Clinical trial NCT02357147
Conditions: Mesothelioma, Malignant
Keywords: Amatuximab Pemetrexed Cisplatin Unresectable Malignant Pleural Mesothelioma ARTEMIS
Sponsor: Morphotek
Start date: 2015-11-03; Completion date: 2018-11-30
Enrollment: 124 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study was originally designed as a multicenter, double-blind, randomized, parallel-group study, using a placebo control or amatuximab 5 milligrams per kilogram (mg/kg), administered weekly, designed to evaluate the safety and efficacy of amatuximab in combination with pemetrexed and cisplatin in participants with unresectable Malignant Pleural Mesothelioma (MPM) who have not received prior systemic therapy.

Per a business decision made by the Sponsor, participants who were randomized to amatuximab and were still on active treatment at the time of the protocol amendment may have consented to continue to receive weekly treatment with amatuximab until disease progression or intolerable toxicity at the discretion of the principal investigator. Participants randomized to placebo or who were in follow-up at the time of the amendment have been discontinued from the study.

Detailed description:

Arms: arm 1: Combination Phase - Amatuximab + Pemetrexed and Cisplatin

Maintenance Phase - Amatuximab arm 2: Combination Phase - Placebo + Pemetrexed and Cisplatin

Maintenance Phase - Placebo
Interventions: intervention 1: Placebo intervention 2: Amatuximab intervention 3: Pemetrexed intervention 4: Cisplatin
Intervention descriptions: intervention 1: Combination Phase - Placebo will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

Maintenance Phase - Placebo will be administered IV (intravenous infusion) once weekly until disease progression. intervention 2: Combination Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

Maintenance Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly until disease progression. intervention 3: Combination Phase - Pemetrexed 500 mg/m\^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles. intervention 4: Combination Phase - Cisplatin 75 mg/m\^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.

Protocol documents:
Prot_000.pdf: 
Clinical Study Protocol
Incorporating Amendment 02
MORAb-009-201
Morphotek, Inc.
FINAL: 30Jan2017  
Confidential
Page 1 of 65
1
TITLE PAGE
Clinical Study Protocol
Study Protocol 
Number:
MORAb-009-201
Study Protocol 
Title:
A Randomized, Double-blind, Placebo-controlled Study of the Safety 
and Efficacy of Amatuximab in Combination with Pemetrexed and 
Cisplatin in Subjects with Unresectable Malignant Pleural 
Mesothelioma
Sponsor:
Morphotek, Inc.
210 Welsh Pool Road
Exton, PA 19341
US
Eisai Co., Ltd. 
4-6-10 Koishikawa
Bunkyo-Ku, 
Tokyo 112 8088
Japan
Investigational 
Product Name:
MORAb-009 (amatuximab)
Indication:
Malignant pleural mesothelioma
Phase:
2
Approval Date:
v1.0
11 Dec 2014 (original protocol)
v2.0
v3.0
24 Apr 2015 (Amendment 01)
30 Jan 2017 (Amendment 02)
IND Number:
12894
EudraCT Number:
2014-004489-85
GCP Statement:
This study is to be performed in full compliance with International 
Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH) and all 
applicable local Good Clinical Practice (GCP) and regulations.  All 
required study documentation will be archived as required by 
regulatory authorities.
Confidentiality 
Statement:
This document is confidential.  It contains proprietary information of 
Morphotek, Inc. (the sponsor).  Any viewing or disclosure of such 
information that is not authorized in writing by the sponsor is strictly 
prohibited.  Such information may be used solely for the purpose of 
reviewing or performing this study.


Clinical Study Protocol
Incorporating Amendment 02
MORAb-009-201
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REVISION HISTORY
Revisions to Version 3.0 (per Amendment 02)
Date:  30 Jan 2017 
Change
Rationale
Affected Protocol 
Sections
A business decision was made to 
discontinue further enrollment in the 
study and significantly amend the 
protocol to discontinue all ongoing study 
procedures and conduct, but provide a 
mechanism for patients already 
randomized to the amatuximab (MORAb-
009) arm to continue to receive ongoing 
study treatment until discontinuation for 
disease progression or tolerability issues.  
Per the amendment, only core information 
necessary for safety monitoring and 
reporting will be collected.  No efficacy 
data will be reported.  Subjects who were 
randomized to placebo and all subjects in 
follow-up have been discontinued from 
the study.  
Significant delays in initiating the 
program, which led to a significant 
shift in the timing of the primary and 
final analyses.  As a result, the original 
rationale for the study is now 
compromised by the introduction of 
newer treatment regimens (eg, 
bevacizumab) and the rapid clinical 
development of several investigational 
agents (eg, immune checkpoint 
inhibitors), such that the program no 
longer aligns with the developing 
standard of care.  No new safety or 
efficacy data were generated during the 
conduct of this trial to date to inform 
this business decision.
Throughout


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Incorporating Amendment 02
MORAb-009-201
Morphotek, Inc.
FINAL: 30Jan2017  
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2
CLINICAL PROTOCOL SYNOPSIS
Compound No.:  Amatuximab (MORAb-009)
Name of Active Ingredient:  amatuximab
Study Protocol Title  
A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Amatuximab in 
Combination with Pemetrexed and Cisplatin in Subjects with Unresectable Malignant Pleural 
Mesothelioma
Investigators
List of investigators to be maintained separately by the sponsor
Sites
List of investigational sites to be maintained separately by the sponsor
Study Period and Phase of Development
Phase 2
Objectives
The primary objective of this amendment is to provide ongoing amatuximab treatment access 
consistent with the primary 009-201 treatment schedule to those trial subjects randomized to the
amatuximab arm who, at the discretion of their investigator, may obtain ongoing clinical benefit.  
The secondary objective of this amendment is to monitor safety of ongoing subjects through the 
collection of serious adverse event information.


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Incorporating Amendment 02
MORAb-009-201
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FINAL: 30Jan2017  
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Study Design
The primary 009-201 study was designed as a multicenter, double-blind, randomized, parallel-group 
study, using a placebo control or amatuximab 5 mg/kg, administered weekly, designed to evaluate the 
safety and efficacy of amatuximab in combination with pemetrexed and cisplatin in subjects with 
unresectable MPM who have not received prior systemic therapy.  Subjects were randomized in a 1:1 
ratio using interactive response technology (IRT).  Subjects were stratified by Performance Status 
(ECOG 0 or 1).  
Subjects who qualified were randomized and entered the Combination Treatment Phase to receive 
Test Article (amatuximab or placebo) on Day 1 of each week, and chemotherapy (pemetrexed and 
cisplatin) on Day 1 of each 21-day cycle, for 6 cycles of treatment.  Following completion of the 
Combination Treatment Phase (ie, after a subject has received at least 4 cycles of Combination 
Treatment), subjects who had not progressed entered the Maintenance Treatment Phase where they 
continued to receive the Test Article on a weekly basis until disease progression.  All subjects were to 
be followed for survival (ie, Follow-up Phase).  
An Independent Data Monitoring Committee (IDMC) performed safety assessments as determined by 
the committee up until the time of this amendment.  No new safety concerns were noted.  
Eisai made a business decision to discontinue any further enrollment in the study as of 11Jan2017 and 
to significantly amend the trial protocol. Per this amendment: 

Subjects who were randomized to amatuximab and are still on active treatment may consent
to continue to receive weekly treatment with amatuximab until disease progression or 
intolerable toxicity at the discretion of the principal investigator (PI).

Subjects randomized to placebo or who were in follow-up have been discontinued from the 
study.

Clinical management and ongoing assessments of subjects will continue per standard of care 
as determined by the PI.

Only serious adverse event (SAE) and subject discontinuation data will be collected by the 
Sponsor.  

Subjects will not be followed for efficacy.      
Number of Subjects
At the time enrollment was closed, 108 subjects were randomized.  The study has been unblinded and
27 total subjects randomized to amatuximab would be eligible to remain in the study for continued
treatment based on investigator discretion and the subject consent.  
Inclusion Criteria
All subjects were enrolled in the study under the inclusion criteria outlined in the previous protocol 
amendment dated 24 Apr 2015.  The following criteria apply to this amendment:
1.
Subjects who were enrolled in the study and randomized to the amatuximab treatment arm 
may, at the discretion of the PI, consent to continue to receive amatuximab therapy until 
disease progression, intolerable toxicity, or withdraw of consent.
2.
Subjects of childbearing potential must be surgically sterile or consent to use a highly 
effective method of contraception throughout the study period. All females will be 
considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at 
least 12 consecutive months, in the appropriate age group, and without other known or 
suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total 
hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). If 


Clinical Study Protocol
Incorporating Amendment 02
MORAb-009-201
Morphotek, Inc.
FINAL: 30Jan2017  
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a patient of childbearing potential is neither surgically sterile nor postmenopausal, highly 
effective contraceptive measures must start either prior to or at Screening and continue 
throughout the entire study period and for at least 6 months after the last dose of 
chemotherapy and at least 30 days after the last dose of amatuximab is administered 
(whichever is later). A highly effective method of contraception is defined as one that results 
in a low failure rate (ie, less than 1% per year) when used consistently and 
correctly. Periodic abstinence, the rhythm method, the withdrawal method, condoms, and 
diaphragms are not acceptable methods of contraception. Women of childbearing potential 
must also refrain from egg cell donation for 6 months after the final dose of investigational 
product.
3.
Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and 
their female partners must meet the criteria above (ie, not of childbearing potential or 
practicing highly effective contraception throughout the study period and for 6 months after 
discontinuation of chemotherapy and for 5 weeks after amatuximab discontinuation 
[whichever is later]). No sperm donation is allowed during the study period and for 90 days 
after amatuximab discontinuation.
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from continuing in this study:
1.
Subjects previously randomized to placebo
2.
Subjects who have not signed the updated informed consent form associated with this 
amendment
3.
Subjects who have radiographic or clinical disease progression or intolerable toxicity such 
that ongoing amatuximab treatment through this study is not appropriate
Study Treatments
Amatuximab 5 mg/kg by intravenous (IV) infusion once weekly. In addition, subjects receive 
pemetrexed 500 mg/m2 followed by cisplatin 75 mg/m2 by IV infusion on Day 1 of each 21-day cycle 
for 6 cycles during the Combination Treatment Phase.
Duration of Treatment
The maximum duration of participation for individual subjects continuing treatment is expected to be 
approximately 6-12 months.  Subjects will no longer be followed for efficacy.  Continuing subjects 
may discontinue for intolerable toxicity of the study drugs, disease progression, or may withdraw 
consent for any other reason at any time without prejudice.
Concomitant Drug/Therapy
In order to prevent hypersensitivity AEs, subjects must be premedicated approximately 30 to 
60 minutes prior to each infusion of amatuximab with acetaminophen 650 mg by mouth and 
diphenhydramine 25 mg to 50 mg by mouth or IV, or the local equivalents. Subjects will also receive 
prophylactic treatment for pemetrexed with folic acid, vitamin B12, and dexamethasone at each cycle 
of Combination Treatment according to the investigational site’s standard practice.  
Assessments
Efficacy Assessments:
No formal analysis of efficacy will be performed.  
Safety Assessments:


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Per this amendment, subjects will continue to receive physical exams, clinical laboratory tests and 
other medical assessments at the discretion of the PI per standard of care practice.  Data from these 
assessments, including any AEs, will be documented in the subject’s medical records but no longer be 
collected by the Sponsor with the exception of SAEs and treatment discontinuation information.
SAE reporting must still meet standard expedited reporting requirements as outlined in this 
amendment.
Pharmacokinetic Assessments:
Samples collected to date may be analyzed.  Per this amendment no additional samples will be 
collected. 
Pharmacodynamic Assessments:
Not applicable
Pharmacogenomic Assessments:
Samples collected to date may be stored and analyzed per the terms of the original informed consent 
form signed by each subject.  Per this amendment no additional samples will be collected. 
Biomarker Assessments: 
Samples collected to date may be stored and analyzed per the terms of the original informed consent 
form signed by each subject.  Per this amendment no additional samples will be collected. 
Bioanalytical Methods
Serum Amatuximab Assay:
Samples collected to date may be analyzed as previously described and results will be summarized in 
a final report.  Per this amendment no additional samples will be collected.  
Amatuximab ADA Analysis:
Samples collected to date may be stored and analyzed per the terms of the original informed consent 
form signed by each subject.  Per this amendment no additional samples will be collected.  
Biomarker Analyses:
Samples collected to date may be stored and analyzed per the terms of the original informed consent 
form signed by each subject. Per this amendment, no additional samples will be collected.
Statistical Methods
No formal efficacy analyses are planned.  All data collected prior to database lock including safety 
data will be summarized and listed as appropriate in an abbreviated final study report. 
Interim Analysis
An interim analysis for futility will not be performed.
Sample Size 
At the time enrollment was stopped 108 subjects were randomized.  Twenty-seven subjects 
randomized to amatuximab were eligible to remain in the study for continued treatment based on 
investigator discretion and the subject consent.


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3
TABLE OF CONTENTS
1
TITLE PAGE.....................................................................................................................1
REVISION HISTORY...............................................................................................................2
2
CLINICAL PROTOCOL SYNOPSIS...............................................................................3
3
TABLE OF CONTENTS...................................................................................................7
4
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS..................................11
5
ETHICS............................................................................................................................13
5.1
Institutional Review Boards/Independent Ethics Committees ..............................13
5.2
Ethical Conduct of the Study.................................................................................13
5.3
Subject Information and Informed Consent...........................................................14
6
INVESTIGATORS AND STUDY PERSONNEL..........................................................15
7
INTRODUCTION ...........................................................................................................15
7.1
Indication ...............................................................................................................15
7.1.1
Current Therapeutic Options........................................................................15
7.1.2
MORAb-009 (Amatuximab)........................................................................16
7.1.2.1
Mechanism of Action...........................................................................16
7.1.2.2
Clinical Experience With Amatuximab...............................................16
7.1.2.2.1
Phase 1 Clinical Studies.................................................................16
7.1.2.2.2
Phase 2 Clinical Studies.................................................................19
7.1.2.3
Common Serious Adverse Events Expected to Occur in the Study 
Population Even in the Absence of Amatuximab and Study Drug 
Exposure ..............................................................................................23
7.2
Study Rationale......................................................................................................23
8
STUDY OBJECTIVES....................................................................................................23
8.1
Primary Objective..................................................................................................23
8.2
Secondary Objectives.............................................................................................24
9
INVESTIGATIONAL PLAN..........................................................................................24
9.1
Overall Study Design and Plan..............................................................................24
9.1.1
Screening Phase ...........................................................................................24
9.1.2
Randomization/Combination Treatment Phase ...........................................24
9.1.2.1
Test Article Administration (Amatuximab) Only Visits .....................25
9.1.3
Maintenance Treatment Phase.....................................................................25
9.1.4
End of Treatment Visit.................................................................................25
9.1.5
Follow-Up Phase..........................................................................................25
9.1.6
End of Study ................................................................................................25
9.2
Selection of Study Population................................................................................25


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9.2.1
Inclusion Criteria .........................................................................................25
9.2.2
Exclusion Criteria ........................................................................................26
9.2.3
Removal of Subjects From Therapy or Assessment....................................26
9.3
Treatments..............................................................................................................27
9.3.1
Treatments Administered.............................................................................27
9.3.2
Identity of Investigational and Noninvestigational Products.......................28
9.3.2.1
Amatuximab.........................................................................................28
9.3.2.2
Pemetrexed...........................................................................................29
9.3.2.3
Cisplatin...............................................................................................29
9.3.2.4
Chemical Name, Structural Formula of Investigational Product.........29
9.3.2.5
Labeling for Investigational Product ...................................................29
9.3.2.6
Storage Conditions...............................................................................29
9.3.3
Method of Assigning Subjects to Treatment Groups...................................30
9.3.4
Selection of Doses in the Study...................................................................30
9.3.5
Selection and Timing of Dose for Each Subject..........................................30
9.3.6
Blinding........................................................................................................30
9.3.7
Concomitant Therapy...................................................................................30
9.3.7.1
Premedications.....................................................................................31
9.3.7.1.1
Premedications for Amatuximab ...................................................31
9.3.7.1.2
Premedications for Pemetrexed .....................................................32
9.3.7.2
Drug-Drug Interactions........................................................................32
9.3.7.3
Prohibited Concomitant Therapies and Drugs.....................................32
9.3.8
Treatment Compliance.................................................................................32
9.3.9
Drug Supplies and Accountability...............................................................33
9.4
Study Assessments.................................................................................................34
9.4.1
Assessments.................................................................................................34
9.4.1.1
Screening Assessments ........................................................................34
9.4.1.2
Efficacy Assessments...........................................................................34
9.4.1.2.1
Follow-Up for Survival..................................................................34
9.4.1.2.2
Computed Tomography Scan or Magnetic Resonance Imaging ...34
9.4.1.2.3
Quality of Life Assessment (LCSS-Meso) ....................................34
9.4.1.2.4
Performance Status (DPSM)..........................................................34
9.4.1.3
Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, and 
Other Biomarker Assessments.............................................................34
9.4.1.3.1
Pharmacokinetic Assessments .......................................................34
9.4.1.3.2
Pharmacodynamic, Pharmacogenomic, and Other Biomarker, 
Assessments...................................................................................34


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9.4.1.4
Safety Assessments..............................................................................35
9.4.1.4.1
Adverse Events and Other Events of Interest ................................35
9.4.1.4.2
Serious Adverse Events and Other Events of Interest ...................37
9.4.1.4.3
Adverse Events of Interest.............................................................38
9.4.1.4.4
Laboratory Measurements .............................................................39
9.4.1.4.5
Vital Signs and Weight Measurements..........................................40
9.4.1.4.6
Physical Examinations...................................................................40
9.4.1.4.7
Electrocardiograms ........................................................................40
9.4.2
Schedule of Procedures/Assessments ..........................................................40
9.4.2.1
Schedule of Procedures/Assessments ..................................................40
9.4.2.2
Description of Procedures/Assessments Schedule...............................43
9.4.3
Reporting of Serious Adverse Events, Pregnancy, and Other Events of 
Interest..........................................................................................................43
9.4.3.1
Reporting of Serious Adverse Events..................................................43
9.4.3.2
Reporting of Pregnancy and Exposure to Study Drug Through 
Breastfeeding .......................................................................................44
9.4.3.3
Reporting of Other Events of Interest..................................................44
9.4.3.3.1
Reporting of Adverse Events Associated With Study Drug 
Overdose, Misuse, Abuse, or Medication Error ............................44
9.4.3.4
Expedited Reporting ............................................................................45
9.4.3.5
Breaking the Blind...............................................................................45
9.4.3.6
Regulatory Reporting of Adverse Events ............................................45
9.4.4
Completion/Discontinuation of Subjects from Study (EOS).......................45
9.4.5
Abuse or Diversion of Study Drug ..............................................................45
9.4.6
Confirmation of Medical Care by Another Physician .................................46
9.5
Data Quality Assurance .........................................................................................46
9.5.1
Data Collection ............................................................................................46
9.5.2
Clinical Data Management ..........................................................................47
9.6
Statistical Methods.................................................................................................47
9.6.1
Statistical and Analytical Plans....................................................................47
9.6.1.1
Safety Analyses....................................................................................47
9.6.2
Determination of Sample Size .....................................................................47
9.6.3
Interim Analysis for Futility ........................................................................47
9.6.3.1
Independent Data Monitoring Committee ...........................................47
9.6.3.2
Interim Analysis for Futility Assessments...........................................47
9.6.4
Other Statistical/Analytical Issues ...............................................................48
10
REFERENCE LIST .........................................................................................................49


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11
PROCEDURES AND INSTRUCTIONS (ADMINISTRATIVE PROCEDURES).......51
11.1
Changes to the Protocol .........................................................................................51
11.2
Adherence to the Protocol......................................................................................51
11.3
Monitoring Procedures...........................................................................................52
11.4
Recording of Data..................................................................................................53
11.5
Identification of Source Data.................................................................................53
11.6
Retention of Records..............................................................................................53
11.7
Auditing Procedures and Inspection......................................................................54
11.8
Handling of Amatuximab ......................................................................................54
11.9
Publication of Results ............................................................................................55
11.10 Disclosure and Confidentiality ..............................................................................55
11.11 Discontinuation of Study .......................................................................................55
11.12 Subject Insurance and Indemnity...........................................................................56
12
APPENDICES .................................................................................................................57
LIST OF IN-TEXT TABLES
Table 1
Treatments Administered...........................................................................28
Table 2
Formulation of Amatuximab......................................................................28
Table 3
Schedule of Procedures/Assessments in Study MORAb-009-201............41
LIST OF APPENDICES
Appendix 1
National Cancer Institute Common Terminology Criteria for 
Hypersensitivity Adverse Events...............................................................58
Appendix 2
Medical Dictionary for Regulatory Activities (MedDRA) Preferred 
Terms and Codes for Interstitial Lung Diseases Standardized 
MedDRA Query.........................................................................................63


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4
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Term
ADA
anti-drug antibody
ADL
activities of daily living
AE
adverse event
AEI
adverse event of interest
ASCO
American Society of Clinical Oncology
β-hCG
beta-human chorionic gonadotropin
BSA
body surface area
CA
Competent Authority
CA125
cancer antigen 125
CFR
Code of Federal Regulations
Cmin
minimum observed concentration
CR
complete response
CRA
clinical research associate
CRO
contract research organization
CT
computed tomography
DCR
disease control rate
DHAE
drug hypersensitivity adverse event
DPSM
duration of performance status maintenance
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EOS
end of study
EOT
end of treatment
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GPI
glycosylphosphatidylinositol
ICF
informed consent form
ICH
International Conference on Harmonisation 
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IgG1/κ
immunoglobulin G subtype 1-kappa
Investigational product
amatuximab (MORAb-009)
IRB
Institutional Review Board


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Abbreviation
Term
IV
intravenous
IRT
Interactive Response Technology
LCSS-Meso
Lung Cancer Symptom Scale for mesothelioma
MedDRA
Medical Dictionary for Regulatory Activities
MORAb-009
amatuximab, the monoclonal antibody to be tested in this 
protocol
MPM
malignant pleural mesothelioma
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
NCI CTCAE
National Cancer Institute Common Terminology Criteria for 
Adverse Events
NSAID
nonsteroidal antiinflammatory drug
NSCLC
non-small cell lung cancer
ORR
objective response rate
OS
overall survival
PD
progressive disease
PI
principal investigator
PFS
progression-free survival
PK
pharmacokinetic(s)
PR
partial response
QOL
quality of life
RECIST
Response Evaluation Criteria in Solid Tumors
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
stable disease
SOC
system organ class
SOP
standard operating procedure
SPECT
single photon emission-computerized tomography
SUSAR
suspected unexpected serious adverse response
TEAE
treatment-emergent adverse event
TMF
Trial Master File
TRAE
treatment-related adverse event
US
United States 


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5
ETHICS
5.1
Institutional Review Boards/Independent Ethics Committees
The protocol, informed consent form (ICF), and appropriate related documents must be 
reviewed and approved by an Institutional Review Board (IRB) or Independent Ethics 
Committee (IEC) constituted and functioning in accordance with International Conference on 
Harmonisation (ICH) E6 (Good Clinical Practice), Section 3, and any local regulations (eg, 
Federal Regulations, Title 21 CFR Part 56, for United States [US] studies).  Any protocol 
amendment or revision to the ICF will be resubmitted to the IRB/IEC for review and 
approval, except for changes involving only logistical or administrative aspects of the study 
(eg, change in Clinical Research Associate[s] [CRAs], change of telephone number[s]).  
Documentation of IRB/IEC compliance with the ICH E6 and any local regulations regarding 
constitution and review conduct will be provided to the sponsor.
Documentation of study approval from the IRB/IEC chairman must be sent to the principal 
investigator (PI) with a copy to the sponsor before study start and the release of any Test 
Article to the site by the sponsor or its designee (ICH E6, Section 4.4).  If the IRB/IEC 
decides to suspend or terminate the study, the investigator will immediately send the notice 
of study suspension or termination by the IRB/IEC to the sponsor.
Study progress is to be reported to IRB/IECs annually (or as required) by the investigator or 
sponsor, depending on local regulatory obligations.  If the investigator is required to report to 
the IRB/IEC, he/she will forward a copy to the sponsor at the time of each periodic report.  
The investigator(s) or the sponsor will submit, depending on local regulations, periodic 
reports and inform the IRB/IEC of any reportable adverse events (AEs) per ICH guidelines 
and local IRB/IEC standards of practice.  Upon completion of the study, the investigator will 
provide the IRB/IEC with a brief report of the outcome of the study, if required.
At the end of the study, the sponsor should notify the IRB/IEC and Competent Authority 
(CA) within 90 days.  The end of the study will be the time of data cutoff for the final 
analysis.  It is estimated that the study will end in December, 2017.
In the case of early termination/temporary halt of the study, the investigator should notify the 
IRB/IEC and CA within 15 calendar days, and a detailed written explanation of the reasons 
for the termination/halt should be given.
5.2
Ethical Conduct of the Study
This study will be conducted in accordance with standard operating procedures of the 
sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice 
(GCP) guidelines as required by the following:

Principles of the World Medical Association Declaration of Helsinki (2013)


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
ICH E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the 
Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, 
International Conference on Harmonisation of Pharmaceuticals for Human Use

Title 21 of the US Code of Federal Regulations (US 21 CFR) regarding clinical studies, 
including Part 50 and Part 56 concerning informed subject consent and IRB regulations 
and applicable sections of US 21 CFR Part 312

European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 
2001/20/EC for studies conducted within any European Union (EU) country.  All 
suspected unexpected serious adverse responses (SUSARs) will be reported, as required, 
to the Competent Authorities of all involved EU member states.

Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law 
No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP.

Other applicable regulatory authorities requirements or directives
5.3
Subject Information and Informed Consent
As part of administering the informed consent document, the investigator must explain to 
each subject the nature of the study, its purpose, the procedures involved, the expected 
duration, the potential risks and benefits involved, any potential discomfort, potential 
alternative procedure(s) or course(s) of treatment available to the subject, and the extent of 
maintaining confidentiality of the subject’s records.  Each subject must be informed that 
participation in the study is voluntary, that he/she may withdraw from the study at any time, 
and that withdrawal of consent will not affect his/her subsequent medical treatment or 
relationship with the treating physician.
This informed consent should be given by means of a standard written statement, written in 
nontechnical language.  The subject should understand the statement before signing and 
dating it and will be given a copy of the signed document.  If a subject is unable to read, an 
impartial witness should be present during the entire informed consent discussion.  
Certified translated ICFs will be provided by the sponsor in those languages required or 
requested by investigational sites.
After the ICF and any other written information to be provided to subjects is read and 
explained to the subject, and after the subject has orally consented to participation in the 
study and, if capable of doing so, has signed and personally dated the ICF, the witness should 
sign and personally date the consent form.  The subject will be asked to sign an ICF during
Screening before any study-specific procedures are performed.  No subject can enter the 
study before his/her informed consent has been obtained.
An unsigned copy of an IRB/IEC-approved ICF must be prepared in accordance with 
ICH E6, Section 4, and all applicable local regulations. The basic elements of informed 
consent as specified in the ethical conduct provisions of US 21 CFR 50.25 (2011) and 
ICH E6 (2002) will be followed.  Each subject must sign an approved ICF before study 
participation.  The form must be signed and dated by the appropriate parties.  The original, 


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signed ICF for each subject will be verified by the sponsor and kept on file according to local 
procedures at the site.  
The subject should be informed in a timely manner if new information becomes available 
that may be relevant to the subject’s willingness to continue participation in the study.  The 
communication of this information should be documented.
6
INVESTIGATORS AND STUDY PERSONNEL
This amendment will be implemented by qualified investigators under the sponsorship of 
Morphotek, Inc. (the sponsor) at approximately 20 investigational sites globally.
The name and telephone and fax numbers of the medical monitor and other contact personnel 
at the sponsor and of the contract research organization (CRO) are listed on the Study 
Contact Sheet within the investigational site regulatory file provided to each site.
7
INTRODUCTION
Amatuximab (also known as MORAb-009) is a high-affinity monoclonal IgG1/κ antibody 
raised against human mesothelin.  Mesothelin is a glycosylphosphatidylinositol-linked 
cytoplasmic membrane glycoprotein which is present in a restricted set of normal adult 
tissues, such as the mesothelium (Ordonez, 2003A).  Immunohistochemistry has shown that 
mesothelin is overexpressed in virtually all mesotheliomas and pancreatic ductal 
adenocarcinomas and in a high percentage of epithelial ovarian cancers and non-small cell 
lung cancers (NSCLCs) (Ordonez, 2003B).  Although the normal biological function of 
mesothelin is unknown, growing evidence suggests that it may play a role in tumorogenesis 
and metastasis (Kelly, et al., 2012).  Its limited expression in normal human tissue and high 
expression in tumor makes mesothelin an excellent target antigen for antibody-based 
immunotherapy (Kelly, et al., 2012). 
7.1
Indication
The indication under study is malignant pleural mesothelioma (MPM). 
7.1.1
Current Therapeutic Options
MPM is an aggressive disease with poor prognosis.  Although patients with a limited tumor 
burden may benefit from surgical resection, most patients have advanced disease at diagnosis 
and are not candidates for cytoreductive surgery (Sugarbaker, et al., 1996).  For patients who 
are not eligible for curative surgery, the median survival with supportive care alone is 
6 months whereas with the current standard treatment, a combination of cisplatin and 
pemetrexed, the median survival is 12 months (Vogelzang, et al, 2003) and this has not been 
improved upon by the addition of other investigational agents (eg, CBP501; Krug, et al.,
2014).  Various investigational agents are currently in clinical development for mesothelioma 
including immune checkpoint inhibitors.


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7.1.2
MORAb-009 (Amatuximab) 
7.1.2.1
Mechanism of Action
Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein which 
is present in a restricted set of normal adult tissues, such as the mesothelium (Ordonez, 
2003A).  Immunohistochemistry has shown that mesothelin is overexpressed in virtually all 
mesotheliomas and pancreatic ductal adenocarcinomas and in a high percentage of epithelial 
ovarian cancers and NSCLCs (Ordonez, 2003B).  Although the normal biological function of 
mesothelin is unknown, growing evidence suggests that it may play a role in tumorogenesis 
and metastasis (Kelly, et al., 2012).  Its limited expression in normal human tissue and high 
expression in tumor makes mesothelin an excellent target antigen for antibody-based 
immunotherapy (Kelly, et al., 2012).
Amatuximab is a high-affinity monoclonal IgG1/κ antibody raised against human 
mesothelin.  Data from various in vitro and in vivo studies (Hassan, et al., 2007) indicate that 
amatuximab may have potential efficacy for the treatment of tumors which overexpress 
mesothelin.  These data demonstrated the highly specific binding of amatuximab to target 
malignancies in vitro in immunohistochemistry staining studies.  They also showed the 
biological activity of amatuximab on inhibiting mesothelin-bearing cell binding to the 
mesothelin ligand.  Next, data demonstrated the capability of amatuximab to elicit an 
antibody-dependent cell-mediated cytotoxic response in vitro on mesothelin-bearing human 
tumor cells.  In addition, it has been shown that amatuximab had positive in vivo data in a 
rodent xenograft model of mesothelin-overexpressing human cancer cells.
Results from these preclinical studies, nonhuman primate toxicology studies, and early-phase 
clinical studies indicate that amatuximab is a potentially useful anticancer agent 
(MORAb-009 Investigator’s Brochure, 2014).  Please refer to the Investigator’s Brochure for 
additional information on the safety of amatuximab.
7.1.2.2
Clinical Experience With Amatuximab
As of January 2017, a total of 262 subjects have been exposed to amatuximab in Phase 1 or 2 
studies.  The clinical studies are summarized in the amatuximab Investigator’s Brochure 
(MORAb-009 Investigator Brochure, 2014).  No new safety or efficacy data was obtained 
from the current study 009-201 that was relevant to the Sponsor’s determination to 
discontinue active enrollment.
7.1.2.2.1
PHASE 1 CLINICAL STUDIES
MORAb-009-001
This was a Phase 1, multiple-dose, open-label, dose-escalation cohort study conducted in 
subjects with advanced pancreatic adenocarcinoma, mesothelioma, mesothelin-expressing 
ovarian tumors, or NSCLC who had failed standard chemotherapy (Hassan, et al., 2010).  A 
total of 24 subjects with advanced mesothelin-expressing tumors received doses of 


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12.5 mg/m2 (n = 3), 25 mg/m2 (n = 3), 50 mg/m2 (n = 3), 100 mg/m2 (n = 6), 200 mg/m2
(n = 3), or 400 mg/m2 (n = 6) of amatuximab, administered as IV infusions.  Subjects 
received 4 weekly infusions on Days 1, 8, 15, and 22.  After a 35-day treatment and 
observation period, subjects who had stable or improving disease by objective criteria could 
continue on treatment until disease progression occurred.
Of the 24 subjects, 13 had advanced mesothelioma, 7 had pancreatic cancer, and 4 had 
ovarian cancer.  The median number of amatuximab infusions was 4 (range 1 to 
24 infusions).  Twenty subjects had tumor response assessments recorded. Of these, 
11 subjects had stable disease (SD) recorded as their best overall tumor response, and 
9 subjects had progressive disease (PD) recorded as their best overall response.
Of the 24 subjects who received amatuximab, 22 subjects (91.7%) reported a total of 
120 treatment-emergent adverse events (TEAEs).  The maximum tolerated dose (MTD) was 
determined to be 200 mg/m2.  At the 400-mg/m2 dose level, 2 subjects experienced 
dose-limiting toxicities (Grade 4 transaminitis and Grade 3 serum sickness).  
Hypersensitivity AEs occurred in 7 of the 24 subjects.  All hypersensitivity AEs were 
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 
v.3.0 (2006) Grade 1 or Grade 2, with the exception of Grade 3 serum sickness in 1 subject.  
Thus, although other contributing causes of these AEs were present, 200 mg/m2 was 
considered the maximum tolerated dose.  Seven subjects had SD and received additional 
cycles of therapy, including 1 subject with previously progressive metastatic pancreatic 
cancer who received 6 additional cycles of amatuximab and demonstrated SD for over 
6 months.
The results of this Phase 1 clinical trial in subjects with mesothelin-expressing advanced 
solid tumors demonstrated that amatuximab had an acceptable safety profile in these 
subjects, with a low incidence of immunogenicity.  The single-agent maximum tolerated dose 
with weekly administration was 200 mg/m2.  Amatuximab serum concentrations increased in 
a dose-dependent fashion.  While no objective responses were seen, disease stabilization was 
observed in several heavily pretreated subjects. 
MORAb-009-006
This was a single-center, single-dose, open-label, pilot study of amatuximab, conducted in 
adult subjects with mesothelin over-expressing tumors to determine the biodistribution of 
111Indium (111In)-labeled amatuximab in tumor and nontumor tissues in subjects with 
advanced mesothelin over-expressing cancers (pancreatic, mesothelioma, ovarian, or 
NSCLC).  Subjects were required to have measurable disease that had progressed through 
prior therapy and that included a nonhepatic lesion for imaging that was ≥1.5 cm, as defined 
by modified Response Evaluation Criteria in Solid Tumors. Subjects received an initial 50-
mg “cold” (ie, nonradiolabeled) dose of amatuximab followed by a single “hot” dose of 111In-
radiolabeled amatuximab (5 mCi) administered IV over 15 minutes.  (Initially, unlabeled 
amatuximab [total dose 50 mg] was administered 0.5 to 6 hours prior to the radiolabeled test 
article to saturate any nonspecific binding and shed antigen.  This unlabeled infusion was 
discontinued with the protocol amendment dated 12 Jul 2012; Data on file).


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Serial single photon emission-computerized tomography (SPECT) imaging was performed at 
2 to 4 hours, 24 to 48 hours, and 96 to 168 hours after the hot infusion to determine binding 
to tumor and nontumor tissue.  
Six subjects (4 males; 2 females) were enrolled in the study (Data on file).  Four subjects 
were diagnosed with mesothelioma and 2 with pancreatic adenocarcinoma.  Five subjects 
received both an initial 50-mg “cold” (ie, nonradiolabeled) dose of amatuximab and a single 
“hot” dose of 111In-radiolabeled amatuximab; 1 subject enrolled after the protocol 
amendment of 12 Jul 2012 and received only the “hot” dose of amatuximab.  All 6 enrolled 
subjects completed the study.
Of the 6 subjects who received amatuximab, 1 subject experienced 4 AEs: nausea, shoulder 
pain, and 2 events of pyrexia.
111In-radiolabeled amatuximab was shown to be effective in producing sufficient Tumor: 
Background ratio activity in mesothelioma and pancreatic cancer tumors with a favorable 
dosimetry profile.  Higher uptake was seen in the mesotheliomas as compared with the 
pancreatic cancers.
MORAb-009-J081-102
This was a multiple-dose, open-labeled Phase 1 study (MORAb-009-J081-102) in Japan to 
assess the safety of amatuximab at doses of 50, 100, and 200 mg/m2 in subjects with solid 
tumors (Data on file).  Amatuximab was administered over 4-week cycles, with infusions 
once weekly on Days 1, 8, 15, and 22.  From Cycle 2 onward, amatuximab administration 
was allowed to be continued at the same dosing regimen unless subjects met the 
discontinuation criteria.
A total of 17 subjects entered the study and received at least 1 dose of amatuximab; 
7 subjects each in the 50 and 200 mg/m2 groups and 3 subjects in the 100 mg/m2 group.  A 
total of 17 subjects were enrolled, 12 males and 5 females.  The median age was 62.0 years 
(range: 56 to 79 years) (Data on file).  The tumor types reported at Screening (primary 
disease at first diagnosis) were colorectal cancer (7 subjects, 41.2%), pancreatic 
adenocarcinoma (6 subjects, 35.3%), head and neck cancer and mesothelioma (2 subjects 
each, 11.8%).
Of the 17 subjects who received amatuximab, 15 subjects (88.2%) experienced TEAEs, and 
13 subjects (76.5%) experienced TEAEs that were considered related to administration of 
Test Article.  TEAEs of Grade 3 or 4 were reported in 9 subjects (52.9%).  There were no 
apparent dose-related trends in frequency or severity of TEAEs.  The most frequently 
reported TEAEs in the total group (N = 17) were fatigue (8 subjects; 47.1%); pyrexia 
(7 subjects; 41.2%); aspartate aminotransferase increased and decreased appetite (6 subjects 
each; 35.3%); vomiting and somnolence (5 subjects each; 29.4%); and nausea, blood lactate 
dehydrogenase increased, and weight decreased (4 subjects each; 23.5%).  The most 
frequently reported treatment-related adverse events (TRAEs) in the total group (N = 17) 
were fatigue (5 subjects; 29.4%) and pyrexia (4 subjects; 23.5%).


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One subject in the 200 mg/m2 group experienced Grade 5 interstitial lung disease, and 
1 subject in the 50 mg/m2 group experienced Grade 4 blood bilirubin increased.  The most 
frequently reported TEAEs of Grade 3 or higher in the total group (N = 17) were 
hyperglycemia and hyponatremia (2 subjects each; 11.8%).  TRAEs with Grade 3 or higher 
were interstitial lung disease (1 subject; 5.9%, Grade 5) and cytokine release syndrome 
(1 subject; 5.9%, Grade 3).
There were no apparent dose-related trends in frequency or severity of TEAEs for the whole 
treatment period.
Eight subjects (47.1%) experienced a total of 14 treatment-emergent serious adverse events 
(SAEs) in this study, and SAEs in 3 subjects (3 events) were considered to be related to study 
drug.  The most frequently reported SAEs were jaundice and cytokine release syndrome 
(2 subjects each; 11.8%).
Five subjects (29.4%) experienced adverse events of interest (AEIs) classified by the 
investigators during the study.  The most frequently reported AEIs were cytokine release 
syndrome (3 subjects; 17.6%), and pyrexia and hot flush (2 subjects each; 11.8%).
Dose-limiting toxicities were reported in 2 subjects; 1 subject in the 50 mg/m2 group 
experienced Grade 3 cytokine release syndrome, and 1 subject at 200 mg/m2 experienced 
Grade 5 interstitial lung disease.  
During the study, anti-drug antibodies (ADA) were detected in 8 of 17 subjects.  During 
treatment, ADA were detected in 4 of 4 subjects without premedication and in 4 of 13
subjects with premedication.
Based on the criteria as defined in the protocol, tolerability of amatuximab at 50, 100, and 
200 mg/m2 was confirmed.  The MTD of this study was determined to be 200 mg/m2. 
However, the actual MTD of amatuximab might be higher than 200 mg/m2, since a dose 
above 200 mg/m2 was not investigated in this study. 
7.1.2.2.2
PHASE 2 CLINICAL STUDIES
MORAb-009-002
MORAb-009-002 was a randomized, placebo-controlled, double-blind Phase 2 study.  
Eligible subjects were randomized to receive amatuximab 5 mg/kg plus gemcitabine 
1000 mg/m2 once weekly or placebo plus gemcitabine 1000 mg/m2 once weekly (Data on 
file).  Cycle 1 was 8 weeks in duration, with treatment administration on Day 1 of Weeks 1 
through 7; no study medication was administered in Week 8.  Cycle 2 and all subsequent 
cycles were 4-week cycles with study drug administration on Day 1 of Weeks 1 through 3; 
no study medication was administered on Week 4.  A total of 155 subjects were randomized 
to the study (77 to amatuximab and 78 to placebo); 148 subjects (73 on amatuximab, 
75 on placebo) received at least 1 dose of study medication.


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Based on the results of the primary analysis, amatuximab was not statistically superior to 
placebo in overall survival (OS).  The 2 treatment groups were comparable with respect to 
key secondary endpoints of objective response rate (ORR) and progression-free survival 
(PFS).  
The safety profiles of the 2 regimens were similar.  All 73 subjects who received amatuximab 
experienced at least 1 AE.  A greater percentage of subjects in both the amatuximab 
(94.5%) treatment group and the placebo (89.3%) treatment group had AEs considered 
related to chemotherapy administration compared with AEs considered related to 
amatuximab (67.1%) or placebo (60.0%) administration.  This was also true for Grade 3 or 
higher AEs.  A total of 21 (28.8%) subjects receiving amatuximab and 17 (22.7%) subjects 
receiving placebo experienced AEs resulting in discontinuation of study medication.  A total 
of 25 (34.2%) subjects receiving amatuximab experienced hypersensitivity AEs during the 
study compared with 16 subjects receiving placebo (21.3%).  A hypersensitivity AE for 
1 subject receiving amatuximab was classified as a possibly-related SAE, and 1 subject 
receiving placebo had a hypersensitivity AE that was classified as an unrelated SAE.  All 
other hypersensitivity AEs were Grade 2 or less in severity.  As hypersensitivity AEs are 
expected with administration of a chimeric monoclonal antibody, the hypersensitivity AEs in 
this study were anticipated.  SAEs of thrombocytopenia, neutropenia, and anemia were 
primarily considered related to gemcitabine administration.  The addition of amatuximab did 
not negatively affect these laboratory values (Data on file). 
A preliminary exposure-response analysis was conducted on this study which revealed that, 
across all subjects (placebo and amatuximab), amatuximab exposure was not a significant 
predictor of either PFS or OS.
These data, plus the preliminary data from the 2 subjects with pancreatic cancer in the 111In-
radiolabeled amatuximab study, may help explain the lack of difference in the results of 
adding amatuximab to gemcitabine as compared to placebo plus gemcitabine.
MORAb-009-003
MORAb-009-003 was an open-label, Phase 2 study adding amatuximab, 5 mg/kg
administered on Days 1 and 8, to the combination of pemetrexed, 500 mg/m2, and cisplatin, 
75 mg/m2, administered on Day 1 of 21-day cycles for up to 6 cycles in the treatment of 
systemic-therapy-naïve subjects with unresectable MPM (Data on file).  For those subjects 
who completed at least 4 cycles of the Combination Therapy and had not progressed, they 
were allowed to enroll in the single-agent Maintenance Therapy phase. Eighty-nine subjects 
were enrolled. The median age of the subjects was 67 years; 77.5% were male, and 88% had 
stage III/IV disease.  The median number of amatuximab plus pemetrexed and cisplatin 
cycles administered to these subjects was 5 (range 1-7); single-agent amatuximab was 
administered to 56 (62.9%) subjects.  The Kaplan-Meier estimate of 6 month PFS was 59.3% 
(95% CI: 47.1, 69.6) which did not meet the primary efficacy objective for this study. The 
median PFS was 6.3 months (95% CI: 6.0, 7.8).


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Although the median PFS was not significantly different from the historical results of 
pemetrexed and cisplatin alone, the median OS in this study was 14.8 months (95% CI: 12.4, 
18.8), which is 6 to 8 weeks longer than expected from the historical results of 
pemetrexed/cisplatin.  There were no complete responses (CR).  Twenty-nine subjects 
(34.5%) had partial responses (PR) (ORR: 34.5% [95% CI: 24.5, 45.7]) and 47 subjects 
(56%) had stable disease as the best response. The disease control rate (DCR) was 90.5%.  
As of the end of study, 05 Dec 2013, 11 subjects were still living.
Among the most common AEs seen in ≥ 15% of subjects during the Combination Therapy 
phase were nausea (71%), fatigue (58%), anorexia (45%), vomiting (32%), constipation 
(32%), anemia (29%), neutropenia (29%), diarrhea (28%), and weight decrease (19%). 
Hypersensitivity reactions (12%) as well as infusion related reactions (8%) were also seen.  
The SAEs during the Combination Therapy phase were hypersensitivity reactions 
(4 subjects), neutropenia (4 subjects), atrial fibrillation (4 subjects), hyponatremia 
(3 subjects), anemia (3 subjects), dehydration (2 subjects), fatigue (2 subjects), noncardiac 
chest pain (2 subjects), pyrexia (2 subjects), and pneumothorax (2 subjects). AEs which led 
to discontinuation of treatment were: hypersensitivity reactions to amatuximab (8 subjects), 
increasing serum creatinine (6 subjects), fatigue (3 subjects), neutropenia (2 subjects), 
worsening in the subjects’ general condition (2 subjects), nausea and vomiting (2 subjects), 
development of a pneumothorax (2 subjects), and 1 subject each for anemia, 
thrombocytopenia, dyspnea, pericarditis and pericardial effusion.  
During the amatuximab Maintenance Therapy phase, the most common AEs (seen in more 
than 15% of subjects) were dyspnea (32%), nausea (25%), noncardiac chest pain (23%), 
fatigue (20%), and peripheral neuropathy (18%).  SAEs seen during the Maintenance 
Therapy phase were dyspnea (4 subjects) and fatigue (1 subject). AEs which led to 
discontinuation of treatment were hyperbilirubinemia (1 subject), peritonitis (1 subject), and 
cardiopulmonary arrest (1 subject). The latter was reported in a 58-year old 
 who 
suffered a cardiac arrest related to cocaine use, 1 week after the first dose of maintenance 
amatuximab, from which 
 was successfully resuscitated. 
AEIs for this study were defined as: Cytokine Release Syndrome; Flushing; Fever; 
Rigors/chills; Sweating/diaphoresis; Pruritus/itching; Urticaria; Bronchospasm/wheezing; 
and Bronchial edema. In addition, Drug Hypersensitivity Adverse Events (DHAE) were 
defined as the subset of programmatically-identified AEIs that have serologic evidence of an 
immunologic response to amatuximab (ie, positive human anti-drug antibody [ADA] which 
are defined as a treatment-induced or treatment-boosted ADA). The determination of DHAE 
status for each of the programmatically-identified AEIs described above was dependent on 
serum ADA sample results obtained on or subsequent to the onset date of the AEI. There 
could be multiple subsequent ADA samples. If the serum ADA results are positive for at 
least 1 of these samples, the AEI was considered a DHAE.
A total of 54 DHAEs in 25 (28.1%) subjects receiving amatuximab/pemetrexed/cisplatin 
combination therapy and 19 DHAEs in 7 (12.5%) subjects receiving single-agent 
maintenance were reported.  In the subjects receiving combination therapy, the most common 
PPD
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DHAEs were chills (9 subjects, 10.1%), hypersensitivity (9 subjects, 10.1%), and 
infusion-related reaction (6 subjects, 6.7%).  In the subjects receiving single-agent 
maintenance therapy, the most common DHAEs were chills (3 subjects, 5.4%), dyspnea 
(2 subjects, 3.6%) and infusion-related reaction (2 subjects, 3.6%). Seven (7.9%) DHAEs 
resulted in subject discontinuation from amatuximab.  The majority of DHAEs occurred after 
infusion 3 (25 events in 15 subjects) or infusion 4 (24 events in 17 subjects).  None were 
reported beyond infusion 20.
Population Pharmacokinetics
Results of the population pharmacokinetics (PK) study of amatuximab (Gupta, et al., 2014; 
MORAb-009 Investigator’s Brochure, 2014) were as follows:

The PK of amatuximab following IV infusion was adequately described by a 
2 compartment model with parallel linear and nonlinear elimination over the dose range 
of 12.5 to 400 mg/m2

Body weight was identified to affect volume of distribution of the central compartment

The presence of human ADA, as defined by the presence of ADA at a titer of greater than 
64, was found to increase linear clearance which would result in lower concentrations of 
amatuximab

Median serum concentration time profile of amatuximab indicates that after 5 weeks of 
continuous weekly dosing 89% of steady-state concentration is achieved

After taking into account the effect of weight, age (33 – 90 years), race (Japanese vs. 
non-Japanese), and gender did not influence amatuximab PK

Baseline albumin (2.38 – 5.46 g/dL) did not influence amatuximab PK
Preliminary Pharmacokinetic/Pharmacodynamic Analyses of Amatuximab Efficacy in 
MORAb-009-003
Results of the Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Analyses 
of Amatuximab Efficacy study (Gupta, et al., 2014; MORAb-009 Investigator’s Brochure, 
2014) were as follows:

Amatuximab minimum observed serum concentrations (Cmin) were a significant predictor 
of both PFS and OS where higher concentrations were associated with longer PFS and 
OS.  Subjects achieving Cmin concentrations above median had a median PFS and OS of 
238 and 583 days, respectively.  

Based on the multivariate parametric survival model, amatuximab exposure was a 
significant predictor of OS in the presence of an effect of baseline Karnofsky 
Performance Status score and tumor type

Results of the PK simulations showed that 5 mg/kg of amatuximab, administered weekly, 
will achieve median Cmin concentration of 83.1 μg/mL, and approximately 80% of 
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
Weekly administration of amatuximab, 5 mg/kg, would lead to higher Cmin
concentrations which may lead to a statistically significant and clinically meaningful 
benefit in OS, as well as PFS, versus the standard therapy of pemetrexed plus cisplatin in 
subjects with unresectable MPM
7.1.2.3
Common Serious Adverse Events Expected to Occur in the Study Population 
Even in the Absence of Amatuximab and Study Drug Exposure
The following symptoms and signs are expected to occur commonly in this study population, 
and may result in a SAE:  noncardiac chest pain, cough, dyspnea, pleural effusion and 
pneumothorax (NCCN, 2013).
The following AEs have been commonly seen with the use of pemetrexed in combination 
with cisplatin: vomiting, neutropenia, leukopenia, anemia, stomatitis/pharyngitis, 
thrombocytopenia and constipation (Alimta, 2013).
7.2
Study Rationale
On 11Jan2017, Eisai notified study investigators that the decision was made to discontinue 
further enrollment in the study and significantly amend the protocol to discontinue all 
ongoing study procedures and conduct, but provide a mechanism for patients already 
randomized to the amatuximab (MORAb-009) arm to continue to receive ongoing study 
treatment until discontinuation for disease progression or tolerability issues.  Per the 
amendment, only core information necessary for safety monitoring and reporting will be 
collected.  No efficacy data will be reported.  Subjects who were randomized to placebo and 
all subjects in follow-up have been discontinued from the study.  
The principal factor driving this business decision was significant delays in initiating the 
program, which led to a significant shift in the timing of the primary and final analyses.  As a 
result, the original rationale for the study is now compromised by the introduction of newer 
treatment regimens (eg, bevacizumab) and the rapid clinical development of several 
investigational agents (eg, immune checkpoint inhibitors), such that the program no longer 
aligns with the developing standard of care.  
It is important to note that there have been no new safety issues identified during the conduct 
of this study to date that are driving this decision.  There is also no new efficacy data that 
informed this decision.
8
STUDY OBJECTIVES
8.1
Primary Objective
The primary objective of this amendment is to provide ongoing amatuximab treatment access 
consistent with the primary 009-201 treatment schedule to those trial subjects randomized to 
the amatuximab arm who, at the discretion of their investigator, may obtain ongoing clinical 
benefit. 


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8.2
Secondary Objectives
The secondary objective of this amendment is to monitor safety of ongoing subjects through
the collection of SAEs.
9
INVESTIGATIONAL PLAN
9.1
Overall Study Design and Plan
The primary 009-201 study was designed as a multicenter, double-blind, randomized, 
placebo-controlled study designed to demonstrate the safety and efficacy of amatuximab in 
subjects with unresectable MPM who have not received prior systemic therapy.  Subjects 
were randomly assigned to receive weekly administration of either amatuximab, 5 mg/kg, or 
placebo in combination with pemetrexed, 500 mg/m2, and cisplatin, 75 mg/m2, on Day 1 of 
each 21-day cycle for 6 cycles followed by single-agent test article maintenance until disease 
progression.  All subjects were to be followed for OS.   
On 11Jan2017 Eisai notified investigators of a business decision to discontinue any further 
enrollment in the study and significantly amend the protocol as described previously.
Per this amendment, subjects enrolled in the study who were randomized to amatuximab and 
are still on active treatment may consent to continue to receive amatuximab at the discretion 
of the PI until disease progression, intolerable toxicity, or withdrawal of consent.
Clinical management and ongoing assessments of subjects will continue per standard of care 
as determined by the PI.  Only serious adverse event and subject discontinuation data will be 
collected by the Sponsor.  Subjects will not be followed for efficacy.  Subjects randomized to 
placebo and all subjects in follow-up have been discontinued from the study.     
At the time enrollment was closed 108 subjects were randomized, 27 to the amatuximab 
treatment arm.  
9.1.1
Screening Phase
The screening phase of the study is complete.
9.1.2
Randomization/Combination Treatment Phase
Subjects who were eligible for this study were randomized in a 1:1 ratio to receive blinded 
treatment with either amatuximab or placebo (ie, Test Article).  All enrolled subjects were 
also assigned to receive the standard-of-care treatments pemetrexed and cisplatin (ie, Study 
Drugs) for six cycles.  Per this amendment, only those active subjects randomized to 
amatuximab are continuing.


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If the subject develops unacceptable toxicity to Study Drugs (pemetrexed or cisplatin) and 
has completed at least 4 cycles (but no more than 6 cycles) during the Combination 
Treatment phase, the subject is eligible to continue on to the Maintenance Treatment Phase 
(see below).
9.1.2.1
Test Article Administration (Amatuximab) Only Visits
Test Article administration only visits will be performed when the Study Drugs (pemetrexed 
and cisplatin) are delayed. For specific details on Test Article administration only visits,
please see the Schedule of Procedures/Assessments.
9.1.3
Maintenance Treatment Phase
Subjects who have not progressed following completion of Combination Treatment will enter 
the Maintenance Treatment Phase where they will continue to receive amatuximab on a 
weekly basis until disease progression.  For specific details on the Maintenance Treatment 
Phase, refer to the Schedule of Procedures/Assessments.
9.1.4
End of Treatment Visit
Upon discontinuation of treatment for documented disease progression or any other reason, 
assessments for the End of Treatment Visit should be performed.  These assessments will be 
conducted (where possible) within 7 days of the last dose of amatuximab.  For specific 
details on the End of Treatment Visit, refer to the Schedule of Procedures/Assessments.
9.1.5
Follow-Up Phase
Following discontinuation of treatment subjects will have a 30-day follow-up visit for 
assessment of adverse events. All adverse event information must be documented in the 
subject’s medical record (source data).  Only SAEs need to be reported to the Sponsor.  
9.1.6
End of Study
The 30-day follow-up visit will also constitute the End of Study visit.  
9.2
Selection of Study Population
9.2.1
Inclusion Criteria
All subjects were enrolled under the inclusion criteria outlined in protocol version 2.0, dated 
24 Apr 2015. The following criteria apply to this amendment:
1. Subjects who were enrolled in the study and randomized to the amatuximab treatment 
arm may, at the discretion of the PI, consent to continue to receive amatuximab 
therapy until disease progression, intolerable toxicity, or withdraw of consent.


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2. Subjects of childbearing potential must be surgically sterile or consent to use a highly 
effective method of contraception throughout the study period. All females will be 
considered to be of childbearing potential unless they are postmenopausal 
(amenorrheic for at least 12 consecutive months, in the appropriate age group, and 
without other known or suspected cause) or have been sterilized surgically (ie, 
bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery
at least 1 month before dosing). If a patient of childbearing potential is neither 
surgically sterile nor postmenopausal, highly effective contraceptive measures must 
start either prior to or at Screening and continue throughout the entire study period 
and for at least 6 months after the last dose of chemotherapy and at least 30 days after 
the last dose of amatuximab is administered (whichever is later). A highly effective 
method of contraception is defined as one that results in a low failure rate (ie, less 
than 1% per year) when used consistently and correctly. Periodic abstinence, the 
rhythm method, the withdrawal method, condoms, and diaphragms are not acceptable 
methods of contraception. Women of childbearing potential must also refrain from 
egg cell donation for 6 months after the final dose of investigational product.
3. Male subjects must have had a successful vasectomy (confirmed azoospermia) or 
they and their female partners must meet the criteria above (ie, not of childbearing 
potential or practicing highly effective contraception throughout the study period and 
for 6 months after discontinuation of chemotherapy and for 5 weeks after amatuximab 
discontinuation [whichever is later]). No sperm donation is allowed during the study 
period and for 90 days after amatuximab discontinuation.
9.2.2
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from continuing in this 
study:
1. Subjects previously randomized to placebo
2. Subjects who have not signed the updated informed consent form associated with this 
amendment
3. Subjects who have radiographic or clinical disease progression, or intolerable toxicity 
such that ongoing amatuximab treatment through this study is not appropriate
9.2.3
Removal of Subjects From Therapy or Assessment
The investigator will discontinue a subject’s study treatment (chemotherapies and/or 
amatuximab) or withdraw the subject from the study if any of the following circumstances 
occur at any time during the subject’s study participation: 

The subject’s continued participation, in the investigator’s judgment, would be 
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
The subject withdraws consent for continued participation or refuses further treatment 
with the study agent(s)

The subject experiences an intolerable toxicity not ameliorable by symptomatic treatment 
or dose schedule modification 

The subject has objective evidence of disease progression or symptomatic deterioration 
(ie, global deterioration of health status)

The subject experiences development or exacerbation of a recurrent illness or other 
factors that results in a delay of the next scheduled treatment by 21 days or more

The subject experiences a hypersensitivity AE of NCI CTCAE v4.03 (2010) Grade 3 that 
cannot be medically managed to a level of Grade 2 (see Section 9.4.1.4.3 and 
Appendix 1)

The subject experiences a hypersensitivity reaction of Grade 4 (see Section 9.4.1.4.3 and 
Appendix 1)

The subject receives other anticancer therapy (eg, chemotherapy or radiotherapy; 
however, local radiotherapy of noncurative intent is allowed) during the Combination 
Treatment or Maintenance Treatment phases

The subject becomes pregnant
If a subject withdraws consent, the date will be documented in the source documents.  The 
End of Treatment and End of Study procedures will be completed and the primary reason for 
discontinuation from treatment will be documented in the source records and reported to the 
Sponsor.  
9.3
Treatments
Subjects continuing in the study will receive the experimental drug amatuximab.  “Study 
Drug” refers to any drug(s) or formulations under evaluation in the study, including the Test 
Article, active controls, and placebo.  The Study Drugs in this study are amatuximab, 
pemetrexed, and cisplatin.
9.3.1
Treatments Administered
All subjects will receive Combination Treatment for six 21-day cycles.  Amatuximab 5mg/kg 
will be administered IV once weekly.  The Study Drugs, pemetrexed 500 mg/m2 and cisplatin 
75 mg/m2, will be administered on Day 1 of each 21-day Combination Treatment cycle for 6 
cycles.  On Day 1 of each cycle, amatuximab will be administered prior to pemetrexed, 
which will be administered prior to cisplatin. 
Subjects who have completed a minimum of 4 cycles of Combination Treatment and who 
have not progressed will enter the Maintenance Treatment Phase where they will continue to 
receive amatuximab on a weekly basis until radiographic disease progression occurs.
Always premedicate subjects to prevent hypersensitivity AEs.  Subjects must be 
premedicated approximately 30 to 60 minutes prior to each infusion of amatuximab with 
acetaminophen 650 mg by mouth and diphenhydramine 25 to 50 mg by mouth or IV, or 


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clinical equivalent per clinic routine and country availability.  Refer to Section 9.3.7.1.1 for 
additional details on premedications for amatuximab.
Refer to Section 9.3.7.1.2 for additional details on premedications for pemetrexed.
The following treatments will be administered to subjects continuing in this study (Table 1).
Table 1
Treatments Administered
9.3.2
Identity of Investigational and Noninvestigational Products
9.3.2.1
Amatuximab
The investigational product, amatuximab, is supplied as a 25 mg/mL solution in 10-mL vials.  
It is a chimeric (mouse/human) IgG1/к antibody that binds to the human mesothelin protein.  
The formulation to be used in this clinical trial is presented in Table 2 (MORAb-009 
Investigator’s Brochure, 2014).
Table 2
Formulation of Amatuximab
Investigational product
Amatuximab (MORAb-009)
Formulation
20 mM glutamate/200 mM sorbitol, ph 5.0 
(pharmaceutical grade)
Strength
25 mg/mL
Route of administration
Intravenous infusion
Manufacturer
Lonza Inc., Slough , UK
Drug Name
Dose
Route of 
Administration
Dose Schedule
Combination Treatment Phase
Amatuximab
5 mg/kg
IV infusion
Once weekly for six 21-day cycles
Plus
Chemotherapy
Pemetrexed
500 mg/m2
IV infusion
Day 1 of each 21-day cycle for 6 cycles
Cisplatin
75 mg/m2
IV infusion
Day 1 of each 21-day cycle for 6 cycles
Maintenance Treatment Phase
Amatuximab
5 mg/kg
IV infusion
Once weekly until disease progression
IV = intravenous.


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9.3.2.2
Pemetrexed
Pemetrexed, a noninvestigational product for this study, is to be administered to all study 
subjects, regardless of randomization assignment.  Pemetrexed will be supplied by the 
investigational site unless prohibited by local regulations or institutional policy.  It is a sterile 
lyophilized powder for IV infusion.  The product is a white to either light yellow or 
green-yellow lyophilized solid.  Each 500-mg vial contains pemetrexed disodium equivalent 
to 500 mg of pemetrexed and 500 mg of mannitol.  Hydrochloric acid and/or sodium 
hydroxide may have been added to adjust pH.
9.3.2.3
Cisplatin
Cisplatin, a noninvestigational product for this study, is to be administered to all study 
subjects, regardless of randomization assignment.  Cisplatin will be supplied by the 
investigational site unless prohibited by local regulations or institutional policy.  It is a sterile 
aqueous solution.  Each mL contains 1 mg of cisplatin and 9 mg sodium chloride in water for 
injection.  Hydrochloric acid and/or sodium hydroxide are added to adjust pH of the solution.
9.3.2.4
Chemical Name, Structural Formula of Investigational Product
Not applicable.
9.3.2.5
Labeling for Investigational Product
Amatuximab will be labeled in accordance with text that is in full regulatory compliance with 
each participating country and is translated into the required language(s) for each of those 
countries.
9.3.2.6
Storage Conditions
Study Drugs (pemetrexed and cisplatin) must be stored as instructed on the label.  
Amatuximab must be kept in a secure location and carefully stored at 2°C to 8°C at the 
investigational site in its original container and protected from light.  Note that all relevant 
site-specific guidelines and country-specific labeling requirements must be followed.  The 
investigator or designee (or if regionally required, the head of the medical institution) is 
responsible for ensuring that the temperature is monitored throughout the total duration of the 
study and that records are maintained; the temperature should be monitored continuously by 
using either an in-house validated data acquisition system, a mechanical recording device, 
such as a calibrated chart recorder, or by manual means, such that minimum and maximum 
thermometric values over a specific time period can be recorded and retrieved as required.
The dose of amatuximab required for a subject is to be taken from as many vials as required.  
Any amatuximab remaining in a vial after withdrawing a subject’s dose is not to be used for 
subsequent doses.  


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Additional details on the storage, handling, and inventory of amatuximab will be provided in 
the Pharmacy Manual.
9.3.3
Method of Assigning Subjects to Treatment Groups
Subjects were assigned to treatments based on a computer-generated randomization scheme 
that was reviewed and approved by a statistician.
9.3.4
Selection of Doses in the Study
The 5-mg/kg dose of amatuximab was selected based on the results of the MORAb-009-003 
study and on the results of exposure-response analysis.  The selection of the dose of 
pemetrexed as well as cisplatin is based on the country-specific labeling requirements.
9.3.5
Selection and Timing of Dose for Each Subject
Amatuximab will be administered on a once-weekly schedule. Detailed instructions for the 
preparation, dilution, and administration of amatuximab are provided in the Pharmacy 
Manual.  The selection of the dosing schedule for pemetrexed and cisplatin is based upon the
country-specific labeling requirements.
At Week 1, Day 1 of each 21-day cycle, the amatuximab) will be administered, followed by 
the chemotherapy (pemetrexed [500 mg/m2] and then cisplatin [75 mg/m2]).  The dosage for 
the chemotherapy will be calculated at Cycle 1, Week 1, Day 1 and adjusted per the 
country-specific labeling requirements.  In the event that the chemotherapy regimen is 
discontinued before the subject reaches the 4th cycle, the subject will discontinue 
amatuximab administration and be discontinued from the study.
Dose reductions can be considered if subjects experience AEs related to the chemotherapy
(pemetrexed and cisplatin).  Dose reductions for toxicities can be made per country-specific 
labeling requirements.  
To date, no AEs attributed to amatuximab have been demonstrated to be dose-related.  
Therefore, no prescribed dose alterations and no dose modifications of amatuximab are 
planned.
9.3.6
Blinding
This study has been unblinded.  Each investigator site has been provided with a list of their
subject numbers and the treatment arm to which each subject was assigned in order to inform 
future medical management decisions.  
9.3.7
Concomitant Therapy
Any concomitant therapy administered to the subject during the course of the study (starting 
at the date of informed consent) until 30 days after the final dose of amatuximab will be 


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recorded in the subject’s medical record.  Additionally, all diagnostic, therapeutic, or surgical 
procedures relating to malignancy should be recorded.  Any medication that is considered 
necessary for the subject’s health and that is not expected to interfere with the evaluation of 
or interact with amatuximab, pemetrexed, or cisplatin may be continued during the study.
Treatment of complications or AEs, or therapy to ameliorate symptoms (including blood 
products, blood transfusions, fluid transfusions, antibiotics, and antidiarrheal drugs), may be 
given at the discretion of the investigator, unless it is expected to interfere with the evaluation 
of (or to interact with) amatuximab, pemetrexed, or cisplatin.
Aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and low-molecular-weight heparin 
are permissible but should be used with caution.  Granulocyte colony-stimulating factor or 
equivalent may be used in accordance with American Society of Clinical Oncology (ASCO), 
institutional, or national guidelines.  Erythropoietin may be used according to ASCO, 
institutional, or national guidelines, but the subject should be carefully monitored for 
increases in red blood cell counts.
9.3.7.1
Premedications
All premedications for amatuximab and Study Drugs must be reported in the subject’s 
medical record.
9.3.7.1.1
PREMEDICATIONS FOR AMATUXIMAB
Subjects must be premedicated to prevent hypersensitivity AEs.  To date, hypersensitivity 
AEs have been observed in the Phase 1 trials as well as in both of the Phase 2 trials.  In order 
to prevent or to reduce the incidence and severity of these types of hypersensitivity AEs, all 
subjects must be premedicated approximately 30 to 60 minutes prior to each infusion of 
amatuximab with acetaminophen 650 mg by mouth and diphenhydramine 25 mg to 50 mg by 
mouth or IV, or clinical equivalent per clinic routine and country availability.  Should 
hypersensitivity AEs occur in spite of these premedications, other suggested treatment 
regimens (ie, secondary prophylaxis of hypersensitivity AEs), are provided below.  
The recommendations below for secondary prophylaxis are based on observations made on 
the Phase 1 and Phase 2 trials conducted to date and on standard clinical practice.  For 
subjects experiencing any hypersensitivity AEs, secondary prophylaxis is recommended and 
will be given at the investigator’s discretion:
•
Grade 1 Events:  Subjects experiencing hypersensitivity AEs consisting of Grade 1 events 
can be managed with secondary prophylaxis for subsequent infusions.  Along with an 
antipyretic of choice (acetaminophen up to a dose of 1000 mg by mouth has been used) and 
concurrent use of diphenhydramine, an H2 receptor antagonist can be considered, such as 
ranitidine (50 mg IV).  Secondary prophylaxis should be administered approximately 
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•
Grade 2 Events:  Subjects experiencing hypersensitivity AEs consisting of Grade 2 events 
can be managed with secondary prophylaxis for subsequent infusions, along with 
diphenhydramine 50 mg IV, ranitidine 50 mg IV, and dexamethasone 20 mg IV.  Secondary 
prophylaxis should be administered approximately 30-60 minutes prior to dosing with 
amatuximab.
Secondary prophylaxis regimens above are recommendations to be given at the investigator’s 
discretion and should be recorded in the subject’s medical record. 
•
Grade 3 and Grade 4 Events:  If a Grade 3 hypersensitivity AE occurs, the subject may be 
continued at the discretion of the investigator, provided the AE can be reduced to and 
maintained at Grade 2 or lower.  In the event that a Grade 4 hypersensitivity AE occurs, the 
subject will be discontinued from treatment with amatuximab and discontinued from the 
study.  
9.3.7.1.2
PREMEDICATIONS FOR PEMETREXED
Subjects must receive prophylactic treatment for pemetrexed with folic acid, vitamin B12, 
and dexamethasone at each cycle of Combination Treatment according to the investigational 
site’s standard practice.  As a general guideline, starting at least 5 days prior to the first dose 
of pemetrexed, subjects will begin treatment with folic acid and vitamin B12 (refer to the 
Schedule of Procedures/Assessments.  Folic acid will be administered at a dose in the range 
of 350 µg to 1 mg by mouth daily.  Vitamin B12 will be administered by intramuscular 
injection at a dose of 1 mg approximately every 9 weeks.  Dexamethasone will be 
administered at a dose of 4 mg by mouth twice daily for 3 days as follows:  the day before, 
the day of, and the day following each infusion of pemetrexed.  (Refer to the country-specific 
labeling requirements.)
9.3.7.2
Drug-Drug Interactions
Not applicable.
9.3.7.3
Prohibited Concomitant Therapies and Drugs
Subjects should not receive other antitumor therapies (eg, chemotherapy, radiotherapy, 
nonstudy monoclonal antibodies, immunomodulators, or immunotherapy) or cytotoxic 
therapy (eg, methotrexate for rheumatoid arthritis) while in the Combination treatment or 
Maintenance Treatment phases; however, local radiotherapy for noncurative intent is 
allowed.  If subjects receive additional antitumor therapies, this will be judged to represent 
evidence of disease progression, and all study drugs will be discontinued. 
9.3.8
Treatment Compliance
Records of treatment compliance for each subject will be kept during the study.  CRAs will 
review treatment compliance during site visits and at the completion of the study.  


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Amatuximab is to be dispensed only to subjects enrolled in the clinical trial.  Infusions of the 
amatuximab are to be administered by appropriately trained and qualified personnel.
9.3.9
Drug Supplies and Accountability
The pharmacist (or qualified designee, as appropriate) will be responsible for the 
accountability of all study treatments/study supplies (dispensing, inventory, and record 
keeping) following the sponsor’s instructions and adherence to GCP guidelines as well as 
local or regional requirements.
Under no circumstances will the investigator allow the amatuximab to be used other than as 
directed by this protocol.  Amatuximab will not be dispensed to any individual who is not 
enrolled in the study.  
The site must maintain an accurate and timely record of the following:  receipt of all 
amatuximab, dispensing of amatuximab to the subject, collection and reconciliation of 
unused amatuximab that are shipped to site but not dispensed to subjects, and return of 
reconciled amatuximab to the sponsor or (where applicable) destruction of reconciled 
amatuximab at the site.  This includes, but may not be limited to:  (a) documentation of 
receipt of amatuximab, (b) Amatuximab dispensing/return reconciliation log, (c) 
Amatuximab accountability log, (d) all shipping service receipts, (e) documentation of 
returns to the sponsor, and (f) documentation of destruction for any destruction of 
amatuximab/study supplies that occurs at the site, where available.  All forms will be 
provided by the sponsor.  Any comparable forms that the site wishes to use must be approved 
by the sponsor.
The amatuximab and inventory records must be made available, upon request, for inspection 
by a designated representative of the sponsor or a representative of a health authority (eg, 
FDA, Medicines and Healthcare Products Regulatory Agency).  
Drug accountability will be reviewed during site pharmacy visits and at the completion of the 
study by the unblinded CRA.
As permissible by site standards, and after drug accountability has been performed by the 
unblinded CRA, empty and partially used amatuximab vials are to be destroyed by the site.  
Destruction will occur following the site’s standard procedures and documentation of 
destruction will be maintained.  If destruction on site is not allowed, arrangements can be 
made to return used vials to the depot.
At the conclusion of the study or by sponsor directive, and upon completion of drug 
accountability and reconciliation procedures by the site’s unblinded personnel and review by 
the unblinded CRA, any unused vials of amatuximab that were shipped to the site but not 
administered to subjects must be destroyed by the site or boxed, sealed, and shipped back to 
the sponsor’s designated central or local depot, following all local regulatory requirements.  
In some regions, the amatuximab may be removed from the site and hand delivered to the 
central or local depot by sponsor representatives.  


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9.4
Study Assessments
9.4.1
Assessments
9.4.1.1
Screening Assessments
All continuing subjects have completed screening assessments as outlined in protocol version 
2.0, date 24 Apr 2015.
9.4.1.2
Efficacy Assessments
No further efficacy assessments are required.   
9.4.1.2.1
FOLLOW-UP FOR SURVIVAL
No longer applicable. 
9.4.1.2.2
COMPUTED TOMOGRAPHY SCAN OR MAGNETIC RESONANCE IMAGING
Investigators may continue to perform CT or MRIs at their discretion per standard clinical 
practice.  No further images or data will be collected by the Sponsor.
9.4.1.2.3
QUALITY OF LIFE ASSESSMENT (LCSS-MESO)
No further assessments are required.
9.4.1.2.4
PERFORMANCE STATUS (DPSM)
No further assessments are required.
9.4.1.3
Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, and Other Biomarker
Assessments
9.4.1.3.1
PHARMACOKINETIC ASSESSMENTS
Samples collected to date may be analyzed.  No further samples will be collected.
9.4.1.3.2
PHARMACODYNAMIC, PHARMACOGENOMIC, AND OTHER BIOMARKER, ASSESSMENTS
Pharmacodynamics
No longer applicable. 
Pharmacogenomics
Samples already collected will be stored and analyzed per the terms of the original informed 
consent form signed by each subject.  No additional samples will be collected.  


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Biomarkers
Samples already collected will be stored and analyzed per the terms of the original informed 
consent form signed by each subject.  No additional samples will be collected.  
9.4.1.4
Safety Assessments
Safety assessments will consist of recording all AEs, including all CTCAE v4.03 grades (for 
both increasing and decreasing severity), all AEIs, and SAEs; regular monitoring of 
hematology, and blood chemistry values; regular monitoring of ECGs; periodic measurement 
of vital signs; and performance of physical examinations at the discretion of the investigator 
per standard of care. 
Assessments will be documented in subject’s medical records and only SAEs will be 
reported to the Sponsor.  
9.4.1.4.1
ADVERSE EVENTS AND OTHER EVENTS OF INTEREST
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered an investigational product.  An AE does not necessarily have a causal 
relationship with the Study Drugs. 
The criteria for identifying AEs in this study are:

Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an investigational product, 
whether or not considered related to the investigational product

Any new disease or exacerbation of an existing disease; however, worsening of the 
primary disease is considered disease progression rather than an AE

Any deterioration in nonprotocol-required measurements of a laboratory value or other 
clinical test (eg, ECG or x-ray) that results in symptoms, a change in treatment, or 
discontinuation of amatuximab and/or chemotherapy

Recurrence of an intermittent medical condition (eg, headache) not present pretreatment 
(ie, prior to the first administration of amatuximab)

An abnormal laboratory test result should be considered an AE if the identified laboratory 
abnormality leads to any type of intervention, whether prescribed in the protocol or not
All AEs, regardless of relationship to study drug or procedure, should be documented 
beginning from the time the subject signs the study ICF through the last visit and for 30 days
after the subject’s last dose of amatuximab.  Abnormal laboratory values should not be listed 
as separate AEs if they are considered to be part of the clinical syndrome that is being 
reported as an AE.  It is the responsibility of the investigator to review all laboratory findings 
in all subjects and determine if they constitute an AE.  Medical and scientific judgment 
should be exercised in deciding whether an isolated laboratory abnormality should be 
classified as an AE.  


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Abnormal ECG (QTc) results, if not otherwise considered part of a clinical symptom that is 
being reported as an AE, should be considered an AE if the QTc interval is more than 500 ms 
and there is an increase of more than 30 ms from baseline.  Any ECG abnormality that the 
investigator considers as an AE should be documented as such.
All AEs must be followed for 30 days after the subject’s last dose of amatuximab, or until 
resolution, whichever comes first.  All SAEs must be followed to resolution or, if resolution 
is unlikely, to stabilization.
Per this amendment all adverse events will documented in the subject’s medical record.  
Only AEs meeting the criteria of serious as described in Section 9.4.1.4.2 will be reported to 
the Sponsor per Section 9.4.3.  
Every effort must be made by the investigator to categorize each AE according to its 
severity and its relationship to the study drugs.
Assessing Severity of Adverse Events
AEs will be graded on a 5-point scale according to CTCAE v4.03.  Investigators will 
document CTCAE grades for all AEs.
Assessing Relationship to Study Drugs
Items to be considered when assessing the relationship of an AE to the study drug(s) are:

Temporal relationship of the onset of the event to the initiation of the study drug

The course of the event, especially the effect of discontinuation of study drug(s) or 
reintroduction of study drug(s), as applicable

Whether the event is known to be associated with the study drug or with other similar 
treatments

The presence of risk factors in the study subject known to increase the occurrence of the 
event

The presence of nonstudy, treatment-related factors that are known to be associated with 
the occurrence of the event
Classification of Causality
The relationship of each AE to the study drug will be recorded in the subject’s medical 
record in response to the following question:
Is there a reasonable possibility that the study drug caused the AE?
Yes (related)
A causal relationship between the study drug and the AE is a reasonable 
possibility.


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No (not related) A causal relationship between the study drug and the AE is not a 
reasonable possibility.
9.4.1.4.2
SERIOUS ADVERSE EVENTS AND OTHER EVENTS OF INTEREST
A SAE is any untoward medical occurrence that at any dose:

Results in death (other than death due to PD as this is the study endpoint)

Is life-threatening (ie, the subject was at immediate risk of death from the AE as it 
occurred; this does not include an event that, had it occurred in a more severe form or 
was allowed to continue, might have caused death)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect (in the child of a subject who was exposed to the 
study drug)
Other important medical events that may not be immediately life-threatening or result in 
death or hospitalization but, when based on appropriate medical judgment, may jeopardize 
the subject or may require intervention to prevent one of the outcomes in the definition of 
SAE listed above should also be considered SAEs.  Medical and scientific judgment should 
be exercised in deciding whether expedited reporting is appropriate in such situations. 
In addition to the above, other events of interest include pregnancy or exposure to study drug 
through breastfeeding; and AEs associated with study drug overdose, misuse, abuse, or 
medication error.  These events of interest are to be captured using the SAE procedures but 
are to be considered as SAEs only if they meet one of the above criteria.  All AEs associated 
with events of interest are to be reported in the subject’s medical record whether or not they 
meet the criteria for SAEs.  
All SAEs must be followed to resolution or, if resolution is unlikely, to stabilization.
The following hospitalizations are not considered to be SAEs because there is no “adverse 
event” (ie, there is no untoward medical occurrence) associated with the hospitalization:

Hospitalizations for respite care 

Planned hospitalizations required by the protocol

Hospitalization planned before informed consent (where the condition requiring the 
hospitalization has not changed after study drug administration)

Hospitalization for administration of study drug or insertion of access for administration 
of study drug

Hospitalization for routine maintenance of a device (eg, battery replacement) that was in 
place before study entry
Death due to disease progression is a study endpoint, and is therefore not considered an SAE 
in this study and does not need to be reported as such.  


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9.4.1.4.3
ADVERSE EVENTS OF INTEREST
The conditions of hypersensitivity AEs and interstitial lung disease AEs are possible with 
administration of any monoclonal antibody and should be considered AEIs.  
Hypersensitivity
The following signs and symptoms are considered hypersensitivity AEs if they occur within 
24 hours of infusion:

Cytokine release syndrome

Flushing

Fever

Rigors/chills

Sweating/diaphoresis

Pruritus/itching

Urticaria

Bronchospasm/wheezing

Bronchial edema
An abbreviated NCI CTCAE v.4.03 for grading some of the most commonly observed
hypersensitivity AEs has been provided in Appendix 1.  Refer to the full NCI CTCAE v.4.03 
for complete event grading information.  All hypersensitivity AEs are to be recorded in the 
subject’s medical record.  Hypersensitivity AEs that meet the definition of a SAE should also 
be reported in an expedited fashion using the SAE form as well in the same manner and 
timeframe as reporting of SAEs (Section 9.4.3.1).  
Hypersensitivity AEs have been seen in the Phase 1 and 2 clinical trials of amatuximab 
during and immediately following the administration of amatuximab.  In general, 
hypersensitivity AEs to monoclonal antibodies are immediate, typically occurring during the 
first few minutes of the first infusion.  However, up to 30% of reactions to monoclonal 
antibodies are delayed and may occur in later infusions (Lenz, 2007). 
Treatment of Hypersensitivity AEs
If a hypersensitivity AE occurs during infusion of amatuximab, the rate of infusion should be 
decreased by at least 50% and then advanced back (up to a maximum of 10 mg/min).  
Otherwise, the infusion should be terminated completely in accordance with standard 
practice at the investigational site or based on the NCI CTCAE v.4.03 (Appendix 1).  
In the event of a hypersensitivity AE, the subject may be treated with an additional 650 mg of 
acetaminophen by mouth, either alone or in combination with diphenhydramine 25 mg to 
50 mg by mouth (Grade 1 reaction) or IV (Grade 2 reaction).  At any point at which the 


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investigator deems necessary, other therapeutic interventions should be initiated based on the 
signs and symptoms and the severity associated with the event.
Secondary Prophylaxis of Hypersensitivity AEs
For subjects who have experienced hypersensitivity AEs, secondary prophylaxis is 
recommended and given at the investigator’s discretion.  Details of secondary prophylaxis 
are outlined in Section 9.3.7.1.1 and below: 

Subjects experiencing hypersensitivity AEs consisting of Grade 1 events can be managed 
with secondary prophylaxis for subsequent infusions.  Along with an antipyretic of 
choice (acetaminophen to a dose of 1000 mg by mouth has been used) and concurrent use 
of diphenhydramine, an H2 receptor antagonist can be considered, such as ranitidine 
(50 mg IV).  Secondary prophylaxis should be administered approximately 30-60 minutes 
prior to dosing with amatuximab.  

Subjects experiencing hypersensitivity AEs consisting of Grade 2 events can be managed 
with secondary prophylaxis for subsequent infusions, along with diphenhydramine 50 mg 
IV, ranitidine 50 mg IV, and dexamethasone 20 mg IV  Secondary prophylaxis should be 
administered approximately 30-60 minutes prior to dosing with amatuximab.
Prophylaxis regimens are given at the investigator’s discretion. 
If a Grade 3 hypersensitivity AE occurs, the subject may be continued at the discretion of the 
investigator, provided the reaction can be reduced to and maintained at Grade 2 or lower.  In 
the event that a Grade 4 hypersensitivity AE occurs, the subject will be discontinued from 
treatment with amatuximab and the study.  
Interstitial Lung Disease 
Interstitial lung disease AEs are defined as AEs identified in the narrow-search Standardized 
MedDRA Query for interstitial lung disease (Appendix 2).  These events have been seen in 
clinical studies with other monoclonal antibodies; therefore, they will be monitored in this 
study and reported to the Sponsor if the meet the criteria of SAEs (see Section 9.4.1.4.2).  
Pregnancy Testing
Serum pregnancy testing (β-hCG) was conducted at Screening in female subjects of 
childbearing potential.
9.4.1.4.4
LABORATORY MEASUREMENTS
Per this amendment, clinical laboratory tests during the Combination Treatment and 
Maintenance Treatment phases will be performed at the discretion of the PI per standard of 
care practice by the local laboratory and results will not be collected by the Sponsor.  


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A laboratory abnormality may meet the criteria to qualify as an AE as described in this 
protocol (see Section 9.4.1.4.1).  In these instances, the AE corresponding to the laboratory 
abnormality will be recorded in the subject’s medical records.  The corresponding local 
laboratory values and local lab normal ranges will not be collected. 
For laboratory abnormalities meeting the criteria of SAEs (see Section 9.4.1.4.2), the site 
must fax or email the SAE report including the laboratory report (as regionally required) to 
the sponsor using the SAE form (see Section 9.4.3.1).
9.4.1.4.5
VITAL SIGNS AND WEIGHT MEASUREMENTS
Vital signs will not be collected during this study due to the absence of clinically significant 
vital sign findings in prior studies.  Any AEs noted as a result of measuring a subject’s vital 
signs as part of standard of care should be recorded in the subject’s medical record.
Body weight will be measured at the time points specified in the Schedule of 
Procedures/Assessments.  If weight increases or decreases by more than 10% compared with 
either Screening or Day 1 of the previous cycle, the amatuximab dosage will be recalculated 
to maintain the specified dose regimen.  
9.4.1.4.6
PHYSICAL EXAMINATIONS
Sites will continue to perform physical examinations at the discretion of the PI per standard 
of care practice.  Documentation of any physical examination will be included in the source 
documentation at the site.  
For postbaseline time points, only body systems where findings are reported as abnormal will 
be identified, and the associated AE will be reported in the subject’s medical record.  
Abnormal changes from baseline that meet the definition of a SAE should be reported as 
described in Section 9.4.3.1.
9.4.1.4.7
ELECTROCARDIOGRAMS
Per this amendment, additional ECGs are not required but may be performed at the 
discretion of the PI.  
For ECG abnormalities meeting criteria of an SAE (see Section 9.4.1.4.2), the site must fax 
or email the SAE report including the ECG report to the sponsor using the SAE form (see
Section 9.4.3.1).
9.4.2
Schedule of Procedures/Assessments
9.4.2.1
Schedule of Procedures/Assessments
Table 3 presents the Schedule of Procedures/Assessments associated with this amendment.


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Table 3
Schedule of Procedures/Assessments in Study MORAb-009-201
Evaluationa
Combination Treatment Phaseb
Maintenance Treatment Phase
Test Article 
(Amatuximab) Admin 
Only Visits
EOT 
Visita
30-Day 
Safety 
Visitc
Week 1
Week 2
Week 3
Week 1
Week 2
Week 3
Day 1
Day 8
Day 15
Day 1
Day 8
Day 15
ICFd
Physical examinatione
Weightf
X
X
Imaging (CT or MRI)g
12-lead ECGh
Hematology and Chemistryi
Premedication (required)j
X
X
X
X
X
X
X
Amatuximab administrationk
X
X
X
X
X
X
X
Chemotherapy administrationl
X
Concomitant medicationsm
X
X
X
X
X
X
X
X
X
Adverse eventsn
X
X
X
X
X
X
X
X
X


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BSA = body surface area; CT = computed tomography; ECG = electrocardiogram; EOT = End of Treatment; ICF = informed consent form;  MRI 
= magnetic resonance imaging
a.
All assessments should be performed within ±2 days of the scheduled visit, unless otherwise specified in the protocol, except for EOT Visit 
assessments, which are to be conducted (where possible) within 7 days of the last dose of Amatuximab.  All assessments should be documented in the 
subject's medical records but will not be collected by the Sponsor.  Only SAEs, amatuximab inventory information, and subject discontinuation will be 
collected per this amendment. 
b.
All subjects will receive combination treatment for six 21-day cycles. On Day 1 of each cycle, Amatuximab will be administered prior to pemetrexed 
which will be administered prior to cisplatin.  Subjects who have completed a minimum of 4 cycles of Combination Treatment and who have not 
progressed may enter the Maintenance Treatment Phase.
c.
A 30 day Follow-up visit will be performed (within ±7 days) after the last dose of amatuximab and will serve as the last time point for which adverse 
events are documented in the subject's medical record and SAEs are to be reported.
d.
Subjects continuing on study for Amendment 02 should be reconsented to the IRB-approved ICF.
e.
Physical examinations should be conducted at the discretion of the investigator per standard of care.
f.
Body weight will be measured during  Day 1 of each cycle and is entered in the IRT system.
g.
CT or MRI scans should conducted at the discretion of the investigator per standard of care.
h.
12-lead ECG should conducted at the discretion of the investigator per standard of care.
i.
Hematology and Chemistry should conducted at the discretion of the investigator per standard of care
j.
All subjects must be premedicated approximately 30 to 60 minutes prior to each infusion of amatuximab with acetaminophen 650 mg by mouth and 
diphenhydramine 25 mg to 50 mg by mouth or IV, or clinical equivalent per clinic routine and country availability.  Starting at least 5 days prior to the 
first dose of pemetrexed, subjects will begin treatment with folic acid and vitamin B12.  Dexamethasone will be administered at a dose of 4 mg by 
mouth twice daily for 3 days as follows:  the day before, the day of, and the day following each infusion of pemetrexed.
k.
Amatuximab must be administered IV once weekly prior to pemetrexed during the Combination Treatment Phase and IV once weekly during the 
Maintenance Treatment Phase.  
l.
Pemetrexed will be given prior to cisplatin. 
m. Concomitant medications are any new, discontinued, or ongoing medications that have been taken within 30 days prior to the first dose of amatuximab 
until 30 days after the last dose of amatuximab.  These should be discussed and documented in the subject's medical record to assist in identification of 
AEs.  
n.
All AEs occurring after the subject signs the ICF and continuing through 30 days after the last infusion of amatuximab should be recorded in the 
subject’s medical record. Serious AEs should be reported in an expedited fashion per standard procedure. Serious AEs that are ongoing at the time of 
discontinuation of amatuximab will be followed until resolution (or until stable if resolution is not expected).


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9.4.2.2
Description of Procedures/Assessments Schedule
Refer to the Schedule of Procedures/Assessments for details regarding the procedures and 
assessments required for this study.
9.4.3
Reporting of Serious Adverse Events, Pregnancy, and Other Events of 
Interest
9.4.3.1
Reporting of Serious Adverse Events
All SAEs, regardless of their relationship to study drugs, must be reported on a 
completed SAE form by email or fax as soon as possible but no later than 24 hours from 
the date the investigator becomes aware of the event.
Reporting deaths due to PD as SAEs is not required, as death associated with disease 
progression.
SAEs, regardless of causality assessment, must be collected from the date of informed 
consent signature through 30 days following the last dose of amatuximab.  SAEs that are 
ongoing at the time of discontinuation of amatuximab will be followed until resolution (or 
until stable if resolution is not expected).
Any SAE judged by the investigator to be related to amatuximab or any protocol-required 
procedure should be reported to the sponsor regardless of the length of time that has passed 
since study completion.
The detailed contact information for reporting of SAEs is provided in the Investigator Study 
File.
For urgent safety issues call:  
 (24/7 number).  
It is very important that the SAE report form be filled out as completely as possible at the 
time of the initial report.  This includes the investigator’s assessment of causality.
Any follow-up information received on SAEs should be forwarded within 24 hours of its 
receipt.  If the follow-up information changes the investigator’s assessment of causality, this 
should also be noted on the follow-up SAE form.
Preliminary SAE reports should be followed as soon as possible by detailed descriptions 
including copies of hospital case reports, autopsy reports, and other documents requested by 
the sponsor.
The investigator must notify his/her IRB/IEC of the occurrence of the SAE in writing, if 
required by their institution.  A copy of this communication must be forwarded to the CRO 
monitor to be filed in the sponsor’s Trial Master File (TMF).
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9.4.3.2
Reporting of Pregnancy and Exposure to Study Drug Through Breastfeeding
Any pregnancy in which the estimated date of conception is either before the end of 
treatment (EOT) Visit of the study and for 30 days following amatuximab discontinuation, 
whichever is longer, must be reported.
If an adverse outcome of a pregnancy is suspected to be related to study drug exposure, this 
should be reported regardless of the length of time that has passed since the exposure to 
amatuximab.
A congenital anomaly, death during perinatal period, an induced abortion, or a spontaneous 
abortion are considered to be an SAE and should be reported in the same time frame and in 
the same format as all other SAEs (see Reporting of Serious Adverse Events 
[Section 9.4.3.1]).
Pregnancies or exposure to study drug through breastfeeding must be reported by fax or 
email as soon as possible but no later than 24 hours from the date the investigator becomes 
aware of the pregnancy.  The contact information for the reporting of pregnancies and 
exposure to study drug through breastfeeding is provided in the Investigator Study File.  The 
Pregnancy Report Form must be used for reporting.  All pregnancies must be followed to 
outcome.  The outcome of the pregnancy must be reported as soon as possible but no later 
than 24 hours from the date the investigator becomes aware of the outcome.
A subject who becomes pregnant must be withdrawn from the study.
9.4.3.3
Reporting of Other Events of Interest
9.4.3.3.1
REPORTING OF ADVERSE EVENTS ASSOCIATED WITH STUDY DRUG OVERDOSE,
MISUSE, ABUSE, OR MEDICATION ERROR
AEs associated with study drug overdose, misuse, abuse, and medication error refer to AEs 
associated with uses of the study drug outside of that specified by the protocol.  Overdose,
misuse, abuse, and medication error are defined as follows:
Overdose
Accidental or intentional use of the study drug in an amount higher 
than the protocol-defined dose
Misuse
Intentional and inappropriate use of study drug not in accordance with 
the protocol
Abuse
Sporadic or persistent intentional excessive use of study drug 
accompanied by harmful physical or psychological effects
Medication error
Any unintentional event that causes or leads to inappropriate study 
drug use or subject harm while the study drug is in the control of site
personnel or the subject.  


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All AEs associated with overdose, misuse, abuse, or medication error should be captured in 
the subject’s medical record and also reported using the procedures detailed in Reporting of 
Serious Adverse Events (Section 9.4.3.1) even if the AEs do not meet serious criteria.  Abuse 
is always to be captured as an AE.  If the AE associated with an overdose, misuse, abuse, or 
medication error does not meet serious criteria, it must still be reported using the SAE form 
and in an expedited manner but should be noted as nonserious on the SAE form.
9.4.3.4
Expedited Reporting
The sponsor must inform investigators and regulatory authorities of reportable events, in 
compliance with applicable regulatory requirements, on an expedited basis (ie, within 
specific time frames).  For this reason, it is imperative that sites provide complete SAE 
information in the manner described above.
9.4.3.5
Breaking the Blind
The study has been unblinded.
9.4.3.6
Regulatory Reporting of Adverse Events
SAEs will be reported by the sponsor or a third party acting on behalf of the sponsor to 
regulatory authorities in compliance with local and regional law and established guidance.  
The format of these reports will be dictated by the local and regional requirements.
All studies that are conducted within any European country will comply with European Good 
Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC.  All 
SUSARs will be reported, as required, to the competent authorities of all involved European 
member states.
9.4.4
Completion/Discontinuation of Subjects from Study (EOS)
Once a subject discontinues amatuximab for any reason, the EOT procedures should be 
completed and documented in the subject's medical record.  
The investigator will promptly explain to the subject involved that all study procedures will 
be discontinued for that subject and provide appropriate medical treatment and other 
necessary measures for the subject.  A subject who has ceased to return for visits will be 
followed up by mail, phone, or other means to gather information such as the reason for 
failure to return, the presence or absence of AEs, and clinical courses of signs and symptoms.  
9.4.5
Abuse or Diversion of Study Drug
Not applicable.


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9.4.6
Confirmation of Medical Care by Another Physician
The investigator will instruct subjects to inform site personnel when they are planning to 
receive medical care by another physician.  At each visit, the investigator will ask the subject 
whether he/she has received medical care by another physician since the last visit or is 
planning to do so in the future.  When the subject is going to receive medical care by another 
physician, the investigator, with the consent of the subject, will inform the other physician 
that the subject is participating in the clinical study.
9.5
Data Quality Assurance
This study will be organized, performed, and reported in compliance with the protocol, 
SOPs, working practice documents, and applicable regulations and guidelines.  
Before any subjects could be enrolled at an investigational site and prior to the conduct of 
any protocol-specific procedures, formal training of investigational site personnel was
conducted.  The investigator and all relevant investigational site staff were trained on all 
aspects of the trial for which they are responsible.  Site personnel were trained at a formal 
initiation visit, and ongoing training will be provided, as necessary.  
Monitoring visits will occur at regular intervals while subjects are actively enrolled into the 
clinical trial.  Through frequent communications with the investigational site, the CRA will 
ensure that the investigation is conducted according to protocol design and all applicable 
regulatory requirements.  Additional details on the monitoring of this clinical trial are 
provided in Section 11.3.
During the course of the clinical trial, investigational sites and all associated clinical trial 
documentation may be subject to quality assurance audits by the sponsor, or their appointed 
representatives, on a planned or an as-needed basis.  In addition, representatives of associated 
regulatory bodies may conduct inspections at their discretion.  The investigator is responsible 
for insuring direct access to all study-related materials for the purpose of these activities.  
9.5.1
Data Collection
Per this amendment data-related study information including AEs, results of any standard of 
care medical or laboratory assessments and information related to amatuximab treatment and 
drug accountability will be documented in the subject’s medical records.   
Amatuximab infusion and inventory data, and the date of treatment discontinuation will be 
entered in the IRT system.  SAEs will be reported as outlined in Section 9.4.3.1.  
At the beginning of the study, an investigator’s study file was established at the 
investigational site.  The investigator/institution is responsible for maintaining the study 
documents as specified in the guideline for ICH GCP and US 21 CFR Part 312 and as 
required by the applicable regulatory requirement(s).  The investigator/institution must take 
measures to prevent accidental or premature destruction of these documents. 


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9.5.2
Clinical Data Management
All software applications used in the collection of data will be properly validated following 
standard computer system validation that is compliant with all regulatory requirements.  
9.6
Statistical Methods
No efficacy analyses will be performed.  Statistical analyses for all other data will be 
performed by the sponsor or designee on data collected prior to this amendment after the 
database is locked.  Statistical analyses will be performed using SAS® or other validated 
statistical software as required.
9.6.1
Statistical and Analytical Plans
No formal statistical analyses of efficacy data will be performed.  Data collected in the 
clinical database prior to this amendment will be summarized and listed, as appropriate, in an 
abbreviated final study report.  The specific analysis methods will be described in a separate 
analysis plan.
9.6.1.1
Safety Analyses
Up until the time of enrollment closure, the IDMC performed periodic safety analyses as 
detailed in the IDMC charter.  No new safety issues were noted.
All safety information entered in the clinical database prior to this amendment will be 
summarized and included in listings.  
Per this amendment, safety information including adverse events should continue to be 
collected by the investigator and documented in subject’s medical record.  SAEs must be 
reported as outlined in Section 9.4.3.1.  
9.6.2
Determination of Sample Size
Not applicable. 
9.6.3
Interim Analysis for Futility
Not applicable.
9.6.3.1
Independent Data Monitoring Committee
The IDMC will no longer review safety data as the study has been unblinded.  
9.6.3.2
Interim Analysis for Futility Assessments
Not applicable.


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9.6.4
Other Statistical/Analytical Issues
Not applicable.


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study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with 
malignant pleural mesothelioma. J Clin Oncol. 2003; 21:2636–2644.
World Medical Association Declaration of Helsinki Ethical Principles for Medical Research 
Involving Human Subjects. 64th WMA General Assembly. Fortaleza, Brazil. Oct 2013.


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11 PROCEDURES AND INSTRUCTIONS (ADMINISTRATIVE 
PROCEDURES)
11.1
Changes to the Protocol
Protocols will be followed as written.  Any change to the protocol requires a written protocol 
amendment or administrative change that must be approved by the sponsor before 
implementation.  Amendments specifically affecting the safety of subjects, the scope of the 
investigation, or the scientific quality of the study require submission to health or regulatory 
authorities as well as additional approval by the applicable IRBs/IECs.  These requirements 
should in no way prevent any immediate action from being taken by the investigator, or by 
the sponsor, in the interest of preserving the safety of all subjects included in the study.  If the 
investigator determines that an immediate change to or deviation from the protocol is 
necessary for safety reasons to eliminate an immediate hazard to the subjects, the sponsor’s 
medical monitor and the IRB/IEC for the site must be notified immediately.  The sponsor 
must notify the health or regulatory authority as required per local regulations.
Protocol amendments that affect only administrative aspects of the study may not require 
submission to health or regulatory authority or the IRB/IEC, but the health or regulatory 
authority and IRB/IEC (or if regionally required, the head of the medical institution) should 
be kept informed of such changes as required by local regulations.  In these cases, the 
sponsor may be required to send a letter to the IRB/IEC and the Competent Authorities (or, if 
regionally required, the head of the medical institution) detailing such changes.
11.2
Adherence to the Protocol
The investigator will conduct the study in strict accordance with the protocol (refer to 
ICH E6, Section 4.5).
In general, protocol violations include deviations from inclusion/exclusion criteria, from 
concomitant medication restrictions, and from any other protocol requirement that could, at 
least hypothetically, result in significant risk to the subject and/or affect the outcome of the 
clinical trial.  Protocol violations will be noted in the final Clinical Study Report.  
A deviation is defined as nonadherence to the protocol procedures or schedule as defined by 
the protocol or the primary endpoint that does not place the subject at any added or 
significant risk or affect the data quality or the outcome of the clinical trial (eg, a missed 
procedure, an out-of-window site visit).  
Only subjects who meet protocol-defined eligibility criteria may be enrolled in this clinical 
trial.  If any protocol eligibility criteria or procedures are unclear, the investigator or 
investigational site personnel should contact the CRA.  If the question requires medical 
interpretation, the sponsor’s medical monitor should be consulted.  All protocol violations 
and deviations should be reported to the IRB/IEC according to the standard practices of the 
investigational site and applicable regulatory requirements. 


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Data review will be performed in an ongoing manner during trial conduct to assess protocol 
deviations and violations.  The sponsor will convene a data review meeting at least once prior 
to database lock to classify findings as either protocol deviations or violations. 
11.3
Monitoring Procedures
The sponsor’s and/or CRO’s CRA will maintain contact with the investigator and designated 
staff by telephone, letter, or email between study visits.  Monitoring visits to each site will be 
conducted by the assigned CRAs, as described in the monitoring plan.    The investigator (or 
if regionally required, the head of the medical institution) will allow the CRA to inspect the 
clinical, laboratory, and pharmacy facilities to assure compliance with ICH GCP and local 
regulatory requirements.  The subject’s original medical records (source documents) are to be 
fully available for review by the sponsor’s representatives at regular intervals.  These reviews 
verify adherence to study protocol and data accuracy in accordance with local regulations.  
All records at the site are subject to inspection by the local auditing agency and to IRB/IEC 
review.
In accordance with ICH E6, Section 1.52, source documents include, but are not limited to,
the following:

Clinic, office, or hospital charts

Copies or transcribed health care provider notes that have been certified for accuracy 
after production

Recorded data from automated instruments such as IRT, x-rays, and other imaging 
reports (eg, sonograms, CT scans, magnetic resonance images, radioactive images, ECGs, 
rhythm strips, electroencephalograms, polysomnographs, pulmonary function tests) 
regardless of how these images are stored, including microfiche and photographic 
negatives

Pain, QOL, or medical history questionnaires completed by subjects

Records of telephone contacts

Diaries or evaluation checklists

Drug distribution and accountability logs maintained in pharmacies or by research 
personnel

Laboratory results and other laboratory test outputs (eg, urine pregnancy test result 
documentation and urine dip-sticks)

Correspondence regarding a study subject’s treatment between physicians or memoranda 
sent to the IRBs/IECs
The CRA will perform onsite monitoring visit at each site at regular intervals, as agreed upon 
with the sponsor.  At these interim monitoring visits, the CRA (or unblinded CRA, where 
noted) will perform the following tasks:


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
Review data entered into the subject’s source documents

Check for protocol compliance (including documentation of adequate written informed 
consent, appropriate subject visit dates, documentation of AEs and concomitant 
medications, key safety and biological safety observations, and study agent dosing)

Review the investigational site regulatory file to ensure that all regulatory documentation 
has been updated as necessary and filed appropriately, and reconcile the contents of the 
investigational site regulatory file the TMF  

Review amatuximab accountability and verify compliance with the Pharmacy Manual  
After the last subject at the site has completed the clinical trial, the CRA will return to the 
site for final source data verification and close-out visit.  At this visit, any outstanding issues 
will be resolved and the investigator’s responsibilities for retention of clinical trial 
documentation will be reviewed.
After each investigational site visit, the CRA will discuss relevant findings with the 
investigator and the coordinator.  The results of the monitoring visit will be documented in a 
monitoring visit report, and a follow-up letter will be sent to the site.
11.4
Recording of Data
All data associated with conduct of this amendment will be documented in the subject’s 
medical record.  
Amatuximab infusion and inventory data, and the date of treatment discontinuation will be 
entered in the IRT system.  
11.5
Identification of Source Data
All data from any safety assessments must be reflected in the corresponding source 
documents.  
11.6
Retention of Records
The circumstances of completion or termination of the study notwithstanding, the 
investigator (or if regionally required, the head of the medical institution or the designated 
representative) is responsible for retaining all study documents, including but not limited to 
the protocol, copies of eCRFs, the Investigator's Brochure, and regulatory agency registration 
documents (eg, Form FDA 1572, ICFs, and IRB/IEC correspondence).  In addition, the 
sponsor will send a list of treatment codes by study subject to the investigator after the 
clinical database for this study has been locked. The site should plan to retain study 
documents, as directed by the sponsor and as required per local regulations, for at least 
2 years after the last approval of a marketing application in an ICH region and until there are 
no pending or contemplated marketing applications in an ICH region or at least 3 years have 
elapsed since the formal discontinuation of clinical development of the investigational 
product.


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It is requested that, at the completion of the required retention period or in the event that the 
investigator retires or relocates during the retention period, the investigator contacts the 
sponsor to provide the location where the records are archived, including contact information 
for the responsible party(ies).  This will allow the sponsor to assist in arranging for 
permanent archiving of the study records.
11.7
Auditing Procedures and Inspection
In addition to routine monitoring procedures, the sponsor’s Clinical Quality Assurance 
department conducts audits of clinical research activities in accordance with the sponsor’s 
SOPs to evaluate compliance with the principles of ICH GCP and all applicable local 
regulations.  If a government regulatory authority requests an inspection during the study or 
after its completion, the investigator must inform the sponsor immediately.
11.8
Handling of Amatuximab
All drug supplies are to be used only for this study and not for any other purpose.  All 
amatuximab will be supplied to the unblinded pharmacist (or qualified designee, as 
appropriate) by the sponsor.  Drug supplies must be kept in an appropriate secure area (eg, 
locked) in its original packaging, and stored according to the conditions specified on the 
label.  The pharmacist (or qualified designee, as appropriate) must maintain accurate records
of amatuximab delivery to the investigational site, inventory at the site, use for each subject, 
and amatuximab destruction or return.  Throughout the study, partially-used and empty vials, 
as well as any investigational product deemed unusable (eg, as a result of a temperature 
excursion) must be accounted for.  
On close-out of the site, all remaining used vials and unused vials may be destroyed onsite, 
according to the investigational site’s local destruction policy/standard operating procedures, 
following review of drug accountability records by the unblinded site monitor.  The 
investigational product may also be returned to the sponsor’s designated location if 
previously arranged with the sponsor.  The sponsor will assure that a final report of drug 
accountability to the vial level is prepared and maintained by the investigational site.  
A Drug Dispensing Log will be supplied by the sponsor.  This log must be kept current and 
should contain the following information:

Initial and subsequent inventory on receipt of amatuximab at the investigational site

Identification (subject number and initials) of each subject to whom the amatuximab was 
dispensed

Number of vials of amatuximab used at each visit per subject

Dates and lot numbers of all amatuximab dispensed 

Number and lot numbers of amatuximab vials destroyed 

Number and lot numbers of amatuximab vials returned


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All records and inventory must be available for inspection by the sponsor or its designee (ie, 
the unblinded CRA), the IRB/IEC, and the relevant regulatory agencies.
Additional details on the storage, handling and inventory of amatuximab will be provided in 
the Pharmacy Manual.  
11.9
Publication of Results
As no formal analyses will be performed there are no planned publications of the results.
11.10 Disclosure and Confidentiality
The contents of this protocol and any amendments and results obtained during the study 
should be kept confidential by the investigator, the investigator’s staff, and the IRB/IEC and 
will not be disclosed in whole or in part to others, or used for any purpose other than 
reviewing or performing the study, without the written consent of the sponsor.  No data 
collected as part of this study will be used in any written work, including publications, 
without the written consent of the sponsor.  These obligations of confidentiality and non-use 
shall in no way diminish such obligations as set forth in either the Confidentiality Agreement 
or Clinical Trial Agreement executed between the sponsor/CRO and the 
institution/investigator.
All persons assisting in the performance of this study must be bound by the obligations of 
confidentiality and non-use set forth in either the Confidentiality Agreement or Clinical Trial 
Agreement executed between the institution/investigator and the sponsor/CRO.
The study will be listed on www.clinicaltrials.gov and other registries, as appropriate.
11.11 Discontinuation of Study
The sponsor reserves the right to discontinue the study for medical reasons or any other 
reason at any time.  If a study is prematurely terminated or suspended, the sponsor will 
promptly inform the investigators/institutions and regulatory authorities of the termination or 
suspension and the reason(s) for the termination or suspension.  The IRB/IEC will also be 
informed promptly and provided the reason(s) for the termination or suspension by the 
sponsor or by the investigator/institution, as specified by the applicable regulatory 
requirement(s).
The investigator reserves the right to discontinue the study should his/her judgment so 
dictate.  If the investigator terminates or suspends a study without prior agreement of the 
sponsor, the investigator should inform the institution where applicable, and the 
investigator/institution should promptly inform the sponsor and the IRB/IEC and provide the 
sponsor and the IRB/IEC with a detailed written explanation of the termination or 
suspension.  Study records must be retained as noted above.


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11.12 Subject Insurance and Indemnity
The sponsor will provide insurance for any subjects participating in the study in accordance 
with all applicable laws and regulations.  The terms of insurance will be kept in the 
regulatory files.


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12 APPENDICES


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Appendix 1
National Cancer Institute Common Terminology Criteria for Hypersensitivity Adverse 
Events
NCI CTCAE CATEGORYa
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
IMMUNE SYSTEM DISORDERS
Allergic reaction
Definition:  A disorder 
characterized by an adverse local or 
general response from exposure to 
an allergen.
Transient flushing 
or rash, drug fever 
<38 degrees C
(<100.4 degrees F);
intervention not 
indicated
Intervention or 
infusion interruption 
indicated; responds 
promptly to 
symptomatic treatment 
(eg, antihistamines, 
NSAIDS, narcotics); 
prophylactic 
medications indicated 
for ≤24 hrs
Prolonged (eg, not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion);
recurrence of symptoms 
following initial 
improvement; 
hospitalization indicated 
for clinical sequelae (eg, 
renal impairment, 
pulmonary infiltrates)
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
Anaphylaxis
Definition: A disorder 
characterized by an acute 
inflammatory reaction resulting 
from the release of histamine and 
histamine-like substances from mast 
cells, causing a hypersensitivity 
immune response. Clinically, it 
presents with breathing difficulty, 
dizziness, hypotension, cyanosis 
and loss of consciousness and may 
lead to death.


Symptomatic 
bronchospasm, with or 
without urticaria; 
parenteral intervention 
indicated; allergy-related 
edema/angioedema; 
hypotension
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death


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NCI CTCAE CATEGORYa
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Cytokine release syndrome
Definition: A disorder 
characterized by nausea, headache, 
tachycardia, hypotension, rash, and 
shortness of breath; it is caused by 
the release of cytokines from the 
cells.
Mild reaction; 
infusion 
interruption not 
indicated; 
intervention not 
indicated
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment (eg, 
antihistamines, 
NSAIDS, narcotics, 
IV fluids); 
prophylactic 
medications indicated 
for ≤24 h
Prolonged (eg, not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion); recurrence 
of symptoms following 
initial improvement; 
hospitalization indicated 
for clinical sequelae (eg, 
renal impairment, 
pulmonary infiltrates)
Life-threatening 
consequences; 
pressor or 
ventilatory 
support indicated
Death
Serum sickness
Definition: A disorder 
characterized by a delayed-type 
hypersensitivity reaction to foreign 
proteins derived from an animal 
serum.  It occurs approximately 6 
to21 days following the 
administration of the foreign 
antigen. Symptoms include fever, 
arthralgia, myalgia, skin eruption, 
lymphadenopathy, chest marked 
discomfort and dyspnea.
Asymptomatic; 
clinical or 
diagnostic 
observations only; 
intervention not 
indicated
Moderate arthralgia; 
fever, rash, urticaria, 
antihistamines 
indicated
Severe arthralgia or 
arthritis; extensive rash; 
steroids or IV fluids 
indicated
Life-threatening 
consequences; 
pressor or 
ventilatory 
support indicated
Death
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Fever (in the absence of 
neutropenia, where neutropenia is 
defined as ANC <1.0 x 109/L)
Definition: A disorder 
characterized by elevation of the 
body's temperature above the upper 
limit of normal.
38.0–39.0C
(100.4–102.2F)
>39.0–40.0C
(102.3–104.0F)
>40.0C (>104.0F) for 
≤24 h
>40.0C 
(>104.0F) for 
>24 h
Death


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NCI CTCAE CATEGORYa
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Chills
Definition: A disorder 
characterized by a sensation of cold 
that often marks a physiologic 
response to sweating after a fever.
Mild sensation of 
cold; shivering; 
chattering of teeth
Moderate tremor of 
the entire body; 
narcotics indicated
Severe or prolonged, not 
responsive to narcotics


Infusion related reaction
Definition: A disorder 
characterized by adverse reaction to 
the infusion of pharmacological or 
biological substances
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment (eg, 
antihistamines, 
NSAIDS, narcotics, 
IV fluids); 
prophylactic 
medications
indicated for ≤24hrs 
Prolonged (eg, not 
rapidly responsive to
symptomatic medication 
and/or brief interruption 
of infusion); recurrence 
of symptoms following 
initial improvement; 
hospitalization indicated 
for clinical sequelae 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death
Infusion site extravasation
Definition: A disorder 
characterized by leakage of a 
pharmacologic or a biologic 
substance from the infusion site into 
the surrounding tissue. Signs and 
symptoms include induration, 
erythema, swelling, burning 
sensation and marked discomfort at 
the infusion site.

Erythema with 
associated symptoms 
(eg, edema, pain, 
induration, phlebitis)
Ulceration or necrosis; 
severe tissue damage; 
operative intervention 
indicated
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death


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NCI CTCAE CATEGORYa
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
SKIN AND SUBCUTANEOUS DISORDERS
Pruritus
Definition: A disorder characterized 
by an intense itching sensation.
Mild or localized; 
topical intervention 
indicated
Intense or widespread; 
intermittent; skin 
changes from 
scratching (eg, edema, 
papulation, 
excoriations, 
lichenification, 
oozing/crusts); oral 
intervention indicated; 
limiting instrumental 
activities of daily 
living (ADL)
Intense or widespread; 
constant; limiting 
selfcare ADL or sleep; 
oral corticosteroid or 
immunosuppressive 
therapy indicated


Urticaria 
Definition: A disorder 
characterized by an itchy skin 
eruption characterized by wheals 
with pale interiors and well-defined 
red margins.
Urticarial lesions 
covering <10% 
BSA; topical 
intervention 
indicated
Urticarial lesions 
covering 10–30% 
BSA; oral intervention 
indicated
Urticarial lesions 
covering >30% BSA; IV 
intervention indicated


RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Adult Respiratory Distress 
Syndrome 
Definition: A disorder 
characterized by progressive and 
life-threatening pulmonary distress 
in the absence of an underlying 
pulmonary condition, usually 
following major trauma or surgery.


Present with radiologic 
findings; intubation not 
indicated
Life-threatening 
respiratory or 
hemodynamic 
compromise; 
intubation or 
urgent 
intervention 
indicated
Death


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NCI CTCAE CATEGORYa
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Bronchospasm
Definition: A disorder characterized 
by a sudden contraction of the 
smooth muscles of the bronchial 
wall.
Mild symptoms; 
intervention not 
indicated
Symptomatic; medical 
intervention indicated; 
limiting instrumental 
ADL
Limiting self-care ADL; 
oxygen saturation 
decreased
Life-threatening 
respiratory or 
hemodynamic 
compromise; 
intubation or 
urgent 
intervention 
indicated
Death
Dyspnea 
Definition: A disorder characterized 
by an uncomfortable sensation of 
difficulty breathing.
Shortness of breath 
with moderate 
exertion
Shortness of breath 
with minimal exertion; 
limiting instrumental 
ADL
Shortness of breath at 
rest; limiting selfcare 
ADL
Life-threatening 
consequences; 
urgent 
intervention 
indicated
Death
Laryngeal edema
Definition: A disorder 
characterized by swelling due to an 
excessive accumulation of fluid in 
the larynx.
Asymptomatic; 
clinical or 
diagnostic 
observations only; 
intervention not 
indicated
Symptomatic; medical 
intervention indicated 
(eg, dexamethasone, 
epinephrine, 
antihistamines)
Stridor; respiratory 
distress; hospitalization 
indicated
Life-threatening 
airway 
compromise; 
urgent 
intervention 
indicated (eg, 
tracheotomy or 
intubation)
Death
ADL = activities of daily living; NSAIDS = nonsteroidal antiinflammatory drugs; IV = intravenous.
a)
The full NCI CTCAE v4.03 is available at the following web site: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf


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Appendix 2
Medical Dictionary for Regulatory Activities (MedDRA) 
Preferred Terms and Codes for Interstitial Lung 
Diseases Standardized MedDRA Query
MedDRA Preferred Term
MedDRA Code
Acute interstitial pneumonitis 
10066728
Allergic granulomatous angitis 
10048594
Alveoloar proteinosis 
10001881
Alveolitis 
10001889
Alveolitis allergic 
10001890
Alveolitis fibrosing 
10001892
Alveolitis necrotizing 
10050343
Bronchiolitis 
10006448
Diffuse alveolar damage
10060902
Eosinophilia myalgia syndrome 
10014952
Eosinophilic pneumonia 
10014962
Eosinophilic pneumonia acute 
10052832
Eosinophilic pneumonia chronic 
10052833
Idiopathic pneumonia syndrome 
10063725
Idiopathic pulmonary fibrosis 
10021240
Interstitial lung disease 
10022611
Lung infiltration 
10025102
Necrotising bronchiolitis 
10070831
Obliterative bronchiolitis 
10029888
Pneumonitis 
10035742
Progressive massive fibrosis 
10036805
Pulmonary fibrosis 
10037383
Pulmonary necrosis 
10058824
Pulmonary radiation injury 
10061473
Pulmonary toxicity
10061924
Pulmonary vasculitis 
10037457
Radiation alveolitis 
10037754
Radiation fibrosis – lung 
10037758
Radiation pneumonitis
10037765
Transfusion-related acute lung injury
10052235


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PROTOCOL SIGNATURE PAGE
Study Protocol Number:
MORAb-009-201
Study Protocol Title:
A Randomized, Double-blind, Placebo-controlled Study of the 
Safety and Efficacy of Amatuximab in Combination with 
Pemetrexed and Cisplatin in Subjects with Unresectable 
Malignant Pleural Mesothelioma
Investigational Product
Name:
Amatuximab (MORAb-009)
IND Number:
12894
EudraCT Number:
2014-004489-85
SIGNATURES
Authors:
Morphotek, Inc.
Date
Morphotek, Inc.
Date
PPD
PPD


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INVESTIGATOR SIGNATURE PAGE
Study Protocol Number:
MORAb-009-201
Study Protocol Title:
A Randomized, Double-blind, Placebo-controlled Study of the 
Safety and Efficacy of Amatuximab in Combination with 
Pemetrexed and Cisplatin in Subjects with Unresectable 
Malignant Pleural Mesothelioma
Investigational Product
Name:
Amatuximab (MORAb-009)
IND Number:
12894
EudraCT Number:
2014-004489-85
I have read this protocol and agree to conduct this study in accordance with all stipulations of 
the protocol and in accordance with International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) and all applicable 
local Good Clinical Practice (GCP) guidelines, including the Declaration of Helsinki.
<Name of institution>
Medical Institution
<Name, degree(s)>
Investigator
Signature
Date

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
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5
DETERMINATION OF SAMPLE SIZE
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6
STATISTICAL METHODS
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Study Endpoints
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Study Subjects
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6.2.2
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Data Analysis General Considerations
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Efficacy Analyses
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10 DEFINITIONS AND CONVENTIONS FOR DATA HANDLING
Study Day 1
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11 STATISTICAL SOFTWARE
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13 REFERENCES
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14 APPENDICES
14.1
National Cancer Institute Common Terminology Criteria for 
Hypersensitivity Adverse Events
NCI CTCAE 
CATEGORYa
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
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Medical Dictionary for Regulatory Activities (MedDRA) Version 
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