A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Nab-Paclitaxel and Gemcitabine With or Without Olaratumab in the Treatment of First-Line Metastatic Pancreatic Cancer
Phase: PHASE1
Conditions: Metastatic Pancreatic Cancer
Sponsor: Eli Lilly and Company

 
 
 
Protocol I5B-MC-JGDP(e) 
 
 
A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) 
Study Evaluating Nab-Paclitaxel and Gemcitabine With or Without 
Olaratumab in the Treatment of First-Line Metastatic Pancreatic 
Cancer 
 
 
NCT03086369 
 
 
Approval Date: 20 March 2019 

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Protocol I5B-MC-JGDP(e)
A Phase 1b (Open-Label) / Phase 2 (Randomized, 
Double-Blinded) Study Evaluating Nab-Paclitaxel and 
Gemcitabine With or Without Olaratumab in the Treatment of
First-Line Metastatic Pancreatic Cancer
Confidential Information
The information contained in this protocol is confidential and is intended for the use of clinical investigators.  It 
is the property of Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to 
persons not involved in the clinical investigation of olaratumab (LY3012207), unless such persons are bound 
by a confidentiality agreement with Eli Lilly and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data and/or commercially 
confidential information exempt from public disclosure.  Eli Lilly and Company requests consultation 
regarding release/redaction prior to any public release.  In the United States, this document is subject to 
Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or otherwise disseminated 
without the written approval of Eli Lilly and Company or its subsidiaries.
Olaratumab (LY3012207)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly on 15 September 2016.
Amendment (a) Electronically Signed and Approved by Lilly on 06 December 2016.
Amendment (b) Electronically Signed and Approved by Lilly on 27 February 2017.
Amendment (c) Electronically Signed and Approved by Lilly on 04 December 2017.
Amendment (d) Electronically Signed and Approved by Lilly on 10 December 2018.
Amendment (e) Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 20-Mar-2019 GMT

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Table of Contents
Section
Page
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................11
3.
Introduction ......................................................................................................................19
3.1.
Study Rationale............................................................................................................19
3.2.
Background..................................................................................................................19
3.2.1.
Olaratumab ..........................................................................................................19
3.2.2.
Pancreatic Cancers...............................................................................................20
3.3.
Benefit/Risk Assessment..............................................................................................21
4.
Objectives and Endpoints..................................................................................................23
5.
Study Design.....................................................................................................................24
5.1.
Overall Design .............................................................................................................24
5.2.
Number of Patients.......................................................................................................28
5.3.
End of Study Definition ...............................................................................................28
5.4.
Scientific Rationale for Study Design...........................................................................28
5.4.1.
Rationale for Amendment (a)...............................................................................29
5.4.2.
Rationale for Amendment (b)...............................................................................29
5.4.3.
Rationale for Amendment (c)...............................................................................29
5.4.4.
Rationale for Amendment (d)...............................................................................29
5.4.5.
Rationale for Amendment (e)...............................................................................30
5.5.
Justification for Olaratumab Dose ................................................................................31
6.
Study Population...............................................................................................................33
6.1.
Inclusion Criteria..........................................................................................................33
6.2.
Exclusion Criteria ........................................................................................................35
6.3.
Lifestyle Restrictions....................................................................................................36
6.4.
Screen Failures.............................................................................................................36
7.
Treatments........................................................................................................................37
7.1.
Treatments Administered .............................................................................................37
7.1.1.
Premedication ......................................................................................................37
7.1.1.1.
Olaratumab/Placebo........................................................................................38
7.1.1.2.
Nab-paclitaxel ................................................................................................39
7.1.1.3.
Gemcitabine ...................................................................................................39
7.1.1.4.
Granulocyte-Colony Stimulating Factors........................................................40
7.1.2.
Investigator Responsibilities.................................................................................40
7.1.3.
Packaging and Labelling ......................................................................................40

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7.1.4.
Dose-Limiting Toxicity Determination (Phase 1b) ...............................................41
7.2.
Method of Treatment Assignment ................................................................................41
7.2.1.
Phase 1b...............................................................................................................42
7.2.2.
Phase 2.................................................................................................................42
7.2.3.
Selection and Timing of Doses.............................................................................42
7.3.
Blinding .......................................................................................................................43
7.3.1.
Emergency Unblinding ........................................................................................43
7.3.2.
Inadvertent Unblinding ........................................................................................43
7.4.
Dosage Modification....................................................................................................43
7.4.1.
Dosing and Dose Reductions................................................................................44
7.4.2.
Dose Modifications..............................................................................................45
7.4.2.1.
Hematological Toxicites.................................................................................45
7.4.2.2.
Non-Hematological Toxicities ........................................................................46
7.4.3.
Dose Delays.........................................................................................................47
7.4.4.
Dosing Discontinuation........................................................................................48
7.4.4.1.
Gemcitabine ...................................................................................................48
7.4.4.2.
Nab-paclitaxel ................................................................................................48
7.4.4.2.1.
Hepatic Impairment ..................................................................................48
7.4.4.2.2.
Sepsis .......................................................................................................48
7.4.4.2.3.
Pneumonitis..............................................................................................48
7.4.4.2.4.
Infusion-related Reactions/Hypersensitivity 
Reactions..................................................................................................49
7.4.4.3.
Olaratumab.....................................................................................................49
7.4.4.3.1.
Olaratumab Infusion-Related Reactions ....................................................49
7.5.
Preparation/Handling/Storage/Accountability...............................................................50
7.6.
Treatment Compliance .................................................................................................50
7.7.
Concomitant Therapy...................................................................................................50
7.7.1.
Other Concomitant Medication (CYP2C8 and CYP3A4 
Inhibitors or Inducers)..........................................................................................50
7.7.2.
Supportive Care ...................................................................................................50
7.7.2.1.
Colony Stimulating Factors ............................................................................51
7.7.2.2.
Transfusion of Blood Product.........................................................................51
7.7.2.3.
Antiemetic Therapy........................................................................................51
7.7.3.
Prohibited Therapies ............................................................................................51
7.8.
Treatment after the End of the Study............................................................................51
7.8.1.
Continued Access.................................................................................................51
8.
Discontinuation Criteria ....................................................................................................53
8.1.
Discontinuation from Study Treatment.........................................................................53

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8.1.1.
Discontinuation of All Study Treatment ...............................................................53
8.1.2.
Discontinuation of Olaratumab/Placebo ...............................................................53
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................53
8.2.
Discontinuation from the Study....................................................................................53
8.3.
Lost to Follow-Up........................................................................................................54
9.
Study Assessments and Procedures ...................................................................................55
9.1.
Efficacy Assessments...................................................................................................55
9.1.1.
Appropriateness of Assessments ..........................................................................55
9.2.
Adverse Events ............................................................................................................56
9.2.1.
Definitions ...........................................................................................................56
9.2.2.
AE Reporting.......................................................................................................56
9.2.3.
Serious Adverse Events........................................................................................57
9.2.4.
Suspected Unexpected Serious Adverse Reactions ...............................................58
9.2.5.
Adverse Events of Special Interest .......................................................................58
9.2.6.
Complaint Handling.............................................................................................58
9.3.
Treatment of Overdose.................................................................................................59
9.4.
Safety...........................................................................................................................59
9.4.1.
Other Safety Measures .........................................................................................59
9.4.2.
Safety Monitoring ................................................................................................59
9.4.2.1.
Hepatic Monitoring ........................................................................................60
9.5.
Pharmacokinetics .........................................................................................................60
9.6.
Pharmacodynamics ......................................................................................................61
9.7.
Genetics .......................................................................................................................61
9.7.1.
Whole Blood Samples for Pharmacogenetic Research..........................................61
9.8.
Biomarkers...................................................................................................................61
9.8.1.
Samples for Nonpharmacogenetic Biomarker Research........................................62
9.8.2.
Tissue Samples for Research................................................................................62
9.8.3.
Immunogenicity Assessments ..............................................................................63
9.9.
Patient-Reported Outcomes/Resource Utilization (Phase 2 only)..................................64
9.9.1.
Patient-Reported Outcomes..................................................................................64
9.9.1.1.
Pain assessments.............................................................................................64
9.9.1.2.
EORTC QLQ-30 ............................................................................................65
9.9.1.3.
EQ-5D-5L ......................................................................................................66
9.9.2.
Resource Utilization.............................................................................................66
10.
Statistical Considerations ..................................................................................................67
10.1. Sample Size Determination ..........................................................................................67
10.2. Populations for Analyses..............................................................................................67
10.3. Statistical Analyses ......................................................................................................68

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10.3.1.
Efficacy Analyses ................................................................................................68
10.3.1.1.
Primary Endpoint ...........................................................................................68
10.3.1.2.
Secondary Endpoints ......................................................................................69
10.3.2.
Safety Analyses....................................................................................................70
10.3.3.
Other Analyses.....................................................................................................70
10.3.3.1.
Patient Disposition..........................................................................................70
10.3.3.2.
Patient Characteristics ....................................................................................70
10.3.3.3.
Concomitant Therapy .....................................................................................70
10.3.3.4.
Poststudy-Treatment-Discontinuation Therapy ...............................................71
10.3.3.5.
Treatment Compliance....................................................................................71
10.3.3.6.
Pharmacokinetic Analyses..............................................................................71
10.3.3.7.
Patient Reported Outcomes Analyses - Phase 2 only.......................................71
10.3.3.8.
Biomarker Analyses .......................................................................................72
10.3.3.9.
Healthcare Resource Utilization......................................................................72
10.3.4.
Subgroup Analyses ..............................................................................................72
10.3.5.
Interim Analyses..................................................................................................72
11.
References ........................................................................................................................74

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List of Tables
Table
Page
Table JGDP.1.
Baseline Schedule of Activities ..............................................................11
Table JGDP.2.
On-Study-Treatment Schedule of Activities............................................13
Table JGDP.3.
Post-Study-Treatment Follow-Up Schedule of Activities........................15
Table JGDP.4.
Continued Access Schedule of Activities................................................18
Table JGDP.5.
Objectives and Endpoints .......................................................................23
Table JGDP.6.
Treatment Regimens...............................................................................37
Table JGDP.7.
Olaratumab Infusion-Related Reaction Treatment Guidelines.................39
Table JGDP.8.
Dosing and Dose Reductions for Nab-paclitaxel and Gemcitabine..........45
Table JGDP.9.
Dosing and Dose Reductions for Olaratumab..........................................45
Table JGDP.10.
Dose Recommended and Modifications for Neutropenia and/or 
Thrombocytopenia within a Cycle ..........................................................46
Table JGDP.11.
Guidelines for Dose Modifications due to Non-Hematological 
Study Drugs-Related Toxicities ..............................................................47
Table JGDP.12.
World Health Organization Pain Scale....................................................65

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List of Figures
Figure
Page
Figure JGDP.1.
Illustration of study design of Phase 1b...................................................26
Figure JGDP.2.
Illustration of study design of Phase 2.....................................................27
Figure JGDP.3.
Continued access diagram.......................................................................52

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions ................................................................77
Appendix 2.
Study Governance, Regulatory, and Ethical Considerations....................82
Appendix 3.
Clinical Laboratory Tests........................................................................85
Appendix 4.
Pharmacokinetic, Immunogenicity, and Biomarker Research 
Sampling Schedule .................................................................................87
Appendix 5.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality ............91
Appendix 6.
Creatinine Clearance Formula.................................................................92
Appendix 7.
Protocol Amendment I5B-MC-JGDP(e) Summary:  A Phase 1b 
(Open-Label) / Phase 2 (Randomized, Double-Blinded) Study 
Evaluating Nab-Paclitaxel and Gemcitabine With or Without 
Olaratumab in the Treatment of First-Line Metastatic Pancreatic 
Cancer....................................................................................................93

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1.
Synopsis
Protocol Title:
A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Nab-Paclitaxel and 
Gemcitabine With or Without Olaratumab in the First-Line Treatment of Metastatic Pancreatic Cancer
Rationale:
Study I5B-MC-JGDP (JGDP) is designed to evaluate the safety and efficacy of olaratumab in combination with 
nab-paclitaxel and gemcitabine.
Objectives and Endpoints:
Objectives
Endpoints
Primary
Phase 1b:
to determine a recommended Phase 2 dose of 
olaratumab in combination with nab-paclitaxel and 
gemcitabine
Phase 2:
to compare the efficacy of olaratumab plus 
nab-paclitaxel and gemcitabine with placebo plus nab-
paclitaxel and gemcitabine
Phase 1b
DLTs
Safety (including but not limited to) TEAEs, SAEs, 
and clinical laboratory abnormalities
Phase 2
OS
Secondary
Phase 1b
to characterize the safety and toxicity profile of 
olaratumab plus nab-paclitaxel and gemcitabine
to evaluate the PK and immunogenicity of olaratumab
plus nab-paclitaxel and gemcitabine
to document the antitumor activity observed with 
olaratumab plus nab-paclitaxel and gemcitabine
Phase 2
to assess time-to-event variables
to document the antitumor activity observed with 
olaratumab plus nab-paclitaxel and gemcitabine
to assess PROs: pain, HRQoL, and health status
to determine safety and tolerability of olaratumab in 
combination with nab-paclitaxel and gemcitabine
to assess the PK and immunogenicity of olaratumab 
plus nab-paclitaxel and gemcitabine
Phase 1b
Safety monitoring, including TEAEs, SAE, and deaths
Minimum serum/plasma concentration of olaratumab
plus nab-paclitaxel and gemcitabine
OS, PFS, ORR, and DoR
Phase 2
PFS, DoR
ORR
mBPI-sf, EORTC-QLQ-C30, and EQ-5D-5L
TEAEs, AESI, SAEs, clinical laboratory tests, vital 
signs, physical examinations, hospitalization, and 
deaths
Minimum serum/plasma concentration of olaratumab 
plus nab-paclitaxel and gemcitabine
Abbreviations:  AESI = adverse event of special interest; DLT = dose-limiting toxicity; DoR = duration of response; 
EORTC = European Organisation for Research and Treatment of Cancer HRQoL = Health-related Quality of Life; 
mBPI-sf = modified brief pain index-short form; ORR = objective response rate; OS = overall survival; PFS = 
progression-free survival; PK = pharmacokinetic; PRO = patient-reported outcomes; SAE = serious adverse events; 
TEAE = treatment-emergent adverse events.
Overall Design:
Study JGDP is an open-label, multicenter, nonrandomized Phase 1b study of olaratumab in combination with nab-
paclitaxel and gemcitabine followed by a randomized, double-blinded, placebo-controlled, Phase 2 study of 

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olaratumab plus nab-paclitaxel and gemcitabine versus placebo plus nab-paclitaxel and gemcitabine in patients with 
metastatic (Stage IV) unresectable pancreatic cancer, who have not received prior treatment for metastatic disease.
Number of Patients:
Entered: Approximately 207 (Phase 1b: 27; Phase 2: 180)
Enrolled/Randomized (1:1 randomization [Phase 2 only]): 186 (Phase 1b: 24; Phase 2: 162) Phase 1b:
Approximately 24 patients evaluable for dose-limiting toxicities (DLTs). Patients who are not evaluable 
for DLTs will be replaced.

Phase 2:  approximately 81 patients per treatment arm
Treatment Arms and Duration:
All patients enrolled in this study will receive olaratumab/placebo administered via intravenous (I.V.) infusion in 
combination with nab-paclitaxel and gemcitabine.  After study completion, patients on study treatment who continue 
to experience clinical benefit and no undue risks, in the opinion of the investigator, may continue to receive study 
treatment until one of the criteria for discontinuation is met (see Section 8 for details).
Postdiscontinuation Follow-Up Period Assessments
Terms used to describe the postdiscontinuation of study treatment are defined below:

Postdiscontinuation Follow-Up:  begins the day after the patient and the investigator agree that the patient 
will no longer continue study treatment.
o
The short-term follow-up period begins the day after the patient and the investigator agree that the 
patient will no longer continue study treatment and lasts approximately 30 days.
o
The long-term follow-up period begins 1 day after the short-term follow-up period is completed and 
continues until death or end of trial.
Continued Access/ Follow-Up
The continued access period will apply to this study as long as 1 patient is still on study treatment when study 
completion occurs.  Lilly will notify investigators when the continued access begins.  Continued access follow-up 
(Visit 901) begins 1 day after the patient and the investigator agree that the patient will no longer continue treatment 
in the continued access period and lasts approximately 30 days.
Study Schedule of Activities (Section 2) describes all assessments for the postdiscontinuation, continued access, and 
follow-up periods.
Study Completion and End of Trial
This study will be considered complete following the final analysis/evaluation of OS after approximately 113 events 
(deaths) have been recorded.
The end of trial occurs after study completion and after the last patient has discontinued from the study for one of 
the following reasons:  death, lost to follow-up, patient or investigator decision to withdraw the patient, or Lilly 
decision to stop the study.  Investigators will continue to follow the study schedule of activities for all patients until 
notified by Lilly that the end of trial has occurred.

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2.
Schedule of Activities
Table JGDP.1.
Baseline Schedule of Activities
Relative Day Prior to C1D1
28
7
Instructions
Procedure
Informed consent
X
ICF must be signed before any protocol-specific 
procedures are performed.
Physical examination
X
Including height, weight, and vital signs 
(temperature, blood pressure, pulse rate, and 
respiration rate)
ECOG performance status
X
(Oken et al. 1982) Refer to Section 6.1
Medical history
X
Including assessment of preexisting conditions, 
historical illnesses, and substance usage (such as 
tobacco, alcohol, or caffeine)
Prior and current medication
X
Current medications (including analgesic use) and 
those received within 30 days prior to study 
treatment will be recorded after eligibility is 
confirmed.
AE Collection
X
After consent, collect AEs continuously throughout 
pretreatment period. See Section 9.2.2
Radiologic imaging and, as 
applicable, measurement of palpable 
or visible lesions
X
Perform according to RECIST 1.1 (Eisenhauer et al. 
2009).
Spiral CT with contrast or MRI of the abdomen, 
chest, and pelvis as clinically indicated
On scans available, assess for presence of lung, 
liver, bone and brain metastases. 
Radiologic assessments obtained prior to the date of 
consent may be used if performed within 28 days 
prior to enrollment. 
ECG
X
See Section 9.4.1
Hematology
X
See Appendix 3
Coagulation
X
See Appendix 3 for designation of local or central 
testing.
Clinical chemistry
X
See Appendix 3 for designation of local or central 
testing.
Urinalysis
X
See Appendix 3 for designation of local or central 
testing.
Serum pregnancy test
X
Applies only to women of childbearing potential.  
See Appendix 3 for designation of local or central 
testing.

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PRO assessment (mBPI-sf) 
Phase 2 only
X
Two baseline assessments will be collected, the first 
one within 7 days of the first cycle and the second 
one at Day 1 of the first cycle prior to study 
treatment administration.  Questionnaires should be 
administered to the patient prior to extensive 
interaction with site staff.  See Section 9.9
Tumor Tissue (archival or newly 
obtained biopsy)
X
Any time prior to the first infusion.  Optional 
collection for Phase 1b, mandatory collection for 
Phase 2. See Section 9.8.2
Abbreviations:  AE = adverse event; C1D1 = Cycle 1 Day 1; CTCAE = Common Terminology Criteria for Adverse 
Events; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; ICF = informed consent form; 
mBPI-sf = modified Brief Pain Inventory-short form; PRO = patient-reported outcome; RECIST 1.1 = Response 
Criteria In Solid Tumors Version 1.1 (Eisenhauer et al. 2009).

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Table JGDP.2.
On-Study-Treatment Schedule of Activities
Cycle 1 and beyond
Day within Cycle (±3 days)
D1
D8
D15
D22
(Phase 1b
Only)
Instructions
Procedure
Physical examination
X

Symptom-directed examination

Perform prior to administration of study drug(s).

Including weight, height, and vital signs (temperature, blood pressure, pulse rate, 
and respiration rate)
Concomitant medication
X
X
X
Xa
Refer to Section 7.7
AE collection
X
X
X
Xa
Refer to Section 9.2.2
ECOG performance status
X
Refer to Section 6.1
Radiologic imaging and 
measurement of palpable or visible
lesions
X

Perform according to RECIST 1.1, by the same method used at baseline, every 8 
weeks (±7 days), from the start of study treatment in Phase 1 and from 
randomization in Phase 2 until radiographic disease progression, death, or study 
completion, whichever occurs first. (See Section 5.1)

Perform as scheduled, even if study treatment is delayed or omitted.

Spiral CT with contrast or MRI of the abdomen, chest, and pelvis as clinically 
indicated

At PD, assess scans available for presence of tumor lesions in lung, liver, bone and 
brain
ECG
X
Cycle 1 only.  Perform additional evaluations in the setting of cardiac symptoms and/or 
at the discretion of the investigator.  Refer to Section 9.4.1
Hematology
X
X
X
Xa
3 days prior to administration of study treatment, unless more frequent assessment is 
clinically indicated.  See Appendix 3
Coagulation
X
Perform within 3 days prior to administration of study treatment on Day 1 of every 
other cycle, unless more frequent assessment is clinically indicated.  See Appendix 3
Clinical chemistry
X
X
X
Xa
3 days prior to administration of study treatment, unless more frequent assessment is 
clinically indicated. CA-19.9 collected only on Day 1 of each cycle.  See Appendix 3
Pregnancy test
X
Serum or urine pregnany test.  Applies only to women of childbearing potential.  
Perform on Day 1 of each cycle or per local practice (whichever is shorter duration).  If 
the urine pregnancy test performed on Day 1 of the cycle is positive, confirm with a 
serum pregnancy test (pregnancy test results are not recorded on the eCRF).

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Cycle 1 and beyond
Day within Cycle (±3 days)
D1
D8
D15
D22
(Phase 1b
Only)
Instructions
Procedure
PRO assessments (mBPI-sf; 
EQ-5D-5L; EORTC QLQ C30) -
Phase 2 only
X
Questionnaires should be administered to the patient prior to extensive interaction with 
site staff and must be completed prior to study drug administration in sequential order, 
at the beginning of the visit prior to other study procedures, with the mBPI-sf presented 
first, followed by the EORTC QLQ-C30 and continuing with the EQ-5D-5L. See 
Section 9.9.1
Administer olaratumab
X
X
X
Phase 1b, Cohorts 1 and 2, administered I.V. on Days 1, 8, and 15.  Cohorts 3 and 4,
administered I.V. on Days 1 and 15.  
For Phase 2 portion, olaratumab will be administered on Days 1, 8 and 15. For 
additional detail, (see Table JGDP.6).
Administer nab-paclitaxel
X
X
X
See Section 7.1
Administer gemcitabine
X
X
X
See Section 7.1
Sample collection for
X
For all sample collection, see Appendix 4.
Pharmacodynamics/Biomarkers
Pharmacokinetics
Immunogenicity
Pharmacogenomics
Abbreviations:  AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; D = Day; ECG = electrocardiogram; ECOG = Eastern Cooperative 
Oncology Group; EORTC = European Organisation for Research and Treatment of Cancer; EQ = EuroQol; IG = immunogenicity; I.V. = intravenous(ly); 
mBPI-sf = modified Brief Pain Inventory-short form; PD = progressive disease; PG = pharmacogenomics; PK = pharmacokinetics; PRO = patient-reported outcome; 
RECIST 1.1 = Response Criteria In Solid Tumors Version 1.1.
a
Activities performed only in the Phase 1b portion of the study.  Omit for the Phase 2 portion.

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Table JGDP.3.
Post-Study-Treatment Follow-Up Schedule of Activities
Procedure
Short-Term 
Follow-Upa
Long-Term 
Follow-Upb
Instructions
Physical examination
X
Including weight, and vital signs (temperature, blood pressure, pulse rate, 
and respiration rate)
Concomitant medication
X
Refer to Section 7.7
AE collection
X
Refer to Section 9.2.2
ECOG performance status
X
Refer to Section 6.1
Radiologic imaging and measurement of 
palpable or visible lesions
X
X
For patients who discontinue study treatment for reasons other than 
documented radiographic disease progression, imaging studies and tumor 
assessments are to be obtained q 8 weeks (7 days) according to
RECIST 1.1 (See Section 5.1), irrespective of treatment cycles as calculated
from enrollment in Phase 1b or from randomization for Phase 2, until:

the patient has documented radiographic disease progression, or

study completion, or

start of a new anticancer therapy
After the patient has documented disease progression, radiologic tests are no
longer required.

Spiral CT with contrast or MRI of the abdomen, chest, and pelvis as 
clinically indicated

At PD, assess scans available for presence of tumor lesions in lung, liver, 
bone and brain
ECG
X
See Section 9.4.1
Collection of survival information
X
Perform q 12 weeks (±14 days).  Although preferable to collect during a 
clinic visit, survival information may be collected by contacting the patient 
or family directly (for example, via telephone).  
Collection of post-study-treatment anticancer 
therapy information
X
X
Perform q 12 weeks (±14 days) for the first 2 years after discontinuation 
from study treatment and q 6 mo (±14 days) thereafter until death or study 
completion.
Hematology
X
See Appendix 3
Coagulation
X
See Appendix 3

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Procedure
Short-Term 
Follow-Upa
Long-Term 
Follow-Upb
Instructions
Pregnancy test
X
Serum or urine pregnancy test. Applies only to women of childbearing 
potential.  If the urine test is positive, confirm with a serum pregnancy test 
(pregnancy test results are not recorded on the eCRF). Additional pregnancy 
tests may be done after short-term follow-up if required by local regulation.
Clinical chemistry
X
See Appendix 3
Urinalysis
X
PRO assessments (mBPI-sf; EQ-5D-5L;
EORTC QLQ C30)
Phase 2 only
X
X
PROs will be assessed at the short-term follow-up visit and once during the 
first long-term follow-up visit.
Questionnaires should be administered to the patient prior to extensive 
interaction with site staff and must be completed prior to study drug 
administration in sequential order, at the beginning of the visit prior to other 
study procedures, with the mBPI-sf presented first, followed by the EORTC 
QLQ-C30 and continuing with the EQ-5D-5L. See Section 9.9.1
A written copy of each PRO will be given to the patient at the 30 Days
Follow-Up visit with instructions for completion as part of the first long-
term follow-up visit.  The PROs should be completed in the order described 
for the short-term follow-up visit.  The completed PROs should be placed in 
an envelope addressed and stamped for return to the study site. If long-term 
follow-up visit is conducted via a phone call, every effort should be made 
for the patient to complete the questionnaires during the call, preferably 
before other study questions are asked. Once completed, the questionnaires 
should be mailed or returned back to the site as soon as possible.
Sample collection for:
X
For all sample collection, see Appendix 4.
Pharmacodynamics/Biomarkers
Pharmacokinetics
Immunogenicity
Pharmacogenomics
Abbreviations:  AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Event; ECOG = Eastern Cooperative Oncology Group; eCRF = electronic 
case report form; EORTC = European Organisation for Research and Treatment of Cancer; EQ = EuroQol; mBPI-sf = modified Brief Pain Inventory-short form; 
PD = progressive disease; PRO = patient-reported outcome; q = every; RECIST 1.1 = Response Criteria In Solid Tumors Version 1.1.

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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).  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 visits, the visit 
duration may be shortened. In this case, the follow-up assessments should be completed prior to the initiation of the new therapy.
b
Long-term follow-up period begins the day after the short-term follow-up period is completed and continues until the patient’s death or overall study completion.
Follow-up should be attempted at regularly scheduled intervals (q 12 weeks [±14 days]). This follow-up might be conducted via a request to the patient’s doctor or by 
contacting the patient, his/her family by telephone/mail.  No follow-up procedures will be performed for a patient who withdraws informed consent unless he or she 
has explicitly provided permission and consent to allow for follow-up.

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Table JGDP.4.
Continued Access Schedule of Activities
Study Treatment
Follow-Upa
Visit
501-5XX
901
Procedureb
Instructions
AE collection
X
X
Refer to Section 9.2.2
Pharmacokinetics and Immunogenicity
X
X
Only if a patient experiences an IRR, collect blood samples for PK and 
IG analysis 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.
Administer study drugs
X
Abbreviations:  AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; IG = immunogenicity; IRR = infusion-related reaction; 
PK = pharmacokinetics.
a
Continued access follow-up begins 1 day after the patient and the investigator agree that the patient will no longer continue treatment in the continued access period 
and lasts approximately 30 days. No follow-up procedures will be performed for a patient who withdraws informed consent unless he or she has explicitly provided 
permission and consent to allow for follow-up.  If it is deemed to be in the best interest of the patient to start a new anticancer treatment prior to the scheduled end of 
the follow-up visits, the visit duration may be shortened. In this case, the follow-up assessments should be completed prior to the initiation of the new therapy.
b
Efficacy assessments will be done at the investigator’s discretion based on the standard of care.

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3.
Introduction
3.1.
Study Rationale
Study I5B-MC-JGDP (JGDP) is a Phase 1b/2 trial designed to evaluate the safety and efficacy of 
olaratumab in combination with nab-paclitaxel and gemcitabine in patients with unresectable 
metastatic pancreatic cancer, who had not previously been treated for metastatic disease.
Platelet-derived growth factor receptor (PDGFR)/platelet-derived growth factor (PDGF)
signaling has been shown to be an important signaling regulator in epithelial mesenchymal 
transition in several types of cancer.  Platelet-derived growth factor receptor / platelet-derived 
growth factor signaling has been shown to create an autocrine signaling loop in pancreatic cancer 
that is an active participant in the formation of desmoplastic reaction as well as the activation of 
pancreatic stellate cells – hallmarks of pancreatic cancer and important contributors to the 
pancreatic cancer microenvironment (Mahadevan and Von Hoff 2007).  Thus, the use of 
neutralizing monoclonal antibody specific to human PDGFRα could provide a therapeutic target
in metastatic pancreatic cancer.
Across numerous cancers evaluated based on data from The Cancer Genome Atlas (TCGA) 
research, overexpression of PDGFRα in tumors relative to normal tissue was highest in soft 
tissue sarcoma (STS) (37.1% overexpression) and pancreatic cancer (41.1% overexpression).  
Overexpression of PDGFRα ligands (PDGF-A, -B, and -C) was observed in sarcoma relative to 
normal tissue (PDGF-A 7.6%, PDGF-B 6.7%, and PDGF-C 20%).  Though little to no 
overexpression was observed in pancreatic cancer tumors relative to normal pancreas tissue 
(PDGF-A 0%, PDGF-B 0%, and PDGF-C 5.4%), expression levels in normal pancreas were 
notably higher than expression levels in normal soft tissue, suggesting that despite little to no 
overexpression of PDGF ligands in pancreatic tumors, there are PDGF ligands present and 
overexpression of PDGFRα demonstrates necessary components for PDGF signaling within the 
tumor microenvironment.
Tissue array from human pancreatic cancer tumors show that while not directly expressed on the 
tumor, PDGFRα is expressed in pancreatic cancer tumor stroma (9 of 12 samples) (data in-
house).  The strong stromal component to pancreatic cancer and the associated PDGFRα staining 
seen may provide an opportunity to disrupt the tumor growth and support provided by PDGFRα 
signaling by blocking PDGFRα in pancreatic cancer and its associated tumor stroma 
(Olaratumab Bioinformatic Study Report 2015).
3.2.
Background
3.2.1. Olaratumab
Olaratumab is a recombinant human immunoglobulin G subclass 1 (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 

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phosphorylation of the downstream signaling molecules Akt and mitogen-activated protein
kinase (Loizos et al. 2005).
In 2 Phase 1 dose-escalation trials in patients with solid tumors (I5B-IE-JGDC and I5B-IE-
JGDF) and in the 2 Phase 2 monotherapy studies (I5B-IE-JGDE [glioblastoma] and I5B-IE-
JGDH [GIST]), single-agent olaratumab has consistently been well tolerated, with no dose-
limiting toxicities (DLTs) observed up to a dose of 20 mg/kg administered every 2 weeks (q2w)
and up to a dose of 16 mg/kg administered weekly for 4 weeks followed by 2 weeks off 
treatment for observation. Olaratumab has been safely administered in combination with 
liposomal doxorubicin in Study I5B-MC-JGDA (olaratumab 20 mg/kg q2w) in patients with 
ovarian cancer, and with paclitaxel/carboplatin in Study I5B-IE-JGDB (olaratumab 15 mg/kg on
Days 1 and 8 of a 3-week cycle) in patients with NSCLC.  However, certain toxicities, such as 
neutropenia and infections, were observed at a higher rate for olaratumab plus chemotherapy 
compared with the chemotherapy alone.
In the randomized, double-blind Phase 2 study (I5B-MC-JGDG [JGDG]) in patients with soft 
tissue sarcoma (STS), the combination of olaratumab and doxorubicin had an acceptable, 
monitorable, and manageable safety profile even in light of a significantly higher median 
cumulative doxorubicin exposure in the olaratumab plus doxorubicin arm.  An increase in 
neutropenia, but not in neutropenic sepsis or febrile neutropenia, has been observed in the 
olaratumab plus doxorubicin arm compared with doxorubicin alone. A higher rate of some 
known doxorubicin-induced toxicities, such as, mucositis, nausea/vomiting, and diarrhea, in the 
olaratumab plus doxorubicin arm was observed; however, these toxicities were readily monitored 
and manageable and were predominantly Grade ≤2 in severity.
The combination of olaratumab and doxorubicin resulted in a statistically significant and 
clinically meaningful improvement in median overall survival (OS; 11.8-month improvement; 
hazard ratio [HR] = 0.463, p=0.0003).  An improvement in median progression-free survival 
(PFS) of 2.5 months was observed for olaratumab plus doxorubicin over doxorubicin alone;
(stratified HR=0.672, p=0.0615) and the study met the protocol-defined significance level for the 
primary endpoint. Exposure-response analysis from Study JGDG showed that when trough 
concentration at the end of the first cycle (Cmin1) was used as the pharmacokinetic (PK) endpoint, 
the model predicted an minimum half-maximal effective concentration at the end of the first 
cycle (ECmin150) of approximately 66 μg/mL, which corresponds to the 25th percentile of Cmin1
in the JGDG population.  Patients with Cmin1 concentrations below the ECmin150 progressed 
earlier and had shorter OS than patients with Cmin1 above the ECmin150.
3.2.2. Pancreatic Cancers
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States (US;
ACS 2016). Incidence rates in both sex are highest in North America and Europe and lowest in
Asia and Africa (World Cancer Research Fund International [WWW]).  In 2016, the number of 
new cases and deaths of pancreatic cancer in the US for both sexes are estimated to be 53,070 
and 41,780, respectively (Siegel et al. 2016).  In 2013, there were estimated to be 9,408 new 

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cases of pancreatic cancer in the United Kingdom (UK) in 2013 and 8817 deaths in 2014 (Cancer 
Research UK [WWW]).
Pancreatic ductal adenocarcinoma and its variants account for more than 90% of pancreatic 
malignancies (Tempero et al. 2010).  Difficulty in early detection is a significant factor in the 
overall poor prognosis for patients with pancreatic cancer.  At the time of diagnosis, the tumor 
that is confined to the pancreas is fewer than 10%, and over 50% have distant spread (Howard 
1996), limiting the number of patients who are able to seek surgical resection as a treatment 
option.
Gemcitabine was approved by US Food and Drug Administration in 1996 as treatment for 
metastatic pancreatic cancer and was the standard of care for first-line metastatic pancreatic 
patients.  Since that time, 2 regimens, FOLFIRINOX (Conroy et al. 2011) and gemcitabine plus 
nab-paclitaxel (Von Hoff et al. 2011, 2013), have supplanted gemcitabine as the current standard 
of care for first-line metastatic pancreatic cancer for patients with good performance status (0-1).  
Nab-paclitaxel in combination with gemcitabine was approved in the US in 2013 and in the 
European Union (EU) in 2014 for use in patients with metastatic pancreatic cancer.  
The high-level results of the randomized Phase 3 clinical trial conducted in 861 patients with 
metastatic pancreatic cancer, which compared gemcitabine with a combination of gemcitabine 
and nab-paclitaxel (Von Hoff et al. 2013), demonstrated a median OS of 8.5 months in the 
gemcitabine plus nab-paclitaxel arm compared with 6.7 months in the gemcitabine alone.  The 
HR for death was 0.72 (95% CI:  0.62 to 0.83; p <.001).  Other end points, including PFS and 
response rate (RR), were superior with the combination.  Grade ≥ 3 neutropenia occurred in 38% 
of the patients treated with gemcitabine plus nab-paclitaxel, with 3% of these instances resulting 
in febrile neutropenia.  Twenty-six percent of the patients received growth factors (GFs).  
Cumulative peripheral neuropathy occurred in 17% of the patients treated with gemcitabine plus 
nab-paclitaxel, and it was managed with temporary discontinuation of nab-paclitaxel followed by 
a reduction in dose.  Despite available options for the treatment of metastatic pancreatic cancer, 
there is still a poor prognosis for patients with metastatic disease as evidenced by a 5-year 
survival rate that is less than 3% (SEER 2016).
3.3.
Benefit/Risk Assessment
Olaratumab has demonstrated efficacy in combination with doxorubicin in patients with STS.  
Pancreatic cancer, like STS, is another highly stromal tumor type and preclinical data has 
suggested increased PDGFRα levels in malignant pancreatic tissue, suggesting olaratumab may 
be able to affect PDGFR signaling in pancreatic cancer.  Olaratumab has been used in several 
studies in combination with chemotherapies and has been generally well tolerated, with some 
increase in hematologic toxicity observed.  The current study will evaluate the safety of 
olaratumab in combination with nab-paclitaxel and gemcitabine.  Weekly monitoring of 
hematologic parameters will be conducted to ensure patient safety during the dose 
escalation/Phase 1b portion of the study.  The Phase 2 randomized portion will evaluate nab-
paclitaxel and gemcitabine with or without olaratumab, so all patients will receive standard of 
care treatment in this study. 

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More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated adverse events (AEs) of olaratumab are to be found in the 
Investigator’s Brochure (IB).

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4.
Objectives and Endpoints
Table JGDP.5 shows the objectives and endpoints of the study.
Table JGDP.5.
Objectives and Endpoints
Objectives
Endpoints
Primary
Phase 1b:

to determine a recommended Phase 2 dose of 
olaratumab in combination with nab-paclitaxel and 
gemcitabine
Phase 2:

to compare the efficacy of olaratumab plus nab-
paclitaxel and gemcitabine with placebo plus 
gemcitabine and nab-paclitaxel
Phase 1b

DLTs

Safety (including but not limited to) TEAEs, SAEs, and 
clinical laboratory abnormalities
Phase 2

OS
Secondary
Phase 1b

to characterize the safety and toxicity profile of 
olaratumab plus nab-paclitaxel and gemcitabine
Phase 1b

Safety monitoring, including TEAEs, SAE, and deaths

to evaluate the PK and immunogenicity of olaratumab 
plus nab-paclitaxel and gemcitabine

to document the antitumor activity observed with 
olaratumab plus nab-paclitaxel and gemcitabine

Minimum serum/plasma concentration of olaratumab 
plus nab-paclitaxel and gemcitabine

Anti-drug antibody concentration

OS, PFS, DoR, ORR
Phase 2

to assess time-to-event variables
Phase 2

PFS, DoR

to document the antitumor activity observed with 
olaratumab plus nab-paclitaxel and gemcitabine

ORR

to assess the following PROs:

mBPI-sf, EORTC-QLQ-C30, and EQ-5D-5L

to determine safety and tolerability of olaratumab in 
combination with nab-paclitaxel and gemcitabine

TEAEs, AESIs, SAEs, clinical laboratory tests, vital 
signs, physical examinations, hospitalizations, and 
death

to assess the PK and immunogenicity of olaratumab 
plus nab-paclitaxel and gemcitabine

Minimum serum/plasma concentration of olaratumab 
plus nab-paclitaxel and gemcitabine

Anti-drug antibody concentration
Tertiary/Exploratory

to characterize tumor tissue and blood biomarkers 
relevant to study drugs including but not limited to 
immune cells/immune and tumor microenvironment
functioning, mechanism of action of study drugs, 
cancer-related pathways, and disease state

to assess the relationship between biomarkers and 
clinical outcomes

Markers of immune function, tumor 
microenvironment, drug targets, signaling pathways, 
and disease status
Abbreviations:  AESIs = adverse events of special interest; DLT = dose-limiting toxicity; DoR = duration of 
response; EORTC = European Organisation for Research and Treatment of Cancer; EQ = EuroQol; HRQoL = Health-
related Quality of Life; mBPI-sf = modified Brief Pain Inventory - short form; ORR = objective response rate; 
OS = overall survival; PFS = progression-free survival; PK = pharmacokinetics; PRO = patient-reported 
outcome; SAEs = serious adverse events; TEAEs = treatment-emergent adverse events.

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5.
Study Design
5.1.
Overall Design
Study JGDP is Phase 1b/2 trial.  The Phase 1b portion of the trial will consist of an open-label,
dose-finding study and the Phase 2 portion will be a multicenter, randomized, double-blind, 
parallel, placebo-controlled study in patients with metastatic unresectable pancreatic cancer 
(Stage IV), who have not received prior treatment for metastatic disease.
Phase 1b:
The Phase 1b will commence prior to Phase 2. Study cycles will be 28 days in duration. 
In the Phase 1b portion of the study, a 3 + 3 dose escalation design will be used to evaluate the 
safety and tolerability of olaratumab in combination with gemcitabine and nab-paclitaxel in 
patients with pancreatic cancer and determine a recommended Phase 2 dose of olaratumab.  
Three patients will be treated initially at each dose level.  If no DLTs occur in a cohort of 
3 patients, a new cohort of 3 patients will be treated at the next higher dose level.  If 1 of 
3 patients at any dose level experiences a DLT, that cohort will be expanded to 6 patients.

If no further patient experiences a DLT, the dose escalation can proceed.

If a DLT is observed in ≥2 out of a maximum of 6 patients at any given dose, 
dose escalation will cease and the next lower dose will be the maximum tolerated
dose (MTD).

The dose escalation can proceed if fewer than 2 out of 6 evaluable patients 
experience a DLT.
During the dose escalation, no more than one cohort will be open for enrollment at any given 
time. 
After the MTD has been identified in the dose-escalation phase, approximately 9 patients will be 
enrolled in a cohort expansion.  The purpose of the cohort expansion is to confirm the safety of 
the MTD in approximately 12 to 15 patients (including those in the dose escalation cohort) prior 
to proceeding to the Phase 2 portion of the study.  Continuous evaluation of toxicity in the cohort 
expansion will be performed throughout enrolment in the cohort. If the rate of DLT-like events 
exceeds 33% in the first cycle, the findings will be discussed, and further enrolment may be 
interrupted. If the expansion cohort is discontinued because of toxicity, a new cohort may be 
initiated at a previously tested lower dose level.
In the first cohort, olaratumab will be dosed on Days 1, 8, and 15 (that is, on the same days as 
nab-paclitaxel and gemcitabine dosing as described in their United States Package Insert [USPI]
and Summary of Product Characteristics [SmPC]) at a starting dose of 15 mg/kg.  If the 
15 mg/kg dose of olaratumab is tolerated, enrollment will commence in Cohort 2 at the 20 mg/kg 
dose of olaratumab dosed on Days 1, 8, and 15.  If the 20 mg/kg dose is tolerated, approximately 
9 to 12 additional patients will be enrolled in the cohort expansion to confirm the safety and 
tolerability of the dose.

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If the Cohort 1 olaratumab dose of 15 mg/kg on Days 1, 8, and 15 is not tolerated, dosing of 
olaratumab at 20 mg/kg on Days 1 and 15 may be evaluated (Cohort 3) to determine if 
decreasing the frequency of olaratumab dosing improves the tolerability of olaratumab in 
combination with nab-paclitaxel and gemcitabine (see Figure JGDP.1).  The dose of 20 mg/kg on 
Days 1 and 15 will decrease the total dose administered in the cycle from 15 mg/kg dosed on 
Days 1, 8, and 15 (in Cohort 1) while still providing exposures above the ECmin150 (see 
Section 5.5 for further dose justification).  If the 20 mg/kg dose of olaratumab is tolerated, 
enrollment will commence with planned dose escalation to 25 mg/kg olaratumab on Days 1 and 
15 in the subsequent dose cohort (Cohort 4).  If neither of the initial dose levels in the Day 1, 8, 
and 15 dosing schedule (Cohort 1) and the Days 1 and 15 dosing schedule (Cohort 3) are 
tolerated, enrollment in the study will be stopped.

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Abbreviations:  D = Day; MTD = maximum tolerated dose. 
Note:  Approximately 24 patients will be enrolled into the Phase 1b.  A 3 + 3 dose-
escalation design will be used.  It is planned that between 3 to 6 patients will be 
enrolled at each dose level. After determination of the MTD, a cohort expansion will 
further evaluate the MTD in approximately 9 additional patients.
Figure JGDP.1.
Illustration of study design of Phase 1b.
After determination of the MTD in the dose escalation portion of the study and confirmation of 
the safety and tolerability of that dose in the cohort expansion, a review of safety data, including 
the number and type of DLTs, other safety information, and relevant PK, will be conducted prior 
to proceeding to Phase 2. The decision to proceed to Phase 2 and selection of the recommended 
Phase 2 dose will be made following discussions between the investigators and Lilly clinical 
research personnel.
Phase 1b
3 + 3 Dose Escalation Method
Open-Label 
(N=24)
Cohort 1
Olaratumab: 15 mg/kg 
D1, D8, & D15
Nab-pac/gem  D1, D8, & D15
28-Day cycle
Cohort 2
Olaratumab: 20 mg/kg 
D1, D8, & D15
Nab-pac/gem  D1, D8, & D15
Cohort 3
Olaratumab: 20 mg/kg D1 & D15
Nab-pac/gem  D1, D8, & D15
Cohort 4
Olaratumab: 25 mg/kg D1 & D15
Nab-pac/gem  D1, D8, & D15
Cohort 1 
tolerated
Cohort 1 not 
tolerated
Cohort Expansion
To enroll approximately 
9 patients at the MTD
Cohort 3 
tolerated

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Phase 2:
The Phase 2 portion of the study is a 1:1 randomized, double-blinded, 2-arm study of olaratumab
at a dose and schedule determined from Phase 1b in combination with nab-paclitaxel and 
gemcitabine (Treatment Arm) versus placebo plus nab-paclitaxel-gemcitabine (Control Arm)
(see Section 5.4.4).  Patients will receive nab-paclitaxel (125 mg/m2) via infusion followed by 
gemcitabine (1000 mg/m2) infusion on Days 1, 8, and 15 of each 28-day cycle.  Nab-paclitaxel 
and gemcitabine will be administered following olaratumab/placebo administration.
Patients will receive the study treatment until disease progression or a criterion for 
discontinuation is met.  The primary end point is OS; secondary end points are PFS, duration of 
response (DoR), objective response rate (ORR), patient-reported outcomes (PROs), and safety.
Patients will be assessed for tumor response every 8 weeks. Patients without disease progression 
may continue to receive treatment until the development of unacceptable toxicity, death, or other 
discontinuation criteria are met.
Figure JGDP.2 illustrates the study design of Phase 2.
Abbreviations:  D = Day; IV = intravenous; N = number of patients.
Note:  Dose and schedule of olaratumab will be determined based upon tolerability in 
the Phase 1b portion of the study.
Figure JGDP.2.
Illustration of study design of Phase 2.
After study completion, patients on study treatment who continue to experience clinical benefit 
and no undue risks, in the opinion of the investigator, may continue to receive study treatment 
(Continued Access period) until one of the criteria for discontinuation is met, as described in 
Phase 2
Randomized, Double-Blind
(N=162)
R
A
N
D
O
M
I
Z
E
Treatment Arm (N=81)
Olaratumab*
Nab-paclitaxel (125mg/m2) D1, D8, & D15
Gemcitabine (1,000 mg/m2)  D1, D8, & D15
Control Arm (N=81)
Placebo (equivalent IV infusion)*
Nab-paclitaxel (125mg/m2) 
D1, D8, & D15
Gemcitabine (1,000 mg/m2)  D1, D8, & D15
28-Day cycle
1:1
* Dosing regimen is based on Phase 1b results.
Patients will continue treatment until disease progression or chemotherapy-
related toxicity leading to discontinuation 

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Section 7.8.1. A continued access follow-up visit will occur 30 days (±7 days) after 
discontinuation.
5.2.
Number of Patients
Planned enrollment for each phase is as follows:
Phase 1b:  Approximately 24 patients with metastatic pancreatic cancer who have not received 
chemotherapy for metastatic disease will be evaluated for dose-limiting toxicities (DLTs).  
Patients who are not evaluable for DLTs will be replaced.
Phase 2:  Approximately 162 patients with metastatic pancreatic cancer who have not received 
chemotherapy for metastatic disease will be randomized in a 1:1 ratio to receive either 
olaratumab plus nab-paclitaxel and gemcitabine (Treatment Arm) or placebo plus nab-paclitaxel 
and gemcitabine (Control Arm).
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure for the last patient.
5.4.
Scientific Rationale for Study Design
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States (US; 
ACS 2016). Gemcitabine plus nab-paclitaxel (Von Hoff et al. 2011, 2013) and FOLFIRINOX 
(Conroy et al. 2011) are the 2 current standard of care regimens for first-line metastatic 
pancreatic cancer for patients with good performance status (0-1). Despite available options for 
the treatment of metastatic pancreatic cancer, there is still a poor prognosis for patients with 
metastatic disease as evidenced by a 5-year survival rate that is less than 3% (SEER 2016).
Pancreatic cancer is characterized by a highly stromal tumor microenvironment that is composed 
largely of extracellular matrix proteins, fibroblasts, and pancreatic stellate cells.  This tumor 
microenvironment, or desplasmic reaction, has been associated with worse clinical outcomes in 
pancreatic cancer (Erkan et al. 2008) as well as other tumors (Hasebe et al. 1997). PDGFRα 
expression has been shown to be upregulated in malignant pancreas relative to normal tissue 
(Ebert et al. 1995).  PDGF/PDGFRα signaling in the microenvironment may contribute to both 
the growth and maintenance of the dense tumor microenvironment as well as tumor growth.
Tissue microarrays have shown the presence of PDGFRα in the stroma (46.7% of 210 tissues 
evaluated) of pancreatic cancer in the tissues evaluated (data on file).  The link between PDGF 
and tumor-associated angiogenesis is supported by its expression by tumor cells, and 
overexpression was found to be correlated with microvascular density and poor survival in a 
large variety of human cancers, including pancreatic cancer (Fujimoto et al. 1998).
Blocking PDGFRα by the use of olaratumab has been shown effective in another highly stromal 
tumor type, STS, with recent results showing improvement in OS and PFS.  The ability to inhibit 
PDGFRα signaling in pancreatic cancer may represent an opportunity to disrupt signaling in the 
tumor microenvironment in a manner that could potentially enhance the antitumor activity 

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already observed with gemcitabine plus nab-paclitaxel, an established standard of care regimen 
for the treatment of metastatic pancreatic cancer.
5.4.1. Rationale for Amendment (a)
Amendment (a) updated the Phase 1b design to enroll patients in the Days 1, 8 and 15 cohort 
first, and begin enrollment in the Days 1 and 15 dosing cohorts if the Days 1, 8 and 15 cohort is 
not tolerable. In addition, the design was changed to add a cohort expansion to ensure an 
appropriate number of patients (12 to 15 patients) are evaluated for safety in Phase 1b at the 
highest tolerated dose.
5.4.2. Rationale for Amendment (b)
Amendment (b) revised the definition of DLT based on Food and Drug Administration (FDA)
feedback to include toxicities related to the combination of olaratumab plus gemcitabine and 
nab-paclitaxel.
5.4.3. Rationale for Amendment (c)
Amendment (c) addresses several requests from FDA including language urging caution when 
administering nab-paclitaxel with CYP2C8 or CYP3A4 inhibitors or inducers as well as further 
details regarding the sample size justification.
In addition, this amendment adjusts the study entry criteria-related prior therapies.  DLT 
wordings were clarified to ensure that clinically non-significant AEs are not included in the DLT 
definition.  This amendment describes that a patient’s dose may be re-escalated after a dose 
reduction. The schedule and timing of PROs in the follow-up periods (both long-term and short-
term) have been updated.  Plans for the Phase 2 interim analysis and the Internal Assessment 
Committee (IAC) have been updated. In addition, several administrative items have been 
updated to provide clarity or correct errors.
5.4.4. Rationale for Amendment (d)
Amendment D updates the protocol to include dose and schedule of olaratumab to be 
administered in the Phase 2 part, based on the results of the Phase 1b part of study JGDP. 
In Part 1b of Study JGDP, a total of 22 patients were enrolled and treated with olaratumab plus 
gemcitabine/nab-paclitaxel as of 31 July 2018.  Safety review revealed that the addition of 
olaratumab to the combination of gemcitabine and nab-paclitaxel in pancreatic patients is safe 
and tolerable with a monitorable and manageable side-effect profile.  Both dose levels of 
olaratumab (i.e. 15 mg/kg and 20 mg/kg olaratumab [N = 3 and 19 patients, respectively]) were 
tolerated in combination with gemcitabine/nab-paclitaxel with one DLT reported at the 20 mg/kg 
olaratumab dose level (Grade 4 neutropenia lasting greater than 7 days).  No maximum tolerated 
dose for olaratumab in combination with gemcitabine/nab-paclitaxel was identified.  AEs 
reported were consistent in nature and within the frequency range expected for chemotherapy 
with gemcitabine plus nab-paclitaxel or olaratumab therapy.  Though the MTD of olaratumab 
was not reached, a trend towards a higher number of early Grade ≥3 neutropenia and dose 
reductions in nab-paclitaxel and gemcitabine was noted among patients treated at the 20 mg/kg 

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dose level relative to the 15 mg/kg olaratumab dose level.  Therefore, considering safety and 
exposure-response analyses across olaratumab studies, the recommended dose for the 
randomized part of Study JGDP for olaratumab in combination with gemcitabine plus nab-
paclitaxel was determined as a 20 mg/kg olaratumab loading dose on Days 1, 8, and 15 in 
Cycle 1, followed by 15 mg/kg on Days 1, 8, and 15 in Cycles 2-n.  This selected Phase 2 dose 
and schedule of olaratumab aims to maximize patients achieving concentrations above 
previously identified olaratumab serum levels associated with clinical activity, while also 
minimizing reductions/omissions of the standard-of-care chemotherapy backbone.  This decision 
was mutually agreed upon following discussions between the sponsor and the Study JGDP 
Phase 1b investigators. 
This amendment also formalizes a change from an IAC (internal assessment committee) to an 
IDMC (independent data monitoring committee) for the Phase 2 part of the study to enable 
monitoring of unblinded safety data by the IDMC while maintaining Lilly blinded to safety and 
efficacy interim data. This change is being made prior to any data being reviewed by the IAC.  
In addition, clarifications to the inclusion/exclusion criteria # [1], [3], [5], [9], and [22];
olaratumab premedication; and infusion instructions in alignment with the recent investigators 
brochure are provided.  Some minor editorial changes have been made throughout the protocol to 
improve clarity and practicality of the protocol and secure alignment with the intended study 
design.
5.4.5. Rationale for Amendment (e)
Amendment (e) updates the protocol to include screening criteria for Immunoglobulin E (IgE)
antibodies against galactose-α-1-3-galactose (α-gal) and premedication requirements to mitigate 
the risk for an observed rate of Grade ≥3 infusion-related reactions (IRRs) on Study JGDP that 
was greater than the rate of 3.1% previously observed across the olaratumab program.  Based on 
data from the Phase 1 and Phase 2 portion of Study JGDP, Grade ≥3 IRRs were observed at an 
approximate rate between 5% and 10% of olaratumab-treated patients.
Infusion related reactions are a known Adverse Drug Reaction for olaratumab, and the rate of 
IRR is 12.5% (all grades) and 3.1% (Grade ≥3). Grade ≥3 IRR occur within minutes of first 
infusion of olaratumab. The risk of anaphylactic reaction is associated with elevated IgE 
antibody levels.  Across 8 studies with olaratumab (401 evaluable olaratumab-treated patients), 
IgE antibody levels greater than the manufacturer-specified ULN had a positive predictive value 
of 75% (34.9% - 96.8%) and a negative predictive value of 99% (98.2% - 99.9%) for Grade ≥3 
IRRs, with sensitivity of 75% (34.9% - 96.8%) and specificity of 99% (98.2% - 99.9%). Two 
patients had Grade ≥3 IRR with an IgE antibody level ≤ ULN (0.28 kU/L and <0.10 kU/L, 
respectively).  Prior to this amendment, patients in Study JGDP were tested for pre-existing IgE 
antibody against α-gal as pre-planned retrospective analysis. However, the results of these tests 
were not available prior to first dosing of olaratumab/placebo.  Pre-testing for elevated IgE 
antibody levels against -gal for all untreated patients as part of screening is being implemented 
as a risk mitigation strategy.

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This amendment implements actions to mitigate the risk of increased Grade ≥3 IRRs observed in 
Study JGDP.  Specifically, screening in the Phase 2 portion of the study was modified to include 
immuniogenicity testing, and the inclusion/exclusion criteria were updated to clarify that patients 
with IgE anti-α-gal antibody levels greater than the upper limit of normal will be excluded from 
this study. In addition, the required premedication regimen prior to Cycle 1 Day 1 of 
olaratumab/placebo was clarified to include: dexamethasone (or steroid equivalent); a histamine 
H1 antagonistist (for example, diphenhydramine); and a histamine H2 antagonist (for example, 
ranitidine).  
5.5.
Justification for Olaratumab Dose
Olaratumab will be initially dosed on Days 1, 8, and 15 to dose olaratumab coinciding with the 
dosing schedule of the gemcitabine and nab-paclitaxel backbone chemotherapy regimen.  In the 
event the Day 1, 8, and 15 dosing schedule is not tolerated, dosing of olaratumab on Day 1 and 
15 may be evaluated to determine if less frequent dosing of olaratumab may improve the 
feasibility of the combination.
The starting dose level of olaratumab administered on the Day 1, 8, and 15 schedule will be 
15 mg/kg (Cohort 1).  In monotherapy dose-escalation studies, no DLTs were observed up to 
olaratumab doses of 20 mg/kg every other week and 16 mg/kg weekly for 4 weeks followed by 2 
weeks off treatment for observation.
In prior studies of olaratumab plus chemotherapies (doxorubicin in STS [JGDG], paclitaxel plus 
carboplatin in non-small cell lung cancer [JGDB], mitoxantrone in prostate cancer [JGDD], and 
liposomal doxorubicin in ovarian cancer [JGDA]), olaratumab was generally well tolerated with 
manageable toxicities.  Some increase in hematological AEs (such as neutropenia) was noted 
over chemotherapy alone.  In Studies JGDG and JGDA, despite an increase in neutropenia there 
was no increase in febrile neutropenia upon addition of olaratumab to the respective 
chemotherapies.  In Study JGDB, Grade ≥4 febrile neutropenia was 3.0% on the olaratumab plus 
paclitaxel/carboplatin arm versus 0% on the paclitaxel/carboplatin arm.
In several ongoing studies, a Cycle 1 loading dose of 20 mg/kg has been safely administered in 
on Days 1 and 8 of Cycle 1 in combination with doxorubicin.  The exposures anticipated from 
the starting dose of 15 mg/kg on Day 1, 8, and 15 would be anticipated to be similar to those 
achieved for patients receiving the 20-mg/kg loading dose on Days 1 and 8 of a 3-week cycle.  
Based upon the increase in hematological AEs observed when olaratumab was administered with 
previous chemotherapy regimens, it is anticipated that myelosuppression may be a key safety 
measure in determining the maximum tolerated dose of olaratumab with the combination of 
gemcitabine plus nab-paclitaxel.  Weekly assessment of hematologic parameters will provide 
close monitoring of this toxicity and aid in determining the safety of this combination.
The second dose level, 20 mg/kg (Cohort 2), provides the opportunity to achieve higher serum 
concentrations of olaratumab.  
 
 
 
CCI

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In the event that the Day 1, 8, and 15 dosing schedule is not tolerated, an alternate dosing 
schedule with olaratumab administered on Day 1 and 15 may be explored.
For administration of olaratumab on the Day 1 and 15 schedule, the starting dose is 20 mg/kg 
(Cohort 3).  This dose and schedule of olaratumab has been administered in prior studies (JGDA, 
in combination with liposomal doxorubicin in patients with ovarian cancer).  In addition, a 
loading dose of 20 mg/kg in Cycle 1 (Days 1 and 8 of a 21-day cycle) has been safely
administered in several ongoing studies (JGDJ, JGDI, and JGDK) in combination with 
doxorubicin. 
 
 
After determination of the MTD in the dose escalation portion of the study and confirmation of 
the safety and tolerability of that dose in the cohort expansion, a review of safety data, including 
the number and type of DLTs, other safety information, and relevant PK, will be conducted prior 
to proceeding to Phase 2.  The decision to proceed to Phase 2 and selection of the recommended 
Phase 2 dose will be made following discussions between the investigators and Lilly clinical 
research personnel.
CCI
CCI

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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] have definitive histological or cytological diagnosis of adenocarcinoma of the 
exocrine pancreas that is metastatic (i.e. Stage IV according to AJCC v8) and 
not amenable to resection with curative intent (Amin et al. 2017). The 
definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by 
integrating the histopathological data within the context of the clinical and 
radiographic data.
Eligible patients must be patients for whom nab-paclitaxel-gemcitabine 
therapy is considered by the investigator to be an appropriate treatment.  
Patients with previous radical surgery for pancreatic cancer are eligible after 
progression is documented.
[2]
if present, clinically significant or symptomatic amounts of ascites should be 
drained prior to Day 1
[3]
have sufficient available material from an archived formalin-fixed paraffin-
embedded (FFPE) tumor tissue for biomarker-related studies. If such tissue is 
not available, a newly obtained core or excisional biopsy of a tumor lesion 
must be performed in the Phase 2 portion of the study.
Patients who must undergo a new biopsy that is unsuccessful may not be 
required to have a second attempted biopsy, after consultation with the Lilly 
Medical representative. 
[4]
The patient has measurable or nonmeasurable but evaluable disease as defined 
by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1, 
Eisenhauer et al. 2009). Tumors within a previously irradiated field will be 
designated as “nontarget” lesions unless progression is documented or a 
biopsy is obtained to confirm persistence at least 90 days following 
completion of radiotherapy.
[5]
have had no prior systemic treatment for metastatic disease. Prior adjuvant or 
neo-adjuvant chemotherapy or radiochemotherapy (other than nab-paclitaxel) 
is allowed, if completed ≥3 months prior to enrollment and no lingering 
toxicities are present.
[6]
prior radiation therapy for treatment of cancer is allowed to <25% of the bone 
marrow (Cristy and Eckerman 1987).  Patients must have recovered from the 
acute toxic effects of their treatment prior to study enrollment.
[7]
have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology 
Group (ECOG) scale (Oken et al. 1982)

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[8]
Patients must have discontinued from previous treatments for cancer
(radiotherapy/major surgery, excluding biopsy) 4 weeks prior to study 
treatment.
[9]
have adequate organ function, as defined below:
System
Laboratory Value
Hematologic
ANC
1.5 × 109/L
Platelets
100 × 109/L
Platelet transfusions to meet eligibility reruirements are not 
allowed within 2 weeks prior to the baseline hematology 
profile.
Hemoglobin
9 g/dL
Transfusions to increase the patient’s hemoglobin level to 
9 g/dL are not permitted within 2 weeks prior to the baseline 
hematology profile.
Hepatic
Total bilirubin
1.5 × ULN  
ALT and AST
2.5 × ULN OR
5 × ULN if the liver has tumor involvement
Renal
Serum creatinine OR
Calculated creatinine clearance (see 
Appendix 6)
1.5 × ULN OR
60 mL/min
Coagulation
INR or PT
Normalized ratio ≤1.5 × ULN or prothrombin time
≤1.5 × ULN
aPTT or PTT
PTT or aPTT ≤1.5 × 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.
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 (e.g., tumor involving major vessels or known esophageal varices).
Abbreviations:  aPTT = activated partial thromboplastin time; ALT = alanine aminotransferase; 
ANC = absolute neutrophil count; AST = aspartate aminotransferase; PT = prothrombin time; ULN = upper 
limit of normal.
[10] are at least 18 years old at the time of screening/randomization
[11] If male, the patient is sterile (including vasectomy) or agrees to use an 
effective method of birth control. Refer to Appendix 1 for definitions of 
effective method of contraception and highly effective method of 
contraception.

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[12] If female:
o
is not of childbearing potential due to surgical sterilization confirmed by 
medical history (at least 6 weeks post-surgical bilateral oophorectomy with or 
without hysterectomy or tubal ligation) or menopause
o
is of childbearing potential, has a negative serum or urine pregnancy test 
within 72 hours prior to the first dose of study treatment, agrees to use a 
highly effective method of birth control during the study and for up to 3 
months following the last dose of the study treatment, and is not 
breastfeeding.  If the urine test is positive or cannot be confirmed as negative, 
a serum pregnancy test will be required.  Refer to Appendix 1 for definitions 
of effective method of contraception and highly effective method of 
contraception.
[13] have given written informed consent/assent prior to any study-specific 
procedures
[14] has a life expectancy of at least 3 months in the opinion of the investigators.
6.2.
Exclusion Criteria
Patients will be excluded from the study if they meet any of the following criteria:
[15] have received first line treatment for metastatic pancreatic cancer.
[16] have received prior treatment with nab-paclitaxel.
[17] have a serious concomitant systemic disorder (for example, active infection 
including human immunodeficiency virus, or cardiac disease) or other 
condition that, in the opinion of the investigator, would compromise the 
patient’s ability to adhere to the protocol
[18] have known central nervous system (CNS) malignancy or metastasis 
(screening not required)
[19] have current hematologic malignancies, acute or chronic leukemia
[20] have participated within the last 30 days in a clinical trial involving an 
investigational product.  If the previous investigational product has a long 
half-life, 3 months or 5 half-lives (whichever is longer) should have passed.
[21] are women with a positive pregnancy test or who are lactating
[22] have known endocrine pancreatic tumors or ampullary cancer
[23] are currently enrolled in a clinical trial involving an investigational product or 
any other type of medical research judged not to be scientifically or medically 
compatible with this study
[24] have known additional malignancy that is progressing or required active 
treatments within the past 1 year

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Note:  Participants with basal cell carcinoma of the skin, squamous cell 
carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical 
cancer in situ) that have undergone potentially curative therapy are not 
excluded.
[25] have known allergy to nab-paclitaxel, gemcitabine, or olaratumab (levels of 
IgE antibodies against α-gal that are above the upper limit of normal) or any 
ingredient of olaratumab, nab-paclitaxel, or gemcitabine formulations.
6.3.
Lifestyle Restrictions
This section is not applicable.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
re-screened.  Individuals may be re-screened a maximum of 1 time.  The interval between 
re-screenings should be at least 2 weeks.  Each time re-screening is performed, the individual 
must sign a new informed consent form (ICF) and will be assigned a new identification number.
Repeating of laboratory tests during the screening period, after a patient has not met requisite 
criteria, does not constitute re-screening. Screening laboratory tests may not be repeated more 
than twice in order to meet eligibility during the screening period.

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7.
Treatments
7.1.
Treatments Administered
Table JGDP.6 shows the treatment regimens.  The dosing of nab-paclitaxel and gemcitabine will 
be the same for all cohorts.  The dosing of olaratumab will vary based upon cohorts in the 
Phase 1b.  The Phase 2 dose and schedule of olaratumab/placebo has been selected based upon 
results of the Phase 1b (Section 5.4.4).
Table JGDP.6.
Treatment Regimens
Phase
Drug
Route
Dose
Schedule
q 28-day cycle
Approximate 
Infusion
Duration
Phase 1b
Cohorts 
1 and 2
Olaratumaba
I.V.
15, 20 mg/kg
D1, D8, D15
60 min
nab-paclitaxel
I.V.
125 mg/m2
D1, D8, D15
30 - 40 min
Gemcitabine
I.V.
1000 mg/m2
D1, D8, D15
30 min
Cohorts 
3 and 4
Olaratumaba
I.V.
20, 25 mg/kg
D1, D15
60 min
nab-paclitaxel
I.V.
125 mg/m2
D1, D8, D15
30 - 40 min
Gemcitabine
I.V.
1000 mg/m2
D1, D8, D15
30 min
Phase 2
olaratumab/placeboa
I.V.
I.V.
Cycle 1: 20 mg/kg
Cycle 2-n: 15 mg/kg
D1, D8, D15
D1, D8, D15
60 min
60 min
nab-paclitaxel
I.V.
125 mg/m2
D1, D8, D15
30 - 40 min
gemcitabine
I.V.
1000 mg/m2
D1, D8, D15
30 min
Abbreviations:  D = day; I.V. = intravenous; q = every.
a
For mandatory premedication requirements please see Section 7.1.1.
Patients will receive study treatments in the following order: olaratumab followed by 
nab-paclitaxel followed by gemcitabine.  Omission or discontinuation of one component of the 
regimen may change that sequence, but remaining treatments should still be given in the same 
relative order. 
Olaratumab will be administered as an approximately 60 minute I.V. infusion on Days 1, 8, and 
15 of a 28-day cycle at the doses shown in Table JGDP.6.  In certain instances, longer infusion 
times may be allowed; refer to Pharmacy Manual for more information.  
Patients are required to be monitored for 1 hour after the olaratumab infusions in the first two 
treatment cycles for signs or symptoms of IRRs; see Section 7.4.4.3.1 for full description of 
required olaratumab monitoring period.  Patients should complete the required monitoring period 
prior to the start of any other study treatment (gemcitabine or nab-paclitaxel) administration.
7.1.1. Premedication
All premedication administered must be adequately documented in the electronic case report 
form (eCRF).

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7.1.1.1.
Olaratumab/Placebo
Infusion-related reactions, including Grade ≥3 events, have been observed with olaratumab.  To 
date, all Grade ≥3 IRR events have occurred during the first olaratumab infusion, most of them 
within 30 minutes from the start of infusion. Symptoms of IRRs have included flushing, 
shortness of breath, bronchospasm, fever/chills, and in severe cases have manifested as severe 
hypotension, anaphylactic shock, or cardiac arrest. 
The following premedications need to be administered prior to olaratumab/placebo infusions in 
Study JGDP. Additional premedication may be provided at the investigator’s discretion.

Premedication in Cycle 1:
Premedication is mandatory for all patients during Cycle 1 prior to each dose of 
olaratumab/placebo. Premedicate all patients with the following (or equivalent)
medications 30-60 minutes prior to olaratumab/placebo dosing on Days 1, 8, and 15 of 
Cycle 1:
o
Histamine H1 antagonist (for example, diphenhydramine)
o
Dexamethasone intravenously
o
Histamine H2 antagonist (for example, ranitidine)

Premedication in Cycles 2-n:
For subsequent cycles, premedication with a histamine H1 antagonist (for example, 
diphenhydramine) is recommended prior to each dose of olaratumab/placebo.
In case of prior Grade 1 or 2 IRR to olaratumab, premedication is mandatory prior to
subsequent infusions with olaratumab. After a Grade 1 or 2 IRR, patients should be 
premedicated with the following (or equivalent) medications prior to all subsequent 
olaratumab/placebo infusions:
o
Histamine H1 antagonist (for example, diphenhydramine)
o
Glucocorticoid (for example, dexamethasone) intravenously
o
Acetaminophen orally 
Treatment guidelines for olaratumab IRRs are described in Table JGDP.7.

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Table JGDP.7.
Olaratumab Infusion-Related Reaction Treatment Guidelines
NCI CTCAE Grade
Treatment
Premedication at Subsequent 
Infusions
Grade 1 or 2
Stop infusion and monitor symptoms.
Additional appropriate medical therapy should be given 
according to standard medical practice; may include, but 
is not limited to:
Antihistamines (for example, diphenhydramine 
HCl)
Steroids (for example, dexamethasone)
Acetaminophen
Oxygen
After recovery, the infusion rate should be decreased to 
50% for the duration of the infusion.
Patients should be premedicated 
with antihistamines, steroids, 
acetaminophen, etc., as 
appropriate.
Grades 3 or 4
Stop infusion.
Administer immediate treatment. May include, but is not 
limited to:
Epinephrine
Bronchodilators and/or glucocorticoids for 
symptomatic bronchospasm
I.V. fluids and/or pressors for hypotension
Treatment with olaratumab should be immediately 
and permanently discontinued.
No subsequent dosing
All attempts should be made to obtain an 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.
Appropriate resuscitation equipment should be available in the room and a physician readily available during the 
period of drug administration.
Abbreviations: HCl = hydrochloride; I.V. = intravenous; NCI CTCAE = National Cancer Institute Common 
Terminology Criteria for Adverse Events.
7.1.1.2.
Nab-paclitaxel
Premedication to prevent hypersensitivity reactions is generally not needed prior to the 
administration of nab-paclitaxel.  Severe and sometimes fatal hypersensitivity reactions, 
including anaphylactic reactions, have been reported (Abraxane® Prescribing Information 2015).  
Patients who experience a severe hypersensitivity reaction to nab-paclitaxel should not be re-
challenged with it.
7.1.1.3.
Gemcitabine
Prophylactic antiemetics may be routinely administered to patients during the course of the study 
as per the decision of the investigator.  Additionally, premedication for gemcitabine may be 
administered according to institutional guidelines and/or clinical practice.  
Sites should consult the manufacturer’s instructions for gemcitabine for complete prescribing 
information (including warnings, precautions, contraindications, and adverse reactions) and 
follow institutional procedures for the administration of gemcitabine.

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7.1.1.4.
Granulocyte-Colony Stimulating Factors
Growth factors and erythropoietin are allowed per American Society of Clinical Oncology or
National Comprehensive Cancer Network guidelines. Short-acting G-CSF (for example, 
filgrastim) should be administered at least 24 hours after the last dose of chemotherapy and must 
be discontinued at least 24 hours prior to the next dose of chemotherapy. Longer-acting G-CSF 
(for example, pegfilgrastim) should be given at least 24 hours after the last dose of chemotherapy 
in the cycle.  
Duration of uncomplicated neutropenia before initiation of G-CSF treatment is left to the 
investigator’s discretion. Transfusions are permitted. No other therapy, including routine use of 
GFs or experimental medications (for example, immunotherapy or other unapproved 
medication), will be permitted while the patients are on the study.
7.1.2. Investigator Responsibilities
The investigator or his/her designee is responsible for the following:

explaining the correct use of the drugs and planned duration of each individual’s 
treatment to the study site personnel, the patient, and/or the patient’s legal 
representative

verifying that instructions are followed properly

maintaining accurate records of study treatment dispensing and collection

following the protocol at all times

at the end of the study, returning all unused medication to Lilly or its designee, 
unless Lilly and sites have agreed all unused medication is to be destroyed by the 
site, as allowed by local law

contacting Lilly clinical research personnel prior to screening a subject to ensure 
enrollment availability in the Phase 1b. Refer to Section 7.2.1.

maintaining contact with the Lilly clinical research physician (CRP) to discuss 
DLTs and potential dose changes due to DLTs
The pharmacy manual contains information about preparation and administration of study 
treatment. Section 7.1.1 contains information about any required or suggested premedication.
7.1.3. Packaging and Labelling
Olaratumab/placebo, gemcitabine, and nab-Paclitaxel will be provided by Lilly.  Olaratumab 
drug product is supplied in single-use, 50-mL nominal volume, United States Pharmacopeia
Type I glass vials. Each vial contains 500 mg of olaratumab at a concentration of 10 mg/mL, in 
a sterile, preservative-free solution. Each vial is stoppered with a coated butyl rubber latex-free 
plug stopper and sealed with an aluminum seal and a flip-off cap.
In the event of regional restrictions or supply limitations, commercially available gemcitabine 
and nab-Paclitaxel may be purchased by study sites.  Clinical trial materials will be labeled 
according to the country’s regulatory requirements.

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7.1.4. Dose-Limiting Toxicity Determination (Phase 1b)
Myelosuppression is expected with the nab-paclitaxel and gemcitabine regimen and can lead to 
complications such as fever and neutropenia, sepsis, infection, or bleeding.  These adverse events 
are generally considered DLT-level toxicities and thus can confound DLT determination in the 
setting of combination with olaratumab.  The criteria listed below will be used to determine the 
dose of olaratumab that can be added to nab-paclitaxel and gemcitabine without causing a 
significant increase in toxicity over that expected with nab-paclitaxel-gemcitabine alone.
A DLT is defined as events such as the following, graded according to the NCI-CTCAE version
4.03, when the event occurs within Cycle 1, and is considered to be related to olaratumab in 
combination with nab-paclitaxel plus gemcitabine by the investigator in conjuncture with Lilly:

Any febrile neutropenia

Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by clinically 
significant hemorrhage

Grade 4 neutropenia lasting 7 days or longer

nonhematologic Grade ≥3 toxicity, except for 
- toxicities such as nausea, vomiting, transient electrolyte abnormalities, diarrhea which 
can be controlled with optimal medical management within 48 hours;
- non-clinically significant, treatable, or reversible laboratory abnormalities including
liver function tests, uric acid, electrolytes, etc.

Any other significant toxicity deemed by the primary investigator and Lilly clinical 
research personnel to be dose-limiting (e.g., any toxicity that is possibly related to the 
study medication that requires the withdrawal of the patient from the study during Cycle 
1).
The MTD is defined as the highest olaratumab dose level at which no more than 33% of patients 
experience a DLT during Cycle 1.
Phase 1b
In addition to the DLT assessment period in Cycle 1, safety data beyond Cycle 1 may also be 
taken into consideration prior to a decision to dose escalation or determination of the Phase 2 
dose.  If both dosing regimens do not exceed DLT criteria, factors such as maintaining dose 
intensity of the standard of care treatment regimen and PK may be taken into consideration in 
selecting the dose recommended for use in the Phase 2 portion of the study.
Note:  Infusion-related reactions will not be counted as DLTs, as they occur independent of dose 
level.
7.2.
Method of Treatment Assignment
The following treatments will be administered to enrolled patients in this study every 4 weeks
(28-day cycle).
The Interactive Web Response System (IWRS), which is web-based and accessible 24 hours a 
day will be used in both the Phase 1b and Phase 2 portions of the study.  The IWRS registration 

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consists of assigning the patient a unique study identification number.  Once the patient is 
registered through the IWRS, he/she is considered to be enrolled in the study.
7.2.1. Phase 1b
Investigators are required to contact Lilly clinical research personnel prior to screening a patient 
in Phase 1b. Once enrollment availability is confirmed, sites may proceed with screening of 
patient and registration into Interactive Web Response System (IWRS), which is web-based and 
accessible 24 hours a day.  No dose escalations (that is, to the next cohort) can occur without 
prior discussion and agreement with the responsible Lilly CRP or clinical research scientist.
Phase 1b patients will not be eligible to participate in the Phase 2 portion of the study.
7.2.2. Phase 2
Patients who meet all criteria for enrollment will be randomly assigned via IWRS to receive 
either olaratumab plus nab-paclitaxel and gemcitabine (Treatment Arm) or placebo plus nab-
paclitaxel and gemcitabine (Control Arm).  Approximately 162 patients will be randomized in a 
1:1 ratio.
Randomization will be stratified into 4 groups, one for each combination of the following 2 
baseline factors:

Age group (<70 years versus ≥70 years)

Prior adjuvant/neo-adjuvant therapy (yes versus no)
Once the patient is registered through the IWRS, he/she is considered to be enrolled in the study.  
After randomization, patients should receive their first dose of treatment within 72 hours (3 days) 
whenever possible.  Up to 3 additional days delay of first dose of treatment will be permitted due
to holidays, weekends, bad weather, or other unforeseen circumstances and will not count as a
protocol deviation.
7.2.3. Selection and Timing of Doses
A cycle is defined as an interval of 28 days.  A delay of a cycle due to holiday, weekend, bad 
weather, or other unforeseen circumstances will be permitted for a maximum of 3 days and not 
counted as a protocol deviation.
The actual doses of olaratumab administered will be determined by measuring the patient’s body 
weight in kilograms at the beginning of each cycle.  If the patient’s weight does not fluctuate by 
more than 10% from the weight used to calculate the prior dose, the dose will not need to be 
recalculated.  A 5% variance in the calculated total dose will be allowed for ease of dose 
administration.
The actual doses of nab-paclitaxel and gemcitabine administered will be determined based on 
estimation of body surface area (BSA) in m2 on Day 1 of each 28-day cycle.  If the patient’s 
weight does not fluctuate by more than 10% from the weight used to calculate the prior dose, 
the BSA will not need to be recalculated, unless deemed clinically meaningful (recalculation 

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more frequently is allowed per local practice/standard).  A 5% variance in the calculated total 
dose will be allowed for ease of dose administration.
A patient may continue to receive study treatment until he or she meets one or more of the 
specified reasons for discontinuation (as described in Section 8).
7.3.
Blinding
The Phase 1b portion of this study is open-label.
Phase 2 is a double-blind, placebo-controlled, randomized trial.
To preserve the blinding of the study, a minimum number of Lilly personnel will see the 
randomization table and treatment assignments before the study is completed.
Upon study completion, investigators may unblind patients to study treatment assignment.
7.3.1. Emergency Unblinding
Phase 2
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted.  Patient safety must always be the first 
consideration in making such a determination.  If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the Lilly CRP prior to unblinding 
a patient’s treatment assignment unless this could delay emergency treatment of the patient.  If a 
patient’s treatment assignment is unblinded, Lilly must be notified immediately.
Emergency unblinding for AEs must be performed through the IWRS. All actions resulting in an 
unblinding event are recorded and reported by the IWRS.
7.3.2. Inadvertent Unblinding
Every effort will be made to blind both the patient and the investigator to the identity of the 
treatment, but the inadvertent unblinding of a patient may occur.  If an investigator, site 
personnel, or patient is inadvertently unblinded, the unblinding will not be sufficient cause for 
the patient to be discontinued from study treatment or excluded from study analyses.
Additionally, there may be ethical reasons for the patient to remain on the study treatment.  In 
the event of unblinding, the investigator must obtain specific approval from a Lilly CRP for the 
patient to continue in the study.
7.4.
Dosage Modification
Guidance for dose adjustment, delays, and discontinuation of blinded study drug
(olaratuma/placebo), gemcitabine and nab-paclitaxel due to hematological and 
non-hematological toxicities are presented in Sections 7.4.2, 7.4.3, and 7.4.4, respectively.  
Gemcitabine and nab-paclitaxel are intended to be administered in accordance with standard-of-
care in this study and dose modifications should follow the local labels. Investigators will 
interpret and document whether or not an AE has a reasonable possibility of being related to each 

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of the study drugs, taking into account the disease, concomitant treatments, or pathologies, in 
order to individually adjust study drug(s) doses. 
To begin dosing at each cycle, the following criteria must be fulfilled:

Absolute neutrophil count (ANC) ≥1.5 × 103 cells/µL (≥1500 cells/µL; ≥1.5 × 109/L)

Platelets ≥100 × 103 cells/µL (≥100,000 cells/µL; 100 x 109/L)

Total bilirubin ≤1.5 × upper limit of normal (ULN) for Cycle 1.
For subsequent cycles, monitor and administer as per standard of care with dose 
adjustment based on individual tolerance.

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or 
≤5 × ULN if the transaminase elevation is due to liver metastases

Nonhematologic toxicity must be CTCAE < Grade 2 or must have returned to baseline, 
unless the toxicity is deemed not clinically significant by the investigator (such as 
alopecia) or is a laboratory abnormality that is manageable by institutional standards 
(such as asymptomatic electrolyte disturbances).  Table JGDP.11 provides additional 
guidance for non-hematological toxicities of peripheral neuropathy, cutaneous toxicity 
and mucositis or diarrhea.
In the Phase 1b portion of the study, doses of olaratumab and/or nab-paclitaxel or gemcitabine 
may be delayed, omitted, or reduced if the patient experiences an AE or a DLT-equivalent 
toxicity.
In the Phase 2 portion, investigators will be blinded to treatment assignment (olaratumab versus 
placebo) and should adjust dosing of olaratumab/placebo as if all patients are receiving 
olaratumab.
In the event of an alteration in olaratumab/placebo dose due to an olaratumab/placebo-related 
toxicity, gemcitabine or nab-paclitaxel need not be altered, and the planned gemcitabine or nab-
paclitaxel schedule should be maintained.  Similarly, olaratumab/placebo therapy need not be 
altered for either gemcitabine- or nab-paclitaxel-related toxicity.
Omission or discontinuation of 1 of the study drugs in the combination does not prohibit dosing 
with other study drugs, provided the patient meets dosing criteria.
In case of difficulty in assigning relatedness to one study drug or the other, the doses of all study 
drugs may be delayed, reduced, or omitted.
7.4.1. Dosing and Dose Reductions
Given the known adverse profile of the gemcitabine and nab-paclitaxel combination, it is 
anticipated that bone marrow suppression will be a common reason for dose modification.  In the 
case of toxicity related to myelosuppression and its complications, the relative roles of 
gemcitabine and nab-paclitaxel are often impossible to separate, and thus it is expected such 
toxicity would result in dose reductions of both agents.  In cases where AEs, in the opinion of the 
investigator, are more likely due to one drug than another, adjustment of one of the 
chemotherapy agents and not the other is permissible.  

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Dose level reductions for nab-paclitaxel and gemcitabine are shown in Table JGDP.8.
Table JGDP.8.
Dosing and Dose Reductions for Nab-paclitaxel and Gemcitabine
Nab-paclitaxel
(mg/m2)
Gemcitabine
(mg/m2)
Starting Dose
125
1000
1st Dose Reduction
100
800
2nd Dose Reduction
75
600
Table JGDP.9 summarizes dosing and dose reduction for olaratumab.
Table JGDP.9.
Dosing and Dose Reductions for Olaratumab
Starting Dose (mg/kg)
15
20
25
1st Dose Reduction (mg/kg)
12
15
20
2nd Dose Reduction (mg/kg)
10
12
15
In the Phase 2 portion, patients will be started on a dose of 20 mg/kg in Cycle 1.  In the event a 
patients toxicity in Cycle 1 requires an olaratumab dose reduction, the patient may start Cycle 2 
at the dose of 15 mg/kg olaratumab, provided the toxicity necessitating dose reduction has
adaequately resolved.
If a patient at the lowest dose level experiences toxicity that would necessitate additional dose 
reductions, the patient should discontinue that treatment.
Patients who undergo a dose reduction may be re-escalated at the discretion of the investigator 
once the toxicity requiring dose reduction has returned to Grade ≤1 or baseline.  
In the case of recurrent, persistent toxicity, the investigator should consider permanent dose 
reduction.  
7.4.2. Dose Modifications
7.4.2.1.
Hematological Toxicites
General guidelines for dose modifications for hematologic toxicities are shown in
Table JGDP.10.
Olaratumab has been safely administered without any DLTs or significant myelosuppressive 
toxicity in monotherapy studies.  In studies with cytotoxic chemotherapies, olaratumab has 
shown some increase in myelosuppressive toxicities; however, these toxicities are principally 
driven by the profile of the backbone chemotherapy.  In addition, exposure-response analysis of 
the Study JGDG demonstrated the importance of achieving and maintaining olaratumab serum 
concentrations in a potentially therapeutic range (see also Section 5.5).  For these reasons, 
hematological toxicity management will focus on dose modification of gemcitabine and nab-
paclitaxel per label guidelines, and not by olaratumab dose reductions (Table JGDP.10).  In the 
case of toxicity related to myelosuppression and its complications, the relative roles of 

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gemcitabine and nab-paclitaxel are often impossible to separate, and thus it is expected such 
toxicity would result in dose reductions of both agents. In cases in which AEs, in the opinion of 
the investigator, are more likely due to 1 drug than another, adjustment of 1 of the chemotherapy
agents and not the other is permissible. In the case of toxicities deemed potentially related to 
olaratumab, the investigator may deem it appropriate to reduce or modify olaratumab. 
Table JGDP.10.
Dose Recommended and Modifications for Neutropenia and/or 
Thrombocytopenia within a Cycle
Cycle 
Day
ANCb
(cells/mm3)
Platelet Count
(cells/mm3)
nab-Paclitaxel /
Gemcitabine Dose
Olaratumab Dose
Day 1
<1500
OR
<100,000
Delay dosing until counts 
are above indicated level
Delay dosing until counts 
are above indicated level
Day 8
500 to <1000
OR
50,000 to <75,000
Reduce 1 dose level
Administer, no dose 
reductiona
<500
OR
<50,000
Withhold doses
Withhold dose
Day 15:  if Day 8 doses were reduced or given without modification:
Day 15
500 to <1000
OR
50,000 to <75,000
Reduce 1 dose level from 
the dose level 
administered on Day 8
Administer, no dose 
reductiona
<500
OR
<50,000
Withhold doses
Withhold dose
Day 15:  if Day 8 doses were withheld:
Day 15
≥1000
OR
≥75,000
Reduce 1 dose level from 
Day 1 dose
Administer, no dose 
reduction
500 to <1000
OR
50,000 to <75,000
Reduce 2 dose levels 
from Day 1 dose 
Administer, no dose 
reduction
<500
OR
<50,000
Withhold doses
Withhold dose
Any 
Day
Febrile 
neutropenia
-
-
Withhold doses until fever resolves and
ANC ≥1500 cell/mm3; resume dosing with a 1 dose 
level reduction
Abbreviations:  ANC = absolute neutrophil count; G-CSF = granulocyte colony-stimulating factor; 
Gem = gemcitabine; nab-P = nab-paclitaxel.
a
At the investigator’s discretion.
b
Note that additional guidance for recommended dose delay/modifications for febrile neutropenia is shown in 
Table JGDP.11.
7.4.2.2.
Non-Hematological Toxicities
Table JGDP.11 shows general guidelines for dose modifications due to non-hematological 
toxicities of study drugs. 
For olaratumab IRRs, see Section 7.4.4.3.1.  For IRRs to nab-paclitaxel see Section 7.4.4.2.3.

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Table JGDP.11.
Guidelines for Dose Modifications due to Non-Hematological Study 
Drugs-Related Toxicities
Toxicity
Nab-paclitaxel
Gemcitabine
Olaratumab
Peripheral neuropathy
Grade ≥3
Withhold until improves to 
≤Grade 1; resume dosing 
with a 1 dose level reduction 
from prior dose
No dose reduction
No dose reductiona
Cutaneous toxicity
Grade 2 or 3
Reduce to next lower dose level; discontinue 
treatment if toxicity persists
No dose reductiona
Grade 3 mucositis or 
diarrhea 
Withhold dosing until improves to ≤Grade 1;
resume at next lower dose level.
Investigator’s discretion
Other Non –hematological Toxicity (except IRR to olaratumab)c
Persistent or recurrent 
Grade 2 not resolved 
with best supportive 
care
Investigator discretion
Investigator discretion
Grade 3 or 4
Withhold either one or both drugs as clinically 
indicatedb.  Then resume treatment at the next lower 
dose level 
Withhold until toxicity is ≤Grade 1 
or has returned to pretreatment 
baseline a,b ; If toxicity recurs or is 
Grade 4, treatment may resume at 
a reduced dose. If toxicity 
Grade 4 recurs, discontinue 
olaratumab treatment.
Abbreviation:  ANC = absolute neutrophil count.
a
Dose adjustments are allowed at discretion of investigator for toxicities deemed related to olaratumab/placebo.
b
Except toxicities that can be adaequately controlled with supportive treatment such as asymptomatic electrolyte 
disturbances, hyperlipidemia, skin rash, nausea, or vomiting.
c
Please see also specific discontinuation criteria for olaratumab (Section 7.4.4.3), gemcitabine (Section 7.4.4.1), 
and nab-paclitaxel (Section 7.4.4.2).  
7.4.3. Dose Delays
Treatment may be delayed for up to 28 days to allow a patient sufficient time for recovery from 
study treatment-related toxicity.  If a patient does not recover from the toxicity within 56 days
from the time of last treatment, the patient must be discontinued from study treatment unless the 
investigator, in consultation with the Lilly CRP/CRS, agree that it is in the best interest of the 
patient to continue treatment.  
Delays for nab-paclitaxel due to peripheral neuropathy are allowed to last longer than 28 days for
toxicity to resolve (median duration of delay/resolution of AE to Grade ≤1 was 23 days in 
MPACT study of gemcitabine plus nab-paclitaxel [Von Hoff et al. 2013]).  Gemcitabine and 
olaratumab/placebo should be dosed on the planned schedule during delays for nab-paclitaxel-
related peripheral neuropathy.
If one (or more) study drugs will be withheld (omitted), Day 1 will be the day of administration 
of the first dose of any study drug in that cycle.  If  one (or more) study drugs will be withheld 
(omitted), the regular dosing interval for the non-affected study drug(s) should try to be 
maintained within or between cycles according to the planned treatment schedule (Section 7.1).  

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In certain instances, adjustments to planned dosing may be allowed upon consultation with the 
Sponsor (for instance if all study treatment on day 15 needs to be withhold/omitted that week 
may become the week of rest and the next dose (if counts and chemistries permit) Day 1 of a 
new cycle).  
7.4.4. Dosing Discontinuation
7.4.4.1.
Gemcitabine
Pulmonary toxicity has been reported with the use of gemcitabine. In cases of severe lung
toxicity, gemcitabine therapy should be discontinued immediately and appropriate supportive
care measures instituted.
Gemcitabine should be permanently discontinued for any of the following:

unexplained new or worsening dyspnea or evidence of severe pulmonary toxicity

severe hepatic toxicity

Hemolytic Uremic Syndrome or severe renal impairment

Capillary Leak Syndrome

posterior reversible encephalopathy syndrome
7.4.4.2.
Nab-paclitaxel
7.4.4.2.1. Hepatic Impairment
Exposure and toxicity of paclitaxel can be increased with hepatic impairment or administration 
of nab-paclitaxel in patients.  Do not administer nab-paclitaxel to patients with total bilirubin 
> 5x ULN and/or AST > 10x ULN.
7.4.4.2.2. Sepsis
Sepsis, with or without neutropenia, has been reported with the use of nab-paclitaxel in 
combination with gemcitabine. Biliary obstruction or presence of biliary stent were risk factors 
for severe or fatal sepsis. If a patient becomes febrile (regardless of ANC), initiate treatment 
with broad-spectrum antibiotics. For febrile neutropenia, interrupt nab-paclitaxel and 
gemcitabine until fever resolves and ANC ≥ 1500, then resume treatment at reduced dose levels 
(see Table JGDP.11).
7.4.4.2.3. Pneumonitis
Pneumonitis, including some cases that were fatal, has been reported in patients receiving 
nab-paclitaxel in combination with gemcitabine. Monitor patients for signs and symptoms of 
pneumonitis and interrupt nab-paclitaxel and gemcitabine during evaluation of suspected 
pneumonitis. After ruling out infectious etiology and upon making a diagnosis of pneumonitis, 
permanently discontinue treatment with nab-paclitaxel and gemcitabine.

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7.4.4.2.4. Infusion-related Reactions/Hypersensitivity Reactions
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have 
been reported in patients receiving nab-paclitaxel. Patients who experience a severe 
hypersensitivity reaction to nab-paclitaxel should not be rechallenged with this drug.
7.4.4.3.
Olaratumab
For non-hematological toxicities, refer to Table JGDP.11.
7.4.4.3.1. Olaratumab Infusion-Related Reactions
Olaratumab should be immediately and permanently discontinued for Grade 3 or 4 IRR. For 
olaratumab IRR treatment guidelines see Table JGDP.7. 
Due the observed rate of Grade ≥3 IRRs in the Phase 1 and Phase 2 portions of Study JGDP that 
was greater than the rate of 3.1% previously observed across the olaratumab program, testing for 
IgE anti-α-gal antibodies must be performed as part of screening, and patient with antibody 
levels >ULN should be excluded.
Patients treated with olaratumab (olaratumab/placebo in the Phase 2 portion of the study) should 
be closely monitored for signs and symptoms indicative of a hypersensitivity/infusion-related
reaction 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 (epinephrine, prednisolone 
or equivalents, etc.) are available.  No other study treatment (gemcitabine and/or nab-paclitaxel) 
should be administered during the observation period (premedications for gemcitabine and/or 
nab-paclitaxel are allowed to be administered during the observation period). 
If there is no evidence of an IRR in the first 2 cycles, no observation period is required for 
subsequent treatment cycles. In the event that a Grade 1 or 2 IRR occurs after Cycle 2, the 1-
hour observation period will be reinstituted for a minimum of 2 cycles.  The reinstituted 
observation period may be suspended after 2 cycles if the patient shows no further signs or 
symptoms of an IRR.  If a patient experiences an IRR, all attempts should be made to obtain an 
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 (See Appendix 
4 and Section 9.5).
Signs and symptoms of IRRs may vary in different patient populations and include rigors/tremor, 
back pain/spasms, chills, flushing, dyspnea, pruritus or rash (without urticaria), fever, headache, 
body aches, abdominal pain, nausea, vomiting, and blurred vision. In severe cases, symptoms 
have included wheezing, bronchospasm, hypoxia, chest pain and/or tightness, supraventricular 
tachycardia, hypotension, and paresthesia.
The Lilly medical monitor should be contacted immediately if questions arise concerning the 
grade of the reaction.

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7.5.
Preparation/Handling/Storage/Accountability
Refer to the IB or Pharmacy Manual for detailed storage information of olaratumab and 
gemcitabine.  Investigators should consult the approved nab-paclitaxel package insert for 
complete storage and stability information.
It is the responsibility of the investigator or designee to ensure that a current record of 
investigational product disposition is maintained at each study site where investigational 
products are inventoried and disposed.  Records or logs must comply with applicable regulations 
and guidelines.
7.6.
Treatment Compliance
The study medication, which is administered intravenously, will be administered only at the 
investigational sites by the authorized study site personnel.  As a result, treatment compliance is 
ensured.  The treatment administration data are recorded in the patient’s medical record and 
eCRF.
7.7.
Concomitant Therapy
Premedication guidelines are described in Section 7.1.1.
Patients may receive full supportive care therapies concomitantly during the study, including 
antiemetic treatment as per institutional guidelines. At each visit, appropriate documentation of 
all forms of premedication, supportive care, and concomitant medications must be captured on 
the study eCRF.
Concomitant medications and supportive care must also be documented until 30 days after the 
last dose of investigational product. No other chemotherapy, immunotherapy, radiation therapy, 
surgery for cancer, or experimental medications will be permitted while the patients are on study 
treatment or during short-term follow-up period. Any disease progression requiring other forms 
of specific antitumor therapy will be cause for discontinuation from the study.
7.7.1. Other Concomitant Medication (CYP2C8 and CYP3A4 Inhibitors 
or Inducers)
The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4.  In the absence of formal 
clinical drug interaction studies, caution should be exercised when administering nab-paclitaxel 
concomitantly with medicines known to inhibit (e.g., ketoconazole and other imidazole 
antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, 
and nelfinavir) or induce (e.g., rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) 
either CYP2C8 or CYP3A4.
7.7.2. Supportive Care
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.

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7.7.2.1.
Colony Stimulating Factors
Refer to Section 7.1.1.4.
7.7.2.2.
Transfusion of Blood Product
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, Inclusion Criterion [9]).
7.7.2.3.
Antiemetic Therapy
Both prophylactic and symptom-directed antiemetic therapies are recommended and should be 
used in accordance with institutional guidelines (when existent) and/or at investigator’s 
discretion.
7.7.3. 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 radiation or surgery to symptomatic sites of disease will not be permitted while on 
study.
7.8.
Treatment after the End of the Study
Study completion will occur when the primary analysis of OS has been completed. Investigators
will continue to follow the Schedule of Activities (Section 2) for all patients until notified by 
Lilly that study completion has occurred.
Refer to Section 7.3 for unblinding that occurs after study completion.
7.8.1. Continued Access
After the final analysis of OS has been conducted, patients who are still on study treatment at the 
time of study completion may continue to receive study treatment if they are experiencing 
clinical benefit and no undue risks. Placebo will no longer be administered, and crossover will 
not be permitted. The continued access period (see Figure JGDP.3) will apply to this study only 
if at least 1 patient is still on study treatment when study completion occurs.  Lilly will notify 
investigators when the continued access period begins.

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Figure JGDP.3.
Continued access diagram.
The patient’s continued access to study treatment will end when a criterion for discontinuation is 
met (Section 8).  Continued access follow-up will begin the day after the patient and the 
investigator agree to discontinue study treatment and lasts approximately 30 (±7) days.
Follow-up procedures will be performed as shown in the Continued Access schedule of activities 
in Table JGDP.4.
Patients who are in short-term follow-up when the continued access period begins will continue 
in short-term follow-up until the 30-day short-term follow-up visit is completed.  Long-term 
follow-up does not apply.
Patients who are in long-term follow-up when the continued access period begins will be 
discontinued from long-term follow-up.
Study Treatment Period
a Lilly will notify sites when the continued access period begins and ends. 
b Final analysis of overall survival.  Lilly will notify sites when study completion occurs.
c End of trial occurs at the last visit or last scheduled procedure for the last patient.
Study Completionb
Patient and investigator 
agree to discontinue  
study treatment
Study treatment
Continued access 
follow-up
(approximately 30 days)
Continued Access Perioda
End of Trialc

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Discontinuation of All Study Treatment
Patients will be discontinued from all study treatment in the following circumstances listed 
below.  The reason for discontinuation and the date of discontinuation will be collected for all 
patients:

the patient is enrolled in any other clinical trial involving an investigational product or any 
other type of medical research judged not to be scientifically or medically compatible with 
this study

the patient becomes pregnant during the study

the patient is significantly noncompliant with study procedures

disease progression

unacceptable toxicity

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 
study treatment will occur prior to introduction of the new agent.

the investigator decides that the patient should be discontinued from study treatment

the patient requests to be discontinued from study treatment

the patient’s designee (for example, parents, legal guardian, or caregiver) requests that the 
patient be discontinued from study treatment
Patients who are discontinued from study treatment will have follow-up procedures performed as 
shown in the Schedule of Activities (Section 2).
8.1.2. Discontinuation of Olaratumab/Placebo
Patients will be discontinued from olaratumab if they experience unacceptable toxicity or 
experience an AE that would require a dose reduction below the doses listed in Table JGDP.9.
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If Lilly or the investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, a discussion must occur between the Lilly CRP and the investigator to 
determine if the patient may continue in the study.  If both agree it is medically appropriate 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 study treatment.
8.2.
Discontinuation from the Study
Patients will be discontinued from the study in the following circumstances:

participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

the investigator decides that the patient should be discontinued from the study

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
the patient requests to be discontinued from the study

the patient’s designee (for example, parents, legal guardian, or caregiver) requests that the 
patient be discontinued from the study
Patients who discontinue from the study early will have end-of-study procedures performed as 
shown in the Schedule of Activities (Section 2).
8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Study site personnel are expected to make 
documented diligent attempts to contact patients who fail to return for a scheduled visit or who 
the site is otherwise unable to follow-up.
Study site personnel, or an independent third party, will attempt to collect the survival status for 
all randomized patients who are lost to follow-up, including randomized patients who do not 
receive study treatment, within legal and ethical boundaries.
Public sources may be searched for survival status information.  If the patient’s survival status is 
determined, the survival status will be documented, and the patient will not be considered lost to 
follow-up.
Lilly personnel will not be involved in any attempts to collect survival status information.

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9.
Study Assessments and Procedures
Refer to Section 2 for the Schedule of Activities.  Appendix 3 provides a list of the laboratory
tests that will be performed.  Appendix 4 provides the schedule for collection of samples in this 
study.
Unless otherwise stated in the following subsections, all samples collected for specified 
laboratory tests will be destroyed within 60 days after receipt of confirmed test results.  Certain 
samples may be retained for a longer period, if necessary, to comply with applicable laws, 
regulations, or laboratory certification standards.
9.1.
Efficacy Assessments
Tumor assessments will be performed according to Response Evaluation Criteria In Solid 
Tumors Version 1.1 (RECIST 1.1) for each patient at the times shown in the Schedule of 
Activities (Section 2).  Digital images are to be sent to a third-party organization for storage.
For patients with solid tumors, computed tomography (CT) scans, including spiral CT, are the 
preferred methods of measurement (CT scan thickness recommended to be 5 mm); however, 
magnetic resonance imaging (MRI) is also acceptable in certain situations and if there is a 
concern about radiation exposure associated with CT.  Intravenous and oral contrast is required 
unless medically contraindicated.
The CT portion of a positron emission tomography (PET)-CT scan may be used as a method of 
response assessment if the site can document that the CT is of identical diagnostic quality to a 
diagnostic CT (with intravenous and oral contrast). A PET scan alone or as part of a PET-CT 
may be performed for additional analyses but cannot be used to assess response according to 
RECIST v.1.1 (Eisenhauer et al. 2009).
Patients will be treated until there is documented radiological PD, toxicity requiring cessation of
treatment, withdrawal of consent, or until other withdrawal criteria are met. In the event there is
symptomatic deterioration resulting in treatment discontinuation, radiographic confirmation
should be performed. For patients who discontinue treatment for any reason other than
radiographically documented PD (for example, symptomatic deterioration), radiographic
assessments should continue as scheduled every 8 weeks (±7 days) as calculated from
randomization until objective radiographic evidence of PD.
The method of tumor assessment used at baseline must be used consistently throughout the 
study.  Radiological scan of the thorax, abdomen, and pelvis is required.
See Section 10.3.1 for definitions of the efficacy endpoints.
9.1.1. Appropriateness of Assessments
The measures used to assess safety and efficacy in this study are consistent with those used in 
most conventional oncology trials.

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9.2.
Adverse Events
9.2.1. Definitions
An adverse event (AE) is any untoward medical occurrence in a patient administered a 
pharmaceutical product and that 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 a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product.
A treatment-emergent adverse event (TEAE) is an untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative to the 
pretreatment state, and does not necessarily have to have a causal relationship with this 
treatment.
9.2.2. AE Reporting
The investigator will use NCI-CTCAE version 4.03 (2010) to assign AE terms and severity 
grades.  Documentation should include onset and resolution/stabilization dates, AE grade, 
seriousness, relationship to study treatment, and outcome of the event. AE reporting will begin 
after the patient signs the ICF.
Investigators are responsible for:

monitoring the safety of patients in 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 appropriate medical care of patients during the study

documenting their review of each laboratory safety report

following, through an appropriate health care option, AEs that are serious or otherwise 
medically important, considered related to study treatment or the study, or that caused 
the patient to discontinue study treatment before completing the study.  The patient 
should be followed until the event resolves, stabilizes with appropriate diagnostic 
evaluation, or is reasonably explained.  Frequency of follow-up evaluation is left to the 
discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, study site personnel will record via eCRF any 
change in the preexisting conditions and any new conditions as AEs.  Investigators should record 
their assessment of the potential relatedness of each AE to study procedure or study treatment via 
eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment or a study procedure, taking into account the disease, 

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concomitant treatments, or pathologies. A “reasonable possibility” means that there is a cause 
and effect relationship between the study treatment and/or study procedure and the AE.
Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
Study site personnel must report any dose modifications or treatment discontinuations that result 
from AEs to Lilly or its designee via eCRF, clarifying, if possible, the circumstances leading to 
the dose modification or discontinuation of treatment.
Adverse event will be collected until at least 30 days after the last dose of study treatment.  After 
the 30-day short-term follow-up visit, only new and ongoing serious adverse events (SAEs) 
deemed related to study treatment will be collected.
9.2.3. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization

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 serious, based upon appropriate medical judgment.
Although all AEs after signing the ICF are recorded in the eCRF, SAE reporting begins after the 
patient has signed the ICF and has received study treatment.  However, if an SAE occurs after 
signing the ICF, but prior to receiving study treatment, it needs to be reported ONLY if it is 
considered reasonably possibly related to study procedure.
Study site personnel must notify Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a Lilly-approved method.  If alerts are issued via telephone, they are 
to be immediately followed with official notification on study-specific SAE forms.  This 24-hour 
notification requirement refers to the initial SAE information and all follow-up SAE information.
Pregnancy (during maternal or paternal exposure to study treatment) does not meet the definition 
of an AE but should be reported.  However, to fulfill regulatory requirements any pregnancy 
should be reported following the SAE process to collect data on the outcome for both mother and 
fetus.
Investigators are not obligated to actively seek AEs or SAEs in patients once they have 
discontinued and/or completed the study (the patient summary eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a patient has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.

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Planned hospitalizations or procedures for preexisting conditions that were recorded in the 
patient’s medical history at the time of enrollment should not be considered SAEs.  
Hospitalization or prolongation of hospitalization without a precipitating clinical AE (for 
example, for the administration of study treatment or other protocol-required procedure) should 
not be considered an SAE.
Serious adverse events, including death, caused by disease progression should not be reported 
unless the investigator deems them to be possibly related to study treatment.
9.2.4. Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to study treatment or study procedure.  
United States 21 CFR 312.32 and 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 regulations and associated 
detailed guidances.
9.2.5. Adverse Events of Special Interest
Adverse events of special interest (AESIs) are events that have been identified as safety signals 
during preclinical or early clinical trials or based on class effects of similar drugs.  These events 
will be monitored prospectively in the clinical developmental program.  Each event is defined by 
a careful assessment and grouping of individual related Medical Dictionary for Regulatory 
Activities (MedDRA™) preferred terms.

Infusion-related reactions (IRRs) to olaratumab. As with other monoclonal 
antibodies, hypersensitivity reactions (including fatal reactions) have been 
reported with olaratumab administration.

IRRs to nab-paclitaxel.  Severe and fatal hypersensitivity reactions have been 
reported with administration of nab-paclitaxel.

Pneumonitis – Pneumonitis (including fatal cases) has been reported in patient 
receiving nab-paclitaxel and gemcitabine.
Refer to Section 7.4 for special treatment considerations for dose delays, modifications, and 
discontinuations from olaratumab/placebo and nab-paclitaxel/gemcitabine, including adverse 
events of concern or special interest.  For olaratumab IRRs, refer to Section 7.4.4.3.1 for
instructions on the monitoring and subsequent dosing and premedication adjustments for patients 
who experience an IRR to olaratumab.
9.2.6. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.

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Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
In case of olaratumab overdose, refer to the olaratumab IB.  In case of overdose of the other 
chemotherapeutic agents, refer to the Product Label for the specific agent.
9.4.
Safety
9.4.1. Other Safety Measures
For each patient, electrocardiograms (ECGs), vital signs, laboratory tests, or other tests should be 
collected as shown in the Schedule of Activities (Section 2).  ECGs will be collected centrally 
for patients in the Phase 1 portion of the study and locally for patients in the Phase 2 portion.  
Refer to JGDP Manual of Operation for ECG storage requirement.
Patients must be supine for approximately 5 to 10 minutes before ECG collection and remain 
supine but awake during ECG collection. 
Electrocardiograms may be obtained at additional times, when deemed clinically necessary. 
Collection of more ECGs than expected at a particular time point is allowed when needed 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 and for immediate 
patient management, should any clinically relevant findings be identified.  Any clinically 
significant findings that result in a diagnosis and that occur after the patient receives the first 
dose of study treatment should be reported to Lilly or its designee as an AE via eCRF.
9.4.2. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.  The Lilly CRP will monitor safety data throughout the course of the study. The Lilly
CRP will review trends in safety data, laboratory analytes, and AEs including monitoring of 
AESIs.  Lilly will review SAEs within time frames mandated by company procedures.
A safety review committee (SRC) consisting of the Lilly CRP/CRS, Global Patient Safety (GPS)
physician, statistician, the primary investigator, and ad hoc SCR members as needed will be 
responsible for review of safety data.  The SRC will convene to review data at the end of the 
DLT observation period after Phase 1b is complete prior to initiation of Phase 2.
In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, only members of the Independent Data Monitoring Committee (IDMC) (refer to 
Section 10.3.5) can conduct additional analyses of the safety data.
During the study, Lilly will perform a blinded review of all reports of deaths and SAEs to ensure 
completeness and accuracy.  If a death or other clinical AE is deemed serious, unexpected, and 

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possibly related to study treatment, a limited number of Lilly GPS representatives external to the 
study team will be unblinded for regulatory reporting and safety monitoring purposes.  These
measures will preserve the integrity of the data collected during this study and minimize any 
potential for bias while providing for appropriate safety monitoring.
9.4.2.1.
Hepatic Monitoring
If a patient experiences elevated ALT 5 × ULN and elevated total bilirubin 2 × ULN, clinical 
and laboratory monitoring should be initiated by the investigator.
Details for hepatic monitoring depend upon the severity and persistence of observed laboratory 
test abnormalities. To ensure patient safety and comply with regulatory guidance, the 
investigator is to consult with the Lilly CRP regarding collection of specific recommended 
clinical information and follow-up laboratory tests.  Refer to Appendix 5.
9.5.
Pharmacokinetics
Pharmacokinetic samples will be collected as specified in the Pharmacokinetic, Immunogenicity, 
and Biomarker Research Sampling Schedule (Appendix 4).  Based on the time and dates 
specified in Appendix 4, blood samples will be drawn for all patients for the assessment of 
olaratumab PK.  Serum concentrations of olaratumab obtained at different time points will be 
summarized by descriptive statistics and noncompartmental analysis.  Additional analysis 
utilizing the population pharmacokinetic approach may also be conducted, if deemed necessary.
At the visits and times specified in Appendix 4, venous blood samples of approximately 3 mL 
each will be collected to determine the concentrations of olaratumab in serum.  A maximum of 5 
samples in addition to those shown in Appendix 4 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 Lilly.  It is 
preferred that the blood samples be obtained from a peripheral location.  Blood samples can be 
collected via central access devices, but a sample drawn for PK from any type of central catheter 
cannot be diluted or it will not be viable for analysis.  If multiple samples are obtained centrally, 
the PK sample should be the last specimen drawn to reduce the potential for a diluted or 
improperly drawn sample.  The actual date and time (24-hour clock time) of each sampling will 
be recorded.
These samples will be analyzed at one or more laboratories designated by Lilly.  Serum 
concentrations of olaratumab will be assayed using a validated enzyme-linked immunosorbent 
assay method.
Drug concentration information that could unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded.
The PK samples will be stored at a facility designated by Lilly.  The remaining serum and 
plasma from the samples collected for PK may be pooled and used for exploratory drug 
metabolism work and other exploratory PK/pharmacodynamic work as deemed appropriate.

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Bioanalytical samples collected to measure olaratumab concentrations will be retained for a 
maximum of 1 year following the last patient visit for the study.
9.6.
Pharmacodynamics
Refer to Section 9.8.
9.7.
Genetics
9.7.1. Whole Blood Samples for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis as specified in 
Appendix 4, where local regulations allow.
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to study treatment 
and to investigate genetic variants thought to play a role in metastatic pancreatic cancer.  
Assessment of variable response may include evaluation of AEs or differences in efficacy.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the study site personnel.  Samples will be retained for a 
maximum of 15 years after the last patient visit for the study, or for a shorter period if local 
regulations and/or ethical review boards (ERBs) impose shorter time limits, at a facility selected 
by Lilly.  This retention period enables use of new technologies, response to questions from 
regulatory agencies, and investigation of variable response that may not be observed until later in 
the development of olaratumab or after olaratumab becomes commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing technologies include whole genome and exome 
sequencing, genome-wide association studies, multiplex assays, candidate gene studies, and 
epigenetic analyses.  Regardless of the technology utilized, data generated will be used only for 
the specific research scope described in this section.
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics (PD), mechanism of action, variability of patient response 
(including safety), and clinical outcome.  Sample collection is incorporated into clinical studies 
to enable examination of these questions through measurement of biomolecules including DNA, 
RNA, proteins, lipids, and other cellular elements.
Samples for biomarker research, described in Section 9.8.2, will be collected as specified in
Appendix 4, where local regulations allow.
It is possible that biomarker data for patients in the study have already been generated from 
samples that were collected and analyzed prior to enrolling in this trial.  This may include data 
generated from genetic analyses.  If available, these data may be requested from medical records 
for use in the research described in Section 9.8.2.

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In addition to the required tumor tissue and biomarker samples discussed below, patients may be 
asked to undergo collection of an additional biopsy specimen and blood sample after treatment 
with study drug(s) has been initiated, including potentially after disease progression. Such 
additional biopsies should be performed only if they do not create undue risk to the patient. If 
these additional samples are requested, they will be used to further investigate molecular features 
that may explain treatment response and resistance mechanisms.
9.8.1. Samples for Nonpharmacogenetic Biomarker Research
Blood samples for nonpharmacogenetic biomarker research will be collected as specified in 
Appendix 4, where local regulations allow.
Samples will be examined for biomarkers related to, but not limited to the drug targets, disease 
process, immune cells/immune and tumor microenvironment functioning within the disease state 
and/or cancer-related conditions, pathway associated with cancer and study drugs, variable 
response to olaratumab and/or nab-paclitaxel and gemcitabine, the mechanism of action of study 
drugs, and/or for research-related methods, or validating diagnostic tools or assays.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the study site personnel.
Samples will be retained for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if local regulations and/or ERBs impose shorter time limits, at a facility 
selected by Lilly.  This retention period enables use of new technologies, response to questions 
from regulatory agencies, and investigation of variable response that may not be observed until 
later in the development of olaratumab or after olaratumab becomes commercially available.
9.8.2. Tissue Samples for Research
Phase 1b
Collection of the following tumor tissue samples is optional for all patients participating in 
Phase 1b:

an archived FFPE tumor tissue sample, if not restricted by local regulations and available.  
Note:  if sufficient archival tissue not available, a new biopsy is not required.
Phase 2
Collection of the following tumor tissue samples is required for all randomized patients in 
Phase 2 in order to participate in this study:

an archived FFPE tumor tissue sample; if such tissue is not available, a newly 
obtained core or excisional biopsy of a tumor lesion must be performed.
In addition to the required tumor tissue and biomarker samples discussed above, patients may be 
asked to undergo collection of an additional biopsy specimen and blood sample after treatment 
with study drug(s) has been initiated, including potentially after disease progression. Such 
additional biopsies should be performed only if they do not create undue risk to the patient. If 

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these additional samples are requested, they will be used to further investigate molecular features 
that may explain treatment response and resistance mechanisms.
Tumor tissue samples will be examined for biomarkers related to disease process, pathways 
associated with pancreatic cancer and/or cancer-related conditions, immune cells/immune and 
tumor microenvironment functioning within the disease state and/or cancer-related conditions, 
mechanism of action of olaratumab and/or gemcitabine, nab-paclitaxel, and/or research methods 
or in validating diagnostic tools or assay(s) related to cancer.  The analysis of these tumor tissue 
samples may include the assessment of expression of PDGFRα, PDGFRβ, and canonical ligands 
(PDGFA, B, C, and D).
Formalin-fixed paraffin-embedded tumor tissue obtained from the primary tumor or metastatic 
site should be provided as a block or unstained slides.  Due diligence should be used to make 
sure that tumor sample (not a normal adjacent or a tumor margin sample) is provided.  Pathology 
report accompanying archival tissue may also be requested. The report must be coded with the 
patient number. Personal identifiers, including the patient’s name and initials, must be removed 
from the institutional pathology report prior to submission.  Archival blocks will be sectioned 
and returned to the study site. Slides and tissue samples collected on-study will not be returned.
Samples will be retained for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if local regulations and/or ERBs impose shorter time limits, at a facility 
selected by Lilly or its designee.  This retention period enables use of new technologies, response 
to questions from regulatory agencies, and investigation of variable response that may not be 
observed until later in the development of olaratumab or after olaratumab becomes commercially 
available.
Technologies are expected to improve during the 15-year storage period and therefore cannot be 
specifically named.  However, existing technologies, including mutation profiling, copy number 
variability, gene expression, multiplex assays, and/or immunohistochemistry, may be performed 
on these tissue samples to assess potential associations with these biomarkers and clinical 
outcomes.
9.8.3. Immunogenicity Assessments
Blood samples for immunogenicity testing will be collected as shown in Appendix 4 to 
determine antibody production against olaratumab.  Immunogenicity will be assessed by a 
validated 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.
When possible, immunogenicity analysis will be done from the same blood drawn for PK 
analysis. In the event of an olaratumab/placebo infusion reaction, additional blood samples will 
be collected for additional immunogenicity analysis. These additional samples will be collected 
as close as possible to the onset of the event, at the point of resolution from the event, and within 
30 days after onset of the event.

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Samples will be retained for a maximum of 15 years after last the patient visit for the study, or 
for a shorter period if regulations and ERBs impose shorter time limits, at a facility selected by 
Lilly.  The duration allows Lilly to respond to future regulatory requests related to olaratumab.
9.9.
Patient-Reported Outcomes/Resource Utilization (Phase 2 only)
9.9.1. Patient-Reported Outcomes
In the Phase 2 portion of this study, patient-reported outcome (PRO) for pain will be assessed
using the Brief Pain Inventory Short Form, Modified (mBPI-sf; Cleeland 1991).  Health-related 
quality of life will be assessed with the European Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; Aaronson et al. 1993).  
Health status will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L).  For the 
mBPI-sf, 2 baseline assessments will be collected, the first one within 7 days of the first cycle 
(not on Cycle 1 Day 1) and the second one at Day 1 of the first cycle prior to study treatment 
administration.  For patients who discontinued for reasons other than death or withdrawn 
consent, PRO data shall be collected at the short-term and first long-term follow-up visits in 
accordance with the Study Schedule of Activities.
Paper versions of the questionnaires will be used.  It is recommended that the instruments be 
administered together and in sequence order, at the beginning of the visit prior to other study 
procedures, with the mBPI-sf presented first, followed by the EORTC QLQ-C30 and continuing 
with the EQ-5D-5L.  Whenever possible, if administration is not possible prior to all other 
procedures, at least every effort should be made to administer at the same time point in each 
visit.  Questionnaires should be administered to the patient prior to extensive interaction with site 
staff and must be completed prior to study drug administration.
Patient-reported questionnaires should be completed by patients when a language translation is 
available in which the patient is fluent or literate.
9.9.1.1.
Pain assessments
The mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity.  
In addition to pain intensity (4 items), the mBPI-sf is designed for patients to record the presence 
of pain in general, pain relief, and pain interference with function (general activity, mood, ability 
to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life).  The 
mBPI-sf is administered per the Schedule of Activities (Section 2).  The recall period is the past 
24 hours or last week and completion time is typically 5 to 7 minutes.
Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales 
anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can 
imagine or completely interferes).  The focus of the analysis will be on the “worst pain”.  “Worst 
pain” intensity has been shown to meaningfully impact patients’ lives as indicated by a strong 
correlation with functional interference scores in various types of cancer (Daut et al. 1983; 
Serlin et al. 1995; Ger et al. 1999; McMillan et al. 2000; Shi et al. 2009).  Moreover, a study by 
Stone et al. (2004) suggested that patients’ tendency to focus on the most severe level of pain 

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during a recall period may bias average recalled pain. Therefore, the focus of the analysis will 
be on the “worst pain”.
Analgesic use will be recorded on the eCRF.  Data on each individual prescription and 
over-the-counter analgesic medication will be recorded on the Concomitant Medications eCRF,
including but not limited to drug name and mode of administration.  The use of analgesics should 
be reviewed with the patient during each visit.  Any changes to analgesic use (new or stopped 
analgesics) will be recorded on the eCRF.  Analgesics will be classified into 1 of 6 categories, 
using an analgesic ladder approach with medication category based on a World Health 
Organization Pain scale outlined in Table JGDP.12.  A therapy category will be assigned 
according to the maximum category of therapy routinely administered based on analgesic data 
for that cycle.
For the mBPI-sf, 2 baseline assessments will be collected, the first one within 7 days of the first 
cycle (not on Cycle 1 Day 1) and the second one at Day 1 of the first cycle prior to study 
treatment administration. The baseline mBPI-sf score will be calculated as the average of the 2 
baseline assessments. 
The mBPI-sf population will include all patients who completed the baseline assessment 
(2 assessments within 7 days of Cycle 1 Day 1) followed by at least 1 mBPI-sf “worst pain” 
assessment after 1 cycle of study drug (Cycle 2 Day 1 or later).
Table JGDP.12.
World Health Organization Pain Scale
Code
Description
0
No analgesia
1
Aspirin (for pain, not cardiovascular prophylaxis), acetaminophen, nonsteroidal anti-inflammatory drugs
2
Codeine, hydrocodone, pentazocine, oxycodone
3
Oral morphine, hydromorphone, methadone, transdermal fentanyl
4
Parenteral opiates
5
Neurosurgical procedures (blocks)
9.9.1.2.
EORTC QLQ-30
Broadly used in cancer trials, validated, and available in over 80 different languages, the EORTC
QLQ-C30 is a reliable and validated tool. The EORTC QLQ-C30 v3.0 is a self-administered, 
cancer-specific questionnaire with multidimensional scales. The EORTC QLQ-C30 self-
reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions:

global health status/quality of life (2 items)

functional scales (15 total items addressing either physical, role, emotional, cognitive, or 
social functioning)

symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, 
insomnia, appetite loss, constipation, diarrhea, or financial impact)
The EORTC QLQ-C30 questionnaire is administered per the Schedule of Activities (Section 2).  
The recall period is the past week, completion time is typically 5 to 7 minutes, and the
questionnaire will be scored as described by the EORTC scoring manual (Fayers 2001).  The 
QLQ-C30 population will include all patients who completed the baseline assessment (Cycle 1

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Day 1) followed by at least 1 QLQ-C30 assessment after 1 dose of study drug (Cycle 2 Day 1 or
later).
9.9.1.3.
EQ-5D-5L
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status
(Herdman et al. 2011).  Specifically, this questionnaire is included in this trial to evaluate 
health-state utilities associated with metastatic pancreatic cancer.  These utility measures are an 
important input for economic evaluations concerning the value of treatment interventions.
The EQ-5D-5L is designed to be used in conjunction with other patient-reported measures.  
Patients will complete the 5-dimension (mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression), 5-level (no problem, slight, moderate, severe, or extreme problem) 
assessment according to the Schedule of Activities (Section 2).  A unique EQ-5D health state is 
defined by combining 1 level from each of the 5 dimensions. Additionally, patients will indicate 
their current health status by marking on a visual analogue scale ranging from 100 (best 
imaginable health state) to 0 (worst imaginable health state).
The recall period is “today.”  The EQ-5D-5L is designed for self-completion taking only a few 
minutes to complete.
The EQ-5D-5L population will include all patients who completed the baseline assessment 
(Cycle 1 Day 1) followed by at least 1 EQ-5D-5L assessment after 1 dose of study drug (Cycle 2 
Day 1 or later).
EQ-5D-5L responses may be incorporated into cost utility analyses, but will not be included in 
the clinical study report.
9.9.2. Resource Utilization
Investigators will be asked to document the use of best supportive care (BSC) measures,
concomitant medications, transfusions, and treatment-related hospitalization days. Such
assessments are to be taken throughout the study through the 30-day short-term
postdiscontinuation follow-up visit.

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10. Statistical Considerations
10.1. Sample Size Determination
The Phase 1b portion of the study will sequentially evaluate two alternative dosing schedules 
using a “3 + 3” dose-escalation design.  Based upon the design, the Phase 1b portion may enroll 
up to approximately 24 patients to determine the dose and regimen for olaratumab in 
combination with nab-paclitaxel and gemcitabine recommended for use in the Phase 2 portion of 
the study.
The Phase 2 portion of the study will enroll approximately 162 additional patients, randomized
in a 1:1 fashion between study arms.  The primary analysis of OS will be performed when a 
minimum of 113 OS events have been observed.
An overall study-wise, two-sided alpha level of 0.20 will be applied to the primary endpoint of 
OS.  One interim safety and efficacy analysis and one final efficacy analysis will be performed.  
The interim efficacy analysis will occur after 70 OS events, with OS compared between study 
arms.  There will be no formal hypothesis testing or alpha-spending at the interim analysis with 
respect to efficacy in this study.  The purpose of this interim analysis is solely to inform 
decision-making regarding whether or not to initiate early development of a separate Phase 3 
trial.
Assuming the true OS HR is 0.67, there is at least 80% statistical power at a 1-sided significance 
level of 0.10 (or equivalently a 2-sided significance level of 0.20) to show a statistically 
significant difference in OS between study arms.
Researchers have reported a median OS of 8.5 months in pancreatic cancer patients receiving 
gemcitabine plus nab-paclitaxel versus 6.7 months with gemcitabine alone (Von Hoff et al. 
2013).  If the control arm in the current study performs similarly, the median OS for the 
experimental arm would be approximately 12 to 13 months, consistent with an HR of 0.67. 
Efficacy analysis will be based on intent-to-treat analyses.  In addition, the safety analysis 
requires only 1 dose of study drug to be included, thus patients excluded should be minimal.
10.2. Populations for Analyses
Phase 1b
DLT-evaluable Population:  The DLT-evaluable population will include all enrolled patients 
who complete Cycle 1 or discontinue due to a DLT prior to completing Cycle 1 treatment.
Safety population:  All enrolled patients who receive any quantity of study treatment, regardless 
of their eligibility for the study, will be included in the safety analysis.  Safety evaluation will be 
performed based on the actual initial therapy a patient has received, regardless of any other 
cohort to which he or she was assigned.
Biomarker population:  will include the subset of patients from the ITT population from whom 
a valid assay result has been obtained.  Samples for biomarker research will be collected at times 
specified in Appendix 4, where local regulations allow.

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Phase 2
Intention-to-Treat (ITT) population: will include all randomized patients who received at 
least one dose of assigned treatment.  The ITT analysis of efficacy data will consider allocation 
of patients to treatment groups as randomized and not by actual treatment received.  This 
population will be used for all baseline, efficacy, and health economics analyses.
Per-protocol population: will include all randomized patients who receive at least 1 dose of 
study treatment and do not have any major protocol violations that could potentially affect the 
efficacy conclusions of the study.  This population will be defined in detail in the SAP prior to 
database lock.
Safety population:  will include all randomized patients who received any quantity of study 
treatment, regardless of their eligibility for the study. The safety evaluation will be performed 
based on the first dose of study treatment a patient actually received, regardless of the arm to 
which he or she was randomized. The safety population will be used for all dosing/exposure, 
safety, and resource utilization analyses.
Pharmacokinetic population:  will include all treated patients who received at least 1 full dose 
of study treatment and have baseline and at least 1 postbaseline evaluable PK sample.
Biomarker population:  will include the subset of patients from the ITT population from whom 
a valid assay result has been obtained.  Samples for biomarker research will be collected at times 
specified in Appendix 4, where local regulations allow.
10.3. Statistical Analyses
Statistical analysis of this study will be the responsibility of Lilly or its designee.
Unless otherwise stated, all confidence intervals (CIs) will be reported using a 2-sided 95% level.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the SAP and the clinical study report.  Additional exploratory analyses of the data will be 
conducted as deemed appropriate.
10.3.1. Efficacy Analyses
10.3.1.1. Primary Endpoint
Overall Survival
Overall survival is defined as the time from the date of randomization to the date of death from 
any cause.  For each patient, prior to each data analysis, a reasonable effort will be made to 
obtain the most up-to-date status of the patient (date of death or last date known to be alive).  If 
the patient is alive or lost to follow-up at the time of data analysis, OS data will be censored on 
the last date the patient is known to be alive. For any patient who has withdrawn consent for 

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further follow-up of survival data, OS will be censored at the last date for which the patient 
consented to be followed for the study.
Overall survival will be compared between treatment arms using a stratified log-rank test, 
stratified by the randomization strata.  The corresponding hazard ratio between treatment arms 
will be estimated using a stratified Cox regression model (Cox 1972), stratified by the 
randomization strata. Overall survival curves, the median and survival rates at various time 
points with 95% CI, for each treatment arm will be estimated using the Kaplan-Meier method 
(Kaplan and Meier 1958).  Sensitivity analyses for OS will be described in the SAP.
10.3.1.2. Secondary Endpoints
Progression-Free Survival
Progression-free survival is defined as the time from randomization until the first radiographic 
documentation of progression as defined by RECIST (Version 1.1) or death from any cause in 
the absence of PD.  Patients who die without a reported prior progression will be considered to 
have progressed on the day of their death.  Patients who did not progress or are lost to follow-up 
will be censored at the day of their last radiographic tumor assessment. If no baseline or 
postbaseline radiologic assessment is available, the patient will be censored at the date of 
randomization. If death or PD occurs after 2 or more consecutive missing radiographic visits, 
censoring will occur at the date of the last radiographic visit prior to the missed visits. The use 
of a new anticancer therapy prior to the occurrence of PD will result in censoring at the date of 
last radiographic assessment prior to initiation of new therapy.
Progression-free survival will be compared between treatment arms using a stratified log-rank 
test, stratified by the randomization strata.  The corresponding HR between treatment arms will 
be estimated using a stratified Cox regression model (Cox 1972), stratified by randomization 
strata.  Progression-free survival curves, median PFS, and PFS rates at various time points with 
95% CI for each treatment arm will be estimated using the Kaplan-Meier method (Kaplan and 
Meier 1958).  Sensitivity analyses for PFS will be described in the SAP.
Objective Response Rate
Objective response rate is defined as the number of patients who achieve a best overall response 
of complete response (CR) or partial response (PR) from randomization until PD/recurrence 
divided by the total number of patients randomized to the corresponding treatment arm (ITT 
population).  Patients who do not have a tumor response assessment for any reason will be 
considered non-responders and will be included in the denominator when calculating the 
response rate.  The ORR, with 95% CI, will be summarized for each treatment arm and 
compared between treatment arms using the Cochran-Mantel-Haenszel test adjusting for the 
randomization strata.
Duration of Response
Duration of response is defined as the time from the date measurement criteria for CR or PR
(whichever is first recorded) are first met until the first date that disease is recurrent or objective 

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progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the 
absence of objectively determined disease progression or recurrence.
10.3.2. Safety Analyses
All patients who receive at least 1 dose of any study therapy will be evaluated for safety and 
toxicity.
The MedDRA Version 19.1 or later will be used when reporting AEs by MedDRA terms.  The 
MedDRA Lower Level Term will be used in the treatment-emergent computation.  Treatment-
emergent adverse events will be summarized by System Organ Class (SOC) and by decreasing 
frequency of Preferred Term within SOC.
Phase 2
Safety analyses will include summaries of the following:

AEs, including severity and possible relationship to study drug

SAEs, including possible relationship to study drug

AEs leading to dose adjustments

AESI

IRR

discontinuations from study treatment due to AEs or death

treatment-emergent abnormal changes in laboratory values

treatment-emergent abnormal changes in vital signs and ECGs
10.3.3. Other Analyses
10.3.3.1. Patient Disposition
A detailed description of patient disposition will be provided, including a summary of the 
number and percentage of patients entered into the study, enrolled in the study, and treated as 
well as number and percentage of patients completing the study, as defined in the SAP, or 
discontinuing (overall and by reason for discontinuation).  A summary of all important protocol 
deviations will be provided.
10.3.3.2. Patient Characteristics
Demographic data are collected and reported to demonstrate that the study population represents 
the target patient population considered for regulatory approval.
A summary of baseline patient and disease characteristics, historical diagnoses, preexisting 
conditions, and prior therapies will be reported using descriptive statistics.
10.3.3.3. Concomitant Therapy
A summary of prior and concomitant medications by treatment arm will be reported.

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10.3.3.4. Poststudy-Treatment-Discontinuation Therapy
The numbers and percentages of patients receiving poststudy-treatment-discontinuation 
anticancer therapies will be provided by type of therapy (surgery, radiotherapy, or systemic 
therapy), and by drug class and/or name, overall and by line of therapy.
10.3.3.5. Treatment Compliance
The number of cycles received, dose omissions, dose reductions, dose delays, and dose intensity 
will be summarized for all treated patients by treatment arm.
Study treatment will be administered at the investigator site, therefore treatment compliance is 
assured.
10.3.3.6. Pharmacokinetic Analyses
Pharmacokinetic analyses will be conducted on patients who have received at least 1 dose of the 
study drug and have had sufficient postdose samples collected to allow estimation of PK 
parameters.
In the Phase 1b part, PK parameter estimates will be computed by standard noncompartmental 
methods of analysis for olaratumab.  The maximum concentration (Cmax), time of Cmax (tmax), 
area under the concentration-time curve (AUC), half-life (t1/2), steady-state volume of 
distribution (Vss), clearance (CL), and other relevant parameters that can be calculated from the 
data will be reported from these noncompartmental analyses.
In the Phase 2 part, PK parameters for olaratumab (CL, exposure, Vss, and t1/2) and 
inter-individual PK variability will be computed using nonlinear mixed effect modeling 
implemented in NONMEM.  The version of any software used for the analysis will be 
documented and the program will meet the Lilly requirements of software validation.
If warranted by the data, PK/pharmacodynamic analyses using OS, PFS, and/or other appropriate 
clinical endpoints will also be conducted to characterize the exposure-response relationship in 
this study.
10.3.3.7. Patient Reported Outcomes Analyses - Phase 2 only
Patient-reported outcomes are measured through the following:

mBPI-sf

EORTC QLQ-C30

EQ-5D-5L
For each instrument (mBPI-sf, EORTC QLQ-C30, and EQ-5D-5L), percentage compliance will 
be calculated as the number of completed assessments divided by the number of expected 
assessments (that is, patients still on study and alive).  Percentage compliance and reasons for 
non-compliance will be summarized by treatment arm and time point.
Data will be separately summarized by treatment and time point using descriptive statistics. The 
main efficacy measure for the pain endpoint will be the time to first worsening of the mBPI-sf 
“worst pain” score. Time to first worsening in pain will be described using the method of 

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Kaplan and Meier and analyzes will be made between the 2 arms by a log-rank test.  
“Worsening” will be defined as either a “worst pain” increase of >2 points postbaseline or an 
analgesic drug class increase of >1 level (Farrar et al. 2001; Rowbotham 2001).  However, other 
approaches to defining clinically meaningful worsening in pain might be considered.  Further 
details will be provided in the SAP.
Additionally, time to first worsening of QLQ-C30 scale scores (see Section 9.9.1.2) will be 
analyzed using Kaplan-Meier and Cox methods. Further statistical analysis to be performed for 
PROs will be defined and detailed in the SAP.
The EQ-5D-5L responses may be incorporated into a cost-utility analyses but will not be 
included in the clinical study report. 
10.3.3.8. Biomarker Analyses
The markers in peripheral blood, plasma, serum, and tumor that may indicate 
pharmacodynamics/tailoring effect of olaratumab or the combination partners may be explored 
and characterized by appropriate statistics for the association to clinical outcomes or for the 
characterization by baseline markers.
See Section 9.8 for details regarding biomarker evaluation.
10.3.3.9. Healthcare Resource Utilization
Hospitalizations, transfusions, and concomitant medications during study treatment will be 
summarized descriptively by treatment arm.
Investigators will be asked to document the use of best supportive care measures, concomitant 
medications, transfusions, and treatment-related hospitalization days.  Such assessments are to be 
taken throughout the study through the 30-day short-term postdiscontinuation follow-up visit.
10.3.4. Subgroup Analyses
A prespecified list of subgroups will be identified in the SAP.  The treatment effect within each 
subgroup will be summarized. Other subgroup analyses not specified in the SAP may be 
performed as deemed appropriate.  These subgroups will be based on important characteristics, 
for example, prognostic significance.
10.3.5. Interim Analyses
An interim analysis that includes both safety and efficacy will be conducted.  The analysis will 
occur after at least 70 OS events have been observed among Phase 2 patients.  The interim 
analysis will not be used for purposes of formally testing any efficacy hypotheses.
The results from the interim analyses will be examined by an independent Data Monitoring 
Committee (iDMC). The membership, roles, and responsibilities of the of the iDMC will be 
defined in the SAP or iDMC Charter. The iDMC will review unblinded data. Information that 
may unblind the study during the analyses will not be reported to study sites or blinded study 
team members until the study has been unblinded.

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iDMC safety reviews will be performed for all randomized patients approximately twice per 
year, with the first such review taking place appoximately 6-10 months after the first patient has 
randomized.  Details as to the process and communication plan will be provided in the iDMC 
Charter. 
Unblinding details are specified in the unblinding plan section of the SAP or in a separate 
unblinding plan document.  Further interim analysis may be considered after the last patient has 
been enrolled if deemed appropriate by the Sponsor.

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Appendix 1.
Abbreviations and Definitions
Term
Definition
AE
Adverse event:  any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product and that does not necessarily have a 
causal relationship with this treatment.  An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not related to the medicinal (investigational) product.
α-gal
galactose-α-1-3-galactose
AESI
adverse event of special interest
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the serum concentration time curve
blinding/masking
A procedure in which one or more parties to the trial are kept unaware of the treatment 
assignment.  Unless otherwise specified, blinding will remain in effect until final 
database lock.
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
A double-blind study is one in which neither the patient nor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the patients are 
aware of the treatment received.
BSA
body surface area
CI
confidence interval
Cmax
maximum concentration
CIOMS
Council for International Organizations of Medical Sciences
CL
clearance
CNS
central nervous system
collection database
a computer database where clinical trial data are entered and validated.
CR
complete response
CRP
Clinical research physician:  Individual responsible for the medical conduct of the 
study.  Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician, or other medical officer.

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CT
computed tomography 
CTCAE
Common Terminology Criteria for Adverse Events
DLT
dose-limiting toxicity
DMC
data monitoring committee
DoR
duration of response
ECG
electrocardiogram
ECmin150
half-maximal effective concentration at the end of the first cycle
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
effective method of 
contraception
For all countries except Japan, effective method of contraception means male condom 
with spermicide, female condom with spermicide, diaphragm with spermicide, cervical 
sponge, or cervical cap with spermicide.
For Japan, effective method of contraception means bilateral tubal ligation, male 
condom with spermicide, intrauterine device that has been in place for at least 3 months 
before the first dose of study treatment, or an oral contraceptive pill taken for at least 
3 months before the first dose of study treatment.
Also see the definition of highly effective method of contraception.
Enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the trial are 
those who have been assigned to a treatment.
Enter
Patients entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
EORTC
European Organisation for Research and Treatment of Cancer
ERB
ethical review board
FDA
Food and Drug Administration
GCP
good clinical practice
G-CSF
granulocyte-colony stimulating factor
GF
growth factor
GPS
Global Patient Safety

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highly effective 
method of 
contraception
combined oral contraceptive pill and mini-pill, NuvaRing®, implantable contraceptives, 
injectable contraceptives (such as Depo-Provera®), intrauterine device (such as 
Mirena® and ParaGard®), contraceptive patch for women <90 Kg (<198 pounds), total 
abstinence, or vasectomy
A highly effective method of contraception is defined as one that results in a low failure 
rate (that is, <1% incidence of pregnancy per year) when used consistently and 
correctly, such as contraceptive implants, injectables, combined oral estrogen or 
progestogen-only contraceptives associated with inhibition of ovulation, some 
intrauterine contraceptive devices (IUDs), total abstinence, or a vasectomized partner.
For patients using a hormonal contraceptive method, information regarding the study 
drugs under evaluation and their potential effect on the contraceptive should be 
addressed.
Abstinence as a method of birth control is acceptable if it is the established and 
preferred method of contraception for the patient.
Also see the definition of effective method of contraception.
HR
hazard ratio
IAC
Internal Assessment Committee
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference for Harmonisation
IgE
Immunoglobulin E
IgG1
immunoglobulin G subclass 1
interim analysis
An interim analysis is an analysis of clinical trial data conducted before the final 
reporting database is created/locked.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRR
infusion-related reaction
ITT
intention-to-treat:  The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a patient (that is, the 
planned treatment regimen) rather than the actual treatment given.  It has the 
consequence that patients allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to the 
planned course of treatment.
I.V.
intravenous(ly)
IVRS/IWRS
interactive voice-response system/interactive web-response system

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MedDRA
Medical Dictionary for Regulatory Activities
mBPI-sf
Brief Pain Inventory Short Form Modified
Menopause
include women with either:
(1) spontaneous amenorrhea for at least 12 months, not induced by a medical condition 
such as anorexia nervosa, and not taking medications during the amenorrhea that 
induced the amenorrhea (for example, oral contraceptives, hormones, GnRH, 
antiestrogens, selective estrogen receptor modulators, or chemotherapy), or
(2) spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone level 
>40mIU/mL.
MTD
maximum tolerated dose. MTD is the highest dose of a drug or treatment that does not 
cause unacceptable side effects.
NCI
National Cancer Institute
ORR
objective response rate
OS
overall survival
PD
progressive disease
PDGF
platelet-derived growth factor
PDGFRα
platelet-derived growth factor receptor alpha
PET
positron emission tomography
PFS
progression-free survival
PK
pharmacokinetics
PR
partial response
PRO
patient-reported outcome
PT
prothrombin time
PTT
partial thromboplastin time
Randomize
the process of assigning patients to an experimental group on a random basis
RECIST
Response Evaluation Criteria in Solid Tumors
reporting database
A point-in-time copy of the collection database.  The final reporting database is used to 
produce the analyses and output reports for interim or final analyses of data.
re-screen
to screen a patient who was previously declared a screen failure for the same study
SAE
serious adverse event
SAP
Statistical Analysis Plan

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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 study.
screen failure
Patient who does not meet one or more criteria required for participation in a trial
SD
stable disease
SOC
system organ class
SRC
Safety Review Committee
STS
soft tissue sarcoma
SUSARs
Suspected unexpected serious adverse reactions
t1/2
half-life
TEAE
Treatment-emergent adverse event:   an untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
US
United States
Vss
steady-state volume of distribution

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Appendix 2.
Study Governance, Regulatory, and Ethical 
Considerations
Informed Consent
The investigator is responsible for:

ensuring that the patient understands the potential risks and benefits of participating in 
the study

ensuring that informed consent is given by each patient or, where permitted by local law 
or regulation legal representative.  This includes obtaining the appropriate signatures and 
dates on the ICF prior to the performance of any study procedures and prior to the 
administration of study treatment.

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 trial.
Ethical Review
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).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s).  All ICFs 
must be compliant with the ICH guideline on GCP.
The study site’s ERBs should be provided with the following:

the current IB or package labeling, Patient Information Leaflet, Package Insert, or 
Summary of Product Characteristics and updates during the course of the study

the ICF

relevant curricula vitae
Regulatory Considerations
This study will be conducted in accordance with:

consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 

applicable ICH GCP Guidelines

applicable laws and regulations.
Some obligations of Lilly may be assigned to a third-party organization.
Investigator Information
Physicians with a specialty in Oncology will participate as investigators in this clinical trial.

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Protocol Signatures
Lilly’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.
Final Report Signature
The clinical study report coordinating investigator will sign the final clinical study report for this 
study, indicating agreement that, to the best of his or her knowledge, the report accurately 
describes the conduct and results of the study. 
The investigator with the most enrolled patients will serve as the clinical study report 
coordinating investigator.  If this investigator is unable to fulfill this function, another 
investigator will be chosen by Lilly to serve as the clinical study report coordinating investigator.
The Lilly 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.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

sponsor start-up training to instruct the investigators and study coordinators.  This session 
will give instruction on the protocol, the completion of the CRFs, and study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by mail, 
telephone, and/or fax

review and evaluate CRF data and 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.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide Lilly
applicable regulatory agencies, and applicable ERBs with direct access to original source
documents.

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Data Capture System
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 Lilly provided electronic data capture system.
Case report form data will be encoded and stored in a clinical trial database.  Data managed by a 
central vendor, such as laboratory test data or ECG data, will be stored electronically in the 
central vendor’s database system.  Data will subsequently be transferred from the central vendor 
to the Lilly data warehouse.
Any data for which the paper documentation provided by the patient will serve as the source 
document will be identified and documented by each site in that site’s study file.  Paper 
documentation provided by the patient may include, for example, a paper diary to collect patient-
reported outcome (PRO) measures (for example, a rating scale), a daily dosing schedule, or an 
event diary.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Study and Site Closure
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.

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Appendix 3.
Clinical Laboratory Tests
All laboratory screening evaluations are to be performed within 28 days prior to 
enrollment/randomization, unless otherwise specified.  Eligibility for inclusion in this clinical 
trial will be based on local clinical laboratory results (not transcribed onto eCRFs); duplicate 
samples will be submitted to the central laboratory where indicated below.  For patient and study 
site convenience and safety, treatment decisions may be based upon results of tests performed 
locally.  Discrepancies between local and central laboratory that may have an impact on 
eligibility or treatment decisions will not be considered protocol deviations.  On-study clinical 
laboratory tests assayed for patient safety (such as hematology, serum chemistry, coagulation, 
and pregnancy tests) are to be collected prior to study treatment.

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Clinical Laboratory Tests
Hematologya
Leukocytes (WBC)
Erythrocytes (RBC)
Neutrophils, segmented and band forms
Hemoglobin
Lymphocytes
Hematocrit
Monocytes
Mean corpuscular volume (MCV)
Eosinophils
Mean corpuscular hemoglobin concentration (MCHC)
Basophils
Platelets
Coagulationc
aPTT or PTT
INR or PT
Clinical Chemistrya
Serum Concentrations of:
Alanine aminotransferase (ALT)
Cholesterol
Albumin
Creatine kinase (CK)
Alkaline phosphatase
Creatinine
Aspartate aminotransferase (AST)
Glucose random, nonfasting
Bilirubin, direct
Magnesium
Bilirubin, total
Potassium
Blood urea nitrogen (BUN)
Sodium
Calcium
Uric acid
CA-19.9c,e
Urinalysisc
Blood
Protein
Glucose
Specific gravity
Ketones
Urine leukocyte esterase
pH
Pregnancy Testc
Serum pregnancy test (females only)b
Urine pregnancy test,c,d
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase ; BUN = blood urea nitrogen; 
CA19.9 = cancer antigen 19.9; INR = International normalized ratio; PT = prothrombin time; PTT = partial 
thromboplastin time; RBC = red blood cells; WBC = white blood cells.
a
Tests performed at local laboratories for patient enrollment/management/safety must submit duplicate samples 
for testing at a Lilly-designated laboratory.
b
Serum pregnancy test will be performed at screening on women of childbearing potential.  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 clinical research physician or scientist regarding if dosing should occur and which 
follow-up laboratory tests are performed.
c
Local or investigator-designated laboratory.
d
While on-study, urine pregnancy test will be performed in females 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 urine 
pregnancy test performed on Day 1 of each cycle is positive, confirm with a serum pregnancy test.
e
CA-19.9 will be collected on Day 1 of each cycle.  

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Appendix 4.
Pharmacokinetic, Immunogenicity, and 
Biomarker Research Sampling Schedule
It is essential that the exact infusion start and stop times (actual clock readings) are recorded.  
The exact time of collection of each venous blood sample will be based on the clock used to 
record infusion times.  It is essential that the pharmacokinetic blood samples not be withdrawn 
from the same site as the drug infusion.
For samples collected within the first 24 hours of the respective olaratumab administration, 
sample collection times may vary ± 10% or as specified in the PK sampling schedule.

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Pharmacokinetic, Immunogenicity, and Biomarker Research Sampling Schedule – Phase 
1b (Cohorts 1 and 2)
Cycle
Day
Dosing
Sampling Time
Olaratumab
PKa, c
Plasma for 
Biomarkers
Whole 
Blood for 
PGx e
IGb, c
Screening
0-28
X
1
1
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
≤ 5 min post-olaratumab
X
Observation (1 hr)
60 ± 10 min post-
olaratumab
X
4 ± 0.4 hr post-olaratumab
X
2
24 ± 3 hr post-olaratumab
X
5
Anytime
X
8
Prior to olaratumabd
X
X
Olaratumab (1 hr)
≤ 5 min post-infusion
X
15
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
≤ 5 min post-infusion
X
Observation (1 hr)
60 ± 10 min post-
olaratumab
X
nab-Paclitaxel (0.5 hr)
2 ± 0.25 hr post-nab-
paclitaxel
X
16
24 ± 3 hr post-olaratumab
X
19
Anytime
X
22
Anytime
X
2
1
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
8
Prior to olaratumabd
X
Olaratumab (1 hr)
15
Prior to olaratumabd
X
Olaratumab (1 hr
≤ 5 min post-infusion
X
3
1
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
≤ 5 min post-olaratumab
X
60 ± 10 min post-
olaratumab
X
4 ± 0.4 hr post-olaratumab
X
2
24 ± 3 hr post-olaratumab
X
5
Anytime
X
8
Prior to olaratumabd
X
Olaratumab (1 hr)
≤ 5 min post-olaratumab
X
15
Prior to olaratumabd
X
Olaratumab (1 hr)
≤5 min post-infusion 
X
60 ± 10 min post-
olaratumab
X
4 ± 0.4 hr post-olaratumab
X
16
24 ± 3 hr post-olaratumab
X
17
Anytime
X
19
Anytime
X
4
1
Prior to olaratumabd
X
5 and then 
every other 
cycle
1
Prior to olaratumabd
X
X
30-day 
follow-up 
visit
Anytime
X
X
X

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Abbreviations:  IG = immunogenicity; IRR = infusion-related reaction; PK = pharmacokinetic.
a
Samples of approximately 3 mL of whole blood will be drawn without anticoagulant for measurement of olaratumab in 
serum.
b
For the immunogenicity assay for IgE anti-α-gal antibody screening, approx. 10 mL of whole blood will be drawn.
c
If a patient experiences an IRR to olaratumab/placebo, 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 
(±3 days) after the IRR.
d
Pretreatment samples may be collected any time during the day of the clinical visit, prior to the start of the olaratumab 
infusion and must be taken prior to administering any premedication.

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Pharmacokinetic, Immunogenicity, and Biomarker Research Sampling Schedule – Phase 
2
Cycle
Day
Dosing
Sampling Time
Olaratumab
PKa, c
Plasma for 
Biomarkers
Whole 
Blood for 
PGx e
IGb, c
Screening
0-28 f
X
1
1
Prior to olaratumab/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
8
Prior to olaratumab/placebod
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
15
Prior to olaratumab
dose/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
nab-Paclitaxel (1 hr)
≤5 min. post-nab-paclitaxel
X
2
1
Prior to olaratumab/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
8
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
15
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
3
1
Prior to olaratumab/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
8
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
15
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
4
1
Prior to olaratumab/placebod
X
5 and then every 
other cycle
1
Prior to olaratumab/placebod
X
X
30-day follow-up 
visit
Anytime
X
X
X
Abbreviations:  IG = immunogenicity; IRR = Infusion-related reaction; PK = pharmacokinetic.
a
Samples of approximately 3 mL of whole blood will be drawn without anticoagulant for measurement of olaratumab in 
serum.
b
For the immunogenicity assay for IgE anti-α-gal antibody screening, approx. 10 mL of whole blood will be drawn.
c
If a patient experiences an IRR to olaratumab/placebo, 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 
(±3 days) after the IRR.
d
Pretreatment samples may be collected any time during the day of the clinical visit, prior to the start of the olaratumab 
infusion and must be taken prior to administering any premedication.
e
Sample collected predose Cycle 1 Day 1.
f
For patients who are in screening and have not started treatment during the temporary hold, the screening window will be 
extended an additional 14-days.

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Appendix 5.
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 (HGB)
Hematocrit (HCT)
Hepatic Coagulationa
Erythrocytes (RBC)
Prothrombin time (PT)
Leukocytes (WBC)
Prothrombin time, INR
Neutrophilsb
Lymphocytes
Hepatic Serologiesa,c
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets (PLT)
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
Alanine aminotransferase (ALT)
Recommended Autoimmune Serology:
Aspartate aminotransferase (AST)
Anti-nuclear antibodya
Gamma-glutamyl transferase (GGT)
Anti-smooth muscle antibodya
Creatine phosphokinase (CPK)
Anti actin antibodya
Abbreviations:  CRF = case report form; IgG = immunoglobulin G; IgM = immunoglobulin M; INR = international 
normalized ratio; RBC = red blood cells; WBC = white blood cells.
a
Assayed by Lilly-designated laboratory.
b
Neutrophils reported by automated differential hematology instruments include both segmented and band 
forms. Whenever a manual differential is needed to report the neutrophils, the segmented and band forms should 
be added together and recorded on the CRF, unless the CRF specifically provides an entry field for bands.
c
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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Appendix 6.
Creatinine Clearance Formula
Note:  This formula is to be used for calculating creatinine clearance (CrCl) from local 
laboratory results only.  
For serum creatinine concentration in 
mg/dL:
CrCl =
(mL/min) 
(140 – agea) (wta)    0.85 (if female), or 1.0 (if male)
72 serum creatinine (mg/dL)
For serum creatinine concentration in mol/L:
CrCl  =
(mL/min)
(140 – agea) (wta)  0.85 (if female), or 1.0 (if male)
0.81 serum creatinine (mol/L)
Abbreviations:  CrCl = creatinine clearance; wt = weight.
a
Age in years, weight in kilograms.
Source:  Cockcroft and Gault 1976.

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Appendix 7.
Protocol Amendment I5B-MC-JGDP(e) 
Summary:  A Phase 1b (Open-Label) / Phase 2 
(Randomized, Double-Blinded) Study Evaluating Nab-
Paclitaxel and Gemcitabine With or Without Olaratumab in 
the Treatment of First-Line Metastatic Pancreatic Cancer
Overview
Protocol I5B-MC-JGDP: A Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) 
Study Evaluating Nab-Paclitaxel and Gemcitabine With or Without Olaratumab in the Treatment 
of First-Line Metastatic Pancreatic Cancer) has been amended.  The new protocol is indicated by 
amendment (e) and will be used to conduct the study in place of any preceding version of the 
protocol.
The protocol was amended to include screening criteria for IgE antibodies against α-gal and 
premedication requirements to mitigate the risk for an observed rate of Grade ≥3 IRRs on 
Study JGDP that was greater than the rate of 3.1% previously observed across the olaratumab 
program.
The changes made to this protocol are as follows: 
Key/Clarifying Changes:

Updated an exclusion criterion for patients who have levels of IgE antibodies against 
α-gal greater than the upper limit of normal (Section 6.2).

Removed an exclusion criterion for patients receiving warfarin (Section 6.2).

Updated Premedication Cycle 1 guidelines for olaratumab/placebo to include 
premedication 30-60 minutes prior to dosing and add Histamine H2 antagonist
(Section 7.1.1.1). 

Updated tables for PK, Immunogenicity, and Biomarker Research Sampling Schedule to 
include IgE anti-α-gal antibody screening for Phase 1b and 2 and alter the screening 
window in Phase 2 (Appendix 4).
…

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
Protocol I5B-MC-JGDP(de)
A Phase 1b (Open-Label) / Phase 2 (Randomized, 
Double-Blinded) Study Evaluating Nab-Paclitaxel and 
Gemcitabine With or Without Olaratumab in the Treatment of 
First-Line Metastatic Pancreatic Cancer
5. Study Design
…
5.4.5. Rationale for Amendment (e)
Amendment (e) updates the protocol to include screening criteria for Immunoglobulin E (IgE) 
antibodies against galactose-α-1-3-galactose (α-gal) and premedication requirements to mitigate 
the risk for an observed rate of Grade ≥3 infusion-related reactions (IRRs) on Study JGDP that 
was greater than the rate of 3.1% previously observed across the olaratumab program.  Based on 
data from the Phase 1 and Phase 2 portion of Study JGDP, Grade ≥3 IRRs were observed at an 
approximate rate between 5% and 10% of olaratumab-treated patients.
Infusion related reactions are a known Adverse Drug Reaction for olaratumab, and the rate of 
IRR is 12.5% (all grades) and 3.1% (Grade ≥3).  Grade ≥3 IRR occur within minutes of first 
infusion of olaratumab.  The risk of anaphylactic reaction is associated with elevated IgE 
antibody levels.  Across 8 studies with olaratumab (401 evaluable olaratumab-treated patients), 
IgE antibody levels greater than the manufacturer-specified ULN had a positive predictive value 
of 75% (34.9% - 96.8%) and a negative predictive value of 99% (98.2% - 99.9%) for Grade ≥3 
IRRs, with sensitivity of 75% (34.9% - 96.8%) and specificity of 99% (98.2% - 99.9%).  Two 
patients had Grade ≥3 IRR with an IgE antibody level ≤ ULN (0.28 kU/L and <0.10 kU/L, 
respectively).  Prior to this amendment, patients in Study JGDP were tested for pre-existing IgE 
antibody against α-gal as pre-planned retrospective analysis.  However, the results of these tests 
were not available prior to first dosing of olaratumab/placebo.  Pre-testing for elevated IgE 
antibody levels against -gal for all untreated patients as part of screening is being implemented 
as a risk mitigation strategy.
This amendment implements actions to mitigate the risk of increased Grade ≥3 IRRs observed in 
Study JGDP.  Specifically, screening in the Phase 2 portion of the study was modified to include 
immuniogenicity testing, and the inclusion/exclusion criteria were updated to clarify that patients 

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with IgE anti-α-gal antibody levels greater than the upper limit of normal will be excluded from 
this study.  In addition, the required premedication regimen prior to Cycle 1 Day 1 of 
olaratumab/placebo was clarified to include:  dexamethasone (or steroid equivalent); a histamine 
H1 antagonistist (for example, diphenhydramine); and a histamine H2 antagonist (for example, 
ranitidine).  
6. Study Population
…
6.2. Exclusion Criteria
…
[25] have known allergy to nab-paclitaxel, gemcitabine, or olaratumab (levels of 
IgE antibodies against α-gal that are above the upper limit of normal) or any 
ingredient of olaratumab, nab-paclitaxel, or gemcitabine formulations.
[30] are currently receiving warfarin and are unable to be switched to low 
molecular weight heparin or oral Factor II or Xa inhibitor with half-life less 
than 24 hours and achieve stable coagulation prior to first dose of study 
treatment.
…
7. Treatments
…
7.1. Treatments Administered
…
7.1.1. Premedication
…
7.1.1.1. Olaratumab/Placebo
Infusion-related reactions (IRRs), including Grade ≥3 events, have been observed with 
olaratumab.  To date, all Grade ≥3 IRR events have occurred during the first olaratumab 
infusion, most of them within 30 minutes from the start of infusion. Symptoms of IRRs have 
included flushing, shortness of breath, bronchospasm, fever/chills, and in severe cases have 
manifested as severe hypotension, anaphylactic shock, or cardiac arrest. 
The following premedications need to be administered prior to olaratumab/placebo infusions in 
Study JGDP. Additional premedication may be provided at the investigator’s discretion.

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
Premedication in Cycle 1:
Premedication is mandatory for all patients during Cycle 1 prior to each dose of 
olaratumab/placebo. Premedicate all patients with the following (or equivalent)
medications 30-60 minutes prior to olaratumab/placebo dosing on Days 1, 8, and 15 of 
Cycle 1:
o
Histamine H1 antagonist (for example, diphenhydramine)
o
Dexamethasone intravenously
o
Histamine H2 antagonist (for example, ranitidine)

Premedication in Cycles 2-n:
For subsequent cycles, premedication with a histamine H1 antagonist (for example, 
diphenhydramine) is recommended prior to each dose of olaratumab/placebo.
…

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7.4.4. Dosing Discontinuation
…
7.4.4.3. Olaratumab
…
7.4.4.3.1. Olaratumab Infusion-Related Reactions
Olaratumab should be immediately and permanently discontinued for Grade 3 or 4 IRR.  For 
olaratumab IRR treatment guidelines see Table JGDP.7. 
Due the observed rate of Grade ≥3 IRRs in the Phase 1 and Phase 2 portions of Study JGDP that 
was greater than the rate of 3.1% previously observed across the olaratumab program, testing for 
IgE anti-α-gal antibodies must be performed as part of screening, and patient with antibody 
levels >ULN should be excluded.
…
Appendix 1. Abbreviations and Definitions
…
α-gal
galactose-α-1-3-galactose
…
IgE
Immunoglobulin E
…
Appendix 4. Pharmacokinetic, Immunogenicity, and 
Biomarker Research Sampling Schedule
…

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Pharmacokinetic, Immunogenicity, and Biomarker Research Sampling Schedule – Phase 
1b (Cohorts 1 and 2)
Cycle
Day
Dosing
Sampling Time
Olaratumab
PKa, c
Plasma for 
Biomarkers
Whole 
Blood for 
PGx e
IGb, c
Screening
0-28
X
1
1
Prior to olaratumabd
X
X
X
X
Olaratumab (1 hr)
≤ 5 min post-olaratumab
X
Observation (1 hr)
60 ± 10 min post-
olaratumab
X
4 ± 0.4 hr post-olaratumab
X
2
24 ± 3 hr post-olaratumab
X
5
Anytime
X
8
Prior to olaratumabd
X
X
Olaratumab (1 hr)
≤ 5 min post-infusion
X
15
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
≤ 5 min post-infusion
X
Observation (1 hr)
60 ± 10 min post-
olaratumab
X
nab-Paclitaxel (0.5 hr)
2 ± 0.25 hr post-nab-
paclitaxel
X
16
24 ± 3 hr post-olaratumab
X
19
Anytime
X
22
Anytime
X
2
1
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
8
Prior to olaratumabd
X
Olaratumab (1 hr)
15
Prior to olaratumabd
X
Olaratumab (1 hr
≤ 5 min post-infusion
X
3
1
Prior to olaratumabd
X
X
X
Olaratumab (1 hr)
≤ 5 min post-olaratumab
X
60 ± 10 min post-
olaratumab
X
4 ± 0.4 hr post-olaratumab
X
2
24 ± 3 hr post-olaratumab
X
5
Anytime
X
8
Prior to olaratumabd
X
Olaratumab (1 hr)
≤ 5 min post-olaratumab
X
15
Prior to olaratumabd
X
Olaratumab (1 hr)
≤5 min post-infusion 
X
60 ± 10 min post-
olaratumab
X
4 ± 0.4 hr post-olaratumab
X
16
24 ± 3 hr post-olaratumab
X
17
Anytime
X
19
Anytime
X
4
1
Prior to olaratumabd
X
5 and then every 
other cycle
1
Prior to olaratumabd
X
X
30-day follow-up 
visit
Anytime
X
X
X
Abbreviations:  IG = immunogenicity; IRR = infusion-related reaction; PK = pharmacokinetic.
a
Samples of approximately 3 mL of whole blood will be drawn without anticoagulant for measurement of olaratumab in 
serum.

I5B-MC-JGDP(e) Clinical Protocol
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b
For the immunogenicity assay for IgE anti-α-gal antibody screening, approx. 10 mL of whole blood will be drawn.
c
If a patient experiences an IRR to olaratumab/placebo, 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 
(±3 days) after the IRR.
d
Pretreatment samples may be collected any time during the day of the clinical visit, prior to the start of the olaratumab 
infusion and must be taken prior to administering any premedication.
…

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Pharmacokinetic, Immunogenicity, and Biomarker Research Sampling Schedule – Phase 
2
Cycle
Day
Dosing
Sampling Time
Olaratumab
PKa, c
Plasma for 
Biomarkers
Whole 
Blood for 
PGx e
IGb, c
Screening
0-28 f
X
1
1
Prior to olaratumab/placebod
X
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
8
Prior to olaratumab/placebod
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
15
Prior to olaratumab
dose/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
nab-Paclitaxel (1 hr)
≤5 min. post-nab-paclitaxel
X
2
1
Prior to olaratumab/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
8
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
15
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
3
1
Prior to olaratumab/placebod
X
X
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
8
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
15
Prior to olaratumab/placebod
X
Olaratumab (1 hr)
≤5 min post-
olaratumab/placebo
X
4
1
Prior to olaratumab/placebod
X
5 and then every 
other cycle
1
Prior to olaratumab/placebod
X
X
30-day follow-up 
visit
Anytime
X
X
X
Abbreviations:  IG = immunogenicity; IRR = Infusion-related reaction; PK = pharmacokinetic.
a
Samples of approximately 3 mL of whole blood will be drawn without anticoagulant for measurement of olaratumab in 
serum.
b
For the immunogenicity assay for IgE anti-α-gal antibody screening, approx. 10 mL of whole blood will be drawn.
c
If a patient experiences an IRR to olaratumab/placebo, 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 
(±3 days) after the IRR.
d
Pretreatment samples may be collected any time during the day of the clinical visit, prior to the start of the olaratumab 
infusion and must be taken prior to administering any premedication.
e
Sample collected predose Cycle 1 Day 1.
f
For patients who are in screening and have not started treatment during the temporary hold, the screening window will be 
extended an additional 14-days.

Leo Document ID = 95b4c6d4-4d79-47e4-8835-85112b52e612
Approver: 
Approval Date & Time: 20-Mar-2019 13:57:21 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 20-Mar-2019 15:49:52 GMT
Signature meaning: Approved
PPD
PPD