohort has stopped due to DLT.
Patients who are not evaluable for pharmacokinetics, but who complete 1 cycle of therapy, may 
be replaced upon consultation with the investigator(s) and the Lilly CRP to ensure adequate PK 
data collection, unless enrollment to that cohort has stopped due to a DLT.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 36
LY3009120
8.
Safety, Pharmacokinetic, Pharmacodynamic, and 
Efficacy Data Collection
8.1.
Safety Evaluations
The safety and tolerability of LY3009120 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 plan that will permit initial characterization of the safety profile of LY3009120 
in patients.  Study procedures and their timing (including tolerance limits for timing) are 
described in the Study Schedule (Attachment 1).
Blood and urine samples will be collected at the times specified in the Study Schedule 
(Attachment 1).  Standard laboratory tests, including chemistry, hematology, ECGs, and 
urinalysis panels, will be performed.  A serum pregnancy test will be administered to females of 
child bearing potential.  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 adverse event and serious adverse event follow-up evaluation is left to 
the discretion of the investigator.
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 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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 37
LY3009120
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. Any minor version of CTCAE v 4.0 (for example 
version 4.0X) may be used for this study. Minor CTCAE v 4.0 updates from the NCI will not 
necessitate a protocol amendment.
CTCAE v4.0 will serve as the reference document for choosing appropriate terminology for, and 
grading the severity of, all AEs and other symptoms. 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 CRF.  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 (MedDRA) dictionary.
Cases of pregnancy that occur during maternal or paternal exposures to study drug should be 
reported.  Upon documentation of pregnancy, the patient must be removed from the study and 
treatment with study drug must be stopped immediately.  Data on fetal outcome and 
breastfeeding should be collected, if feasible, for regulatory reporting and drug safety evaluation.
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 designated data transmission methods, 
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 designated data transmission 
methods.
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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 38
LY3009120

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
Previously planned (prior to signing the ICF) surgeries and non-disease related elective surgeries 
planned during the course of study, should not be reported as SAEs unless the underlying 
medical condition has worsened or appeared during the course of the study.
Preplanned hospitalizations or procedures for 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.
Death due to disease progression should not be reported as an SAE unless the investigator deems 
it to be related to the use of study drug(s).
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.  Refer to Attachment 5
(Recommendations for Reporting Serious Adverse Events) for a list of recommended 
information to have available when contacting Lilly to report an SAE.  If alerts are issued via 
telephone, they 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.
8.1.2.2.
Adverse Event and Serious Adverse Event Reporting
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.  For patients who do not enroll 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 39
LY3009120
in the trial (that is, receive at least 1 dose of LY3009120), 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 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 
to when he/she receives the last dose of study drug.
8.1.2.2.3. Follow-Up Visit
All AEs and SAEs, regardless of relatedness to study drug or protocol procedures, occurring 
during the follow-up visit (Visit 801) must be reported to Lilly or its designee.  The follow-up 
visit starts following the last dose of study drug.  At the end of the follow-up visit, the patient 
will be required to have specific safety assessments (Attachment 1).  The timing of these safety 
assessments is 30 ± 3 days after the last dose of study drug.
Following the safety assessments, which mark the end of the first follow-up visit (Visit 801), a
long-term follow-up will begin for dermatological assessment.  Dermatological assessment will 
be performed every 2 months up to 6 months post-treatment discontinuation (long-term follow-
up Visits 802, 803, and 804), after which the patient will be discontinued from the study, unless 
there is an ongoing AE or SAE that is possibly related to study drug.  In this instance, the patient 
should be followed in subsequent follow-up visits, 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.  During the long-
term follow-up period (V802 to V804), ongoing or new AEs/SAEs possibly related to study 
drug(s) or protocol procedures are required to be reported.
After V804, if an additional follow-up period is necessary, new or ongoing AEs and new SAEs
are not required to be reported, unless the investigator feels the events were related to either 
study drug, drug delivery system, or a protocol procedure.
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 (DCSI) in the Investigator’s Brochure 
(IB) and that the investigator identifies as related to study drug or procedure.  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 JBDA 8.1.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 40
LY3009120
Table JBDA 8.1.
Adverse Event and Serious Adverse Reporting Guidelines for 
Study JBDA
Timing
Types of AEs/SAEs Reported 
Prestudy (baseline assessments)
(Starts at the signing of informed consent and ends 
just before the first dose of study drug)
Preexisting conditions
All AEs/SAEs regardless of relatedness
On therapy
(Starts at first dose of study drug(s) and ends at last 
dose of study drug(s))
All AEs/SAEs regardless of relatedness
Follow-up Visit (Visit 801)
(Starts just after the last dose of study drugs(s) and 
ends when end of study safety assessments are 
completed 30 ± 3 days after last dose of study drugs(s) 
OR the planned end of the cycle)
All AEs/SAEs regardless of relatedness
Long-term Follow-up Visits (Visits 802, 803, 804)
(Dermatological assessment every 2 months while on 
therapy and continuing up to 6 months after 
discontinuation of LY3009120)
Ongoing or new AEs/SAEs possibly related to study 
drug(s) or protocol procedures
Subsequent Follow-up visits, if necessary
Ongoing AEs possibly related to study drugs or protocol 
procedures
All SAEs related to protocol procedures or study drug
Abbreviations:  AEs = adverse events; SAEs = serious adverse events.
8.1.3. Other Safety Measures
8.1.3.1.
Eye Safety Monitoring
Ophthalmological assessments will be performed as specified in the Study Schedule (Attachment
1) and as clinically indicated.  Technical details and sequence of eye assessments will be defined 
in a study-specific Ophthalmology Manual provided to the sites.
Eye testing will include

Distance acuity (Visual acuity charts using refraction-based visual acuity measurement)

Ophthalmoscopy

Slit lamp exam

Retinal photography

OCT with Spectral Domain Optical Coherence Tomography (SD-OCT) scan of the 
macula

Fundus autofluorescence imaging
Imaging data and functional visual data from the screening visit will be provided from the local 
ophthalmologist to the Investigator.
8.1.3.2.
Dermatological Safety Monitoring
New primary cutaneous malignancies have been reported with B-Raf inhibitors.  Although 
LY3009120 is a pan-Raf inhibitor, which may mitigate some of the increased risk of cutaneous 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 41
LY3009120
malignancies hypothesized to be related to paradoxical Ras activation by B-Raf inhibition, 
dermatological evaluations will be performed as specified in the Study Schedule (Attachment 1) 
(at baseline, every 2 cycles while on therapy, and for up to 6 months following discontinuation of 
LY3009120).
8.1.3.3.
Electrocardiograms
For each patient, a 12-lead digital electrocardiogram (ECG) will be collected 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.
Consecutive replicate ECGs (usually triplicates) will be obtained at approximately 1-minute 
intervals.
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.
On Cycle 1 Day 1 and on Cycle 1 Day 15, a 3-hour post-dose ECG will be collected to coincide 
the ECG at the anticipated maximal plasma concentrations (Cmax) with the pharmacokinetic 
sampling in order to evaluate concentration-QT relationship for LY3009120.
On Cycle 1 Day 15 a baseline ECG will be collected to coincide the ECG at the anticipated 
steady-state plasma concentration (Css) with PK sampling in order to evaluate concentration-QT 
relationship for LY3009120.
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 1 of the replicate ECGs from each time point.
Digital ECGs will be electronically transmitted to a central ECG laboratory designated by Lilly.  
The central ECG laboratory will perform a basic quality control check (for example, 
demographics and study details) then store the ECGs in a database.  At a future time, the stored 
ECG data may be overread at the central ECG laboratory for further evaluation of machine-read 
measurements or to meet regulatory requirements.
The machine-read ECG intervals and heart rate may be used for data analysis and report writing 
purposes unless an overread of the ECGs is conducted prior to completion of the final study 
report (in which case the overread data would be used).

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 42
LY3009120
8.1.4. Safety Monitoring
The Lilly CRP or CRS will monitor safety data throughout the course of the study.
Lilly will review SAEs within time frames mandated by standard operating procedures, and will 
review trends, laboratory analytes, and AEs at periodic intervals.
If a study patient experiences elevated ALT ≥5X upper limit of normal (ULN) and elevated total 
bilirubin ≥2X ULN, clinical and laboratory monitoring should be initiated by the investigator.
For patients entering the study with ALT ≥3X ULN, monitoring should be triggered at ALT ≥2X 
baseline.
Details for hepatic monitoring depend upon the severity and persistence of observed laboratory 
test abnormalities.  To ensure patient safety and comply with regulatory guidance, the 
investigator is to consult with the Lilly CRP 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/drug delivery systems are reported directly to the 
manufacturers of those drugs/devices in accordance with the package insert.
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 adverse 
events 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 tests that will be performed for this study.
Attachment 4 lists the schedule for PK and PD sample collections in this study.
Attachment 8 provides a summary of the estimated maximum number and volume of invasive 
samples, for all sampling, during the study.
8.2.1. Samples for Study Qualification and Health Monitoring
Blood and urine samples will be collected at the times specified in the study schedule 
(Attachment 1).

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 43
LY3009120
Standard laboratory tests, including hematology and urinalysis panels, will be performed and
analyzed by a local laboratory. Chemistry panels will be performed and analyzed centrally.  
Enrollment or dose adjustment decisions may be based upon chemistry results performed at a
local laboratory; however, a sample must be sent to the central lab. These central chemistry
laboratory results will be used for subsequent safety analyses. In the event of minor
discrepancies between local and central laboratory results, the investigator may use the local
results for treatment decisions, and the central laboratory results will remain part of the safety
database. Discrepancies between local and central results that may have an impact on treatment
decisions will not be considered protocol violations. A serum pregnancy test, for females with 
child-bearing potential, will be performed locally.
Investigators must document their review of each laboratory safety report.
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.
8.2.2. Samples for B-Raf Mutational Status Assessment
Information on the B-Raf mutational status will be collected for all patients enrolled in the study.
Historical test results: Results from historical tests will be acceptable.
Archived tissue: For patients who do not have historical B-Raf test results available, genetic 
analysis will be performed on any available adequate archived specimen of the patient’s tumor.
Study tumor biopsies: Patients who do not have historical B-Raf testing results or adequate 
archival tumor tissue will undergo a pre-treatment tumor biopsy before receiving the first dose of 
study drug. Tumor tissue biopsies will be taken either by core needle or excisional biopsy.  The 
size of the sample will be dependent upon the procedure utilized to obtain the sample.  Patients 
will be able to receive treatment before the results of the biopsy are available.
8.2.3. Samples for Drug Concentration Measurements
8.2.3.1.
Pharmacokinetic Samples
Pharmacokinetic samples will be collected as specified in the Pharmacokinetic and 
Pharmacodynamic Sampling Schedule (Protocol Attachment 4).
Blood samples of approximately 3 mL will be drawn into EDTA tubes for measurement of 
LY3009120.  A maximum of 5 additional PK samples per patient (15 mL) may be drawn during 
the study if warranted and agreed upon by both the investigator and sponsor.  Instructions and 
supplies for the collection, handling, and shipping of blood or tissue samples will be provided by 
either the sponsor or the central laboratory.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 44
LY3009120
The actual dose and timing (24-hour clock time) of each dose and sampling will be recorded as 
well as the time of the nearest meal associated to the dose received.
These samples will be analyzed at a laboratory designated by the sponsor.  Plasma 
concentrations of LY3009120 will be assayed using a validated LCMS method.
All bioanalytical samples will be stored in the United States.
The remaining plasma from the samples collected for PK may be pooled and used for 
exploratory metabolism work as deemed appropriate.
In Part B, urine samples may be collected for the first 10 hours after dose administration from up 
to 3 patients for exploratory metabolism work as deemed appropriate.  Measure and record total 
urine volumes collected.  Aliquots of the urine (approximately 10 mL) will be frozen and stored 
until qualitatively analyzed for LY3009120 and other potential metabolites.  Because the urinary 
work is considered exploratory, failure to obtain a urine sample for any reason will not be 
considered a protocol violation.
Bioanalytical samples collected to measure study-drug concentration and metabolism, and/or 
protein binding will be retained for a maximum of 2 years following last patient visit for the 
study.
8.2.3.1.1. Identification of LY3009120 Metabolites in Urine and Plasma
While every effort should be made to collect all urine samples for exploratory work, failure to 
obtain a sample for any reason will not be considered a protocol violation.  Urine will be used for 
exploratory metabolite identification and quantification of parent concentrations.  Total urine 
output for approximately 10 hours post-dose of LY3009120 will be recorded, pooled and 
refrigerated.  The total urine volume will be recorded, and samples of approximately 10 mL will 
be stored frozen.  The remaining urine will be discarded. Supplies required for the collection and 
shipment of the patients’ stored samples will be supplied by the sponsor.  Sample handling and 
shipment to the central laboratory will occur per instructions given to the study site.  All urine 
samples will be stored in the United States and will be retained for a maximum of 2 years 
following the last patient visit for the study.  Some PK plasma samples may be used to identify 
the structures of LY3009120 metabolites to determine the concentrations of those metabolites at 
the discretion of the sponsor.  Plasma and urine samples will be analyzed at laboratories 
designated by the sponsor.  LY3009120 metabolite identification and quantification will be 
conducted by bioanalytical techniques deemed appropriate by the sponsor.
8.2.4. Pharmacodynamic and Tailoring Biomarker Tumor Samples
Pharmacodynamic and tailoring biomarker tumor samples will be collected as specified in the 
Study Schedule (Attachment 1) and PK, PD and Pharmacokinetic and Exploratory Blood Plasma 
Sampling Schedule (Attachment 4). Either blocks or precut, unstained slides from any available 
archival diagnostic specimen of the patient’s tumor will be collected for biomarker-related 
studies.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 45
LY3009120
8.2.4.1.
Tissue Collection for Pharmacodynamic Studies
Part A: Mandatory tumor biopsies should be collected prior to treatment (following 
determination of eligibility [≤14 days of C1 D1]) and after 4 weeks of treatment (C1 D28 ±
14 days) for patients added to any cohort that will be expanded to determine MTD and/or for 
patients added to any cohort expanded to explore potential for Phase 2 dosing on the basis of PK 
data.  Biopsy samples taken within 6 months prior to enrollment will also be permitted as long as 
patients have not received any recent therapies for the disease prior to starting LY3009120. 
Sponsor will need to review and approve the timing of in-treatment biopsies performed outside 
of the allowed 14-day window.
Part B: Mandatory tumor biopsies should be collected before treatment (following 
determination of eligibility [≤14 days of C1 D1]) and after 2 weeks of treatment (C1 D15 ± 
5 days). Biopsy samples taken within 6 months before enrollment will also be permitted as long 
as patients have not received any recent therapies for the disease prior to starting LY3009120.  
Tumor tissue biopsies taken either by core needle or excisional biopsy are acceptable provided 
adequate slides can be obtained. Cytologic samples and fine-needle aspiration specimens are not 
acceptable. Pathology notes accompanying the archived diagnostic tissue may also be requested.
Details for the handling and shipping of tumor biopsy samples will be provided in a separate 
document. Instructions and supplies required for the collection, processing, and shipment of the 
patients’ samples will be provided by the sponsor.
The tumor tissue 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.
8.2.4.2.
Tissue Collection for Tailoring Biomarker Studies
Tumor and plasma specimens will be collected throughout the study for the assessment of 
predictive biomarkers related to the activity of LY3009120, for exploratory research on new 
biomarkers related, but not limited, to the Raf pathway, and for evaluation of tumor specific 
biomarkers depending on evolving science.
Archived tissue: Precut, unstained slides from any available archival specimen of the patient’s 
tumor will be requested (but not required) for patients enrolled in Part A.
Study tumor biopsies: 
For Part A and Part B: Mandatory tumor biopsies will be collected as indicated in 
Section 8.2.4.1.
Tumor tissue biopsies will be taken either by core needle or excisional biopsy. The size of the 
sample will be dependent upon the procedure utilized to obtain the sample. These 
biomarker-related studies will include, but may not be limited to, protein and/or genetic analyses 
of the tumor specimen.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 46
LY3009120
8.2.4.2.1. Collection Procedures of Plasma Samples for Exploratory Biomarkers
Approximately 10 mL of anticoagulated blood will be collected before treatment in Cycle 1 and 
again during treatment on C1 D28 (± 3 days) by venipuncture or through a central line into 
EDTA tubes at times specified in Attachment 4.  Plasma samples will then be stored frozen.  In 
Part B, samples will also be collected during treatment on Day 28 (± 3 days) of each cycle
starting with Cycle 2 for a maximum of 9 to 12 cycles and during follow-up Visit 801.  
8.2.5. Pharmacogenetic Samples
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 ethical review boards (ERBs) allow, a blood sample will be collected for 
pharmacogenetic (PGx) analysis. It is a 1-time collection, as noted in the Study Schedule 
(Attachment 1). Samples will be stored and exploratory analysis may be performed to identify 
genetic variants that might play a role in tumor biology or to evaluate their association with 
observed clinical outcomes to LY3009120.
In the event of an unexpected AE or the observation of unusual response, the samples may be
genotyped and analysis may be performed to evaluate a genetic association with response to 
LY3009120. These investigations may be limited to a focused candidate gene study or, if 
appropriate, genome wide association studies may be performed to identify regions of the 
genome associated with the variability observed in drug response. 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.
Samples will be identified by the patient number (coded) and stored for up to 15 years after the 
last patient visit for the study at a facility selected by the sponsor. The duration allows the 
sponsor to respond to regulatory requests related to the study drug. The sample and any data 
generated from it can only be linked back to the patient by investigator site personnel.
8.3.
Efficacy Evaluations
A secondary objective of the study is to document any antitumor activity.  Refer to Attachment 1
and Attachment 9 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)
Each patient’s full extent of disease will also be assessed with the following procedures:

Tumor measurement of palpable or visible lesions (refer to RECIST 1.1)

Evaluation of tumor markers, if indicated.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 47
LY3009120

Evaluation of performance status (refer to the ECOG scale, Attachment 6).
To confirm objective responses, all lesions should be radiologically assessed, and the same 
radiologic method used for the initial response determination should be repeated at least 4 weeks 
following the initial observation of an objective response, using the sample method that was used 
at baseline.  If a patient is discontinued from the study, repeat radiology assessments may be 
omitted if clear clinical signs of progressive disease are present.
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, PD 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 electronic CRF 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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 48
LY3009120
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 CRFs, and study procedures

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by mail, 
telephone, and/or fax

review and evaluate CRF data and/or use standard computer edits to detect errors in data 
collection.

conduct a quality review of the database.
In addition, Lilly or its representatives will 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 IRB/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.
After the study is completed, a copy of the eCRF data and a copy of all the trial components will 
be sent on CD-ROM to the sponsor.  A CD-ROM will also be sent to each investigative site 
containing only the eCRF data from that site.
Any data for which paper documentation provided by the patient will serve as the source 
document will be identified and documented by each site in that site’s study file.  Paper 
documentation provided by the patient may include, for example, a paper diary to collect patient-
reported outcome (PRO) measures (for example, a rating scale), a daily dosing schedule or an 
event diary.
For data handled by a data management contract research organization (CRO), CRF data and 
some or all data that are related will be managed and stored electronically in the CRO system.  
After the final database lock at the CRO, validated data will be transferred to sponsor.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 49
LY3009120
Any diagnostic data collected from a contracted vendor will be stored electronically in that 
central vendor’s database system.  Data will subsequently be transferred from the central vendor 
according to the contract.
Any data for which the electronic CRF will serve as the source document will be identified and 
documented by each site in that site’s study file.
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.
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.
ECG data will be stored electronically in the central database system of Lilly’s central review 
organization.  Data will subsequently be transferred from the central review organization system 
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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 50
LY3009120
10. Data Analyses
10.1. General Considerations
Approximately 80 patients may be enrolled in this multicenter, open-label Phase 1 study with 
dose escalation followed by dose confirmation. During dose escalation, approximately 30 to 
35 patients will be enrolled into cohorts sequentially and without randomization to dose.  During 
dose confirmation, approximately 45 patients will be enrolled.
Statistical analysis of this study will be the responsibility of Eli Lilly and Company. The
analyses for this study will be descriptive, except for possible exploratory analysis as deemed
appropriate. Data analyses will be provided by dose groups and for all study patients combined
wherever appropriate. For continuous variables, summary statistics will include number of
patients, mean, median, standard deviation, minimum, and maximum. Categorical endpoints
will be summarized using number of patients, frequency, and percentages. Missing data will not
be imputed.
The interpretation of the study results will be the responsibility of the investigator with the Lilly
CRP or CRS, pharmacokineticist, and statistician. The CRP or CRS 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.
Exploratory analyses of the data not described below will be conducted as deemed appropriate.
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.
10.3. Patient Characteristics
Patient characteristics will include a summary of the following:

Patient demographics

Baseline disease characteristics

Prior disease-related therapies

Concomitant medications.
Other patient characteristics will be summarized as deemed appropriate.
10.4. Safety Analyses
All patients who receive at least 1 dose of LY3009120 will be evaluated for safety and toxicity.  
Adverse event terms and severity grades will be assigned by the investigator using CTCAE, 
Version 4.0).
Safety analyses will include summaries of the following:

adverse events, including severity and possible relationship to study drug

dose adjustments

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 51
LY3009120

laboratory values 

vital signs 

DLTs at each dose level 

ECG readings.
In addition, after each cohort, the toxicity-band method will be used to summarize the posterior 
distribution of probability of a DLT.
10.5. Pharmacokinetic Analyses
Pharmacokinetic analyses will be conducted on patients who have received at least 1 dose of the 
study drug and have had samples collected.
Pharmacokinetic parameter estimates for LY3009120 will be calculated by standard 
noncompartmental methods of analysis.
The primary parameters for analysis will be maximum concentration (Cmax) and area under the 
concentration-time curve (AUC0-tlast, AUC0-∞or AUC,ss) of LY3009120.  Other 
noncompartmental parameters, such as time of half-life (t1/2), apparent clearance (CL/F), and 
apparent volume of distribution (V/F) may be reported.  Additional exploratory 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.
Pharmacokinetic parameter estimates will be evaluated to delineate effects of dose 
proportionality log-transformed Cmax and AUC estimates will be assessed to estimate ratios of 
geometric means and the corresponding 90% confidence intervals (CIs).
10.6. Pharmacodynamic Analyses 
Pharmacodynamic data from all patients undergoing PD assessments will be analyzed.
Biomarker data from all patients undergoing biomarker assessments will be analyzed by 
appropriate statistical methods. These data may include, but are not limited to IHC, genetic 
mutations that are hypothesized to be related to safety, efficacy, drug disposition or pathways 
associated with the mechanism of action of LY3009120.
10.7. Pharmacokinetic/Pharmacodynamic Analyses 
The PK data will be combined, and analyses may be conducted to determine a relationship
between exposure and clinical PD effect (eg, phospho-ERK, p27, and/or Ki67 protein expression 
in tumors), data permitting. This model may be used to help reassess the dose cohort escalation
and schedule as the study progresses. If deemed necessary, exploratory PK/PD analysis may be 
employed to evaluate relationships between LY3009120 exposure and measurements of 
pharmacologic effects or safety.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 52
LY3009120
10.8. Efficacy
The study was not designed to make an efficacy assessment.  However, any tumor response data 
will be tabulated according to study part and patient cohort.  In Part A, blood tumor markers, if 
applicable, will be drawn at baseline and Day 1 of each cycle.
10.9. Interim Analyses
During Part A, patient safety will be assessed prior to each dose escalation to ensure nothing 
precludes administration of larger doses to future study patients. In addition to reviewing AEs 
and laboratory measurements, available PK/PD profiles of LY3009120 will be reviewed per 
cohort. Based on these interim results, modifications (eg, reductions in dose increment or 
changes in dosing schedule) to the dose-escalation strategy or other design elements may be 
made to ensure patient safety. The study investigators and the Lilly CRP will make the 
determination regarding dose escalation based upon their review of the safety/tolerability data 
and the PK data from the previous cohorts. In addition, an interim review will be conducted 
prior to proceeding to Part B including safety, PK, and PD. All relevant data will be reviewed to 
confirm the estimation of the MTD. The decision to proceed to Part B will be made following 
discussions between the investigators and Lilly clinical research personnel.
During Part B, interim analyses may be conducted in each cohort to review available safety, PK, 
PD, and efficacy data once enrollment to that particular cohort (A, B, or C) has completed and all 
evaluable patients in that cohort have either completed 3 cycles of therapy or discontinued from 
the treatment.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 53
LY3009120
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 
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 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 submitted to the ERB and 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:

the current IB and updates during the course of the study

ICF

relevant curricula vitae
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
(CIOMS) International Ethical Guidelines
2) the International Conference on Harmonisation (ICH) Good Clinical Practices (GCP) 
Guideline [E6]
3) applicable laws and regulations.
The investigator or designee will promptly submit the protocol to applicable ERB(s).

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 54
LY3009120
All or some of the obligations of the sponsor will be assigned to a CRO.
An identification code assigned by the investigator 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.
11.3.3. Final Report Signature
The final report coordinating investigator or designee will sign the clinical study report for this 
study, indicating agreement that, to the best of his or her knowledge, the report accurately 
describes the conduct and results of the study.
The investigator with the most enrolled patients will serve as the final report coordinating 
investigator.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the final report coordinating investigator.
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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 55
LY3009120
12. References
Ahronian LG, Sennott EM, Van Allen EM, Wagle N, Kwak EL, Faris JE, Godfrey JT, 
Nishimura K, Lynch KD, Mermel CH, Lockerman EL, Kalsy A, Gurski JM Jr, Bahl S, 
Anderka K, Green LM, Lennon NJ, Huynh TG, Mino-Kenudson M, Getz G, Dias-Santagata 
D, Iafrate AJ, Engelman JA, Garraway LA, Corcoran RB. Clinical acquired resistance to RAF 
inhibitor combinations in BRAF-mutant colorectal cancer through MAPK pathway alterations. 
Cancer Discov. 2015;5(4):358-367.
Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with 
overdose control. Stat Med. 1998;17(10):1103-1120.
Beeram M, Patnaik A, Rowinsky EK.  Raf: a strategic target for therapeutic development against 
cancer. J Clin Oncol. 2005;23(27):6771-6790.
Belum VR, Fischer A, Choi JN, Lacouture ME. Dermatological adverse events from BRAF 
inhibitors: a growing problem. Curr Oncol Rep. 2013;15(3):249-259.
Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, 
Version 4.0, DCTD, NCI, NIH, DHHS. 2009. Publish date: 29 May 2009.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, 
Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day 
SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee 
RJ, Flaherty KT, McArthur GA; BRIM-3 Study Group. Improved survival with vemurafenib 
in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-2516.
Choe CH, McArthur GA, Caro I, Kempen JH, Amaravadi RK. Ocular toxicity in BRAF mutant 
cutaneous melanoma patients treated with vemurafenib. Am J Ophthalmol. 
2014;158(4):831-837.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 
1976;16(1):31-41.
Corcoran RB, Dias-Santagata D, Bergethon K, Iafrate AJ, Settleman J, Engelman JA. BRAF 
gene amplification can promote acquired resistance to MEK inhibitors in cancer cells 
harboring the BRAF V600E mutation. Sci Signal. 2010;3(149):ra84.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett 
MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, 
Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, 
Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, 
Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, 
Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, 
Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human 
cancer. Nature. 2002;417(6892):949-954.
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.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 56
LY3009120
Flaherty KT, McArthur G. BRAF, a target in melanoma: implications for solid tumor drug 
development. Cancer. 2010;116(21):4902-4913.
Friday BB, Adjei AA. Advances in targeting the Ras/Raf/MEK/Erk mitogen-activated protein 
kinase cascade with MEK inhibitors for cancer therapy. Clin Cancer Res. 2008;14(2):342-326.
Goodman SN, Zahurak ML, Piantadosi S. Some practical improvements in the continual 
reassessment method for phase I studies. Stat Med. 1995;14(11):1149-1161.
Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, Emery CM, 
Stransky N, Cogdill AP, Barretina J, Caponigro G, Hieronymus H, Murray RR, Salehi-
Ashtiani K, Hill DE, Vidal M, Zhao JJ, Yang X, Alkan O, Kim S, Harris JL, Wilson CJ, Myer 
VE, Finan PM, Root DE, Roberts TM, Golub T, Flaherty KT, Dummer R, Weber BL, Sellers 
WR, Schlegel R, Wargo JA, Hahn WC, Garraway LA. COT drives resistance to RAF 
inhibition through MAP kinase pathway reactivation. Nature. 2010;468(7326):968-972.
Joseph EW, Pratilas CA, Poulikakos PI, Tadi M, Wang W, Taylor BS, Halilovic E, Persaud Y, 
Xing F, Viale A, Tsai J, Chapman PB, Bollag G, Solit DB, Rosen N. The RAF inhibitor 
PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective 
manner. Proc Natl Acad Sci U S A. 2010;107(33):14903-14908.
Madhunapantula SV, Robertson GP. Is B-Raf a good therapeutic target for melanoma and other 
malignancies? Cancer Res. 2008;68(1):5-8.
Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, 
Stubbs H, Lee DY, Singh A, Drew L, Haber DA, Settleman J. Elevated CRAF as a potential 
mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res. 
2008;68(12):4853-4861.
Murray PT, Ratain MJ. Estimation of the glomerular filtration rate in cancer patients: a new 
formula for new drugs. J Clin Oncol. 2003;21(14):2633-2635.
Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, 
Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS. Melanomas acquire 
resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 
2010;468(7326):973-977.
Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to phase I 
cancer trials. Stat Med. 2008;27(13):2420-2439.
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.
Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, Shi H, Atefi M, Titz B, 
Gabay MT, Salton M, Dahlman KB, Tadi M, Wargo JA, Flaherty KT, Kelley MC, Misteli T, 
Chapman PB, Sosman JA, Graeber TG, Ribas A, Lo RS, Rosen N, Solit DB. RAF inhibitor 
resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 
2011;480(7377):387-390.
O’Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for phase 1 
clinical trials in cancer. Biometrics 1990;46(1):33-48.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 57
LY3009120
Rasco DW, Olszanski AJ, Patnaik A, Espino G, Neuwirth R, Faucette S, Bargfrede M, Gangolli 
EA, Walker RM, Kneissl M, Bozon V. MLN2480, an investigational oral pan-RAF kinase 
inhibitor, in patients (pts) with relapsed or refractory solid tumors: Phase I study. Poster 
presented at: Annual Meeting of the American Society of Clinical Oncology; 31 May
2013-4 June 2013; Chicago, IL.
Rizzo JD, Somerfield MR, Hagerty KL, Seidenfeld J, Bohlius J, Bennett CL, Cella DF, 
Djulbegovic B, Goode MJ, Jakubowski AA, Rarick MU, Regan DH, Lichtin AE; American 
Society of Clinical Oncology; American Society of Hematology. Use of epoetin and 
darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American 
Society of Hematology clinical practice guideline update. J Clin Oncol. 2008;26(1):132-149. 
Epub 2007 Oct 22. Erratum in: J Clin Oncol. 2008;26(7):1192.
Shi H, Kong X, Ribas A, Lo RS. Combinatorial treatments that overcome PDGFRβ-driven 
resistance of melanoma cells to V600EB-RAF inhibition. Cancer Res. 2011;71(15):5067-
5074.
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.
Sullivan RJ, Flaherty KT. Resistance to BRAF-targeted therapy in melanoma. Eur J Cancer.
2013;49(6):1297-1304.
Urner-Bloch U, Urner M, Stieger P, Galliker N, Winterton N, Zubel A, Moutouh-de Parseval L, 
Dummer R, Goldinger SM. Transient MEK inhibitor-associated retinopathy in metastatic 
melanoma. Ann Oncol. 2014;25(7):1437-1441.
Villanueva J, Vultur A, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, 
Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D'Andrea K, 
Pushparajan A, Hayden JE, Brown KD, Laquerre S, McArthur GA, Sosman JA, Nathanson 
KL, Herlyn M. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in 
melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 
2010;18(6):683-695.
Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen 
CM, Macconaill LE, Hahn WC, Meyerson M, Garraway LA. Dissecting therapeutic resistance
to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29(22):3085-
3096.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 58
LY3009120
Attachment 1.
Protocol JBDA Study Schedule

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 59
LY3009120
Part A: Baseline Assessments
Relative Day Prior to 
Day 1 of Cycle 1
28
14
3
Comments
Informed Consent 
Informed Consent Form signed (prior to performance of any 
protocol-specific tests/procedures)
Chest X-ray
X
May be omitted in patients having a chest CT scan for their 
radiological tumor assessment
Radiological Tumor 
Assessment
X
Medical History
X
Including any alcohol/tobacco habits
Physical Exam
X
Vital Signs 
X
Including temperature, blood pressure, pulse rate, 
respiration rate
ECOG Performance Status
X
ECG (central)
X
Central collection and storage.
Hematology (local)
X
aPTT, PT, PT/INR (local)
X
Serum Chemistry 
X
Urinalysis (local)
X
Tumor Measurement 
(Palpable or Visible)
X
CTCAE v 4.0 Grading 
(Preexisting conditions)
X
To be reported only after study eligibility is confirmed.
Concomitant Meds
X
Tumor Markers, if 
applicable (local)
X
If applicable to tumor type of the patient.  
Exploratory blood plasma 
sample
X
EDTA tube baseline collection after eligibility confirmed
Study Tumor Biopsy
(designated expansion 
cohorts)
X
Biopsy should be taken only after study eligibility is 
confirmed (mandatory).  Biopsy samples taken within 
6 months prior to enrollment will also be permitted as long 
as patients have not received any recent therapies for the 
disease prior to starting LY3009120. 
Tumor Biopsy B-Raf Status 
Assessment (only for
patients that do not have 
historical B-Raf testing 
results or adequate archived 
tissue available for B-Raf 
retesting)
X
Patients will be able to receive treatment before biopsy 
results are available.
Archived Tumor Sample
X
Paraffin-embedded tumor tissue (optional).  Sent after study 
eligibility is confirmed.
Pregnancy Test (local)
X
Negative results required prior to Cycle 1, Day 1.  Only to 
be performed on women of childbearing potential.
Eye Safety Assessments
X
Dermatological Evaluation
X

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 60
LY3009120
Abbreviations:  aPTT = activated partial thromboplastin time; CT = computed tomography; CTCAE = Common 
Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology 
Group; Meds = medications; PD = pharmacodynamic; PT/INR = prothrombin time/international normalized 
ratio.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 61
LY3009120
Part A: During and Poststudy Assessments
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
2
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after 
last dose of study drug; Visits 802, 
803, and 804 are each 2 months in 
duration and will start after Visit 801.
LY3009120
X
X
X
Physical Exam
X
X
X
X
X
X
X
After C1D1, ± 3 days while on 
treatment; Will not need to be 
repeated if performed ≤3 days from 
C1D1.
Eye Assessments
X
X
At baseline, at the end of Cycle 1 and 
Cycle 2, and every 2 cycles afterwards 
(end of C4, C6 and so on) up to 7 days 
before start of next cycle, and at other 
time points if clinically indicated.
Dermatological 
Evaluation
X
X
At baseline, every 2 cycles while on 
therapy, and every 2 months for up to 
6 months following discontinuation of 
LY3009120.
Weight
X
X
X
After C1D1, ± 3 days while on 
treatment
Vital Signs 
X
X
X
X
X
X
X
X
X
Temperature, PR, RR, BP.  After 
C1D1, ± 3 days while on treatment.
ECG
X
X
X
X
In cycle 1 only, on days with PK 
assessments, ECGs will be performed 
before patients receive morning dose 
of study drug at the site and 3 hours 
post-dosing. 
After C2D1, ± 3 days while on 
treatment. 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 62
LY3009120
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
2
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after 
last dose of study drug; Visits 802, 
803, and 804 are each 2 months in 
duration and will start after Visit 801.
Hematology
X
X
X
X
X
X
X
X
X
X
After C2D1, ± 3 days while on 
treatment.  On days with PK 
assessment it will be performed before 
patients receive morning dose of study 
drug at the site.
Serum Chemistry
X
X
X
X
X
X
X
X
X
X
After C2D1, ± 3 days while on 
treatment; On days with PK 
assessment it will be performed before 
patients receive morning dose of study 
drug at the site.
Urinalysis
X
X
X
After C1D1, ± 3 days while on 
treatment; will not need to be 
performed if completed less than 
3 days before Cycle 1 Day 1.
CTCAE v 4.0 Grading
X
X
X
X
Throughout study as needed.
Concomitant Meds
X
X
X
X
Throughout study as needed.
ECOG Performance 
Status
X
X
X
After C1D1, ± 3 days while on 
treatment
PK Sampling 
X
X
X
X
X
See PK Sampling Attachment 4 for 
exact timing.
Tumor Measurement 
(Palpable or Visible)
X
X
X
X
After C1D1, ± 3 days while on 
treatment
Radiological Tumor 
Assessment
X
X
X
Approximately every 8 weeks (every 
other cycle, end of C2, C4, and so on).  
Up to 7 days before start of next 
cycle.
Blood Tumor Markers, 
if applicable
X
X
X
If applicable to tumor type of the 
patient (± 3 days while on treatment)

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 63
LY3009120
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
2
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after 
last dose of study drug; Visits 802, 
803, and 804 are each 2 months in 
duration and will start after Visit 801.
Pharmacogenetic blood 
sample, stored 
(mandatory)
X
Study Tumor Biopsy 
(Part A, designated 
expansion cohorts)
X
± 14 days
Exploratory blood 
plasma sample
X
Abbreviations:  BP = blood pressure; CTCAE = Common Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative 
Oncology Group; PK = pharmacokinetic; PD = pharmacodynamic; PR = pulse rate; RR= respiration rate.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 64
LY3009120
Part B: Baseline Assessments
Relative Day Prior to 
Day 1 of Cycle 1
28
14
3
Comments
Informed Consent 
Informed Consent Form signed (prior to performance of any 
protocol-specific tests/procedures)
Chest X-ray
X
May be omitted in patients having a chest CT scan for their 
radiological tumor assessment
Radiological Tumor 
Assessment
X
Medical History
X
Including any alcohol/tobacco habits
Physical Exam
X
Vital Signs 
X
Including temperature, blood pressure, pulse rate, 
respiration rate
ECOG Performance Status
X
ECG 
X
Central collection and storage
Hematology (local)
X
aPTT, PT, PT/INR (local)
X
Serum Chemistry 
X
Urinalysis (local)
X
Tumor Measurement 
(Palpable or Visible)
X
CTCAE v 4.0 Grading 
(Preexisting conditions)
X
To be reported only after study eligibility is confirmed.
Concomitant Meds
X
Exploratory blood plasma 
sample
X
EDTA tube collection after eligibility confirmed
Study Tumor Biopsy 
(Part B, all cohorts)
X
Biopsy should be taken only after study eligibility is 
confirmed (mandatory). 
Pregnancy Test (local)
X
Negative results required prior to Cycle 1, Day 1.  Only to 
be performed on women of childbearing potential. 
Eye Safety Assessments
X
Dermatological Evaluation
X
Abbreviations:  aPTT = activated partial thromboplastin time; CT = computed tomography; CTCAE = Common 
Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology 
Group; Meds = medications; PD = pharmacodynamic; PT/INR = prothrombin time/international normalized 
ratio.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 65
LY3009120
Part B: During and Poststudy Assessments
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after last 
dose of study drug; Visits 802, 803, and 
804 are each 2 months in duration and 
will start after Visit 801.
LY3009120
X
X
X
Physical Exam
X
X
X
X
X
X
X
After C1D1, ± 3 days while on 
treatment; Will not need to be repeated 
if performed ≤3 days from C1D1.
Eye Assessments
X
X
At baseline, at the end of Cycle 1 and 
Cycle 2, and every 2 cycles afterwards
(end of C4, C6, and so on) up to 7 days 
before start of next cycle, and at other 
time points if clinically indicated.
Assessment can also be performed on 
the D1 of the next cycle (predose). 
Dermatological 
Evaluation
X
X
At baseline, every 2 cycles while on 
therapy, and every 2 months for up to 
6 months following discontinuation of 
LY3009120.
Weight
X
X
X
After C1D1, ± 3 days while on treatment
Vital Signs 
X
X
X
X
X
X
Temperature, PR, RR, BP.  After C1D1, 
± 3 days while on treatment.
ECG
X
X
X
X
In cycle 1 only, on days with PK 
assessments ECGs will be performed 
before patients receive morning dose of 
study drug at the site and 3 hours post-
dosing 
After C2D1, ± 3 days while on 
treatment. 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 66
LY3009120
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after last 
dose of study drug; Visits 802, 803, and 
804 are each 2 months in duration and 
will start after Visit 801.
Hematology
X
X
X
X
X
X
X
X
X
X
After C2D1, ± 3 days while on 
treatment; On days with PK assessment 
it will be performed before patients 
receive morning dose of study drug at 
the site.
Serum Chemistry
X
X
X
X
X
X
X
X
X
X
After C2D1, ± 3 days while on 
treatment; On days with PK assessment 
it will be performed before patients 
receive morning dose of study drug at 
the site.
Urinalysis
X
X
X
After C1D1, ± 3 days while on 
treatment; will not need to be performed 
if completed less than 3 days before 
Cycle 1 Day 1.
CTCAE v 4.0 Grading
X
X
X
X
Throughout study as needed.
Concomitant Meds
X
X
X
X
Throughout study as needed.
ECOG Performance 
Status
X
X
X
After C1D1, ± 3 days while on treatment
PK Sampling 
X
X
X
X
X
See PK Sampling Attachment 4 for 
exact timing.
Tumor Measurement 
(Palpable or Visible)
X
X
X
X
After C1D1, ± 3 days while on treatment
Radiological Tumor 
Assessment
X
X
X
Approximately every 8 weeks (every 
other cycle, end of C2, C4, and so on). 
Up to 7 days before start of next cycle.
Urine Metabolite 
Collection
X
To be collected from up to 3 patients 
enrolled in Part B; not a protocol 
violation if not collected.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 67
LY3009120
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after last 
dose of study drug; Visits 802, 803, and 
804 are each 2 months in duration and 
will start after Visit 801.
Pharmacogenetic blood 
sample, stored 
(mandatory)
X
Exploratory blood 
plasma sample
X
X
X
X
To be collected in all patients in Part B
for a maximum of 9 to 12 cycles.
Study Tumor Biopsy 
X
Can be ±5 days
Abbreviations:  BP = blood pressure; CTCAE = Common Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative 
Oncology Group; PK = pharmacokinetic; PD = pharmacodynamic; PR = pulse rate; RR= respiration rate.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 68
LY3009120
Attachment 2.
Protocol JBDA Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologyb:
Clinical Chemistrya
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Magnesium
Erythrocyte count (RBC)
Potassium
Leukocytes (WBC)
Total bilirubin
Neutrophils
Alkaline phosphatase
Lymphocytes
Alanine aminotransferase
Monocytes
Aspartate aminotransferase 
Gamma-glutamyl transpeptidase 
Lactic dehydrogenase
Eosinophils
Blood urea nitrogen 
Basophils
Creatinine
Platelets
Uric acid
Calcium
aPTT
Glucose, random 
PT and PT/INR
Albumin
Total protein
Chloride
Bicarbonate
Urinalysisb:
Specific gravity
Direct bilirubinb, as needed
pH
Creatinine clearanceb
Protein
Glucose
Serum Pregnancy Test (females only)b
Ketones
Blood
Abbreviations:  RBC = red blood cells; WBC = white blood cells; aPTT = activated partial thromboplastin time;  PT 
= prothrombin time; PT/INR = international normalized ratio of prothrombin time.
a
Assayed by Lilly-designated central laboratory.
b
Local or investigator-designated laboratory.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 69
LY3009120
Attachment 3.
Protocol JBDA 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.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time /INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
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 Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Anti-smooth muscle antibodya
CPK 
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase; 
GGT = gamma glutamyl transferase; Ig = immunoglobulin; INR = International Normalised Ratio; RBC = red 
blood cells; WBC = white blood cells.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 70
LY3009120
Attachment 4.
Protocol JBDA Pharmacokinetic and 
Exploratory Blood Plasma Sampling Schedule
Pharmacokinetic Sampling Schedule For Part A
Sample Number
Cycle
Daya
PK Sampling Time for 
LY3009120b
Exploratory Blood Sample
1
1
1
predose
Xc
2
1
1
0.5h 
3
1
1
1h 
4
1
1
2h 
5
1
1
4h 
6
1
1
6h 
7
1
1
8h 
8
1
1
10h
9
1
2
Predose
10
1
15
Predose
11
1
15
0.5h 
12
1
15
1h 
13
1
15
2h 
14
1
15
4h 
15
1
15
6h 
16
1
15
8h 
17
1
15
10h
18
1
28
Predose 
X
19
1
28
0.5h
20
1
28
1h
21
1
28
2h
22
1
28
4h
23
1
28
6h
24
1
28
8h
25
1
28
10h
26
2
1
Predose
a On Cycle 1 Day 1 in Part A only, the evening dose should be omitted to enable characterization of a full PK 
profile.
b Predose PK samples should be collected prior to the morning dose, and all samples collected as close to the 
scheduled times as possible.
c Baseline exploratory blood plasma sample (EDTA tube) can be collected ≤14 days before first dose of 
LY3009120, after eligibility is confirmed and at Cycle 1 Day 28 predose.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 71
LY3009120
Pharmacokinetic Sampling Schedule For Patients in Part B
Sample 
Number
Cycle
Day
PK Sampling Time for 
LY3009120a
Exploratory 
Blood Sampleb
Urine Sampling 
(Part B only- up to 
3 patients)
1
1
1
Predose
X
0 to 10h pooled 
samples (end time 
to coincide with PK 
blood draw)
2
1
1
0.5
3
1
1
1
4
1
1
2
5
1
1
4
6
1
1
6
7
1
1
8
8
1
15
predose
9
1
22
predose
X
10
2
28
predose
X
11
3-n
28
predose
X
12
Follow-up
(Visit 801)
-
-
X
a Predose PK samples should be collected prior to the morning dose, and all samples collected as close to the 
scheduled times as possible.
b Baseline exploratory blood plasma sample (EDTA tube) will be collected ≤14 days before first dose of 
LY3009120 after eligibility is confirmed.  Samples will also be collected during treatment predose on Day 22 of 
Cycle 1, and Day28 of each cycle thereafter; and during follow-up Visit 801.  During treatment this sample will be 
collected for a maximum of 9 to 12 cycles.  

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 72
LY3009120
Attachment 5.
Protocol JBDA 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, 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, test and procedure results 
(if applicable)
Relationship to Study Drug & Protocol Procedures
Concomitant Drug Therapy

indication, total daily dose, duration of treatment, start date, action taken
In Case of Death

cause, autopsy finding (if available), date, relationship to study drug and protocol 
procedures.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 73
LY3009120
Attachment 6.
Protocol JBDA ECOG Performance Status
ECOG Performance Status
Activity Status
Description
0
Fully active, able to carry on all pre-disease performance without 
restriction
1
Restricted in physically strenuous activity but ambulatory and able 
to carry out performance of a light or sedentary nature, for example,
light housework, office work
2
Ambulatory and capable of all selfcare but unable to carry out any 
work activities.  Up and about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 
50% of waking hours
4
Completely disabled.  Cannot carry on any selfcare.  Totally 
confined to bed or chair
5
Dead
Source:  Oken et al. 1982.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 74
LY3009120
Attachment 7.
Protocol JBDA Creatinine Clearance 
Formula
Note:  This formula is to be used for calculating CrCl from local laboratory results only.
For serum creatinine 
concentration in mg/dL:
CrCl =
(140 – agea) (wt) 0.85 (if female), or 1.0 (if male)
(mL/min) 
72 serum creatinine (mg/dL)
For serum creatinine concentration in mol/L:
CrCl =
(140 – agea) (wt) 0.85 (if female), or 1.0 (if male)
(mL/min)
0.81 serum creatinine 
(mol/L)
a age in years, weight (wt) in kilograms.
Reference:  Cockcroft and Gault 1976.
-OR-
GFR(mL/min/1.73m2) = 170 x [PCr]-0.999 x [age]-0.176
x [0.762 if patient is female] x [1.18 if patient is black]
x [SUN]-0.17 x [Alb]+0.318
PCr= Plasma Creatinine, mg/dL; SUN= Serum urea nitrogen, mg/dL; Alb= Serum albumin, g/dL
Source:  Murray and Ratain 2003

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 75
LY3009120
Attachment 8.
Protocol JBDA Sampling Summary
This table summarizes the maximum number of samples and volumes for all sampling, and tests
during the study.  The summary below provides estimates. 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).
Protocol I6X-MC-JBDA Sampling Summary
Purpose
Sample 
Type
Maximum
Amount per Sample
Maximum
Number of Samples
Maximum
Total Amount
Study qualificationa
Blood
12 mL
1
12 mL
Health Monitoring (may be 
more than 1 tube)b
Blood
9 mL
11
99 mL
Drug concentrationc
Blood
3 mL
26
78 mL
Pharmacogenetic stored sample
Blood
10 mL
1
10 mL
Tailoring biomarkers
Blood
10 mL
14
140 mL
PD samplesd (Part A, 
designated expansion cohorts)
Tumor 
tissue
2 biopsies
2 biopsies
Other exploratory sample
(Part B, all cohorts)
Tumor 
tissue
2 biopsies
2 biopsies
B-Raf status assessment biopsyf
Tumor 
tissue
1 biopsy
1 biopsy
Hepatic Monitoringe
Blood
3 - 30 mL
-
-
Total 
Blood: 339 mL
Tissue: 2 biopsies
a Additional samples may be drawn if needed for safety purposes.
b Total volume based on average number of 5 cycles.
c Part A:  26 PK time points; Part B:  9 PK time points.
d Only for patients in designated Part A expansion cohorts as noted in Section 8.2.4.1.
e 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.
f Only for patients without historical B-Raf mutation test results or adequate archived tumor tissue sample available 
for genetic testing (Section 8.2.2).

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 76
LY3009120
Attachment 9. Protocol JBDA RECIST Criteria 1.1
CCI
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).
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 77
LY3009120
CCI
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
  
 
 
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 78
LY3009120
CCI
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 79
LY3009120
CCI
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 80
LY3009120
 
 
 
 
 
 
 
 
 
 
CCI
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 81
LY3009120
 
CCI
 
 
 
 
 
 
 
 
 
 
 
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 82
LY3009120
CCI
 
 
 
 
 
 
 
 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol 
Page 83 
LY3009120 
Attachment 10. Protocol JBDA Toxicity Band Design 
This section introduces the background of Toxicity Band design (Neuenschwander et al. 2008) 
and describes the key elements for this trial.  Simulation results from the Toxicity Band design 
are presented.  These results are also compared with those from the simulation of a traditional 
3+3 design to demonstrate the benefit of implementing a Toxicity Band design in this trial.  
Fixed and Adaptive Clinical Trial Simulator (FACTS) software version 3.2 are used for all the 
simulations. 
1.1 Introduction of CRM type approaches 
The Continual Reassessment Method, and hereafter, CRM (O'Quigley et al. 1990) is the first 
Bayesian model-based approach developed for dose escalation studies.  Compared to the 
traditional 3+3 design that only used current dose level DLT data to estimate the MTD, CRM 
utilizes prior dose toxicity information and all available DLT data to efficiently estimate the 
MTD.  To improve the operating characteristics of CRM, Goodman et al. (1995), among others, 
have proposed modified- CRM (MCRM) procedures to make the model-based designs more 
acceptable in practice.  The major modifications include: 
 Always start at the lowest dose level. 
 Limit the escalation increment. 
 Escalate by cohorts rather than single patients. 
Babb et al. (1998) proposed the Escalation with Overdose Control (EWOC) method that directly 
controls the probability of overdosing during dose escalation.  EWOC is also a CRM-type 
method.  During the escalation, EWOC selects the next dose such that the predicted probability 
that the new dose exceeds the MTD is equal to a pre-specified feasibility bound α= 0.25.  The 
connection between CRM and EWOC is that CRM typically uses the middle (mean, or median) 
of the MTD's posterior distribution as the next recommended dose, whereas EWOC uses the 25th 
percentile.  Therefore, EWOC is a more conservative method than the original CRM method. 
1.2 Toxicity Band design 
All the aforementioned approaches use point estimates of the posterior distributions to 
recommend the next dose.  Neuenschwander et al. (2008) extended the concept of EWOC and 
proposed to consider the uncertainty of the posterior distributions and use interval estimates to 
make the dose recommendation.  We call their approach the Toxicity Band Design. 
The Model 
A two-parameter logistic model is used to model the relationship between dose and probability 
of a DLT: 
logitሼ݌ሺ݀ሻሽൌߙ൅ߚlog ൬݀
݀∗൰,    ߚ൐0.  ሺ1.1ሻ  

I6X-MC-JBDA(d) Phase 1 Oncology Protocol 
Page 84 
LY3009120 
In the model, ݀ is the true dose, ݌ሺ݀ሻ is the probability of a DLT at dose ݀.  ݀∗ is the reference 
dose such that ߙ is interpreted as the log-odds of a DLT at  ݀∗. 
Toxicity Band 
The probability of a DLT is categorized to four bands: 
Under‐dosing: ݌ሺ݀ሻ in ሺ0, 0.20ሿ 
Targeted toxicity: ݌ሺ݀ሻ in ሺ0.20, 0.35ሿ 
Excessive toxicity: ݌ሺ݀ሻ in ሺ0.35, 0.60ሿ 
Unacceptable toxicity: ݌ሺ݀ሻ in ሺ0.60, 1.00ሿ 
The over-dosing means ݌ሺ݀ሻ൐0.35. 
MTD Definition 
The MTD is defined as a safe dose that has the highest probability of DLT in the targeted 
toxicity interval (20 to 35%).  A safe dose means that the probability of DLT larger than 35% is 
below 25%. 
Dose Recommendation 
During the escalation, after each cohort of patients, we 
1) Calculate the posterior probabilities of the four toxicity bands, for each dose. 
2) Exclude the doses such that the posterior probabilities of over-dosing are larger than 0.25 
(JBDA over-dosing control criteria).  The remaining doses are the ones that satisfy the 
overdose control criteria. 
3) Among the remaining doses, the dose with the highest posterior probability in the 
targeted toxicity band will be the model recommendation of the next dose.  
In this study, the escalation will start from the lowest planned dose; the maximum dose 
increment is 100%; and each dose cohort will have a minimum of 3 patients enrolled to it.  The 
Bayesian model-based toxicity band method that incorporates prior expectations about toxicity 
will be fitted to the data at the end of each cohort to recommend a dose for the next cohort.  The 
investigators and Lilly CRP will consider both the model recommendation and the observed 
DLT rate at each cohort to determine the next dose level.  Dose escalation will take into account 
PK and PD information when available.  Additional patients may therefore be enrolled at a 
specific dose level to characterize PK/PD.  Intermediate dose levels will be explored if deemed 
necessary after discussion between the sponsor and investigators. 
1.3 Dose Ranges and Reference Dose 
This study has eight pre-specified doses: 50, 100, 200, 300, 400, 500, 600 and 700 mg BID.  The 
reference dose in model (1.1) is chosen as ݀∗ൌ700, the highest dose.  The model typically has 
satisfactory performance by choosing the highest dose as the reference. 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol 
Page 85 
LY3009120 
1.4 The Prior Distribution on Model Parameters 
A Quantile-based uninformative prior (Neuenschwander et al. 2008) is used to derive a bivariate-
normal prior on (ߙ, logߚ).  This can be achieved by the following two steps: (1) derive a prior 
distribution of probability of DLT at each dose level (2) derive a bivariate-normal prior on (ߙ, 
logߚ) to match the distributions in the previous step. 
Step 1 
After discussing with CRP, PK and Toxicology scientists, we selected the median probability of 
DLT for the lowest dose 50 mg BID and highest dose 700 mg BID as 0.005 and 0.5, 
respectively, based on preclinical experience.  The median probabilities of DLT of the 
intervening doses are calculated by assuming that the probabilities are linear in log (݀/݀∗) on the 
logit scale.  We therefore obtain the prior median probability of DLT for each dose. 
 
Table 1. Prior Median Probability of DLT at Each Dose Level 
Dose Level 
True Dose (mg, BID) 
Median Probability of DLT 
1 
50 
0.005 
2 
100 
0.020 
3 
200 
0.075 
4 
300 
0.155 
5 
400 
0.246 
6 
500 
0.337 
7 
600 
0.423 
8 
700 
0.500 
 
For each dose, the minimally informative unimodal Beta (a,b) distribution is derived as the prior 
distribution for the probability of DLT. 
 For median Probability of DLT <0.5, b = 1 and a(<1) is tuned to match the median 
 For median Probability of DLT >0.5, a = 1 and b(<1) is tuned to match the median 
After obtaining the prior distribution of the probability of DLT, we calculate the 2.5% and 97.5% 
quantiles for each distribution.  Figure 1 shows the three quantiles of each prior distribution. 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol 
Page 86 
LY3009120 
 
Figure 1. Prior probability of DLT at each dose. 
 
Step 2 
Derive a bivariate normal distribution on (ߙ, logߚ) that stochastically gives the best fit to the 
2.5%, 50%, and 97.5% quantiles of the prior probability of DLT at each dose.  Figure 2 is the 
fitting generated by FACTS.  The parameters (ߙ, logߚ) has a bivariate normal distribution with 
Mean = (-0.092, 0.359), SD = (2.507, 0.907), and ρ=.282. 
 
0.0
0.2
0.4
0.6
0.8
1.0
Prob. of DLT: 2.5%, 50%, 97.5% quantiles
Dose
Probability
50
100
200
300
400
500
600
700

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 87
LY3009120
Figure 2. The stochastic fitting for the prior on ( , log )
1.5 Simulation Studies
We perform simulations under different scenarios to investigate the operational characteristics:  
Toxicity band method vs. traditional 3+3.

3-patient cohorts starting from the lowest dose. No dose skipping.

Maximum number of patients:  33

Stopping rules for Tox-band method: max sample size reached or the recommended next 
dose has been treated for 9 Patients: 
We considered 8 scenarios to represent a wide range of possible curves. The true DLT rate of 
the MTD is fixed at 25% across scenarios. Scenario 1 and 2 are toxic cases that have MTD at 
the first and second level. Both scenario 3 and 4 (in blue color) have 300 mg at the MTD with 
either steep or flat curves. Similarly, we design scenario 5 and 6 to have the same MTD at 
400 mg. Scenario 7 has MTD at 500 mg, whereas scenario 8 is a safe case that the MTD is at the 
last dose.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 88
LY3009120
Figure 3. The Pre-specified probability of DLT under each scenario
Table 2. The Pre-specified probability of DLT under each scenario
0.0
0.2
0.4
0.6
0.8
1.0
Pre-specified Prob. of DLT
Dose
Probability
50
100
200
300
400
500
600
700
1
2
3
4
5
6
7
8

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 89
LY3009120
We ran 1000 simulations under each scenario to investigate the operating characteristics of the 
Toxicity Band and 3+3 methods.  The results are summarized in Table 3 and 4.
Table 3. Probability of each dose selected as MTD, mean number of subjects, and mean 
percentages of a DLT under each scenario:  Results based on 1000 
simulations (Toxicity Band Method)
Scenarios
Dose
1
2
3
4
5
6
7
8
50
0.833
0.422
0.084
0.008
0.015
0.002
0.031
0
100
0.159
0.464
0.159
0.068
0.072
0.019
0.138
0.018
200
0.008
0.109
0.247
0.333
0.105
0.047
0.121
0.038
300
0
0.005
0.342
0.512
0.274
0.313
0.126
0.093
400
0
0
0.136
0.076
0.337
0.527
0.204
0.120
500
0
0
0.028
0.003
0.152
0.086
0.233
0.138
600
0
0
0.003
0
0.027
0.005
0.095
0.137
700
0
0
0.001
0
0.018
0.001
0.052
0.456
Mean # of Subj.
10.035
14.358
21.585
22.479
25.020
25.710
25.266
28.977
Mean % of a DLT
39.20
27.54
19.57
17.62
16.26
15.73
15.93
10.79
Table 4. Probability of each dose selected as MTD, mean number of subjects, and mean 
percentages of a DLT under each scenario:  Results based on 1000 
simulations (3+3 Method)
Scenarios
Dose
1
2
3
4
5
6
7
8
50
0.808
0.504
0.133
0.020
0.035
0.008
0.071
0.009
100
0.164
0.344
0.125
0.069
0.080
0.022
0.099
0.023
200
0.028
0.135
0.302
0.389
0.167
0.083
0.153
0.057
300
0
0.017
0.282
0.417
0.295
0.353
0.147
0.090
400
0
0
0.135
0.097
0.269
0.458
0.222
0.135
500
0
0
0.021
0.008
0.118
0.074
0.213
0.162
600
0
0
0.002
0
0.032
0.002
0.076
0.203
700
0
0
0
0
0.004
0
0.019
0.321
Mean # of Subj.
7.605
10.251
16.203
16.554
19.356
19.488
20.331
24.696
Mean % of a DLT
38.76
28.91
19.26
16.95
15.55
14.61
15.93
9.97

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 90
LY3009120
From the results, we can see that, in terms of MTD estimation accuracy, the Toxicity band 
method successfully identified the correct MTD with the highest selection percentages under 
each scenario, whereas 3+3 failed to identify the correct MTD with the highest selection 
percentages at half of the scenarios. The MTD determination based on 3+3 algorithm is 
generally one level lower than the true MTD. Moreover, in general, the Toxicity band method 
has a higher correct MTD selection percentage than the 3+3 design, under each scenario.
In terms of the mean number of subjects, the Toxicity band typically needed 4 to 6 more patients 
compared to the traditional 3+3. The mean percentages of a DLT are in general comparable 
across two methods, which indicates that the Toxicity band method is conservative and safe.
In sum, from the simulation studies, the Toxicity band method has a better MTD estimation 
accuracy, and a comparable safety profile, compared to the traditional 3+3 design.
1.6 Dose confirmation Phase
The MTD identified in the escalation phase will continue to be evaluated by the model during the 
dose confirmation. For each confirmation cohort, about 15 patients will be enrolled to ensure 
adequate safety evaluations.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 91
LY3009120
Attachment 11. Protocol JBDA Protocol Amendment 
I6X-MC-JBDA(d) Summary A Phase 1 Study of 
LY3009120 in Patients with Advanced or Metastatic 
Cancer
Overview
Protocol I6X-MC-JBDA, a Phase 1 Study of LY3009120 in Patients with Advanced or 
Metastatic 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:

Added statement around previously generated genetic data to Section 5.3.4 such that 
these data may be requested from medical records for use in the research described in 
Section 5.3.4.3.

Section 5.3.4.3. was updated to clarify that exploratory biomarker analysis will be 
performed on patients enrolled in all cohorts in Part B and not just in Cohort A.  This was 
also updated in the inclusion criterion [3] for Part B. 

Section 8.2.4.1: added statement regarding mandatory tumor biopsies before treatment 
and 2 weeks after treatment for all patients in Part B.

Requirement of archived tissue for Part B is removed from Section 8.2.4.2 and from the 
Part B Baseline Assessment schedule.

Updated Attachment 1, Part B Baseline Assessment schedule to include study tumor 
biopsy for all cohorts.

Updated Attachment 1, Part B During and Poststudy Assessments to include tumor 
biopsy at Day 15, removed PK sampling at Day 28 Cycle 1, and included PK sampling 
for Day 28 Cycle 2 and beyond to keep it consistent with the information in 
Attachment 4.  Text was also added for eye assessments, such that the Day 28 assessment 
can also be performed on the Day 1 of the next cycle (predose).

Updated Attachment 4, Pharmacokinetic Sampling Schedule For Patients in Part B, to 
remove Cycle 1 Day 1 10 hour PK sampling time, added exploratory blood sampling at 
Cycle 1 Day 22, and removed all PK samplings at Day 28 for Cycle 1.

Other minor formatting changes and changes to text were made for consistency and 
clarity.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 92
LY3009120
Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.
5.3.4. Biomarkers
As part of an ongoing effort by Lilly to better understand how to predict which tumors are more 
likely to respond to LY3009120 treatment, the collection of samples for biomarker research is a 
mandatory part of this study.  Additional details about sampling are summarized in 
Sections 8.2.4 and 8.2.5, Attachment 1, Attachment 4, and Attachment 8.
It is possible that biomarker data for patients in the study have already been generated from 
samples that were collected and analyzed before enrolling in this trial.  These may include data 
generated from genetic analyses.  If available, these data may be requested from medical records 
for use in the research described in Section 5.3.4.3.  
5.3.4.3.
Exploratory Analysis of Predictive Biomarkers
Potential predictive biomarkers of efficacy to LY3009120 will be measured in archived tumor 
tissue, tumor tissue from core or excisional biopsies, and plasma.  Core or excisional biopsies for 
exploratory biomarker analysis will be performed on patients enrolled in all cohorts in Part B 
Cohort A (see Section 6.1.1 Inclusion Criteria Criterion [3]) before receiving the first dose of 
study drug, but this will not delay treatment.  Exploratory biomarker analysis may be performed 
on preexisting archival samples from patients in Part A and Part B.  The predictive biomarkers to 
be studied may include, but not limited to, somatic alterations in cancer-related genes such as 
B-Raf, NRas, KRas, and cKIT.  In plasma, analysis of biomarkers may include, but not limited 
to, potential nucleic acid predictive profiles to better understand the disease process and to 
develop predictive biomarkers.
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.
…
[3]
Part A and Part B Cohort A:  Have a tumor that is safely amenable to core 
needle or excisional biopsies

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 93
LY3009120
[8]
Have discontinued all previous therapies for cancer (including chemotherapy, 
immunotherapy, corticosteroids, and radiotherapy) and recovered from the 
acute effects of therapy (treatment related toxicity resolved to Grade 1 or less) 
for at least 5 half-lives or a maximumminimum of 4 weeks, (at least 42 days 
for mitomycin-C or nitrosoureas, 14 days for radiotherapy), prior to initiating 
study treatment.
8.2.4.1.
Tissue Collection for Pharmacodynamic Studies
Part A: Mandatory tumor biopsies should be collected prior to treatment (following 
determination of eligibility [≤14 days of C1 D1]) and after 4 weeks of treatment (C1 D28 ± 
14 days) for patients added to any cohort that will be expanded to determine MTD and/or for 
patients added to any cohort expanded to explore potential for Phase 2 dosing on the basis of PK 
data.  Biopsy samples taken within 6 months prior to enrollment will also be permitted as long as 
patients have not received any recent therapies for the disease prior to starting LY3009120.  
Sponsor will need to review and approve the timing of in-treatment biopsies performed outside 
of the allowed 14-day window.
Part B: Mandatory tumor biopsies should be collected before treatment (following 
determination of eligibility [≤14 days of C1 D1]) and after 2 weeks of treatment (C1 D15 ± 
5 days). Biopsy samples taken within 6 months before enrollment will also be permitted as long 
as patients have not received any recent therapies for the disease prior to starting LY3009120.  
Tumor tissue biopsies taken either by core needle or excisional biopsy are acceptable provided 
adequate slides can be obtained.  Cytologic samples and fine-needle aspiration specimens are not 
acceptable.  Pathology notes accompanying the archived diagnostic tissue may also be requested.
Details for the handling and shipping of tumor biopsy samples will be provided in a separate 
document.  Instructions and supplies required for the collection, processing, and shipment of the 
patients’ samples will be provided by the sponsor.
The tumor tissue 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.
8.2.4.2.
Tissue Collection for Tailoring Biomarker Studies
Tumor and plasma specimens will be collected throughout the study for the assessment of 
predictive biomarkers related to the activity of LY3009120, for exploratory research on new 
biomarkers related, but not limited, to the Raf pathway, and for evaluation of tumor specific 
biomarkers depending on evolving science.
Archived tissue:  Precut, unstained slides from any available archival specimen of the patient’s 
tumor will be required from patients enrolled in Part B and will be requested (but not required) 
for patients enrolled in Part A.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 94
LY3009120
Study tumor biopsies: In addition, patients enrolled in Part B Cohort A (Section 6.1.1 Inclusion 
Criteria [3]) will undergo a mandatory pre-treatment tumor biopsy before receiving the first dose 
of study drug.    
For Part A and Part B: Mandatory tumor biopsies will be collected as indicated in 
Section 8.2.4.1.
Tumor tissue biopsies will be taken either by core needle or excisional biopsy.  The size of the 
sample will be dependent upon the procedure utilized to obtain the sample.  These 
biomarker-related studies will include, but may not be limited to, protein and/or genetic analyses 
of the tumor specimen.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 95
LY3009120
Attachment 1.  Protocol JBDA Study Schedule
Part B: Baseline Assessments
Relative Day Prior to 
Day 1 of Cycle 1
28
14
3
Comments
Informed Consent 
Informed Consent Form signed (prior to performance of any 
protocol-specific tests/procedures)
Chest X-ray
X
May be omitted in patients having a chest CT scan for their 
radiological tumor assessment
Radiological Tumor 
Assessment
X
Medical History
X
Including any alcohol/tobacco habits
Physical Exam
X
Vital Signs 
X
Including temperature, blood pressure, pulse rate, 
respiration rate
ECOG Performance Status
X
ECG 
X
Central collection and storage
Hematology (local)
X
aPTT, PT, PT/INR (local)
X
Serum Chemistry 
X
Urinalysis (local)
X
Tumor Measurement 
(Palpable or Visible)
X
CTCAE v 4.0 Grading 
(Preexisting conditions)
X
To be reported only after study eligibility is confirmed.
Concomitant Meds
X
Exploratory blood plasma 
sample 
X
EDTA tube collection after eligibility confirmed
Study Tumor Biopsy 
(Part B, Cohort A only all
cohorts)
X
Biopsy should be taken only after study eligibility is 
confirmed (mandatory). 
Archived Tumor Sample
X
Paraffin-embedded tumor tissue (mandatory).  Sent after 
study eligibility is confirmed.
Pregnancy Test (local)
X
Negative results required prior to Cycle 1, Day 1.  Only to 
be performed on women of childbearing potential. 
Eye Safety Assessments
X
Dermatological Evaluation
X
Abbreviations:  aPTT = activated partial thromboplastin time; CT = computed tomography; CTCAE = Common 
Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology 
Group; Meds = medications; PD = pharmacodynamic; PT/INR = prothrombin time/international normalized 
ratio.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 96
LY3009120
Part B: During and Poststudy Assessments
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after last 
dose of study drug; Visits 802, 803, and 
804 are each 2 months in duration and 
will start after Visit 801.
LY3009120
X
X
X
Physical Exam
X
X
X
X
X
X
X
After C1D1, ± 3 days while on 
treatment; Will not need to be repeated 
if performed ≤3 days from C1D1.
Eye Assessments
X
X
At baseline,  at the end of Cycle 1 and 
Cycle 2, and every 2 cycles afterwards 
(end of C4, C6, and so on) up to 7 days 
before start of next cycle, and at other 
time points if clinically indicated. 
Assessment can also be performed on 
the D1 of the next cycle (predose).
Dermatological 
Evaluation
X
X
At baseline, every 2 cycles while on 
therapy, and every 2 months for up to 
6 months following discontinuation of 
LY3009120.
Weight
X
X
X
After C1D1, ± 3 days while on treatment
Vital Signs 
X
X
X
X
X
X
Temperature, PR, RR, BP.  After C1D1, 
± 3 days while on treatment.
ECG
X
X
X
X
In cycle 1 only, on days with PK 
assessments ECGs will be performed 
before patients receive morning dose of 
study drug at the site and 3 hours post-
dosing 
After C2D1, ± 3 days while on 
treatment. 

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 97
LY3009120
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after last 
dose of study drug; Visits 802, 803, and 
804 are each 2 months in duration and 
will start after Visit 801.
Hematology
X
X
X
X
X
X
X
X
X
X
After C2D1, ± 3 days while on 
treatment; On days with PK assessment 
it will be performed before patients 
receive morning dose of study drug at 
the site.
Serum Chemistry
X
X
X
X
X
X
X
X
X
X
After C2D1, ± 3 days while on 
treatment; On days with PK assessment 
it will be performed before patients 
receive morning dose of study drug at 
the site.
Urinalysis
X
X
X
After C1D1, ± 3 days while on 
treatment; will not need to be performed 
if completed less than 3 days before 
Cycle 1 Day 1.
CTCAE v 4.0 Grading
X
X
X
X
Throughout study as needed.
Concomitant Meds
X
X
X
X
Throughout study as needed.
ECOG Performance 
Status
X
X
X
After C1D1, ± 3 days while on treatment
PK Sampling 
X
X
X
X
X
X
See PK Sampling Attachment 4 for 
exact timing.
Tumor Measurement 
(Palpable or Visible)
X
X
X
X
After C1D1, ± 3 days while on treatment
Radiological Tumor 
Assessment
X
X
X
Approximately every 8 weeks (every 
other cycle, end of C2, C4, and so on).  
Up to 7 days before start of next cycle.
Urine Metabolite 
Collection
X
To be collected from up to 3 patients 
enrolled in Part B; not a protocol 
violation if not collected.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 98
LY3009120
Cycle 1
Cycle 2
Cycle 3-n
Follow-Up
Comments
Relative Day Within a 
Cycle
1
8
15
22
28
1
8
15
22
28
1
28
Visit 
801
Visits 802, 
803, and 804 
(Long-term 
Follow-up)
Visit 801 is 30 days (± 3 days) after last 
dose of study drug; Visits 802, 803, and 
804 are each 2 months in duration and 
will start after Visit 801.
Pharmacogenetic blood 
sample, stored 
(mandatory)
X
Exploratory blood 
plasma sample
X
X
X
X
X
To be collected in all patients in Part B 
for a maximum of 9 to 12 cycles. 
Study Tumor Biopsy 
X
Can be ±5 days
Abbreviations:  BP = blood pressure; CTCAE = Common Terminology Criteria for Adverse Events; ECG = electrocardiogram; ECOG = Eastern Cooperative 
Oncology Group; PK = pharmacokinetic; PD = pharmacodynamic; PR = pulse rate; RR= respiration rate.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 99
LY3009120
Attachment 4.  Protocol JBDA Pharmacokinetic and Exploratory Blood Plasma Sampling 
Schedule
Pharmacokinetic Sampling Schedule For Patients in Part B
Sample 
Number
Cycle
Day
PK Sampling Time for 
LY3009120a
Exploratory 
Blood Sampleb
Urine Sampling 
(Part B only- up to 
3 patients)
1
1
1
predose
X
0 to 10h pooled 
samples (end time 
to coincide with PK 
blood draw)
2
1
1
0.5
3
1
1
1
4
1
1
2
5
1
1
4
6
1
1
6
7
1
1
8
8
1
1
10
98
1
15
predose
109
1
22
predose
X
11
1
28
predose
X
12
1
28
0.5
13
1
28
1
14
1
28
2
15
1
28
4
16
1
28
6
17
1
28
8
18
1
28
10
1910
2
28
predose
X
2011
3-n
28
predose
X
2112
Follow-up 
(Visit 801)
-
-
X
a Predose PK samples should be collected prior to the morning dose, and all samples collected as close to the 
scheduled times as possible.
b Baseline exploratory blood plasma sample (EDTA tube) will be collected ≤14 days before first dose of 
LY3009120 after eligibility is confirmed.  Samples will also be collected during treatment predose on Day 22 of 
Cycle 1, and Day28 of each cycle thereafter; and during follow-up Visit 801.  During treatment this sample will be 
collected for a maximum of 9 to 12 cycles.

I6X-MC-JBDA(d) Phase 1 Oncology Protocol
Page 100
LY3009120
Attachment 8.  Protocol JBDA Sampling Summary
This table summarizes the maximum number of samples and volumes for all sampling, and tests 
during the study.  The summary below provides estimates.  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).
Protocol I6X-MC-JBDA Sampling Summary
Purpose
Sample 
Type
Maximum
Amount per Sample
Maximum
Number of Samples
Maximum
Total Amount
Study qualificationa
Blood
12 mL
1
12 mL
Health Monitoring (may be 
more than 1 tube)b
Blood
9 mL
11
99 mL
Drug concentrationc
Blood
3 mL
26
78 mL
Pharmacogenetic stored sample
Blood
10 mL
1
10 mL
Tailoring biomarkers
Blood
10 mL
14
140 mL
PD samplesd (Part A, 
designated expansion cohorts)
Tumor 
tissue
2 biopsies
2 biopsies
Other exploratory sample 
(Part B, Cohort Aall cohorts)
Tumor 
tissue
1 biopsy 2 biopsies
1 biopsy2 
biopsies
B-Raf status assessment biopsyf
Tumor 
tissue
1 biopsy
1 biopsy
Hepatic Monitoringe
Blood
3 - 30 mL
-
-
Total 
Blood: 339 mL
Tissue: 2 biopsies
a Additional samples may be drawn if needed for safety purposes.
b Total volume based on average number of 5 cycles.
c Part A:  26 PK time points; Part B:  18 9 PK time points.
d Only for patients in designated Part A expansion cohorts as noted in Section 8.2.4.1.
e 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.
f Only for patients without historical B-Raf mutation test results or adequate archived tumor tissue sample available 
for genetic testing (Section 8.2.2).

PPD
Leo Document ID = e01811d3-1bff-4d54-86e1-85d73545ead3
Approver: 
Approval Date & Time: 08-Jan-2016 03:37:45 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 08-Jan-2016 21:42:32 GMT
Signature meaning: Approved
PPD