A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a Single Agent and in Combination With Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients With Relapsed or Refractory Solid Tumors
Phase: PHASE1
Conditions: Neoplasm Metastasis
Sponsor: Eli Lilly and Company

I5B-MC-JGDN(b) Phase 1 Oncology Protocol 
A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a Single Agent and in 
Combination with Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric 
Patients with Relapsed or Refractory Solid Tumors 
 
NCT02677116 
 
Approval Date: 14-Feb-2018 
 
 
 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 1
LY3012207
1.
Protocol I5B-MC-JGDN(b)
A Phase 1, Open-Label, Dose-Escalation Study of 
Olaratumab as a Single Agent and in Combination with 
Doxorubicin, Vincristine/Irinotecan, or High-Dose 
Ifosfamide in Pediatric Patients with Relapsed or 
Refractory Solid Tumors
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 
olaratumab (LY3012207), unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries. This document and its associated 
attachments are subject to United States Freedom of Information Act (FOIA) Exemption 4.
Olaratumab (LY3012207)
This Phase 1 study is a multicenter, open-label, dose-escalation study of olaratumab 
(LY3012207) as a single agent and in combination with either doxorubicin, 
vincristine/irinotecan, or high-dose ifosfamide in pediatric patients with relapsed or 
refractory solid tumors.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly: 16 November 2015           
Amendment (a) Electronically Signed and Approved by Lilly: 22 September 2016
Amendment (b) Electronically Signed and Approved by Lilly
on approval date provided below
Approval Date: 14-Feb-2018 GMT

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 2
LY3012207
2.
Synopsis
This Phase 1 study is a multicenter, open-label, dose-escalation study of olaratumab 
(LY3012207) as a single agent and in combination with either doxorubicin, 
vincristine/irinotecan, or high-dose ifosfamide in pediatric patients with relapsed or refractory 
solid tumors.
Clinical Protocol Synopsis:  Study I5B-MC-JGDN
Name of Investigational Product:  Olaratumab (LY3012207)
Title of Study:  A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a Single Agent and in 
Combination with Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients with Relapsed 
or Refractory Solid Tumors
Number of Planned Patients:
Entered/Screened: Approximately 110
Enrolled:  Minimum 24
                 Maximum 79
Phase of Development:  1
Length of Study:
Planned first patient visit:  11 February 2016
Planned last patient visit:  05 June 2019
Objectives:
The primary objective of this study is to determine a recommended dose of olaratumab in combination with at least 
one of the studied chemotherapy regimens in pediatric patients based on any dose-limiting toxicities (DLTs) as well 
as olaratumab serum exposure-matching between the adult and pediatric populations.
The secondary objectives of this study are:

to investigate the pharmacokinetics (PK) of olaratumab as monotherapy and in combination with either 
doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients;

to assess the possible development of antibodies against olaratumab (immunogenicity) in pediatric patients; 
and

to document any antitumor activity (including progression-free survival and objective response rate [ORR]) 
observed with olaratumab in combination with either doxorubicin, vincristine/irinotecan, or high-dose 
ifosfamide in pediatric patients.
The exploratory objective of this study is:

to identify exploratory biomarkers associated with tumor response and/or safety.
Study Design:  Study JGDN is a multicenter, dose-escalation, open-label Phase 1 pediatric safety clinical trial with 
3 distinct components, Part A, Part B, and Part C.
Part A will consist of at least 12 evaluable pediatric patients.  These patients will be treated for 1 cycle (21 days) of 
olaratumab monotherapy at 15 mg/kg on Day 1 and Day 8 (adult dose for which efficacy was observed in 
Study I5B-IE-JGDG).  If the patient does not experience a DLT in the first cycle of monotherapy, or meet any other 
criteria for discontinuation, the patient will then receive olaratumab (15 mg/kg) plus one of 3 standard chemotherapy 
regimens (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per investigator discretion).  Treatment will 
continue until disease progression or other discontinuation criteria are met.
Part B will be initiated after the following criteria have been met:

Acceptable safety results, which must include a minimum of 6 evaluable patients, and the PK profile from 
Part A monotherapy.

At least one of the 15 mg/kg combination arms has met the following DLT criteria: less than one-third 
(that is, approximately 33.3% [minimum of 3 patients]) DLT rate.  Only the combination arms in Part A 
that have met these criteria may be studied in Parts B and C.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 3
LY3012207
Part B patients will be treated for 1 cycle (21 days) of olaratumab monotherapy at 20 mg/kg on Day 1 and Day 8
then receive olaratumab (20 mg/kg) plus one of 3 standard chemotherapy regimens described in Part A. Part B will 
be complete when at least 10 patients (regardless of assigned chemotherapy arm) are evaluable for safety of
olaratumab 20 mg/kg monotherapy.  Part C will be initiated when at least 10 patients (regardless of chemotherapy 
arm) are evaluable for safety of olaratumab 20 mg/kg from Part B. Part C patients will receive olaratumab 
(20 mg/kg) in combination with any of the 3 chemotherapy regimens (per investigator discretion) from Cycle 1 
onward (i.e no olaratumab monotherapy in Cycle 1 of Part C).  Parts B and C together will enroll up to 45 patients 
(15 per chemotherapy arm).  Treatment will continue until disease progression or other discontinuation criteria are 
met.
Diagnosis and Main Criteria for Inclusion and Exclusions: Eligible patients will be <18 years of age with a 
diagnosis of relapsed or refractory solid tumors not amenable to curative treatment, for whom chemotherapy with 
doxorubicin, vincristine/irinotecan, or high-dose ifosfamide is deemed appropriate by the investigator.  In addition,
the patient must have adequate performance status by Lansky or Karnofsky and adequate hematologic, organ, and 
coagulation function.  The patient must not have a hematologic malignancy, uncontrolled intercurrent illness, or 
active infection.
Test Product, Dosage, and Mode of Administration:
Olaratumab:  for intravenous (IV) use, supplied in single-use 500 mg/50 mL vials containing 10 mg/mL of product 
in histidine buffer, administered to patients as an IV infusion at 15 or 20 mg/kg on Day 1 and Day 8 of each cycle.  
Cycles are 21 days in length.
Doxorubicin:  will be administered intravenously.  Doxorubicin (37.5 mg/m2) is to be administered on Day 1 and 
Day 2 of each 21-day cycle, for up to 6 cycles or a cumulative dose of 450 mg/m2.
Dexrazoxane:  may be administered at a 10:1 ratio (dexrazoxane:doxorubicin) at the investigator’s discretion via IV 
injection, beginning 30 minutes prior to each doxorubicin infusion for the prevention of cardiotoxicity.  It is 
recommended that all patients receiving doxorubicin also receive dexrazoxane.  Dexrazoxane should be 
administered after completion of the olaratumab infusion, prior to administration of doxorubicin.  
Vincristine:  will be administered intravenously.  Vincristine (patients ≥ 10 kg: 1.5 mg/m2, patients <10 kg:  
0.05mg/kg.  Dose is capped at 2 mg) is to be administered on Day 1 and Day 8 of each 21-day cycle.
Irinotecan:  will be administered intravenously.  Irinotecan (50 mg/m2) is to be administered on Days 1, 2, 3, 4, and 
5 of each 21-day cycle.
Ifosfamide:  will be administered intravenously.  Ifosfamide (2.8 g/m2) is to be administered on Days 1, 2, 3, 4, and 
5 of each 21-day cycle, for up to 6 cycles or a cumulative dose of 84 g/m2.  
Mesna:  commercial formulations will be used and administered intravenously.  Mesna should be administered at a 
minimum dose equal to 60% of the ifosfamide dose according to institutional guidelines.  
Planned Duration of Treatment:
The planned duration of treatment is not fixed; patients will remain on study until they fulfill one of the criteria for 
study discontinuation.  
Follow-up in post-treatment discontinuation:  30 days (±7 days) for patients with disease progression.  For patients 
who have discontinued study treatment due to toxicity or reasons other than progressive disease, follow-up will 
continue every 6 weeks (±7 days) until progression.
Criteria for Evaluation:
Efficacy:  
Radiographic assessments will be performed at baseline and then every 2 cycles (±7 days) until radiographic 
documentation of progressive disease.  Response Evaluation Criteria In Solid Tumors, Version 1.1 criteria should be 
used for all solid tumors with the exception of central nervous system tumors.  Response Assessment in Neuro-
Oncology Criteria or Macdonald Criteria should be used for central nervous system tumors.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 4
LY3012207
Safety:  The safety and tolerability of the study treatment is determined by reported adverse events (AEs), physical 
exam including vital signs, clinical laboratory tests, electrocardiograms, and results of echocardiogram / multigated 
acquisition scans.  Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®) and graded using National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) Version 4.0 and summarized by System Organ Class and preferred term.
Pharmacokinetic/Pharmacodynamic:
Blood samples will be collected at various time points for PK assessment for olaratumab levels and the levels of the 
combination chemotherapies.  Blood samples will be collected at various time points for immunogenicity analysis.
Tailoring Genetics and Biomarkers:
Samples will be collected at various time points for nonpharmacogenomic biomarker research.  A whole blood 
sample will be collected for pharmacogenomics analysis.
Tumor Tissue Biomarker:
Patients may provide a previously archived primary or metastatic tumor tissue sample (paraffin block or unstained 
slides).  Additional voluntary pre- and post-treatment tumor tissue samples may be requested for further biomarker 
research.
Statistical Methods:
The primary objective of this study is to determine a safe dose of olaratumab alone or in combination with 
chemotherapy regimens that can be administered to pediatric patients.  The study will enroll a minimum of 
12 patients in Part A.  Safety reviews will be performed prior to opening Parts B and  C of the study.
Safety:
Adverse events (AEs), including treatment-emergent AEs, will be listed and summarized in frequency tables using 
MedDRA.  Severity of AEs will be classified using CTCAE Version 4.0.  Other safety data, such as laboratory tests, 
echocardiography, and vital signs, will be listed and summarized, if appropriate.
Pharmacokinetics:  The PK parameters of olaratumab will be computed by nonlinear mixed effect modeling using 
.  PK data collected for doxorubicin will be analyzed using descriptive methods.
Immunogenicity:  Incidence of anti-olaratumab antibodies and any additional related assays will be tabulated.  
Correlation to olaratumab drug level, activity, and safety will be assessed, as appropriate.
Efficacy:  Exploratory efficacy analysis will be performed to investigate antitumor activity within each combination 
arm.  Progression-free survival curves and the median with 90% confidence interval (CI) will be estimated using 
Kaplan-Meier method.  The objective response rate (ORR = complete response [CR] + partial response [PR]) and 
disease control rate (DCR=CR + PR + stable disease) and the 90% exact CI will be tabulated for each cohort.
Biomarkers:  Analyses will be performed on biomarkers relevant to pathways associated with soft tissue sarcoma, 
the mechanism of action of olaratumab, and/or cancer-related conditions.  Assay results will be summarized and 
correlated with clinical outcomes.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 5
LY3012207
3.
Table of Contents
A Phase 1, Open-Label, Dose-Escalation Study of 
Olaratumab as a Single Agent and in Combination with 
Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide 
in Pediatric Patients with Relapsed or Refractory Solid
Tumors
Section
Page
1.
Protocol I5B-MC-JGDN(b)  A Phase 1, Open-Label, Dose-
Escalation Study of Olaratumab as a Single Agent and in 
Combination with Doxorubicin, Vincristine/Irinotecan, or High-Dose 
Ifosfamide in Pediatric Patients with Relapsed or Refractory Solid 
Tumors ...............................................................................................................................1
2.
Synopsis .............................................................................................................................2
3.
Table of Contents................................................................................................................5
4.
Abbreviations and Definitions...........................................................................................12
5.
A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a 
Single Agent and in Combination with Doxorubicin, 
Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients 
with Relapsed or Refractory Solid Introduction.................................................................17
5.1.
Rationale and Justification for the Study ......................................................................17
5.2.
Objectives ....................................................................................................................19
5.2.1.
Primary Objective ................................................................................................19
5.2.2.
Secondary Objectives...........................................................................................19
5.2.3.
Exploratory Objectives.........................................................................................19
5.3.
General Introduction to Olaratumab .............................................................................20
5.3.1.
Mechanism of Action and In Vitro/In Vivo Activity.............................................23
5.3.2.
Nonclinical Pharmacokinetics/Pharmacodynamics...............................................28
5.3.3.
Nonclinical Toxicology........................................................................................28
5.4.
Rationale for Selection of Dose....................................................................................29
6.
Investigational Plan...........................................................................................................31
6.1.
Study Population..........................................................................................................31
6.1.1.
Inclusion Criteria .................................................................................................31
6.1.2.
Exclusion Criteria ................................................................................................33
6.2.
Summary of Study Design............................................................................................34
6.2.1.
Primary Endpoint.................................................................................................37
6.2.2.
Study Completion and End of Trial......................................................................37
6.3.
Discontinuations ..........................................................................................................37

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 6
LY3012207
6.3.1.
Discontinuation of Patients...................................................................................37
6.3.2.
Discontinuation of Study Sites .............................................................................39
6.3.3.
Discontinuation of the Study................................................................................39
7.
Treatment..........................................................................................................................40
7.1.
Materials and Supplies .................................................................................................40
7.2.
Study Drug Administration ..........................................................................................40
7.2.1.
Premedication ......................................................................................................40
7.2.2.
Dosing Schedule ..................................................................................................42
7.2.3.
Dose Progression through Study Parts..................................................................45
7.2.3.1.
Dose-Limiting Toxicity Determination and Maximum 
Tolerated Dose Definition...............................................................................46
7.2.3.2.
Dose-Escalation Method.................................................................................46
7.2.4.
Dose Adjustments and Delays..............................................................................47
7.2.4.1.
Olaratumab.....................................................................................................48
7.2.4.1.1.
Infusion-Related Reactions .......................................................................48
7.2.4.1.2.
Hematologic Toxicity ...............................................................................49
7.2.4.1.3.
Nonhematologic Toxicity..........................................................................50
7.2.4.2.
Doxorubicin Dose Adjustments ......................................................................51
7.2.4.2.1.
Hematologic Toxicity ...............................................................................51
7.2.4.2.2.
Cardiac Monitoring for Doxorubicin-Associated 
Cardiotoxicity...........................................................................................52
7.2.4.2.3.
Hepatic Impairment ..................................................................................52
7.2.4.3.
Vincristine Dose Adjustments.........................................................................53
7.2.4.3.1.
Hematologic Toxicity ...............................................................................53
7.2.4.3.2.
Nonhematologic Toxicity..........................................................................53
7.2.4.3.2.1.
Neurologic Toxicity............................................................................53
7.2.4.3.2.2.
Hepatic Toxicity .................................................................................54
7.2.4.4.
Irinotecan Dose Adjustments..........................................................................54
7.2.4.4.1.
Hematologic Toxicities.............................................................................54
7.2.4.4.2.
Diarrhea and Cholinergic Reactions..........................................................55
7.2.4.5.
Ifosfamide Dose Adjustments.........................................................................56
7.2.4.5.1.
Urotoxic Effects........................................................................................56
7.2.4.5.2.
Proximal Tubular Damage ........................................................................56
7.2.4.5.3.
Central Nervous System............................................................................57
7.2.4.5.4.
Other Toxicities ........................................................................................57
7.3.
Method of Assignment to Treatment ............................................................................58
7.4.
Blinding .......................................................................................................................58
7.5.
Concomitant Therapy...................................................................................................58

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 7
LY3012207
7.5.1.
Supportive Care ...................................................................................................59
7.5.1.1.
Dexrazoxane...................................................................................................59
7.5.1.2.
Mesna.............................................................................................................59
7.5.1.3.
Hydration .......................................................................................................59
7.5.1.4.
Granulocyte-Colony Stimulating Factors and Erythroid 
Growth Factors...............................................................................................59
7.5.1.5.
Transfusion of Blood Products........................................................................60
7.5.1.6.
Antiemetic Therapy........................................................................................60
7.5.2.
Prohibited Therapies ............................................................................................60
7.5.2.1.
Effect of CYP3A4, CYP2D6, and P-gp Inhibitors and 
Inducers on Doxorubicin ................................................................................60
7.6.
Treatment Compliance .................................................................................................60
7.6.1.
Evaluable Patients................................................................................................60
8.
Safety, Pharmacokinetic, Pharmacodynamic, and Efficacy Data 
Collection .........................................................................................................................62
8.1.
Safety Evaluations........................................................................................................62
8.1.1.
Safety Data Collection and Review ......................................................................62
8.1.2.
Adverse Events ....................................................................................................62
8.1.2.1.
Serious Adverse Events ..................................................................................64
8.1.2.2.
Adverse Event and Serious Adverse Event Reporting .....................................65
8.1.2.2.1.
Prior to Administration of Study Drug(s) ..................................................65
8.1.2.2.2.
On Therapy...............................................................................................65
8.1.2.2.3.
Follow-Up Visit........................................................................................65
8.1.2.3.
Suspected Unexpected Serious Adverse Reactions..........................................66
8.1.2.4.
Summary of AE/SAE Reporting Guidelines ...................................................66
8.1.3.
Other Safety Measures .........................................................................................67
8.1.3.1.
Electrocardiograms.........................................................................................67
8.1.3.2.
Echocardiograms and Multigated Acquisition (MUGA) 
Scan ...............................................................................................................68
8.1.4.
Safety Monitoring ................................................................................................68
8.1.5.
Complaint Handling.............................................................................................69
8.2.
Sample Collection and Testing.....................................................................................69
8.2.1.
Samples for Study Qualification and Health Monitoring.......................................69
8.2.2.
Pharmacokinetic Samples.....................................................................................69
8.2.3.
Samples for Tailoring Genetics Biomarkers .........................................................70
8.2.4.
Samples for Immunogenicity Research.................................................................71
8.2.5.
Tailoring Biomarker Samples...............................................................................71
8.3.
Efficacy Evaluations ....................................................................................................72
8.4.
Procedure/Sampling Compliance..................................................................................72

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 8
LY3012207
9.
Data Management Methods...............................................................................................74
9.1.
Data Quality Assurance................................................................................................74
9.2.
Data Capture Systems ..................................................................................................74
9.2.1.
Case Report Form ................................................................................................74
9.2.2.
Ancillary Data......................................................................................................75
10.
Data Analyses ...................................................................................................................76
10.1. General Considerations ................................................................................................76
10.2. Patient Disposition .......................................................................................................76
10.3. Patient Characteristics ..................................................................................................76
10.4. Safety Analyses............................................................................................................76
10.5. Pharmacokinetic Analyses............................................................................................76
10.6. Immunogenicity Analyses ............................................................................................77
10.7. Efficacy Analyses ........................................................................................................77
10.8. Interim Analyses ..........................................................................................................77
10.9. Biomarker Analyses.....................................................................................................78
11.
Informed Consent, Ethical Review, and Regulatory Considerations ..................................79
11.1. Informed Consent.........................................................................................................79
11.2. Ethical Review.............................................................................................................79
11.3. Regulatory Considerations ...........................................................................................80
11.3.1.
Investigator Information.......................................................................................80
11.3.2.
Protocol Signatures ..............................................................................................80
11.3.3.
Final Report Signature .........................................................................................80
12.
References ........................................................................................................................81

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 9
LY3012207
List of Tables
Table
Page
Table JGDN.5.1. Chemotherapeutic Agents Used in Combination with Olaratumab .................20
Table JGDN.5.2. Summary of Common Adverse Events (Grade 3 and Grade ≥4)
Study JGDG
Safety Population (Phase 2) ...........................................................................22
Table JGDN.7.1. Treatment Regimens/Dosing Schedule (Parts A and B)..................................44
Table JGDN.7.2 Treatment Regimens/Dosing Schedule (Part C) .............................................45
Table JGDN.7.3. Olaratumab Dose Levels and Adjustments for Olaratumab-related 
Toxicities.......................................................................................................47
Table JGDN.7.4. General Guidelines for Olaratumab Dose Modification Due to 
Hematologic Toxicity Deemed Related to Olaratumab...................................50
Table JGDN.7.5. General Guidelines for Dose Modification Due to Nonhematologic 
Toxicities Related to Olaratumab...................................................................51
Table JGDN.7.6. General Guidelines for Doxorubicin Dose Modification Due to 
Neutropenia...................................................................................................52
Table JGDN.7.7. General Guidelines for Doxorubicin Dose Modification Due to 
Elevated Serum Total Bilirubin Concentrations .............................................53
Table JGDN.7.8. General Guidelines for Dose Modification of Vincristine due to 
Toxicity.........................................................................................................54
Table JGDN.7.9. General Guidelines for Vincristine Dose Modification Due to Elevated 
Serum Total Bilirubin Concentrations............................................................54
Table JGDN.7.10.
Dose Levels and Adjustments for Irinotecan.............................................55
Table JGDN.7.11.
General Guidelines for Dose Modification of Irinotecan due to 
Toxicity.........................................................................................................56
Table JGDN.7.12.
Dose Modification of Ifosfamide due to Renal Impairment .......................57
Table JGDN.7.13.
General Guidelines for Dose Modification of Ifosfamide due to 
Toxicity.........................................................................................................57
Table JGDN.7.14.
Dose Modification of Ifosfamide due to Hepatic Impairment ....................58
Table JGDN.8.1. Adverse Event and Serious Adverse Reporting Guidelines for Patients 
Enrolled in Study JGDN ................................................................................67

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 10
LY3012207
List of Figures
Figure
Page
Figure JGDN.5.1.
Olaratumab significantly reduces proliferation in the MG-63 Human 
Osteosarcoma cell line as a single agent and in combination with 
doxorubicin. ..................................................................................................24
Figure JGDN.5.2.
Olaratumab blocks PDGF-dependent activation of downstream 
signaling proteins in the MG-63 human osteosarcoma cell line using 
Western blot detection.  Phospho protein order (red rectangles, top to 
bottom): pCREB, pERK, pAKT, pWNK1......................................................25
Figure JGDN.5.3.
Activity of olaratumab in the A-204 human rhabdoid mouse 
xenograft model.  Note that “3G3” is the internal designation for 
olaratumab.....................................................................................................26
Figure JGDN.5.4.
Activity of olaratumab as a single agent and in combination with 
doxorubicin in 2 mouse models of human osteosarcoma.  Note that 
IMC-3G3 is the internal designation for olaratumab.......................................26
Figure JGDN.5.5.
Activity of olaratumab in the ST162 human rhabdomyosarcoma 
patient-derived mouse xenograft model.  Note that the red bar indicates 
the dosing period. ..........................................................................................27
Figure JGDN.5.6.
Activity of olaratumab and doxorubicin on ST1547 human 
leiomyosarcoma xenograft model. .................................................................28
Figure JGDN.6.1.
Illustration of Part A of the study design. ..................................................35
Figure JGDN.6.2.
Illustration of Part B of the study design. ..................................................36
Figure JGDN.6.3.
Illustration of Part C of the study design. ..................................................36

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 11
LY3012207
List of Attachments
List of Protocol Attachments
Attachment
Page
Attachment 1.
Protocol JGDN Study Schedule .....................................................................84
Attachment 2.
Protocol JGDN Clinical Laboratory Tests....................................................110
Attachment 3.
Protocol JGDN Hepatic Monitoring Tests for Treatment Emergent 
Abnormality ................................................................................................111
Attachment 4.
Protocol JGDN Pharmacokinetic and Immunogenicity Sampling 
Schedule......................................................................................................112
Attachment 5.
Protocol JGDN Recommendations for Reporting 
Serious Adverse Events ...............................................................................115
Attachment 6.
Protocol JGDN Creatinine Clearance Formula.............................................116
Attachment 7.
Protocol JGDN Sampling Summary.............................................................117
Attachment 8.
Protocol JGDN RECIST Criteria 1.1 ...........................................................118
Attachment 9.
Protocol JGDN List of CYP3A4, CYP2D6, and P-gp Inhibitors and 
Inducers of Doxorubicin ..............................................................................125
Attachment 10.
Protocol JGDN Protocol Amendment 
I5B-MC-JGDN(b) Summary 
A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a 
Single Agent and in Combination with Doxorubicin, 
Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients 
with Relapsed or Refractory Solid Tumors...................................................127

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 12
LY3012207
4.
Abbreviations and Definitions
Term
Definition
ADA
anti-drug antibody
AE
Adverse event:  Any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product that does not 
necessarily have a causal relationship with this treatment.  An adverse event 
(AE) can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with 
the use of medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product.
ALT
alanine aminotransferase
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
area under the plasma concentration-time curve
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).
CHF
congestive heart failure
CI
confidence interval
Cmin
minimum plasma concentration
Cmin,1
minimum serum concentration at the end of Cycle 1
CNS
central nervous system
collection database
A computer database where clinical trial data are entered and validated.
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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 13
LY3012207
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
CRF/eCRF
case report form/electronic case report form:  Sometimes referred to as clinical 
report form, a printed or electronic form for recording study participants’ data 
during a clinical study, as required by the protocol.
CRP
clinical research physician
CRS
clinical research scientist
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DCR
disease control rate
DLT
dose-limiting toxicity
ECG
electrocardiogram
ECHO
echocardiogram
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.
GCP
good clinical practice
G-CSF
granulocyte colony stimulating factors
HIV
human immunodeficiency virus
HR
hazard ratio
IB
Investigator’s Brochure

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 14
LY3012207
ICF
informed consent form
ICH
International Conference on Harmonisation
IgG1
immunoglobulin subclass G1
INR
international normalized ratio
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.
IRR
infusion-related reaction
IV
intravenous
IWRS
Interactive Web Response System
legal representative
An individual, judicial, or other body authorized under applicable law to 
consent on behalf of a prospective patient, to the patient’s participation in the 
clinical study.
Lilly Safety System
Global safety database that tracks and reports serious adverse and spontaneous 
events occurring while using a drug/drug delivery system.
LMS
leiomyosarcoma
LVEF
left ventricular ejection fraction
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
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

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 15
LY3012207
mRNA
messenger ribonucleic acid
MTD
maximum tolerated dose
MUGA
multigated acquisition
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NOAEL
no-observable-adverse-effects level
open-label
A study in which there are no restrictions on knowledge of treatment allocation, 
therefore the investigator and the study participants are aware of the drug 
therapy received during the study.
ORR
objective response rate
OS
overall survival
patient
a subject with a defined disease
PD
pharmacodynamic
PDGF
platelet-derived growth factor
PDGFR
platelet-derived growth factor receptor
PDX
patient-derived xenograft
PET
positron emission tomography
PFS
progression-free survival
P-gp
P-glycoprotein
PK
pharmacokinetic
PopPK
population pharmacokinetics
PR
partial response
PT
prothrombin time
PTT or aPTT
partial thromboplastin time
RANO
Response Assessment in Neuro-Oncology
RECIST
Response Evaluation Criteria In Solid Tumors
refractory disease
as disease progression after receiving at least one course of standard 
chemotherapy without prior demonstration of a radiographic response to 
chemotherapy

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 16
LY3012207
relapsed disease
disease progression following demonstration of a radiographic response of the 
primary tumor and or metastatic site or occurrence of new site of disease on or 
off oncologic therapy
reporting database
A point-in-time copy of the collection database.  The final reporting database is 
used to produce the analyses and output reports for interim or final analyses of 
data.
re-screen
To screen a patient who was previously declared a screen failure for the same 
study
RT
radiation therapy
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
SD
stable disease
sponsor
The party who takes responsibility for the initiation, management and/or 
financing of a clinical study.
STS
soft tissue sarcoma
study completion
This study will be considered complete after all patients have completed 
treatment and their safety summary visit.
SUSAR
suspected unexpected serious adverse reactions
TBI
total body irradiation
TCGA
The Cancer Genome Atlas
TE
treatment-emergent
TK
toxicokinetics
TPO
third-party organization
ULN
upper limit of normal

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 17
LY3012207
5.
A Phase 1, Open-Label, Dose-Escalation Study of 
Olaratumab as a Single Agent and in Combination with 
Doxorubicin, Vincristine/Irinotecan, or High-Dose 
Ifosfamide in Pediatric Patients with Relapsed or 
Refractory Solid Introduction
5.1.
Rationale and Justification for the Study
Platelet-derived growth factor receptor α (PDGFRα) autocrine signaling has been implicated in 
the pathogenesis of sarcomas (Fleming et al. 1992; McDermott et al. 2009), which are 
recognized to originate from PDGFR-positive mesenchymal cells.  An analysis of publicly 
available genomic data, including those from The Cancer Genome Atlas (TCGA 2014), shows 
messenger ribonucleic acid (mRNA) overexpression for PDGFRα and platelet-derived growth 
factors (PDGFs) in sarcoma, further implicating this autocrine loop in the pathogenesis of soft 
tissue sarcoma (STS) (data on file).  Preclinical studies of olaratumab as a single agent or in 
combination with chemotherapy have demonstrated antitumor activity in human sarcoma 
xenograft models.
The PDGFR pathway has also been implicated in several pediatric tumors such as gliomas 
(Paugh et al. 2013), sarcomas including rhabdomyosarcoma (Ehnman et al. 2013), osteosarcoma 
(McGary et al. 2002), and Ewing sarcoma (Dubois et al. 2010). In pediatric sarcomas and 
gliomas, several types of genetic alterations, including gene amplification, translocations, and 
activating mutations, resulted in ligand and/or receptor overexpression.  PDGFR gene expression 
in pediatric rhabdomyosarcoma demonstrated decreased failure-free survival for patients with 
tumors that overexpressed either PDGFRα or PDGFRβ mRNA (DuBois and Demetri 2007).
Olaratumab (LY3012207) is a recombinant human immunoglobulin subclass G1 (IgG1) 
monoclonal antibody (mAb) that specifically binds to PDGFRα and has demonstrated activity in 
in vitro and in vivo systems on cancer models known to be driven by a PDGF-PDGFRα 
autocrine loop (Gerber et al. 2012; ImClone Report 4881-10, and data on file).  Once bound to 
PDGFRα, olaratumab blocks PDGF binding and PDGF-induced PDGFRα activation (Loizos et 
al. 2005).  Olaratumab as a single agent has demonstrated in vivo antitumor activity in human 
sarcoma xenograft models.  In addition, the combination of olaratumab plus doxorubicin had 
statistically significant antitumor activity compared to the effects of either monotherapy in 
leiomyosarcoma (LMS) and osteosarcoma xenograft models (ImClone Report 3276-05, ImClone 
Report 3521-05).  The benefit of the doxorubicin plus olaratumab treatment was associated with 
increased tumor cell apoptosis in SKLMS-1 and KHOS/NP xenograft models (LMS and 
osteosarcoma) as compared to both agents on their own (ImClone Report 3764-06, 
ImClone Report 3614-06).  Additional preclinical data (Section 5.3.1) indicated that olaratumab 
showed antitumor activity in pediatric xenografts models, both as a single agent and in 
combination with doxorubicin.
The importance of PDGFRα activity in sarcomas and the preclinical evidence of activity of 
olaratumab in sarcoma (as a single agent or in combination with chemotherapy) provided the 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 18
LY3012207
rationale for evaluating the clinical efficacy and safety of olaratumab plus doxorubicin in the 
treatment of patients with advanced STS in the Phase 1b/2 Study I5B-IE-JGDG (JGDG).  
Patients with Kaposi’s sarcoma and gastrointestinal stromal tumor were not included in the 
study.
As of 22 August 2015, a total of 497 adult patients had been treated with olaratumab.  In the 
randomized portion of Study JGDG (doxorubicin alone or in combination with olaratumab), a 
total of 129 patients with advanced STS were treated.  Interim efficacy and safety data available 
from this study demonstrate a positive benefit-risk assessment for olaratumab treatment 
(discussed in Section 5.3).
Altogether, preclinical and clinical data support exploring olaratumab in combination with 
standard chemotherapy regimens for patients with sarcomas and other pediatric tumors. The 
present Phase 1 study (JGDN) has been developed based on regulatory input and advice from 
external experts, who recommended minimizing the exposure to single-agent therapy in 
pediatrics prior to continuing on standard combination chemotherapy regimens commonly used 
for specific tumor subtypes.  In this regard, the proposed study intends to enroll pediatric patients 
aged from 0 to less than 18 years of age with solid tumors for 1 cycle of olaratumab 
monotherapy and subsequently move to standard therapies with either doxorubicin, or
vincristine/irinotecan, or high-dose ifosfamide.  Olaratumab monotherapy will start at 15 mg/kg, 
a dose which was efficacious in adults (Study JGDG). A dose of 15 mg/kg olaratumab is
expected to achieve a similar serum exposure level in both the pediatric and adult populations
(see Section 5.4). Furthermore, in 2 previous Phase 1 dose-escalation trials (I5B-IE-JGDC 
[JGDC] and I5B-IE-JGDF [JGDF]) and in the 2 Phase 2 monotherapy studies (I5B-IE-JGDE 
[JGDE] and I5B-IE-JGDH [JGDH]) in adults, single-agent olaratumab has consistently been 
well tolerated, with no dose-limiting toxicities (DLTs) observed up to a dose of 16 mg/kg weekly 
times 4 doses in a 6 week cycle, 20 mg/kg administered every 2 weeks, and up to a dose of 15 
mg/kg administered of Day 1 and Day 8 of a 21-day cycle.
The primary objective in Study JGDN will be to assess the safety profile of olaratumab as a 
single agent and in combination with either doxorubicin, vincristine/irinotecan, or high-dose 
ifosfamide.  The secondary objectives will include the pharmacokinetic (PK) profile of 
olaratumab as a single agent and in combination with doxorubicin, vincristine/irinotecan, or 
high-dose ifosfamide and the antitumor activity of the combination chemotherapies.  These 
regimens are recommended according to standard clinical practice in pediatric patients (Sandler 
et al. 2001; Carli et al. 2003; Mascarenhas et al. 2010).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 19
LY3012207
The study consists of 3 parts.  Part A will consist of approximately 12 evaluable pediatric 
patients treated for 1 cycle (21 days) of olaratumab monotherapy at 15 mg/kg on Day 1 and 
Day 8.  If the patient does not experience a DLT in the first cycle of monotherapy, or meet any 
other criteria for discontinuation, the patient will then receive olaratumab (15 mg/kg) plus one of 
3 standard chemotherapy regimens (doxorubicin or vincristine/irinotecan or high-dose
ifosfamide per investigator discretion). Part B patients will be treated for 1 cycle of olaratumab 
monotherapy at 20 mg/kg on Day 1 and Day 8 then receive olaratumab (20 mg/kg) plus one of 
3 standard chemotherapy regimens described in Part A.  Part B will be complete when at least 10 
patients (regardless of assigned chemotherapy arm) are evaluable for safety of olaratumab 
20 mg/kg monotherapy. Part C will be initiated after confirmation of safety of olaratumab 
20 mg/kg from Part B.  Part C patients will receive olaratumab (20 mg/kg) in combination with 
any of the 3 chemotherapy regimens (per investigator discretion) from Cycle 1 onward (i.e no 
olaratumab monotherapy in Cycle 1 of Part C). Parts B and C together will enroll up to 45
patients (15 per chemotherapy arm). Treatment will continue until disease progression or other 
discontinuation criteria are met.
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 dose of olaratumab in 
combination with at least one of the studied chemotherapy regimens in pediatric patients based 
on any DLTs as well as olaratumab serum exposure-matching between the adult and pediatric 
populations.
5.2.2. Secondary Objectives
The secondary objectives of this study are:

to investigate the PK of olaratumab as monotherapy and in combination with either 
doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients;

to assess the possible development of antibodies against olaratumab (immunogenicity) in 
pediatric patients; and

to document any antitumor activity (including progression-free survival [PFS] and 
objective response rate [ORR]) observed with olaratumab in combination with either
doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients.
5.2.3. Exploratory Objectives
The exploratory objective of this study is:

to identify exploratory biomarkers associated with tumor response and/or safety.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 20
LY3012207
5.3.
General Introduction to Olaratumab
Olaratumab is a recombinant human mAb of the IgG1 subclass.  It is composed of 4 polypeptide 
chains, 2 identical heavy (γ) chains consisting of 457 amino acids each and 2 identical light (κ) 
chains consisting of 214 amino acids each. The heavy chain subunit contains 2 consensus 
sequences for potential N-linked glycosylation.  Olaratumab selectively binds to PDGFRα.
Olaratumab has been studied in adult patients with advanced and metastatic cancer.  As of 
30 June 2015, adverse event (AE) information is available for 497 adult patients administered 
olaratumab from 2 Phase 1 monotherapy studies in patients with advanced solid tumors and 
6 Phase 2 studies, including monotherapy and combination therapy studies. Olaratumab was 
well tolerated in Phase 1 monotherapy dose-escalation trials (JGDC and JGDF) (dose ranging 
from 4 to 20 mg/kg administered as 1-hour intravenous [IV] infusions once a week, once every 
2 weeks, or on Day 1 and Day 8 of a 21-day cycle) and no DLTs were observed.
In the Phase 2 trials, olaratumab was given both as a single agent and in combination with other 
chemotherapeutic agents (Table JGDN.5.1) in adult patients with various solid tumor types.  In 
general, olaratumab was well tolerated, with an acceptable and monitorable toxicity profile.  The 
observed safety profile in the combination trials was generally consistent with the safety profile 
of combination chemotherapeutic agents.  No hepatic or renal safety issues were identified in the 
clinical development program either as olaratumab monotherapy or in combination with other 
chemotherapies.
Table JGDN.5.1.
Chemotherapeutic Agents Used in Combination with Olaratumab
Tumor Type
Chemotherapy
Ovarian
Liposomal doxorubicin
Non-small cell lung 
Paclitaxel and carboplatin
Prostate
Mitozantren and prednisone
Soft tissue sarcoma
Doxorubicin
In Study JGDG (adult STS), olaratumab in combination with doxorubicin has an acceptable and 
monitorable safety profile and supports a positive benefit-risk profile in light of the efficacy data.
Lilly has identified infusion-related reactions (IRR) as an important identified risk of olaratumab.  
As with other mAbs, hypersensitivity reactions have been reported with olaratumab 
administration.  IRRs have been primarily Grade 1-2.
Study JGDG was an open-label, randomized Phase 1b/2 study that enrolled doxorubicin-naïve 
patients with advanced STS not amenable to treatment with surgery or radiotherapy. The 
investigational Arm A received olaratumab (15 mg/kg) on Day 1 and Day 8 plus doxorubicin 
(75 mg/m²) on Day 1 of each 21-day cycle for up to 8 cycles.  The control Arm B received 
doxorubicin (75 mg/m2) on Day 1 of each 21-day cycle for up to 8 cycles.
The primary analysis of this trial (based on 103 PFS events observed as of the 15 August 2014 
cutoff date) showed that the predefined, statistical, primary endpoint for PFS was met over 
doxorubicin alone, with a stratified PFS hazard ratio (HR) of 0.67 (p=0.0615 relative to the 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 21
LY3012207
protocol-defined two-sided significance level of alpha=0.1999]).  Based on investigator 
assessment, the median PFS was 28.6 weeks (6.6 months) for the investigational arm and 
18.0 weeks (4.1 months) for the control arm. At the time of this analysis, a total of 84 overall 
survival (OS) events were observed.  The combination of olaratumab and doxorubicin provided a
highly statistically significant improvement of 11.8 months over doxorubicin alone (HR=0.463; 
p = 0.0003); the median OS was 26.5 months in the investigational arm and 14.7 months in the 
control arm.
Adverse events of Grade ≥3 were reported in 76.6% of patients in the investigational arm and 
66.2% of patients in the control arm (Table JGDN.5.2).  The Grade ≥3 AEs in Arm A observed 
with highest incidence were neutropenia (consolidated term), anemia (consolidated term), febrile 
neutropenia, thrombocytopenia, and fatigue.  In the control arm, the Grade ≥3 AEs observed 
with highest incidence were neutropenia (consolidated term), febrile neutropenia, and anemia 
(consolidated term).  The incidence of neutropenia was higher in the investigational arm; 
however, the incidences of febrile neutropenia and infections were similar between arms.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 22
LY3012207
Table JGDN.5.2.
Summary of Common Adverse Events (Grade 3 and Grade ≥4)
Study JGDG
Safety Population (Phase 2)
Preferred Term
Arm A
N = 64
n (%)
Median no. of doxorubicin 
infusions=7
Arm B
N = 65
n (%)
Median no. of doxorubicin 
infusions=4
Grade 3 
Grade ≥4
Grade 3 
Grade ≥4
Patients with any AE
24 (37.5)
27 (42.2)
25 (38.5)
20 (30.8)
Neutropeniaa
12 (18.8)
23 (35.9)
5 (7.7)
17 (26.2)
Anemiad
8 (12.5)
0
6 (9.2)
0
Febrile Neutropenia
7 (10.9)
1 (1.6)
9 (13.8)
0
Fatigue
6 (9.4)
0
2 (3.1)
0
Thrombocytopenia
5 (7.8)
2 (3.1)
3 (4.6)
2 (3.1)
Infections and Infestationsc
5 (7.8)
0
4 (6.2)
3 (4.6)
Mucositisb
2 (3.1)
0
3 (4.6)
0
Hypokalemia
2 (3.1)
0
2 (3.1)
0
Lymphopenia
2 (3.1)
0
1 (1.5)
0
Diarrhea
2 (3.1)
0
0
0
Abdominal Paing
2 (3.1)
0
0
0
Musculoskeletal Painf
5 (7.8)
0
0
0
Infusion-Related Reactione
0
2 (3.1)
0
0
Nausea
1 (1.6)
0
2 (3.1)
0
Decreased Appetite
1 (1.6)
0
0
0
Dry Mouth
1 (1.6)
0
0
0
Dehydration
1 (1.6)
0
0
0
Constipation
0
0
1 (1.5)
0
Dyspnea
0
0
1 (1.5)
0
Cardiac arrhythmias
0
0
1 (1.5)
0
Cardiac dysfunctions
1 (1.6)
0
0
0
Abbreviations:  AE = adverse event; MedDRA = Medical Dictionary for Regulatory Activities; N = number of 
randomized patients; n = number of patients with given event.
Data cut-off date:  16 May 2015.
a
Consolidated term comprising the following preferred terms:  leukopenia, neutropenia, neutrophil count 
decreased, white blood cell count decreased.
b
Consolidated term comprising the following preferred terms:  mucosal inflammation, oropharyngeal pain, 
stomatitis.
c
Includes all preferred terms within the MedDRA system organ class of Infections and Infestations.
d
Consolidated term comprising the following preferred terms:  anemia, hemoglobin decreased.
e
Consolidated term comprising the following preferred terms:  hypersensitivity, infusion-related reaction, infusion 
site erythema, injection site pain.
f
Consolidated term comprising the following preferred terms:  back pain, musculoskeletal chest pain, 
musculoskeletal pain.
g
Consolidated term comprising the following preferred terms: abdominal pain upper, abdominal pain.
Note.  Arm A = Olaratumab + Doxorubicin; Arm B = Doxorubicin.
Source: JGDG CSR Table JGDG 12.16
More information about the known and expected benefits, risks, and reasonably anticipated AEs 
may be found in the Investigator’s Brochure (IB).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 23
LY3012207
5.3.1. Mechanism of Action and In Vitro/In Vivo Activity
Olaratumab is a recombinant human IgG1-type monoclonal antibody that binds to PDGFRα.  This 
antibody possesses high affinity binding for PDGFRα and blocks PDGF-AA, -BB, and -CC from 
binding to the receptor.  In addition to blocking ligand-induced cell mitogenesis and receptor 
autophosphorylation, olaratumab inhibits ligand-induced phosphorylation of the downstream 
signaling molecules Akt and mitogen-activated protein kinase.
PDGF/PDGFRα signaling plays a role in both organ and tissue development, as well as in 
pathogenesis of nonmalignant diseases (for example, pulmonary fibrosis) and malignant cancers
(Östman and Heldin 2007).  Many cancer types have been shown to consistently express PDGFRα 
on tumor tissues, including osteosarcoma, chondrosarcoma, prostate cancer, breast cancer, ovarian 
cancer, and others (Fleming et al. 1992; de Jong et al. 1998; Östman and Heldin 2007).  In 
malignant disease, the PDGF/PDGFRα axis is effective in promoting tumor growth and 
proliferation through both autocrine and paracrine mechanisms (Forsberg et al. 1993; Östman and 
Heldin 2007).  PDGFRα is expressed on stromal cells, as well as the cancer cells themselves, 
within certain tumors.  Furthermore, studies have shown that PDGF/PDGFRα signaling affects 
tumor vasculature through paracrine mediation of vascular endothelial growth factor production 
(Shah et al. 2010).
Olaratumab has demonstrated activity on cancer models known to be driven by exogenous 
PDGF stimulation as well as a PDGF-PDGFRα autocrine loop in both in vitro and in vivo
systems (Gerber et al. 2012; Study Reports 4881-10 and C-3G3-1).  PDGFRα autocrine signaling 
has been implicated in the pathogenesis of sarcomas (Fleming et al. 1992), which are 
hypothesized to originate from PDGFR-positive mesenchymal cells.  An analysis of publicly 
available genomic data, including those from TCGA, shows mRNA overexpression for PDGFRα 
and PDGFs in sarcoma, further implicating this autocrine loop in the pathogenesis of STS 
(Study Report BIX-PDGFRA-1).
In vitro olaratumab treatment blocks PDGF-dependent proliferation of the MG-63 human 
osteosarcoma cell line and enhances the antiproliferative effects of doxorubicin 
(Figure JGDN.5.1).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 24
LY3012207
Abbreviations:  Dox = doxorubicin; Olara = olaratumab; 
PDGF-AA/CC = platelet-derived growth factor(s) AA and/or CC.
Figure JGDN.5.1.
Olaratumab significantly reduces proliferation in the MG-63 Human 
Osteosarcoma cell line as a single agent and in combination with 
doxorubicin.
Furthermore, in this same cell line olaratumab treatment completely blocks downstream 
signaling through a variety of PDGF-activated signaling molecules such as AKT, ERK, and 
CREB (Figure JGDN.5.2).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 25
LY3012207
Abbreviations:  3G3 = olaratumab; PDGF-AA = platelet-derived growth factor-AA.
Figure JGDN.5.2.
Olaratumab blocks PDGF-dependent activation of downstream 
signaling proteins in the MG-63 human osteosarcoma cell line 
using Western blot detection.  Phospho protein order (red 
rectangles, top to bottom): pCREB, pERK, pAKT, pWNK1.
Olaratumab as a single agent has demonstrated in vivo antitumor activity in a human (SKLMS-1; 
adult) leiomyosarcoma (LMS) xenograft model (Loizos et al. 2005) and the A-204 human
(pediatric) rhabdoid mouse xenograft model (Figure JGDN.5.3).  In addition, the combination of 
olaratumab plus doxorubicin had statistically significant antitumor activity compared to the 
effects of either monotherapy in LMS and osteosarcoma (KHOS/NP; pediatric) xenograft models 
(ImClone Report 3276-05; ImClone Report 3521-05 and Figure JGDN.5.4 Graph A, p < 0.0001 
vs. control).  The combination of olaratumab plus doxorubicin was also tested in a 
patient-derived xenograft (PDX) model (“TTX”) established from a tumor tissue harvested from 
an osteosarcoma patient biopsy (adult) (Bruheim et al. 2004).  In this osteosarcoma PDX model, 
antitumor activity of olaratumab plus doxorubicin (T/C% = 2, p<0.0001 vs. control) was 
significantly enhanced compared to doxorubicin alone (Study Report OPDX3G3-1, and 
Figure JGDN.5.4 Graph B). Olaratumab as a single agent has demonstrated in vivo antitumor 
activity in a human alveolar rhabdomyosarcoma PDX model ST162 (Figure JGDN.5.5).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 26
LY3012207
Abbreviations:  IgG = immunoglobulin G; SEM = standard error of measure.
Figure JGDN.5.3.
Activity of olaratumab in the A-204 human rhabdoid mouse 
xenograft model.  Note that “3G3” is the internal designation for 
olaratumab.
Figure JGDN.5.4.
Activity of olaratumab as a single agent and in combination with 
doxorubicin in 2 mouse models of human osteosarcoma. Note that 
IMC-3G3 is the internal designation for olaratumab.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 27
LY3012207
Abbreviation:  PDGFRα = platelet-derived growth factor receptor alpha.
Note that “3G3” is the original designation for olaratumab and is specific for human 
PDGFR; 1E10 is an anti-mouse PDGFRmonoclonal antibody and targets mouse 
stromal PDGFRCombined the 2 antibodies are used to mimic the effects of 
olaratumab on human patients
Figure JGDN.5.5.
Activity of olaratumab in the ST162 human rhabdomyosarcoma 
patient-derived mouse xenograft model.  Note that the red bar 
indicates the dosing period.
Olaratumab in combination with doxorubicin significantly impairs the growth of the ST1547 
patient-derived LMS xenograft model, which is known to express PDGFRand PDGF-C 
(Figure JGDN.5.6).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 28
LY3012207
Abbreviation:  PDGFR= platelet-derived growth factor receptor alpha.
Note that “3G3” is the original designation for olaratumab and is specific for human 
PDGFR; 1E10 is an anti-mouse PDGFRmonoclonal antibody and targets mouse 
stromal PDGFRCombined the 2 antibodies are used to mimic the effects of 
olaratumab on human patients.
Figure JGDN.5.6.
Activity of olaratumab and doxorubicin on ST1547 human 
leiomyosarcoma xenograft model.
5.3.2. Nonclinical Pharmacokinetics/Pharmacodynamics
The PK profile of olaratumab was characterized in mice and the pharmacokinetics and 
toxicokinetics (TK) were determined as part of the monkey toxicology studies.  The PK and TK 
of olaratumab in mice and monkeys were generally consistent with that expected for a 
monoclonal antibody, characterized by a moderate elimination half-life and clearance and a 
volume of distribution approximately equal to the vascular space.  Increases in exposure were 
generally proportional to or greater than proportional to the increase in dose.  Accumulation of 
olaratumab was evident after repeated dosing in monkeys.
5.3.3. Nonclinical Toxicology
The nonclinical safety of olaratumab has been adequately assessed in 3 repeat-dose Good 
Laboratory Practice studies in cynomolgus monkeys.  It was not possible to directly assess 
crossreactivity in tissue-binding experiments, as olaratumab could not be used for the purposes 
of immunohistochemical staining (Study IM1236P).  However, in addition to 
immunoprecipitation of PDGFRin several cynomolgus tissues and the ability to block 
PDGFRsignaling in cynomolgus skin fibroblasts, direct binding of olaratumab to the 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 29
LY3012207
extracellular domain of cynomolgus PDGFR, with similar affinity to human PDGFR, has 
been demonstrated.  The toxicity, TK, and immunogenicity of olaratumab were investigated after 
administration by IV infusion over 5, 13, or 39 weeks to male and female monkeys.  In the 
5-week toxicity study, olaratumab was administered at dose levels of 5, 16, and 50 mg/kg at 
Weeks 1, 3, 4, and 5.  In the 13- and 39-week studies, olaratumab was administered once per 
week at dose levels of 7.5, 24, and 75 mg/kg.  Mortality, clinical signs, body weight, and food 
consumption were monitored throughout the treatment and recovery periods.  Hematology, 
coagulation, clinical chemistry, urinalysis, ophthalmology, electrocardiograms (ECGs), heart 
rate, and blood pressure recordings were analyzed during the treatment and recovery phases.  
The 13-week and 39-week studies included an immunophenotyping analysis of lymphocyte 
subsets.  Terminal procedures included a full macroscopic examination, organ weight 
determination, and a comprehensive histopathological evaluation.  Development and 
reproductive toxicity studies of olaratumab in animals have not been conducted.
No clear olaratumab treatment-related adverse effects were noted in any study.  A single female 
treated for 39 weeks with 75 mg/kg was noted with mildly to moderately increased alanine 
aminotransferase, minimal individual cell necrosis, and moderate infiltrates in the liver, but this 
effect was not considered clearly attributable to treatment nor was it considered adverse.  
Therefore, the no-observable-adverse-effects levels (NOAELs) were established as the highest 
test doses: 50 mg/kg in the 5-week study and 75 mg/kg in the 13- and 39-week studies.
In summary, weekly administration of olaratumab by IV infusion for up to 39 weeks was well 
tolerated and not associated with the development of any adverse effects.  The monkey serum 
minimum concentration (Cmin; 1164 µg/mL) at the 75-mg/kg NOAEL in the 39-week study was 
approximately 4.5-fold greater than the threshold Cmin believed to be needed for antitumor 
activity based on tumor xenograft models (260 µg/mL).  The area under the concentration curve 
from time 0 to 168 hours (AUC[0-168hr]) following the last infusion of 75 mg/kg in the 39-week 
study (284976 hr•µg/mL) was approximately 16.5-fold greater than exposures of olaratumab that 
are anticipated to be needed for antitumor activity in humans based on animal tumor models 
(AUC[0-96hr] = 17184 hr•µg/mL).  Therefore, the 39-week cynomolgus monkey study adequately 
evaluated the safety of olaratumab at exposures that appreciably exceed those anticipated to be 
evaluated and effective in humans with advanced cancer.
5.4.
Rationale for Selection of Dose
The current dose-selection strategy for the pediatric population is based on the efficacy, safety, 
and PK data for olaratumab across previous Phase 1 and Phase 2 studies in adults.
During clinical development, in Phase 1 dose-escalation trials (JGDC and JGDF) and in Phase 2 
monotherapy studies (JGDE and JGDH), olaratumab has been consistently well tolerated, with 
no DLTs observed in the dose-escalation studies up to a dose of 16 mg/kg weekly times 4 doses 
in a 6-week cycle, 20 mg/kg administered every 2 weeks, and up to a dose of 15 mg/kg 
administered on Day 1 and Day 8 of a 21-day cycle.  When used in combination with other 
therapeutic agents, an increase of toxicities such as neutropenia and infections were observed in 
combination with liposomal doxorubicin (olaratumab dose of 20 mg/kg every 2 weeks) and with 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 30
LY3012207
paclitaxel/carboplatin (olaratumab dose of 15 mg/kg on Day 1 and Day 8 every 3 weeks).  In 
Study JGDG (15 mg/kg on Day 1 and Day 8 of a 21-day cycle), an increase in neutropenia and 
mucositis, but not in neutropenic sepsis or febrile neutropenia, have been observed.  These 
toxicities are acceptable and monitorable and are consistent with the toxicity profile of 
doxorubicin.
Results from a currently ongoing population PK (PopPK) modeling analysis indicate that the 
serum levels of olaratumab obtained at the dose of 15 mg/kg are best described by a 
2-compartment model with linear clearance.  This suggests that the dose of 15 mg/kg used in 
Study JGDG provides serum concentrations such that target-mediated drug disposition is 
maintained at its near maximum throughout the course of treatment once steady state is reached.
Survival data from Study JGDG show that the combination of olaratumab 15 mg/kg with 
doxorubicin 75 mg/m2 provides a significant benefit compared to single-agent doxorubicin in 
patients with advanced metastatic STS, without an increase in serious toxicity.  A matched 
case-control analysis per exposure quartiles based on the trough olaratumab serum concentration 
at the end of Cycle 1 (Cmin,1) suggests that only patients in the lowest exposure quartile (Cmin,1 < 
61 µg/mL, N=15) tend to experience disease progression within the first 2 cycles of treatment 
and, unlike the other quartiles, do not show PFS or OS improvement.  In addition, a PopPK 
analysis performed on PK data collected from adult cancer patients indicates that body weight is 
the main covariate to olaratumab clearance.  A dose of 15 mg/kg olaratumab is thus expected to 
achieve a similar serum exposure level in the pediatric population compared to the adult 
populations.  However, as the relationship between body weight and olaratumab clearance is less 
than fully proportional, potentially sub-therapeutic olaratumab serum exposures might be 
observed in patients with very low body weight.  Study JGDN therefore manages this possibility 
by escalating olaratumab to a dose of 20 mg/kg in order to ensure that the pediatric population be 
exposed to olaratumab serum levels previously associated with clinical benefit.  The decision to 
dose escalate will be based on safety data collected during the first 2 cycles of treatment of 
JGDN Part A.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 31
LY3012207
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 1 time.  The interval before re-screening should be 
at least 2 weeks.  When re-screening is performed, the individual must sign a new informed 
consent form (ICF) and will be assigned a new identification number.
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]
The patient must have histological or cytological evidence of a diagnosis of 
solid tumor, excluding lymphomas and melanoma, but including central 
nervous system (CNS) tumors, that is relapsed or refractory, not be amenable 
to curative treatment, and for whom chemotherapy with doxorubicin,
vincristine/irinotecan, or ifosfamide is deemed appropriate by the investigator.  
For patients with CNS tumors, neurologic deficits in patients with CNS 
tumors must have been stable for at least 7 days prior to study enrollment.
[2]
The patient has the presence of measurable and/or nonmeasurable but 
evaluable disease as defined by the Response Evaluation Criteria In Solid 
Tumors (RECIST Version 1.1) (Eisenhauer et al. 2009; refer to
Attachment 8). Response Assessment in Neuro-Oncology (RANO) Criteria 
(Wen et al. 2010) or Macdonald Criteria (Macdonald et al. 1990) should be 
used for CNS tumors.
[3]
The patient is <18 years of age at the time of first dose of study drug.
[4]
The patient, or patient’s parent/guardian, has given written informed consent 
and authorization for release of health information for research prior to any 
study-specific procedures being performed.
[5]
The patient has a Lansky (<16 years of age; Lansky et al. 1987) or Karnofsky 
(≥16 years of age; Karnofsky et al. 1948) performance score of at least 50.
[6]
The patient has adequate hematologic, organ, and coagulation function
≤2 weeks (14 days) prior to first dose of study drug:

Absolute neutrophil count (ANC) 750/mm3. Granulocyte 
colony-stimulating factor (G-CSF) cannot be administered ≤1 week 
(7 days) prior to first dose of study drug.  Pegfilgrastim cannot be 
administered ≤2 weeks (14 days) prior to first dose of study drug.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 32
LY3012207

Platelets 75,000/mm3. Platelet transfusion to meet this enrollment 
criterion is not allowed within the preceding 5 days of first dose of study 
drug.

Hemoglobin 8 g/dL.  Transfusions with packed red blood cells is 
allowed.

Total bilirubin (sum of conjugated + unconjugated) 1.5 X upper limit of 
normal (ULN) for age.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
3.0 times ULN.  If the liver has tumor involvement, AST and ALT 
equaling 5.0 times ULN are acceptable.

Serum creatinine is based on age/gender as follows:
Age
Maximum Serum
Creatinine (mg/dL)
Male
Female
1 month to < 6 months
0.4
0.4
6 months to < 1 year
0.5
0.5
1 to < 2 years
0.6
0.6
2 to < 6 years
0.8
0.8
6 to < 10 years
1.0
1.0
10 to < 13 years
1.2
1.2
13 to < 16 years
1.5
1.4
≥ 16 years
1.7
1.4
The threshold creatinine values in this table were derived from the Schwartz formula for 
estimating glomerular filtration rate (Attachment 6).

The patient has an adequate coagulation function as defined by International 
Normalized Ratio ≤1.5 or prothrombin time ≤1.5 x ULN, and partial 
thromboplastin time ≤1.5 x ULN if not receiving anticoagulation therapy.  For 
patients receiving anticoagulants, exceptions to these coagulation parameters 
are allowed if they are within the intended or expected range for their 
therapeutic use. Patients must have no history of active bleeding (defined as 
within 14 days of first dose of study drug) or pathological condition that 
carries a high risk of bleeding (for example, tumor involving major vessels or 
known esophageal varices).
[7]
Female patients of child-bearing potential must have a negative serum 
pregnancy test within 7 days prior to Cycle 1 Day 1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 33
LY3012207
[8]
Both female and male patients of child-bearing potential must agree to use 
highly effective contraceptive precautions during the trial and up to 3 months 
following the last dose of olaratumab, or longer if appropriate for other study 
drugs according to their label.  A highly effective method of birth control is 
defined as one that results in a low failure rate (that is, <1% per year) when 
used consistently and correctly, such as implants, injectables, combined oral 
contraceptives, some intrauterine contraceptive devices, sexual abstinence, or 
a vasectomized partner.
[9]
Patients must have fully recovered from the acute toxic effects of all prior 
anticancer therapies or must adhere to post-treatment conditions as follows:

Myelosuppressive chemotherapy:  at least 21 days after the last dose of 
myelosuppressive chemotherapy (or 42 days if prior nitrosourea)

Hematopoietic growth factors: at least 14 days after the last dose of a long-acting 
growth factor (for example, Neulasta®) or 7 days for short-acting growth factor.  
For agents that have known adverse events (AEs) occurring beyond 7 days after 
administration, this period must be extended beyond the time during which AEs
are known to occur.  The duration of this interval must be discussed with Lilly 
clinical research physician or clinical research scientist (CRP/CRS).

Biologic (anti-neoplastic agent):  at least 7 days after the last dose of a biologic 
agent

Antibody therapy:  at least 3 half-lives after the last treatment

Radiation:  14 days since local palliative radiation therapy (RT) (small port); 
150 days if patient has had prior total body irradiation (TBI), craniospinal RT, or 
50% or greater pelvic radiation; 42 days for other substantial radiation (such as 
metaiodobenzylguanidine therapy)

Stem Cell Infusion without TBI:  at least 84 days must have elapsed after 
transplant or stem cell infusion

Corticosteroids:  for patients with CNS lesions, the dose of corticosteroids should 
be stable for at least 1 week.
6.1.2. Exclusion Criteria
Potential study patients may not be included in the study if any of the following apply during 
screening.
[10] Have received treatment within 21 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) or are concurrently enrolled in any 
other type of medical research judged not to be scientifically or medically 
compatible with this study.
[11] Patients that have had bone marrow or solid organ transplant are excluded.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 34
LY3012207
[12] The patient has uncontrolled intercurrent illness including, but not limited to, 
an ongoing/active infection requiring parenteral antibiotics, symptomatic 
congestive heart failure (CHF), severe myocardial insufficiency, cardiac 
arrhythmia, cardiomyopathy, or a psychiatric illness/social situation that 
would limit compliance with study requirements.
[13] The patient has an active fungal, bacterial, and/or known severe viral infection 
including HIV or viral (A, B, or C) hepatitis (screening is not required).
[14] Female patients who are pregnant or breastfeeding are excluded.
[15] If the patient is to be enrolled in the doxorubicin combination arm, a left 
ventricular dysfunction (LVEF < 50%) or shortening fraction of <27% by 
echocardiogram (either multigated acquisition [MUGA] or echocardiogram 
[ECHO] are required, not both).
[16] Patients that have received prior anthracycline therapy if the patient is to be 
enrolled in the doxorubicin combination arm.
[17] The patient has a corrected QT interval of >480 msec on screening ECG if the 
patient is to be enrolled in the doxorubicin combination arm.
6.2.
Summary of Study Design
Study JGDN is a multicenter, dose-escalation, open-label Phase 1 pediatric safety clinical trial
with 3 distinct components, Part A, Part B, and Part C.
Part A will consist of at least 12 evaluable pediatric patients.  Given the expected diversity of age 
and body weight in the study population, this sample size is expected to provide the necessary 
amount of PK information in order to characterize the disposition of olaratumab in the pediatric 
population.
Patients will be treated for 1 cycle (21 days) of olaratumab monotherapy at 15 mg/kg on Day 1 
and Day 8 (adult dose for which efficacy was observed in Study JGDG).  If the patient does not 
experience a DLT in the first cycle of monotherapy, or meet any other criteria for 
discontinuation, the patient will then receive olaratumab (15 mg/kg) plus one of 3 standard 
chemotherapy regimens (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per 
investigator discretion).  Treatment will continue until disease progression or other 
discontinuation criteria are met.
During Cycle 1 monotherapy, if the DLT rate is >1/3 (that is, greater than 4 out of 12 patients), 
then the dose of olaratumab will be reduced to 10 mg/kg.  If the DLT rate is >1/3 in the first 
cycle (Cycle 2) of any of the combination therapy arms, then appropriate dose de-escalation of 
olaratumab for that combination will occur.  Another cohort with at least 3 patients will be 
studied for that combination with olaratumab at 10 mg/kg.
Part A of the study design is illustrated in Figure JGDN.6.1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 35
LY3012207
Abbreviations:  D = day; DLT = dose-limiting toxicity; N = number of patients; 
n = number of cycles.
Figure JGDN.6.1.
Illustration of Part A of the study design.
Part B will be initiated after the following criteria have been met:

Acceptable safety results, which must include a minimum of 6 evaluable patients, and
the PK profile from Part A monotherapy.

At least one of the 15 mg/kg combination arms has met the following DLT criteria: less 
than one-third (that is, approximately ~33.3% [minimum of 3 patients]) DLT rate.  Only 
the combination arms in Part A that have met these criteria may be studied in Part B.
Part B patients will be treated for 1 cycle (21 days) of olaratumab monotherapy at 20 mg/kg on 
Day 1 and Day 8 then receive olaratumab (20 mg/kg) plus one of 3 standard chemotherapy 
regimens described in Part A. Part B will be complete when at least 10 patients (regardless of 
assigned chemotherapy arm) are evaluable for safety of olaratumab 20 mg/kg monotherapy.  
Treatment will continue until disease progression or other discontinuation criteria are met.
In Part B, if a patient has a DLT during the Cycle 1 monotherapy, the subsequent olaratumab 
dose will be reduced to 15 mg/kg, and the patient will receive combination therapy in Cycle 2.
During Cycle 1 monotherapy, if the DLT rate is >1/3 (that is, greater than 4 out of 12 patients), 
then the dose of olaratumab will be reduced to 15 mg/kg for patients subsequently enrolled.  If 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 36
LY3012207
the DLT rate is >1/3 in any of combination therapy arms, then appropriate dose de-escalation of 
olaratumab for that combination will occur.
Part B is illustrated in Figure JGDN.6.2.
Abbreviations:  D = day; DLT = dose-limiting toxicity; N = number of patients; 
n = number of cycles.
Figure JGDN.6.2.
Illustration of Part B of the study design.
Part C will receive olaratumab (20 mg/kg) in combination with any of the 3 chemotherapy 
regimens from Cycle 1 onwards (ie. no olaratumab monotherapy in Cycle 1).  Treatment will 
continue until disease progression or other discontinuation criteria are met.
Part C is illustrated in Figure JGDN.6.3.
Abbreviations:  DLT = dose-limiting toxicity; n = number of cycles.
Figure JGDN.6.3.
Illustration of Part C of the study design.
Parts B and C together will enroll up to 45 patients (15 per chemotherapy arm).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 37
LY3012207
The planned duration of treatment is not fixed; patients will remain on study until they fulfill one 
of the criteria for study discontinuation (Section 6.3).  Patients on study treatment who continue 
to experience clinical benefit and no undue risks may continue olaratumab monotherapy after 
completion of chemotherapy until one of the criteria for discontinuation is met if deemed 
medically appropriate in the opinion of the investigator and following discussion and agreement 
by the medical monitor. This study will enroll a minimum of 24 (maximum of 79) pediatric 
patients, including a minimum of 10 osteosarcoma patients and 10 rhabdomyosarcoma patients 
across all treatment arms, if possible.  The goal will be to enroll approximately 20 evaluable 
patients in each combination arm (across Parts A, B, and C) to characterize the safety and PK 
profile of olaratumab and the respective chemotherapeutic agents, and to inform dose choice for 
potential later-phase studies.
Refer to Attachment 1 for the Study Schedule.
6.2.1. Primary Endpoint
Primary endpoint is defined as DLT and PK data exposure matching. The primary endpoint 
analysis will occur after the final patient enrolled has been evaluated for at least 2 cycles.
6.2.2. Study Completion and End of Trial
Any patient enrolled in Part A or Part B that has completed at least 1 cycle of treatment or 
discontinued due to an AE (during Cycle 1), and completed the required post-treatment safety 
assessment, will be considered to have completed the monotherapy portion of the study. Patients 
in Part A or Part B completing Cycle 1 who do not continue to Cycle 2 will be considered 
evaluable for monotherapy DLTs and PK.  Any patient enrolled in Part A or Part B that has 
completed at least 2 cycles of treatment or discontinued due to an AE (during Cycle 2), and 
completed the required post-treatment safety assessment, will be considered to have completed 
the study. Any patient enrolled in Part C that has completed 1 cycle of treatment or discontinued 
due to an AE (during Cycle 1), and completed the required post-treatment safety assessment, will 
be considered to have completed the study.  However, in all parts of the study, additional cycles 
of therapy may continue as long as the patient is receiving benefit and no criteria for 
discontinuation have been met. All secondary and exploratory endpoint analyses will be updated 
at study completion.
The end of trial occurs after the last patient has discontinued study treatment and completed any 
applicable follow-up.
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 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 38
LY3012207
the sponsor CRP or CRS 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 or CRS does not agree with the 
investigator’s determination that it is medically appropriate for the patient to continue. The 
investigator must obtain documented approval from the Lilly CRP to allow the inadvertently 
enrolled patient to continue in the study with or without investigational product.
In addition, patients will be discontinued from the study drug in the following circumstances:

Enrollment in any other clinical trial involving an investigational product or enrollment in 
any other type of medical research judged not to be scientifically or medically compatible 
with this study.

Investigator/Physician Decision
o
the investigator/physician decides that the patient should be discontinued from the 
study or study drug(s)
o
if the patient, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study drug(s) occurs prior to introduction of the other 
agent

Patient, parent or legal guardian decision
o
the patient or the patient’s designee (for example, parents or legal guardian) 
requests to be discontinued from the study or study drug

Sponsor Decision
o
Lilly stops the study or stops the patient’s participation in the study for medical, 
safety, regulatory, or other reasons consistent with applicable laws, regulations, 
and GCP

The patient has radiographic progressive disease or significant symptomatic disease 
deterioration characterized as progression of disease, in the opinion of investigator, in the 
absence of radiographic evidence of progressive disease.

The patient experiences unacceptable toxicity (for example, a persistent moderate toxicity 
that is intolerable to the patient).

The patient is noncompliant with study procedures and/or treatment (Section 7.6).
The reason for and date of discontinuation will be collected for all patients.  The date of 
discontinuation (for any of the above reasons) from study treatment is to be reported on the
electronic case report form (eCRF).  Patients who discontinue will have follow-up procedures 
performed as shown in the Study Schedule (Attachment 1).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 39
LY3012207
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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 40
LY3012207
7.
Treatment
7.1.
Materials and Supplies
Olaratumab will be provided to the sites by Lilly.
Olaratumab for injection is supplied in single-use 500 mg/50 mL vials containing 10 mg/mL of 
olaratumab in histidine buffer, administered to patients as an IV infusion at 10, 15, or 20 mg/kg.
Other drug products (i.e. doxorubicin hydrochloride, dexrazoxane, vincristine sulfate, irinotecan 
hydrochloride, and ifosfamide) to be used in Study JGDN will be supplied by Lilly, but
commercially available supply may be used as directed by Lilly for cases of regional restrictions 
or supply limitations.  
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 the following:

explaining the correct use of the investigational agent(s) and planned duration of each 
individual’s treatment to the patient, site personnel, legal representative,

verifying that instructions are followed properly,

maintaining accurate records of study drug dispensation, destruction, and collection,

and returning or destroying all unused medication to Lilly or its designee at the end of the 
study.
Note: In some cases, sites may destroy the material if, during the investigator site selection, the 
evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose clinical trial materials.
Patients or the parent/guardian 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. Premedication
Infusion-related reactions (IRR), including Grade 3/4 IRR events, have been observed with 
olaratumab.  To date, Grade 3/4 IRR have only been reported during the first cycle of olaratumab 
treatment. Therefore, in Cycle 1 (both Day 1 and Day 8 doses) all patients should receive 
premedication with dexamethasone (or equivalent medication) and an H1 antagonist 
intravenously 30 to 60 minutes prior to olaratumab infusion.  Additional premedication may be 
provided at investigator discretion.
For all subsequent cycles, all patients should receive premedication with an H1 antagonist (for 
example, diphenhydramine) intravenously 30 to 60 minutes prior to each dose of olaratumab. 
Additional premedication may be provided at investigator discretion.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 41
LY3012207
Patients with a prior Grade 1 or Grade 2 olaratumab IRR must receive antihistamine and 
additional premedication (described in Section 7.2.4.1.1).  All premedication administered must 
be adequately documented in the eCRF.
Doxorubicin
Given the emetogenic potential of doxorubicin, premedication with antiemetics per institutional 
guidelines is recommended.  
If doxorubicin premedication is required prior to the doxorubicin infusion, this must be done 
after the completion of the olaratumab infusion, not before the olaratumab infusion.  This 
premedication may be administered immediately following the end of observation period (if 
applicable) or after the completion of the olaratumab infusion.
Dexrazoxane may be administered at a 10:1 ratio (dexrazoxane:doxorubicin) at the investigator’s 
discretion via IV injection, beginning within 30 minutes prior to each doxorubicin infusion for 
the prevention of cardiotoxicity.  It is recommended that all patients receiving doxorubicin also
receive dexrazoxane.
Vincristine
Laxatives and/or stool softeners may be used preemptively during vincristine-containing cycles.
Irinotecan
A prophylactic treatment with antiemetics is recommended before each treatment with 
irinotecan. Nausea and vomiting have been frequently reported. For patients with vomiting 
associated with delayed diarrhea, hospitalization should be considered.
If irinotecan premedication is required prior to the irinotecan infusion, this must be done after the 
completion of the olaratumab infusion, not before the olaratumab infusion.  This premedication 
may be administered immediately following the end of the observation period (if applicable) or 
after the completion of the olaratumab infusion.
Ifosfamide
When the treatment includes ifosfamide, mesna should be administered at a minimum dose equal 
to 60% of the ifosfamide dose according to institutional guidelines, including divided dose or 
continuous infusion.  .
Ifosfamide is associated with moderate emetic potential, antiemetics are recommended to prevent 
nausea or vomiting.
Ifosfamide should be given with extensive hydration consisting of oral or intravenous fluid 
(2 L/m2 IV) to prevent bladder toxicity or according to institutional guidelines.  The criteria to 
start chemotherapy may also include a urine-specific gravity < 1.010 or according to institutional 
guidelines.
If ifosfamide premedication is required prior to the ifosfamide infusion, this must be done after 
the completion of the olaratumab infusion, not before the olaratumab infusion.  This 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 42
LY3012207
premedication may be administered immediately following the end of the observation period (if 
applicable) or after the completion of the olaratumab infusion.
7.2.2. Dosing Schedule
If any study drug is discontinued (olaratumab or chemotherapy), the patient will be discontinued 
from the trial.  A change of body weight ≥10% (increase or decrease) from baseline will result in 
re-calculation of dose to be administered.
The following treatments will be administered in this study every 3-week (21-day) ± 3 day cycle 
(Table JGDN.7.1 and Table JGDN.7.2).
Part A:
Cycle 1
Olaratumab as IV infusion on Day 1 and Day 8 (at 15 mg/kg)
Cycle 2 and beyond
Olaratumab as IV infusion on Day 1 and Day 8 (at 15mg/kg, or 10 mg/kg if de-escalated), 
AND
Doxorubicin as IV infusion on Day 1 and Day 2 (at 37.5 mg/m2; up to 6 cycles or a cumulative 
dose of 450 mg/m2)
OR
Vincristine as IV on Day 1 and Day 8 (patients ≥ 10 kg: 1.5 mg/m2, patients <10 kg:  
0.05 mg/kg.  Dose is capped at 2 mg) plus irinotecan as IV on Days 1, 2, 3, 4, 5 (at 50 mg/m2),
OR
Ifosfamide as IV on Days 1, 2, 3, 4, and 5 (at 2.8 g/m2; up to 6 cycles or a cumulative dose of 
84 g/m2).  Treatment beyond 84 g/m2 requires consultation with the Lilly CRP/CRS.
Part B:
Cycle 1
Olaratumab as IV infusion on Day 1 and Day 8 (at 20 mg/kg)
Cycle 2 and beyond
Olaratumab as IV infusion on Day 1 and Day 8 (at 20 mg/kg),
AND
Doxorubicin as IV infusion on Day 1 and Day 2 (at 37.5 mg/m2; up to 6 cycles or a cumulative 
dose of 450 mg/m2)
OR
Vincristine as IV on Day 1 and Day 8 (patients ≥ 10 kg: 1.5 mg/m2, patients <10 kg:  
0.05 mg/kg.  Dose is capped at 2 mg) plus irinotecan as IV on Days 1, 2, 3, 4, 5 (at 50 mg/m2),

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 43
LY3012207
OR
Ifosfamide as IV on Days 1, 2, 3, 4, and 5 (at 2.8 g/m2; up to 6 cycles or a cumulative dose of 
84 g/m2). Treatment beyond 84 g/m2 requires consultation with the Lilly CRP/CRS.
Part C:
All Cycles
Olaratumab as IV infusion on Day 1 and Day 8 (at 20 mg/kg),
AND
Doxorubicin as IV infusion on Day 1 and Day 2 (at 37.5 mg/m2; up to 6 cycles or a cumulative 
dose of 450 mg/m2)
OR
Vincristine as IV on Day 1 and Day 8 (patients ≥ 10 kg: 1.5 mg/m2, patients <10 kg:  
0.05 mg/kg.  Dose is capped at 2 mg) plus irinotecan as IV on Days 1, 2, 3, 4, and 5 (at 50 
mg/m2),
OR
Ifosfamide as IV on Days 1, 2, 3, 4, and 5 (at 2.8 g/m2; up to 6 cycles or a cumulative dose of 
84 g/m2).  Treatment beyond 84 g/m2 requires consultation with the Lilly CRP/CRS.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 44
LY3012207
Table JGDN.7.1.
Treatment Regimens/Dosing Schedule (Parts A and B)
Study Drug
Dose
Route
Timing
Cycle 1
Olaratumaba
Part A
15 mg/kg
IV
approximately 1 hour infusion on 
Day 1 and Day 8 of each 21-day 
cycle
Part B
20 mg/kg
Cycle 2-n
Olaratumaba
Part A
15 mg/kg
IV
approximately 1 hour infusion 
Day 1 and Day 8 of each 21-day 
cycle
Part B
20 mg/kg
1-hour observation periodb followed by 
Doxorubicinc,dg
Parts A and B
37.5 mg/m2
IV
Day 1 and Day 2 of each 21-day 
cycle 
OR
Vincristinee
Parts A and B
1.5 mg/m2
IV
Day 1 and Day 8 of each 21-day 
cycle
Irinotecang
Parts A and B
50 mg/m2
IV
Days 1, 2, 3, 4, and 5 of each 
21-day cycle
OR
Ifosfamidefg
Parts A and B
2.8 g/m2
IV
approximately 2 to 3 hour infusion 
on Days 1, 2, 3, 4, and 5 of each 
21-day cycle
Abbreviations:  eCRF = electronic case report form; IV = intravenous.
a
Administer premedication prior to infusion of olaratumab.  Recommended premedication agents include 
histamine H1 antagonists such as diphenhydramine hydrochloride (or equivalent).  Additional premedication 
may be provided at the investigator’s discretion.  Premedication must be provided in the setting of a prior 
Grade 1-2 infusion-related reaction, as detailed in Section 7.2.4.1.  All premedication administered must be 
adequately documented in the eCRF.
b A 1-hour observation period is required after the administration of the first and second doses of olaratumab.  If
there is no evidence of an infusion-related reaction during the initial 2 cycles of olaratumab, then no observation 
period is required for subsequent treatment cycles.  In the event an infusion-related reaction occurs thereafter, 
then the 1-hour observation period should be reinstituted; see Section 7.2.4.1.
c
Administer doxorubicin for up to 6 cycles only or cumulative dose of 450 mg/m2.
d Administer doxorubicin according to institutional guidelines and/or clinical practice as an IV injection or as an 
infusion in less than 60 minutes (+10 minutes).  Decrease the rate of doxorubicin administration if erythematous 
streaking along the vein proximal to the site of infusion or facial flushing occurs.
e
For patients weighing less than 10 kg, the dose of vincristine should be 0.05 mg/kg.  The dose is capped at 2 mg 
for all patients.
f
Administer ifosfamide for up to 6 cycles only or a cumulative dose of 84 g/m2.  Treatment beyond 84 g/m2
requires consultation with the Lilly clinical research physician/clinical research scientist.
g    For sequential day chemotherapy, it is recommended to allow a minimum of 20 hours between dosing, unless      
institutional standard varies.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 45
LY3012207
Table JGDN.7.2
Treatment Regimens/Dosing Schedule (Part C)
Study Drug
Dose
Route
Timing
Cycle 1-n
Olaratumaba
20 mg/kg
IV
approximately 1 -hour infusion on Day 1 and Day 8 
of each 21-day cycle
1-hour observation periodb followed by 
Doxorubicinc,d,g
37.5 mg/m2
IV
Day 1 and Day 2 of each 21-day cycle 
OR
Vincristinee
1.5 mg/m2
IV
Day 1 and Day 8 of each 21-day cycle
Irinotecang
50 mg/m2
IV
Days 1, 2, 3, 4, and 5 of each 21-day cycle
OR
Ifosfamidef,g
2.8 g/m2
IV
approximately 2- to 3 -hour infusion on Days 1, 2, 3, 
4, and 5 of each 21-day cycle
Abbreviations:  eCRF = electronic case report form; IV = intravenous.
a
Administer premedication prior to infusion of olaratumab.  Recommended premedication agents include 
histamine H1 antagonists such as diphenhydramine hydrochloride (or equivalent).  Additional premedication 
may be provided at the investigator’s discretion.  Premedication must be provided in the setting of a prior 
Grade 1-2 infusion-related reaction, as detailed in Section 7.2.4.1.  All premedication administered must be 
adequately documented in the eCRF.
b A 1-hour observation period is required after the administration of the first and second doses of olaratumab.  If 
there is no evidence of an infusion-related reaction during the initial 2 cycles of olaratumab, then no observation 
period is required for subsequent treatment cycles.  In the event an infusion-related reaction occurs thereafter, 
then the 1-hour observation period should be reinstituted; see Section 7.2.4.1.
c
Administer doxorubicin for up to 6 cycles only or cumulative dose of 450 mg/m2.
d Administer doxorubicin according to institutional guidelines and/or clinical practice as an IV injection or as an 
infusion in less than 60 minutes (+10 minutes).  Decrease the rate of doxorubicin administration if erythematous 
streaking along the vein proximal to the site of infusion or facial flushing occurs.
e
For patients weighing less than 10 kg, the dose of vincristine should be 0.05 mg/kg.  The dose is capped at 2 mg 
for all patients.
f
Administer ifosfamide for up to 6 cycles only or a cumulative dose of 84 g/m2.  Treatment beyond 84 g/m2
requires consultation with the Lilly clinical research physician/clinical research scientist.
g  For sequential day chemotherapy, it is recommended to allow a minimum of 20 hours between dosing, unless 
institutional standard varies.
7.2.3. Dose Progression through Study Parts
Safety will be the primary criteria for the dose escalation or de-escalation of both olaratumab 
monotherapy and the combination regimens.  No dose escalation can occur without prior 
discussion and agreement between the investigators and the Lilly CRP/CRS/Lilly study team; the 
decision will be documented in writing. Sites will be notified of this decision 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 46
LY3012207
Part B will be initiated after acceptable safety results from Part A, including a minimum of 6 
evaluable patients, and the PK profile from Part A monotherapy.  Part B will be complete when 
at least 10 patients (regardless of assigned chemotherapy arm) are evaluable for safety of
olaratumab 20 mg/kg monotherapy.
Part C will open for enrollment after a complete safety review of the first 10 patients (regardless 
of chemotherapy arm) to complete Part B monotherapy (olaratumab 20 mg/kg).  This safety 
review will be performed by the Lilly CRP/CRS/Lilly study team and investigators and 
documented in writing.  Sites will be notified of this decision in writing.  
7.2.3.1.
Dose-Limiting Toxicity Determination and Maximum Tolerated Dose 
Definition
A DLT is defined as an adverse event (AE) during the first 21 days 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) v 4.0:

CTCAE Grade 3 nonhematologic toxicity.   Exceptions will be made for:
o
Grade 3 febrile neutropenia without complications,
o
Grade 3 events of nausea, vomiting, diarrhea, transient electrolyte 
abnormalities, and constipation that can be controlled with optimal 
medical management within 48 hours, and
o
transient Grade 3 elevations of ALT and/or AST lasting fewer than 8 days, 
without evidence of other hepatic injury may not be considered a DLT if 
agreed by the study investigator and Lilly CRP/CRS.

Grade 4 neutropenia that lasts longer than 2 weeks

Grade ≥3 thrombocytopenia complicated by hemorrhage

Any hematologic toxicity that causes a cycle delay of >14 days

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)
7.2.3.2.
Dose-Escalation Method
Part B will be initiated after the following criteria have been met:

Acceptable safety results, which must include a minimum of 6 evaluable patients, and
the PK profile from Part A monotherapy

At least one of the 15 mg/kg combination arms has met the following DLT criteria: less 
than one third (that is, approximately 33.3% [minimum of 3 patients]) DLT rate.  Only 
the combination arms in Part A that have met these criteria may be studied in Parts B and 
C.
In Part A, if the DLT rate is >1/3 (that is, greater than 4 out of 12 patients) during Cycle 1 
monotherapy, then the dose of olaratumab will be reduced to 10 mg/kg.  In Part B, if the DLT 
rate is >1/3 during Cycle 1 monotherapy, then the dose of olaratumab will be reduced to 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 47
LY3012207
15 mg/kg.  In Part C, if the DLT rate is >1/3 during Cycle 1 combination therapy, then the dose 
of olaratumab will be reduced to 15 mg/kg.
If the DLT rate is >1/3 in the first cycle (Parts A and B Cycle 2, or Part C Cycle 1) of any of the 
chemotherapy arms, then appropriate dose de-escalation (Table JGDN.7.3) of olaratumab for that 
combination will occur.
7.2.4. Dose Adjustments and Delays
In the event that a patient experiences a DLT or a DLT-equivalent (a DLT occurring in Cycle 3 
or later of Parts A and B or Cycle 2 or later of Part C), treatment will be interrupted.  Dosing can 
be resumed after resolution of the toxicity to baseline levels at the next lower dose level
(Table JGDN.7.3) already deemed safe upon discussion with the Lilly CRP/CRS.  For Grade 3/4 
toxicities that are not dose-limiting, see Section 7.2.4.1.2 for hematologic toxicities and 
Section 7.2.4.1.3 for nonhematologic toxicities.
Table JGDN.7.3.
Olaratumab Dose Levels and Adjustments for Olaratumab-related 
Toxicities
Dose at Enrollment
Dose Reduction
First
Second
Third
Dose level 3
20 mg/kg
15 mg/kg
10 mg/kg 
discontinue olaratumab
Dose level 2
15 mg/kg
10 mg/kg
discontinue olaratumab
Dose level 1
10 mg/kg
discontinue olaratumab
In the event of alteration of olaratumab therapy due to an olaratumab-related toxicity, 
chemotherapy need not be altered, and the planned chemotherapy schedule should be 
maintained.  In the event that olaratumab treatment is discontinued for reason of toxicity, the 
patient should be discontinued from the study.
Similarly, olaratumab therapy should not be altered for chemotherapy-related toxicity, even if the 
chemotherapy dose is modified.  In the event that chemotherapy is discontinued for reason of 
toxicity, the patient should be discontinued from the study.
To begin dosing at each cycle, the following criteria must be fulfilled:

ANC ≥750/mm3

Platelets ≥75,000/mm3

Hemoglobin ≥8 g/dL

Total bilirubin 1.5 x ULN

AST and ALT ≤3.0 x ULN, or ≤5 x ULN if the transaminase elevation is due to liver 
metastases

Any nonhematologic toxicity that are NCI-CTCAE, v4.0 Grade <2 or equivalent severity 
to baseline
Treatment may be delayed for up to 14 days to allow a patient sufficient time for recovery from 
study drug-related toxicity.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 48
LY3012207
The following information (in this section and the following subsections) pertains to dose 
modifications and delays for and management of AEs of concern, which may or may not be 
associated with olaratumab therapy, including the following:

IRR (see Section 7.2.4.1.1)

Hematologic toxicity (see Section 7.2.4.1.2)

Nonhematologic toxicity (see Section 7.2.4.1.3)
The following information (in this section and the following subsections) pertains to dose 
modifications and delays for and management of AEs of concern, which may or may not be 
associated with doxorubicin therapy, including the following:

Hematologic toxicity (see Section 7.2.4.2.1)

Cardiovascular toxicity (see Section 7.2.4.2.2)

Hepatic impairment (see Section 7.2.4.2.3)
The following information (in this section and the following subsections) pertains to dose 
modifications and delays for and management of AEs of concern, which may or may not be 
associated with vincristine therapy, including the following:

Hematologic toxicity (see Section 7.2.4.3.1)

Nonhematologic toxicity (see Section 7.2.4.3.2)
The following information (in this section and the following subsections) pertains to dose 
modifications and delays for and management of AEs of concern, which may or may not be 
associated with irinotecan therapy, including the following:

Hematologic toxicity (see Section 7.2.4.4.1)

Diarrhea and cholinergic reactions (see Section 7.2.4.4.2)
The following information (in this section and the following subsections) pertains to dose 
modifications and delays for and management of AEs of concern, which may or may not be 
associated with ifosfamide therapy, including the following:

Urotoxic effects (see Section  7.2.4.5.1)

Proximal tubular damage (see Section 7.2.4.5.2)

Central nervous system (see Section 7.2.4.5.3)

Other Toxicities (see Section 7.2.4.5.4)
7.2.4.1.
Olaratumab
7.2.4.1.1. Infusion-Related Reactions
As with other monoclonal antibodies, hypersensitivity reactions may occur during or following 
olaratumab administration.
Patients treated with olaratumab should be closely monitored for signs and symptoms indicative 
of an infusion reaction by the medical staff from the start of the infusion until at least 1 hour after 
the end of the infusion in an area where emergency medical resuscitation equipment and other 
agents (for example, epinephrine, prednisolone equivalents, etc.) are available.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 49
LY3012207
Olaratumab infusion reactions will be defined according to the NCI-CTCAE Version 4.0 
definition of infusion-related reactions.
Symptoms occurring during or following infusion of investigational therapy may also be defined 
according to AE categories such as allergic reaction, anaphylaxis, or cytokine release syndrome 
(NCI-CTCAE Version 4.0 section “Immune system disorders”).  In the setting of symptoms 
occurring during or following infusion of investigational therapy, investigators are encouraged to 
use the AE term “infusion-related reaction” and any additional terms (including those not listed 
here) that best describe the event.
In general, if a patient experiences a Grade 1 or 2 IRR, the infusion should stop and the patient 
should be treated with an antihistamine (for example, diphenhydramine hydrochloride), 
glucocorticoid (for example, dexamethasone), acetaminophen (or equivalent), and oxygen (as 
indicated), according to standard medical practices.  After recovery, the infusion rate should be 
decreased 50% for the duration of the infusion.  If subsequent infusions are then tolerated with 
the use of premedications as above and a 50% decrease in infusion rate, the infusion rate may be 
increased to a rate deemed appropriate by the investigator, as long as it does not exceed 25 
mg/min.
A Grade 3 or 4 IRR will require immediate treatment, including, but not limited to, the use of 
epinephrine, bronchodilators, and/or glucocorticoids for symptomatic bronchospasm, IV fluids 
and/or pressors for hypotension, and immediate and permanent discontinuation of olaratumab 
with appropriate supportive care.
For a patient who has had a Grade 1 or 2 olaratumab infusion reaction in a previous cycle, 
patients should be premedicated with antihistamine and glucocorticoid (for example 
dexamethasone) intravenously 30 to 60 minutes prior to olaratumab infusion, and acetaminophen 
(or equivalent) for all subsequent infusions.  Additional premedication may be provided at 
investigator discretion.
If a patient experiences an IRR to olaratumab, all attempts should be made to obtain 
anti-olaratumab antibody and olaratumab PK blood samples as close to the onset of the event as 
possible, at the resolution of the event, and 30 days (±3 days) following the event.  The 
procedure for sample collection and handling is described in a separate procedural manual.
7.2.4.1.2. Hematologic Toxicity
Table JGDN.7.4 summarizes the olaratumab dose modifications required in case of 
olaratumab-related hematologic toxicities during any cycle.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 50
LY3012207
Table JGDN.7.4.
General Guidelines for Olaratumab Dose Modification Due to 
Hematologic Toxicity Deemed Related to Olaratumab
Toxicity
Required Dose Modification
Neutropenia
  ANC Grade 1-3
No dose modification required
  ANC <500/mm3 (Grade ≥4)
No treatment administered; treatment cycle delayed
  At retreatment:
  If  Grade ≥3 neutropenic fever/infection has 
occurred
Withhold dose until ANC is ≥ 750/mm3; for the 
15-mg/kg cohort (Part A), reduce dose to 10 mg/kg; for 
the 20-mg/kg cohort (Part B and Part C), reduce dose to 
15 mg/kg. 
  If Grade 4 neutropenia lasting >1 week has occurred
Withhold dose until ANC is ≥ 750/mm3; for the 
15-mg/kg cohort (Part A), reduce dose to 10 mg/kg; for 
the 20-mg/kg cohort (Part B and Part C), reduce dose to 
15 mg/kg.
  Grade 4 ANC without fever/infection lasting
    ≤ 1 week
Administer the next olaratumab at full dose at 
investigator’s discretion with recommended use of 
prophylactic G-CSFs
  Second incidence of either:  
  1) Grade ≥3 neutropenic fever/infection
  2) Grade 4 neutropenia lasting > 1 week
For the 15-mg/kg cohort (Part A) that have been reduced 
to 10-mg/kg, discontinue olaratumab; for the 20-mg/kg 
cohort (Part B and Part C) that have been reduced to 15-
mg/kg, a second dose level reduction to 10 mg/kg
Thrombocytopenia
  Platelets <75,000/mm3
No treatment administered; treatment delayed until 
resolved to ≥75,000/mm3
Anemia
  Hemoglobin <8 g/dL 
No treatment administered; treatment delayed until 
resolved to ≥8 g/dL, transfusion with packed red blood 
cells allowed
Abbreviations:  ANC = absolute neutrophil count; G-CSFs = granulocyte colony-stimulating factors.
7.2.4.1.3. Nonhematologic Toxicity
Specific guidelines for dose adjustments in patients who experience olaratumab IRRs may be 
found in Section 7.2.4.1.1.
General guidelines for dose modification for other nonhematologic toxicities related to 
olaratumab are shown in Table JGDN.7.5.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 51
LY3012207
Table JGDN.7.5.
General Guidelines for Dose Modification Due to Nonhematologic 
Toxicities Related to Olaratumab
Reaction Grade
Required Dose Modification
Grade 1
No dose modification is required.
Grade 2
At the investigator’s discretion, the patient may continue to receive olaratumab per protocol, 
provided that the event does not pose a serious health risk or is easily treated.
Grade 3 
For a Grade 3 toxicity not adequately controlled with appropriate supportive care, the dose 
must be withheld until toxicity is ≤ Grade 1 or has returned to pretreatment baseline; then 
treatment may resume at a reduced dose of 10 mg/kg for the 15-mg/kg cohort (Part A) and 
reduced dose of 15 mg/kg for the 20-mg/kg cohort (Part B and Part C).  If toxicity recurs after 
therapy resumes, then treatment should be discontinued for the 15-mg/kg cohort (Part A) or 
the dose reduced to 10 mg/kg for the 20-mg/kg cohort (Part B and Part C).
Grade 4
The dose must be withheld until dose toxicity is ≤ Grade 1 or has returned to baseline.  
Permanent discontinuation should be considered for any patient experiencing Grade 4 
non-hematologic toxicity assessed as related to olaratumab. However, if resumption of 
dosing is deemed appropriate by the investigator, treatment may resume only after 
consultation with the Lilly study physician, with the dose reduced to 10 mg/kg for the 
15-mg/kg cohort (Part A); dose reduced to 15 mg/kg for the 20-mg/kg cohort (Part B and Part 
C).  If Grade 4 toxicity recurs after therapy resumes, treatment with olaratumab will be 
discontinued.
7.2.4.2.
Doxorubicin Dose Adjustments
The dose adjustments and delays for doxorubicin apply to patients treated with olaratumab plus 
doxorubicin.
7.2.4.2.1. Hematologic Toxicity
Doxorubicin will not be administered if the patient’s ANC is <750/mm3 or if the platelet count is 
<75,000/mm3.  When necessary, the next treatment cycle should be delayed until the ANC is 
≥750/mm3 and the platelet count is ≥75,000/mm3 and nonhematologic toxicities have resolved.  
For patients who experience Grade ≥3 neutropenic fever or infection, doxorubicin should be held 
until resolved and doxorubicin should be administered at the full dose at investigator’s discretion 
with recommended use of prophylactic G-CSFs.  If a patient experiences a second incidence of 
neutropenic fever/infection, then doxorubicin should be reduced to 28 mg/m2 on Day 1 and 
Day 2 will be necessary (75% of the starting dose). If used, dexrazoxane should be adjusted to 
maintain a 10:1 ratio with doxorubicin.  Therapeutic and prophylactic use of Neulasta®
(pegfilgrastim) or other G-CSFs will be allowed per current American Society of Clinical 
Oncology (ASCO; Smith et al. 2006) and National Comprehensive Cancer Network (NCCN 
2015) guidelines or at the investigator’s discretion.  For patients with Grade 4 ANC without 
fever/infection, retreatment will be allowed at the investigator’s discretion with the full dose of 
doxorubicin (37.5 mg/m2 on Day 1 and Day 2) with recommended use of G-CSFs per current 
ASCO guidelines (Smith et al. 2006).  See Table JGDN.7.6 for doxorubicin dose modification 
for neutropenia.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 52
LY3012207
Table JGDN.7.6.
General Guidelines for Doxorubicin Dose Modification Due to 
Neutropenia
Toxicity
Required Dose Modificationa
ANC <750/mm3
No doxorubicin administered; treatment cycle delayed
At retreatment:
If Grade ≥3 neutropenic fever/infection has occurred
Retreatment with doxorubicin at full dose at 
investigator’s discretion with recommended use of 
prophylactic G-CSFs
Grade 4 ANC without fever/infection
Second incidence of either:  
1) Grade ≥3 neutropenic fever/infection
2) Grade 4 neutropenia lasting longer than 1 week
Reduce to approximately 28 mg/m2 doxorubicin on 
Day 1 and Day 2
Abbreviations:  ANC = absolute neutrophil count; G-CSFs = granulocyte colony-stimulating factors.
a
Dexrazoxane should be adjusted to maintain a 10:1 ratio with doxorubicin.
7.2.4.2.2. Cardiac Monitoring for Doxorubicin-Associated Cardiotoxicity
Cardiotoxicity is a recognized risk of doxorubicin that increases with higher cumulative drug 
exposure.  Cardiac monitoring is conducted by a combination of monitoring of clinical 
parameters, ECG, and ECHO / MUGA scan.
ECG changes, arrhythmias, tachycardia, and/or chest pain should be managed based on the 
specific findings.
An ECHO/MUGA scan is required within 28 days prior to first dose of study drug for all patients 
receiving doxorubicin.  Thereafter, ECHO or MUGA scans must be performed at the end of 
Cycles 2, 4, and 6 and when clinically indicated.  If doxorubicin cardiotoxicity has been 
observed, an ECHO or MUGA should be performed at the 30-day follow-up visit.  Additional 
ECHO/MUGA may be performed if clinically indicated or at the investigator’s discretion.
If there is a decrease in LVEF to or below 40% or an absolute decrease of 20%, then doxorubicin 
will be discontinued.  If there is an absolute decrease in the shortening fraction of >10% or the 
shortening fraction is below 29%, then doxorubicin will be discontinued.  Doxorubicin should 
also be discontinued if the patient develops Grade 3 or 4 left ventricular systolic dysfunction 
(symptomatic CHF).  If doxorubicin is discontinued for the above changes in LVEF, olaratumab 
should also be discontinued.
The diagnostic method used at baseline for cardiovascular assessments (for example, ECHO or 
MUGA scans) should be the same method used throughout the study, unless there is clinical or 
instrumental evidence that further investigations are needed.
7.2.4.2.3. Hepatic Impairment
Doxorubicin is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C 
or serum bilirubin >5.0 mg/dL).
Decrease the dose of doxorubicin in patients with elevated serum total bilirubin concentrations as 
noted in Table JGDN.7.7.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 53
LY3012207
Table JGDN.7.7.
General Guidelines for Doxorubicin Dose Modification Due to 
Elevated Serum Total Bilirubin Concentrations
Serum Bilirubin Concentration
Doxorubicin Dose Reduction
>1.5 to 3 mg/dL
50% of initial dose
3.1 to 5 mg/dL
25% of initial dose
Greater than 5 mg/dL
Do not initiate doxorubicin
Discontinue doxorubicin
7.2.4.3.
Vincristine Dose Adjustments
The dose adjustments and delays for vincristine apply to patients treated with olaratumab plus 
vincristine and irinotecan.
7.2.4.3.1. Hematologic Toxicity
Vincristine does not appear to have any constant or significant effect upon the platelets or the red 
blood cells; however, anemia and thrombocytopenia have been reported.  Due to concerns of 
neurotoxicity, the ASCO guideline recommends that vincristine be capped at a maximum dose of 
2 mg. No dose adjustment is required. Therapeutic and prophylactic use of Neulasta 
(pegfilgrastim) or other G-CSFs will be allowed according to the current ASCO (Smith et al. 
2006) and NCCN guidelines (NCCN 2015) or at the investigator’s discretion.
7.2.4.3.2. Nonhematologic Toxicity
Table JGDN.7.8 provides the general guidelines for dose modifications of vincristine due to 
toxicity.
7.2.4.3.2.1.
Neurologic Toxicity
Vincristine-related sensory and motor neuropathies are common and are cumulative. Monitor 
patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, 
hyporeflexia, areflexia, neuralgia, jaw pain, decreased vibratory sense, cranial neuropathy, ileus, 
burning sensation, arthralgia, myalgia, muscle spasm, or weakness, both before and during 
treatment. Orthostatic hypotension may occur. The risk of neurologic toxicity is greater if 
vincristine is administered to patients with preexisting neuromuscular disorders or when other 
drugs with risk of neurologic toxicity are being given. The most frequent manifestations of 
nervous system toxicity are as follows:
Peripheral neuropathy, the earliest indication of which is the depression of the Achilles reflex. 
Later loss of other deep tendon reflexes occurs and is accompanied by peripheral paresthesias, 
pain, and tingling. If therapy is prolonged or high doses are administered, wrist and foot drop, 
ataxia, a slapping gait, and difficulty in walking may occur. Young children may refuse to walk 
due to extremity pain.
Cranial nerve neuropathy may lead to vocal cord paresis or paralysis (hoarseness, weak voice), 
ocular motor nerve dysfunction (ptosis, strabismus), bilateral facial nerve palsies, or jaw pain. 
Severe jaw pain can occur within a few hours of the first dose of vincristine. Cranial nerve
toxicities tend to be bilateral and reversible when treatment with vincristine is discontinued.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 54
LY3012207
Autonomic neuropathy is manifested as constipation (which can be severe), abdominal pain,
urinary retention, and paralytic ileus. Laxatives or stool softeners should be considered routinely 
to prevent constipation. These symptoms resolve with time and may not occur with subsequent
treatment. If bladder atony occurs, vincristine should be held until symptoms resolve. 
Worsening neuropathy requires dose delay, reduction, or discontinuation.
Table JGDN.7.8.
General Guidelines for Dose Modification of Vincristine due to 
Toxicity
Toxicity/Worst Counts in Cycle
Vincristine Dose Reduction
  Neurotoxicity
       Grade 1 or 2 
Full dose
       Grade 3 or 4
Hold until Grade ≤1 then 50% of initial dose a
  Severe paralytic ileus
Hold until normal bowel movement then 50% of 
initial dose
  Grade 3 other related nonhematologic/organ toxicity
Hold
  Grade 4 other related nonhematologic/organ toxicity
Discontinue
a
Reescalation to 75% or full dose should be considered at the start of each vincristine containing cycle based on 
patient’s symptoms.
7.2.4.3.2.2.
Hepatic Toxicity
Fatal liver toxicity and elevated levels of aspartate aminotransferase have occurred with vincristine 
use. Monitor hepatic function tests. Reduce or interrupt vincristine for hepatic toxicity
(Table JGDN.7.9).
Table JGDN.7.9.
General Guidelines for Vincristine Dose Modification Due to 
Elevated Serum Total Bilirubin Concentrations
Serum Bilirubin Concentration
Vincristine Dose Reduction
<2.1 mg/dL
Full dose
2.1 to 4 mg/dL
50% of initial dose
4.1 to 6 mg/dL
25% of initial dose
Greater than 6 mg/dL
Do not initiate vincristine
Discontinue vincristine
7.2.4.4.
Irinotecan Dose Adjustments
Dose levels and adjustments for irinotecan are shown in Table JGDN.7.10.  General guidelines 
for irinotecan dose modifications are shown in Table JGDN.7.11.
7.2.4.4.1. Hematologic Toxicities
Irinotecan may cause severe myelosuppression and deaths due to sepsis following severe 
myelosuppression. Therapy should be temporarily discontinued if neutropenic fever occurs or if 
the ANC is <750/mm3. The dose of irinotecan should be reduced according to
Table JGDN.7.11. Patients with abnormal glucuronidation of bilirubin, such as Gilbert's 
syndrome, may also be at greater risk of myelosuppression when receiving irinotecan. A new 
cycle of therapy should not begin until the granulocyte count has recovered to ≥750/mm3 and the 
platelet count has recovered to ≥75,000/mm3.  Treatment should be delayed 1 to 2 weeks to 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 55
LY3012207
allow for recovery from treatment-related toxicities. If the patient has not recovered after a 
2-week delay, consideration should be given to discontinuing irinotecan.
7.2.4.4.2. Diarrhea and Cholinergic Reactions
Irinotecan may cause severe, dose-limiting, and potentially fatal diarrhea. Early diarrhea has 
occurred during or shortly after infusion and may be accompanied by symptoms of rhinitis, 
increased salivation, miosis, lacrimation, diaphoresis, flushing, and abdominal cramping. 
Atropine 0.01 mg/kg IV (maximum dose: 0.4 mg) may be used to prevent or treat symptoms of 
early diarrhea. Late diarrhea has occurred >24 hours after irinotecan administration and can be 
prolonged, leading to life-threatening dehydration and electrolyte imbalance. Treat late diarrhea 
promptly with loperamide until a normal pattern of bowel movements returns; fluid and 
electrolyte replacement may be needed for dehydration. Provide antibiotic support (cefixime has 
been used in children whose diarrhea persisted >24 hours despite loperamide) if patient develops 
persistent diarrhea, ileus, fever, or severe neutropenia. Interrupt or reduce subsequent irinotecan 
doses if NCI CTCAE Grade 3 (increase of 7-9 stools daily, or incontinence, or severe cramping) 
or Grade 4 (increase ≥10 stools daily, grossly bloody stool, or need for parenteral support) late 
diarrhea occurs. Cases of colitis complicated by ulceration, bleeding, ileus, and infection have 
been reported. Renal impairment and acute renal failure have been reported, possibly due to 
dehydration secondary to diarrhea.  A new cycle of therapy should not begin until treatment-
related diarrhea is fully resolved.  If the patient has not recovered after a 2-week delay, 
consideration should be given to discontinuing irinotecan.
Table JGDN.7.10.
Dose Levels and Adjustments for Irinotecan
Dose at Enrollment
Dose Reduction
-1 dose level
-2 dose levels
3 dose levels
50 mg/m²/d
25% reduction
50%  reduction 
discontinue irinotecan

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 56
LY3012207
Table JGDN.7.11.
General Guidelines for Dose Modification of Irinotecan due to 
Toxicity
Toxicity
During a Cycle of Therapy
Neutropenia
    Grade 3 (500 to 749/mm3)
Hold dose until resolved to ≥750/mm3; no dose reduction
    Grade 4 (<500/mm3)
Hold dose until resolved to ≥750/mm3 and then decrease by 
1 dose level
Neutropenic fever
Hold dose until resolved
Diarrhea
    Grade 2 (4–6 stools/day > pretreatment)
Hold dose; no dose reduction
    Grade 3 (7–9 stools/day > pretreatment)
Hold dose until resolved to ≤2 and then decrease by 1 dose level
    Grade 4 (≥10 stools/day > pretreatment)
Hold dose until resolved to ≤2 and then decrease by 2 dose levels
Other nonhematologic toxicities
    Grade 2
Hold dose; no dose reduction
    Grade 3
Hold dose until resolved to ≤2 and then decrease by 1 dose level
    Grade 4
Hold dose until resolved to ≤2 and then decrease by 2 dose levels
7.2.4.5.
Ifosfamide Dose Adjustments
7.2.4.5.1. Urotoxic Effects
The incidence of urotoxic effects without an uroprotector can be up to 40% and is dose
dependent; coadministration with mesna and adequate hydration are mandatory. Patients may
present with hematuria, symptomatic cystitis, or bladder fibrosis. Past or concomitant radiation 
of the bladder or busulfan treatment may increase the risk of hemorrhagic cystitis. Several 
methods of treatment for established hematuria have been described: bladder irrigation with 
water or normal saline, intravesical instillation of astringents (alum, silver nitrate), systemic 
administration of antifibrinolytics (aminocaproic acid, tranexamic acid), cystoscopy to evacuate 
the bladder of clots, continuous bladder irrigation, and intravesical prostaglandins. For severe or 
refractory hematuria, intravesical formalin, phenol, or prostaglandin has been used ± surgical 
intervention (electrocautery, cryosurgery, diversion of urine flow, hypogastric artery ligation, or 
cystectomy).  Ifosfamide should be discontinued or dose reduced for macroscopic hematuria.
7.2.4.5.2. Proximal Tubular Damage
Glomerular, proximal, or distal tubular impairment may all occur, often in combination and may
progress even after ifosfamide has been discontinued. Proximal tubular damage often presents as 
Fanconi syndrome with low serum bicarbonate, proteinuria, glucosuria, aminoaciduria, and 
hypochloremic metabolic acidosis. Risk factors for the development of nephrotoxicity include 
age less than 5 years; preexisting renal impairment; prior treatment with cisplatin; concurrent use 
of nephrotoxic drugs, reduced renal reserve (unilateral nephrectomy, renal radiation); 
hydronephrosis; and total cumulative dose. Renal impairment may increase the risk of 
myelosuppression and possibly, cardiotoxicity. Mesna does not appear to be protective against 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 57
LY3012207
the proximal tubular abnormalities induced by ifosfamide.  Dose modifications of ifosfamide due 
to renal impairment are shown in Table JGDN.7.12.
Table JGDN.7.12.
Dose Modification of Ifosfamide due to Renal Impairment
Creatinine Clearance (mL/Min)
Ifosfamide Dose Reduction
>60
Full dose
40-60
75% of initial dose
20-40
50% of initial dose
<20
Discontinue
7.2.4.5.3. Central Nervous System
Central nervous system toxicity appears to be dose dependent, and is variable in onset, but 
usually resolves when ifosfamide is discontinued. Incidence is higher with higher doses, 
concomitant use of aprepitant, electrolyte imbalances, renal/ hepatic impairment or preexisting 
CNS disorders. It may manifest as transient mental status changes (somnolence, confusion, 
hallucination, disorientation, and lethargy), cerebellar dysfunction, extrapyramidal symptoms, 
transient weakness, cranial nerve dysfunction or seizure activity. Methylene blue, which may act 
as an electron acceptor or decrease chloracetaldehyde formation, has been suggested as treatment 
or prophylaxis of ifosfamide induced encephalopathy.
7.2.4.5.4. Other Toxicities
General guidelines for ifosfamide dose modification are shown in Table JGDN.7.13.  Dose 
modifications of ifosfamide due to hepatic impairment are shown in Table JGDN.7.14.
Table JGDN.7.13.
General Guidelines for Dose Modification of Ifosfamide due to 
Toxicity
Worst Toxicity /Counts in 
Previous Cycle
Ifosfamide Dose Reductiona
Febrile neutropenia
First episode:  maintain full dose and include GCSF at subsequent cycles.
Subsequent episodes: Decrease 20%
Platelets <75,000/mm3
If less than 1 week duration:  maintain full dose
If greater than 1 week duration:  Decrease 20%
Thrombocytopenic bleeding
Decrease 20%
Somnolence or other signs of 
encephalopathy
Hold; methylene blue 50 mg intravenous every 4 hours until resolution. 
Consider prophylactic methylene blue for subsequent cycles. Consider 
discontinuing or dose reduction for next cycle.
Grade 3 related organ / 
nonhematologic
Decrease 20%
Grade 3 or 4 neurotoxicity
Discontinue
Grade 4 related organ / 
nonhematologic
Discontinue
a
Do not retreat until absolute neutrophil count ≥ 750/mm3, platelets ≥ 75,000/mm3 and toxicity recovered to ≤ 
Grade 2.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 58
LY3012207
Table JGDN.7.14.
Dose Modification of Ifosfamide due to Hepatic Impairment
Bilirubin
AST/ALT
Ifosfamide Dose Reduction*
1-2 X ULN
And/or
<2 X ULN
Full dose
2-4 X ULN
2-5 X ULN
75% of initial dose
>4 X ULN
>5 ULN
Discontinue
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal.
a
Based on clinical judgment – less conservative adjustments can be considered if hepatic changes are secondary to 
metastases rather than hepatic cirrhosis or hepatitis.
7.3.
Method of Assignment to Treatment
Patients who meet all criteria for enrollment will be assigned to receive olaratumab 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 site will register the patient by 
assigning the patient a unique study identification number via the Interactive Web Response 
System (IWRS), which is accessible 24 hours a day. Study drug will be allocated to patients 
using the IWRS.  No dose escalations (that is, initiating Parts B and C for a chemotherapy 
combination) can occur without prior discussion and agreement with the responsible Lilly CRP 
or CRS.
In Part A, if investigators have eligible patients who have consented concurrently, more than 
3 patients may be entered for a particular chemotherapy combination 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
All concomitant medications should be recorded throughout the patient’s participation in the 
study.
Concomitant medications and supportive care therapies must also be documented at the time of 
discontinuation and at the 30-day short-term follow-up visit.
With the exceptions listed in the sections below, no other chemotherapy, investigational 
medications, other anticancer therapy, immunotherapy, hormonal cancer therapy, radiation, or 
surgery for cancer will be permitted while patients are on study treatment.  Palliative 
radiotherapy (of ≤14 calendar days, e.g., for a solitary skeletal metastasis) after Cycle 7 may be 
allowed as long as the patient has not developed another reason for study discontinuation and 
other sites of disease are available for response assessment.  Palliative radiation may not occur 
prior to discussion with the study medical monitor and written approval.  

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 59
LY3012207
Appropriate documentation for all forms of premedications, supportive care, and concomitant 
medications (for example, medications such as sedatives, antibiotics, analgesics, antihistamines, 
corticosteroids, erythropoietin; procedures such as paracentesis, thoracentesis; or blood products 
such as blood cells, platelets, fresh frozen plasma transfusions) must be captured on the eCRF.
If premedication is required prior to the chemotherapy infusion, this must be done after the 
completion of olaratumab infusion, not before the olaratumab infusion.
7.5.1. Supportive Care
Patients should receive full supportive care, if necessary.  Patients will receive supportive care as 
judged by their treating physician.  If it is unclear whether a therapy should be regarded as 
supportive care, the investigator should consult the Lilly CRP.  Use of any supportive care 
therapy must be captured on the eCRFs.
7.5.1.1.
Dexrazoxane
For patients in the doxorubicin combination arm, dexrazoxane may be administered starting with
the first dose of doxorubicin at the investigator’s discretion according to instructions provided in 
the Pharmacy Manual for this study, beginning within 30 minutes prior to each doxorubicin 
infusion for the prevention of cardiotoxicity.  It is recommended that all patients receiving 
doxorubicin receive dexrazoxane.  Investigators should consult the dexrazoxane information 
provided in the Pharmacy Manual for this study for administration information (including 
warnings, precautions, contraindications, adverse reactions, and dose modifications).
Note that as the dose of dexrazoxane administered is dependent on the dose of doxorubicin 
administered, any dose modifications to doxorubicin will require a corresponding dose 
modification to dexrazoxane in order to maintain a dosage ratio of 10:1 
(dexrazoxane:doxorubicin).
7.5.1.2.
Mesna
For patients in the ifosfamide arm, mesna should be administered at a minimum dose equal to 
60% of the ifosfamide dose according to institutional guidelines, including divided dose or 
continuous infusion.  
Note that as the dose of mesna administered is dependent on the dose of ifosfamide administered, 
any dose modifications to ifosfamide will require a corresponding dose modification to mesna in 
order to maintain the correct dosage (mesna = minimum 60% ifosfamide).
7.5.1.3.
Hydration
Ifosfamide should be given with extensive hydration consisting of oral or intravenous fluid 
(2 L/m2 IV) to prevent bladder toxicity or according to institutional guidelines.  The criteria to 
start chemotherapy may also include a urine-specific gravity < 1.010 or according to institutional 
guidelines.
7.5.1.4.
Granulocyte-Colony Stimulating Factors and Erythroid Growth Factors
Following the first dose of combination chemotherapy , the use of G-CSFs such as Neulasta®
(pegfilgrastim) and erythroid stimulating factors (for example, erythropoietin) are permitted, 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 60
LY3012207
including prophylactic use, during investigational therapy at the discretion of the investigator or
according to ASCO guidelines (Smith et al. 2006) and NCCN guidelines (NCCN 2015).
7.5.1.5.
Transfusion of Blood Products
Transfusions of red blood cells, platelets, or other blood products are permitted at the 
investigator’s discretion, but may not be used to meet hematologic criteria for inclusion in the 
study (refer to Section 6.1.1, Inclusion Criterion [6]).
7.5.1.6.
Antiemetic Therapy
Both prophylactic and symptom-directed anti-emetic therapy are recommended and should be 
used in accordance with institutional guidelines (when existent) and/or at investigator’s 
discretion.
7.5.2. Prohibited Therapies
Additional concurrent chemotherapy, radiation therapy, biologic response modifiers, or other 
investigational or approved anticancer agents may not be administered to patients on this study.  
Palliative radiotherapy (of ≤14 calendar days, e.g., for a solitary skeletal metastasis) after Cycle 
7 may be allowed as long as the patient has not developed another reason for study 
discontinuation and other sites of disease are available for response assessment.  Palliative 
radiation may not occur prior to discussion with the study medical monitor and written approval.  
7.5.2.1.
Effect of CYP3A4, CYP2D6, and P-gp Inhibitors and Inducers on 
Doxorubicin
Doxorubicin is a major substrate of cytochrome P450 (CYP)3A4 and CYP2D6, and P-
glycoprotein (P-gp).  Clinically significant interactions have been reported with inhibitors of 
CYP3A4, CYP2D6, and/or P-gp, resulting in increased concentration and clinical effect of 
doxorubicin.  Inducers of CYP3A4 (for example, phenobarbital, phenytoin, and St. John’s Wort) 
and P-gp inducers may decrease the concentration of doxorubicin.  Avoid concurrent use of 
doxorubicin with inhibitors and inducers of CYP3A4, CYP2D6, or P-gp.  Refer to Attachment 9
for a list.
7.6.
Treatment Compliance
Study drugs will be administered intravenously at the investigational site, under the direction of 
the investigator.  As a result, a patient’s compliance with study drug administration is ensured.  
Patients should attend scheduled clinic visits and must comply with study criteria under their 
control.  Deviation(s) from the prescribed dosage regimen should be recorded on the eCRF.
7.6.1. Evaluable Patients
Patients who withdraw from the study before receiving study drug(s) will be replaced and will 
not be included in the safety or efficacy assessments.  Safety analyses will be conducted on all 
patients who have been exposed to study drug, regardless of whether they are deemed evaluable 
for other assessments.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 61
LY3012207
Any patient from Parts A or B who is discontinued from the study before completing 1 cycle of 
olaratumab treatment will be deemed non-evaluable for assessment of olaratumab monotherapy, 
unless the patient experiences a DLT prior to withdrawal. Any patient who is discontinued from 
the study before completing 1 cycle of combination chemotherapy treatment (Cycle 2 for Parts A 
or B or Cycle 1 for Part C) will be deemed non-evaluable for assessment of a combination 
chemotherapy, unless the patient experiences a DLT or DLE-equivalent prior to withdrawal.  
If a patient from Parts A or B is noncompliant during Cycle 1 due to reasons other than drug-
related toxicity, he or she will be considered non-evaluable for olaratumab monotherapy and may 
be replaced.  If a patient from Parts A or B is noncompliant during Cycle 2 or a patient from Part 
C is noncompliant during Cycle 1 due to reasons other than drug-related toxicity, he or she will 
be considered non-evaluable for combination chemotherapy and may be replaced.
Nonevaluable patients may be replaced to ensure that enough patients complete 1 cycle of 
olaratumab monotherapy or combination chemotherapy, unless accrual to that cohort has stopped 
due to a DLT.
Patients who are not evaluable for pharmacokinetics, but who complete 1 cycle of olaratumab 
monotherapy or 1 cycle of combination chemotherapy, may be replaced to ensure adequate PK 
data, unless accrual to that cohort has stopped due to a DLT.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 62
LY3012207
8. Safety, Pharmacokinetic, Pharmacodynamic, and 
Efficacy Data Collection
8.1.
Safety Evaluations
The safety and tolerability of olaratumab have been assessed in nonclinical toxicology and 
clinical studies and the results from these studies are detailed in the IB.  This Phase 1 study 
contains detailed safety monitoring that will permit initial characterization of the safety profile of 
olaratumab in pediatric patients.  Study procedures and their timing, including collection of 
blood and urine samples, are described in the Study Schedule (Attachment 1).
Standard laboratory tests, including chemistry, hematology, coagulation and urinalysis panels, 
will be performed.  A serum pregnancy test will be administered if applicable.  Other clinical 
laboratory tests will also be collected.  Attachment 2 lists the specific tests that will be performed 
for this study.
8.1.1. Safety Data Collection and Review
Investigators are responsible for monitoring the safety of patients who have entered into this 
study and for alerting Lilly or its designee to any event that seems unusual, even if this event 
may be considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of the patient during the study.
The investigator remains responsible for following, through an appropriate health care option,
AEs that are serious, considered related to study treatment or the study, or that caused the patient 
to discontinue before completing the study.  The patient should be followed until the event is 
resolved, the event is no longer considered to be drug-related, the event becomes stable or 
returns to baseline, a new treatment is initiated for the patient, or the patient dies or is lost to 
follow-up.  Frequency of AE and serious adverse event (SAE) follow-up evaluation is left to the 
discretion of the investigator.
The timing of all safety evaluations is shown in the Study Schedule (Attachment 1).  
Table JGDN.8.1 presents a summary of AE and SAE reporting guidelines.  Table JGDN.8.1 also 
shows which database or system is used to store AE and SAE data.
8.1.2. Adverse Events
Lilly has standards for reporting AEs that are to be followed regardless of applicable regulatory 
requirements that may be less stringent.  A clinical study AE is any untoward medical occurrence 
in a patient or clinical investigation subject administered a pharmaceutical product and which 
does not necessarily have a causal relationship with this treatment.  An 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 
it is 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 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 63
LY3012207
designee as an AE.  Lack of drug effect is not an AE in clinical studies because the purpose of 
the clinical study is to establish drug effect.
The investigator, monitor, and sponsor will review the collected data regularly for evidence of 
AEs.  All patients will be assessed routinely for AEs as outlined in the study schedule.  All AEs 
observed will be graded using CTCAE v 4.0.
The NCI-CTCAE v 4.0 will serve as the reference document for choosing appropriate 
terminology for, and grading the severity of, all AEs and other symptoms. All AEs observed 
will be graded using CTCAE v 4.0.  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.  For AEs without matching terminology within the NCI-CTCAE v 4.0 
criteria, the investigator will be responsible for selecting the appropriate system organ class and 
assessing severity grade based on the intensity of the event.  Note that both CTCAE term (actual 
or coded) and severity grade must be selected by study site personnel and collected on the eCRF.  
This collection is in addition to verbatim text used to describe the AE.
In addition to collecting the AE verbatim, the CTCAE term, and the CTCAE severity grade, AE 
verbatim text will also be mapped by the sponsor or designee to corresponding terminology 
within the Medical Dictionary for Regulatory Activities (MedDRA™) dictionary.
Cases of pregnancy that occur during maternal or paternal exposures to study drug should be 
reported.  Data on fetal outcome and breastfeeding should be collected, if feasible, for regulatory 
reporting and drug safety evaluation.
Upon documentation of pregnancy, the patient must be removed from the study and treatment 
with study drug(s) must be stopped immediately.
For all enrolled patients, study site personnel will record the occurrence and nature of each 
patient’s preexisting condition(s), including clinically significant signs and symptoms of the 
disease under treatment in the study.  While the patient is on study, site personnel will record any 
change in these preexisting condition(s) and the occurrence and nature of any AEs.  In addition,
all AEs related to protocol procedures are reported to Lilly or designee.
If a patient's dosage is reduced or treatment is discontinued as a result of an AE, study site 
personnel must clearly report to Lilly or its designee via eCRF the circumstances and data 
leading to any such dosage reduction or discontinuation of treatment.
Investigators will be instructed to report to Lilly or its designee their assessment of the potential 
relatedness of each AE to protocol procedure or study drug via eCRF.
The investigator decides whether he or she interprets the observed AEs as either related to 
disease, 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 64
LY3012207

Possibly related:  a cause and effect relationship between the study treatment and 
the AE has not been demonstrated at this time and is not probable, but is also not 
impossible.

Unrelated:  without question, the AE is definitely not associated with the study 
treatment.
As per Lilly’s standard operating procedures, all “related” and “possibly related” AEs and SAEs 
will be defined as related to study drug.
8.1.2.1.
Serious Adverse Events
Serious adverse event collection begins after the patient has signed informed consent and has
received study drug. If a patient experiences an SAE after signing informed consent, but prior to
receiving study drug, the event will not be reported as serious unless the investigator feels the
event may have been caused by a protocol procedure.
Planned surgeries should not be reported as SAEs unless the underlying medical condition has 
worsened during the course of the study.
Planned hospitalizations or elective procedures for underlying preexisting conditions that are 
already recorded in the patient’s medical history at the time of study enrollment should not be 
considered SAEs.  Hospitalization or prolongation of hospitalization without a precipitating 
clinical AE (for example, for the administration of study therapy or other protocol-required 
procedure) should not be considered SAEs.
An SAE is any adverse event during this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization (except for study drug 
administration)

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

considered significant by the investigator for any other reason
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.
Serious adverse events due to disease progression, including death, should not be reported unless 
the investigator deems them to be possibly related to the study drug.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 65
LY3012207
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.
If an investigator becomes aware of SAEs occurring after the patient’s participation in the trial 
has ended, and the investigator believes that the SAEs are related to a protocol procedure or 
study drug, the investigator should report the SAEs to the sponsor, and the SAEs will be entered 
in the Lilly Safety System.
Information on SAEs expected in the study population independent of drug exposure and that 
will be assessed by the sponsor in aggregate periodically during the course of the trial may be 
found in the IB.
For recommendations on reporting SAEs, see Attachment 5.
8.1.2.2.
Adverse Event and Serious Adverse Event Reporting
Data on SAEs that occur before the end of trial will be stored in the collection database and the 
Lilly Safety System.
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 ICF.  For patients who do not enroll in the trial (that is, 
have not received at least 1 dose of olaratumab), only AEs and SAEs related to protocol 
procedures are required to be reported.
8.1.2.2.2. On Therapy
All AEs and SAEs, regardless of relatedness to study drug(s) or protocol procedures, occurring 
while the patient is receiving study drug must be reported to Lilly or its designee.  A patient is 
considered to be receiving study drug from the time he/she receives the first dose of study drug 
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(s) or protocol procedures, occurring 
during the follow-up visit (Visit 801) must be reported to Lilly or its designee.  The follow-up 
visit (Visit 801) starts one day after the decision is made to discontinue the patient from the 
study.  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 days ± 7 days after the
decision is made to discontinue the patient from the study.
Following the safety assessments, which mark the end of the follow-up visit (Visit 801), 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 
long-term 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 66
LY3012207
If it is deemed to be in the best interest of the patient to start a new anticancer treatment prior to 
the scheduled end of the follow-up visit, the follow-up visit duration may be shortened. In this 
case, the follow-up assessments should be completed prior to the initiation of the new therapy.
After the follow-up visit (Visit 801), AEs are not required to be reported unless the investigator 
feels the AEs were related to either study drug, drug delivery system, or a protocol procedure. If 
an investigator becomes aware of an SAE believed to be related to protocol procedures or study
drug, the investigator should report the SAE to the sponsor, and the SAE will be entered in the
Lilly Safety System.
8.1.2.3.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious adverse events that are 
not listed in the Development Core Safety Information in the IB and that the investigator 
identifies as related to study drug or procedure.  The United States 21 CFR 312.32, the European 
Union Clinical Trial Directive 2001/20/EC, and the associated detailed guidances or national 
regulatory requirements in participating countries require the reporting of SUSARs.  Lilly has 
procedures that will be followed for the recording and expedited reporting of SUSARs that are 
consistent with global regulatory regulations and the associated detailed guidances.
8.1.2.4.
Summary of AE/SAE Reporting Guidelines
The AE and SAE reporting guidelines for enrolled patients are summarized in Table JGDN.8.1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 67
LY3012207
Table JGDN.8.1.
Adverse Event and Serious Adverse Reporting Guidelines for 
Patients Enrolled in Study JGDN
Timing
Types of AEs/SAEs Reported
Collection 
Database
Lilly Safety 
System
Prestudy (baseline assessments)
(Starts at the signing of informed consent 
and ends just before the first dose of study 
drug)
Preexisting conditions
All AEs
All SAEs regardless of relatedness
x
x
x
x
On therapy
(Starts at first dose of study drug(s) and 
ends at last dose of study drug(s))
All AEs
All SAEs regardless of relatedness
x
x
x
Follow-up Visit (Visit 801)
(Starts one day after the decision is made 
to discontinue patient from study and ends 
when end of study safety assessments are 
completed [approximately 30 days later])
All AEs
All SAEs regardless of relatedness
x
x
x
Subsequent Follow-up visits, if necessary 
for patient monitoring
Ongoing AEs possibly related to study 
drug(s), or protocol procedures
All SAEs related to protocol
procedures or study drug
x
x
x
Patient no longer on study
All SAEs related to protocol 
procedures or study drug that the 
investigator becomes aware of
x
Abbreviations:  AEs = adverse events; SAEs = serious adverse events.
8.1.3. Other Safety Measures
8.1.3.1.
Electrocardiograms
For each patient, a 12-lead digital ECG will be collected according to the Study Schedule 
(Attachment 1).
Consecutive replicate ECGs (3 readings) will be obtained, whenever feasible for the patient, 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.
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 first 
dose of study drug, 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

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 68
LY3012207
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 then conduct a full overread on 1 of the replicate ECGs 
(including all intervals).  A report based on data from this overread will be issued to the 
investigative site.  For each set of replicates, the RR and QT intervals and heart rate will be 
determined on the ECGs that were not fully overread.  These data are not routinely reported back 
to the investigative site.
All data from the overreads will be placed in the Lilly database for analytical and study report 
purposes.  Any clinically significant finding that was not present on the fully overread ECG but 
was present on the partially overread ECG (where only RR, QT, and heart rate are assessed) will 
be reported to the investigator and to Lilly.
If there are differences in ECG interpretation between the investigator (or qualified designee) 
and the cardiologist at the central ECG laboratory, the investigator’s (or qualified designee’s) 
interpretation will be used for study entry and immediate subject management.  Interpretations 
from the cardiologist at the central ECG laboratory will be used for data analysis and 
report-writing purposes.
The investigator (or qualified designee) must document his/her review of one of the replicate 
ECGs printed at the time of collection, the final overread ECG report issued by the central ECG 
laboratory, and any alert reports.
8.1.3.2.
Echocardiograms and Multigated Acquisition (MUGA) Scan
Refer to Section 7.2.4.2.2.
8.1.4. Safety Monitoring
The Lilly CRP or CRS will monitor safety data throughout the course of the study.
Representatives from Lilly Global Patient Safety will specifically monitor SAEs.  Lilly will 
review SAEs within time frames mandated by company standard operating procedures.  The 
Lilly CRP/CRS will, as is appropriate, consult with the functionally independent Global Patient 
Safety therapeutic area physician or clinical research scientist, and periodically review:

trends in safety data

laboratory analytes

adverse events

If a study patient experiences elevated ALT >5X 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 69
LY3012207
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/CRS regarding collection of specific recommended 
clinical information and follow-up laboratory tests (see Attachment 3).
8.1.5. Complaint Handling
Lilly collects complaints on study drugs used in clinical studies in order to ensure the safety of 
study participants, monitor quality, and facilitate process and product improvements.
Complaints related to concomitant drugs are reported directly to the manufacturers of those 
drugs in accordance with the package insert.
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 7 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 to determine whether patients meet 
inclusion/exclusion criteria and to monitor patient health. Investigators must document their
review of each laboratory safety report and include a determination of the clinical significance of
abnormal labs.
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. Pharmacokinetic Samples
At the visits and times specified in the Pharmacokinetic and Immunogenicity Sampling Schedule 
(Attachment 4), venous blood samples will be collected to determine the serum concentrations of 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 70
LY3012207
olaratumab and plasma concentrations of doxorubicin and doxorubicinol, vincristine, irinotecan
(and its active metabolite SN-38), and ifosfamide.  A maximum of 6 samples may be collected at 
additional time points during the study if warranted and agreed upon between both the 
investigator and Lilly. Instructions for the collection and handling of blood samples will be 
provided by the sponsor.  The actual date and time (24-hour clock time) of each sampling will be 
recorded.
These samples will be analyzed at a laboratory designated by the sponsor.  Serum concentrations 
of olaratumab will be assayed using a validated enzyme-linked immunosorbent assay method.  
Doxorubicin and doxorubicinol, vincristine, irinotecan, SN-38, and ifosfamide concentrations in 
plasma will be analyzed using specific liquid chromatography with tandem mass spectrometry 
assays.
The PK samples will be stored at a facility designated by the sponsor.  The remaining plasma 
from the samples collected for pharmacokinetics may be pooled and used for exploratory 
metabolism work as deemed appropriate.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.
8.2.3. Samples for Tailoring Genetics Biomarkers
There is growing evidence that genetic variation may impact a patient’s response to therapy.  
Variable response to therapy may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion, the mechanism of action of the drug, the disease 
etiology, and/or the molecular subtype of the disease being treated.  Therefore, where local 
regulations and ERBs allow, a blood sample will be collected for pharmacogenetic analysis as 
specified in the Sampling Schedule (Attachment 1).  These samples are not being collected to 
create a biobank for conducting unspecified disease or population genetic research either now or 
in the future.
Samples may be used to investigate variable response to study treatment and to investigate 
genetic variants thought to play a role in cancer.  Assessment of variable response may include 
evaluation of AEs or differences in efficacy.  These studies may include but are not limited to the 
PGDFRα pathway to evaluate their association with observed response to study treatment.
In the event of an unexpected AE or the observation of unusual response, the pharmacogenetic 
biomarker samples may be genotyped and analysis may be performed to evaluate a genetic 
association with response to olaratumab.  These investigations may be limited to a focused 
candidate gene study or, if appropriate, genome-wide analysis may be performed to identify 
regions of the genome associated with the variability observed in drug response.  The 
pharmacogenetic biomarker samples will only be used for investigations related to disease and 
drug or class of drugs under study in the context of this clinical program.  They will not be used 
for broad exploratory unspecified disease or population genetic analysis.
Samples will be retained for a maximum of 15 years after the last patient visit, or as local 
regulations and ERBs allow, for the study at a facility selected by the sponsor.  This retention 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 71
LY3012207
period enables use of new technologies, response to regulatory questions, and investigation of 
variable response that may not be observed until later in drug development or when the drug is 
commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome-wide association studies, candidate gene studies, and epigenetic analyses.  
Regardless of the technology utilized, genotyping data generated will be used only for the 
specific research scope described in this section.
Samples will be destroyed according to a process consistent with local regulation.
8.2.4. Samples for Immunogenicity Research
Blood samples for immunogenicity testing will be collected at the visits and times specified in 
the Pharmacokinetic and Immunogenicity Sampling Schedule (Attachment 4) to determine 
antibody production against olaratumab.  Immunogenicity will be assessed by a validated serum 
assay designed to detect anti-drug antibodies in the presence of olaratumab.  Antibodies may be 
further characterized and/or evaluated for their ability to neutralize the activity of olaratumab.
Immunogenicity may be further characterized by performing additional related assays. In the 
event of an IRR, additional samples will be evaluated (see Attachment 4).
Samples may be stored for a maximum of 15 years following last patient visit for the trial at a 
facility selected by the sponsor to enable further analysis of immune responses to olaratumab.  
The duration allows the sponsor to respond to regulatory requests related to olaratumab.
8.2.5. Tailoring Biomarker Samples
Collection of samples for other biomarker research is also part of this study.  Tumor tissue and 
plasma samples will be collected.
Required samples for biomarker research to be collected from all patients in this study are the 
following:

plasma
Optional samples for biomarker research that should be collected from patients in the study 
where possible are the following:

tumor tissue (archival or new biopsy)
Samples will be collected for potential non-pharmacogenetic biomarker research.  Tumor tissue 
and plasma samples will be collected at the times specified in the Sampling Schedule 
(Attachment 1).
Samples may be used for research on the drug target, disease process, pathways associated with 
cancer, mechanism of action of olaratumab, and/or research method or in validating diagnostic 
tools or assays related to cancer.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 72
LY3012207
Where local regulations and ERBs allow, these samples will be collected for biomarker research 
as discussed below and specified in the Sampling Schedule (Attachment 1).
Samples will be retained for a maximum 15 years after the last patient visit for the study at a 
facility selected by the sponsor.  This retention period enables use of new technologies, response 
to regulatory questions, and investigation of variable response that may not be observed until 
later in drug development or when the drug is commercially available.
8.3.
Efficacy Evaluations
A secondary objective of the study is to document any antitumor activity.  Imaging studies and 
tumor assessments are to be obtained every 2 cycles (±7 days), until documented progression for 
patients with complete response (CR), partial response (PR), or stable disease (SD).
For patients who have discontinued study treatment due to toxicity or reasons other than 
progressive disease, imaging studies and tumor assessments are to be obtained every 6 weeks 
(±7 days) until progression.  For these patients, details on subsequent anticancer treatment 
(start/stop dates and treatments administered) and first post-study treatment disease progression 
date should be recorded.
Each patient will be assessed by one or more of the following radiologic tests for tumor 
measurement:

Computed tomography (CT) scan

Magnetic resonance imaging (MRI)

Chest x-ray
Each patient’s full extent of disease will also be assessed with the following:

Tumor measurement by RECIST v1.1 (Eisenhauer et al. 2009) should be used for 
all tumors with the exception of CNS tumors. RANO (Wen et al. 2010) or 
Macdonald (Macdonald et al. 1990) criteria should be used for CNS tumors.

Evaluation of tumor markers, if indicated

Evaluation of performance status (Lansky [Lansky et al. 1987] or Karnofsky 
[Karnofsky et al. 1948] scale)
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 6 weeks
(2 cycles) 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 73
LY3012207
The collection times of safety assessments, PK samples, pharmacodynamics (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 eCRF.
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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 74
LY3012207
9.
Data Management Methods
9.1.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

sponsor start-up training to instruct the investigators and study coordinators.  This session 
will give instruction on the protocol, the completion of the eCRFs, and study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by mail, 
telephone, and/or fax

review and evaluate eCRF 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 institutional 
review board/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.
Any data for which paper documentation provided by the patient or parent/guardian 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 measures (for example, a rating scale), a daily dosing schedule or an 
event diary.
For data handled by a data management third-party organization (TPO), CRF data and some or 
all data that are related will be managed and stored electronically in the TPO system.  
Subsequent to the final database lock, validated data will be transferred to the Lilly data 
warehouse, using standard Lilly file transfer processes.
For data handled by the sponsor internally, CRF data and some or all data that are related will be 
managed by the sponsor and stored electronically in the sponsor’s system.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 75
LY3012207
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 data 
warehouse.
Bioanalytical data will be stored electronically in the bioanalytical laboratory’s database.  Data 
will subsequently be transferred from the bioanalytical laboratory to the Lilly data warehouse.
Electrocardiogram 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 data warehouse.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 76
LY3012207
10. Data Analyses
10.1. General Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company.
The interpretation of the study results will be the responsibility of Lilly CRP, CRS, 
pharmacokineticist, and statistician.  The CRP, 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.
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/listing 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 olaratumab will be evaluated for safety and toxicity.  
Adverse event terms and severity grades will be assigned by the investigator using CTCAE, 
Version 4.0.  Adverse events will be characterized by the frequency of observed toxicities 
(treatment-emergent adverse events, SAEs, deaths, and discontinuations due to AEs).
Safety analyses will include summaries of the following:

AEs, including severity and possible relationship to study drug

dose adjustments

laboratory values

vital signs

DLTs at each dose level

ECG readings

ECHO/MUGA scanning

immunogenicity data
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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 77
LY3012207
Mean population PK parameters for olaratumab in serum (clearance, volume of distribution) and 
inter-individual PK variability will be computed for this study using nonlinear mixed-effect 
modeling implemented in 
 in order to describe the dose-concentration relationship in 
the target population.  Covariate effects (such as age, weight, and sex) on the PK parameters of 
olaratumab in serum will also be investigated.
Pharmacokinetic data collected for doxorubicin and doxorubicinol, vincristine, irinotecan, and 
ifosfamide will be analyzed using descriptive statistics.
Additional analyses such as exposure-response using appropriate efficacy or safety clinical 
endpoints may be performed, if warranted by the data.
The version of any software used for the analysis will be documented, and the program will meet 
Lilly requirements of software validation.  It is possible that other validated equivalent PK 
software programs may be utilized if appropriate, warranted, and approved by global PK 
management.
The population PK and PK/PD analyses will be reported as separate standalone reports for this 
study.
10.6. Immunogenicity Analyses
Incidence of treatment-emergent anti-olaratumab antibodies will be tabulated.  The potential 
impact of immunogenicity on olaratumab exposure will be evaluated in the population PK 
modeling exercises where immunogenicity will be evaluated as a covariate.  In addition, 
graphical assessments will be conducted, as appropriate, to compare drug exposure between 
treatment-emergent anti-drug antibody (ADA)-negative and treatment-emergent (TE) 
ADA-positive patients at correspondent visits, or before and after TE-ADA development for 
patients who developed TE-ADA.
In the event of an IRR, the immunogenicity and olaratumab serum concentrations will be 
tabulated.
10.7. Efficacy Analyses
Exploratory efficacy analysis will be performed to investigate antitumor activity within each 
combination arm.  Progression-free survival curves and the median with 90% confidence interval 
(CI) will be estimated using Kaplan-Meier method (Kaplan and Meier 1958).  The objective 
response rate (ORR=CR+PR) and disease control rate (DCR=CR+PR+SD) and the 90% exact CI
will be tabulated for each cohort. Additional analyses may be performed as necessary. The 
details will be outlined in the statistical analysis plan (SAP).
10.8. Interim Analyses
No interim analyses are planned for this study.  If an unplanned interim analysis is deemed 
necessary, the sponsor will determine if it is necessary to amend the protocol.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 78
LY3012207
Since this is a dose-finding study, data will be reviewed on a cohort-by-cohort basis during the 
study, until the maximum-tolerated dose (MTD) is determined.  The purpose of these cohort-by-
cohort reviews is to evaluate the safety data at each dose level and determine if a DLT has been 
observed that would suggest MTD has been met or exceeded.  The investigators and the Lilly
study team will make the determination regarding dose escalation based upon their review of the 
safety and tolerability data as described in this protocol.
10.9. Biomarker Analyses
Exploratory biomarker assay results will be summarized and correlated with clinical outcomes.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 79
LY3012207
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.
A legal representative must give informed consent for a child to participate in this study.  In 
addition to informed consent given by the legal representative, the child may be required to give 
documented assent, if capable.
In this protocol, the term "informed consent" includes all consent and assent given by patients or 
their legal representatives.
11.2. Ethical Review
Lilly or its representatives must approve all ICFs before they are used at investigative sites(s).  
All ICFs must be compliant with the ICH guideline on GCP.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  The ERB(s) will review the protocol as required.
The study site’s ERB(s) should be provided with the following:

the current IB and updates during the course of the study

ICF

relevant curricula vitae

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 80
LY3012207
11.3. Regulatory Considerations
This study will be conducted in accordance with:
1) consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences
International Ethical Guidelines
2) the ICH GCP Guideline [E6]
3) applicable laws and regulations
The investigator or designee will promptly submit the protocol to applicable ERB(s).
Some of the obligations of the sponsor will be assigned to a TPO.
An identification code assigned 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 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 81
LY3012207
12. References
Bruheim S, Bruland OS, Beistol K, Maelandsmo GM, Fodstad O. Human osteosarcoma 
xenografts and their sensitivity to chemotherapy. Pathol Oncol Res. 2004;10(3):133-141.
Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, 
Version 4.0, DCTD, NCI, NIH, DHHS. 2009. Publish date: 29 May 2009.
Carli M, Passone E, Perilongo G, Bisogno G. Ifosfamide in Pediatric Solid Tumors. Oncology. 
2003;65(suppl 2):99-104.
de Jong JS, van Diest PJ, van der Valk P, Baak JP. Expression of growth factors, growth 
inhibiting factors, and their receptors in invasive breast cancer. I: An inventory in search of 
autocrine and paracrine loops. J Pathol. 1998;184(1):44-52.
DuBois S, Demetri G. Markers of antiogenesis and clinical features in patients with sarcoma.  
Cancer. 2007;109(5):813-819.
Dubois SG, Marina N, Glade-Bender J. Angiogenesis and vascular targeting in Ewing sarcoma. 
Cancer.2010;116(3):749-757.
Ehnman M, Missiaglia E, Folestad E, Selfe J, Strell C, Thway K, Brodin B, Peitras K, Shipley J, 
Östman A, Eriksson U. Distinct effects of ligand-induced PDGFRα and PDGFRβ signaling in 
the human rhabdomyosarcoma tumor cell and stroma cell compartments. 
2013;73(7):2139-2149.
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.
Fleming TP, Saxena A, Clark WC, Robertson JT, Oldfield EH, Aaronson SA, Ali IU. 
Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal 
growth factor receptor in human glial tumors. Cancer Res. 1992;52(16):4550-4553.
Forsberg K, Valyi-Nagy I, Heldin CH, Herlyn M, Westermark B. Platelet-derived growth factor 
(PDGF) in oncogenesis: development of a vascular connective tissue stroma in 
xenotransplanted human melanoma producing PDGF-BB. Proc Natl Acad Sci USA. 
1993;90(2):393-397.
Gerber DE, Gupta P, Dellinger MT, Toombs JE, Peyton M, Duignan I, Malaby J, Bailey T, 
Burns C, Brekken RA, Loizos N. Stromal platelet-derived growth factor receptor α (PDGFRα) 
provides a therapeutic target independent of tumor cell PDGFRα expression. Mol Cancer 
Ther. 2012;11(11):2473-2482.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. JAMA. 
1958;53(282):457-481.
Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH. The use of nitrogen mustards in the 
palliative treatment of carcinoma with particular reference to bronchogenic carcinoma. 
Cancer. 1948;1(4):634-669.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 82
LY3012207
Lansky SB, List MA, Lansky LL, Ritter-Sterr C, Miller DR. The measurement of performance in 
childhood cancer patients. Cancer. 1987;60(7):1651-1656.
Loizos N, Xu Y, Huber J, Liu M, Lu D, Finnerty B. Targeting the platelet derived growth factor 
receptor α with a neutralizing human monoclonal antibody inhibits the growth of tumor 
xenografts: implications as a potential therapeutic target. Mol Cancer Ther. 
2005;4(3):369-379.
Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies 
of supratentorial malignant glioma. J Clin Oncol. 1990;8(7):1277-1280.
Mascarenhas L, Lyden ER, Breitfeld PP, Walterhouse DO, Donaldson SS, Paidas CN, 
Parham DM, Anderson JR, Meyer WH, Hawkins DS. Randomized phase II window trial of 
two schedules of irinotecan with vincristine in patients with first relapse or progression of 
rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol. 
2010;28(30):4658-4663.
McDermott U, Ames RY, Iafrate AJ, Maheswaran S, Stubbs H, Greninger P, McCutcheon K, 
Milano R, Tam A, Lee DY, Lucien L, Brannigan BW, Ulkus LE, Ma XJ, Erlander MG, 
Haber DA, Sharma SV, Settleman J. Ligand-dependent platelet-derived growth factor receptor 
(PDGFR)-alpha activation sensitizes rare lung cancer and sarcoma cells to PDGFR kinase 
inhibitors. Cancer Res. 2009;69(9):3937-3946.
McGary EC, Weber K, Mills L, Doucet M, Lewis V, Lev DC, Fidler IJ, Bar-Eli M. Inhibition of 
platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel 
tyrosine kinase inhibitor STI571. Clin Cancer Res. 2002;8(11):3584-3591.
[NCCN] National Comprehensive Cancer Network. NCCN guidelines. 2015. Available at: 
http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed October 27, 
2015.
Ostman A, Heldin CH. PDGF receptors as targets in tumor treatment. Adv Cancer Res. 
2007;97:247-274.
Paugh BS, Zhu X, Qu C, Endersby R, Diaz AK, Zhang J, Bax DA, Carvalho D, Reis RM, 
Onar-Thomas A, Broniscer A, Wetmore C, Zhang J, Jones C, Ellison DW, Baker SJ. Novel 
oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res.
2013;73(20):6219-6229.
Sandler E, Lyden E, Ruymann F, Maurer H, Wharam M, Parham D, Link M, and Crist W.
Efficacy of ifosfamide and doxorubicin given as a phase II “window” in children with newly 
diagnosed metastatic rhabdomyosarcoma: a report from the intergroup rhabdomyosarcoma 
study group. Med Pediatr Oncol. 2001;37:442-448.
Schwartz GJ, Gauthier B. A simple estimate of glomerular filtration rate in adolescent boys. 
J Pediatr. 1985;106(3):522-526.
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular 
filtration rate in children derived from body length and plasma creatinine. Pediatrics.
1976;58(2):259-263.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 83
LY3012207
Shah GD, Loizos N, Youssoufian H, Schwartz JD, Rowinsky EK. Rationale for the development 
of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the 
platelet-derived growth factor receptor alpha. Cancer. 2010;116(4 suppl):1018-1026.
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.
[TCGA] The Cancer Genome Atlas. 2014. Available at: http://cancergenome.nih.gov/. Accessed 
May 13, 2015.
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, DeGroot J, 
Wick W, Gilbert MR, Lassman AB, Tsie C, Mikkelsen T, Wong ET, Chamberlain MC, 
Stupp R, Lamborn KR, Voglebaum MA, van den Bent MJ, Chang SM. Updated response 
assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology
Working Group. J Clin Oncol 2010;28(11):1963-1972.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 84
LY3012207
Attachment 1.
Protocol JGDN Study Schedule

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 85
LY3012207
JGDN Study Schedule, Screening and Baseline Assessments (All Parts)
Relative Day Prior to 
Cycle 1 Day 1
≤28
≤14
≤7
Comments
Eligibility Assessments
Informed Consent
X
Written informed consent must be obtained prior to any study-specific screening evaluations.
Medical History
X
Lansky/Karnofsky 
performance status
X
To be assessed by the investigator.
ECG
X
Consecutive replicate ECGs (3 readings) will be obtained, whenever feasible for the patient, at approximately 
1-minute intervals.
ECHO or MUGA
X
For patients that will receive doxorubicin, ECHO or MUGA must be performed within 28 days prior to C1D1.
Safety Assessments
Physical Exam
X
Physical exam includes height, weight, and BSA measurement.
Vital Signs
X
Vital sign measurements include temperature, pulse rate, and blood pressure.
Concomitant 
Medication Assessment
X
Concomitant medications will be recorded including any taken within 30 days prior to study medication.
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
Screening evaluations done within 7 days prior to C1D1 do not have to be repeated unless otherwise specified.
Coagulation Profile
X
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a microscopic analysis.  If routine analysis indicates > 2+ 
proteinuria, then a 24-hour urine must be collected and must demonstrate ≤1000 mg of protein in 24 hours, or 
urine protein/creatinine ratio < 1, prior to proceeding to treatment.  Screening evaluations done within 7 days 
prior to C1D1 do not have to be repeated unless otherwise specified.
Pregnancy Test
X
Serum β-HCG pregnancy test (women of childbearing potential only) within 7 days prior to C1D1.  If the serum 
pregnancy test performed for inclusion purposes is positive, confirm by repeating the serum and performing a 
urine pregnancy test.
Genetic (whole blood) 
Sample)
X
See Section 8.2.3 (whole blood sample).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 86
LY3012207
Relative Day Prior to 
Cycle 1 Day 1
≤28
≤14
≤7
Comments
Efficacy Assessments
Imaging Studies 
(CT/MRI/chest x-ray)
X
For rapidly growing tumors, scans should be performed ≤14 days prior to C1D1.  Scans performed prior to the 
date of consent may be used provided they are within 28 days of C1D1.  RECIST v1.1 should be used for all
tumors with the exception of CNS tumors; RANO or Macdonald criteria should be used for CNS tumors.
RECIST v1.1, RANO, 
or Macdonald Tumor 
Assessments
X
Other Assessments
Biomarker Sampling
X
Biopsy/Tumor Tissue 
Submission
X
Optional sample from archived or new tumor tissue
Abbreviations:  BSA = body surface area; C1D1 = Cycle 1 Day 1; CNS = central nervous system; CT = computed tomography; ECG = electrocardiogram; 
ECHO = echocardiogram; HCG = human chorionic gonadotropin; MRI = magnetic resonance imaging; MUGA = multigated acquisition; RANO = Response 
Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors Version 1.1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 87
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Doxorubicin (Parts A and B)
All evaluations must be done on the day of study drug administration.  In case of dose interruption, these evaluations will also be done 
at minimum frequency every 21 days (±3 days).
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 8
(±3)
Day 15
(±3)
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
X
ECG
X
X
Consecutive replicate ECGs will be obtained (3 readings), whenever 
feasible for the patient, at approximately 1-minute intervals.
ECHO or MUGA
X
ECHO or MUGA scans must be performed at the end of Cycles 2, 4, and 6 
and when clinically indicated.  Additional ECHO/MUGA may be 
performed at the investigator’s discretion.
Safety Assessments
Physical Exam
X
X
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
X
X
Vital sign measurements include temperature, pulse rate, and blood 
pressure. Cycle 1: Obtain vital signs prior to and after the completion of 
the olaratumab infusion.  In Cycle 2 and later: On Day 1, obtain vital signs 
prior to and after the completion of the olaratumab infusion (prior to 
dexrazoxane, if used; or if not used, then prior to doxorubicin) and within 1 
hour after completion of the doxorubicin infusion.  On Day 2, obtain vital 
signs prior to dexrazoxane infusion (patients receiving dexrazoxane and 
doxorubicin) or prior to doxorubicin infusion (patients receiving 
doxorubicin only) and within 1 hour after completion of the doxorubicin 
infusion.  On Day 8, obtain vital signs prior to and after the completion of 
the olaratumab infusion.
Adverse Event Assessment
X
X
X
X
X
All AEs considered at least possibly-related to study treatment will be 
followed until resolution, stabilization, return to baseline, or until deemed 
irreversible.
Concomitant Medication 
Assessment
X
X
X
X
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 88
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 8
(±3)
Day 15
(±3)
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
X
X
Hematology measurements must be collected on Day 15 only during 
Cycle 2 and Cycle 3.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 2 Day 1.
Chemistry Profile
X
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a microscopic 
analysis.  If routine analysis indicates > 2+ proteinuria, then a 24-hour urine 
must be collected and must demonstrate ≤1000 mg of protein in 24 hours 
or urine protein/creatinine ratio < 1, prior to proceeding to the next cycle.
Pregnancy Test
X
X
Urine pregnancy test on Day 1 of every cycle or per local practice 
(whichever is of shorter duration) and at short-term follow-up visit.  If the 
urine pregnancy test performed on Day 1 of the cycle is positive, confirm 
with a serum pregnancy test.
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity sample will be collected at the same 
time as the PK sample.  If a patient experiences an IRR to olaratumab, 
blood samples for immunogenicity and PK analysis will be taken at the 
following time points:  (1) as soon as possible after the onset of the IRR, 
(2) at the resolution of the IRR, and (3) 30 days after the IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are be obtained every 2 cycles (±7 
days) until documented progression for patients with CR, PR, or SD.  
RECIST v1.1 should be used for all tumors with the exception of CNS 
tumors; RANO or Macdonald criteria should be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time points
Biomarker Sampling
X
During treatment, a single sample will be collected prior to dosing at Cycle 
3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and tumor type.  May be 
collected any time during or after Cycle 2 Day 1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 89
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 8
(±3)
Day 15
(±3)
Premedication
Premedication prior to 
olaratumab administration
X
X
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients should receive 
premedication with dexamethasone (or equivalent medication) and an H1 
antagonist intravenously 30–60 minutes prior to olaratumab infusion.  
Additional premedication may be provided at investigator discretion.
For all subsequent cycles, all patients should receive premedication with an 
H1 antagonist (for example, diphenhydramine) intravenously 30–60 
minutes prior to each dose of olaratumab.  Additional premedication may 
be provided at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab infusion reaction in a 
previous cycle, patients should be premedicated with antihistamine and 
glucocorticoid (for example, dexamethasone) intravenously 30–60 minutes 
prior to olaratumab infusion, and acetaminophen (or equivalent) for all 
subsequent infusions.  Additional premedication may be provided at 
investigator discretion.
Administer dexrazoxane
X
X
Dexrazoxane may be given at 10:1 ratio (dexrazoxane to doxorubicin) prior 
to doxorubicin on Day 1 and Day 2 at the investigator' discretion.  
Dexrazoxane is recommended for all patients receiving doxorubicin.
Clinical Drug Supplies
Administer olaratumab
X
X
X
X
When the maximum dose of doxorubicin has been reached, olaratumab will 
not be continued and the patient should be discontinued from the study.
Administer doxorubicin
X
X
Doxorubicin to be administered at 37.5 mg/m2 on Day 1 and Day 2 to be 
continued for 6 Cycles or a cumulative dose of 450 mg/m2
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; ECHO = echocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; MUGA = multigated acquisition; 
PK = pharmacokinetics; PR = partial response; RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid 
Tumors Version 1.1; SD = stable disease.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 90
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Doxorubicin (Part C)
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
ECG
X
Baseline ECG can be used for C1D1 if completed within 7 days.
Consecutive replicate ECGs will be obtained (3 readings), whenever feasible for the 
patient, at approximately 1-minute intervals.
ECHO or MUGA
X
ECHO or MUGA scans must be performed PRIOR to Cycles 1, 3, and 5 and results must 
be available prior to doxorubicin administration for those cycles.  Additional 
ECHO/MUGA may be performed at the investigator’s discretion as clinically indicated.
Safety Assessments
Physical Exam
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
Vital sign measurements include temperature, pulse rate, and blood pressure. On Day 1, 
obtain vital signs prior to and after the completion of the olaratumab infusion (prior to 
dexrazoxane, if used; or if not used, then prior to doxorubicin) and within 1 hour after 
completion of the doxorubicin infusion.  On Day 2, obtain vital signs prior to dexrazoxane 
infusion (patients receiving dexrazoxane and doxorubicin) or prior to doxorubicin infusion 
(patients receiving doxorubicin only) and within 1 hour after completion of the 
doxorubicin infusion.  On Day 8, obtain vital signs prior to and after the completion of the 
olaratumab infusion.
Adverse Event Assessment
X
X
X
All AEs considered at least possibly related to study treatment will be followed until 
resolution, stabilization, return to baseline, or until deemed irreversible.
Concomitant Medication 
Assessment
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
Hematology measurements must be collected on Day 15 only during Cycle 1 and Cycle 2.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 1 Day 1.  Baseline value can be used for 
C1D1 if completed within 7 days.
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a microscopic analysis.  If routine 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 91
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
analysis indicates > 2+ proteinuria, then a 24-hour urine must be collected and must 
demonstrate ≤1000 mg of protein in 24 hours or urine protein/creatinine ratio <1, prior to 
proceeding to the next cycle.
Pregnancy Test
X
Urine pregnancy test on Day 1 of every cycle or per local practice (whichever is of shorter 
duration) and at short-term follow-up visit.  If the urine pregnancy test performed on Day 
1 of the cycle is positive, confirm with a serum pregnancy test.
Immunogenicity
See Attachment 4 for specific time 
points.
When possible, an immunogenicity sample will be collected at the same time as the PK 
sample.  If a patient experiences an IRR to olaratumab, blood samples for immunogenicity 
and PK analysis will be taken at the following time points:  (1) as soon as possible after 
the onset of the IRR, (2) at the resolution of the IRR, and (3) 30 days after the IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are to be obtained every 2 cycles (-7 days) until 
documented progression for patients with CR, PR, or SD.  RECIST v1.1 should be used 
for all tumors with the exception of CNS tumors; RANO or Macdonald criteria should be 
used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time 
points
Biomarker Sampling
X
During treatment, a single sample will be collected prior to dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and tumor type.  May be collected any 
time during or after Cycle 1 Day 1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 92
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
Premedication
Premedication prior to 
olaratumab administration
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients should receive premedication with 
dexamethasone (or equivalent medication) and an H1 antagonist intravenously 30–60 
minutes prior to olaratumab infusion.  Additional premedication may be provided at 
investigator discretion.
For all subsequent cycles, all patients should receive premedication with an H1 antagonist 
(for example, diphenhydramine) intravenously 30–60 minutes prior to each dose of 
olaratumab.  Additional premedication may be provided at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab infusion reaction in a previous cycle, 
patients should be premedicated with antihistamine and glucocorticoid (for example, 
dexamethasone) intravenously 30–60 minutes prior to olaratumab infusion, and 
acetaminophen (or equivalent) for all subsequent infusions.  Additional premedication 
may be provided at investigator discretion.
Administer dexrazoxane
X
X
Dexrazoxane may be given at 10:1 ratio (dexrazoxane to doxorubicin) prior to 
doxorubicin on Day 1 and Day 2 at the investigator discretion.  Dexrazoxane is 
recommended for all patients receiving doxorubicin.
Clinical Drug Supplies
Administer olaratumab
X
X
Administer doxorubicin
X
X
Doxorubicin to be administered at 37.5 mg/m2 on Day 1 and Day 2 to be continued for 6 
Cycles or a cumulative dose of 450 mg/m2.
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; ECHO = echocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; MUGA = multigated acquisition; PK 
= pharmacokinetics; PR = partial response; RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors 
Version 1.1; SD = stable disease.
a
A delay of up to 3 days will be permitted due to holidays, weekends, inclement weather, or other unforeseen circumstances, including unexpected changes in 
patient schedules, and will not count as a protocol deviation.  However, assessments must be done prior to treatments and the interval between cycles may not 
be less than 21 days. In later cycles, longer delays may be allowed in consultation with Lilly medical representative.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 93
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Vincristine and Irinotecan (Parts A and B)
All evaluations must be done on the day of study drug administration.  In case of dose interruption, these evaluations will also be done 
at minimum frequency every 21 days (±3 days).
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Eligibility Assessments
Lansky/Karnofsky performance 
status
X
X
ECG
X
X
Consecutive replicate ECGs will be 
obtained (3 readings), whenever feasible 
for the patient, at approximately 
1-minute intervals.
Safety Assessments
Physical Exam
X
X
X
X
Physical exam includes weight and BSA 
measurement.
Vital Signs
X
X
X
X
X
X
X
X
Vital sign measurements include 
temperature, pulse rate, and blood 
pressure. Cycle 1: Obtain vital signs 
prior to and after the completion of the 
olaratumab infusion.  In Cycle 2 and 
later: On Day 1, obtain vital signs prior 
to and after the completion of the 
olaratumab infusion (prior to vincristine) 
and within 1 hour after completion of the 
irinotecan infusion.  On Days 2-5, obtain 
vital signs prior to irinotecan infusion 
and within 1 hour after completion of the 
infusion.  On Day 8, obtain vital signs 
prior to and after the completion of the 
olaratumab infusion (prior to vincristine) 
and within 1 hour after completion of the 
vincristine infusion.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 94
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Adverse Event Assessment
X
X
X
X
X
X
X
X
All AEs considered at least possibly-
related to study treatment will be 
followed until resolution, stabilization, 
return to baseline, or until deemed 
irreversible.
Concomitant Medication 
Assessment
X
X
X
X
X
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
X
X
Hematology measurements must be 
collected on Day 15 only during Cycle 2 
and Cycle 3.
Coagulation Profile
X
Perform every other cycle beginning at 
Cycle 2 Day 1.
Chemistry Profile
X
X
Urinalysis
X
Includes a routine urinalysis, and if 
clinically indicated, a microscopic 
analysis.  If routine analysis indicates 
> 2+ proteinuria, then a 24-hour urine 
must be collected and must demonstrate 
≤1000 mg of protein in 24 hours, or
urine protein/creatinine ratio < 1, prior 
to proceeding to the next cycle.
Pregnancy Test
X
X
Urine pregnancy test on Day 1 of every 
cycle or per local practice (whichever is 
of shorter duration) and at short-term 
follow-up visit.  If the urine pregnancy 
test performed on Day 1 of the cycle is 
positive, confirm with a serum 
pregnancy test.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 95
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity 
sample will be collected at the same time 
as the PK sample.  If a patient 
experiences an IRR to olaratumab, blood 
samples for immunogenicity and PK 
analysis will be taken at the following 
time points:  (1) as soon as possible after 
the onset of the IRR, (2) at the resolution 
of the IRR, and (3) 30 days after the 
IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments 
are be obtained every 2 cycles (±7 days) 
until documented progression for 
patients with CR, PR, or SD.  RECIST 
v1.1 should be used for all tumors with 
the exception of CNS tumors; RANO or 
Macdonald criteria should be used for 
CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time points.
Biomarker Sampling
X
During treatment, a single sample will 
be collected prior to dosing at Cycle 3 
Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for 
biomarkers and tumor type.  May be 
collected any time during or after Cycle 
2 Day 1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 96
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Premedication
Premedication prior to 
olaratumab administration
X
X
X
X
In Cycle 1 (both Day 1 and Day 8 
doses), all patients should receive 
premedication with dexamethasone (or 
equivalent medication) and an H1 
antagonist intravenously 30–60 minutes 
prior to olaratumab infusion.  Additional 
premedication may be provided at 
investigator discretion.
For all subsequent cycles, all patients 
should receive premedication with an H1 
antagonist (for example, 
diphenhydramine) intravenously 30–60 
minutes prior to each dose of 
olaratumab.  Additional premedication 
may be provided at investigator 
discretion.
For a patient who has had a Grade 1 or 2 
olaratumab infusion reaction in a 
previous cycle, patients should be 
premedicated with antihistamine and 
glucocorticoid (for example 
dexamethasone) intravenously 30–60 
minutes prior to olaratumab infusion, 
and acetaminophen (or equivalent) for 
all subsequent infusions.  Additional 
premedication may be provided at 
investigator discretion.
Vincristine Premedication
X
X
Laxatives and/or stool softeners should 
be used preemptively during vincristine 
containing cycles.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 97
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Irinotecan Premedication
X
X
X
X
X
A prophylactic treatment with 
antiemetics is recommended before each 
treatment with irinotecan.
Clinical Drug Supplies
Administer olaratumab
X
X
X
X
Administer vincristine
X
X
Administer irinotecan
X
X
X
X
X
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; PK = pharmacokinetics; PR = partial response; 
RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors Version 1.1; SD = stable disease.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 98
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Vincristine and Irinotecan (Part C)
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Eligibility Assessments
Lansky/Karnofsky performance 
status
X
ECG
X
Consecutive replicate ECGs will be obtained (3 readings), 
whenever feasible for the patient, at approximately 
1-minute intervals.
Safety Assessments
Physical Exam
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
X
X
X
Vital sign measurements include temperature, pulse rate, 
and blood pressure. On Day 1, obtain vital signs prior to 
and after the completion of the olaratumab infusion (prior 
to vincristine) and within 1 hour after completion of the 
irinotecan infusion.  On Days 2-5, obtain vital signs prior to 
irinotecan infusion and within 1 hour after completion of 
the infusion.  On Day 8, obtain vital signs prior to and after 
the completion of the olaratumab infusion (prior to 
vincristine) and within 1 hour after completion of the 
vincristine infusion.
Adverse Event Assessment
X
X
X
X
X
X
All AEs considered at least possibly related to study 
treatment will be followed until resolution, stabilization, 
return to baseline, or until deemed irreversible.
Concomitant Medication 
Assessment
X
X
X
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
Hematology measurements must be collected on Day 15 
only during Cycle 1 and Cycle 2.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 1 Day 1.  
Baseline value can be used for C1D1 if completed within 7 
days.
Chemistry Profile
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 99
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a 
microscopic analysis.  If routine analysis indicates > 2+ 
proteinuria, then a 24-hour urine must be collected and 
must demonstrate ≤1000 mg of protein in 24 hours, or urine 
protein/creatinine ratio <1, prior to proceeding to the next 
cycle.
Pregnancy Test
X
Urine pregnancy test on Day 1 of every cycle or per local 
practice (whichever is of shorter duration) and at short-term 
follow-up visit.  If the urine pregnancy test performed on 
Day 1 of the cycle is positive, confirm with a serum 
pregnancy test.
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity sample will be collected 
at the same time as the PK sample.  If a patient experiences 
an IRR to olaratumab, blood samples for immunogenicity 
and PK analysis will be taken at the following time points:  
(1) as soon as possible after the onset of the IRR, (2) at the 
resolution of the IRR, and (3) 30 days after the IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are to be obtained 
every 2 cycles (±7 days) until documented progression for 
patients with CR, PR, or SD.  RECIST v1.1 should be used 
for all tumors with the exception of CNS tumors; RANO or 
Macdonald criteria should be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time points.
Biomarker Sampling
X
During treatment, a single sample will be collected prior to 
dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and 
tumor type.  May be collected any time during or after 
Cycle 1 Day 1.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 100
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Premedication
Premedication prior to 
olaratumab administration
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients 
should receive premedication with dexamethasone (or 
equivalent medication) and an H1 antagonist intravenously 
30–60 minutes prior to olaratumab infusion.  Additional 
premedication may be provided at investigator discretion.
For all subsequent cycles, all patients should receive 
premedication with an H1 antagonist (for example, 
diphenhydramine) intravenously 30–60 minutes prior to 
each dose of olaratumab.  Additional premedication may be 
provided at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab 
infusion reaction in a previous cycle, patients should be 
premedicated with antihistamine and glucocorticoid (for 
example, dexamethasone) intravenously 30–60 minutes 
prior to olaratumab infusion, and acetaminophen (or 
equivalent) for all subsequent infusions.  Additional 
premedication may be provided at investigator discretion.
Clinical Drug Supplies
Administer olaratumab
X
X
Administer vincristine
X
X
Administer irinotecan
X
X
X
X
X
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; PK = pharmacokinetics; PR = partial response; 
RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors Version 1.1; SD = stable disease.
a
A delay of up to 3 days will be permitted due to holidays, weekends, inclement weather, or other unforeseen circumstances, including unexpected changes in 
patient schedules, and will not count as a protocol deviation.  However, assessments must be done prior to treatments and the interval between cycles may not 
be less than 21 days. In later cycles, longer delays may be allowed in consultation with Lilly medical representative.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 101
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Ifosfamide (Parts A and B)
All evaluations must be done on the day of study drug administration.  In case of dose interruption, these evaluations will also be done 
at minimum frequency every 21 days (±3 days).
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
X
ECG
X
X
Consecutive replicate ECGs will be obtained 
(3 readings), whenever feasible for the 
patient, at approximately 1-minute intervals.
Safety Assessments
Physical Exam
X
X
X
X
Physical exam includes weight and BSA 
measurement.
Vital Signs
X
X
X
X
X
X
X
X
Vital sign measurements include temperature, 
pulse rate, and blood pressure. Cycle 1:
Obtain vital signs prior to and after the 
completion of the olaratumab infusion.  In 
Cycle 2 and later: On Day 1, obtain vital 
signs prior to and after the completion of the 
olaratumab infusion (prior to ifosfamide) and 
within 1 hour after completion of the 
ifosfamide infusion.  On Days 2-5, obtain 
vital signs prior to ifosfamide infusion and 
within 1 hour after completion of the 
infusion.  On Day 8, obtain vital signs prior 
to and after the completion of the olaratumab 
infusion. 
Adverse Event Assessment
X
X
X
X
X
X
X
X
All AEs considered at least possibly-related
to study treatment will be followed until 
resolution, stabilization, return to baseline, or 
until deemed irreversible.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 102
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Concomitant Medication 
Assessment
X
X
X
X
X
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
X
X
Hematology measurements must be collected 
on Day 15 only during Cycle 2 and Cycle 3.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 
2 Day 1.
Chemistry Profile
X
X
Urinalysis
X
Includes a routine urinalysis, and if clinically 
indicated, a microscopic analysis.  If routine 
analysis indicates > 2+ proteinuria, then a 24-
hour urine must be collected and must 
demonstrate ≤1000 mg of protein in 24 
hours, or urine protein/creatinine ratio < 1, 
prior to proceeding to the next cycle.
Pregnancy Test
X
X
Urine pregnancy test on Day 1 of every cycle 
or per local practice (whichever is of shorter 
duration) and at short-term follow-up visit.  If 
the urine pregnancy test performed on Day 1 
of the cycle is positive, confirm with a serum 
pregnancy test.
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity sample 
will be collected at the same time as the PK 
sample.  If a patient experiences an IRR to 
olaratumab, blood samples for 
immunogenicity and PK analysis will be 
taken at the following time points:  (1) as 
soon as possible after the onset of the IRR, 
(2) at the resolution of the IRR, and (3) 30 
days after the IRR.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 103
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are 
be obtained every 2 cycles (±7 days) until 
documented progression for patients with 
CR, PR, or SD.  RECIST v1.1 should be used 
for all tumors with the exception of CNS 
tumors; RANO or Macdonald criteria should 
be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time points
Biomarker Sampling
X
During treatment, a single sample will be 
collected prior to dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for 
biomarkers and tumor type.  May be 
collected any time during or after Cycle 2 
Day 1.
Premedication
Premedication prior to 
olaratumab administration
X
X
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all 
patients should receive premedication with 
dexamethasone (or equivalent medication) 
and an H1 antagonist intravenously 30–60 
minutes prior to olaratumab infusion.  
Additional premedication may be provided at 
investigator discretion.
For all subsequent cycles, all patients should 
receive premedication with an H1 antagonist 
(for example, diphenhydramine) 
intravenously 30–60 minutes prior to each 
dose of olaratumab.  Additional 
premedication may be provided at 
investigator discretion.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 104
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
For a patient who has had a Grade 1 or 2 
olaratumab infusion reaction in a previous 
cycle, patients should be premedicated with 
antihistamine and glucocorticoid (for 
example, dexamethasone) intravenously 30–
60 minutes prior to olaratumab infusion, and 
acetaminophen (or equivalent) for all 
subsequent infusions.  Additional 
premedication may be provided at 
investigator discretion.
Mesna Administration
X
X
X
X
X
Administer at a minimum 60% of the 
ifosfamide dose according to institutional 
guidelines.  
Clinical Drug Supplies
Administer olaratumab
X
X
X
X
When the maximum dose of ifosfamide has 
been reached (or has been discontinued), 
olaratumab will not be continued and the 
patient should be discontinued from the 
study.
Administer ifosfamide
X
X
X
X
X
Administer ifosfamide for up to 6 cycles or a 
cumulative dose of 84 g/m2.  Treatment 
beyond 84 g/m2 requires consultation with 
the Lilly CRP/CRS.
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; PK = pharmacokinetics; PR = partial response; 
RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; SD = stable disease.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 105
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Ifosfamide (Part C)
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
ECG
X
Consecutive replicate ECGs will be obtained (3 readings), 
whenever feasible for the patient, at approximately 1-minute 
intervals.
Safety Assessments
Physical Exam
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
X
X
X
Vital sign measurements include temperature, pulse rate, and 
blood pressure. On Day 1, obtain vital signs prior to and after 
the completion of the olaratumab infusion (prior to ifosfamide) 
and within 1 hour after completion of the ifosfamide infusion.  
On Days 2-5, obtain vital signs prior to ifosfamide infusion and 
within 1 hour after completion of the infusion.  On Day 8, obtain 
vital signs prior to and after the completion of the olaratumab 
infusion. 
Adverse Event Assessment
X
X
X
X
X
X
All AEs considered at least possibly related to study treatment 
will be followed until resolution, stabilization, return to baseline, 
or until deemed irreversible.
Concomitant Medication 
Assessment
X
X
X
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
Hematology measurements must be collected on Day 15 only 
during Cycle 1 and Cycle 2.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 1 Day 1.
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a 
microscopic analysis.  If routine analysis indicates > 2+ 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 106
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
proteinuria, then a 24-hour urine must be collected and must 
demonstrate ≤1000 mg of protein in 24 hours, or urine 
protein/creatinine ratio <1, prior to proceeding to the next cycle.
Pregnancy Test
X
Urine pregnancy test on Day 1 of every cycle or per local 
practice (whichever is of shorter duration) and at short-term 
follow-up visit.  If the urine pregnancy test performed on Day 1 
of the cycle is positive, confirm with a serum pregnancy test.
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity sample will be collected at 
the same time as the PK sample.  If a patient experiences an IRR 
to olaratumab, blood samples for immunogenicity and PK 
analysis will be taken at the following time points:  (1) as soon 
as possible after the onset of the IRR, (2) at the resolution of the 
IRR, and (3) 30 days after the IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are to be obtained every 
2 cycles (±7 days) until documented progression for patients 
with CR, PR, or SD.  RECIST v1.1 should be used for all 
tumors with the exception of CNS tumors; RANO or Macdonald 
criteria should be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time points
Biomarker Sampling
X
During treatment, a single sample will be collected prior to 
dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and tumor 
type.  May be collected any time during or after Cycle 1 Day 1.
Premedication
Premedication prior to 
olaratumab administration
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients should 
receive premedication with dexamethasone (or equivalent 
medication) and an H1 antagonist intravenously 30–60 minutes 
prior to olaratumab infusion.  Additional premedication may be 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 107
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
provided at investigator discretion.
For all subsequent cycles, all patients should receive 
premedication with an H1 antagonist (for example, 
diphenhydramine) intravenously 30–60 minutes prior to each 
dose of olaratumab.  Additional premedication may be provided 
at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab infusion 
reaction in a previous cycle, patients should be premedicated 
with antihistamine and glucocorticoid (for example, 
dexamethasone) intravenously 30–60 minutes prior to 
olaratumab infusion, and acetaminophen (or equivalent) for all 
subsequent infusions.  Additional premedication may be 
provided at investigator discretion.
Mesna Administration
X
X
X
X
X
Administer at a minimum 60% of the ifosfamide dose according 
to institutional guidelines.  
Clinical Drug Supplies
Administer olaratumab
X
X
Administer ifosfamide
X
X
X
X
X
Administer ifosfamide for up to 6 cycles or a cumulative dose of 
84 g/m2.  Treatment beyond 84 g/m2 requires consultation with 
the Lilly CRP/CRS.
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; PK = pharmacokinetics; PR = partial response; 
RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; SD = stable disease.
a
A delay of up to 3 days will be permitted due to holidays, weekends, inclement weather, or other unforeseen circumstances, including unexpected changes in 
patient schedules, and will not count as a protocol deviation.  However, assessments must be done prior to treatments and the interval between cycles may not 
be less than 21 days. In later cycles, longer delays may be allowed in consultation with Lilly medical representative.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 108
LY3012207
JGDN Study Schedule, Follow-up Assessments (All Parts)
Day
Follow-up
Comments
Short-Terma
Long-Termb
30 days (±7) after 
discontinuation 
date
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
ECG
X
Consecutive replicate ECGs will be obtained (3 readings), whenever 
feasible for the patient, at approximately 1-minute intervals.
ECHO or MUGA
X
For patients on the doxorubicin arm:  if doxorubicin cardiotoxicity has 
been observed, an ECHO or MUGA should be performed at the 30-day 
follow-up visit.  Additional ECHO/MUGA may be performed at the 
investigator’s discretion.
Safety Assessments
Physical Exam
X
Physical exam includes weight.
Vital Signs
X
Vital sign measurements include temperature, pulse rate, and blood 
pressure.
Adverse Event Assessment
X
All AEs considered at least possibly-related to study treatment will be 
followed until resolution, stabilization, return to baseline, or until deemed 
irreversible.
Concomitant Medication 
Assessment
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
Coagulation Profile
X
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a microscopic 
analysis.
Pregnancy Test
X
If the urine pregnancy test is positive, confirm with a serum pregnancy test.
Immunogenicity
X
See Attachment 4 for details.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 109
LY3012207
Day
Follow-up
Comments
Short-Terma
Long-Termb
30 days (±7) after 
discontinuation 
date
Efficacy Assessments
Imaging Studies (CT/MRI)
X
(if applicable)
X
For patients who have discontinued study treatment due to toxicity or 
reasons other than progressive disease, imaging studies and tumor 
assessments are to be obtained every 6 weeks (±7 days) until progression or 
initiation of other anticancer therapy.  RECIST v1.1 should be used for all 
tumors with the exception of CNS tumors; RANO or Macdonald criteria 
should be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
(if applicable)
X
Subsequent Anti-Cancer
Treatments, and Associated 
Disease Progression Date
X
For all patients, details on subsequent anticancer treatment (start/stop dates 
and treatments administered) and first post-study treatment disease 
progression date should be recorded.
Other Assessments
PK Sampling
X
See Attachment 4 for details.
Biomarker Sampling
X
Abbreviations:  AE = adverse event; CNS = central nervous system; CRF = case report form; CT = computed tomography; ECG = electrocardiogram; 
ECHO = echocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; MUGA = multi-gated acquisition; PK = pharmacokinetics; 
RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors.
a
Short-term follow-up begins the day after the patient and the investigator agree that the patient will no longer continue study treatment and lasts approximately
30 days (±7 days).  The date of this agreement is to be reported on the CRF as the date of discontinuation from study treatment.
b Long-term follow-up begins the day after short-term follow-up is completed.  Patients that discontinue study treatment for reasons other than progression will
be followed every 6 weeks (±7 days) until progression.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 110
LY3012207
Attachment 2.
Protocol JGDN Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologya
Clinical Chemistrya
Hemoglobin
Serum Concentrations of the following:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Mean cell volume (MCV)
Total bilirubin
Mean cell hemoglobin concentration (MCHC)
Alkaline phosphatase
Leukocytes (WBC)
Alanine aminotransferase (ALT)
Neutrophils
Aspartate aminotransferase (AST)
Lymphocytes
Gamma glutamyl transferase (GGT)
Monocytes
Blood urea nitrogen (BUN) or Blood Urea
Eosinophils
Creatinine
Basophils
Urate
Platelets
Calcium
Glucose, random
Coagulation Testa
Albumin
Prothrombin time (PT)
Total protein
International normalized ratio (INR)
Chloride
Partial thromboplastin time (PTT or aPTT)
Thyroid-stimulating hormone
Direct bilirubin
Urinalysisa,c
Bicarbonate
Specific gravity
Magnesium
pH
Phosphate
Protein
Glucose
Pregnancy testa,d
Ketones
Blood
Exploratory Biomarker Testsb
Urine leukocyte esterase
Otherb
Immunogenicity samples
PK samples
Abbreviations:  CRP = clinical research physician; PK = pharmacokinetics; RBC = red blood cells; UPC = urine 
protein/creatinine; WBC = white blood cells.
a
Assayed by local or investigator-designated laboratory.
b
Samples will be assayed by Lilly-designated laboratory.
c
If urinary protein is ≥2+ at evaluations, a 24-hour urine collection (to assess protein) must be collected and must be ≤1000 mg 
of protein in 24 hours, or alternatively, a urine protein/creatinine ratio ≤1, prior to proceeding to the next cycle. Note: UPC 
ratio of spot urine is an estimation of the 24-hour urine protein excretion – a UPC ratio of 1 is roughly equivalent to a 24-hour 
urine protein of 1000 mg. UPC ratio is calculated using one of the following formulae: 

[urine protein]/[urine creatinine] – if both protein and creatinine are reported in mg/dL 

[(urine protein) x 0.088]/[urine creatinine] – if urine creatinine is reported in mmol/L
d
Serum pregnancy test will be performed at screening in female patients of childbearing potential only (if the baseline serum 
test is positive, a repeat serum and urine pregnancy test will be done; if those results are positive, the investigator is to consult 
with the Lilly CRP regarding if dosing should occur and which follow-up laboratory tests are performed).  While on-study, 
urine pregnancy test will be performed in female patients of childbearing potential only on Day 1 of every cycle or per local 
practice (whichever is of shorter duration) and at short-term follow-up visit.  If the serum pregnancy test performed for 
inclusion purposes is positive confirm by repeating the serum and performing a urine pregnancy test.  If the urine pregnancy 
test performed on Day 1 of each cycle is positive, confirm with a serum pregnancy test.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 111
LY3012207
Attachment 3.
Protocol JGDN 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
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
F-Actin Smooth Muscle Antibody IgGa
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 local or investigator-designated laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 112
LY3012207
Attachment 4.
Protocol JGDN Pharmacokinetic and 
Immunogenicity Sampling Schedule

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 113
LY3012207
Pharmacokinetic and Immunogenicity Sampling (Parts A and B)
Sample Number
Cycle
Day
Sampling Time
Olaratumab PKa
Combination 
agents PKb
Immunogenicityc
1
1
1
Prior to olaratumab infusion
X
X
2
8
Within 5 min post olaratumab infusion
X
3
2
1
Within 15 min prior to olaratumab infusion
X
X
4
1
Within 5 min post chemotherapy infusion
X
X
5
8
Within 5 min post olaratumab infusion
X
6
3 and then every 
other cycle
1
Within 15 min prior to olaratumab infusion
X
X
7
30-day follow-up (Visit 801)
Any time
X
X
Abbreviation:  PK = pharmacokinetics.
a
A 2.5-mL (1 mL if patient has 19kg) blood sample will be collected (to generate serum for bioanalysis).
b A 2-mL (1 mL if patient has 19kg) blood sample will be collected (to generate plasma for bioanalysis).
c
A 3.5-mL blood sample will be collected (to generate serum for anti-olaratumab antibody analysis).
Pharmacokinetic and Immunogenicity Sampling (Part C)
Sample 
Number
Cycle
Day
Sampling Time
Olaratumab PKa
Combination 
agents PKb
Immunogenicityc
1
1
1
Prior to olaratumab infusion
X
X
2
1
Within 5 min post chemotherapy 
infusion
X
X
3
8
Within 5 min post olaratumab 
infusion
X
4
2
1
Within 15 min prior to olaratumab 
infusion
X
X
5
8
Within 5 min post olaratumab 
infusion
X
6
3 and then every 
other cycle
1
Within 15 min prior to olaratumab 
infusion
X
X
7
30-day follow-up (Visit 
801)
Any time
X
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 114
LY3012207
Abbreviation:  PK = pharmacokinetics.
a
A 2.5-mL (1 mL if patient has 19 kg) blood sample will be collected (to generate serum for bioanalysis).
b
A 2-mL (1 mL if patient has 19 kg) blood sample will be collected (to generate plasma for bioanalysis).
c
A 3.5-mL blood sample will be collected (to generate serum for anti-olaratumab antibody analysis).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 115
LY3012207
Attachment 5.
Protocol JGDN 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.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 116
LY3012207
Attachment 6.
Protocol JGDN Creatinine Clearance 
Formula
Protocol JGDN will use the Schwartz formula for the determination of creatinine clearance.
All Females and Pre-adolescent Males:
Ccr (mL/min/1.73 m2) = 0.55 x Height (cm)/Scr (mg/dL)
Adolescent Males:
Ccr (mL/min/1.73 m2) = 0.70 x Height (cm)/Scr (mg/dL)
Note:  Ccr = creatinine clearance and Scr = serum creatinine
Source:  Schwartz et al. 1976; Schwartz and Gauthier 1985.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 117
LY3012207
Attachment 7.
Protocol JGDN Sampling Summary
This table summarizes the maximum number of samples (venipunctures, biopsies), volumes for
all sampling, and tests (study qualification, health monitoring, drug concentration, tailoring
biomarkers, immunogenicity, and exploratory) 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 I5B-MC-JGDN Sampling Summary
Purpose
Sample 
Type
Maximum Amount 
per Sample
Maximum 
Number 
Samples
Maximum Total 
Amount
Study qualificationa
Blood
5 mL
4
10 mL
Health Monitoring (may be more than 
1 tube)b
Blood
5 mL
33
98 mL
Tissue 
Biopsy
5 mm
0.5 oz
1 cc
1
5 mm
0.5 oz
1 cc
Drug concentration
Blood
2-2.5 mL (1 mL if 
patient has 19kg)
11
27 mL (13 mL if patient 
has 19kg)
Tailoring biomarkers
Blood
4 mL
3
12 mL
Tumor 
tissue
FFPE block or slides
1
FFPE block or slides
Pharmacogenetic (DNA) Sample
Blood
0.5 mL
1
0.5 mL
Immunogenicity
Blood
3.5 mL
7
24.5 mL
Hepatic Monitoringb
Blood
3 - 30 mL
-
-
Total blood per patient completing 
9 cycles and Short-term follow up visit
Blood
172 mL (158 mL if 
patient has 19kg)
Abbreviations:  DNA = deoxyribonucleic acid; FFPE = formalin-fixed, paraffin-embedded.
a
Additional samples may be drawn if needed for safety purposes.
b
Based on laboratory safety values, unscheduled hepatic monitoring testing may be performed as part of patient 
follow-up, in consultation with the designated medical monitor.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 118
LY3012207
Attachment 8.
Protocol JGDN RECIST Criteria 1.1
Response and progression will be evaluated in this study using the international criteria proposed 
by the New Response Evaluation Criteria In Solid Tumors (RECIST): Revised RECIST 
Guideline (version 1.1; Eisenhauer et al. 2009).
Measurability of Tumor at Baseline
Tumor lesions/lymph nodes will be categorized at baseline as measurable or nonmeasurable.  
Measurable disease is defined by the presence of at least 1 measurable lesion.
Measurable 
Tumor lesions:  Measured in at least 1 dimension (longest diameter in the plane of measurement 
is to be recorded) with a minimum size of:

10 mm by computed tomography (CT) or magnetic resonance imaging (MRI) 
scan (slice thickness 5 mm)

10 mm caliper measurement by clinical exam (non-measurable lesions if cannot 
be accurately measured with calipers) 20 mm by chest X-ray.
Malignant lymph nodes:  To be considered pathologically enlarged and measurable, a lymph 
node must be 15 mm in short axis when assessed by CT scan (CT scan thickness recommended 
to be 5 mm).
Nonmeasurable 
All other lesions, including small lesions (longest diameter <10 mm or pathological lymph nodes 
with 10 to <15 mm short axis) as well as truly nonmeasurable lesions.  Lesions considered truly 
non-measurable include:  leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pulmonis, inflammatory breast disease, lymphangitis involvement of skin or 
lung, abdominal masses/abdominal organomegaly identified by physical exam that is not 
measureable by reproducible imaging techniques.
Special Considerations for Lesion Measurability
Bone lesions:

Bone scan, PET scan or plain films are not considered adequate imaging 
techniques to measure bone lesions.

Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as 
CT or MRI, can be considered measurable lesions if the soft tissue component 
meets the definition of measurability.

Blastic bone lesions are non-measurable.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 119
LY3012207
Cystic lesions:  

Simple cysts should not be considered as malignant lesions (neither measurable 
nor nonmeasurable) 

Cystic lesions thought to represent cystic metastases can be considered as 
measurable lesions, if they meet the definition of measurability.  If noncystic 
lesions are presented in the same patients, these are preferred for selection as 
target lesions.
Lesions with Prior Local Treatment:

Tumor lesions situated at a previously irradiated area, or in an area subjected 
to other loco-regional therapy, are non-measurable unless there has been 
demonstrated progression in the lesion.
Baseline Documentation of Target and Non-Target Lesion
Target Lesions
When more than 1 measurable lesion is present at baseline, all lesions up to a maximum of 5 
lesions total (and a maximum of 2 lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline. Non-nodal Target 
lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, and can be reproduced in repeated measurements.  
Measurable lymph nodes are target lesions if they meet the criteria of a short axis of 15 mm by 
CT scan.  All measurements are to be recorded in the case record form (CRF) in millimeters (or 
decimal fractions of centimeters [cm]).
Nontarget Lesions
All other lesions (or sites of disease) are identified as nontarget lesions (chosen based on their 
representativeness of involved organs and the ability to be reproduced in repeated measurements) 
and should be recorded at baseline.  Measurement of these lesions are not required but should be 
followed as ‘present,’ ‘absent,’ or in rare cases ‘unequivocal progression.’  In addition, it is 
possible to record multiple nontarget lesions involving the same organ as a single item on the 
CRF (for example, multiple liver metastases recorded as one liver lesion).
Lymph nodes with short axis 10 mm but <15 mm should be considered nontarget lesions.  
Nodes that have a short axis <10 mm are considered nonpathological and are not recorded or 
followed.
Specifications by Methods of Measurement
All measurements should be recorded in metric notation, using a ruler or calipers if clinically 
assessed.  All baseline evaluations should be performed as closely as possible to the beginning of 
treatment and never more than 4 weeks before the beginning of the treatment.
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up.  Imaging-based evaluation is 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 120
LY3012207
should always be done rather than clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessed by clinical exam.
An adequate volume of a suitable contrast agent should be given so that the metastases are 
demonstrated to best effect and a consistent method is used on subsequent examinations for any 
given patient.  If prior to enrollment it is known a patient is not able to undergo CT scans with IV 
contrast due to allergy or renal insufficiency, the decision as to whether a non-contrast CT or 
MRI (with or without IV contrast) should be used to evaluate the patient at baseline and follow-
up should be guided by the tumor type under investigation and the anatomic location of the 
disease.
Clinical Lesions:  Clinical lesions will only be considered measurable when they are superficial 
and 10 mm diameter as assessed using calipers (for example, skin nodules).  For the case of 
skin lesions, documentation by color photography, including a ruler to estimate the size of the 
lesion is recommended.  When lesions can be evaluated by both clinical exam and imaging, 
imaging evaluation should be undertaken since it is more objective and may be reviewed at the 
end of the study.
Chest X-ray:  Chest CT is preferred over chest X-ray when progression is an important endpoint.  
Lesions on chest X-ray may be considered measurable if they are clearly defined and surrounded 
by aerated lung.
CT and MRI:  CT scan is the best currently available and reproducible method to measure lesions 
selected for response assessment.  Measurability of lesions on CT scan is based on the 
assumption that CT slice thickness is 5 mm.  When CT scan have slice thickness >5 mm, the 
minimum size for a measurable lesion should be twice the slice thickness.  MRI is also 
acceptable in certain situations (for example, for body scans).  If there is concern about radiation 
exposure at CT, MRI may be used instead of CT in selected instances.
Ultrasound:  Ultrasound should not be used to measure lesion size.  Ultrasound examinations 
cannot be reproduced in their entirety for independent review at a later date and, because they are 
operator dependent, it cannot be guaranteed that the same technique and measurements will be 
taken from one assessment to the next.  If new lesions are identified by ultrasound in the course 
of the study, confirmation by CT or MRI is advised.
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor evaluation is 
not advised.  However, such techniques can be useful to confirm complete pathological response 
when biopsies are obtained or to determine relapse in trials where recurrence following complete 
response or surgical resection is an endpoint.
Tumor Markers:  Tumor markers alone cannot be used to assess tumor response.  If markers are 
initially above the upper normal limit, they must normalize for a patient to be considered in 
complete response (CR).  Specific guidelines for both prostate-specific antigen (PSA) response 
(in recurrent prostate cancer) and CA-125 response (in recurrent ovarian cancer) have been 
published.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 121
LY3012207
Cytology, Histology:  These techniques can be used to differentiate between partial responses 
(PR) and complete response (CR) in rare cases if required by protocol (for example, residual 
lesions in tumor types such as germ cell tumors, where known residual benign tumors can 
remain).  When effusions are known to be a potential adverse effect of treatment (for example, 
with certain taxane compounds or angiogenesis inhibitors), the cytological confirmation of the 
neoplastic origin of any effusion that appears or worsens during treatment can be considered if 
the measurable tumor has met criteria for response or stable disease (SD) in order to differentiate 
between response (or SD) and progressive disease (PD).
Pet Scan (FDG-PET, PET CT):  PET is not recommended for lesion assessment. If a new lesion 
is found by PET, another assessment must be done by CT, unless the PET CT is of diagnostic 
quality.  If CT is done to confirm the results of the earlier PET scan, the date of progression must 
be reported as the earlier date of the PET scan.
Bone Scan:  If lesions measured by bone scan are reported at baseline, it is necessary to repeat 
the bone scan when trying to identify a complete response (CR) or partial response (PR) in target 
disease or when progression in bone is suspected.
Response Criteria
Evaluation of Target Lesions 
Complete Response (CR):  Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm.  Tumor marker 
results must have normalized.
Partial Response (PR):  At least a 30% decrease in the sum of diameter of target lesions, taking 
as reference the baseline sum diameters.
Progressive Disease (PD):  At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (including the baseline sum if that is the smallest).  
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase 
of at least 5 mm.  The appearance of one or more new lesions is also considered progression.
For equivocal findings of progression (for example, very small and uncertain new lesions; cystic 
changes or necrosis in existing lesions), treatment may continue until the next scheduled 
assessment.  If at the next scheduled assessment, progression is confirmed, the date of 
progression should be the earlier date when progression was suspected.
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
Not Evaluable:  When an incomplete radiologic assessment of target lesions is performed or 
there is a change in the method of measurement from baseline that impacts the ability to make a 
reliable evaluation of response. 
Evaluation of Nontarget Lesions
Complete Response:  Disappearance of all nontarget lesions and normalization of tumor marker 
level.  All lymph nodes must be non-pathological or normal in size (<10mm short axis).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 122
LY3012207
Non-CR/ non-PD:  Persistence of 1 or more nontarget lesions and/or maintenance of tumor 
marker level above the normal limits.
Progressive Disease:  Unequivocal progression of existing nontarget lesions.  The appearance of 
1 or more new lesions is also considered progression.
Not Evaluable: When a change in method of measurement from baseline occurs and impacts the 
ability to make a reliable evaluation of response.
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
the earliest of objective progression or start of new anticancer therapy, taking into account any 
requirement for confirmation.  The patient’s best overall response assignment will depend on the 
findings of both target and nontarget disease and will also take into consideration the appearance 
of new lesions.  The Best Overall Response will be calculated via an algorithm using the 
assessment responses provided by the investigator over the course of the trial.
Time Point Response
It is assumed that at each protocol-specified time point, a response assessment occurs.  (When no 
imaging/measurement is done at all at a particular time point, the patient is not evaluable (NE) at 
that time point.)  Table 1 provides a summary of the overall response status calculation at each 
time point for patients who have measurable disease at baseline.
Table 1.
Time Point Response: Patients with Target (Nontarget) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Abbreviations:  CR = complete response; PR = partial response; SD = stable disease.; PD = progressive disease; 
NE = inevaluable. 
Table 2 is to be used when patients have nonmeasurable disease only.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 123
LY3012207
Table 2.
Time Point Response: Patients with Nontarget Disease Only
Nontarget Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
Abbreviations:  CR = complete response; PD = progressive disease ; NE = inevaluable.
a
non-CR/non-PD is preferred over SD for nontarget disease. 
Frequency of Tumor Re-Evaluation
A baseline tumor evaluation must be performed within 4 weeks before patient begins study 
treatment. Frequency of tumor re-evaluation while on and adapted to treatment should be 
protocol-specific and adapted to the type and schedule of treatment.  In the context of Phase 2 
studies where the beneficial effect therapy is not known, follow-up every 6-8 weeks is 
reasonable.  Normally, all target and non-target sites are evaluated at each assessment using the 
same method.  However, bone scans may need to be repeated only when CR is identified in 
target disease or when progression in bone is suspected.
Confirmatory Measurement/Duration of Response
Confirmation:
The main goal of confirmation of objective response in clinical trials is to avoid overestimating 
the response rate observed. The confirmation of response is particularly important in 
nonrandomized trials where response (CR/PR) is the primary end point.  In this setting, to be 
assigned a status of PR/CR, changes in tumor measurements must be confirmed by repeat 
assessments that should be performed no less than 4 weeks after the criteria for response are first 
met.  To confirm a response of CR, a full assessment of all target and nontarget lesions that were 
present at baseline must occur, including those measured by bone scan.  To confirm a PR or SD, 
a full assessment of target lesions that were present at baseline must occur;  assessment of 
nontargets is not required.
However, in randomized trial (Phase 2 or 3) or studies where SD or progression is the primary 
endpoints, confirmation of response is not required.  But, elimination of the requirement may 
increase the importance of central review to protect against bias, in particular of studies which 
are not blinded.
In the case of SD, follow-up measurements must have met the SD criteria at least once after start 
of treatment at a minimum interval not less than 6 weeks measured from first dose.
Duration of Overall Response
The duration of overall response is measured from the time measurement criteria are first met for 
CR or PR (whichever is first recorded) until the first date that disease is recurrent or objective 
progression is observed (taking as reference for PD the smallest measurements recorded on 
study).

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 124
LY3012207
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented.
Duration of Stable Disease
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for objective progression are met, taking as reference the 
smallest sum on study (if the baseline sum is the smallest, that is the reference for calculation of 
PD).  
Independent Review of Response and Progression
When objective response (CR + PR) is the primary end point, and when key drug development 
decisions are based on the observation of a minimum number of responders, it is recommended 
that all claimed responses be reviewed by an expert(s) independent of the study.  If the study is a 
randomized trial, ideally reviewers should be blinded to treatment assignment.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 125
LY3012207
Attachment 9.
Protocol JGDN List of CYP3A4, CYP2D6, 
and P-gp Inhibitors and Inducers of Doxorubicin
CYP3A4 Inducers
Strong CYP3A4 Inhibitors
Moderate CYP3A4 Inhibitors
Aminoglutethimide
Clarithromycin
Amiodarone
Bosentan
Chloramphenicol
Amprenavir
Carbamazepine
Cobicistat
Aprepitant
Efavirenz (in liver only)
Conivaptan
Atazanavir
Fosphenytoin
Cremophor EL
Cimetidine
Nafcillin
Cyclosporine
Ciprofloxacin
Nevirapine
Delavirdine
Clotrimazole
Oxcarbazepine
Diclofenac
Darunavir
Pentobarbital
Diltiazem
Darunavir and ritonavir
Phenobarbital
Elvitegravir and ritonavir
Desipramine
Phenytoin
Enoxacin
Doxycycline
Primidone
Fosamprenavir
Dronedarone
Rifabutin
Grapefruit juice
Efavirenz
Rifampin
Indinavir
Erythromycin
Rifapentine
Indinavir and ritonavir
FK1706
St. John's wort
Itraconazole
Fluconazole
Ketoconazole
Fluvoxamine
Lopinavir and ritonavir
Haloperidol
Mibefradil
Imatinib
Miconazole
Metronidazole
Nefazodone
Norfloxacin
Nelfinavir
Protease inhibitors
Nicardipine
Quinidine
Posaconazole
Schisandra sphenanthera extract
Quinidine
Sertraline
Ritonavir
Tetracycline
Saquinavir
Tofisopam
Telithromycin
Verapamil
Theophylline
Troleandomycin
Voriconazole

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 126
LY3012207
CYP2D6 Inducers
CYP2D6 Inhibitors
P-glycoprotein 1 (P-gp) Inhibitors
Dexamethasone
Amiodarone
Amiodarone
Rifampin
Celecoxib
Azithromycin
Chloroquine
Captopril
Chlorpromazine
Clarithromycin
Cimetidine
Cyclosporine
Citalopram
Piperine
Clomipramine
Quercetin
Codeine
Quinidine
Deiavirdine
Quinine
Desipramine
Reserpine
Dextroprpoxyphene
Ritonavir
Diltiazem
Tariquidar
Doxorubicin
Verapamil
Entacapone (high dose)
Fluoxetine
Fluphenazine
Fluvaxamine
Haloperidol
Labetalol
Lobeline
Lomustine
Methadone
Mibefradil
Moclobemide
Nortuloxeline
Paroxetine
Perphenazine
Propafenone
Quinacrine
Quinidine
Ranitadine (ranitidine, Zantac)
Risperidone (weak)
Ritonavir
Serindole
Sertraline (weak)
Thioridazine
Valproic acid
Venlafaxine (weak)
Vinblastine
Vincristine
Vinorelbine
Yohimbine

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 127
LY3012207
Attachment 10.
Protocol JGDN Protocol Amendment 
I5B-MC-JGDN(b) Summary 
A Phase 1, Open-Label, Dose-Escalation Study of 
Olaratumab as a Single Agent and in Combination with 
Doxorubicin, Vincristine/Irinotecan, or High-Dose 
Ifosfamide in Pediatric Patients with Relapsed or 
Refractory Solid Tumors
Overview
Protocol I5B-MC-JGDN “A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a 
Single Agent and in Combination with Doxorubicin, Vincristine/Irinotecan, or High-Dose 
Ifosfamide in Pediatric Patients with Relapsed or Refractory Solid Tumors” has been amended.  
The new protocol is indicated by Amendment (b) and will be used to conduct the study in place 
of any preceding version of the protocol.
The protocol was amended to allow the addition of Part C and allow site sourcing of non-
investigational study drugs.  In Part C, patients will not receive olaratumab monotherapy and will 
directly enter into combination chemotherapy.  This will occur after documentation for safety of 
olaratumab 20mg/kg monotherapy in Part B.  The rationale for this is to improve the risk-benefit 
ratio for patients by allowing known active therapy in combination with olaratumab at study 
entry.
The overall changes and rationale for the changes made to this protocol are as follows:

Part C was added to the study design and updated throughout the protocol.

An update to the number of planned patients as well as the planned last patient 
visit was updated due to adding Part C.

The duration of treatment was updated to allow patients with clinical benefit to continue 
on monotherapy until one of the criteria for discontinuation is met. 

Contraceptive language was clarified in the inclusion criteria (Section 6.1.1). 

Comparator drug language was updated, in Section 7.1, to account for potential supply 
shortage and product availability. 

Premedication language was updated in Section 7.2.1 to reflect current standard practice. 

A clarification to Section 7.5 regarding concomitant palliative radiotherapy was added.

A clarification to the premedication timing language in Section 7.5 was made to ensure 
premedications are given appropriately. 

Mesna language was better clarified to reflect current standard practice. 

Palliative radiotherapy language was better explained in Section 7.5.2.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 128
LY3012207

The schedule of events (baseline, treatment, and follow-up) was updated to reflect 
clarifications, standard practices, and the addition of Part C.

The PK sample schedule was updated to reflect the addition of Part C.  

Other minor editorial changes were made to add clarity.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 129
LY3012207
Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.
Clinical Protocol Synopsis:  Study I5B-MC-JGDN
Name of Investigational Product:  Olaratumab (LY3012207)
Title of Study:  A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a Single Agent and in 
Combination with Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients with Relapsed 
or Refractory Solid Tumors
Number of Planned Patients:
Entered/Screened:  Approximately 10010
Enrolled:  Minimum  24
                 Maximum 709
Phase of Development:  1
Length of Study:
Planned first patient visit:  11 February 2016
Planned last patient visit:   1105 JuneFebruary 2019
Objectives:
The primary objective of this study is to determine a recommended dose of olaratumab in combination with at least 
one of the studied chemotherapy regimens in pediatric patients based on any dose-limiting toxicities (DLTs) as well 
as olaratumab serum exposure-matching between the adult and pediatric populations.
The secondary objectives of this study are:

to investigate the pharmacokinetics (PK) of olaratumab as monotherapy and in combination with either 
doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients;

to assess the possible development of antibodies against olaratumab (immunogenicity) in pediatric patients; 
and

to document any antitumor activity (including progression-free survival and objective response rate [ORR]) 
observed with olaratumab in combination with either doxorubicin, vincristine/irinotecan, or high-dose 
ifosfamide in pediatric patients.
The exploratory objective of this study is:

to identify exploratory biomarkers associated with tumor response and/or safety.
Study Design:  Study JGDN is a multicenter, dose-escalation, open-label Phase 1 pediatric safety clinical trial with 
3 distinct components, Part A, Part B, and Part BC.
Part A will consist of at least 12 evaluable pediatric patients.  These patients will be treated for 1 cycle (21 days) of 
olaratumab monotherapy at 15 mg/kg on Day 1 and Day 8 (adult dose for which efficacy was observed in 
Study I5B-IE-JGDG).  If the patient does not experience a DLT in the first cycle of monotherapy, or meet any other 
criteria for discontinuation, the patient will then receive olaratumab (15 mg/kg) plus one of 3 standard chemotherapy 
regimens (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per investigator discretion).  Treatment will 
continue until disease progression or other discontinuation criteria are met.
Part B and Part C will be initiated after the following criteria have been met:

Acceptable safety results, which must include a minimum of 6 evaluable patients, and the PK profile from 
Part A monotherapy.

At least one of the 15 mg/kg combination arms has met the following DLT criteria:  less than one-third 
(that is, approximately 33.3% [minimum of 3 patients]) DLT rate.  Only the combination arms in Part A 
that have met these criteria may be studied in Parts B and C.
Part B will consist of at least 12 evaluable pediatric patients.  These patients will be treated for 1 cycle (21 days) of 
olaratumab monotherapy at 20 mg/kg on Day 1 and Day 8.  If the patient does not experience a DLT in the first 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 130
LY3012207
cycle of monotherapy, or meet any other criteria for discontinuation, then patient will then receive olaratumab 
(20mg/kg) plus one of 3 standard chemotherapy regimens described in Part A that have successfully passed the DLT 
criteria described above for Part A (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per investigator 
discretion).  Part B will be complete when at least 10 patients (regardless of assigned chemotherapy arm) are 
evaluable for safety of olaratumab 20mg/kg monotherapy.  Part C will be initiated when at least 10 patients 
(regardless of chemotherapy arm) are evaluable for safety of olaratumab 20 mg/kg monotherapy from Part B.  Part C 
patients will receive olaratumab (20 mg/kg) in combination with any of the 3 chemotherapy regimens (per 
investigator discretion) from Cycle 1 onward (i.e. no olaratumab monotherapy will be given in Part C).  Part B and 
C together will enroll up to 45 patients (15 per chemotherapy arm).  Treatment will continue until disease 
progression or other discontinuation criteria are met.
Diagnosis and Main Criteria for Inclusion and Exclusions:  Eligible patients will be <18 years of age with a 
diagnosis of relapsed or refractory solid tumors not amenable to curative treatment, for whom chemotherapy with 
doxorubicin, vincristine/irinotecan, or high-dose ifosfamide is deemed appropriate by the investigator.  In addition, 
the patient must have adequate performance status by Lansky or Karnofsky and adequate hematologic, organ, and 
coagulation function.  The patient must not have a hematologic malignancy, uncontrolled intercurrent illness, or 
active infection.
Test Product, Dosage, and Mode of Administration:
Olaratumab:  for intravenous (IV) use, supplied in single-use 500 mg/50 mL vials containing 10 mg/mL of product 
in histidine buffer, administered to patients as an IV infusion at 15 or 20 mg/kg on Day 1 and Day 8 of each cycle.  
Cycles are 21 days in length.
Doxorubicin:  will be supplied by Lilly and administered intravenously.  Doxorubicin (37.5 mg/m2) is to be 
administered on Day 1 and Day 2 of each 21-day cycle, for up to 6 cycles or a cumulative dose of 450 mg/m2.
Dexrazoxane:  will be supplied by Lilly and may be administered at a 10:1 ratio (dexrazoxane:doxorubicin) at the 
investigator’s discretion via IV injection, beginning 30 minutes prior to theeach doxorubicin infusion for the 
prevention of cardiotoxicity.  and its useIt is recommended inthat all patients receiving 5 or more cycles of 
doxorubicin also receive dexrazoxane.  Dexrazoxane should be administered after completion of the olaratumab 
infusion, prior to administration of doxorubicin.  Doxorubicin should be administered within approximately 
30 minutes of receiving dexrazoxane.
Vincristine:  will be supplied by Lilly and administered intravenously.  Vincristine (patients ≥ 10 kg: 1.5 mg/m2, 
patients <10 kg:  0.05mg/kg.  Dose is capped at 2 mg) is to be administered on Day 1 and Day 8 of each 21-day 
cycle.
Irinotecan:  will be supplied by Lilly and administered intravenously.  Irinotecan (50 mg/m2) is to be administered 
on Days 1, 2, 3, 4, and 5 of each 21-day cycle.
Ifosfamide:  will be supplied by Lilly and administered intravenously.  Ifosfamide (2.8 g/m2) is to be administered 
on Days 1, 2, 3, 4, and 5 of each 21-day cycle, for up to 6 cycles or a cumulative dose of 84 g/m2.  Mesna:  
commercial formulations will be used and administered intravenously.  Mesna should be administered at a minimum 
dose equal to 60% of the ifosfamide dose according to institutional guidelines. The mesna dose should be divided 
equally between 3 infusions given together with the ifosfamide infusion, 4 hours after the ifosfamide infusion, and 
8 hours after the infusion.
Planned Duration of Treatment:
The planned duration of treatment is not fixed; patients will remain on study until they fulfill one of the criteria for 
study discontinuation.
Follow-up in post-treatment discontinuation:  30 days (±7 days) for patients with disease progression.  For patients 
who have discontinued study treatment due to toxicity or reasons other than progressive disease, follow-up will 
continue imaging studies and tumor assessments are to be obtained every 6 weeks (±7 days) until progression.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 131
LY3012207
Criteria for Evaluation:
Efficacy:  
Radiographic assessments will be performed at baseline and then every 2 cycles (±7 days) until radiographic 
documentation of progressive disease.  Response Evaluation Criteria In Solid Tumors, Version 1.1 criteria should be 
used for all solid tumors with the exception of central nervous system tumors.  Response Assessment in Neuro-
Oncology Criteria or Macdonald Criteria should be used for central nervous system tumors.
Safety:  The safety and tolerability of the study treatment is determined by reported adverse events (AEs), physical 
exam including vital signs, clinical laboratory tests, electrocardiograms, and results of echocardiogram / multigated 
acquisition scans.  Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®) and graded using National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) Version 4.0 and summarized by System Organ Class and preferred term.
Pharmacokinetic/Pharmacodynamic:
Blood samples will be collected at various time points for PK assessment for olaratumab levels and the levels of the 
combination chemotherapies.  Blood samples will be collected at various time points for immunogenicity analysis.
Tailoring Genetics and Biomarkers:
Samples will be collected at various time points for nonpharmacogenomic biomarker research.  A whole blood 
sample will be collected for pharmacogenomics analysis.
Tumor Tissue Biomarker:
Patients may provide a previously archived primary or metastatic tumor tissue sample (paraffin block or unstained 
slides).  Additional voluntary pre- and post-treatment tumor tissue samples may be requested for further biomarker 
research.
Statistical Methods:
The primary objective of this study is to determine a safe dose of olaratumab alone or in combination with 
chemotherapy regimens that can be administered to pediatric patients.  The study will enroll a minimum of 
12 patients in Part A.  A sSafety reviews will be performed prior to movingopening into Parts B and C of the study.
Safety:
Adverse events (AEs), including treatment-emergent AEs, will be listed and summarized in frequency tables using 
MedDRA.  Severity of AEs will be classified using CTCAE Version 4.0.  Other safety data, such as laboratory tests, 
echocardiography, and vital signs, will be listed and summarized, if appropriate.
Pharmacokinetics:  The PK parameters of olaratumab will be computed by nonlinear mixed effect modeling using 
  PK data collected for doxorubicin will be analyzed using descriptive methods.
Immunogenicity:  Incidence of anti-olaratumab antibodies and any additional related assays will be tabulated.  
Correlation to olaratumab drug level, activity, and safety will be assessed, as appropriate.
Efficacy:  Exploratory efficacy analysis will be performed to investigate antitumor activity within each combination 
arm.  Progression-free survival curves and the median with 90% confidence interval (CI) will be estimated using 
Kaplan-Meier method.  The objective response rate (ORR = complete response [CR] + partial response [PR]) and 
disease control rate (DCR=CR + PR + stable disease) and the 90% exact CI will be tabulated for each cohort.
Biomarkers:  Analyses will be performed on biomarkers relevant to pathways associated with soft tissue sarcoma, 
the mechanism of action of olaratumab, and/or cancer-related conditions.  Assay results will be summarized and 
correlated with clinical outcomes.
5.1. Rationale and Justification for the Study

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 132
LY3012207
The study consists of 23 parts.  Part A will consist of approximately 12 evaluable pediatric 
patients treated for 1 cycle (21 days) of olaratumab monotherapy at 15 mg/kg on Day 1 and Day 
8.  If the patient does not experience a DLT in the first cycle of monotherapy, or meet any other 
criteria for discontinuation, the patient will then receive olaratumab (15 mg/kg) plus one of 3 
standard chemotherapy regimens (doxorubicin or vincristine/irinotecan or high-dose ifosfamide 
per investigator discretion).  Part B will consist of at least 12 evaluable pediatric patients.  These 
patients will be treated for 1 cycle (21 days) of olaratumab monotherapy at 20 mg/kg on Day 1 
and Day 8.  If the patient does not experience a DLT in the first cycle of monotherapy, or meet 
any other criteria for discontinuation, then patient will then receive olaratumab (20mg/kg) plus 
one of 3 standard chemotherapy regimens described in Part A.  Part B will be complete when at 
leat 10 patients (regardless of chemotherapy arm) are evaluable for safety of olaratumab 20 
mg/kg from Part B.  Part C will be initiated after confirmation of safety of olaratumab 20 mg/kg 
from Part B.  Part C patients will receive olaratumab (20 mg/kg) in combination with any of the 
3 chemotherapy regimens (per investigator discretion) from Cycle 1 onward (i.e no olaratumab 
monotherapy in Cycle 1 of  Part C).   described in Part A that have successfully passed the DLT 
criteria described above for Part A (doxorubicin or vincristine/irinotecan or high-dose ifosfamide 
per investigator discretion).  Parts B and C together will enroll up to 45 patients (15 per 
chemotherapy arm).  Treatment will continue until disease progression or other discontinuation 
criteria are met.
5.3. General Introduction to Olaratumab

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 133
LY3012207
Preferred Term
Arm A
N = 64
n (%)
Median no. of doxorubicin 
infusions=7
Arm B
N = 65
n (%)
Median no. of doxorubicin 
infusions=4
Grade 3 
Grade ≥4
Grade 3 
Grade ≥4
Patients with any AE
24 (37.5)
27 (42.2)
25 (38.5)
20 (30.8)
Neutropeniaa
12 (18.8)
23 (35.9)
5 (7.7)
17 (26.2)
Anemiad
8 (12.5)
0
6 (9.2)
0
Febrile Neutropenia
7 (10.9)
1 (1.6)
9 (13.8)
0
Fatigue
6 (9.4)
0
2 (3.1)
0
Thrombocytopenia
5 (7.8)
2 (3.1)
3 (4.6)
2 (3.1)
Infections and Infestationsc
5 (7.8)
0
4 (6.2)
3 (4.6)
Mucositisb
2 (3.1)
0
3 (4.6)
0
Hypokalemia
2 (3.1)
0
2 (3.1)
0
Lymphopenia
2 (3.1)
0
1 (1.5)
0
Diarrhea
2 (3.1)
0
0
0
Abdominal Paing
2 (3.1)
0
0
0
Musculoskeletal Painf
5 (7.8)
0
0
0
Infusion-Related Reactione
0
2 (3.1)
0
0
Nausea
1 (1.6)
0
2 (3.1)
0
Decreased Appetite
1 (1.6)
0
0
0
Dry Mouth
1 (1.6)
0
0
0
Dehydration
1 (1.6)
0
0
0
Constipation
0
0
1 (1.5)
0
Dyspnea
0
0
1 (1.5)
0
Cardiac arrhythimias
0
0
1 (1.5)
0
Cardiac dysfunctions
1 (1.6)
0
0
0
Abbreviations:  AE = adverse event; MedDRA = Medical Dictionary for Regulatory Activities; N = number of 
randomized patients; n = number of patients with given event.
Data cut-off date:  16 May 2015.
a
Consolidated term comprising the following preferred terms:  leukopenia, neutropenia, neutrophil count 
decreased, white blood cell count decreased.
b
Consolidated term comprising the following preferred terms:  mucosal inflammation, oropharyngeal pain, 
stomatitis.
c
Includes all preferred terms within the MedDRA system organ class of Infections and Infestations.
d
Consolidated term comprising the following preferred terms:  anemia, hemoglobin decreased.
e
Consolidated term comprising the following preferred terms:  hypersensitivity, infusion-related reaction, infusion 
site erythema, injection site pain.
f
Consolidated term comprising the following preferred terms:  back pain, musculoskeletal chest pain, 
musculoskeletal pain.
g
Consolidated term comprising the following preferred terms: abdominal pain upper, abdominal pain.
Note.  Arm A = Olaratumab + Doxorubicin; Arm B = Doxorubicin.
Source: JGDG CSR TableJGDG 12.16
5.4 Rationale for Selection of Dose
During clinical development, in Phase 1 dose-escalation trials (JGDC and JGDF) and in Phase 2 
monotherapy studies (JGDE and JGDH), olaratumab has been consistently well tolerated, with 
no DLTs observed in the dose-escalation studies up to a dose of 16 mg/kg weekly times 4 doses 
in a 6-week cycle, 20 mg/kg administered every 2 weeks, and up to a dose of 15 mg/kg 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 134
LY3012207
administered ofn Day 1 and Day 8 of a 21-day cycle.  When used in combination with other 
therapeutic agents, an increase of toxicities such as neutropenia and infections were observed in 
combination with liposomal doxorubicin (olaratumab dose of 20 mg/kg every 2 weeks) and with 
paclitaxel/carboplatin (olaratumab dose of 15 mg/kg on Day 1 and Day 8 every 3 weeks).  In 
Study JGDG (15 mg/kg on Day 1 and Day 8 of a 21-day cycle), an increase in neutropenia and 
mucositis, but not in neutropenic sepsis or febrile neutropenia, have been observed.  These 
toxicities are acceptable and monitorable and are consistent with the toxicity profile of 
doxorubicin.
6.1.1. Inclusion Criteria
[1]
The patient must have histological or cytological evidence of a diagnosis of 
solid tumor, excluding lymphomas and melanoma, but including central 
nervous system (CNS) tumors, that is relapsed or refractory, not be amenable 
to curative treatment, and for whom chemotherapy with doxorubicin,
vincristine/irinotecan, or ifosfamide is deemed appropriate by the investigator.  
For patients with CNS tumors, neurologic deficits in patients with CNS 
tumors must have been stable for at least 7 days prior to study enrollment.
[6]
The patient has adequate hematologic, organ, and coagulation function 
≤2 weeks (14 days) prior to first dose of study drug:

Absolute neutrophil count (ANC) 750/mm3.  Granulocyte 
colony-stimulating factor (G-CSF) cannot be administered ≤1 week 
(7 days) prior to first dose of study drug.  Pegfilgrastinm cannot be 
administered ≤2 weeks (14 days) prior to first dose of study drug.
[8]
Both female and male patients of child-bearing potential must agree to use 
highly effective contraceptive precautions during the trial and up to 3 months 
following the last dose of study drugolaratumab, or longer ifas appropriate for 
other study drugs according to their label.  A highly effective method of birth 
control is defined as one that results in a low failure rate (that is, <1% per 
year) when used consistently and correctly, such as implants, injectables, 
combined oral contraceptives, some intrauterine contraceptive devices, sexual 
abstinence, or a vasectomized partner.
6.2 Summary of Study Design
Study JGDN is a multicenter, dose-escalation, open-label Phase 1 pediatric safety clinical trial 
with 23 distinct components, Part A, Part B, and Part BC.
Part B will consist of at least 12 evaluable pediatric patients.  These patients will be treated for 1 
cycle (21 days) of olaratumab monotherapy at 20 mg/kg on Day 1 and Day 8.  If the patient does 
not experience a DLT in the first cycle of monotherapy, or meet any other criteria for 
discontinuation, then patient will then receive olaratumab (20mg/kg) plus one of 3 standard 
chemotherapy regimens described in Part A that have successfully passed the DLT criteria 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 135
LY3012207
described above for Part A (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per 
investigator discretion).  Part B will be complete when at least 10 patients (regardless of assigned 
chemotherapy arm) are evaluable for safety of olaratumab 20mg/kg monotherapy.  Treatment 
will continue until disease progression or other discontinuation criteria are met.
Figure JGDN.6.2 was deleted and replaced with the following:
Abbreviations:  D = day; DLT = dose-limiting toxicity; n = number of cycles.
Part C will receive olaratumab (20 mg/kg) in combination with any of the 3 chemotherapy 
regimens from Cycle 1 onwards (ie. no olaratumab monotherapy in Cycle 1).  Treatment will 
continue until disease progression or other discontinuation criteria are met.
Part C is illustrated in Figure JGDN.6.3
Abbreviations:  DLT = dose-limiting toxicity; n = number of cycles.
Figure JGDN.6.3.
Illustration of Part C of the study design.
Parts B and C together will enroll up to 45 patients (15 per chemotherapy arm).
The planned duration of treatment is not fixed; patients will remain on study until they fulfill one 
of the criteria for study discontinuation (Section 6.3).  Patients on study treatment who continue 
to experience clinical benefit and no undue risks may continue olaratumab monotherapy after 
completion of chemotherapy until one of the criteria for discontinuation is met if deemed 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 136
LY3012207
medically appropriate in the opinion of the investigator and following discussion and agreement 
by the medical monitor.
This study will enroll a minimum of 24 (maximum of 709) pediatric patients, including a 
minimum of 10 osteosarcoma patients and 10 rhabdomyosarcoma patients across all treatment 
arms, if possible.  The goal will be to enroll approximately 20 evaluable patients in each 
combination arm (across Parts A, B, and BC) to characterize the safety and PK profile of 
olaratumab and the respective chemotherapeutic agents, and to inform dose choice for potential 
later-phase studies.
6.2.1. Primary Endpoint
Primary endpoint is defined as DLT and PK data exposure matching.  The primary endpoint 
analysis will occur after the final patient enrolled has been evaluated for at least 2 cycles
(Cycle 1 is monotherapy; Cycle 2 is combination therapy).
6.2.2. Study Completion and End of Trial
Any patient enrolled in Part A or Part B that has completed at least 1 cycle of treatment or 
discontinued due to an AE (during Cycle 1), and completed the required post-treatment safety 
assessment, will be considered to have completed the monotherapy portion of the study. Patients 
in Part A or Part B completing Cycle 1 who do not continue to Cycle 2 will be considered 
evaluable for monotherapy DLTs and PK.  Any patient enrolled in Part A or Part B that has 
completed at least 2 cycles of treatment or discontinued due to an AE (during Cycle 2), and 
completed the required post-treatment safety assessment, will be considered to have completed 
the study. Any patient enrolled in Part C that has completed 1 cycle of treatment or discontinued 
due to an AE (during Cycle 1), and completed the required post-treatment safety assessment, will 
be considered to have completed the study.  However, in all parts of the study, additional cycles 
of therapy may continue as long as the patient is receiving benefit and no criteria for 
discontinuation have been met. All secondary and exploratory endpoint analyses will be updated 
at study completion.
7.1 Materials and Supplies
Olaratumab will be provided to the sites by Lilly.
Olaratumab for injection is supplied in single-use 500 mg/50 mL vials containing 10 mg/mL of 
olaratumab in histidine buffer, administered to patients as an IV infusion at 10, 15, or 20 mg/kg.
Doxorubicin hydrochloride, dexrazoxane, vincristine sulfate, irinotecan hydrochloride, and 
ifosfamide will be supplied by Lilly
Other drug products (i.e. doxorubicin hydrochloride, dexrazoxane, vincristine sulfate, irinotecan 
hydrochloride, and ifosfamide) to be used in Study JGDN will be supplied by Lilly, but 
commercially available supply may be used as directed by Lilly for cases of regional restrictions 
or supply limitations.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 137
LY3012207
Where commercially available, mesna will be supplied by the sites.  In the event that there are 
regional restrictions or supply limitations, mesna may be provided to the sites by Lilly.
Clinical study materials will be labeled according to the country’s regulatory requirements.
7.2.1. Premedication
Doxorubicin
Given the emetogenic potential of doxorubicin, premedication with antiemetics per institutional 
guidelines is recommended.  Additional premedication may be provided at investigator 
discretion.
Dexrazoxane may be administered at a 10:1 ratio (dexrazoxane:doxorubicin) at the investigator’s 
discretion via IV injection, beginning within 30 minutes prior to each doxorubicin infusion for 
the prevention of cardiotoxicity.  It is recommended that all patients receiving doxorubicin also 
receive dexrazoxane.
Vincristine
Laxatives and/or stool softeners shouldmay be used preemptively during vincristine-containing 
cycles.
Ifosfamide
When the treatment includes ifosfamide, mesna should be administered at a minimum dose equal 
to 60% of the ifosfamide dose according to institutional guidelines, including divided dose or 
continuous infusion. The mesna dose maybe divided equally between 3 infusions:
1. together with the ifosfamide infusion, 
2. 4 hours after the ifosfamide infusion, and 
3. 8 hours after the infusion.
7.2.2. Dosing Schedule
The following treatments will be administered in this study every 3-week (21-day) ± 3 day cycle 
(Table JGDN.7.1 and Table JGDN.7.2)
Part C:
All Cycles
Olaratumab as IV infusion on Day 1 and Day 8 (at 20 mg/kg),
AND
Doxorubicin as IV infusion on Day 1 and Day 2 (at 37.5 mg/m2; up to 6 cycles or a cumulative 
dose of 450 mg/m2)
OR

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 138
LY3012207
Vincristine as IV on Day 1 and Day 8 (patients ≥ 10 kg: 1.5 mg/m2, patients <10 kg:  
0.05 mg/kg.  Dose is capped at 2 mg) plus irinotecan as IV on Days 1, 2, 3, 4, and 5 (at 50 
mg/m2),
OR
Ifosfamide as IV on Days 1, 2, 3, 4, and 5 (at 2.8 g/m2; up to 6 cycles or a cumulative dose of 
84 g/m2).  Treatment beyond 84 g/m2 requires consultation with the Lilly CRP/CRS.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 139
LY3012207
Table JGDN.7.1.
Treatment Regimens/Dosing Schedule (Part A and Part B)
Study Drug
Dose
Route
Timing
Cycle 1
Olaratumaba
Part A
15 mg/kg
IV
approximately 1 hour infusion on 
Day 1 and Day 8 of each 21-day 
cycle
Part B
20 mg/kg
Cycle 2-n
Olaratumaba
Part A
15 mg/kg
IV
approximately 1 hour infusion 
Day 1 and Day 8 of each 21-day 
cycle
Part B
20 mg/kg
1-hour observation periodb followed by 
Doxorubicinc,dg
Parts A and B
37.5 mg/m2
IV
Day 1 and Day 2 of each 21-day 
cycle 
OR
Vincristinee
Parts A and B
1.5 mg/m2
IV
Day 1 and Day 8 of each 21-day 
cycle
Irinotecang
Parts A and B
50 mg/m2
IV
Days 1, 2, 3, 4, and 5 of each 
21-day cycle
OR
Ifosfamidefg
Parts A and B
2.8 g/m2
IV
approximately 2 to 3 hour infusion 
on Days 1, 2, 3, 4, and 5 of each 
21-day cycle
Abbreviations:  eCRF = electronic case report form; IV = intravenous.
a
Administer Ppremedication is recommended prior to infusion of olaratumab.  Recommended premedication 
agents include histamine H1 antagonists such as diphenhydramine hydrochloride (or equivalent).  Additional 
premedication may be provided at the investigator’s discretion.  Premedication must be provided in the setting of 
a prior Grade 1-2 infusion-related reaction, as detailed in Section 7.2.4.1.  All premedication administered must 
be adequately documented in the eCRF.
b A 1-hour observation period is required after the administration of the first and second doses of olaratumab.  If
there is no evidence of an infusion-related reaction during the initial 2 cycles of olaratumab, then no observation 
period is required for subsequent treatment cycles.  In the event an infusion-related reaction occurs thereafter, 
then the 1-hour observation period should be reinstituted; see Section 7.2.4.1.
c
Administer doxorubicin for up to 6 cycles only (Cycles 2-7) or cumulative dose of 450 mg/m2.
d Administer doxorubicin according to institutional guidelines and/or clinical practice as an IV injection or as an 
infusion in less than 60 minutes (+10 minutes).  Decrease the rate of doxorubicin administration if erythematous 
streaking along the vein proximal to the site of infusion or facial flushing occurs.
e
For patients weighing less than 10 kg, the dose of vincristine should be 0.05 mg/kg.  The dose is capped at 2 mg 
for all patients.
f
Administer ifosfamide for up to 6 cycles only (Cycles 2-7) or a cumulative dose of 84 g/m2.  Treatment beyond 
84 g/m2 requires consultation with the Lilly clinical research physician/clinical research scientist.
g   For sequential day chemotherapy, it is recommended to allow a minimum of 20 hours between dosing, unless         
institutional standard varies.
Table 7.2
Treatment Regimens/Dosing Schedule (Part C)

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 140
LY3012207
Study Drug
Dose
Route
Timing
Cycle 1-n
Olaratumaba
20 mg/kg
IV
approximately 1 hour infusion on Day 1 and Day 8 of 
each 21-day cycle
1-hour observation periodb followed by 
Doxorubicinc,d,g
37.5 mg/m2
IV
Day 1 and Day 2 of each 21-day cycle 
OR
Vincristinee
1.5 mg/m2
IV
Day 1 and Day 8 of each 21-day cycle
Irinotecang
50 mg/m2
IV
Days 1, 2, 3, 4, and 5 of each 21-day cycle
OR
Ifosfamidef,g
2.8 g/m2
IV
approximately 2 to 3 hour infusion on Days 1, 2, 3, 4, 
and 5 of each 21-day cycle
Abbreviations:  eCRF = electronic case report form; IV = intravenous.
a
Administer premedication prior to infusion of olaratumab.  Recommended premedication agents include 
histamine H1 antagonists such as diphenhydramine hydrochloride (or equivalent).  Additional premedication 
may be provided at the investigator’s discretion. Premedication must be provided in the setting of a prior 
Grade 1-2 infusion-related reaction, as detailed in Section 7.2.4.1.  All premedication administered must be 
adequately documented in the eCRF.
b A 1-hour observation period is required after the administration of the first and second doses of olaratumab.  If 
there is no evidence of an infusion-related reaction during the initial 2 cycles of olaratumab, then no observation 
period is required for subsequent treatment cycles.  In the event an infusion-related reaction occurs thereafter, 
then the 1-hour observation period should be reinstituted; see Section 7.2.4.1.
c
Administer doxorubicin for up to 6 cycles only or cumulative dose of 450 mg/m2.
d Administer doxorubicin according to institutional guidelines and/or clinical practice as an IV injection or as an 
infusion in less than 60 minutes (+10 minutes).  Decrease the rate of doxorubicin administration if erythematous 
streaking along the vein proximal to the site of infusion or facial flushing occurs.
e
For patients weighing less than 10 kg, the dose of vincristine should be 0.05 mg/kg.  The dose is capped at 2 mg 
for all patients.
f
Administer ifosfamide for up to 6 cycles only or a cumulative dose of 84 g/m2.  Treatment beyond 84 g/m2
requires consultation with the Lilly clinical research physician/clinical research scientist.
g  For sequential day chemotherapy, it is recommended to allow a minimum of 20 hours between dosing, unless 
institutional standard varies.
7.2.3. Dose Progression through Study Parts-Escalation from Part A to Part B
Safety will be the primary criteria for the dose escalation or de-escalation of both olaratumab 
monotherapy and the combination regimens.  No dose escalation can occur without prior 
discussion and agreement between the investigators and the Lilly CRP/CRS/Lilly study team; the 
decision will be documented in writing.  Sites will be notified of this decision 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.
Part B will be initiated after acceptable safety results from Part A, including a minimum of 6 
evaluable patients, and the PK profile from Part A monotherapy.  Part B will be complete when 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 141
LY3012207
at least 10 patients (regardless of assigned chemotherapy arm) are evaluable for safety of 
olaratumab 20mg/kg monotherapy .
Part  C will open for enrollment after a complete safety review of the first 10 patients (regardless 
of chemotherapy arm)   to complete Part B  monotherapy (olaratumab 20 mg/kg).  Once safety of 
olaratumab 20/mg/kg is determined, Part C will open for enrollment.  This safety review will be 
performed by the Lilly CRP/CRS/Lilly study team and investigators and documented in writing.  
Sites will be notified of this decision in writing.
7.2.3.2. Dose-Escalation Method
Part B will be initiated after the following criteria have been met:

Acceptable safety results, which must include a minimum of 6 evaluable patients, and 
the PK profile from Part A monotherapy

At least one of the 15 mg/kg combination arms has met the following DLT criteria: less 
than one third (that is, approximately 33.3% [minimum of 3 patients]) DLT rate.  Only 
the combination arms in Part A that have met these criteria may be studied in Parts B and 
C.
In Part A, if the DLT rate is >1/3 (that is, greater than 4 out of 12 patients) during Cycle 1 
monotherapy, then the dose of olaratumab will be reduced to 10 mg/kg.  In Part B, if the DLT 
rate is >1/3 during Cycle 1 monotherapy, then the dose of olaratumab will be reduced to 
15 mg/kg.  In Part C, if the DLT rate is >1/3 during Cycle 1 combination therapy, then the dose 
of olaratumab will be reduced to 15 mg/kg.
If the DLT rate is >1/3 in the first cycle (Parts A and B Cycle 2, or Part C Cycle 1) of any of the 
chemotherapy arms, then appropriate dose de-escalation of olaratumab for that combination will 
occur.
7.2.4. Dose Adjustments and Delays
In the event that a patient experiences a DLT or a DLT-equivalent (a DLT occurring in Cycle 3 
of later of Parts A and B or Cycle 2 or later of Part C), treatment will be interrupted.  Dosing can 
be resumed after resolution of the toxicity to baseline levels at the next lower dose level (Table 
JGDN.7.23) already deemed safe upon discussion with the Lilly CRP/CRS.  For Grade 3/4 
toxicities that are not dose-limiting, see Section 7.2.4.1.2. for hematologic toxicities and Section 
7.2.4.1.3 for nonhematologic toxicities.
7.2.4.1.1. Infusion-Related Reactions
In general (may vary if patient recently received premedication), if a patient experiences a 
Grade 1 or 2 IRR, the infusion should stop and the patient should be treated with an 
antihistamine (for example, diphenhydramine hydrochloride), glucocorticoid (for example, 
dexamethasone), acetaminophen (or equivalent), and oxygen (as indicated), according to 
standard medical practices.  After recovery, the infusion rate should be decreased 50% for the 
duration of the infusion.  If subsequent infusions are then tolerated with the use of 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 142
LY3012207
premedications as above and a 50% decrease in infusion rate, the infusion rate may be increased 
to a rate deemed appropriate by the investigator, as long as it does not exceed 25 mg/min.
A Grade 3 or 4 IRR will require immediate treatment, including, but not limited to, the use of 
epinephrine, bronchodilators, and/or glucocorticoids for symptomatic bronchospasm, IV fluids 
and/or pressors for hypotension, and immediate and permanent discontinuation of olaratumab 
with appropriate supportive care.
7.2.4.1.2. Hematologic Toxicity
Table JGDN.7.34 summarizes the olaratumab dose modifications required in case of 
olaratumab-related hematologic toxicities during any cycle.
Table JGDN.7.34.
General Guidelines for Olaratumab Dose Modification Due to 
Hematologic Toxicity Deemed Related to Olaratumab
Toxicity
Required Dose Modification
Neutropenia
  ANC Grade 1-3
No dose modification required
  ANC <500/mm3 (Grade ≥4)
No treatment administered; treatment cycle delayed
  At retreatment:
  If  Grade ≥3 neutropenic fever/infection has 
occurred
Withhold dose until ANC is ≥ 750/mm3; for the 
15-mg/kg cohort (Part A), reduce dose to 10 mg/kg; for 
the 20-mg/kg cohort (Part B and Part C), reduce dose to 
15 mg/kg. 
  If Grade 4 neutropenia lasting >1 week has occurred
Withhold dose until ANC is ≥ 750/mm3; for the 
15-mg/kg cohort (Part A), reduce dose to 10 mg/kg; for 
the 20-mg/kg cohort (Part B and Part C), reduce dose to 
15 mg/kg.
  Grade 4 ANC without fever/infection lasting
    ≤ 1 week
Administer the next olaratumab at full dose at 
investigator’s discretion with recommended use of 
prophylactic G-CSFs
  Second incidence of either:  
  1) Grade ≥3 neutropenic fever/infection
  2) Grade 4 neutropenia lasting > 1 week
For the 15-mg/kg cohort (Part A) that have been reduced 
to 10-mg/kg, discontinue olaratumab; for the 20-mg/kg 
cohort (Part B and Part C) that have been reduced to 15-
mg/kg, a second dose level reduction to 10 mg/kg
Thrombocytopenia
  Platelets <75,000/mm3
No treatment administered; treatment delayed until 
resolved to ≥75,000/mm3
Anemia
  Hemoglobin <8 g/dL 
No treatment administered; treatment delayed until 
resolved to ≥8 g/dL, transfusion with packed red blood 
cells allowed
Abbreviations:  ANC = absolute neutrophil count; G-CSFs = granulocyte colony-stimulating factors.
7.2.4.1.3.
Nonhematologic Toxicity

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 143
LY3012207
General guidelines for dose modification for other nonhematologic toxicities related to 
olaratumab are shown in Table JGDN.7.45.
Table JGDN.7.45.
General Guidelines for Dose Modification Due to Nonhematologic 
Toxicities Related to Olaratumab
Reaction Grade
Required Dose Modification
Grade 1
No dose modification is required.
Grade 2
At the investigator’s discretion, the patient may continue to receive olaratumab per protocol, 
provided that the event does not pose a serious health risk or is easily treated.
Grade 3 
For a Grade 3 toxicity not adequately controlled with appropriate supportive care, the dose
must be withheld until toxicity is ≤ Grade 1 or has returned to pretreatment baseline; then 
treatment may resume at a reduced dose of 10 mg/kg for the 15-mg/kg cohort (Part A) and 
reduced dose of 15 mg/kg for the 20-mg/kg cohort (Part B and Part C).  If toxicity recurs after 
therapy resumes, then treatment should be discontinued for the 15-mg/kg cohort (Part A) or 
the dose reduced to 10 mg/kg for the 20-mg/kg cohort (Part B and Part C).
Grade 4
The dose must be withheld until dose toxicity is ≤ Grade 1 or has returned to baseline.  
Permanent discontinuation should be considered for any patient experiencing Grade 4 
non-hematologic toxicity assessed as related to olaratumab.  However, if resumption of 
dosing is deemed appropriate by the investigator, treatment may resume only after 
consultation with the Lilly study physician, with the dose reduced to 10 mg/kg for the 
15-mg/kg cohort (Part A); dose reduced to 15 mg/kg for the 20-mg/kg cohort (Part B and Part 
C).  If Grade 4 toxicity recurs after therapy resumes, treatment with olaratumab will be 
discontinued.
7.2.4.2. Doxorubicin Dose Adjustments
The dose adjustments and delays for doxorubicin apply to patients treated with olaratumab plus 
doxorubicin.
7.2.4.3.2.1. Neurologic Toxicity
Autonomic neuropathy is manifested as constipation (which can be severe), abdominal pain, 
urinary retention, and paralytic ileus.  Laxatives or stool softeners should be givenconsidered
routinely to prevent constipation.  These symptoms resolve with time and may not occur with 
subsequent treatment.  If bladder atony occurs, vincristine should be held until symptoms 
resolve.  Worsening neuropathy requires dose delay, reduction, or discontinuation.
Table JGDN.7.78.
General Guidelines for Dose Modification of Vincirstine due to 
Toxicity
Toxicity/Worst Counts in Cycle
Vincristine Dose Reduction
  Neurotoxicity
       Grade 1 or 2 
Full dose
       Grade 3 or 4
Hold until Grade ≤1 then 50% of initial dose a
  Severe paralytic ileus
Hold until normal bowel movement then 50% of 
initial dose
  Respiratory symtoms (for example, 
bronchospasm)pneumonitis)
Discontinue

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 144
LY3012207
  Grade 3 other related nonhematologic/organ toxicity
Hold
  Grade 4 other related nonhematologic/organ toxicity
Discontinue
a
Reescalation to 75% or full dose should be considered at the start of each vincristine containing cycle based on 
patient’s symptoms.
7.2.4.5.1. Urotoxic Effects
The incidence of urotoxic effectsurotoxic effects without an uroprotector can be up to 40% and 
is dose dependent; coadministration with mesna and adequate hydration are mandatory.  Patients 
may present with hematuria, symptomatic cystitis, or bladder fibrosis.  Past or concomitant 
radiation of the bladder or busulfan treatment may increase the risk of hemorrhagic cystitis.  
Several methods of treatment for established hematuria have been described:  bladder irrigation 
with water or normal saline, intravesical instillation of astringents (alum, silver nitrate), systemic 
administration of antifibrinolytics (aminocaproic acid, tranexamic acid), cystoscopy to evacuate 
the bladder of clots, continuous bladder irrigation, and intravesical prostaglandins.  For severe or 
refractory hematuria, intravesical formalin, phenol, or prostaglandin has been used ± surgical 
intervention (electrocautery, cryosurgery, diversion of urine flow, hypogastric artery ligation, or 
cystectomy).  Ifosfamide should be discontinued or dose reduced for macroscopic hematuria.
7.3 Method of Assignment to Treatment
Patients who meet all criteria for enrollment will be assigned to receive olaratumab 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 site will register the patient by 
assigning the patient a unique study identification number via the Interactive Web Response 
System (IWRS), which is accessible 24 hours a day.  Study drug will be allocated to patients 
using the IWRS.  No dose escalations (that is, initiating Parts B and C for a chemotherapy 
combination) can occur without prior discussion and agreement with the responsible Lilly CRP 
or CRS.
7.5 Concomitant Therapy
With the exceptions listed in the sections below, no other chemotherapy, investigational 
medications, other anticancer therapy, immunotherapy, hormonal cancer therapy, radiation, or 
surgery for cancer will be permitted while patients are on study treatment.  Palliative 
radiotherapy (of ≤14 calendar days, e.g., for a solitary skeletal metastasis) after Cycle 7 may be 
allowed as long as the patient has not developed another reason for study discontinuation and 
other sites of disease are available for response assessment.  Palliative radiation may not occur 
prior to discussion with the study medical monitor and written approval.  
Appropriate documentation for all forms of premedications, supportive care, and concomitant 
medications (for example, medications such as sedatives, antibiotics, analgesics, antihistamines, 
corticosteroids, erythropoietin; procedures such as paracentesis, thoracentesis; or blood products 
such as blood cells, platelets, fresh frozen plasma transfusions) must be captured on the eCRF.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 145
LY3012207
Appropriate documentation for all forms of premedications, supportive care, and concomitant 
medications (for example, medications such as sedatives, antibiotics, analgesics, antihistamines, 
corticosteroids, erythropoietin; procedures such as paracentesis, thoracentesis; or blood products 
such as blood cells, platelets, fresh frozen plasma transfusions) must be captured on the eCRF.
If doxorubicin premedication is required prior to the doxorubicinchemotherapy infusion, this 
must be done after the completion of olaratumab infusion, not before the olaratumab infusion.
7.5.1.2. Mesna
For patients in the ifosfamide arm, mesna should be administered at a minimum dose equal to 
60% of the ifosfamide dose according to institutional guidelines, including divided dose or 
continuous infusion.  The mesna dose should be divided equally between 3 infusions given 
together with the ifosfamide infusion, 4 hours after the ifosfamide infusion, and 8 hours after the 
infusion.
7.5.2. Prohibited Therapies
Additional concurrent chemotherapy, radiation therapy, biologic response modifiers, or other 
investigational or approved anticancer agents may not be administered to patients on this study.  
Palliative radiotherapy (of ≤14 calendar days, e.g., for a solitary skeletal metastasis) after Cycle 
7 may be allowed as long as the patient has not developed another reason for study 
discontinuation and other sites of disease are available for response assessment.  Palliative 
radiation may not occur prior to discussion with the study medical monitor and written approval.  
Palliative radiation or surgery to symptomatic sites of disease will not be permitted while on 
study.
7.6.1. Evaluable Patients
Any patient from Parts A or B who is discontinued from the study before completing 1 cycle of 
olaratumab treatment will be deemed non-evaluable for assessment of olaratumab monotherapy, 
unless the patient experiences a DLT prior to withdrawal. Any patient who is discontinued from 
the study before completing 1 cycle of combination chemotherapy treatment (Cycle 2 for Parts A 
or B or Cycle 1 for Part C) will be deemed non-evaluable for assessment of a combination 
chemotherapy, unless the patient experiences a DLT or DLE-equivalent prior to withdrawal.  
If athe patient from Parts A or B is noncompliant during Cycle 1 due to reasons other than drug-
related toxicity, he or she will be considered non-evaluable for olaratumab monotherapy and may 
be replaced.  If athe patient from Parts A or B is noncompliant during Cycle 2 or a patient from 
Part C is noncompliant during Cycle 1 due to reasons other than drug-related toxicity, he or she 
will be considered non-evaluable for combination chemotherapy and may be replaced.
Nonevaluable patients may be replaced to ensure that enough patients complete 1 cycle of 
olaratumab monotherapy or combination chemotherapy, unless accrual to that cohort has stopped 
due to a DLT.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 146
LY3012207
Patients who are not evaluable for pharmacokinetics, but who complete 1 cycle of olaratumab 
monotherapy or 1 cycle of combination chemotherapy (Cycle 2), may be replaced to ensure 
adequate PK data, unless accrual to that cohort has stopped due to a DLT.
Attachment 1. Protocol JGDN Study Schedule

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 147
LY3012207
JGDN Study Schedule, Screening and Baseline Assessments (All Parts)
Relative Day Prior to 
Cycle 1 Day 1
≤28
≤14
≤7
Comments
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
To be assessed by the investigator.
Efficacy Assessments
Imaging Studies 
(CT/MRI/chest x-ray)
X
For rapidly growing tumors, scans should be performed ≤14 days prior to C1D1.  Scans performed prior to the date 
of consent may be used provided they are within 218 days of C1D1.  RECIST v1.1 should be used for all tumors 
with the exception of CNS tumors; RANO or Macdonald criteria should be used for CNS tumors.
RECIST v1.1, RANO, 
or Macdonald Tumor 
Assessments
X
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Doxorubicin (Parts A and B)
All evaluations must be done on the day of study drug administration.  In case of dose interruption, these evaluations will also be done 
at minimum frequency every 21 days (±3 days).
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Doxorubicin (Part C)
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
ECG
X
Baseline ECG can be used for C1D1 if completed within 7 days.
Consecutive replicate ECGs will be obtained (3 readings), whenever feasible for the 
patient, at approximately 1-minute intervals.
ECHO or MUGA
X
ECHO or MUGA scans must be performed PRIOR to Cycles 1, 3, and 5 and results must 
be available prior to doxorubicin administration for those cycles.  Additional 
ECHO/MUGA may be performed at the investigator’s discretion as clinically indicated.
Safety Assessments

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 148
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
Physical Exam
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
Vital sign measurements include temperature, pulse rate, and blood pressure. On Day 1, 
obtain vital signs prior to and after the completion of the olaratumab infusion (prior to 
dexrazoxane, if used; or if not used, then prior to doxorubicin) and within 1 hour after 
completion of the doxorubicin infusion.  On Day 2, obtain vital signs prior to dexrazoxane 
infusion (patients receiving dexrazoxane and doxorubicin) or prior to doxorubicin infusion 
(patients receiving doxorubicin only) and within 1 hour after completion of the 
doxorubicin infusion.  On Day 8, obtain vital signs prior to and after the completion of the 
olaratumab infusion.
Adverse Event Assessment
X
X
X
All AEs considered at least possibly-related to study treatment will be followed until 
resolution, stabilization, return to baseline, or until deemed irreversible.
Concomitant Medication 
Assessment
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
Hematology measurements must be collected on Day 15 only during Cycle 1 and Cycle 2.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 1 Day 1.  Baseline value can be used for 
C1D1 if completed within 7 days.
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a microscopic analysis.  If routine 
analysis indicates > 2+ proteinuria, then a 24-hour urine must be collected and must 
demonstrate ≤1000 mg of protein in 24 hours or urine protein/creatinine ratio < 1, prior to 
proceeding to the next cycle
Pregnancy Test
X
Urine pregnancy test on Day 1 of every cycle or per local practice (whichever is of shorter 
duration) and at short-term follow-up visit.  If the urine pregnancy test performed on Day 
1 of the cycle is positive, confirm with a serum pregnancy test.
Immunogenicity
See Attachment 4 for specific time 
points.
When possible, an immunogenicity sample will be collected at the same time as the PK 
sample.  If a patient experiences an IRR to olaratumab, blood samples for immunogenicity 
and PK analysis will be taken at the following time points:  (1) as soon as possible after 
the onset of the IRR, (2) at the resolution of the IRR, and (3) 30 days after the IRR.
Efficacy Assessments

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 149
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are to be obtained every 2 cycles (-7 days) until 
documented progression for patients with CR, PR, or SD.  RECIST v1.1 should be used 
for all tumors with the exception of CNS tumors; RANO or Macdonald criteria should be 
used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time 
points
Biomarker Sampling
X
During treatment, a single sample will be collected prior to dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and tumor type.  May be collected any 
time during or after Cycle 1 Day 1.
Premedication
Premedication prior to 
olaratumab administration
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients should receive premedication with 
dexamethasone (or equivalent medication) and an H1 antagonist intravenously 30–60 
minutes prior to olaratumab infusion.  Additional premedication may be provided at 
investigator discretion.
For all subsequent cycles, all patients should receive premedication with an H1 antagonist 
(for example, diphenhydramine) intravenously 30–60 minutes prior to each dose of 
olaratumab.  Additional premedication may be provided at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab infusion reaction in a previous cycle, 
patients should be premedicated with antihistamine and glucocorticoid (for example, 
dexamethasone) intravenously 30–60 minutes prior to olaratumab infusion, and 
acetaminophen (or equivalent) for all subsequent infusions.  Additional premedication 
may be provided at investigator discretion.
Administer dexrazoxane
X
X
Dexrazoxane may be given at 10:1 ratio (dexrazoxane to doxorubicin) prior to 
doxorubicin on Day 1 and Day 2 at the investigator' discretion.  Dexrazoxane is 
recommended for all patients receiving doxorubicin.
Clinical Drug Supplies
Administer olaratumab
X
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 150
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 1a
Day 2a
Day 8a
Day 15a
Administer doxorubicin
X
X
Doxorubicin to be administered at 37.5 mg/m2 on Day 1 and Day 2 to be continued for 6 
Cycles or a cumulative dose of 450 mg/m2
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; ECHO = echocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; MUGA = multigated acquisition; PK 
= pharmacokinetics; PR = partial response; RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors 
Version 1.1; SD = stable disease.
a
A delay of up to 3 days  will be permitted due to holidays, weekends, inclement weather or other unforeseen circumstances, including unexpected 
changes in patient schedules, and will not count as a protocol deviation.  However, assessments must be done prior to treatments and the interval 
between cycles may not be less than 21 days.  In later cycles, longer delays may be allowed in consultation with Lilly medical representative.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 151
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Vincristine and Irinotecan (Part A and B)
All evaluations must be done on the day of study drug administration.  In case of dose interruption, these evaluations will also be done 
at minimum frequency every 21 days (±3 days).
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Vincristine and Irinotecan (Part C)
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Eligibility Assessments
Lansky/Karnofsky performance 
status
X
ECG
X
Consecutive replicate ECGs will be obtained (3 readings), 
whenever feasible for the patient, at approximately 
1-minute intervals.
Safety Assessments
Physical Exam
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
X
X
X
Vital sign measurements include temperature, pulse rate, 
and blood pressure. On Day 1, obtain vital signs prior to 
and after the completion of the olaratumab infusion (prior 
to vincristine) and within 1 hour after completion of the 
irinotecan infusion.  On Days 2-5, obtain vital signs prior to 
irinotecan infusion and within 1 hour after completion of 
the infusion.  On Day 8, obtain vital signs prior to and after 
the completion of the olaratumab infusion (prior to 
vincristine) and within 1 hour after completion of the 
vincristine infusion.
Adverse Event Assessment
X
X
X
X
X
X
All AEs considered at least possibly-related to study 
treatment will be followed until resolution, stabilization, 
return to baseline, or until deemed irreversible.
Concomitant Medication 
X
X
X
X
X
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 152
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Assessment
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
Hematology measurements must be collected on Day 15 
only during Cycle 1 and Cycle 2.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 1 Day 1.  
Baseline value can be used for C1D1 if completed within 7 
days.
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a 
microscopic analysis.  If routine analysis indicates > 2+ 
proteinuria, then a 24-hour urine must be collected and 
must demonstrate ≤1000 mg of protein in 24 hours, or 
urine protein/creatinine ratio < 1, prior to proceeding to the 
next cycle.
Pregnancy Test
X
Urine pregnancy test on Day 1 of every cycle or per local 
practice (whichever is of shorter duration) and at short-term 
follow-up visit.  If the urine pregnancy test performed on 
Day 1 of the cycle is positive, confirm with a serum 
pregnancy test.
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity sample will be collected 
at the same time as the PK sample.  If a patient experiences 
an IRR to olaratumab, blood samples for immunogenicity 
and PK analysis will be taken at the following time points:  
(1) as soon as possible after the onset of the IRR, (2) at the 
resolution of the IRR, and (3) 30 days after the IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are to be obtained 
every 2 cycles (±7 days) until documented progression for 
patients with CR, PR, or SD.  RECIST v1.1 should be used 
for all tumors with the exception of CNS tumors; RANO or 
RECIST v1.1, RANO, or 
Macdonald Tumor Assessments
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 153
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Macdonald criteria should be used for CNS tumors.
Other Assessments
PK Sampling
See Attachment 4 for specific time points.
Biomarker Sampling
X
During treatment, a single sample will be collected prior to 
dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and 
tumor type.  May be collected any time during or after 
Cycle 1 Day 1.
Premedication
Premedication prior to 
olaratumab administration
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients 
should receive premedication with dexamethasone (or 
equivalent medication) and an H1 antagonist intravenously 
30–60 minutes prior to olaratumab infusion.  Additional 
premedication may be provided at investigator discretion.
For all subsequent cycles, all patients should receive 
premedication with an H1 antagonist (for example, 
diphenhydramine) intravenously 30–60 minutes prior to 
each dose of olaratumab.  Additional premedication may be 
provided at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab 
infusion reaction in a previous cycle, patients should be 
premedicated with antihistamine and glucocorticoid (for 
example dexamethasone) intravenously 30–60 minutes 
prior to olaratumab infusion, and acetaminophen (or 
equivalent) for all subsequent infusions.  Additional 
premedication may be provided at investigator discretion.
Clinical Drug Supplies
Administer olaratumab
X
X
Administer vincristine
X
X
Administer irinotecan
X
X
X
X
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 154
LY3012207
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; PK = pharmacokinetics; PR = partial response; 
RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors Version 1.1; SD = stable disease.
a
A delay of up to 3 days   will be permitted due to holidays, weekends, inclement weather or other unforeseen circumstances, including unexpected changes in 
patient schedules, and will not count as a protocol deviation.  However, assessments must be done prior to treatments and the interval between cycles may not 
be less than 21 days.  In later cycles, longer delays may be allowed in consultation with Lilly medical representative.
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Ifosfamide (Part A and B)
All evaluations must be done on the day of study drug administration.  In case of dose interruption, these evaluations will also be done 
at minimum frequency every 21 days (±3 days).
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1
Cycle 2-n
Day 1
(±3)
Day 8
(±3)
Day 1
(±3)
Day 2
(±3)
Day 3
(±3)
Day 4
(±3)
Day 5
(±3)
Day 8
(±3)
Day 15 
(±3)
Premedication
Mesna Administration
X
X
X
X
X
Administer at a minimum 60% of the 
ifosfamide dose according to institutional 
guidelines.  The mesna dose should be 
divided equally between 3 infusions given 
together with the ifosfamide infusion, 4 
hours after the ifosfamide infusion, and 8 
hours after the infusion.

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 155
LY3012207
JGDN Study Schedule, Treatment Period for Olaratumab in Combination with Ifosfamide (Part C)
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
Eligibility Assessments
Lansky/Karnofsky 
performance status
X
ECG
X
Consecutive replicate ECGs will be obtained (3 readings), 
whenever feasible for the patient, at approximately 1-minute 
intervals.
Safety Assessments
Physical Exam
X
X
Physical exam includes weight and BSA measurement.
Vital Signs
X
X
X
X
X
X
Vital sign measurements include temperature, pulse rate, and 
blood pressure. On Day 1, obtain vital signs prior to and after 
the completion of the olaratumab infusion (prior to ifosfamide) 
and within 1 hour after completion of the ifosfamide infusion.  
On Days 2-5, obtain vital signs prior to ifosfamide infusion and 
within 1 hour after completion of the infusion.  On Day 8, obtain 
vital signs prior to and after the completion of the olaratumab 
infusion. 
Adverse Event Assessment
X
X
X
X
X
X
All AEs considered at least possibly-related to study treatment 
will be followed until resolution, stabilization, return to baseline, 
or until deemed irreversible.
Concomitant Medication 
Assessment
X
X
X
X
X
X
Laboratory Assessments (See Attachment 2 for details)
Hematology Profile
X
X
X
Hematology measurements must be collected on Day 15 only 
during Cycle 1 and Cycle 2.
Coagulation Profile
X
Perform every other cycle beginning at Cycle 1 Day 1.
Chemistry Profile
X
Urinalysis
X
Includes a routine urinalysis, and if clinically indicated, a 
microscopic analysis.  If routine analysis indicates > 2+ 
proteinuria, then a 24-hour urine must be collected and must 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 156
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
demonstrate ≤1000 mg of protein in 24 hours, or urine 
protein/creatinine ratio < 1, prior to proceeding to the next cycle.
Pregnancy Test
X
Urine pregnancy test on Day 1 of every cycle or per local 
practice (whichever is of shorter duration) and at short-term 
follow-up visit.  If the urine pregnancy test performed on Day 1 
of the cycle is positive, confirm with a serum pregnancy test.
Immunogenicity
See Attachment 4 for specific time points.
When possible, an immunogenicity sample will be collected at 
the same time as the PK sample.  If a patient experiences an IRR 
to olaratumab, blood samples for immunogenicity and PK 
analysis will be taken at the following time points:  (1) as soon 
as possible after the onset of the IRR, (2) at the resolution of the 
IRR, and (3) 30 days after the IRR.
Efficacy Assessments
Imaging Studies (CT/MRI)
X
Imaging studies and tumor assessments are to be obtained every 
2 cycles (±7 days) until documented progression for patients 
with CR, PR, or SD.  RECIST v1.1 should be used for all 
tumors with the exception of CNS tumors; RANO or Macdonald 
criteria should be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
Other Assessments
PK Sampling
See Attachment 4 for specific time points
Biomarker Sampling
X
During treatment, a single sample will be collected prior to 
dosing at Cycle 3 Day 1.
Biopsy/Tumor Tissue 
Submission
X
Optional tumor tissue from biopsy for biomarkers and tumor 
type.  May be collected any time during or after Cycle 1 Day 1.
Premedication
Premedication prior to 
olaratumab administration
X
X
In Cycle 1 (both Day 1 and Day 8 doses), all patients should 
receive premedication with dexamethasone (or equivalent 
medication) and an H1 antagonist intravenously 30–60 minutes 
prior to olaratumab infusion.  Additional premedication may be 

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 157
LY3012207
Day
Treatment Period 21-Day Cycles
Comments
Cycle 1-n
Day 
1a
Day 
2a
Day 
3a
Day 
4a
Day 
5a
Day 
8a
Day 15a
provided at investigator discretion.
For all subsequent cycles, all patients should receive 
premedication with an H1 antagonist (for example, 
diphenhydramine) intravenously 30–60 minutes prior to each 
dose of olaratumab.  Additional premedication may be provided 
at investigator discretion.
For a patient who has had a Grade 1 or 2 olaratumab infusion 
reaction in a previous cycle, patients should be premedicated 
with antihistamine and glucocorticoid (for example, 
dexamethasone) intravenously 30–60 minutes prior to 
olaratumab infusion, and acetaminophen (or equivalent) for all 
subsequent infusions.  Additional premedication may be 
provided at investigator discretion.
Mesna Administration
X
X
X
X
X
Administer at a minimum 60% of the ifosfamide dose according 
to institutional guidelines.  
Clinical Drug Supplies
Administer olaratumab
X
X
Administer ifosfamide
X
X
X
X
X
Administer ifosfamide for up to 6 cycles or a cumulative dose of 
84 g/m2.  Treatment beyond 84 g/m2 requires consultation with 
the Lilly CRP/CRS.
Abbreviations:  AE = adverse event; BSA = body surface area; CNS = central nervous system; CR = complete response; CT = computed tomography; 
ECG = electrocardiogram; IRR = infusion-related reaction; MRI = magnetic resonance imaging; PK = pharmacokinetics; PR = partial response; 
RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; SD = stable disease.
a
A delay of up to 3 days  will be permitted due to holidays, weekends, inclement weather or other unforeseen circumstances, including unexpected changes in 
patient schedules, and will not count as a protocol deviation.  However, assessments must be done prior to treatments and the interval between cycles may not 
be less than 21 days.  In later cycles, longer delays may be allowed in consultation with Lilly medical representative.
JGDN Study Schedule, Follow-up Assessments (All Parts)
Day
Follow-up
Comments

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 158
LY3012207
Short-Terma
Long-Termb
30 days (±7) after 
discontinuation 
date
Patients who discontinued 
for reasons other than 
progressive disease
Efficacy Assessments
Imaging Studies (CT/MRI)
X
(if applicable)
X
For patients who have discontinued study treatment due to toxicity or 
reasons other than progressive disease, imaging studies and tumor 
assessments are to be obtained every 6 weeks (±7 days) until progression 
or initiation of other anti-cancer therapy.  RECIST v1.1 should be used for 
all tumors with the exception of CNS tumors; RANO or Macdonald criteria 
should be used for CNS tumors.
RECIST v1.1, RANO, or 
Macdonald Tumor 
Assessments
X
(if applicable)
X
Subsequent Anti-Cancer 
Treatments, and Associated 
Disease Progression Date
X
For all patients who have discontinued study treatment due to toxicity or 
reasons other than progressive disease, details on subsequent anticancer 
treatment (start/stop dates and treatments administered) and first post-study 
treatment disease progression date should be recorded.
Attachment 4.  Protocol JGDN Pharmacokinetic and Immunogenicity Sampling Schedule
Pharmacokinetic and Immunogenicity Sampling (Part A and Part B)
Sample Number
Cycle
Day
Sampling Time
Olaratumab PKa
Combination 
agents PKb
Immunogenicityc
1
1
1
Prior to olaratumab infusion
X
X
2
8
Within 5 min post olaratumab infusion
X
3
2
1
Within 15 min prior to olaratumab infusion
X
X
4
1
Within 5 min post chemotherapy infusion
X
X
5
8
Within 5 min post olaratumab infusion
X
6
3 and then every 
other cycle
1
Within 15 min prior to olaratumab infusion
X
X
7
30-day follow-up (Visit 801)
Any time
X
X

I5B-MC-JGDN(b) Phase 1 Oncology Protocol
Page 159
LY3012207
Abbreviation:  PK = pharmacokinetics.
a
A 2.5-mL (1 mL if patient has 19kg) blood sample will be collected (to generate serum for bioanalysis).
b A 2-mL (1 mL if patient has 19kg) blood sample will be collected (to generate plasma for bioanalysis).
c
A 3.5-mL blood sample will be collected (to generate serum for anti-olaratumab antibody analysis).
Pharmacokinetic and Immunogenicity Sampling (Part C)
Sample 
Number
Cycle
Day
Sampling Time
Olaratumab PKa
Combination 
agents PKb
Immunogenicityc
1
1
1
Prior to olaratumab infusion
X
X
2
1
Within 5 min post chemotherapy 
infusion
X
X
3
8
Within 5 min post olaratumab 
infusion
X
4
2
1
Within 15 min prior to olaratumab 
infusion
X
X
5
8
Within 5 min post olaratumab 
infusion
X
6
3 and then every 
other cycle
1
Within 15 min prior to olaratumab 
infusion
X
X
7
30-day follow-up (Visit 
801)
Any time
X
X
Abbreviation:  PK = pharmacokinetics.
a
A 2.5-mL (1 mL if patient has 19kg) blood sample will be collected (to generate serum for bioanalysis).
b A 2-mL (1 mL if patient has 19kg) blood sample will be collected (to generate plasma for bioanalysis).
c
A 3.5-mL blood sample will be collected (to generate serum for anti-olaratumab antibody analysis).