Clinical trial NCT03941093
Conditions: Pancreatic Cancer Non-resectable
Keywords: locally advanced pancreatic cancer unresectable pancreatic cancer
Sponsor: FibroGen
Start date: 2019-05-10; Completion date: 2024-06-11
Enrollment: 284 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine plus nab-paclitaxel (G/NP) or FOLFIRINOX in the treatment of participants with locally advanced, unresectable pancreatic cancer.

Detailed description:
Participants will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab with either G/NP or FOLFIRINOX, placebo with G/NP or FOLFIRINOX.

Each participant may receive up to 6 cycles of treatment (each treatment cycle is 28 days). Tumor tissue will be collected during resection to determine surgical outcome and for biomarker analysis. Tumor response will be evaluated by changes in CT scan, FDG-PET, CA 19-9, and NCCN® guidelines.

All participants randomized will have a safety follow-up visit approximately 28 days after the last dose of study treatment and a final safety follow-up phone call at approximately 60 days after the last dose.

Participants who complete study treatment will be evaluated for surgical exploration for possible R0 or R1 resection. Surgery will occur at least 4 weeks after the last dose (allowing for a wash-out period from treatment) and only after receipt of the recommendation from the central review board with regards to surgical eligibility. Surgery will occur no longer than 8 weeks after the last dose. Participants who undergo surgery will be evaluated for surgical complications for at least an additional 90 days following discharge from surgery.

Participants who are ineligible for surgical exploration (i.e. participants who did not complete study treatment or do not meet any of the protocol defined criteria or had a contraindication to surgery) will continue in the Follow-up period and receive treatment as per standard of care (SOC) for each institution.

All participants will be followed for disease progression (if not previously detected) or recurrence following resection (local progression or metastatic disease). Participants will also be followed for any additional anti-cancer therapy received for their pancreatic cancer. All participants will be followed for survival (until death) or until the last participant to complete treatment reaches 18 months post-treatment.

Arms: arm 1: Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX arm 2: Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX
Interventions: intervention 1: Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX intervention 2: Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX
Intervention descriptions: intervention 1: Drug: Pamrevlumab is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion.

Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: FOLFIRINOX is a combination of several agents administered on Days 1 and 15 of each 28 day treatment cycle via IV infusion. The specific agents are Oxaliplatin, Folinic Acid, Irinotecan, and Fluorouracil. intervention 2: Drug: Placebo is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion.

Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: FOLFIRINOX is a combination of several agents administered on Days 1 and 15 of each 28 day treatment cycle via IV infusion. The specific agents are Oxaliplatin, Folinic Acid, Irinotecan, and Fluorouracil.

Protocol documents:
Prot_000.pdf: 
TITLE PAGE 
PROTOCOL TITLE: 
A Phase 3, Randomized, Double-Blind Study of 
Pamrevlumab or Placebo in combination with either 
Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX 
as Neoadjuvant Treatment in Patients with Locally 
Advanced, Unresectable Pancreatic Cancer 
PROTOCOL NUMBER: 
FGCL-3019-087 
PHASE: 
Phase 3 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
KEY SPONSOR CONTACT(S): 
Name: 
 
Title: 
 
Telephone: 
 
 
Mobile: 
 
E-mail Address: 
 
IND NUMBER:  
EudraCT NUMBER: 
011952 
2019-001925-28 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
INDICATION: 
Locally Advanced Unresectable Pancreatic Cancer 
ORIGINAL PROTOCOL: 
05 November 2018 
Amendment 1.0:
Amendment 2.0: 
22 March 2019
27 September 2019 
Amendment 3.0: 
05 August 2020 
Amendment 4.0: 
25 October 2021 
Amendment 5.0: 
16 May 2022 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to FibroGen, Inc. No 
part of this document or any of the information contained herein may be transmitted, disclosed, 
shared, reproduced, published or utilized by any persons without prior written authorization by 
FibroGen, Inc.
NCT03941093


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INVESTIGATOR SIGNATURE PAGE STUDY ACKNOWLEDGEMENT 
A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in combination with 
either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients 
with Locally Advanced, Unresectable Pancreatic Cancer 
FGCL-3019-087 
Original: 05 November 2018 
Amendment 1.0: 22 March 2019 
Amendment 2.0: 27 September 2019 
Amendment 3.0: 05 August 2020 
Amendment 4.0: 25 October 2021 
Amendment 5.0: 16 May 2022 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and the current Investigator’s Brochure (IB), 
and I agree that it contains all necessary details for me and my staff to conduct this study as 
described. I will conduct this study as outlined herein and will make a reasonable effort to 
complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by FibroGen, Inc. I will discuss this material with them to ensure that they 
are fully informed about the drugs and the study. 
I will conduct the trial in accordance with the guidelines of Good Clinical Practice (GCP) 
including the archiving of essential documents, the Declaration of Helsinki, and any applicable 
local health authority, and Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) requirements. 
Investigator Name (Printed) 
Institution 
Signature 
Date 
Please return a copy of this signature page to FibroGen (or designee). Please retain the 
original for your study files. 


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CONFIRMATION OF PROTOCOL APPROVAL 
Original Protocol Date: 05 November 2018 
Amendment 1.0: 22 March 2019 
Amendment 2.0: 27 September 2019 
Amendment 3.0: 05 August 2020 
Amendment 4.0: 25 October 2021 
Amendment 5.0: 16 May 2022 
This protocol (FGCL-3019-087) is approved by FibroGen. 
IND Number: 011952 
EudraCT Number: 2019-001925-28 
FibroGen, Inc. 
Date 
*See appended final page for 21 CFR part 11compliant approval


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AMENDMENT 5.0: 
KEY CHANGES FROM AMENDMENT 4.0 
The protocol has been edited for clarity, consistency, and quality of content (typos, grammatical 
errors, flow, etc.). A redline version documenting all changes from the previous version of this 
document is available upon request. 
Description of Key Change 
Rationale for Change 
Section(s) Affected 
Per Protocol (PP) Population is added. 
Primary and secondary endpoints will 
also be conducted for PP population. 
This will distinguish between ITT and PP 
Population.  
Section 9.2.2 
Objective Response Rate (ORR) was 
added as a secondary endpoint and the 
ordering of secondary endpoints was 
clarified. 
ORR was added as a standard endpoint for 
oncology trials. 
Protocol Synopsis, 
Sections 3.2.3, 9.3.4 
Updates to exploratory endpoints 
Quality of Life (QOL) endpoint has been 
changed to exploratory and will be analyzed 
by mixed effect model for repeated 
measurements (MMRM) model.  
Additionally, a new exploratory endpoint was 
included to compare the number of cycles 
completed between arms.  Other 
administrative updates were made as well. 
Protocol Synopsis, 
Sections 3.2.4, 9.3.4 
Revised Exclusion Criteria 12, 13 and 
14 and prohibited conmed sections 
Removed specificity of exclusion criteria 
indicating that they only apply to subjects 
receiving G/NP chemotherapy as it may apply 
to other chemotherapy agents.  Specified that 
caution should be used when administering 
CYP inhibitors or inducers to subjects 
receiving FOLFIRINOX.  Specified that live 
vaccines should not be administered to 
subjects receiving FOLFIRINOX for 3 
months post end of treatment. 
Protocol Synopsis, 
Sections 5.2, 6.1.6.2. 
Updated statistical methods 
Statistical methods were revised/updated to 
align with updates made to Interim Analysis 
Plan and the Statistical Analysis Plan. 
Specifically, the objective of interim analysis 
of OS was changed to test lack of benefit from 
test of no harm. 
Protocol Synopsis, 
Sections 9.1, 9.2.2., 
9.3.1, 9.3.4.3, 
9.3.4.4, 9.3.4.5, 
9.3.4.6, 9.3.7 and 
9.4 


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1.
PROTOCOL SYNOPSIS
Study Title: 
A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or 
Placebo in combination with either Gemcitabine Plus Nab-
paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients 
with Locally Advanced, Unresectable Pancreatic Cancer 
Protocol Number: 
FGCL-3019-087 
Investigational Product: 
FG-3019 (Pamrevlumab) 
Study Phase: 
Phase 3 
Indication: 
Locally Advanced Unresectable Pancreatic Cancer 
Number of Subjects Planned: Approximately 280 
Number of Sites Planned: 
Approximately 100 (Global) 
OBJECTIVES 
Primary Objective: 
•
To evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab in
combination with either gemcitabine plus nab-paclitaxel (G/NP) or FOLFIRINOX
when compared to treatment with either G/NP or FOLFIRINOX alone in locally
advanced, unresectable pancreatic cancer.
Secondary Objectives: 
•
To evaluate the effect of neoadjuvant treatment with pamrevlumab in combination
with either G/NP or FOLFIRINOX on Event-Free Survival.
ENDPOINTS 
Primary Endpoint: 
•
The primary endpoint is overall survival (OS), defined as the time from randomization
to death due to any cause
Key Secondary Endpoint - Event-Free Survival (EFS) for Accelerated Approval: 
•
The EFS endpoint would be a composite time-to-event endpoint, the event being
‘treatment failure’ defined as the earliest occurrence of:
a) Failure to achieve disease-free status locally after completion of neoadjuvant
treatment  and/or after surgery (i.e., resection failure or progression that precludes
surgery)
b) Local or distant recurrence, or
c) Death


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Secondary Endpoints: 
•
Progression-free survival (PFS), defined as the time from randomization until
objective tumor progression or death (whichever occurs first)
•
RECIST 1.1 – Best Overall Objective Response Rate (ORR), defined as the proportion 
of patients who achieve CR (Complete Response) or PR (Partial Response) during
treatment period
Exploratory Endpoints: 
•
Change in Patient Reported Outcomes (PROs) as measured by:
− Mean change from baseline during the treatment period in physical function by
EORTC-QLQ-C30 
− Mean change from baseline during the treatment period in abdominal pain by NCI-
PRO-CTCAE 
− Mean change from baseline during the treatment period in fatigue by NCI-PRO-
CTCAE 
•
Proportion of all randomized subjects in whom R0 or R1 resection is achieved
•
Difference in OS between resected and non-resected subjects
•
The proportion of subjects considered eligible for surgical exploration per
protocol-defined criteria
•
Mean change from baseline during the treatment period in CA19-9
•
Change in FDG-PET SUVmax and metabolic tumor volume (MTV) at EOT when
compared to baseline
•
Correlative analyses of baseline CTGF serum levels with clinical outcomes
•
PK exposure-response analysis
•
Histological analysis in tumor tissues collected during resection
•
Evaluation of CTGF as prognostic/predictive biomarker
•
Evaluation of other selected protein and nucleic acid markers in plasma samples
•
Evaluation of number of chemotherapy cycles between the two arms
STUDY DESIGN 
This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of 
neoadjuvant treatment with pamrevlumab or placebo in combination with either G/NP or 
FOLFIRINOX in the treatment of locally advanced, unresectable pancreatic cancer subjects. 
Approximately 280 subjects will be enrolled. 


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STUDY PERIODS 
Screening Period (up to 30 days): 
Subjects will be evaluated per the protocol inclusion/exclusion criteria to determine eligibility 
for participation in this trial. During screening, a central review board (including radiologists 
and surgeons) will confirm if subjects have locally advanced, unresectable disease prior to 
enrollment. This central review board will also review each subjects’ baseline CT scan to 
determine the degree of superior mesenteric artery (SMA) encasement and whether or not they 
have unreconstructible disease for the purposes of stratification at randomization. The central 
review board will also evaluate subjects’ baseline PET scan to determine SUVmax. Protocol 
assessments will be completed during screening visits in accordance with Schedule of 
Assessments (SOA) to establish a baseline profile, including: demographics, medical history, 
clinical status and disease stage for each subject. Subjects determined to be eligible for 
participation will be enrolled in the trial and randomized to study treatment. Investigators will 
choose the chemotherapy treatment regimen (either G/NP or FOLFIRINOX), in collaboration 
with their subjects, during the screening period. 
Randomization: 
Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab 
with G/NP or FOLFIRINOX or placebo with G/NP or FOLFIRINOX. Subjects will be 
stratified at randomization by chemotherapy treatment regimen (G/NP or FOLFIRINOX), SMA 
encasement (> or ≤ 180 degrees), unreconstructible disease and geographic region. 
Neoadjuvant Treatment Period (~24-30 weeks): 
Subjects will receive up to 6 cycles of study treatment. Subjects’ clinical status and safety will 
be regularly evaluated. Efficacy assessments will be performed routinely to evaluate subjects’ 
quality of life and disease state. CT scans will be performed approximately every 8 weeks and 
evaluated by central imaging until disease progression is noted.  If disease progression occurs 
during the neoadjuvant treatment period, subjects will be discontinued from study treatment and 
continue in the follow-up period. RECIST response will be evaluated by central radiology. 
Eligibility Assessment for Surgical Exploration: 
Eligibility for surgical exploration will be evaluated for all subjects who complete study 
treatment. To be considered eligible for surgical exploration a subject must meet at least one of 
the four protocol-defined criteria and have no contraindication to surgery, as outlined below: 
The protocol-defined criteria for surgical eligibility are: 
•
Reduction in CA19-9 level ≥ 50%
•
FDG-PET SUVmax decrease by ≥ 30% at EOT when compared to baseline
•
Partial response [PR], complete response [CR], or stable disease [SD] per
RECIST 1.1 at EOT
•
Meet the definition of resectable or borderline resectable per NCCN®
Version 2.2018


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Contraindications to surgical eligibility are: 
•
Development of distant metastases or local progression per RECIST 1.1
•
Performance status of Karnofsky score ≤ 50
•
Unreconstructible disease as determined by central radiological/surgical review
•
Other conditions that are considered by PI or surgeon to be contraindications to
surgery
The site will be required to provide information to the central review board following the 
subject’s EOT visit (i.e. CT scan, PET scan, CA19-9 values).  The central review board will 
determine RECIST response, PET SUVmax response, unreconstructible disease and NCCN 
status.  CA19-9 response will be determined by the central lab.  The site will provide additional 
information to the central review board following the subject’s Safety Follow-up Visit (i.e. 
subject performance status and a summary of any existing medical 
conditions/contraindications).  Considering all the information provided, the central review 
board (to include radiologists, surgeons and oncologists) will then determine whether or not a 
subject is eligible for surgical exploration per protocol. The central review board will provide 
their assessment of surgical eligibility to the site within 5 business days of receipt of all 
required information (approximately 1 week after the Safety Follow-up Visit). After the 
recommendation from central review board is received at the site, the PI and surgeon will make 
the final decision as to whether or not a subject will undergo surgery. All instances of 
discordance between the determination of eligibility for surgical exploration by the central 
review board and the action taken by the site with regards to surgical exploration will be 
documented in the clinical database. 
Subjects who undergo surgical exploration within the protocol specified window will be 
followed for surgical complications and outcomes per protocol.  Tissue samples will be 
collected during resection and provided to central pathology. 
Subjects who do not undergo surgical exploration (e.g. subjects who did not complete treatment 
or do not meet any of the protocol defined criteria or had a contraindication to surgery) will 
continue in the Follow-up period and receive treatment as per standard of care (SOC) for each 
institution. 
Surgery: 
Surgery will occur at least 4 weeks after the last dose (allowing for a wash-out period from 
treatment) and only after receipt of the recommendation from the central review board with 
regards to surgical eligibility. Surgery will occur no longer than 8 weeks after the last dose. 
An outcome of R0 or R1 will be considered a ‘Resection Achieved’ while an outcome of R2 or 
partial resection will be considered a ‘Resection Not Achieved’.  Final surgical outcomes for all 
‘Resection Achieved’ subjects will be determined by the central pathology lab.  The 
sponsor/sites remain blinded to the central pathology lab assessments until their final analysis. 
If a subject undergoes surgical exploration, but the surgeon is unable to perform resection (e.g. 
due to identification of metastases or extensive vascular involvement), it will be considered a 
‘Resection Not Attempted’. 


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Surgery will be performed in accordance with institutional standards and SOPs. Surgeons 
performing surgery for this study will be trained on the protocol, including criteria for surgical 
exploration. All subjects who undergo surgical exploration will be followed for surgical safety 
for 90 days (+/- 3 days) post discharge. 
Safety Follow-up: 
All subjects randomized will have a safety follow-up visit approximately 28 days after the last 
dose of study treatment and a final safety follow-up phone call at 60 days post last dose. 
However, if the investigator becomes aware of any serious adverse event that may be possibly 
related to study treatment after this protocol-required reporting period, the investigator may 
report the event to FibroGen within 24 hours following the investigator’s knowledge of the 
event. 
Follow-up Period: 
Subjects will be followed for disease progression (if not previously detected) or recurrence 
following resection (local or distant recurrence).  For subjects who complete treatment without 
evidence of disease progression and do not undergo resection, CT scans will continue to be 
performed approximately every 8 weeks and evaluated by central imaging until progression is 
detected (per RECIST 1.1).  For subjects who undergo resection, follow-up CT scans to 
evaluate recurrence of disease will be evaluated by central imaging and performed 
approximately; every 4 months up to 2 years post-resection and every 6 months from 2 years to 
5 years post-resection.  The investigator may perform an “off schedule” CT scan at any time 
post resection if recurrence of disease is suspected clinically; these scans will be submitted to 
central imaging for review and confirmation of recurrence/disease progression.  Subjects in 
follow-up will also be followed for any additional anti-cancer therapy received for their 
pancreatic cancer. All subjects will be followed for survival (until death) or until study closure 
(expected when the last subject to complete treatment reaches 18 months post-treatment). 
Guidance was provided to all sites regarding conduct of this clinical trial during the COVID-19 
global pandemic.  Details are also captured within the body of the protocol. 


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SUBJECT ELIGIBILITY CRITERIA 
Key Inclusion Criteria: 
• Understand and sign informed consent; be willing to comply with study procedures, 
including surgery 
• Age >18 years 
• Histologically or cytologically proven diagnosis of pancreatic ductal 
adenocarcinoma (PDAC) 
• Locally advanced and unresectable pancreatic cancer according to 
NCCN Guidelines® Version 2.2018 as determined by central imaging 
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors 
RECIST 1.1 criteria as determined by central imaging 
• ECOG performance status of 0 or 1 
• Adequate liver, bone marrow, and renal function 
• Less than grade 2 pre-existing peripheral neuropathy 
Key Exclusion Criteria: 
• Prior chemotherapy or radiation for pancreatic cancer 
• Previous (within the past 3 years) or concurrent malignancy diagnosis except 
non-melanoma skin cancer and in situ carcinomas (excluding in-situ breast cancer) 
• No major surgery for 4 weeks prior to signing consent form. Biliary stents are 
permitted. 
• Subjects with a history of; interstitial pneumonia, HCV, HBV or HIV infection  
• Subjects who have been administered a live vaccine within 4 weeks prior to the first 
administration of therapy 
• Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or 
CYP3A4  


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STUDY TREATMENT 
Investigators and their subjects will choose to be treated with either Gemcitabine plus Nab-
paclitaxel or FOLFIRINOX in combination with pamrevlumab or placebo in the neoadjuvant 
treatment period.  Only one chemotherapy treatment regimen may be administered in 
combination with pamrevlumab or placebo during the treatment period. 
Dose and Mode of Administration: 
Study treatment will be administered in accordance with the schedule outlined below. 
Pamrevlumab (or Placebo) - 35 mg/kg, IV, Days 1 and 15 of each cycle; additional dose 
given on Day 8 of Cycle 1 only 
and 
Gemcitabine - 1000 mg/m2 by IV infusion on Days 1, 8 and 15 of each 28-day treatment cycle 
Nab-paclitaxel - 125 mg/m2 by IV infusion on Days 1, 8 and 15 of each 28-day treatment cycle 
OR 
FOLFIRINOX 
Oxaliplatin – 85 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment cycle 
Folinic Acid/Leucovorin – 400 mg/m2 by IV infusion on Days 1 and 15 of each 28-day 
treatment cycle 
Irinotecan* – 180 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment cycle 
Fluorouracil* – 400 mg/m2 by IV infusion (bolus infusion) on Days 1 and 15 of each 28-day 
treatment cycle 
Fluorouracil – 2400 mg/m2 by IV infusion (46 hour continuous infusion) on Days 1-3 and 
Days 15-17 of each 28 day treatment cycle 
*Doses may be adjusted per local/institutional guidelines to support modified FOLFIRINOX dosing regimen
(mFOLFIRINOX) 
Other Important Information: 
Regular supportive care as clinically indicated is permitted during this trial. 
Pamrevlumab should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies. 
Gemcitabine, nab-paclitaxel or FOLFIRINOX should not be administered to subjects with a 
history of allergic or anaphylactic reaction to these products or their excipients. 
Interactions between the gemcitabine, nab-paclitaxel or FOLFIRINOX and concomitant 
medications are described in their respective package inserts/SmPCs.   
In accordance with the product package insert (SmPC), certain drugs that inhibit or induce 
CYP3A4 or CYP2C8 should be used with caution in subjects receiving the Nab-paclitaxel or 
FOLFIRINOX.   


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Live vaccines are prohibited for subjects receiving the G/NP or FOLFIRINOX chemotherapy 
regimen during the treatment period and for 3 months after the last dose of study therapy. 
Female subjects of childbearing potential are required to use highly effective contraception 
methods during the conduct of the study and for 6 months after the last dose of study drug. 
Male subjects with partners of childbearing potential are required to use highly effective 
contraception methods during the conduct of the study and for 6 months after the last dose of 
study drug. 
DATA MONITORING COMMITTEE 
An independent Data Monitoring Committee (DMC) will be established. A DMC charter will 
establish the rules, meeting frequency, and scope of responsibilities of the committee. 
STATISTICAL METHODS 
Sample Size Calculations: 
The study is planned to enroll approximately 280 subjects with 1:1 randomization ratio to the 
two treatment arms. This sample size is estimated based on the assumption that the median OS 
for the pamrevlumab arm and the placebo arm are 24 and 16.3 months, respectively. This 
improvement represents a hazard ratio (HR) of 0.68. With this HR, 233 deaths will provide at 
least 80% power with a significance level of 0.05. With the enrollment of approximately 280 
subjects, 233 deaths are estimated by the end of the Follow-up period. 
Based on the treatment effect on EFS has a hazard ratio 0.60, then 161 events would be 
required to provide 75% power when using a stratified log-rank statistic with (one-sided) 0.005 
false positive error rate. 
Statistical Analysis Methods: 
Event free survival (EFS) will be used as a surrogate endpoint for OS at a pre-planned interim 
analysis. A hierarchical approach for analysis is described.  If the interim analysis of the effect 
of pamrevlumab on EFS is statistically significant at two-sided p=0.01, then that alpha will be 
carried forward to the final analysis of OS, which then would be conducted at the two-sided 
p=0.05 level.  If the effect of pamrevlumab on EFS is not statistically significant at two-sided 
p=0.01, then the final analysis of pamrevlumab’s effect on OS would be conducted at the two-
sided p=0.04 level.  
At the time approximately 161 EFS events occur in the trial (or more depending on completion 
of accrual), the DMC will conduct an  interim look of OS for lack of benefit analysis, using an 
O’Brien-Fleming monitoring boundary, if the EFS analysis rejects the null hypotheses at an 
alpha level of 0.01. Following the completion of the interim analysis for EFS/OS, procedures 
will be in place to avoid pre-judgment of OS data by properly maintaining its confidentiality 
until final OS analysis is complete or unless there is agreement with the Regulatory agency to 
do otherwise. 
All efficacy endpoints will be analyzed using the ITT or PP population and safety will be 
analyzed using the safety population. 


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The OS, event-free survival (EFS), and progression-free survival (PFS) endpoints will be 
analyzed using the Cox proportional hazard model adjusting for randomization stratification 
factors.  
The exploratory endpoints of mean change from baseline during the treatment period in 
physical function by EORTC-QLQ-C30, mean change from baseline during the treatment 
period in abdominal pain by NCI-PRO-CTCAE, mean change from baseline during the 
treatment period in fatigue by NCI-PRO-CTCAE will be analyzed using a MMRM model. All 
analyses will be adjusted by the randomization factors.  
Resection rate will be analyzed using Cochran-Mantel-Haenszel (CMH) test adjusting for 
randomization stratification factors.  
Continuous variables will be presented by descriptive statistics: n, mean, standard deviation or 
standard error, median, minimum, and maximum. Categorical variables will be presented by 
counts of subjects and percentage. Two-sided 95% confidence intervals will be included for the 
key efficacy parameters. 
Safety Analyses: 
Treatment-emergent adverse events (TEAEs) will be summarized by treatment arm. Treatment-
emergent deaths, serious TEAEs, TEAEs with grade 3 or 4 per CTCAE criteria, and TEAEs 
leading to study or treatment discontinuation will be summarized separately. 
Surgical complications, clinically significant changes from baseline in vital signs, laboratory 
tests, and ECGs will be assessed. 
Human anti-human antibody data will be summarized in a separate report. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
and the applicable regulatory requirement(s), including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR SIGNATURE PAGE STUDY ACKNOWLEDGEMENT ...............................2 
INVESTIGATOR STATEMENT ...................................................................................................2 
CONFIRMATION OF PROTOCOL APPROVAL.........................................................................3 
AMENDMENT 5.0: KEY CHANGES FROM AMENDMENT 4.0 ...........................................4 
1. 
PROTOCOL SYNOPSIS .............................................................................................5 
TABLE OF CONTENTS ...............................................................................................................14 
LIST OF TABLES .........................................................................................................................19 
LIST OF FIGURES .......................................................................................................................19 
2. 
INTRODUCTION ......................................................................................................20 
2.1. 
Description of Pamrevlumab ......................................................................................20 
2.2. 
Locally Advanced Unresectable Pancreatic Cancer ...................................................20 
2.2.1. 
Relevance of Connective Tissue Growth Factor (CTGF) in Pancreatic 
Cancer .........................................................................................................................21 
2.3. 
Rationale .....................................................................................................................22 
2.3.1. 
Nonclinical Studies .....................................................................................................22 
2.3.2. 
Clinical Studies ...........................................................................................................22 
2.3.3. 
Dose Rationale ............................................................................................................23 
2.3.4. 
Safety Summary ..........................................................................................................24 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................26 
3.1. 
Objectives ...................................................................................................................26 
3.1.1. 
Primary Objective .......................................................................................................26 
3.1.2. 
Secondary Objectives .................................................................................................26 
3.2. 
Endpoints ....................................................................................................................26 
3.2.1. 
Primary Endpoint ........................................................................................................26 
3.2.2. 
Key Secondary Endpoint - Event-Free Survival (EFS) for Accelerated 
Approval .....................................................................................................................26 
3.2.3. 
Secondary Endpoints ..................................................................................................26 
3.2.4. 
Exploratory Endpoints ................................................................................................27 
4. 
INVESTIGATIONAL PLAN .....................................................................................28 
4.1. 
Overall Study Design ..................................................................................................28 
4.1.1. 
Estimated Study Duration ...........................................................................................30 


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4.1.2. 
Randomization ............................................................................................................31 
4.1.3. 
Treatment Assignment ................................................................................................32 
4.2. 
Blinding ......................................................................................................................32 
4.2.1. 
Maintenance of Blinding ............................................................................................32 
4.2.2. 
Planned and Unplanned Unblinding of Treatment Assignment .................................32 
4.2.3. 
Unblinding of Treatment Assignment for Interim Analysis .......................................32 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................33 
5.1. 
Subject Inclusion Criteria ...........................................................................................33 
5.2. 
Subject Exclusion Criteria ..........................................................................................34 
5.3. 
Subject Withdrawal Criteria .......................................................................................34 
5.3.1. 
Withdrawal Criteria from Neoadjuvant Treatment Period .........................................35 
5.3.2. 
Withdrawal Criteria for Follow-up Period .................................................................35 
5.4. 
Replacement of Study Subjects ..................................................................................35 
5.5. 
Study Termination ......................................................................................................35 
6. 
TREATMENT OF SUBJECTS ..................................................................................36 
6.1. 
Study Treatment ..........................................................................................................36 
6.1.1. 
Pamrevlumab (FG-3019) or Placebo ..........................................................................36 
6.1.2. 
Gemcitabine and Nab-paclitaxel .................................................................................36 
6.1.3. 
FOLFIRINOX .............................................................................................................37 
6.1.4. 
Dose Schedules and Modifications .............................................................................37 
6.1.4.1. 
Dose Omissions and Modified Schedules (Gemcitabine plus Nab-paclitaxel) ..........38 
6.1.4.2. 
Dose Omissions and Modified Schedules (FOLFIRINOX) .......................................39 
6.1.4.3. 
Dose Modifications .....................................................................................................39 
6.1.5. 
Treatment Compliance ................................................................................................39 
6.1.6. 
Concomitant Medications ...........................................................................................40 
6.1.6.1. 
Permitted Concomitant Medications ..........................................................................40 
6.1.6.2. 
Prohibited Concomitant Medications .........................................................................40 
6.1.6.3. 
Contraception Requirements ......................................................................................41 
6.2. 
Study Drug Materials and Management .....................................................................41 
6.2.1. 
FibroGen Investigational Product (Pamrevlumab) or Placebo ...................................41 
6.2.2. 
Formulation .................................................................................................................42 
6.2.3. 
Study Drug Packaging and Labeling ..........................................................................42 
6.2.4. 
Study Drug Storage .....................................................................................................42 


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6.2.5. 
Study Drug Preparation ..............................................................................................42 
6.2.6. 
Study Drug Administration .........................................................................................42 
6.2.7. 
Study Drug Handling and Disposal ............................................................................43 
7. 
ASSESSMENTS OF EFFICACY ..............................................................................44 
7.1. 
Study Assessments ......................................................................................................44 
7.1.1. 
Screening Period .........................................................................................................44 
7.1.1.1. 
Role of Central Review in Determining Eligibility for Participation and 
Defining Stratification Factors ...................................................................................44 
7.1.2. 
Neoadjuvant Treatment Period ...................................................................................45 
7.1.3. 
Safety Follow-up ........................................................................................................45 
7.1.4. 
Determination of Eligibility for Surgical Exploration ................................................45 
7.1.4.1. 
Role of Central Review in Determination of Eligibility for Surgical 
Exploration .................................................................................................................46 
7.1.5. 
Surgical Exploration/Surgical Resection ....................................................................47 
7.1.6. 
Follow-up Period ........................................................................................................47 
7.1.7. 
Missed Visits ..............................................................................................................48 
7.1.8. 
Unscheduled Visits .....................................................................................................48 
7.1.9. 
Early Withdrawal from Treatment ..............................................................................48 
7.2. 
Assessments ................................................................................................................48 
7.2.1. 
Vital Signs (Including Weight and Height) ................................................................49 
7.2.2. 
Physical Exam ............................................................................................................49 
7.2.3. 
Electrocardiogram (ECG or EKG) .............................................................................49 
7.2.4. 
Laboratory Evaluations ...............................................................................................49 
7.2.4.1. 
Central Laboratory Evaluations ..................................................................................49 
7.2.4.2. 
Local Laboratory Evaluations .....................................................................................50 
7.2.4.3. 
Pharmacokinetics and Pharmacodynamics .................................................................50 
7.2.5. 
Performance Status .....................................................................................................51 
7.2.5.1. 
Eastern Cooperative Oncology Group (ECOG) .........................................................51 
7.2.5.2. 
Karnofsky Performance Scale Index ..........................................................................51 
7.2.6. 
Carbohydrate Antigen 19-9 (CA 19-9) .......................................................................52 
7.2.7. 
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scan .................52 
7.2.8. 
Computer Tomography (CT) Scan .............................................................................52 
7.2.9. 
Patient Reported Outcomes (PROs) ...........................................................................52 


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7.2.9.1. 
EORTC-QLQ-C30 ......................................................................................................53 
7.2.9.2. 
PRO-CTCAE™ ..........................................................................................................53 
7.2.10. 
Surgical Outcomes and Complications .......................................................................53 
7.2.10.1. 
Surgical Complications ...............................................................................................53 
7.2.10.2. 
Surgical Outcomes ......................................................................................................53 
8. 
ASSESSMENTS OF SAFETY ..................................................................................54 
8.1. 
Background .................................................................................................................54 
8.2. 
Definitions ..................................................................................................................54 
8.2.1. 
Definition of an Adverse Event (AE) .........................................................................54 
8.2.2. 
Definition of a Serious Adverse Event (SAE) ............................................................54 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events ........................55 
8.3.1. 
Adverse Event Reporting Period ................................................................................55 
8.3.2. 
Adverse Event Eliciting/Reporting .............................................................................55 
8.3.3. 
Assessing Adverse Event Severity .............................................................................56 
8.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug ......................................56 
8.3.5. 
Reporting Serious Adverse Events .............................................................................57 
8.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review 
Board / Independent Ethics Committee ......................................................................58 
8.3.5.2. 
Deaths .........................................................................................................................58 
8.3.6. 
Pregnancies: Reporting and Follow-up of Subjects and Female Partners of 
Subjects .......................................................................................................................58 
8.3.7. 
Abnormal Laboratory Findings ..................................................................................59 
8.3.8. 
Disease Progression ....................................................................................................59 
8.3.9. 
Special Reporting Situations .......................................................................................59 
8.3.10. 
Safety Monitoring .......................................................................................................60 
8.3.10.1. 
Data Monitoring Committee (DMC) ..........................................................................60 
9. 
STATISTICS ..............................................................................................................61 
9.1. 
Sample Size Determination ........................................................................................61 
9.2. 
Analysis Populations ..................................................................................................61 
9.2.1. 
Intent to Treat (ITT) Population .................................................................................61 
9.2.2. 
Per Protocol (PP) Population ......................................................................................61 
9.2.3. 
Safety Population ........................................................................................................61 
9.3. 
Statistical Analysis ......................................................................................................62 


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9.3.1. 
General Considerations ...............................................................................................62 
9.3.2. 
Subject Enrollment and Disposition ...........................................................................62 
9.3.3. 
Demographics and Baseline Characteristics ...............................................................62 
9.3.4. 
Efficacy Analyses .......................................................................................................62 
9.3.4.1. 
Analysis of Overall Survival (Primary Endpoint) ......................................................62 
9.3.4.2. 
Analysis of Event-free Survival (EFS) (Surrogate Endpoint for Accelerated 
Approval) ....................................................................................................................63 
9.3.4.3. 
Analysis of Progression-free Survival (PFS) ..............................................................63 
9.3.4.4. 
Analysis of Best Overall Objective Response Rate (ORR) ........................................63 
9.3.4.5. 
Analysis of Physical Functioning  by EORTC-QLQ-C30 .........................................64 
9.3.4.6. 
Analysis of Abdominal Pain and Fatigue Score by NCI-PRO-CTCAE.....................64 
9.3.5. 
Pharmacokinetic Analyses ..........................................................................................64 
9.3.6. 
Safety Analyses ..........................................................................................................64 
9.3.7. 
Sensitivity Analyses ....................................................................................................65 
9.4. 
Interim Analysis ..........................................................................................................65 
9.5. 
Statistical Analysis Plan .............................................................................................65 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................66 
10.1. 
Data Quality Assurance ..............................................................................................66 
10.2. 
Audit and Inspection ...................................................................................................66 
11. 
ETHICS ......................................................................................................................67 
11.1. 
Ethical Considerations ................................................................................................67 
11.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee ...................................................................................................................67 
11.3. 
Subject Information and Consent ...............................................................................67 
11.4. 
Subject Confidentiality ...............................................................................................68 
12. 
DATA HANDLING AND RECORD KEEPING ......................................................69 
12.1. 
Source Documents ......................................................................................................69 
12.2. 
Direct Access to Source Documents ...........................................................................69 
12.3. 
Data Collection, Handling, and Verification ..............................................................69 
12.4. 
Protocol Deviations ....................................................................................................69 
12.5. 
Retention of Data ........................................................................................................70 
12.6. 
Financial Disclosure ...................................................................................................70 
13. 
PUBLICATION POLICY ..........................................................................................71 


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14. 
REFERENCES ...........................................................................................................72 
APPENDICES ...............................................................................................................................74 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................75 
APPENDIX 2. PHARMACOKINETIC AND PHARMACODYNAMIC SAMPLING 
TIMES.................................................................................................................79 
APPENDIX 3. PERFORMANCE STATUS SCALES ..............................................................80 
APPENDIX 4. CLAVIEN-DINDO CLASSIFICATION OF SURGICAL 
COMPLICATIONS ............................................................................................81 
APPENDIX 5:  NCCN GUIDELINES VERSION 2.2018 .........................................................82 
 
LIST OF TABLES 
Table 1: 
FG-3019 (or Placebo): Dose, Route, and Administration ..........................................36 
Table 2: 
Gemcitabine and Nab-paclitaxel: Dose, Route and Administration ...........................37 
Table 3: 
Laboratory Tests .........................................................................................................50 
 
LIST OF FIGURES 
Figure 1: 
FGCL-3019-087 Study Schema .................................................................................31 
Figure 2: 
Central Review Schema for Determination of Eligibility for Surgical 
Exploration .................................................................................................................47 
 


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2. 
INTRODUCTION 
2.1. 
Description of Pamrevlumab 
Pamrevlumab is a recombinant fully human immunoglobulin G1 (IgG) kappa monoclonal 
antibody that binds to connective tissue growth factor (CTGF) and is being developed for 
treatment of diseases in which tissue fibrosis has a major pathogenic role. These diseases include 
liver fibrosis due to hepatitis, idiopathic pulmonary fibrosis, certain fibrotic cancers and 
Duchenne muscular dystrophy (DMD). Pamrevlumab (MW ~150 kDa) is produced by 
mammalian Chinese hamster ovary (CHO) fed-batch cell culture system. Pamrevlumab contains 
1,326 amino acids and binds with high affinity to domain 2 of CTGF (dissociation constant: 
Kd=0.1–0.2 nM). 
2.2. 
Locally Advanced Unresectable Pancreatic Cancer 
Pancreatic ductal adenocarcinoma is an aggressive cancer with poor prognosis; the median OS is 
5 to 8 months and 5-year survival is 8.2% (SEER, 2018). This positions PDAC to have the worst 
outcome of all gastrointestinal cancers and the fourth leading cause of cancer related mortality. 
The incidence of PDAC increased by 1.2% annually between 2000 and 2012, likely due to 
increasing incidences of obesity and type II diabetes mellitus in the US and worldwide 
(American Cancer Society, 2016). 
Pancreatic cancer has notably been resistant to chemotherapy. Gemcitabine alone has been 
shown to improve PFS and OS and was approved for use in locally advanced and metastatic 
pancreatic cancer in 1996 (Burris 1997). Most clinical studies in PDAC focus on patients with 
metastatic disease and have demonstrated only modest improvements in OS. Recently approved 
therapies include nab-paclitaxel in combination with gemcitabine, which improved OS by 1.8 
months compared with gemcitabine alone, and FOLFIRINOX [oxaliplatin, irinotecan, 5-FU, and 
leucovorin]) alone, which improved OS by 3.7 months compared to gemcitabine  
(Von Hoff 2013; Conroy 2011).  
In general, surgical resection offers patients the best chance at long-term survival (5 year 
survival 27%) and possibly a cure, but the majority of patients present with advanced 
unresectable disease at the time of diagnosis. A large meta-analysis of available therapies from 
1996 to 2009 reported that neoadjuvant therapy increased the resectability rate in unresectable 
and borderline resectable patients to 30%, with the increase of median OS from 10.2 months to 
20.5 months (Gillen 2010). This data provides a strong rationale for neoadjuvant therapy 
followed by resection in order to improve OS in LAPC. However, no SOC exists for neoadjuvant 
therapy in patients with LAPC. 
Recent trials in LAPC have explored the effects of single agent chemotherapy in combination 
with radiotherapy on OS (Mukherjee 2013). A 6-months treatment with standard-of-care 
chemotherapy alone or chemo-radiation in patients with LAPC only led to a 6% surgical 
resection rate in treated patients, with a median follow-up of 36.7 months, the median overall 
survival from the date of the first randomization was not significantly different between 
chemotherapy at 16.5 months and chemoradiotherapy at 15.2 months (p = 0.83). Although the 
LAP07 trial failed to show a survival benefit with the use of radiation therapy (Hammel 2016), 
other trials (e.g., ECOG 4201 [Loehrer 2011]) have led to the opposite conclusion. In terms of 


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treatment, there has also been an increased interest in combination chemotherapies followed by 
surgery with curative intent (Dean 2016, Hammel 2016) for LAPC patients. 
In the LAPACT trial, the neoadjuvant therapy with gemcitabine/nab-paclitaxel was used in 110 
LAPC patients for 6 cycles. The resection rate established in this trial was 15%, and 1 year OS 
rate was 72% (long term OS not reported to date). This trial establishes benchmark resection rate 
for LAPC patients following combination therapy with gemcitabine/nab-paclitaxel  
(Hammel 2018). 
Significant progress has been made in recent years with systematic chemotherapies of LAPC. In 
a study using a nab-paclitaxel plus gemcitabine combination, 77% of 177 patients had at least a 
50% reduction in CA19-9 levels, and CA19-9 response was found to be an independent 
prognostic factor for OS (Reni 2017). In the LAPACT study, serum CA19-9 concentrations 
decreased after 6 cycles of chemotherapy in most patients and 15 % of them underwent curative-
intent surgery (Philip 2020). In a meta-analysis about FOLFIRINOX in LAPC, the authors 
reported a median OS of 24.2 months; in addition, 25 (9%) of patients could have a surgical 
resection, of whom 78 (4%) had an R0 resection (Suker 2016). 
In LAPC, a novel endpoint is needed that would have considerable reliability in predicting the 
effects on OS of both neoadjuvant therapies and surgical resection.  Surgery has not only a 
therapeutic role in LAPC, but also a diagnostic role in our proposed definition of EFS, in that it 
is used to assess local disease-free status at the end of induction therapy.  However, to achieve 
sensitivity as well to the presence and the impact of microscopic distal disease, the proposed 
definition of EFS is based on time to detected disease, either through surgery for local disease or, 
in a manner analogous to ‘DFS in the adjuvant setting,’ through subsequent detection of local or 
distal disease by CT, or to death.  
The LAPC patient population represents a high unmet need as no standard of care has been 
established in prospective, randomized trials. At the same time, increasing efficacy of 
neoadjuvant therapies in LAPC justifies revisiting study endpoint in order to better reflect 
treatment efficacy beyond effects on duration of OS.  Based on our nonclinical tumor model data 
and clinical data we believe that pamrevlumab with its antifibrotic mechanism of action and 
when combined in a neoadjuvant setting with SOC chemotherapy, may provide the unique 
opportunity to impact both event-free survival in LAPC and OS. 
2.2.1. 
Relevance of Connective Tissue Growth Factor (CTGF) in Pancreatic Cancer 
Connective tissue growth factor is a secreted glycoprotein produced by fibroblasts and 
myofibroblasts, endothelial cells, activated stellate cells, and other cell types. Its expression is 
induced by a variety of regulatory modulators, including TGF-β and vascular endothelial growth 
factor, as well as environmental conditions such as hypoxia, pressure, and increased tissue 
stiffness. Cellular functions modulated by CTGF include secretion and/or organization of 
extracellular matrix, cell proliferation, survival, adhesion, migration, and epithelial to 
mesenchymal transition. These biological activities are associated with aberrant tissue repair 
(i.e., fibrosis) and tumorigenesis. Elevated CTGF expression is detected in many tumor types, in 
particular, PDAC and invasive breast carcinoma (Wenger 1999, Xie 2001). Among 19 samples 
of pancreatic tumors, 15 showed an average 59-fold increase of CTGF expression, compared 
with a 4.5-fold increase observed in chronic pancreatitis (Wenger 1999). CTGF was identified as 


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an invasion-specific gene in PDAC (Ryu 2001) and is highly expressed within the neoplastic 
epithelium (Iacobuzio-Donahue 2002). In any specific tumor, CTGF can be expressed by PDAC 
tumor cells, by stellate or stromal cells within the tumor, or by both cell types (Hidalgo 2012, 
Wenger 1999, Iacobuzio-Donahue 2002, Frazier 1997, Hartel 2004). 
2.3. 
Rationale 
2.3.1. 
Nonclinical Studies 
FibroGen has evaluated the efficacy/pharmacology, pharmacokinetics and nonclinical safety of 
pamrevlumab per ICH guidelines to support the clinical development of pamrevlumab in 
pancreatic cancer. Pharmacodynamic studies were conducted in various tumor models to 
evaluate pamrevlumab as a modulator of tumor cell survival, chemoresistance, and tumor cell 
invasion/migration. The pharmacokinetics of pamrevlumab have been characterized following 
single oral doses in rats, rabbits, and monkeys and after repeated oral doses in toxicity studies in 
mice, rats, rabbits and monkeys. The nonclinical safety of pamrevlumab was evaluated in 
repeated dose toxicity studies in mice, rats and monkeys. Cross-Reactivity studies with 
pamrevlumab have been conducted with mouse and human tissues. The potential effects of 
pamrevlumab on wound healing have been evaluated in an abdominal wound healing model in 
rats. 
Summaries of all completed, nonclinical studies supporting the pancreatic cancer indication can 
be found in the current version of the Investigator’s Brochure. 
2.3.2. 
Clinical Studies 
Pamrevlumab is in clinical development for the treatment of pancreatic cancer. The Sponsor has 
conducted 2 clinical studies in pancreatic cancer: Study FGCL-MC3019-028 (Study 028) was 
completed in June 2014 and Study FGCL-3019-069 (Study 069) in which the study treatment 
and surgery periods have been completed and analyzed. 
The results of Study 028, an open label study, indicate that pamrevlumab can be safely combined 
with gemcitabine and erlotinib without increased toxicity in advanced Stage 3 and Stage 4 
pancreatic cancer patients. The efficacy results (including positive drug-biomarker activity) show 
potential survival benefit with pamrevlumab treatment, combined with gemcitabine and erlotinib, 
particularly in subjects with higher Day 15 pamrevlumab Cmin values. These results underscore 
the potential validity of combined treatments that target both stroma and cancer cells in PDAC. 
Finally, the results also indicate the potential value of CTGF as a predictive biomarker and 
support further evaluation of pamrevlumab in combination with chemotherapy in a properly 
controlled and adequately powered study comparing SOC chemotherapy to SOC plus 
pamrevlumab. 
The encouraging results from Study 028 led to the initiation of the Phase 1/2 study, Study 069, 
using gemcitabine/nab-paclitaxel +/- pamrevlumab in a neoadjuvant setting. 
In Study 069, the addition of pamrevlumab to gemcitabine and nab-paclitaxel appears to 
positively impact eligibility for surgical exploration and resection rates in the treatment arm 
when compared to control. Seventy-one percent (17/24 patients) were eligible for surgical 
exploration in the treatment arm compared to 15% (2/13 patients) in the control arm. Thirty-three 
percent (8/37 patients) were resected in the treatment arm (4-R0, 4-R1) compared to 8% (1/13 


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patients) in the control arm (1-R0). The expanded criteria used to determine surgical eligibility 
by inclusion of CA 19.9 and PET response allowed patients who otherwise would not be eligible 
to undergo surgical exploration. 
In this ongoing study, the TEAEs have been similar to what was seen in the previous pancreatic 
cancer study with pamrevlumab (Study 028) and are consistent with what has been observed in 
pancreatic cancer patients treated with gemcitabine and nab-paclitaxel. To date, there are no 
apparent safety signals associated with the addition of pamrevlumab to gemcitabine and nab-
paclitaxel, and the triple combination appears to be well tolerated by subjects with LAPC. 
The improved eligibility for surgical exploration and resection rates in the treatment arm when 
compared to the control, provide direct rationale for the development of a larger Phase 3 study. 
Summaries of all completed, clinical studies supporting the pancreatic cancer indication can be 
found in the current version of the Investigator’s Brochure. 
2.3.3. 
Dose Rationale 
Analysis of data from a dose finding study FGCL-3019-028 (Study 028) supported the dose 
regimen used in the Phase 1/2 study FGCL-3019-069 (Study 069). In Study 028, pamrevlumab 
was tested in combination with gemcitabine and erlotinib in subjects with Stage 3 or 4 pancreatic 
adenocarcinoma. 
The efficacy analyses indicated potential survival benefit, particularly in those subjects with 
greater pamrevlumab Day 15 Cmin values. Higher pamrevlumab Cmin values lower baseline 
CTGF levels (<median) were associated with longer median OS and higher 1-year OS rates, 
prolonged PFS, and CA19-9 reductions in this study population. For example, a Day 15 Cmin 
level ≥ 150 µg/mL compared to < 150 µg/mL was associated with statistically significantly 
longer OS (9.0 vs 4.4 months [p=0.0244]) and a greater proportion of subjects surviving to at 
least 1 year (34.2% vs 10.8% [p=0.0258]). 
The analysis of final data showed that a pamrevlumab dose of 35 mg/kg given biweekly resulted 
a mean Day 15 Cmin values of > 150 µg/mL (mean ± SD of 169 ± 47 µg/mL). The next dose 
level (45 mg/kg biweekly) did not increase the mean Day 15 Cmin values (mean ± SD of 166 ± 63 
µg/mL). Therefore, a dose of 35 mg/kg biweekly is supported based on these efficacy analyses. 
Additionally, a dose justification evaluation was performed with data from Phase 1 dose 
escalation studies as well as data from FGCL-3019-028 and FGCL-3019-069 using exposure-
efficacy analysis. The summary of the exposure-efficacy analysis is below: 
Justification for Pamrevlumab Dose of 35 mg/kg Q2W for LAPC 
• A regimen of pamrevlumab of 35 mg/kg Q2W increases the percent of subjects 
eligible for surgery and achieving resection in LAPC. 
• Exposure-response models for resection predicts that increasing the dose to 45 mg/kg 
Q2W only increases the probability of resection by 2% while decreasing the dose to 
25 mg/kg Q2W decreases the probability by 4% 
 
 
 


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Secondary Evidence from Study 028 (88% Metastatic) 
• The dose-response (1-yr OS) model predicts that OS plateaus beyond 25 mg/kg. The 
dose-response model predicts that increasing the dose from 35 to 45 mg/kg Q2W only 
increases the probability of 1-yr OS by 1%, while decreasing the dose to 25 mg/kg 
Q2W decreases the probability by 4%. 
Safety Assessment 
• No relationship between reported serious TEAEs and exposure when pamrevlumab 
was combined with Gemcitabine and Erlotinib (Study 028) 
• No relationship between reported serious TEAEs when pamrevlumab was combined 
with Gemcitabine and Nab-paclitaxel (Study 069) 
Based on the above, the dose regimen and duration for this study is the same as previously 
evaluated in Study FGCL-3019-069 (35 mg/kg Q2W).  This dose will be administered in 
combination with either the G/NP or FOLFIRINOX treatment regimen.   
2.3.4. 
Safety Summary 
In Study 028, pamrevlumab was tested in combination with gemcitabine and erlotinib in 
chemotherapy naïve subjects with Stage 3 and 4 pancreatic adenocarcinoma. All 75 subjects 
were included in the Safety population and at least 1 TEAE was reported for each. A total of 65 
subjects had ≥ 1 TEAE following the first dose of pamrevlumab but prior to the administration of 
other study drugs. The most frequently reported TEAEs after the administration of pamrevlumab 
and prior to gemcitabine and erlotinib were nausea, abdominal pain, constipation, decreased 
appetite, and fatigue. The most common TEAEs reported following the administration of 
chemotherapy were: fatigue, nausea, diarrhea, vomiting, and abdominal pain. There was no 
apparent imbalance between the cohorts or dose dependent effect in the type or severity of 
TEAEs. 
In Study 069, 37 subjects were enrolled in an overall 2:1 ratio to one of two treatment arms; 
pamrevlumab with gemcitabine plus nab-paclitaxel (Arm A) or gemcitabine plus nab-paclitaxel 
alone (Arm B). Twenty-four subjects were randomized to Arm A and 13 subjects were 
randomized to Arm B. All 37 subjects were included in the Safety population. Overall, a total of 
36 subjects had at least 1 TEAE; 24 subjects in Arm A and 12 subjects in Arm B. The most 
common TEAEs reported in Arm A vs. Arm B were: fatigue (75.0% vs 76.9%), nausea (70.8% 
vs 53.8%), alopecia (66.7% vs 53.8%), edema peripheral (58.3% vs 38.5%), decreased appetite 
(50% vs 38.5%) and diarrhea (50.0% vs 53.8%). 
The only TEAE assessed by the Investigator as possible related to pamrevlumab but not to 
gemcitabine/nab-paclitaxel was an influenza like illness in one subject that was Grade 1 and non-
serious. The majority of TEAEs reported are listed as an adverse drug reaction in the product 
labeling for gemcitabine and/or nab-paclitaxel. 
There were no notable changes in laboratory results, vital signs, electrocardiograms, or physical 
findings. Overall, TEAEs were typical of those observed in subjects with the underlying medical 
condition and/or typical of adverse reactions associated with gemcitabine and nab-paclitaxel. To 
date, there are no apparent safety signals associated with the addition of pamrevlumab to 


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gemcitabine and nab-paclitaxel, and the triple combination appears to be well tolerated by 
subjects with LAPC. 
No deaths secondary to AEs and/or related to pamrevlumab were reported. 
For additional information on the safety of pamrevlumab in pancreatic cancer patients and in 
other indications, please refer to the current version of the Investigator’s Brochure. 


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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Objectives 
3.1.1. 
Primary Objective 
The primary objective of this trial is to evaluate the efficacy and safety of neoadjuvant treatment 
with pamrevlumab in combination with either gemcitabine plus nab-paclitaxel (G/NP) or 
FOLFIRINOX when compared to treatment with G/NP alone or with FOLFIRINOX alone in 
locally advanced, unresectable pancreatic cancer. 
3.1.2. 
Secondary Objectives 
The secondary objective of this trial is to evaluate the effect of neoadjuvant treatment with 
pamrevlumab in combination with either G/NP or FOLFIRINOX on event-free survival. 
3.2. 
Endpoints 
3.2.1. 
Primary Endpoint 
The primary endpoint of this trial is overall survival (OS), defined as the time from 
randomization to death due to any cause. 
3.2.2. 
Key Secondary Endpoint - Event-Free Survival (EFS) for Accelerated Approval 
The EFS endpoint is a composite time-to-event endpoint, the event being ‘treatment failure’ 
defined as the earliest occurrence of: 
a. Failure to achieve disease-free status locally after completion of neoadjuvant 
treatment and/or after surgery (i.e., resection failure or progression that precludes 
surgery); or 
b. Local or distant recurrence; or 
c. Death 
3.2.3. 
Secondary Endpoints 
The secondary endpoints of this trial are: 
• Progression-free survival (PFS), defined as the time from randomization until 
objective tumor progression or death (whichever occurs first) [Ref: 
https://www.fda.gov/media/71195/download] 
• RECIST 1.1 – Best Overall Objective Response Rate (ORR), defined as the 
proportion of patients who achieve CR (Complete Response) or PR (Partial 
Response) during treatment period 
 
All secondary endpoints of this trial will be tested hierarchically in the order listed above.   
 


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3.2.4. 
Exploratory Endpoints 
Exploratory endpoints for this trial are: 
• Change in Patient Reported Outcomes (PROs) as measured by: 
− Mean change from baseline during the treatment period in physical function  by 
EORTC-QLQ-C30  
− Mean change from baseline during the treatment period in abdominal pain by 
NCI-PRO-CTCAE  
− Mean change from baseline during the treatment period fatigue by NCI-PRO-
CTCAE  
• Proportion of all randomized subjects in whom R0 or R1 resection is achieved. 
• Difference in OS between resected and non-resected subjects 
• The proportion of subjects considered eligible for surgical exploration per protocol 
defined criteria 
• Mean change from baseline during the treatment period in CA19-9  
• Change in FDG-PET SUVmax and metabolic tumor volume (MTV) at EOT when 
compared to baseline 
• Correlative analyses of baseline CTGF serum levels with clinical outcomes 
• PK exposure-response analysis 
• Histological analysis in tumor tissues collected during resection 
• Evaluation of CTGF as prognostic/predictive biomarker 
• Evaluation of other selected protein and nucleic acid markers in plasma samples 
• Evaluation of number of chemotherapy cycles between the two arms 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of 
neoadjuvant treatment with pamrevlumab or placebo in combination with either G/NP or 
FOLFIRINOX, in the treatment of locally advanced unresectable pancreatic cancer (LAPC) 
subjects. Approximately 280 subjects will be enrolled in this trial, across approximately 
100 study centers in the following locations: North America, Europe and Asia Pacific. 
Investigators will have the option to choose between prescribing either G/NP or FOLFIRINOX 
prior to randomization. 
Subjects will be randomized in a 1:1 ratio to the addition of either pamrevlumab or placebo to 
the prescribed chemotherapy treatment regimen (G/NP or FOLFIRINOX). Subjects will be 
stratified at randomization by chemotherapy treatment regimen (G/NP or FOLFIRINOX), SMA 
encasement (> or ≤ 180 degree), unreconstructible disease and geographic region. 
This trial has five study periods: 
• Screening 
• Neoadjuvant Treatment 
• Evaluation for Surgical Exploration 
• Surgery 
• Follow-up 
In the screening period, subjects will be evaluated per the protocol inclusion/exclusion criteria to 
determine eligibility for participation in this trial. Protocol assessments will be completed during 
the screening period in accordance with SOA (see Appendix 1) to establish a baseline profile, 
including: demographics, medical history, clinical status and disease stage for each subject. 
During screening, a central review board (including radiologists and surgeons) will confirm 
subjects have locally advanced, unresectable disease prior to enrollment. This central review 
board will also review each subjects’ baseline CT scan to determine the degree of SMA 
encasement and whether or not they have unreconstructible disease for the purposes of 
stratification at randomization. See Section 7.1.1 for details. 
In the Neoadjuvant Treatment period, randomized subjects will receive up to 6 cycles 
(~24-30 weeks) of study treatment. Subjects’ clinical status and safety will be evaluated 
regularly along with efficacy assessments to evaluate subjects’ quality of life and disease state as 
described in Section 7 and the SOA (Appendix 1). If disease progression is noted during the 
treatment period, subjects will be discontinued from study treatment.  Subjects who discontinue 
treatment early for any reason will complete End of Treatment (EOT) visit and continue in the 
Follow-up period. Subjects who complete study treatment will be evaluated to determine 
eligibility for surgical exploration and may undergo surgical resection prior to continuing in the 
Follow-up period. 
For overall Safety Follow-up, all subjects enrolled will have a safety follow-up visit 
approximately 28 days after the last dose of study treatment and a final safety follow-up phone 


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call at approximately 60 days post last dose. For details regarding safety follow- up and 
reporting, see Section 8. 
Eligibility for surgical exploration will be evaluated for all subjects who complete study 
treatment (i.e. at least 11 of 13 planned doses of pamrevlumab or placebo and at least one dose of 
pamrevlumab or placebo in each cycle and no withdrawal of treatment due to AE or other 
reasons). The site will be required to provide information following the subject’s EOT visit (i.e. 
CT scan, PET scan, CA19-9 values) and Safety Follow-up Visit (i.e. performance status and a 
summary of any existing medical conditions/contraindications) to the central review board (to 
include radiologists, surgeons and oncologists) who will then determine whether or not a subject 
is eligible for surgical exploration per protocol. The central review board will provide their 
assessment of surgical eligibility to the site within 5 business days of receipt of all the required 
information (approximately 1 week after the Safety Follow-up Visit). After the recommendation 
from central review board has been received by the site, the PI and surgeon will make the final 
decision as to whether or not a subject will undergo surgery. All instances of discordance 
between the determination of eligibility for surgical exploration by the central review board and 
the action taken by the site with regards to surgical exploration will be documented in the clinical 
database. See Section 7.1.3 for details. 
Subjects who do not undergo surgical exploration (e.g. did not complete study treatment, do not 
meet any of the protocol-defined criteria for surgical eligibility or have a contraindication to 
surgery, or site decision not to proceed with surgery) will continue in the Follow-up period and 
be followed for progression, survival and additional anti-cancer therapies. 
Surgery will occur at least 4 weeks after last dose (allowing for a wash-out period from 
treatment) and only after receipt of the recommendation from the central review board with 
regards to surgical eligibility. Surgery will occur no longer than 8 weeks after the last dose.  
An outcome of R0 or R1 will be considered a ‘Resection Achieved’ while an outcome of R2 or 
partial resection will be considered a ‘Resection Not Achieved’.  Final surgical outcomes (R0 
and R1) for all ‘Resection Achieved’ subjects will be determined by the central pathology lab.  
The sponsor/sites remain blinded to the central pathology lab assessment until their final 
analysis. 
If a subject undergoes surgical exploration, but the surgeon is unable to perform resection (e.g. 
due to identification of metastases or extensive vascular involvement), it will be considered as 
‘Resection Not Attempted’. 
All subjects who undergo surgical exploration within the protocol specified window will have 
tissue collected and sent to central pathology for review and will be followed for surgical 
complications for 90 days post discharge. 
In the Follow-up period, all subjects will be followed for disease progression (if not previously 
detected) or recurrence (local or distant) following resection. Subjects will be followed for 
survival and any additional anti-cancer therapy received for their pancreatic cancer until the last 
subject to complete treatment has been followed for approximately 18 months post-last dose (i.e. 
at this time it is expected that 233 death events will have occurred to support final analysis of 
OS).  Subjects may receive second line therapy at the investigator’s discretion. 
A schematic overview of the study is provided in Figure 1. A detailed overview of assessments 
and the timing of assessments is provided in Appendix 1 and 2. 


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4.1.1. 
Estimated Study Duration 
It is anticipated that enrollment will be complete within 3-4 years from first subject enrolled. All 
subjects will complete up to 6 cycles of study treatment and at least 60 days of safety follow-up 
post last dose. All subjects will be followed in the Follow-up Period until the total number of 
deaths reported reaches 233 or the sponsor terminates the study.  It is anticipated that 233 deaths 
will occur by the time the last subject to complete treatment has been followed for approximately 
18 months. Therefore, some subjects could remain on study for approximately 6 years.


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Figure 1: 
FGCL-3019-087 Study Schema 
4.1.2. 
Randomization 
Approximately 280 subjects will be prescribed treatment with either G/NP or FOLFIRINOX, 
and then randomized 1:1 to receive either pamrevlumab or placebo, resulting in approximately 
140 subjects per treatment arm. Each subject will receive a unique study ID number in the 
screening and randomization process. Details are outlined in the randomization plan. 
Subjects will be stratified at randomization according to the following factors: 
• Chemotherapy treatment regimen (G/NP or FOLFIRINOX) 
• SMA encasement (> or ≤ 180°) 
• Unreconstructible disease (yes or no) 
• Geographic region (North America/Europe or Asia Pacific) 
Each region represents a specific surgical skills or general surgical outcomes and as subjects are 
randomized, the Interactive Response System (IXRS) will assign the treatment arms dynamically 
to ensure an equal distribution of subjects in both treatment groups across each region. Countries 
will be assigned to one of the two regions based on their general standard of care and surgical 
performance.  
 
Patient 
Populationa
Arm A 
G/NP or FOLFIRINOX 
+ Pamrevlumab
Arm B
G/NP or FOLFIRINOX 
+ Placebo
Randomization
• Randomization 1:1
• Stratification
• Chemotherapy 
regimen (G/NP or 
FOLFIRINOX)
• SMA > or ≤ 180◦ 
• Unreconstructible 
or reconstructible 
disease
• Geographic region
All subjects will be 
followed for disease 
progression or 
recurrence, survival 
and additional anti-
cancer therapy during 
Follow-up
Ineligible for 
Surgical 
Exploration 
Follow-up and 
SL/SOCc
SCREENING PERIOD
NEOADJUVANT 
TREATMENT PERIOD
FOLLOW-UP PERIOD
Eligible for 
Surgical 
Exploration
Successful 
Resection 
Abbreviations: G=Gemcitabine; NP=Nab-Paclitaxel; PD=Progressive Disease; SL=Second Line Therapy; SOC=Standard of Care
aCentral review team (including radiologists and surgeons) will confirm subjects have locally advance unesectable disease prior to enrollment. See Section 7.1.1.1 for 
details.
bSubjects must meet at least ONE of the four protocol-defined criteria, which include; CA19-9 decline ≥ 50%, PET SUVmax decline > 30%, RECIST response (CR, PR or SD), 
resectable or borderline resectable per NCCN and have NO contraindication to surgery.  A central review team (including radiologists, surgeons and oncologists) will 
determine whether a subject is eligible for surgical exploration per protocol.  See Section 7.1.4 and 7.1.4.1 for details.
cSecond-Line Treatment may be administered as per the investigator/institutional SOC
• Locally advanced 
pancreatic cancer 
(LAPC)
•  Non-resectable 
(NR) per NCCN 
criteria
• ECOG 0-1
6 cycles 
(28 days/cycle) 
Resection 
Failure
Recurrence 
(local progression or 
distant mets)
Progression or 
Discontinuation
EVALUATION FOR 
SURGICAL 
EXPLORATIONb 
SURGERY


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4.1.3. 
Treatment Assignment 
Within each stratum, subjects will be randomized 1:1 to one of two treatment arms: 
Arm A: pamrevlumab + either G/NP or FOLFIRINOX 
Arm B: placebo + either G/NP or FOLFIRINOX 
4.2. 
Blinding 
This is a double-blind, placebo-controlled study. The Investigator, study site staff, subjects, and 
selected Sponsor study team and designees are blinded to study drug assignment. 
4.2.1. 
Maintenance of Blinding 
The study blind will be maintained for all parties specified above throughout the study with the 
exception of the scenarios outlined in Section 4.2.2. and 4.2.3. Pamrevlumab and placebo will be 
identical in appearance, packaging, and labeling in order to maintain the study blind. 
4.2.2. 
Planned and Unplanned Unblinding of Treatment Assignment 
Investigators, study site staff and subjects will remain blinded to treatment assignments until 
study completion. 
Any unplanned, intentional or unintentional, breaking of the blind should be reported and 
documented. Breaking the blind (for a single subject) should be considered only when 
knowledge of the treatment assignment is deemed essential by the Investigator for the subject’s 
care. All Principal Investigators are granted access to the IRT system and assigned a role which 
will allow them to rapidly unblind a patient in the event of an emergency.  It is not required to 
discuss this action with the sponsor (or designee) prior to its execution.   
4.2.3. 
Unblinding of Treatment Assignment for Interim Analysis 
Details regarding the maintenance of the blind for the study team, sites and other staff during the 
interim analysis will be provided in a Data Access Plan. 
 


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5. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
5.1. 
Subject Inclusion Criteria 
In order to be eligible for inclusion in this trial, a subject must meet all of the following: 
1. Understand and sign informed consent; be willing to comply with study procedures, 
including surgery 
2. Age ≥ 18 years 
3. Be a male, or non-pregnant and non-lactating female 
4. Negative serum B-hCG pregnancy test at screening for women of childbearing potential 
5. Male subjects with partners of childbearing potential and female subjects of childbearing 
potential are required to use highly effective contraception methods during the conduct of 
the study and for 6 months after the last dose of study drug 
6. Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma 
(PDAC) 
7. Locally advanced pancreatic cancer considered unresectable according to 
NCCN Guidelines® Version 2.2018 as determined by central imaging 
8. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 
1.1 criteria as determined by central imaging 
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
10. Adequate liver function:  
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper 
limit of normal (ULN),  
• Bilirubin ≤ 1.5 x ULN or in subjects with biliary stenting ≤ 2.0 x ULN 
• Alkaline phosphatase < 2.5 x ULN 
• Patients with elevated alkaline phosphatase, total bilirubin, AST and ALT, who have 
subsequently undergone biliary stenting and their liver tests are improving, do not 
need to wait for their alkaline phosphatase to become < 2.5x ULN if their total 
bilirubin, AST and ALT have improved to within required study levels and the 
alkaline phosphatase is decreasing. 
11. Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin > 9.0 g/dl 
and absolute neutrophil count (ANC) >1,500 cells/mm3 
12. Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min 
13. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE) 


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5.2. 
Subject Exclusion Criteria 
Subjects will be ineligible for and excluded from this trial if any of the following apply: 
1. Prior chemotherapy or radiation for pancreatic cancer 
2. Previous (within the past 3 years) or concurrent malignancy diagnosis except 
non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer) 
3. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are 
permitted. 
4. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal 
antibodies. 
5. History of allergy or hypersensitivity to any of the chemotherapy agents being prescribed 
or their excipients 
6. Any medical or surgical condition that may place the subject at increased risk while on 
study 
7. Any condition potentially decreasing compliance to study procedures 
8. Exposure to another investigational drug within 28 days of first dosing visit, or 
5 half-lives of the investigational drug (whichever is longer) 
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic 
infections, symptomatic congestive heart failure, unstable angina pectoris, clinically 
significant cardiac arrhythmia, or psychiatric illness/social situations that would limit 
compliance with study requirements 
10. Documented history of drug or alcohol abuse within 6 months of signing informed 
consent 
11. Any medical condition that, in the opinion of the investigator, may pose a safety risk to a 
subject in this trial, may confound the assessment of safety and efficacy, or may interfere 
with study participation 
12. Subjects with a history of; interstitial pulmonary disease, HCV, HBV or HIV infection  
13. Subjects who have been administered a live vaccine within four weeks prior to the first 
administration of therapy 
14. Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4  
15. Subjects with poorly controlled comorbid conditions, including; congestive heart failure 
(CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus 
(DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited 
function 
 
5.3. 
Subject Withdrawal Criteria 
Subjects may choose to withdraw from study treatment at any time. 
 


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5.3.1. 
Withdrawal Criteria from Neoadjuvant Treatment Period 
Reasons a subject will be discontinued from study treatment include the following: 
• Progressive Disease 
• Adverse Event 
• Lost to Follow-Up 
• Non-compliance with study drug 
• Physician decision 
• Pregnancy 
• Major protocol deviation that substantially affects subject safety or assessment of 
efficacy endpoints 
• Withdrawal of Consent 
Discontinued subjects should be evaluated in the clinic for EOT visit, followed for safety and 
continue in the Follow-up period. 
A subject that meets the Treatment Compliance requirements (i.e. receives at least 11 of 13 
planned doses of pamrevlumab or placebo, receives at least one dose of pamrevlumab or placebo 
in each cycle) and has no withdrawal of treatment due to AE or other reasons will be considered 
as having completed the study treatment. 
5.3.2. 
Withdrawal Criteria for Follow-up Period 
Reasons a subject will be discontinued from the study follow-up period include the following: 
• Lost to Follow-up 
• Withdrawal of Consent 
A subject who dies during follow-up (or at any time during the trial) is considered as having 
completed the trial. 
5.4. 
Replacement of Study Subjects 
Subjects will not be replaced in this study. 
5.5. 
Study Termination 
FibroGen reserves the right to close any investigational site(s) or terminate the study at any time 
for any reason. Reasons for the closure of the study site or termination of a study by FibroGen 
may include (but are not limited to): 
• Successful completion of the study at the investigational site 
• Failure of the Investigator to comply with the protocol, GCP guidelines or local 
requirements 
• Safety concerns 
• Inadequate recruitment of subjects by the Investigator 


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6.
TREATMENT OF SUBJECTS
6.1. 
Study Treatment
Study treatment is administered over a 28-day cycle, for up to six cycles. If dosing delays occur 
due to AEs or scheduling conflicts, for example, it is acceptable to extend a single treatment 
cycle to a total of 42 days and the neoadjuvant treatment period by an additional 6 weeks. 
Therefore, the total duration of the neoadjuvant treatment period could be approximately 24-30 
weeks.  
Information regarding storage, handling, preparation and administration of pamrevlumab can be 
found in the FG-3019 Investigator’s Brochure and the study IP Manual. This information for the 
chemotherapy agents, gemcitabine, nab-paclitaxel and FOLFIRINOX, can be found in the 
package inserts for the products. 
6.1.1. 
Pamrevlumab (FG-3019) or Placebo 
The dose, route, infusion rate and schedule for the administration of pamrevlumab is provided in 
Table 1. 
Table 1: 
FG-3019 (or Placebo): Dose, Route, and Administration 
Agent 
Dose 
Route 
Frequency 
Infusion Rate 
FG-3019 
(or matching placebo) 
35 mg/kg 
IV 
Day 1 and 15 of each 
cycle, with an 
additional dose on 
Day 8 of Cycle 1 only 
Infuse over 1-hour (±  15 minutes) 
after completion of chemotherapy 
infusions 
Note: 
DO NOT ADMINSITER FG-3019 AS AN IV PUSH OR BOLUS INJECTION, OR CONCURRENTLY 
IN THE IV LINE WITH OTHER AGENTS. 
Dosing for pamrevlumab (or placebo) will be based on the weight obtained on Day 1 of each 
dosing Cycle (i.e. Cycle 1 Day 1, Cycle 2 Day 1, etc). The total dose of pamrevlumab (or 
placebo) is not to exceed 4.1g. Subjects weighing more than 117kg will receive the maximum 
allowable dose of 4.1g. The volume of fluid infused must not exceed 410mL. 
If split visit scheduling is implemented, the subject may be scheduled for a visit one day prior to 
dosing to complete study procedures per SOA.  In these instances, it is acceptable to use the 
weight collected the day prior to dosing to calculate the dose. 
6.1.2. 
Gemcitabine and Nab-paclitaxel 
The dose, route, and schedule for administration of gemcitabine and nab-paclitaxel used in both 
treatment arms is provided in Table 2.   


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Table 2: 
Gemcitabine and Nab-paclitaxel: Dose, Route and Administration 
Regimen Description 
Agent 
Dose 
Route 
Frequency 
Infusion Rate 
Nab-paclitaxel 
125 mg/m2 
IV 
Days 1, 8, 15 
IV over 30 minutes 
Gemcitabine 
1000 mg/m2 
IV, following nab-
paclitaxel 
Days 1, 8, 15 
IV over 30 minutes 
6.1.3. 
FOLFIRINOX 
The dose, route and schedule for administration of FOLFIRINOX used in both treatment arms is 
provided in Table 3.  The regimen below represents full dose FOLFIRINOX.  Modified 
FOLFIRINOX (mFOLFIRINOX) may be administered at the investigator’s discretion.  
Typically, for mFOLFIRINOX, the Irinotecan dose is reduced by 25% and the fluorouracil bolus 
dose is reduced by 20%.  This mFOLFIRINOX regimen has been associated with good 
tolerability and comparable efficacy when compared to the full dose (Cavanna et al 2019).  
Investigators may also administer a mFOLFIRINOX regimen per their institutional guidelines.  
The different chemotherapy agents used in the FOLFIRINOX regimen are administered in the 
order listed below. 
Table 3:  
FOLFIRINOX: Dose, Route and Administration 
Regimen Description 
Agent 
Dose 
Route 
Frequency 
Infusion Rate 
Oxaliplatin 
85 
mg/m2 
IV 
Days 1 and 15 of each 
28-day cycle 
IV over 2 hours (±30 mins) 
Folinic Acid or 
Leucovorin 
400 
mg/m2 
IV 
Days 1 and 15 of each 
28-day cycle 
IV over 2 hours (±30 mins) 
Irinotecan* 
180 
mg/m2 
IV 
Days 1 and 15 of each 
28-day cycle 
IV over 90 mins (±15 mins) 
(may begin 30 minutes into Folinic 
Acid infusion) 
Fluorouracil* 
400 
mg/m2 
IV 
Days 1 and 15 of each 
28-day cycle 
IV administered bolus infusion 
Fluorouracil 
2400 
mg/m2 
IV 
Days 1-3 and Days 
15-17 of each 28-day 
cycle 
IV continuous infusion of 46 hours 
(±30 mins) 
*NOTE: mFOLFIRINOX may be administered at the investigator’s discretion and per their institutional guidelines.   
 
6.1.4. 
Dose Schedules and Modifications 
If, for administrative reasons, treatment cannot be administered on the planned visit date, dosing 
may be administered plus or minus 2 days from the scheduled visit date per protocol.  
Additional, guidance on dose omissions or delays is outlined in the section below. 


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Study treatments must be infused in the following order: 
1. Nab-paclitaxel (chemotherapy agent) 
2. Gemcitabine (chemotherapy agent) 
3. Pamrevlumab or Placebo 
OR 
1. FOLFIRINOX (chemotherapy agents) 
2. Pamrevlumab or Placebo 
It is only permitted for subjects to receive pamrevlumab or placebo in combination with ONE 
chemotherapy treatment regimen during the neoadjuvant treatment period.  It is not permitted to 
begin the trial on one chemotherapy regimen and switch to another before End of Treatment (i.e. 
in combination with pamrevlumab or placebo). 
6.1.4.1. 
Dose Omissions and Modified Schedules (Gemcitabine plus Nab-paclitaxel) 
Day 1 Dose  
If both chemotherapy agents (G + NP) are held on Day 1 of the cycle, dosing with 
pamrevlumab or placebo should be delayed.  The cycle will not be considered to start until 
the day the study treatment is actually administered to the subject (ie, 1-2-3-Rest, X-1-2-3-
Rest, 1-2-3-Rest, etc).  If only one chemotherapy agent is held (G or NP) on Day 1, dosing 
with pamrevlumab or placebo should be administered.   
Day 8 Dose  
In Cycle 1, if one or both chemotherapy agents are held on Day 8, dosing with pamrevlumab 
or placebo should continue on schedule.  The Day 8 visit may also be delayed and given in 
combination with chemotherapy if the investigator feels the subject will be able to tolerate 
chemotherapy treatment at a later date.  Any delay of more than two weeks should be 
discussed with the medical monitor.  In all subsequent cycles (2-6), dosing with 
pamrevlumab or placebo does not occur on Day 8 visit so the cycle continues per protocol 
with one dose of chemotherapy not given/missed (ie, 1-2-3-Rest, 1-X-3-Rest, 1-2-3-Rest).  
Day 15 Dose  
If chemotherapy agents are held or missed on Day 15 of the cycle, dosing with pamrevlumab 
or placebo should continue on schedule followed by a week of rest to complete the 28-day 
cycle if the investigator feels this is safe and in the subject’s best interest.  However, the Day 
15 visit may also be delayed and given in combination with chemotherapy if the investigator 
feels the subject will be able to tolerate chemotherapy treatment at a later date.  Any delay of 
more than two weeks should be discussed with the medical monitor.   
If all chemotherapy agents are withdrawn (permanently discontinued), dosing with pamrevlumab 
or placebo must also be withdrawn.  Subjects will be discontinued from study treatment and 
continue in the Follow-up Period. 


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6.1.4.2. 
Dose Omissions and Modified Schedules (FOLFIRINOX) 
Day 1 Dose  
If all chemotherapy agents are held or missed on Day 1 of the cycle, dosing with 
pamrevlumab or placebo should be delayed.  The cycle will not be considered to start until 
the day the dose is actually administered to the subject (ie, 1-2-3-Rest, X-1-2-3-Rest, 1-2-3-
Rest, etc).   If only some chemotherapy agents are held on Day 1, dosing with pamrevlumab 
or placebo should be administered.   
Day 8 Dose (Cycle 1 only) 
Pamrevlumab or placebo is administered on Day 8 of Cycle 1 only.  Delays to the Day 8 dose 
in Cycle 1 should be discussed with the medical monitor. 
Day 15 Dose  
If chemotherapy agents are held or missed on Day 15 of the cycle, dosing with pamrevlumab 
or placebo should continue on schedule followed by a week of rest to complete the 28-day 
cycle if the investigator feels this is safe and in the subject’s best interest.  However, the Day 
15 visit may also be delayed and given in combination with chemotherapy if the investigator 
feels the subject will be able to tolerate chemotherapy treatment at a later date.  Any delay of 
more than two weeks should be discussed with the medical monitor.   
If all chemotherapy agents are withdrawn (permanently discontinued), dosing with pamrevlumab 
or placebo must also be withdrawn.  Subjects will be discontinued from study treatment and 
continue in the Follow-up Period. 
6.1.4.3. 
Dose Modifications 
It is the Investigator’s responsibility to modify the doses of gemcitabine and/or nab-paclitaxel in 
accordance with the product package insert guidelines for managing toxicities.   
It is the Investigator’s responsibility to modify the doses of FOLFIRINOX or mFOLFIRINOX in 
accordance with local or institutional guidance for managing toxicities.   
Chemotherapy doses may be further modified, withheld or withdrawn at the investigator’s 
discretion in the interest of subject safety and tolerability.    
Dose modifications for pamrevlumab are not allowed.  However, if an infusion reaction is 
suspected the infusion may be slowed, temporarily stopped or completely stopped before the full 
dose is administered (see Section 6.2.6 for details). 
6.1.5. 
Treatment Compliance 
All treatments are administered at the investigational site by qualified personnel and documented 
in the corresponding case report form (CRF). 
Subjects must receive at least 11 doses of pamrevlumab or placebo to be considered as having 
completed all treatment cycles.  Only one dose of pamrevlumab/placebo may be omitted per 
treatment cycle and no more than two doses total for a subject to be considered compliant and as 
having completed all cycles of treatment.  If two consecutive doses of pamrevlumab/placebo are 
omitted or more than two doses total within the treatment period are omitted for a subject, they 
will be considered as having not completed all cycles of treatment due to non-compliance with 


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study drug.  Delays of more than 2 weeks or interruptions (missed doses) that exceed two 
consecutive doses should be discussed with the medical monitor.   
6.1.6. 
Concomitant Medications 
6.1.6.1. 
Permitted Concomitant Medications 
Regular supportive care as clinically indicated is permitted during this trial. 
6.1.6.1.1. COVID-19 Vaccines 
FibroGen recommends a time separation between the administration of a COVID-19 vaccine and 
blinded study drug (pamrevlumab or placebo) of at least 48 hours.  While there are not safety 
concerns anticipated with the co-administration of pamrevlumab and COVID-19 vaccines, the 
time separation may allow for better interpretation of any adverse events and their relationship to 
the vaccine or study drug.    
6.1.6.2. 
Prohibited Concomitant Medications 
Pamrevlumab should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies. 
Gemcitabine, nab-paclitaxel or FOLFIRINOX agents should not be administered to subjects with 
a history of allergy or hypersensitivity to these products or their excipients. 
Radiation therapy and/or chemotherapy other than that prescribed per protocol is not allowed 
during the neoadjuvant treatment period and prior to surgical exploration. 
Certain drugs that inhibit or induce CYP3A4 or CYP2C8 should be used with caution during 
study therapy administration.  Specifically those outlined below: 
CYP2C8 and CYP3A4 
Inhibitors 
 
CYP2C8 and CYP3A4 
Inducers 
Ketoconazole 
 
Rifampicin 
Imidazole antifungals 
 
Carbamazepine 
Erythromycin 
 
Phenytoin 
Fluoxetine 
 
Efavirenz 
Gemfibrozil 
 
Nevirapine 
Clopidogrel 
 
Cimetidine 
 
Ritonavir 
 
Saquinavir 
 
Indinavir 
 
Nelfinavir 
 
 
If a subject is taking a CYP2C8 or CYP3A4 inhibitor or inducer listed above as a chronic 
medication (i.e. long term use to manage an element of their medical history) at the time they are 
being screened for the trial and they cannot switch to a different medication, they should be 
excluded from the trial.  Additionally, the use of the CYP inhibitors an inducers listed above 
should be avoided and only used with caution during the study for all patients receiving 
treatment with Nab-paclitaxel or FOLFIRINOX.    


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Live vaccines are prohibited for subjects receiving the G/NP or FOLFIRINOX chemotherapy 
regimen during study therapy administration and for 3 months after the last dose of study 
therapy. 
Interactions between the gemcitabine, nab-paclitaxel or FOLFIRINOX and concomitant 
medications are described in their respective package inserts.   
With regards to restrictions or recommendations related to chemotherapy agents, the sponsor’s 
expectation and guidance is that each site follow the product label over the protocol as labels can 
vary by product, country, manufacturer, etc. and offer the most up to date guidance for 
investigators to safely manage the treatment of their patients. 
6.1.6.3. 
Contraception Requirements 
A non-clinical study evaluating the potential effects of pamrevlumab on embryo-fetal 
development has not been conducted. No adverse effects of pamrevlumab administration were 
observed in a study of rat male and female fertility. This study also includes treatment with 
chemotherapy agents which are potentially genotoxic. 
Therefore, female subjects of childbearing potential are required to use highly effective 
contraception methods during the conduct of the study and for 6 months after the last dose of 
study drug. 
Male subjects with partners of childbearing potential are required to use highly effective 
contraception methods during the conduct of the study and for 6 months after the last dose of 
study drug. 
Investigators should counsel male subjects on the conservation of sperm prior to treatment due to 
the possibility of irreversible infertility/testicular damage due to the therapy with nab-paclitaxel 
and gemcitabine as noted in the SmPCs. 
Additionally, investigators should counsel subjects on any additional contraceptive requirements 
outlined in the SmPCs for the prescribed chemotherapy agents. 
A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and 
until becoming post-menopausal unless permanently sterile. Permanent sterilization methods 
include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. (CTGF, 2014) 
6.2. 
Study Drug Materials and Management 
This section of the protocol provides information and instruction regarding pamrevlumab 
(or placebo).  Similar information for the chemotherapy agents can be found in the package 
inserts for those products. Additional details regarding study drug material and management can 
be found in the Study Investigational Product (IP) Manual. 
6.2.1. 
FibroGen Investigational Product (Pamrevlumab) or Placebo 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF and is 
formulated as solution for administration by IV infusion. 
Matching placebo is formulated as solution to be administered in a manner that is identical to 
pamrevlumab infusion. 


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6.2.2. 
Formulation 
Pamrevlumab is supplied in single-use glass vials containing either 10 mL or 50 mL of a sterile, 
preservative-free solution (100 mg pamrevlumab/vial or 500 mg pamrevlumab/vial, 
respectively). The solution is composed of 10 mg/mL pamrevlumab, 1.60 mg/mL L-histidine, 
3.08 mg/mL L-histidine HCl, 8.01 mg/mL sodium chloride, and 0.05 mg/mL polysorbate 20, 
resulting in a solution with a tonicity of approximately 290 mmol/kg and a pH of 6.0. 
The placebo formulation is of identical composition as the pamrevlumab formation, except for 
the absence of pamrevlumab. 
6.2.3. 
Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice and local regulatory 
guidelines. 
6.2.4. 
Study Drug Storage 
Vials of pamrevlumab and placebo must be stored refrigerated (2°C to 8°C), in a temperature- 
controlled and monitored environment, in the carton provided and protected from light, and in a 
securely locked area to which access is limited to appropriate study personnel. Documentation of 
the storage conditions must be maintained by the site for the entire period of study participation. 
Details regarding the reporting of temperature excursions can be found in the study IP Manual. 
6.2.5. 
Study Drug Preparation 
Pamrevlumab or placebo is infused undiluted after pooling the contents of the calculated number 
of vials in an empty infusion bag (total volume of fluid must not exceed 410 mL), according to 
the Dose Preparation Instructions in the Investigational Product (IP) Manual. 
Once prepared, the IP infusion is stable at room temperature for up to 6 hours. Otherwise, if 
prepared IP is not used immediately it should be stored and refrigerated at 2-8ºC (to prevent 
microbial growth, as it does not contain preservatives) and used within 48 hours or be discarded.   
Pamrevlumab or placebo infusion solutions are administered by IV infusion, using an infusion 
set with a 0.2 µm in-line filter. 
6.2.6. 
Study Drug Administration 
Pamrevlumab/placebo infusion should be administered over 1 hour ± 15 minutes. Subjects 
should be carefully monitored for reaction during the first infusion with a physician available as 
needed. Subjects will remain at the study site for 1 hour after the end of the infusion for clinical 
observation.  The post-infusion observation period may be reduced to 30 minutes if the subject 
has had no infusion-related AEs for three consecutive infusions. The IV access should remain in 
place and be maintained per site procedures until the end of this post treatment observation 
period. If a subject has an infusion reaction, the infusion rate may be slowed or temporarily 
stopped, depending on the severity of symptoms. If a subject experiences an infusion reaction 
and continues pamrevlumab dosing, a physician must be immediately available during 
subsequent infusions and observation periods until the subject does not have any infusion 
reaction for three sequential infusions. 


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Pamrevlumab will be administered in a hospital or ambulatory setting with adequate facilities for 
managing medical emergencies for at least three infusions to confirm the subject does not have 
an infusion reaction. The study site must have trained staff and medications for the treatment of 
acute reactions, including anaphylaxis, immediately available. There is no specific treatment for 
a pamrevlumab overdose or infusion reaction. Signs and symptoms should be managed with 
appropriate standard of care treatment. 
Premedication, such as antihistamines, corticosteroids or nonsteroidal anti-inflammatory drugs 
(NSAIDs) are not normally administered before infusions of pamrevlumab. 
Premedication may be used for subjects who experience infusion reactions at the discretion of 
the investigator after discussion with the Medical Monitor. 
6.2.7. 
Study Drug Handling and Disposal 
All study drug provided by the Sponsor should be retained at the site until otherwise instructed in 
writing by the Sponsor (or designee). The Sponsor (or designee) will perform drug accountability 
and reconciliation for all study drug received at the site prior to approving study drug 
return/destruction. Upon completion of accountability/reconciliation or upon completion of the 
study or termination of the investigational site, all used, unused, partially used study drug, and all 
study drug that was not dispensed will be shipped to a destruction site designated by the Sponsor 
(or designee) for destruction. Study drug may be destroyed on site according to local/institutional 
policies by the pharmacy/authorized staff with approval from Sponsor (or designee). Please refer 
to the IP Returns Instruction Manual for additional information on study drug accountability. 


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7. 
ASSESSMENTS OF EFFICACY 
7.1. 
Study Assessments 
A signed and dated IRB/IEC-approved informed consent must be obtained before any study-
specific assessments are performed. Assessments that are part of routine care are not considered 
study-specific and may be used at screening to determine eligibility. All subjects will be 
screened for eligibility before enrollment. Only eligible subjects will be enrolled into the study 
and randomized. 
During the COVID-19 global pandemic, all sites were approved to conduct study assessments 
(i.e. physical exams, AE/CM review, etc) via telehealth visits if this was the only feasible option 
available. 
7.1.1. 
Screening Period 
All screening procedures must be performed within 30 days of Cycle 1 Day 1. Study procedures 
to be performed during the screening period can be found in the Schedule of Assessments 
(Appendix 1).  In order to avoid unnecessarily repeating study screening procedures (i.e. CT 
scans that would increase radiation exposure risk, delays due to COVID, etc) short extensions 
(up to 14 days maximum) to the screening window may be granted with prior approval from the 
Medical Monitor.   
Sites must confirm that all inclusion criteria (see Section 5.1) have been met and no exclusion 
criteria (see Section 5.2) have been met prior to making a request for randomization. A 
diagnostic biopsy is required for histological confirmation of pancreatic ductal adenocarcinoma 
(PDAC). Central laboratory samples will be collected and the results will be used to determine 
eligibility. CT scans will be sent to the central review board for evaluation to confirm subjects 
have locally advanced unresectable disease. If the site has performed additional staging 
procedures per SOC (i.e. laparoscopy or staging MRI) that indicate metastatic disease, these 
results may also be considered by the site in the final determination of eligibility. 
All subjects will be entered in IXRS and those who are eligible for participation will be 
randomized in the trial. All randomized subjects will be entered in the clinical database (EDC). 
7.1.1.1. 
Role of Central Review in Determining Eligibility for Participation and Defining 
Stratification Factors 
A central review board (to include radiologists and surgeons) will confirm subjects have locally 
advanced unresectable disease prior to enrollment through a review of the CT scan 
(per RECIST 1.1 and NCCN Version 2.2018) collected during screening. If available, any 
additional clinical data (i.e. MRIs, biopsy results, and historical CT scans) should be provided to 
the central review board at baseline as supplemental information to the central readers regarding 
any possible metastatic tumors on the screening scan.  The results provided by the central review 
board will be used to determine eligibility. 
The central review board will provide an assessment of SMA encasement and unreconstructible 
disease to the sites during screening to support stratification at randomization for any subjects 
determined to be eligible. 
Process details surrounding the central review can be found in the Imaging Manual. 


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7.1.2. 
Neoadjuvant Treatment Period 
All subjects will be treated with pamrevlumab or placebo in combination with gemcitabine and 
nab-paclitaxel or FOLFIRINOX for up to six 28-day cycles. Study procedures are described 
below and will be performed in accordance with the SOA (see Appendix 1). Subjects who 
complete study treatment will undergo evaluation to determine their eligibility for surgical 
exploration (see Section 4).  CT scans will be performed approximately every 8 weeks and 
evaluated by central imaging until disease progression is noted.  If disease progression is noted 
during the neoadjuvant treatment period, subjects will be discontinued from study treatment.  
Subjects who discontinue treatment early (see Section 5.3) will complete an EOT visit and 
continue in the follow-up period. 
7.1.3. 
Safety Follow-up 
All subjects enrolled will have a safety follow-up visit approximately 28 days after the last dose 
of study treatment and a final safety follow-up phone call approximately 60 days post last dose 
of study treatment. After the protocol-required reporting period (60 days after the last dose), the 
investigator does not need to actively monitor subjects for serious adverse events (SAEs). 
However, if the investigator becomes aware of a SAE that may be possibly related to study 
treatment after the protocol-required reporting period, the investigator may report the event to 
FibroGen as outlined in Section 8. SAEs reported outside of the protocol-required reporting 
period will be captured within the safety database only as clinical trial cases for the purposes of 
expedited reporting. 
7.1.4. 
Determination of Eligibility for Surgical Exploration 
To be considered eligible for surgical exploration, a subject must meet at least one of the four 
protocol-defined criteria and have no contraindication to surgery as outlined below: 
The protocol-defined criteria for surgical eligibility are: 
• Reduction in CA 19-9 level ≥ 50%  
• FDG-PET SUVmax decrease by ≥ 30% at EOT when compared to baseline 
• Partial response [PR], complete response [CR] or stable disease [SD] per RECIST 1.1 
at EOT 
• Resectable or borderline resectable per NCCN® Version 2.2018 
Contraindications to surgical eligibility are: 
• Development of distant metastases or local progression per RECIST 1.1 
• Performance status of Karnofsky score ≤ 50 
• Unreconstructible disease as determined by central radiological/surgical review 
• Other conditions that are considered by the PI/surgeon to be contraindications to 
surgery 
The central review board (to include radiologists, surgeons and oncologists) will review 
information provided by the site and determine whether a subject is eligible for surgical 
exploration per protocol. The PI/surgeon will ultimately decide whether a subject will undergo 
surgery. See Section 7.1.4.1 for details. 


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Subjects who do not undergo surgical exploration (e.g. subjects who did not complete study 
treatment, do not meet any of the protocol-defined criteria for surgical eligibility or have a 
contraindication to surgery at the time of evaluation) will continue in the Follow-up period.  
All subjects who do undergo surgical exploration within the protocol specified window will be 
followed for surgical safety and outcomes. 
7.1.4.1. 
Role of Central Review in Determination of Eligibility for Surgical Exploration 
CT and PET scans collected at EOT will be evaluated by the central review board to confirm 
whether a subject has met the protocol-defined criteria for RECIST 1.1, SUVmax, 
NCCN Version 2.2018 criteria response and/or whether they have unreconstructible disease. The 
site will also provide the central review board with CA19-9 values to confirm response per the 
protocol defined criteria. 
Additionally, the site will provide the central review board with required information for their 
assessment of the subject’s performance status and a summary of existing 
conditions/contraindications following the Safety Follow-up Visit. Conditions that may be 
contraindications to surgery will be reported to the central review board through the Safety 
Follow-up visit. Medical co-morbidities that occur after the Safety Follow-up visit and preclude 
surgery will not be provided to the central review board, and therefore will not be considered in 
the determination of surgical eligibility, but will be considered by site in their decision making 
process regarding surgical exploration. These co-morbidities will be documented in the clinical 
database. 
The central review board will provide their assessment of surgical eligibility to the site within 
5 business days of receipt of all required information (approximately 1 week after the Safety 
Follow-up Visit). After the recommendation from the central review board is received at the site, 
the PI/surgeon will make the final decision as to whether or not a subject will undergo surgery. 
All instances of discordance between the determination of eligibility for surgical exploration by 
the central review board and the final action taken by the site with regards to surgical exploration 
will be documented in the clinical database. 
Figure 2 provides an overview of the central review process. Details can be found in the 
Central Imaging Protocol and Study Reference Manual. 


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Figure 2: 
Central Review Schema for Determination of Eligibility for Surgical 
Exploration 
 
7.1.5. 
Surgical Exploration/Surgical Resection 
 
Surgery will occur at least 4 weeks after last dose (allowing for a wash-out period from 
treatment) and only after receipt of the recommendation from the central review board with 
regards to surgical eligibility.  
An outcome of R0 or R1 will be considered a ‘Resection Achieved’ while an outcome of R2 or 
partial resection will be considered a ‘Resection Not Achieved’.  Final surgical outcomes (R0 
and R1) for all ‘Resection Achieved’ subjects will be determined by the central pathology lab.  
The sponsor/sites remain blinded to the central pathology lab assessment until their final 
analysis. 
If a subject undergoes surgical exploration, but the surgeon is unable to perform resection (e.g. 
due to identification of metastases or extensive vascular involvement), it will be considered a 
‘Resection Not Attempted’. 
Surgery will be performed in accordance with institutional standards and SOPs. All surgeons 
performing surgery for this study will be trained on the protocol. All subjects who undergo 
surgical exploration within the protocol specified window will have tissue samples collected and 
sent to central pathology and will be followed for surgical complications for 90 days post 
discharge. 
7.1.6. 
Follow-up Period 
All subjects will be followed for disease progression (if not previously noted) or recurrence 
(local or distant) following resection, survival and any additional anti-cancer therapy received 
during the Follow-up period. Follow-up visits (telehealth visits or phone calls are acceptable) 
should occur approximately every 3 months post last dose.   
For some subjects, CT scans may continue to be performed and submitted for central review 
during the follow-up period.  For subjects who complete treatment without evidence of disease 
progression and do not undergo resection, CT scans will continue to be performed approximately 


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every 8 weeks (±14 days) and evaluated by central imaging until progression is detected (per 
RECIST 1.1).  For subjects who undergo resection, follow-up CT scans to evaluate recurrence of 
disease will be evaluated by central imaging and performed approximately; every 4 months up to 
2 years post-resection and every 6 months from 2 years to 5 years post-resection.  The 
investigator may perform an “off schedule” CT scan at any time post resection if recurrence of 
disease is suspected clinically; these scans will be submitted to central imaging for 
review/confirmation of recurrence/disease progression.  CT scans conducted post resection 
during the Follow-up Period may be performed within 1 month (i.e. ± 30 days) of the suggested 
intervals above. 
All subjects will be followed for survival (until death) or until the last subject to complete 
treatment has been followed for approximately 18 months post-last dose (i.e. at this time it is 
expected that 233 death events will have occurred to support final analysis of OS). Subjects may 
receive second-line therapy at the investigator’s discretion. 
7.1.7. 
 Missed Visits 
Study treatment may be withheld/interrupted due to safety reasons, resulting in a “missed” visit. 
Study visits may be delayed for a total window not to exceed + 6 weeks over the course of the 
treatment period. Adjustments to the dosing schedule for pamrevlumab/placebo should be 
discussed with the study Medical Monitor as outlined in Section 6.1.3. If a visit is missed and not 
rescheduled, it will be captured accordingly in the clinical database. 
7.1.8. 
Unscheduled Visits 
Unscheduled visits/assessments may be required at the discretion of the investigator. 
Unscheduled visit data will be captured accordingly in the clinical database. 
7.1.9. 
Early Withdrawal from Treatment 
Subjects who prematurely discontinue treatment during the neoadjuvant treatment period should 
be strongly encouraged to complete the final efficacy evaluations scheduled for the EOT visit as 
specified in the SOA (Appendix 1). These subjects must be followed for safety for at least 60 
days following their last dose of study drug. Discontinued subjects will continue in the Follow-
up period and be followed for progression (if not previously noted), survival and additional anti-
cancer therapies for pancreatic cancer. 
7.2. 
Assessments 
Refer to the Schedule of Assessments (Appendix 1 and 2) for details regarding the timing 
and frequency of study assessments. 


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7.2.1. 
Vital Signs (Including Weight and Height) 
Vital signs to be collected include heart rate, blood pressure, respirations, temperature and 
weight: 
• Heart rate should be collected as beats/min 
• Systolic and diastolic blood pressure should be collected from subjects in seated 
position 
• Respirations should be collected as breaths/min 
• Temperature should be taken as oral or tympanic and captured as °F or °C 
• Weight should be collected in lbs or kgs 
• Height is collected during screening only. 
7.2.2. 
Physical Exam 
A full physical exam is required during screening and on Day 1 of each treatment cycle. All 
other physical exams may be abbreviated unless a full physical exam is warranted in the opinion 
of the investigator. A full physical exam may include, but is not limited to, review of the 
following systems: 
• General Appearance, HEENT, Lungs, Heart, Chest & Back, Abdomen, Extremities, 
Neurologic, Skin 
7.2.3. 
Electrocardiogram (ECG or EKG) 
EKGs will be performed in accordance with institutional standards at screening, Day 1 of each 
Cycle and EOT. 
7.2.4. 
Laboratory Evaluations 
Details regarding sample collection, preparation and transport can be found in the central lab 
manual. 
7.2.4.1. 
Central Laboratory Evaluations 
The following labs will be evaluated by a central laboratory in accordance with the SOA 
(Appendix 1): 


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Table 3: 
Laboratory Tests 
CBC: 
Chemistry Panel: 
Absolute neutrophil count (ANC) 
Bicarbonate 
Eosinophils 
BUN 
Erythrocyte count (RBC) 
Calcium 
Hematocrit 
Creatinine 
INR 
Chloride 
PTT/PT 
Magnesium 
Hemoglobin 
Glucose 
Leukocyte count (WBC) 
 ALP 
Lymphocytes 
ALT 
Mean corpuscular volume 
AST 
Monocytes 
Bilirubin, total 
Neutrophils 
Albumin 
Platelets 
Phosphorous 
CRP 
 Potassium 
Basophils 
 Sodium 
Other:  CA 19-9 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
CBC = complete blood count; CRP = C-reactive protein; INR = international normalized ratio, PT/PTT = prothrombin 
time/partial thromboplastin time; RBC = red blood cell; WBC = white blood cell. 
Central lab results obtained during the screening period will be used to determine subject 
eligibility for participation in the trial. Central lab results will be reviewed by the investigator for 
clinical significance and to determine appropriate reporting of adverse events (see Section 8.3.7). 
Central lab results for CA19-9 will be used to determine eligibility for surgical exploration. 
During screening, a serum pregnancy test will be performed by the central lab for any females of 
child-bearing potential (WOCBP).  For WOCBP, serum or urine pregnancy tests should be 
performed approximately monthly thereafter at the site level per the SOA in Appendix 1. 
Local lab results may be used to evaluate subject condition prior to dosing.  
7.2.4.2. 
Local Laboratory Evaluations 
Whenever possible, and as outlined above, central lab samples should be collected/used for the 
purposes of this trial.  However, during the COVID-19 global pandemic, all sites were approved 
to use local labs if it was not possible to collect/use central labs (i.e. due to local/site restrictions 
or due to lab kit shortages).  Any instance in which local labs were used will be documented in 
the clinical database and local lab results will be captured.  Sites using local labs must submit 
their local lab ranges for reference. 
7.2.4.3. 
Pharmacokinetics and Pharmacodynamics 
Additional samples will be collected to evaluate PK, HAHA, HAHA-NA and CTGF in 
accordance with the SOA in Appendix 1. The central laboratory will manage the storage of 
these samples while analysis will be performed at the specialty lab specified in the central lab 
manual. 


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7.2.4.3.1. Pharmacokinetics 
Plasma samples will be collected in all subjects for evaluation of Cmax and Cmin trough levels of 
pamrevlumab (FG-3019) according to the SOA in Appendix 2. A central laboratory will measure 
plasma FG-3019 levels using a validated assay. For the analysis of Cmax and Cmin data, it is 
critical to accurately record the dosing time and date in addition to the sampling collection time 
and date. 
7.2.4.3.2. Human Anti-Human Antibodies (HAHA) and Connective Tissue Growth Factor 
(CTGF) 
Plasma samples will be collected for evaluation of human anti-human antibodies (HAHA) and 
connective tissue growth factor (CTGF) in all subjects according to the SOA in Appendix 1.  
Central laboratories will measure HAHA and CTGF level using validated assays. 
HAHA-NA samples will be collected from all subjects at the Safety Follow-up visit.  These 
samples will undergo evaluation for neutralizing antibodies for all samples/subjects with 
positive/specific HAHA results. The prevalence and duration of binding and neutralizing 
antibodies and the effect of these antibodies on the pharmacokinetics, pharmacodynamics 
markers, efficacy, and safety of pamrevlumab will be assessed.  
7.2.4.3.3. Pharmacodynamics and Biomarkers (Blood and Tumor Tissue) 
Tumor tissue will be collected from all resected subjects for histological analysis and 
examination of nucleic acids. Plasma samples will be collected from all subjects according to the 
SOA in Appendix 1 to support the exploratory analysis of protein and nucleic acid markers. Final 
decisions about the specific markers to be evaluated in tumor tissue or plasma samples collected 
for exploratory analysis will be made at the time of analysis and will be based on the review of 
medical literature, additional data regarding FG-3019’s mechanism of action, preliminary results 
and availability of material for assay. Details regarding the collection and storage of tumor tissue 
will be outlined in the Central Pathology Manual. 
7.2.5. 
Performance Status 
7.2.5.1. 
Eastern Cooperative Oncology Group (ECOG) 
These scales and criteria are used by doctors and researchers to assess how a patient's disease is 
progressing, to assess how the disease affects the daily living abilities of the patient, and to 
determine appropriate treatment and prognosis (Oken, 1982). The ECOG performance scale will 
be used to evaluate subject’s performance status during screening and throughout the trial. See 
Appendix 1. 
7.2.5.2. 
Karnofsky Performance Scale Index 
The Karnofsky Performance Scale Index is an assessment tool for functional impairment 
(Appendix 3). It can be used to assess the prognosis in individual patients. In most serious 
illnesses, the lower the Karnofsky score, the worse the likelihood of survival (Boeck, 2007). The 
Karnofsky performance scale will be used to evaluate subject’s performance at EOT only. 
Karnofsky performance scores will be evaluated by the central review team in determination of 
eligibility for surgical exploration per protocol. 


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7.2.6. 
Carbohydrate Antigen 19-9 (CA 19-9) 
CA 19-9 is a tumor marker that is used primarily in the management of pancreatic cancer  
(Poruk, 2013). CA 19-9 levels will be measured at baseline and regularly throughout the study. 
CA 19-9 results will be evaluated by the central laboratory. CA19-9 results will be evaluated by 
the central review team in determination of eligibility for surgical exploration per protocol. 
7.2.7. 
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scan 
Studies have shown FDG-PET may be useful in treatment response assessment and may have 
potential in guiding the management of patients with PDAC (Yeh, 2018). An FDG-PET scan 
will be performed at baseline and EOT to evaluate SUVmax and metabolic tumor volume in the 
primary pancreatic tumor. If a subject discontinues treatment early, an EOT PET scan is required 
unless the baseline PET was performed less than 8 weeks from EOT.  All PET scans will be 
performed and evaluated in accordance with the central imaging protocol. PET scans will be 
evaluated by the central review team in determination of eligibility for surgical exploration per 
protocol. 
7.2.8. 
Computer Tomography (CT) Scan 
CT scans will be performed using pancreatic protocols and in accordance with the central 
imaging charter until progression. Central imaging will conduct RECIST reads on all CT scans 
collected during screening, the neoadjuvant treatment period and follow-up as outlined in the 
SOA (Appendix 1).   
Baseline CT scans (collected during the screening period) will be evaluated by the central 
radiological/surgical review team to confirm subjects have locally advanced, unresectable 
disease prior to enrollment. Central radiological/surgical review team will also review each 
subjects’ baseline CT scan to determine the degree of SMA encasement and whether or not they 
have unreconstructible disease for the purposes of stratification at randomization. 
All CT scans collected during the study will be evaluated by the central review team for 
progression per RECIST until progression is noted.  EOT CTs, for subjects who complete all 6 
cycles of treatment, will be evaluated at EOT by the central review team in determination of 
eligibility for surgical exploration per protocol. 
If a subject cannot tolerate a contrast CT or other reasons, MRIs may be performed.  If MRIs are 
performed during screening or the neoadjuvant treatment period due to contrast intolerance or 
other reasons, they will be sent to central imaging for review.   
7.2.9. 
Patient Reported Outcomes (PROs) 
Patient reported outcome (PRO) data will be collected in all subjects to evaluate the most 
important patient reported symptoms, treatment related symptoms and functional impacts that 
may be responsive to treatment. EORTC-QLQ-C30 and PRO CTCAE™ questionnaires will be 
administered as specified in the SOA (prior to dosing in all applicable instances) 
(see Appendix 1).  
At the study outset, all PRO data was being captured as direct entry by the subject via electronic 
device (ePRO).  During the COVID-19 global pandemic, all sites were approved to use paper 
versions of the PRO/QOL questionnaires.  Use of paper questionnaires will be documented and 
the results will be transcribed into the clinical database. 


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7.2.9.1. 
EORTC-QLQ-C30 
EORTC QLQ-C30 is a health related quality of life questionnaire (HRQOL) developed to assess 
the quality of life of cancer patients. EORTC QLQ-C30 Version 3.0 is the most recent version 
and will be used for this study. This questionnaire will be collected on Day 1 of each treatment 
cycle (prior to dosing), at EOT and the Safety Follow-up visit. 
7.2.9.2. 
PRO-CTCAE™ 
The following symptoms from the PRO-CTCAE™ library will be included in a symptom 
specific patient questionnaire: decreased appetite, nausea, vomiting, diarrhea, abdominal pain 
and fatigue. This questionnaire will be collected on Days 1, 8 and 15 in the first three treatment 
cycles (Cycles 1-3), on Days 1 and 15 in the last three treatment cycles (Cycles 4-6) and at the 
EOT and Safety Follow-up Visit.  
7.2.10. 
Surgical Outcomes and Complications 
All subjects that undergo surgery within the protocol specified window (at least 4 weeks after the 
last dose and no longer than 8 weeks after the last dose) will be followed for surgical outcomes 
and complications for 90 days after their discharge. Surgical safety will be assessed by the 
collection of surgical outcomes measures and surgical complications that occur during this 
timeframe. 
7.2.10.1. Surgical Complications 
All surgical complications that occur will be collected and graded in severity according to the 
Clavien-Dindo Classification (Appendix 4).  
7.2.10.2. Surgical Outcomes 
The following surgical outcomes will be measured: 
• Type of procedure/resection 
• Resection outcome 
•  >10 lymph nodes 
• Operative time >10 hours 
• Length of hospital stay 
• Estimated blood loss (EBL) at time of surgery 
• Transfusions; units of blood 
• Return to operating room within 30 days 
 


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8. 
ASSESSMENTS OF SAFETY 
8.1. 
Background 
Adverse event reports from investigators are the critical building blocks to the development of 
the safety profile of the Study Drug. Subjects will be asked non-leading questions in general 
terms to determine the occurrence of AEs, according to the schedule outlined in Appendix 1. In 
addition, all AEs reported spontaneously during the course of the study will be recorded. The 
investigator must immediately (within 24 hours of awareness) report to the sponsor or designated 
safety management vendor all SAEs, regardless of whether the investigator believes they are 
related to the study drug. 
8.2. 
Definitions 
8.2.1. 
Definition of an Adverse Event (AE) 
An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The 
event does not necessarily have a causal relationship with study treatment. The investigator is 
responsible for ensuring that any adverse events observed by the investigator or reported by the 
subject as defined in the study protocol are recorded in the subject’s medical record. The 
definition of adverse events includes worsening of a pre-existing medical condition. Worsening 
indicates that the pre-existing medical condition (eg, diabetes, migraine headaches and gout) has 
increased in severity, frequency, and/or duration, and/or has an association with a significantly 
worse outcome. A pre-existing condition that has not worsened during the study or involves an 
intervention such as elective surgery or a medical procedure while on study, is not considered an 
adverse event. (Section 8.3.1). 
8.2.2. 
Definition of a Serious Adverse Event (SAE) 
A serious adverse event is any adverse event or suspected adverse reaction that results in any of 
the following outcomes: 
• Death, 
• A life-threatening AEs (i.e., if in the view of the investigator or sponsor, the subject 
was at immediate risk of death at the time of the event). Life-threatening does not 
refer to an event which hypothetically might have caused death if it were more 
severe, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 
• A congenital anomaly or birth defect, or 
• Is considered a medically important event not meeting the above criteria, but which 
may jeopardize a subject or may require medical or surgical intervention to prevent 
one of the other criteria listed in this definition. Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or 
at home, and blood dyscrasias or convulsions that do not result in inpatient 
hospitalization. 


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Please note that death is an outcome, not an event; the primary cause of death would be the 
adverse event. 
Surgical procedures, per se, are not SAEs. The condition requiring the surgical procedure, 
however, may be an SAE. 
Scheduled or pre-planned hospitalization or prolongation of a hospitalization due to standard of 
care assessments and procedures (including elective procedures) do not warrant reporting as 
adverse events unless resulting observations are deemed by the Investigator to meet the 
definition of an adverse event. 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
8.3.1. 
Adverse Event Reporting Period 
The safety reporting period begins after the subject has signed the informed consent and ends 60 
days after the last dose of study drug. Only SAEs need to be reported following consent and prior 
to first dose.  While both AEs and SAEs need to be reported from first dose through 60 days post 
last dose.   The investigator should notify FibroGen of any death or other SAEs occurring after a 
subject has discontinued or terminated study participation that may reasonably be related to this 
study (Section 8.3.5). Pregnancy reporting requirements are outlined in Section 8.3.6. 
Adverse events will be followed until resolved, stable, or until the subject’s last study visit or 
subject is lost to follow-up. 
8.3.2. 
Adverse Event Eliciting/Reporting 
During the AE reporting period, study site personnel will actively seek information from each 
subject at each visit to collect any AE occurring since the previous visit. All AEs will be 
collected in response to a general question about the subject’s well-being and any possible 
changes from the baseline or previous visit, but shall not be specifically solicited. There will be 
no directed questioning or solicitation for any specific AE. This does not preclude the site from 
collecting and recording any AEs reported by the subject to site personnel at any other time. 
Whenever possible, diagnoses should be recorded when signs and symptoms are due to a 
common etiology, as determined by qualified medical study staff. The investigator is responsible 
for reviewing laboratory test results and determining whether an abnormal value in an individual 
study subject represents a clinically significant change from the subject’s baseline values. In 
general, abnormal laboratory findings without clinical significance (based on the investigator's 
judgment) are not to be recorded as adverse events. However, laboratory value changes that 
require treatment or adjustment in current therapy are considered adverse events. Where 
applicable, clinical sequelae (not the laboratory abnormality) are to be recorded as the adverse 
event. The investigator is expected to follow reported adverse events until stabilization or 
reversibility. 


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The following attributes must be assigned to each AE: 
• Description (Investigator’s verbatim term describing the event) 
• Dates of onset and resolution 
• Severity 
• Relationship to study drug 
• Outcome 
• Action taken regarding study drug 
• Other treatment required 
• Determination of “seriousness” 
8.3.3. 
Assessing Adverse Event Severity 
AEs, including abnormal clinical laboratory values, should be graded using the National Cancer 
Institute (NCI) Common Terminology Criteria for AE (CTCAE) v 5.0 guidelines. For terms not 
specified as part of NCI CTCAE, the following guidelines should be used to determine grade: 
All AEs will be assessed for severity using the following criteria: 
• Grade 1, Mild: Asymptomatic or mild symptoms which the subject finds easily 
tolerated. The event is of little concern to the subject and/or of little-or-no clinical 
significance; intervention not indicated. 
• Grade 2, Moderate: The subject has enough discomfort to cause interference with or 
change in some of their age-appropriate instrumental activities of daily living (e.g., 
preparing meals, shopping for groceries or clothes, using the telephone, managing 
money); local or noninvasive intervention indicated. 
• Grade 3, Severe: The subject is incapacitated and unable to work or participate in 
many or all usual activities. The event is of definite concern to the subject and/or 
poses substantial risk to the subject’s health or well-being; likely to require medical 
intervention and/or close follow-up, including but not limited to hospitalization or 
prolongation of hospitalization. 
• Grade 4, Life-threatening: The subject was at immediate risk of death from the 
event as it occurred. 
• Grade 5, Death: Fatal AE. 
8.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug 
Most of the information about the safety of a drug prior to marketing comes from clinical trials; 
therefore, AE reports from investigators are critically important. The assessment of whether an 
AE is causally related to the study drug(s) using an evidence-based approach is critical in order 
to appropriately describe the safety profile of study drug(s). Default reporting of individual 
events as possibly related is uninformative and does not meaningfully contribute to the 
development of the study drug’s safety profile. 


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The investigator must provide an evidence-based assessment of the relationship of the AE to 
study drug in accordance with the guidance below. Absence of an alternative cause would not 
normally be considered sufficient evidence to assess an event as related to study drug. 
• Related: 
− Any event for which there is sufficient evidence to suggest that the study drug 
may have caused the event. For example, an unanticipated medical condition 
occurs which resolves with study drug interruption and re- occurs with re-
administration of study drug; another example is a typical drug-related medical 
condition such as a rash that occurred shortly after first dose of study drug. 
• Not Related: 
− The event represents a pre-existing underlying disease that has not worsened on 
study 
− The event has the same characteristics of a known side-effect associated with a 
co-medication 
− The event is an anticipated medical condition of anticipated severity for the study 
population 
− The most plausible explanation for the event is a factor that is independent of 
exposure to study drug 
8.3.5. 
Reporting Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by the 
investigator or reported by the subject that occur after signing of the informed consent/assent 
through 60 days after the last dose of pamrevlumab are recorded in the subject’s medical record 
and are submitted to FibroGen. All SAEs must be submitted to FibroGen within 24 hours 
following the investigator’s knowledge of the event via the SAE report form. Additionally, 
pamrevlumab related SAEs (including deaths) that occur after the safety follow-up visit through 
the end of the long-term follow-up will be reported. 
If a subject is permanently withdrawn from protocol required therapies because of a serious 
adverse event, this information must be submitted to FibroGen. FibroGen will report serious 
adverse events and/or suspected unexpected serious adverse reactions as required to regulatory 
authorities, investigators/institutions, and central IRBs/IECs in compliance with all reporting 
requirements according to local regulations and Good Clinical Practice (GCP). 
There is no requirement to monitor study subjects for serious adverse events following the 
protocol-required reporting period or after end of study. However, these serious adverse events 
can be reported to FibroGen. In some countries (e.g. European Union [EU] member states), 
investigators are required to report serious adverse events that they become aware of after end of 
study. If serious adverse events are reported, the investigator is to report them to FibroGen 
within 24 hours following the investigator’s knowledge of the event. Serious adverse events 
reported outside of the protocol-required reporting period will be captured within the safety 
database as clinical trial cases for the purposes of expedited reporting; these cases will not be 
included in the clinical study report. 


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To report an SAE, the investigator must complete an SAE Report Form and fax or email the 
completed form to the Sponsor or its designated safety management vendor. 
Full details of the SAE should also be recorded on the medical records and in the CRF. The 
following minimum information is required: 
• Subject number, sex and age 
• The date of report 
• A description of the SAE (event, seriousness of the event) 
• Causal relationship to the study drug 
Follow-up information for the event should be sent promptly. 
For each SAE observed, the investigator should obtain all of the information available about the 
event, including (but not limited to): hospital discharge diagnoses, hospital discharge note, death 
certificate, appropriate laboratory findings (including autopsies and biopsy results), and clinical 
examinations (including radiological examinations and clinical consultations). 
8.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review 
Board / Independent Ethics Committee 
The investigator is responsible for notifying his/her Institutional Review Board (IRB) or Ethics 
Committee (EC) of SAEs in accordance with local regulations. The Sponsor, or its designated 
safety vendor, will provide a copy of expedited safety reports to the investigator that it intends to 
submit to global regulatory authorities. 
8.3.5.2. 
Deaths 
The investigator will report the fatal event to the Sponsor’s medical monitor. The investigator 
must provide a causal assessment of the relationship of the event to the study drug according to 
the guidance in Section 8.3.5. 
If the death occurred within the AE collection and reporting period (signed ICF to 60 days after 
last dose) and meets the reporting criteria, the investigator must submit the SAE Report Form in 
the same manner as described above in Section 8.3.5. If the investigator becomes aware of a 
death occurring after the AE reporting period and considers it related to study drug, it will be 
reported as an SAE. 
8.3.6. 
Pregnancies: Reporting and Follow-up of Subjects and Female Partners of 
Subjects 
The outcome of all pregnancies for a female study participant or female partners of a male study 
participant should be followed up and documented as described. If a female subject or a partner 
of a male subject becomes pregnant while the subject is receiving study treatment or within 6 
months after the last dose of study treatment, a Pregnancy Report Form must be completed and 
submitted to Sponsor or designated safety management vendor within 24 hours of the 
investigator becoming aware of the pregnancy. The investigator must follow-up to completion of 
the pregnancy to ascertain its outcome (e.g., spontaneous miscarriage, elective termination, 
ectopic pregnancy, normal birth or congenital abnormality) and whether any AEs occur during 
the pregnancy or birth. The outcome of the pregnancy must be reported by the investigator on a 


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Pregnancy Outcome Report Form, which should be sent to the Sponsor and/or its designated 
safety vendor within 24 hours of the investigator becoming aware of the outcome. 
Pregnancy itself is not an AE unless there is a suspicion that the investigational product under 
study may have interfered with the effectiveness of a contraceptive medication. Pregnancies are 
followed up to outcome even if the subject was discontinued from the study. Congenital 
abnormalities/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. 
If a lactation case occurs while the female subject is taking protocol-required therapies or within 
60 days after the last dose of study treatment, report the lactation case to FibroGen. In addition to 
reporting a lactation case during the study, investigators should monitor for lactation cases that 
occur after the last dose of protocol-required therapies through 6 months after the last dose of 
pamrevlumab. Any lactation case should be reported to FibroGen’s Safety within 24 hours of the 
investigator’s knowledge of event. 
8.3.7. 
Abnormal Laboratory Findings 
An abnormal laboratory finding in absence of any other signs or symptoms is not necessarily an 
AE. The investigator must review and assess all results provided by the central laboratory 
throughout the study in a timely manner, and determine whether any abnormal laboratory values 
are clinically significant (CS) or not clinically significant (NCS), and whether there are 
associated signs and symptoms. Laboratory abnormalities should be considered clinically 
significant when they occur after taking study medication, reflect a meaningful change from the 
screening value(s), and require active management (e.g., abnormalities that require study 
treatment dose modification, discontinuation, more frequent follow-up assessments, etc.). 
Clinically significant laboratory abnormalities will be reported as AEs. If the abnormal 
laboratory finding is accompanied by signs or symptoms, report the signs and symptoms as the 
AE in lieu of the abnormal laboratory value. If a diagnosis is available, report the diagnosis. 
8.3.8. 
Disease Progression 
Disease progression assessed by radiographs or other methods should not be reported as an 
adverse event, unless the outcome is fatal during the safety reporting period. Deaths related to 
progression of the underlying disease outside of the safety reporting period should be recorded 
on the corresponding page of the CRF (unless the patient has withdrawn consent). 
8.3.9. 
Special Reporting Situations 
Special reporting situations include: 
• Overdose (any dose greater than 4.1g) 
• Suspected abuse/misuse 
• Inadvertent or accidental exposure 
• Medication error (e.g. incorrect dose administered) 
• Drug-drug interactions 
Report special situations to FibroGen Safety within 24 hours of the investigator’s knowledge of 
the event.  See Study Reference Manual for detailed reporting instructions. 


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8.3.10. 
Safety Monitoring 
8.3.10.1. Data Monitoring Committee (DMC) 
In addition to routine safety monitoring, an independent Data Monitoring Committee (DMC) 
will be established to review safety data on an ongoing basis. A DMC charter will establish the 
procedures, meeting frequency, and scope of responsibilities of the committee. The DMC will 
be comprised of individuals with relevant expertise who are external to the study and are not 
directly involved with the study conduct.   
The sponsor proposes to convene the DMC within 21 days after the first 10 subjects have 
received at least 3 cycles of investigational drug in combination with the FOLFIRINOX regimen 
to specifically evaluate the safety of this combination. After this initial DMC meeting and if no 
additional signal has been identified in addition to what is seen with FOLFIRINOX, the DMC 
will meet approximately every 6 months during the study, in accordance with the DMC Charter. 


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9. 
STATISTICS 
9.1. 
Sample Size Determination 
The study is planned to enroll approximately 280 subjects.  All subjects will be prescribed either 
gemcitabine plus nab-paclitaxel (G/NP) or FOLFIRINOX prior to randomization, and then will 
be randomized with 1:1 randomization ratio to the addition of either pamrevlumab or placebo.  
This sample size is estimated based on the assumption that the median OS for the pamrevlumab 
arm and the placebo arm is 24 and 16.3 months, respectively. The assumptions of overall 
survival are based on the FGCL-3019-069 study results for G/NP + pamrevlumab and G/NP 
alone.  This improvement represents a hazard ratio (HR) of 0.68. With this HR, 233 deaths will 
provide at least 80% power when using a test statistics with a 2-sided significance level of 5%. 
With the enrollment of approximately 280 subjects, 233 deaths are estimated by the end of the 
follow-up period. 
If the treatment effect on EFS has a hazard ratio 0.60, then 161 events would be required to 
provide 75% power when using a stratified log-rank statistic with (one-sided) 0.005 false 
positive error rate. 
For the assessment of OS, all patients will be followed for approximately 18 months after the last 
subject enrolled completes treatment which will occur about 48 months after the start of the trial, 
to achieve 233 events, (i.e., deaths). With 233 events, the trial would have at least 80% power to 
detect a hazard ratio of 0.68, when using a stratified log-rank statistic having (two-sided) 
significance level of 5%.  
9.2. 
Analysis Populations 
9.2.1. 
Intent to Treat (ITT) Population 
The ITT Population is defined as all randomized subjects regardless of whether or not study 
treatment is received.  The primary analysis of efficacy will be based on the ITT population. 
Subjects will be analyzed according to the treatment randomized. 
9.2.2. 
Per Protocol (PP) Population 
The Per Protocol (PP) Population is defined as all subjects who have completed the 6-cycle study 
treatment, had baseline and at least one post-baseline tumor assessment. 
9.2.3. 
Safety Population 
The Safety Population is defined as all randomized subjects who have received study medication. 
The primary analysis of safety will be based on the Safety population.  Subjects will be analyzed 
according to the treatment received. 
 


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9.3. 
Statistical Analysis 
9.3.1. 
General Considerations 
 
After approximately 233 deaths are reached, the final analysis for the primary endpoint and 
secondary endpoints will be conducted.  A gate-keeping strategy will be employed to ensure 
overall control of the type I error rate. The secondary efficacy hypotheses will be relevant only if 
the primary efficacy null hypothesis is first rejected.  
 
Following the rejection of the primary efficacy null hypothesis, each secondary hypothesis will 
be tested.  Each treatment effect testing will be relevant only if the preceding tests have been 
rejected at the same 5% level of significance (two-sided) as for the primary endpoint. The testing 
order for the secondary endpoints is as the order listed in section 3.2.3 of the protocol. 
A hierarchical approach will be implemented.  If the analysis of the effect of pamrevlumab on 
EFS is statistically significant at two-sided p=0.01, then that alpha will be carried forward to the 
final analysis of OS, which then would be conducted at the two-sided p=0.05 level.  If the effect 
of pamrevlumab on EFS is not statistically significant at two-sided p=0.01, then the final 
analysis of pamrevlumab’s effect on OS would be conducted at the two-sided p=0.04 level.  
When the interim analysis of EFS is conducted (i.e. when approximately 161events have 
occurred), an interim look of OS will also be conducted at that time by the DMC for lack of 
benefit analysis. The final analysis of OS will occur when 233 OS events have occurred, which is 
estimated to occur approximately 48 months into the trial.  
The sponsor likely will pursue a regulatory submission for an accelerated approval if the effect 
of pamrevlumab on EFS at the interim analysis is statistically significant at two-sided p=0.01.   
After the interim analysis, to protect the integrity of the OS data for the final analysis, 
confidentiality of the emerging OS data will be maintained (Fleming 2018). 
A Data Access Plan describes the strategy for maintaining confidentiality of the emerging OS 
data until final database lock of the FGCL-3019-087 trial. 
9.3.2. 
Subject Enrollment and Disposition 
The number (%) of subjects who completed or discontinued the study and reasons for early 
discontinuation will be summarized by treatment for subjects in the ITT population. 
9.3.3. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized for subjects in the ITT 
population. 
9.3.4. 
Efficacy Analyses 
9.3.4.1. 
Analysis of Overall Survival (Primary Endpoint)  
Overall survival (OS) is defined as the time from randomization until death from any cause and 
is measured in the intent-to-treat population.  
For subjects who are alive at data cut or at study closure, the recorded date of last known alive, 
last contact date, or the date of the last clinic visit is defined as the censoring date for OS. 


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The OS will be summarized using the Kaplan-Meier method. The Cox proportional hazard 
model including treatment and stratification factors: chemotherapy treatment regimen, SMA 
encasement, unreconstructible disease and geographic region, will be used to compare the 2 
treatment arms and to estimate the hazard ratio and the corresponding 95% confidence interval.  
9.3.4.2. 
Analysis of Event-free Survival (EFS) (Surrogate Endpoint for Accelerated 
Approval) 
The EFS endpoint would be a composite time-to-event endpoint, the event being ‘treatment 
failure’ defined as the earliest occurrence of: 
a) Failure to achieve disease-free status locally after completion of neoadjuvant treatment 
and/or after surgery (i.e., resection failure or progression that precludes surgery); or 
b) Local or distant recurrence; or 
c) Death 
For subjects who did not have the event at data cut or at study closure, the latest date of the 
following events will be defined as the censoring date: last post-baseline CT, last post-baseline 
PET scan, the last known record of ‘Not progressed’, surgical exploration, date of surgery 
cancellation.  EFS will be summarized using the Kaplan-Meier method. The Cox proportional 
hazard model including treatment and stratification factors: chemotherapy treatment regimen, 
SMA encasement, unreconstructible disease and geographic region will be used to compare the 
treatment effect and to estimate the hazard ratio and corresponding 95% CI. 
9.3.4.3. 
Analysis of Progression-free Survival (PFS) 
PFS is defined as the time from randomization until disease progression or death, whichever 
occurs first (FDA Guidance, 2018).  
For subjects who did not have progression at data cut or at study closure, the latest date of the 
following events will be defined as the censoring date: last post-baseline CT, last post-baseline 
PET scans, the last known record of ‘Not Progressed’. 
PFS will be summarized descriptively using the Kaplan-Meier method. The Cox proportional 
hazard model including treatment and stratification factors: chemotherapy treatment regimen, 
SMA encasement, unreconstructible disease and geographic region will be conducted to compare 
treatment effect and to estimate the hazard ratio and corresponding 95% CI. 
9.3.4.4. 
Analysis of Best Overall Objective Response Rate (ORR) 
Best overall objective response rate (ORR) is one of the secondary endpoints where objective 
response is defined as a complete response (CR) or partial response (PR) according to RECIST 
1.1. Objective response will be based on the best overall response recorded from Day 1 until 
centrally-assessed progressive disease (PD), death, or first administration of anti-tumor treatment 
(other than study medication), whichever occurs first. Patients who receive anti-tumor treatment 
other than the study medication prior to reaching a CR or PR, or who die, progress, or drop out 
for any reason prior to reaching a CR or PR will be counted as non-responders in the assessment 
of ORR. Patients without a post-baseline tumor assessment will be considered to be non-
responders. 


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ORR will be summarized by using the analysis of the difference between two proportions for the 
ITT Population and PP Population. Normal approximation method will be used as the sample 
size is larger than 30. Estimation and 95% CI for the ORR for the two arms will be computed 
and difference of the two proportions and its 95% CI will be estimated by SAS PROC FREQ 
procedure. The p-value for testing the difference of the two proportions will be used for 
hypothesis testing for treatment comparison. 
9.3.4.5. 
Analysis of Physical Functioning  by EORTC-QLQ-C30 
The physical functional scale will be scored according to the EORTC- QLQ-C30 scoring 
manual.  For functional scale, the scoring will not be affected if there are at least half of the items 
from the scale answered. All the items that are completed will be used to calculate the raw score 
then through a linear transformation to a standardized score for the scale. The standardized score 
range from 0 to 100; a higher score represents a higher ("better") level of functioning, or a higher 
("worse") level of symptoms. If there are more than half of the items from the scale that are 
missing, then the scale score at the visit will be set to missing. 
Difference between treatment arms in mean change from baseline Physical Functional score at 
selected visits during the treatment period will be assessed using a MMRM model, with 
adjustment for randomization stratification factors. The unstructured covariance will be applied 
first. If the algorithm for unstructured covariance pattern does not converge then heterogeneous 
Toeplitz structure will be used. If this second model does not converge then the (homogeneous) 
Toeplitz structure will be tried, and if all of these covariance structures failed to converge then 
the compound symmetry will be used. 
9.3.4.6. 
Analysis of Abdominal Pain and Fatigue Score by NCI-PRO-CTCAE 
The abdominal pain and fatigue scales will be scored according to the scoring manual.  
Difference between treatment arms in mean change from baseline of the abdominal pain and 
fatigue scores at selected visits during the treatment period will be assessed using a mixed effect 
model for repeated measurements (MMRM), with adjustment for randomization stratification 
factors. 
The unstructured covariance will be applied first. If the algorithm for unstructured covariance 
pattern does not converge then heterogeneous Toeplitz structure will be used. If this second 
model does not converge then the (homogeneous) Toeplitz structure will be tried, and if all of 
these covariance structures failed to converge then the compound symmetry will be used. 
9.3.5. 
Pharmacokinetic Analyses 
The plasma concentrations of the PK samples will be determined by a validated assay, and a plan 
for population PK as well as exposure-response analysis will be provided.  
9.3.6. 
Safety Analyses 
Treatment-emergent adverse events (TEAEs) will be summarized by treatment arm. Treatment-
emergent deaths, serious TEAEs, TEAEs with grade 3 or 4 per CTCAE criteria, and TEAEs 
leading to study or treatment discontinuation will be summarized separately. Surgical 
complications will be summarized by treatment arm. 
Clinically significant changes from baseline in vital signs, laboratory tests, and ECGs will be 
identified. 
Human anti-human antibody data will be summarized in a separate report. 


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9.3.7. 
Sensitivity Analyses 
Sensitivity analyses will be performed to assess overall survival (OS) by center or groups of 
centers which are considered to have similar surgical practices. Overall survival (OS) analysis 
will also be conducted per protocol population. 
If there is a large discrepancy between the two arms in the number of patients who undergo 
surgery, additional analyses to investigate the reasons for the discrepancy will be performed.  
A sub-group analysis will be performed to evaluate the differences in efficacy and safety 
between treatment arms in each subgroup. 
9.4. 
Interim Analysis 
An interim analysis is planned to evaluate EFS as a surrogate endpoint for accelerated approval 
and will be completed when approximately 161 EFS events have occurred. Statistical 
significance occurs when the estimated hazard ratio is 0.667.  When 161 EFS events are 
available at approximately 24 months into the trial, enrollment will be complete (i.e., 280 
patients).   
At the time of this EFS analysis, an interim look of OS will be performed by the DMC for lack 
of benefit analysis, using an O’Brien-Fleming monitoring boundary as a reference..   
After the interim analysis, to protect the integrity of the OS data for the final analysis, 
confidentiality of the emerging OS data will be maintained. (Fleming 2018)Details surrounding 
the planned Interim Analysis will be described in the Interim Analysis Plan (IAP). 
 
9.5. 
Statistical Analysis Plan 
The Statistical Analysis Plan (SAP) will include detailed analysis methods, statistical models, 
definitions, as well as data handling rules.  The SAP will be finalized prior to database lock. 


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10. 
QUALITY CONTROL AND QUALITY ASSURANCE 
10.1. 
Data Quality Assurance 
Quality assurance and quality control systems will be implemented and maintained with 
Standard Operating Procedures by FibroGen and its designee(s), as appropriate, to ensure that 
this clinical study is conducted and data are generated, documented (recorded) and reported in 
compliance with the protocol, ICH E6 (GCP), and other applicable regulations. 
This study will be monitored by FibroGen or designee in accordance with GCP, and may be 
audited or reviewed by an independent Quality Assurance department, IRB/IEC, and/or 
regulatory authorities. This implies that monitors and auditors/inspectors will have the right to 
inspect the study sites at any time during and/or after completion of the study and will have 
direct access to data/source documents, including the subject's file. By participating in this study, 
Investigators agree to this requirement. 
The purpose of trial monitoring is to verify the following: 
• The rights and well-being of human subjects are protected. 
• The reported data are accurate, complete, and verifiable from source documents. 
• All data are collected, tracked, and submitted by the site to FibroGen or designee, 
including unscheduled and missed assessments 
• The reported data are reconciled across all data sources (e.g., laboratory, safety, IRT, 
clinical databases). 
• The conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s). 
Measures will be undertaken to protect the confidentiality of records that could identify subjects, 
respecting the privacy and confidentiality rules in accordance with applicable regulatory 
requirements. 
10.2. 
Audit and Inspection 
Authorized representatives of the sponsor, a regulatory authority, and/or an IRB/IEC may visit 
the investigator site to perform audits or inspections, including source data verification and 
source documentation review. The Investigator will allow the sponsor auditor (or designee), 
regulatory authority or ethics committee representative to inspect the drug storage area, study 
drug stocks, drug accountability records, subject charts (e.g. medical records) and study source 
documents, and other records relative to study conduct. 
The purpose of an audit or inspection is to systematically and independently examine all study-
related activities and documents to determine whether these activities were conducted, and data 
were recorded, analyzed, and accurately reported according to the protocol, ICH GCP guidelines, 
and any applicable regulatory requirements. 
The investigator must contact the sponsor, or its third party representative (CRO), immediately if 
notified by a regulatory authority of an inspection pertaining to this study. 


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11. 
ETHICS 
11.1. 
Ethical Considerations 
The study will be conducted in accordance with applicable regulatory requirements, the 
International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice 
(GCP), the Declaration of Helsinki, any other applicable regulatory requirements, and 
Institutional Review Board (IRB) or independent ethics committee (IEC) requirements. 
11.2. 
Communication with the Institutional Review Board or Independent 
Ethics Committee 
This protocol, the Informed Consent Form, the Investigator’s Brochure, and any information to 
be given to the subject must be submitted to a properly constituted IRB/IEC by the investigator 
for review and approved by the IRB/IEC before the study is initiated and before any 
investigational product is shipped to the investigator. In addition, any subject recruitment 
materials must be approved by the IRB/IEC before the material is used for subject recruitment. 
The investigator is responsible for obtaining reapproval by the IRB/IEC annually or as required 
by the policies and procedures established by the IRB/IEC. Copies of the investigator’s annual 
report and other required reports submitted to the IRB/IEC and copies of the IRB/IEC 
continuance of approval must be furnished to FibroGen or designee. A copy of the signed FDA 
Form 1572 or other qualified investigator statement (as required) must also accompany the above 
approval letter provided to FibroGen. 
Investigators are also responsible for promptly informing the IRB/IEC of any protocol changes 
or amendments, changes to the Investigator’s Brochure, and other safety-related communications 
from FibroGen or its designee. Written documentation of IRB/IEC approval must be received 
before the amendment is implemented. 
Investigators must maintain a list of appropriate qualified persons to whom the investigator has 
delegated significant trial-related duties and update the list as staff and their delegated 
responsibilities change. 
11.3. 
Subject Information and Consent 
Prior to participation in any study-specific procedures, the subject must sign (note: all references 
to “subject” in this section refers to the study subject or his/her legally acceptable representative) 
an IRB/IEC-approved written Informed Consent Form in his/her native language. The approved 
written informed consent must adhere to all applicable laws in regards to the safety and 
confidentiality of the subjects. To obtain and document informed consent, the Investigator should 
comply with applicable regulations, and adhere to ICH GCP standards and the ethical principles 
in the Declaration of Helsinki (October 2008). 
The language in the written information about the study should be as non-technical as practical 
and should be understandable to the subject. Before informed consent is obtained, the 
Investigator should provide the subject ample time and opportunity to inquire about the study 
and to decide whether or not to participate. 
All questions about the study should be answered to the satisfaction of the subject. The written 
Informed Consent Form should be signed and personally dated by the subject and the person 


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who conducted the informed consent discussion, with any additional signatures obtained as 
required by applicable local regulations and IRB/IEC requirements. Each subject will be 
informed that participation is voluntary and that he/she can withdraw from the study at any time. 
All subjects will receive a copy of the signed and dated Informed Consent Form. 
If there are any changes to the IRB/IEC approved ICF during the subjects’ participation in the 
study, the revised ICF must receive the IRB/IEC’s written approval before use and subjects must 
be re-consented to the revised version of the ICF, if/as required by the IRB/IEC. 
Guidance for Clinical Teams: For studies conducted in the United States, each subject must 
provide his or her consent for the use and disclosure of personal health information under the 
U.S. Health Insurance Portability and Accountability Act (HIPAA) regulations by signing a 
HIPAA Authorization Form. The HIPAA Authorization Form may be part of the ICF or may be 
a separate document. IRB review may or may not be required for the HIPAA Authorization 
Form according to study site policies. 
11.4. 
Subject Confidentiality 
The confidentiality of records that could identify subjects should be protected, respecting the 
privacy and confidentiality rules in accordance with applicable regulatory requirements. 
Subject medical information obtained as part of this study is confidential and may only be 
disclosed to third parties as permitted by the Informed Consent and HIPAA Authorization Form 
or separate authorization to use and disclose personal health information signed by the subject, or 
unless permitted or required by law. The subject may request in writing that medical information 
be given to his/her personal physician. 
The processing of personal data in pursuit of this study will be limited to those data that are 
reasonably necessary to investigate the utility of the study medications used in this study. These 
data will be processed with adequate precautions to ensure confidentiality according to local 
laws. 
FibroGen ensures that the personal data are: 
• collected for a specified and legitimate purpose 
• processed fairly and lawfully 
• accurate and up to date 
Explicit consent for the processing of personal data will be obtained prospectively from the 
participating subject. FibroGen and/or designees whose responsibilities require access to 
personal data agree to keep the identity of study subjects confidential. This confidentiality will 
be maintained throughout the complete data processing. 
Study subjects will be entitled to request confirmation of the existence of personal data held by 
FibroGen and will have the right to rectify erroneous or inaccurate data prior to database lock. 


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12. 
DATA HANDLING AND RECORD KEEPING 
12.1. 
Source Documents 
Source documents are original documents, data, and records necessary for the reconstruction and 
evaluation of the clinical study. The investigator or designee will prepare and maintain adequate 
and accurate source documents. These documents are designed to record all observations and 
other pertinent data for each subject enrolled in this clinical study. Source documents must be 
adequate to reconstruct all data transcribed onto the CRFs and resolved queries. 
12.2. 
Direct Access to Source Documents 
The investigator must provide direct access to source data and source documents for trial-related 
monitoring, audits, IRB/IEC review, and regulatory authority inspection. Direct access includes 
examining, analyzing, verifying, and reproducing any records and reports that are important to 
the evaluation of the study. The investigator is obligated to inform and obtain the consent of the 
subject to permit such individuals to have access to his/her study-related records, including 
personal information and medical records. 
12.3. 
Data Collection, Handling, and Verification 
All required data will either be entered onto CRFs by authorized site personnel or will be 
provided as a data transfer from authorized service providers (such as laboratory results from a 
central laboratory). Data will be entered or uploaded into a validated, clinical database compliant 
with 21 CFR Part 11 regulations. 
All subject data will be reviewed by Sponsor and/or designee. Data that appear inconsistent, 
incomplete or inaccurate will be queried for site clarification. 
Medical history, adverse events and medications will be coded using industry standard 
dictionaries (e.g., MedDRA and World Health Organization Drug [WHODrug]) Dictionary. 
The investigator is responsible for reviewing, verifying, and approving all subject data (i.e. CRFs 
and queries) throughout the duration of the study and prior to study completion, ensuring that all 
data are verifiable with source documents. 
12.4. 
Protocol Deviations 
Unless there is a safety concern, there should be no deviations or violations of the study protocol. 
In the event of a safety concern, the Investigator or designee must document and explain the 
reason for any deviation from the approved protocol. The Investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard to study 
participants without prior IRB/IEC approval. Immediately after the implemented deviation or 
change, the Investigator must submit a report explaining the reasons for the protocol violation or 
deviation to the IRB/IEC, FibroGen, and to the regulatory authorities, if required. 
During the COVID-19 global pandemic, sites may have deviated from the protocol due to 
local/site restrictions that were beyond their control.  A study specific memo was issued to all 
sites providing guidance for conducting this clinical trial during COVID.  Protocol deviations 
related to COVID will be captured in the final protocol deviation listing. 


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12.5. 
Retention of Data 
A FibroGen representative will inform the Investigator in writing when it is acceptable to dispose 
of any study records. To enable evaluation and/or audits from regulatory authorities or FibroGen 
or designee, the Investigator agrees to keep records, including the identity of all participating 
subjects (eg, subject identification code list and all source documents), all original signed ICFs, 
copies of all CRFs, original laboratory reports, detailed records of drug disposition and all 
essential documents for the conduct of a clinical study. To comply with international regulations, 
the records should be retained by the Investigator 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 until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. However, the Investigator 
may need to retain these documents for a longer period if required by the applicable regulatory 
requirements or by an agreement with FibroGen. 
12.6. 
Financial Disclosure 
The Investigator’s disclosable financial interests must be obtained prior to initiation of the study 
site, at completion of the study at the investigational site, and 1 year following study completion. 
The Investigator should promptly update this information if any relevant changes occur during 
the above described period. 
Disclosable financial interests will be recorded on the Investigator Financial Disclosure Form. 
Any Investigator(s) added as investigational staff to the form FDA 1572 must complete the 
Investigator Financial Disclosure Form at the beginning of his/her participation in the study. The 
Investigator Financial Disclosure Form for any Investigator(s) leaving the clinical site prior to 
study completion will be obtained prior to study completion. 


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13.
PUBLICATION POLICY
The data and results of the study will be owned solely by FibroGen and shall be confidential 
information of FibroGen, subject to the Investigator's publication rights, described below and if 
any outlined in the Clinical Trial Agreement. It is understood by the Investigator that FibroGen 
may use the information developed in this clinical study in connection with the development of 
its compounds and therefore, may disclose it as required to other clinical investigators, the 
Licensing Authority or to regulatory agencies of other governments. To allow for the use of the 
information derived from this clinical study, the Investigator understands that he/she has an 
obligation to provide and disclose test results and all data developed during this study to 
FibroGen. 
Any publication or presentation of the results of this clinical study by the Investigator may only 
be made in strict compliance with the provisions of the Clinical Trial Agreement. Any 
publication relating to the study shall be made in collaboration with FibroGen.  The Investigator 
should understand that it is not FibroGen’s intention to prevent publication of the data generated 
in the clinical study. However, FibroGen reserves the right to control the form and timing of such 
publication for commercial reasons.  The Study Center and Investigator shall adhere to the 
publication language as outlined in both the Clinical Trial Agreement and the protocol. To the 
extent there is any conflict or ambiguity between Clinical Trial Agreement and the protocol, the 
publication terms in the Clinical Trial Agreement shall prevail. 


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14.
REFERENCES
American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 
2016. 
Boeck S, Hinke A, Wilkwoski R, Heinemann V. (2007) Importance of performance status for 
treatment outcome in advanced pancreatic cancer. World J Gastroenterology; 13(2): 224-227. 
Burris HA, III, Moore MJ, Andersen J, et al. (1997) Improvements in survival and clinical 
benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A 
randomized trial. J Clin Onco; 15(6):2403-13. 
Cavanna et al. (2019) Modified FOLFIRINOX for unresectable locally advanced/metastatic 
pancreatic cancer.  A real-work comparison of an attenuated with a full dose in a single center 
experience.  OncoTargets and Therapy; 12: 3077-3085. 
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics Guidance for Industry 
(2018) [https://www.fda.gov/media/71195/download] 
Clinical Trial Facilitation Group (CTFG). (2014). Recommendations related to contraception and 
pregnancy testing in clinical trials  
Conroy T, Desseigne F, Ychou M, et al. (2011) FOLFIRINOX versus gemcitabine for metastatic 
pancreatic cancer. N Engl J Med; 364:1817-25. 
Dean AP, Spry N, McGrath A (2016) Nab-paclitaxel plus gemcitabine followed by radiotherapy 
with concurrent 5-FU in locally advanced unresectable pancreatic cancer: A Western Australian 
experience. J Clin Oncol 34:4S, (suppl; abstr 430). 
Ellenberg, Fleming and DeMets. “Data Monitoring Committees in Clinical Trials,” Second 
Edition, 2019 Wiley. 
Frazier KS, Grotendorst GR. (1997) Expression of connective tissue growth factor mRNA in the 
fibrous stroma of mammary tumors. Int J Biochem Cell Biol; 29(1):153-61. 
Fleming TR, Ellenberg SS, DeMets DL.  Data Monitoring Committees: Current Issues. Clinical 
Trials 15(4): 321-328, 2018 
Gillen S, Schuster T, Meyer C, et al. (2010) Preoperative/neoadjuvant therapy in pancreatic 
cancer: A systematic review and meta-analysis of response and resection percentages. PLoS 
Med; 7(4):e1000267. 
Hammel P, Huguet F, Van Laethem JL, et al. (2016) Effect of chemoradiotherapy vs 
chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 
months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA 
315:1844–1853. 
Hammel P, Lacy J, Portales F, et al. (2018) Phase II LAPACT trial of nab-paclitaxel plus 
gemcitabine for patients with locally advanced pancreatic cancer. Gastrointestinal Cancers 
Symposium. Abstract 204. 
Hartel M, di Mola FF, Gardini A, et al. (2004) Desmoplastic reaction influences pancreatic 
cancer growth behavior. World J Surg 2004;28(8):818-25. 


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Hidalgo M, Von Hoff DD. (2012) Translational therapeutic opportunities in ductal 
adenocarcinoma of the pancreas. Clin Cancer Res; 18(16):4249-56. 
Iacobuzio-Donahue CA, Ryu B, Hruban RH, et al. (2002) Exploring the host desmoplastic 
response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of 
primary invasion. Am J Pathol;160(1):91-9. 
Loehrer PJ, Feng Y, Cardenes H, et al. (2011) Gemcitabine alone versus gemcitabine plus 
radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative 
Oncology Group trial. J Clin Oncol 29:4105–4112. 
Mukherjee S, Hurt CN, Bridgewater J, et al. (2013) Gemcitabine-based or capecitabine-based 
chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, 
randomised, phase 2 trial. Lancet Oncol 14:317–326. 
NCCN Guideline ® Version 2.2018. Available from: URL: 
https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. 
Oken, M.M., Creech, R.H., Tormey, D.C., et al. (1982) Toxicity And Response Criteria Of The 
Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655. 
Philip AP, Lacy J, Portales F, Sobrero A, Pazo-Cid R, Manzano Mozo JL, et al. Nab-paclitaxel 
plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, 
open-label phase 2 study. Lancet Gastroenterol Hepatol 2020; 5:285-94.  
Poruk K, Gay D, Brown K, et al. (2013) The Clinical Utility of CA 19-9 in Pancreatic 
Adenocarcinoma: Diagnostic and Prognostic Updates. Curr Mol Med; 13(3): 340-351. 
Reni M, Zanon S, Balzano G, Nobile S, Pircher CC, Chiaravalli M, et al. Selecting patients for 
resection after primary chemotherapy for non-metastatic pancreatic adenocarcinoma. Ann Oncol 
2017;28:2786-92.  
Ryu B, Jones J, Hollingsworth MA, et al, (2001) Invasion-specific genes in malignancy: serial 
analysis of gene expression comparisons of primary and passaged cancers. Cancer Res; 
61(5):1833-8. 
SEER. Available from: URL: https: seer.cancer.gov/pancreas. 
Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. A patient-level meta-
analysis of FOLFIRINOX for locally advanced pancreatic cancer. Lancet Oncol 2016; 17:801-
810. 
Von Hoff DD, Ervin T, Arena FP, et al. (2013) Increased survival in pancreatic cancer with nab 
paclitaxel plus gemcitabine. N Engl J Med 2013;369(18):1691-703. 
Wenger C, Ellenrieder V, Alber B, et al. (1999) Expression and differential regulation of 
connective tissue growth factor in pancreatic cancer cells. Oncogene;18(4):1073-108. 
Xie D, Nakachi K, Wang H, et al. (2001) Elevated levels of connective tissue growth factor, 
WISP-1, and CYR61 in primary breast cancers associated with more advanced features. Cancer 
Res; 61(24):8917-23. 
Yeh R, Dercle L, Garg I, et al. (2018) The Role of 18F-FDG PET/CT and PET/MRI in 
Pancreatic Ductal Adenocarcinoma. Abdom Radiol; 43:415-434. 


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APPENDICES 


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APPENDIX 1. SCHEDULE OF ASSESSMENTS 


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Assessmentsa 
Screening 
Periodb 
Cycle 1 
Cycles 2-6 
End 
of 
Treat
mentc 
Safety 
Follow-
up Visit 
Final 
Safety 
Follow-
up 
Contact 
Surgical 
Resectiond  
Surgical
Follow-upe 
Follow-upf 
30 days 
Day
1 
Day 
8 
Day 
15 
Day 
1 
Day 
8 
Day 
15 
~2 
weeks 
post-
last 
dose 
~28 days 
post-last 
dose 
~60 days 
post-last 
dose 
4-8 weeks 
post-last 
dose 
90 days 
post 
discharge 
Up to 
6 years 
Written Informed Consent 
X 
Inclusion/Exclusion 
Criteriab 
X 
Demographics/Medical 
Historyg 
X 
Vital Signs/Weighth 
(include height at screening)
X 
X 
X 
X 
X 
X 
X 
X 
X 
Disease Stage (TNM) 
X 
X 
Performance statusi
X 
X
 
X 
X 
X 
Physical Examj 
X 
X 
X 
X 
X 
 
X 
X 
X 
12-Lead EKGk 
X 
X 
 
X 
 
X 
CBC/Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Specialty Labs (PK/PD) 
See Appendix 2 for details. 
Pregnancy Testl 
X 
X 
 
X 
 
X 
Chemotherapy Regimen  
(G/NP or FOLFIRINOX) 
See section 6.1.2 or 
6.1.3 for details  
See section 6.1.2 or 
6.1.3 for details 
FG-3019 or placebom 
 
X
Xm
X
X
X
CA19-9n 
 
X
X
X 
X
X
PET 
X 
Xo 
CTp 
X 
Q8W until PD is detected
Xp 
Xp 
EORTC-QLQ-C30q 
 
X
X
X 
X
PRO-CTCAE 
Questionnaireq 
 
X 
X 
X 
X 
Xq 
X 
X 
X 
AEs/CMsr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xr 
Xr 


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Eligibility for Surgical 
Explorations 
X
Surgery/Outcomest 
X 
Surgical Complications 
X
Progression/Survival/ 
Follow-on Treatment  
X 
CBC = complete blood count; CT = computer tomography; ECOG = Eastern Cooperative Oncology Group; EKG = electrocardiogram; EOT = end of treatment; 
FDG PET = [18F]-fluorodeoxyglucose-positron emission tomography. 
a.
All visits (including the EOT visit) should occur within ±2 days of protocol specified time point during the neoadjuvant treatment period. The Safety Follow-up and
the Surgical Follow-up visit should occur within ±3 days of the specified time point. Visit windows should be calculated based on the previous study visit date, NOT
Cycle 1 Day 1.
b.
All screening activities should be conducted within 30 days prior to Day 1 Cycle 1.  A diagnostic biopsy, which may be performed per SOC, is required for
histological or cytological confirmation of PDAC.
c.
Subjects who complete 6 cycles of study treatment or discontinue early will undergo an End of Treatment visit approximately 2 weeks following their last dose. All
final efficacy assessments will be performed. Subjects who complete 6 cycles of treatment will be evaluated by the central review team to determine eligibility for
surgical exploration.
d.
All surgeries will occur within 4-8 weeks from the subjects’ last dose. Surgery will be performed in accordance with institutional standards and SOPs. Surgeons
performing surgery for this study will be trained on the protocol. Tumor tissue will be collected during surgical resection and provided to central pathology for
determination of surgical outcome.
e.
All subjects who undergo surgical exploration will be followed for surgical safety for 90 days (± 3 days) post discharge, in accordance with the institutions’ standard
of care. A clinic visit should be scheduled to review surgical complications (if any) and collect CA19-9.
f.
All subjects will be followed in Long Term Follow-up for progression, survival and any additional anti-cancer therapy (follow-on treatment for pancreatic cancer)
until the last subject to complete treatment has been followed for 18 months post-last dose. It is recommended that Long Term Follow-up be conducted approximately
every 3 months.
g.
Medical history includes smoking history.
h.
Height is collected during screening only.
i.
ECOG to be evaluated at baseline, Day 1 of each treatment Cycle, and EOT. Karnofsky scores will be evaluated at EOT only.
j.
A full physical exam is required during screening and on Day 1 of each treatment cycle.
k.
A 12-lead EKG will be performed during screening, on Day 1 of each cycle and EOT.
l.
A serum pregnancy test is required for all females of childbearing potential during screening. The central lab will provide results for the screening serum pregnancy
test. Additionally, any female of childbearing potential must have a negative serum or urine pregnancy test confirmed at the site on Day 1 of each cycle (prior to study
drug administration) and at EOT.
m.
Dosing for pamrevlumab (or placebo) will be based on the weight obtained on Day 1 of each dosing cycle (i.e., Cycle 1 Day 1, Cycle 2 Day 1. An additional dose of
pamrevlumab or placebo to be administered on Day 8 of Cycle 1 only. Pamrevlumab (or placebo) to be infused over 1 hour (± 15 minutes) following infusion of
chemotherapy agents.


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o.
If a subject discontinues treatment early, an EOT PET scan is required unless the baseline PET was performed less than 8 weeks from EOT.
p.
A baseline CT scan will be conducted during the screening period and approximately every 8 weeks thereafter until disease progression is detected by
central imaging review:
• For subjects who complete 6 cycles of treatment, the EOT scan will be evaluated by the central review board in determination of surgical eligibility.
• If a subject completes 6 cycles of treatment without evidence of disease progression, but does not undergo surgical exploration, CT scans should
continue to be collected approximately every 8 weeks and submitted for central review until progression is detected (per RECIST 1.1).
• If a subject undergoes surgical exploration and resection, CT scans should be conducted approximately every 4 months following for up to 2 years
post-resection and approximately every 6 months from 2-5 years post-resection.
• If recurrence of disease is suspected clinically at any time during the post-resection follow-up, a CT scan may be performed “off schedule” and
submitted to central imaging for review/confirmation of progression/recurrence.
q.
All PROs to be collected prior to dosing where applicable. PRO-CTCAE™ questionnaire will be administered on Days 1, 8 and 15 of Cycles 1-3 and
Day 1 and 15 of each treatment cycle thereafter and at the EOT and Safety follow-up visits.
r.
Adverse events and concomitant medications are collected from Day 1 of the study through 60 days following a subject’s last dose of study treatment.
Serious adverse events should be collected/reported from the signing of Informed Consent through 60 days following the subject’s last dose of study
treatment.  A Safety Follow-up visit must be conducted ~28 days post-last dose and a final safety follow-up contact (via phone) must be conducted ~60
days post-last dose.  Additionally, pamrevlumab related SAEs (including deaths) that occur after the safety follow-up visit through the end of the long-
term follow-up will be reported.
s.
Eligibility for surgical exploration per protocol will be determined by a central review board.  However, ultimately, the decision to operate on a subject
lies with the site PI/surgeon. See Section 7.1.4 for details.
t.
Tumor tissue will only be collected during resection.  Surgical outcomes of R0, R1 and R2 will be determined by central pathological review of tissue
samples collected per the study specific pathology protocol during surgical resection. Tissue collected during resection may also be evaluated for
exploratory analysis (i.e. review of slides or digital images for purposes other than determining resection outcome).


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APPENDIX 2. PHARMACOKINETIC AND PHARMACODYNAMIC SAMPLING TIMES 
TIME POINTa 
Pamrevlumab 
(Plasma) 
HAHA 
(Plasma) 
HAHA-NAd 
(Plasma) 
CTGF 
(Plasma) 
Biomarker 
(Plasma) 
Tumor Tissue 
STUDY PERIOD 
DAY 
TIME 
Cycle 1 
1 
Pre-dose b 
X 
X 
X 
X 
Post-dose c 
X 
8 
Pre-dose b 
X 
X 
Post-dose c 
X 
15 
Pre-dose b 
X 
X 
Post-dose c 
X 
Cycle 6 
1 
Pre-dose b 
X 
X 
Post-dose c 
X 
28/EOT 
X 
X 
X 
Safety FU Visit 
28 days 
post last dose 
X 
X 
X 
Surgery 
4-8 weeks 
post last dose 
X 
CTGF = connective tissue growth factor; EOT = end of treatment; HAHA = human anti-human antibody 
a.
For all time points, the actual time of sample collection will be captured.
b.
Pre-dose is within 2 hours prior to the start of the pamrevlumab/placebo infusion.  Recommendation to collect just prior to the start of the chemotherapy infusions.
c.
Post-dose is during 30 minutes to 2 hours post-end pamrevlumab or placebo infusion.
d.
HAHA-NA samples will be collected from all subjects at the Safety Follow-up visit.  Samples/subjects with positive/specific HAHA results will be subject to evaluation of neutralizing
antibody assays and analyses.


Pamrevlumab 
Protocol FGCL-3019-087 Amendment 5.0 
APPENDIX 3. PERFORMANCE STATUS SCALES 
Performance Status Criteria 
ECOG (Zubrod) 
Karnofsky 
Score 
Description 
Score 
Description 
0 
Fully active, able to carry on all pre-
disease performance without restriction. 
100 
Normal, no complaints, no evidence of disease. 
90 
Able to carry on normal activity; minor signs or 
symptoms of disease. 
1 
Restricted in physically strenuous activity 
but ambulatory and able to carry out work 
of a light or sedentary nature; eg, light 
housework, office work. 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
70 
Cares for self, unable to carry on normal activity 
or do active work. 
2 
Ambulatory and capable of all self care 
but unable to carry out any work 
activities. Up and about more than 50% 
of waking hours. 
60 
Requires occasional assistance, but is able to care 
for most of his/her needs. 
50 
Requires considerable assistance and frequent 
medical care. 
3 
Capable of only limited self care, 
confined to bed or chair more than 50% 
of waking hours. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. 
Death not imminent. 
4 
Completely disabled. Cannot carry on 
any self-care. Totally confined to bed or 
chair. 
20 
Very sick, hospitalization indicated. Death not 
imminent. 
10 
Moribund, fatal processes progressing rapidly. 
ECOG = Eastern Cooperative Oncology Group 
Cancer Therapy Evaluation Program 
Revised March 23, 1998 
Common Toxicity Criteria, Version 2.0 
Publish Date: April 30, 1999 
DCTD, NCI, NIH, DHHS March 1998 
Confidential
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Pamrevlumab 
Protocol FGCL-3019-087 Amendment 5.0 
APPENDIX 4. CLAVIEN-DINDO CLASSIFICATION OF SURGICAL 
COMPLICATIONS 
 
Grades Definition 
I 
Any deviation from the normal postoperative course without the need for 
pharmacological treatment or surgical, endoscopic and radiological interventions 
Allowed therapeutic regimens are: drugs as anti-emetics, antipyretics, analgesics, 
diuretics and electrolytes and physiotherapy. This grade also includes wound 
infections opened at the bedside 
II 
Requiring pharmacological treatment with drugs other than such allowed for 
grade I complications. This grade also includes blood transfusion and total 
parenteral nutrition. 
III 
Requiring surgical, endoscopic or radiological intervention. 
A: intervention not under general anaesthesia 
B: intervention under general anaesthesia 
IV 
Life-threatening complication (including central nerve system complications) 
requiring IC/ICU-management. 
A: single organ dysfunction (including dialysis) 
B: multi organ dysfunction 
V 
Death of patient 
Reference: 
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new 
proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 
2004 Aug;240(2):205-13. 
 
 
 
 
 
Confidential
Page 81 of 82


Pamrevlumab 
Protocol FGCL-3019-087 Amendment 5.0 
APPENDIX 5: NCCN GUIDELINES VERSION 2.2018 
Confidential
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Signature Page for VV-CLIN-012753 v1.0
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Approval Task
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SAP_001.pdf: 
FGCL-3019-087 
Statistical Analysis Plan  
Version 2.0
 
 
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STATISTICAL ANALYSIS PLAN 
 
 
STUDY TITLE: 
A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or 
Placebo in combination with either Gemcitabine Plus Nab-
paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients 
with Locally Advanced, Unresectable Pancreatic Cancer 
STUDY DRUG: 
FG-3019 
PROTOCOL NUMBER: 
FGCL-3019-087 
SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
VERSION 
Version 2.0 
RELEASE DATE: 
24 June 2024 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
NCT03941093


FGCL-3019-087 
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Version 2.0
 
 
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The information contained in this document is confidential and proprietary to FibroGen, Inc. No 
part of this document or any of the information contained herein may be transmitted, disclosed, 
shared, reproduced, published or utilized by any persons without prior written authorization by 
FibroGen, Inc 
 
 
SIGNATURE PAGE 
 
 
This document has been signed and dated using 21 CFR part 11 compliant electronic signatures 
(see appended final page). By signing, the signee is attesting that the content of the document is 
compliant with regulatory requirements and guidelines, complete and accurate. 


FGCL-3019-087 
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CHANGES TO PROTOCOL 
Description of Change 
Rationale for Change 
Section affected 
Per Protocol (PP) Population is added in 
the Analysis Population section. 
Primary and secondary endpoints will 
also be conducted for PP population. 
This will distinguish between ITT 
and PP Population  
Section 4.1.1 , 
Section 4.1.2  and 
Section 5.1.2  
Best Overall Objective response rate 
(ORR) is added as a secondary endpoint 
Addition of standard endpoint for 
Oncology study 
Section 4.1.3  
QOL Endpoint has changed to 
Exploratory and will be analyzed by 
MMRM model 
Switch to Exploratory Endpoint 
Section 4.1.4 
Added number of cycles as exploratory 
endpoint 
To compare the number of cycles 
between treatment arms 
Section 4.1.4 
 
REVISION HISTORY 
Version 
Date 
Description 
1.0 
Apr 15, 2022 
 
2.0 
June 24, 2024 
Global study (Cohort 1) is based on protocol Amendment 
5.0. 
Added statistical analysis plan for combined China patients 
from Cohort 1 and Cohort 2 based on protocol Amendment 
5.1 (China-Only). 
Clarified CA19-9 subgroup based on any change from 
baseline in Section 6.6.3.4 
Updated ADA analysis section for clarification.  
Clarified  PFS event and censoring rules in new Table 8.  
Clarified approximately 233 events are needed to achieve at 
least 80% power in Section 3.3. 
Removed Section 6.6.7.7 Response at EOT in SAP v 1.0 
(based on protocol Amendment 4.0) due to an update to 
remove this exploratory endpoint in protocol Amendment 5.  


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TABLE OF CONTENTS 
SIGNATURE PAGE .......................................................................................................................2 
CHANGES TO PROTOCOL ..........................................................................................................3 
REVISION HISTORY.....................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................6 
LIST OF FIGURES .........................................................................................................................7 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
INTRODUCTION ......................................................................................................11 
2. 
STUDY OBJECTIVES ..............................................................................................11 
3. 
STUDY DESIGN .......................................................................................................11 
3.1. 
Overview .....................................................................................................................11 
3.2. 
Study Population .........................................................................................................12 
3.3. 
Sample Size Determination ........................................................................................12 
3.4. 
Randomization and Treatment Assignment ................................................................12 
3.5. 
Dosing Schedule .........................................................................................................12 
3.6. 
Study Assessments......................................................................................................14 
4. 
STUDY ENDPOINTS AND DEFINITIONS ............................................................17 
4.1. 
Study Endpoints ..........................................................................................................17 
4.1.1. 
Primary Endpoint ........................................................................................................17 
4.1.2. 
Event-Free Survival Endpoint for Accelerated Approval ..........................................17 
4.1.3. 
Secondary Endpoints ..................................................................................................17 
4.1.4. 
Exploratory Endpoints ................................................................................................17 
5. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................18 
5.1. 
Analysis Populations ..................................................................................................18 
5.1.1. 
Intent-to-Treat (ITT) Population .................................................................................18 
5.1.2. 
Per-Protocol (PP) Population ......................................................................................18 
5.1.3. 
Safety Population ........................................................................................................18 
5.1.4. 
PK Population .............................................................................................................18 
5.1.5. 
Immunogenicity Analysis Set (IGS) ...........................................................................19 
5.2. 
Multiple Endpoints Hypotheses and Decision Rules ..................................................19 


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5.3. 
Handling of Dropouts or Missing Data ......................................................................19 
5.3.1. 
Handling Missing/Incomplete AE Onset Date ...........................................................19 
5.3.2. 
Handling Missing/Incomplete CM Start/Stop Dates ..................................................20 
5.4. 
Stratification Factors ...................................................................................................21 
5.5. 
Definition of Baseline .................................................................................................22 
5.6. 
Study Day Calculation ................................................................................................22 
5.7. 
Efficacy Analysis Visit Window ................................................................................22 
5.8. 
Interim Analyses and Data Monitoring Committee ....................................................23 
5.9. 
General Layout ...........................................................................................................24 
6. 
STATISTICAL ANALYSES .....................................................................................25 
6.1. 
Subject Enrollment and Disposition ...........................................................................25 
6.2. 
Protocol Deviations ....................................................................................................25 
6.3. 
Demographics and Baseline Disease Characteristics .................................................25 
6.3.1. 
Subject Demographics and Baseline Characteristics ..................................................26 
6.3.2. 
Baseline Disease Stage ...............................................................................................26 
6.3.3. 
Medical History ..........................................................................................................26 
6.4. 
Prior and Concomitant Medications ...........................................................................26 
6.5. 
Study Drug Exposure and Treatment Compliance .....................................................27 
6.5.1. 
Study Drug Exposure ..................................................................................................27 
6.5.2. 
Treatment Compliance ................................................................................................28 
6.6. 
Efficacy Analyses .......................................................................................................29 
6.6.1. 
Interim Analysis ..........................................................................................................29 
6.6.2. 
Multiple Comparison Adjustment ..............................................................................29 
6.6.3. 
Primary Endpoint - Overall Survival (OS) .................................................................30 
6.6.4. 
Event-Free Survival for Accelerated Approval ..........................................................32 
6.6.5. 
Secondary Endpoint - Progression-Free Survival (PFS) ............................................36 
6.6.6. 
Secondary Endpoint – Best Overall Objective Response Rate (ORR) .......................37 
6.6.7. 
Exploratory Endpoints ................................................................................................38 
6.7. 
Safety Analyses ..........................................................................................................42 
6.7.1. 
Adverse Events ...........................................................................................................42 
6.7.2. 
Laboratory Data ..........................................................................................................43 
6.7.3. 
Vital Signs ..................................................................................................................45 


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6.7.4. 
Physical Examinations ................................................................................................45 
6.7.5. 
ECG Data ....................................................................................................................46 
6.7.6. 
Surgical Safety ............................................................................................................46 
6.8. 
Immunogenicity Analysis and PK ..............................................................................46 
6.8.1. 
Terms and Definitions ................................................................................................46 
6.8.2. 
Statistical Analysis for Characterization of ADA Immune Response ........................47 
6.8.3. 
Clinical Implication of ADA Immune Response ........................................................48 
7. 
VALIDATION AND QUALITY ASSURANCE ......................................................49 
8. 
REFERENCES ...........................................................................................................49 
9. 
APPENDICES ............................................................................................................50 
9.1. 
Appendix 1: Schedule of Assessments .......................................................................50 
9.2. 
Appendix 2: General Specifications for Tables, Listings and Figures .......................55 
9.2.1. 
Software Used .............................................................................................................55 
9.2.2. 
General ........................................................................................................................55 
9.2.3. 
Table/Listing/Figure Output File Type and Organization ..........................................55 
9.2.4. 
Page Layout ................................................................................................................55 
9.2.5. 
Titles and Footnotes ....................................................................................................56 
9.2.6. 
Table, Listing, Figure Metadata ..................................................................................57 
9.2.7. 
Significant Digits of Summary Statistics ....................................................................57 
9.2.8. 
Figure Specifications ..................................................................................................58 
9.2.9. 
Unit Conversion ..........................................................................................................59 
9.3. 
Appendix 3: RECIST (1.1) Criteria ............................................................................59 
9.4. 
Appendix 4: TNM and AJCC Staging Definitions .....................................................61 
9.5. 
Appendix 5: CTCAE Toxicity Grading for Laboratory Tests ....................................62 
9.6. 
Appendix 6: Terminology Used in This Study ...........................................................63 
9.7. 
Appendix 7: China CDE Requirements ......................................................................65 
9.8. 
Appendix 8: Analyses of Data from China Patients ...................................................65 
 
LIST OF TABLES 
Table 1: 
Dosing Schedule .........................................................................................................13 
Table 2: 
Analysis Visit Window ...............................................................................................22 


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Table 3: 
Classification of Prior and Concomitant Medications ................................................27 
Table 4: 
Scheduled Doses of Study Drugs .............................................................................28 
Table 5: 
Fixed Sequence Testing Order of Primary and Secondary Endpoints .......................29 
Table 6: 
Censoring Rules for EFS Analysis (FDA Censoring Rules) ......................................34 
Table 7: 
Censoring Rule for EFS Analysis (EMA Censoring Rules) .......................................36 
Table 8:   PFS Event and Censoring Definitions ........................................................................37 
Table 9: 
Definition of TEAE and Study Period When AE Occurred. ................................42 
Table 10: Laboratory Tests .........................................................................................................43 
Table 11: Potentially Clinically Significant (PCS) Values in Vital Signs ..................................45 
Table 12: Schedule of Assessments ............................................................................................51 
Table 13: Specifications for Page Layout ...................................................................................56 
Table 14: Significant Digits of Summary Statistics ....................................................................58 
Table 15: Time Point Response: Patients with Target and Non-Target Lesions ........................60 
Table 16: Overall Response:  Patients with Target and Non-Target Lesions .............................60 
Table 17: CTCAE Toxicity Grading for Chemistry ...................................................................62 
Table 18: CTCAE Toxicity Grading for Serum Hematology .....................................................63 
 
LIST OF FIGURES 
Figure 1: 
EFS Event Determination Criteria Flowchart .............................................................33 
 
 
 
 


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LIST OF ABBREVIATIONS 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AJCC 
American Joint Committee on Cancer 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate Aminotransferase 
ATC 
Anatomic Therapeutic Class 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
BP 
Blood Pressure 
CA 19-9 
Carbohydrate Antigen 19-9 
CBC 
Complete Blood Count 
CI 
Confidence Interval 
Cmin 
the minimum blood plasma concentration reached by a drug during the time 
interval between administration of two doses 
Cmax 
the maximum (or peak) serum concentration that a drug achieves in a specified 
compartment or test area of the body after the drug has been administered and 
before the administration of a second dose 
CM 
Concomitant Medications 
CMH 
Cochran-Mantel-Haenszel 
CR 
Complete Response 
CRF 
Case Report Form 
CS 
Clinically Significant 
CT 
Computer Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTGF 
Connective Tissue Growth Factor 
CV 
Coefficient of Variation 
DMC 
Data Monitoring Committee 
EBL 
Estimated Blood Loss 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 


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EFS 
Event-Free Survival 
EMA 
European Medicines Agency 
EORTC QLQ-C30 
European Organization for the Research and Treatment of Cancer Quality of Life 
Questionnaire 
EOT 
End of Treatment 
FDA 
Food and Drug Administration 
FDG 
Fluorodeoxyglucose 
FDG-PET 
[18F]-Fluorodeoxyglucose-Positron Emission Tomography 
FG-3019 
Pamrevlumab 
G/NP 
Gemcitabine plus Nab-paclitaxel 
HAHA 
Human Anti-Human Antibodies 
HR 
Hazard Ratio 
IAP 
Interim Analysis Plan 
IEC 
Independent Ethics Committees 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IV 
Intravenous  
KM 
Kaplan-Meier 
LAPC 
Locally Advanced unresectable Pancreatic Cancer 
LLN 
Lower Limit of Normal for a laboratory parameter 
LS 
Least Squares 
MAR 
Missing at Random 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed effect Model Repeat Measurement 
MRB 
Multidisciplinary Review Board 
MRI 
Magnetic Resonance Imaging 
MTV 
Metabolic Tumor Volume 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NCS 
Not Clinically Significant 
ORR 
Best Overall Objective Response Rate 
OS 
Overall Survival 
PCS 
Potentially Clinically Significant 


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PD 
Progressive Disease 
PE 
Physical Examination 
PF 
Physical Functioning 
PET 
Positron Emission Tomography 
PFS 
Progression-Free Survival 
PH 
Proportional Hazards 
PK 
Pharmacokinetic(s) 
PP 
Per-Protocol 
PR 
Partial Response 
PROs 
Patient Reported Outcomes 
PT 
Preferred Term 
RBC 
Red Blood Cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RMST 
Restricted Mean Survival Time 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Stable Disease  
SDTM 
Study Data Tabulation Model 
SE 
Standard Error 
SMA 
Superior Mesenteric Artery 
SMQ 
Standardized MedDRA Queries 
SOC 
System Organ Class 
Std 
Standard Deviation 
SUVmax 
Maximum Standardized Uptake Value 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
TLF 
Tables, Listings, Figures 
TNM 
Tumor Node Metastasis 
ULN 
Upper Limit of Normal 
VS 
Vital Sign 
WBC 
White Blood Cell 
WHODrug 
World Health Organization Drug Dictionary 


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1. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) documents planned analyses for Study FGCL-3019-087 
Amendment 5.0 (May 16, 2022) and Amendment 5.1 (China-Only, Aug 16, 2022) entitled “A 
Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in combination with 
either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients 
with Locally Advanced, Unresectable Pancreatic Cancer”. And it is an update from the previous 
SAP V1.0 based on Study FGCL-3019-087 Protocol Amendment 4.0 (Oct 25, 2021). 
This SAP includes statistical analysis methods, statistical models, definitions, and data handling 
rules. It supersedes the statistical section in the protocol in case of any difference. 
2. 
STUDY OBJECTIVES 
The primary objective of this trial is: 
• To evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab in 
combination with either gemcitabine plus nab-paclitaxel (G/NP) or FOLFIRINOX 
when compared to treatment with either G/NP or FOLFIRINOX alone in locally 
advanced, unresectable pancreatic cancer. 
The secondary objective of this trial is: 
• To evaluate the effect of neoadjuvant treatment with pamrevlumab in combination 
with either G/NP or FOLFIRINOX on Event-Free Survival. 
3. 
STUDY DESIGN 
3.1. 
Overview 
This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of 
neoadjuvant treatment with pamrevlumab or placebo in combination with either G/NP or 
FOLFIRINOX, in the treatment of locally advanced unresectable pancreatic cancer (LAPC) 
subjects. Approximately 280 subjects will be enrolled in this trial, across approximately 100 
study centers in the following locations: North America, Europe, and Asia Pacific. 
When completion of global study enrollment (approximately N=280, Cohort 1) is reached, China 
sites will continue enrollment in Cohort 2 until the planned number of subjects in China is 
achieved. 
This trial has five periods: 
• Screening Period (up to 30 days) 
• Neoadjuvant Treatment Period (~24-30 weeks) 
• Evaluation for Surgical Exploration (~ 4-5 weeks after last dose) 
• Surgery (~4-8 weeks after last dose) 
• Follow-up Period (Up to 6 years) 


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A schematic overview of the study, including study period timeframes, is provided in Figure 1 of 
the protocol. 
3.2. 
Study Population 
Patients with locally advanced unresectable pancreatic cancer. 
3.3. 
Sample Size Determination 
The study is planned to enroll approximately 280 subjects with 1:1 randomization ratio to the 
two treatment arms.  
Sample size estimation was based on the assumption that the median Overall Survival (OS) duration 
for the pamrevlumab arm and the placebo arm are 24 and 16.3 months, respectively. This 
improvement represents a hazard ratio (HR) of 0.68. With this HR, approximately 233 deaths will 
provide at least 80% power with a two-sided significance level of 0.05. With the enrollment of 
approximately 280 subjects, 233 deaths will be estimated by the end of the Follow-up period.  
Based on the treatment effect on EFS having an HR of 0.60, 161 events would be required to 
provide 75% power using a stratified log-rank test with a one-sided 0.005 false positive error 
rate. 
3.4. 
Randomization and Treatment Assignment 
Subjects will be randomized 1:1 to one of two treatment arms: 
• Arm A: pamrevlumab + either G/NP or FOLFIRINOX 
• Arm B: placebo + either G/NP or FOLFIRINOX 
Subjects will be stratified at randomization according to the following factors: 
• Chemotherapy treatment regimen (G/NP or FOLFIRINOX) 
• SMA (Superior Mesenteric Artery) encasement (> or ≤ 180°) 
• Unreconstructible disease (yes or no) 
• Geographic region (North America/Europe or Asia Pacific) 
Randomization will be conducted centrally across all sites using an Interactive Response System. 
3.5. 
Dosing Schedule 
Each treatment cycle is 28 days long and subjects may receive up to six cycles of treatment. 
Basically, investigators and their subjects will choose to be treated with either gemcitabine plus 
nab-paclitaxel or FOLFIRINOX as the backbone chemotherapy treatment regimen to be 
administered in combination with pamrevlumab or placebo as shown in Table 1. 


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Table 1: 
Dosing Schedule 
Arm A 
Arm B 
Pamrevlumab, 35 mg/kg by IV infusion on Days 
1 and 15 of each 28-day treatment cycle. An 
additional dose will be given on Day 8 of the first 
cycle. 
Placebo, 35 mg/kg by IV infusion on Days 1 and 
15 of each 28-day treatment cycle. An additional 
dose will be given on Day 8 of the first cycle. 
AND 
• 
Gemcitabine, 1000 mg/m2 by IV infusion on Days 1, 8, and 15 of each 28-day treatment cycle. 
• 
Nab-paclitaxel, 125 mg/m2 by IV infusion on Days 1, 8, and 15 of each 28-day treatment cycle. 
OR FOLFIRINOX  
• 
(Oxaliplatin – 85 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment cycle 
• 
Folinic Acid/Leucovorin – 400 mg/m2 by IV infusion on Days 1 and 15 of each 28-day 
treatment cycle 
• 
Irinotecan* – 180 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment cycle 
• 
Fluorouracil* – 400 mg/m2 by IV infusion (bolus infusion) on Days 1 and 15 of each 28-day 
treatment cycle 
• 
Fluorouracil – 2400 mg/m2 by IV infusion (46-hour continuous infusion) on Days 1-3 and 
Days 15-17 of each 28-day treatment cycle) 
 * Doses may be adjusted per local/institutional guidelines to support modified FOLFIRINOX dosing regimen  
(mFOLFIRINOX) 
 
Arm A treatment consists of: 
• Pamrevlumab, 35 mg/kg by IV infusion on Days 1 and 15 of each 28-day 
treatment cycle. An additional dose will be given on Day 8 of the first cycle. 
AND 
• Gemcitabine, 1000 mg/m2 by IV infusion on Days 1, 8 and 15 of each 28-day 
treatment cycle. 
• Nab-paclitaxel, 125 mg/m2 by IV infusion on Days 1, 8 and 15 of each 28-day 
treatment cycle. 
OR FOLFIRINOX  
• (Oxaliplatin – 85 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment 
cycle 
• Folinic Acid/Leucovorin – 400 mg/m2 by IV infusion on Days 1 and 15 of each 
28-day treatment cycle 
• Irinotecan* – 180 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment 
cycle 
• Fluorouracil* – 400 mg/m2 by IV infusion (bolus infusion) on Days 1 and 15 of each 
28-day treatment cycle 


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• Fluorouracil – 2400 mg/m2 by IV infusion (46-hour continuous infusion) on Days 1-3 
and Days 15-17 of each 28-day treatment cycle) 
Arm B treatment consists of: 
• Placebo, 35 mg/kg by IV infusion on Days 1 and 15 of each 28-day treatment 
cycle. An additional dose will be given on Day 8 of the first cycle. 
AND 
• Gemcitabine, 1000 mg/m2 by IV infusion on Days 1, 8 and 15 of each 28-day 
treatment cycle. 
• Nab-paclitaxel, 125 mg/m2 by IV infusion on Days 1, 8 and 15 of each 28-day 
treatment cycle. 
OR FOLFIRINOX 
• (Oxaliplatin – 85 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment 
cycle 
• Folinic Acid/Leucovorin – 400 mg/m2 by IV infusion on Days 1 and 15 of each 
28-day treatment cycle 
• Irinotecan* – 180 mg/m2 by IV infusion on Days 1 and 15 of each 28-day treatment 
cycle 
• Fluorouracil* – 400 mg/m2 by IV infusion (bolus infusion) on Days 1 and 15 of each 
28-day treatment cycle 
• Fluorouracil – 2400 mg/m2 by IV infusion (46-hour continuous infusion) on Days 1-3 
and Days 15-17 of each 28-day treatment cycle) 
*Doses may be adjusted per local/institutional guidelines to support modified FOLFIRINOX 
dosing regimen (mFOLFIRINOX) 
3.6. 
Study Assessments 
The schedule of assessment is provided in Appendix Section 9.1. 
Eligibility for surgical exploration is evaluated for all subjects who complete 6 cycles of study 
treatment. Subjects who undergo surgical exploration within the protocol-specified window are 
followed for surgical complications and outcomes per protocol. Tissue samples are collected 
during resection and provided to central pathology. Subjects who do not undergo surgical 
exploration (e.g., subjects who did not complete 6 cycles of treatment or do not meet any of the 
protocol defined criteria or had a contraindication to surgery) continue in the Follow-up period to 
be followed for progression, survival and additional anticancer therapies.  Subjects in the 
Follow-up period may receive treatment as per Standard of Care for each institution. 
Vital Signs (VS): Vital signs are collected including heart rate, blood pressure, respirations, 
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Physical Exam (PE): A full physical exam is required during screening and on Day 1 of each 
treatment cycle. All other physical exams may be abbreviated unless a full physical exam is 
warranted in the opinion of the investigator. 
Electrocardiogram (ECG): ECGs are performed in accordance with institutional standards at 
screening, Day 1 of each cycle and EOT. 
Laboratory Evaluations: Labs are evaluated by a central laboratory (lab). Central lab results 
obtained during the screening period are used to determine subject eligibility for participation in 
the trial. Central lab results are reviewed by the investigator for clinical significance and to 
determine appropriate reporting of adverse events. Central lab results for CA19-9 are used to 
determine eligibility for surgical exploration. Local lab results were not captured in the database. 
However local lab results were approved to be used during COVID-19 in case sites were 
restricted from central lab and /or when central lab kits were in shortage due to COVID-19. 
These local lab results will be captured in the clinical database.  
Pharmacokinetics and Pharmacodynamics: Additional samples are collected to evaluate PK, 
HAHA, HAHA-NA and CTGF. 
Pharmacokinetics: Plasma samples are collected in all subjects for evaluation of Cmax and Cmin 
trough levels of pamrevlumab (FG-3019). A central laboratory measures plasma pamrevlumab 
levels using a validated assay. For the analysis of Cmax and Cmin data, it is critical to accurately 
record the dosing time and date in addition to the sampling collection time and date. 
HAHA and CTGF: Plasma samples are collected for evaluation of human anti-human 
antibodies (HAHA), also named as ADA, HAHA-NA and connective tissue growth factor 
(CTGF) in all subjects. Central laboratories measure HAHA and CTGF level using validated 
assays. 
Pharmacodynamics and Biomarkers: Tumor tissue are collected from all resected subjects for 
histological analysis and examination of nucleic acids. Plasma samples are collected from all 
subjects to support the exploratory analysis of protein and nucleic acid markers. 
Eastern Cooperative Oncology Group (ECOG): The ECOG performance scale is used to 
evaluate subject’s performance status during screening and throughout the trial. 
Karnofsky Performance Scale Index: The Karnofsky performance scale is used to evaluate 
subject’s performance at EOT only. Karnofsky performance scores are evaluated by the central 
review team in determination of eligibility for surgical exploration per protocol. 
Carbohydrate Antigen 19-9 (CA 19-9): CA 19-9 levels are measured at baseline and regularly 
throughout the study. CA 19-9 results are evaluated by the central laboratory.  
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scan: An FDG-PET scan 
is performed at baseline and EOT to evaluate SUVmax and metabolic tumor volume (MTV) in 
the primary pancreatic tumor. Central imaging will evaluate all PET scans collected for the 
study. 
Computer Tomography (CT) Scan: CT scans are performed using pancreatic protocols and in 
accordance with the central imaging charter until progression. Central imaging will conduct 
Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 reads on all CT scans collected 
during screening, the neoadjuvant treatment period and follow-up. 


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Baseline CT scans (collected during the screening period) are evaluated by the central 
radiological/surgical review team to confirm subjects have locally advanced, unresectable 
disease prior to enrollment.  
All CT scans collected during the study are evaluated by the central review team for progression 
per RECIST 1.1 until progression is noted. EOT CTs, for subjects who complete all 6 cycles of 
treatment, are evaluated at EOT by the central review team in determination of eligibility for 
surgical exploration per protocol. 
If a subject cannot tolerate a contrast CT, Magnetic Resonance Imaging (MRIs) may be 
performed. If MRIs are performed during screening or the neoadjuvant treatment period due to 
contrast intolerance, they will be sent to central imaging for review. 
Patient Reported Outcomes (PROs): PROs data are collected in all subjects to evaluate the 
most important patient reported symptoms, treatment-related symptoms and functional impacts 
that may be responsive to treatment. EORTC QLQ-C30 and PRO-CTCAE™ questionnaires are 
administered as specified in Appendix 1 in protocol (prior to dosing in all applicable instances). 
• EORTC QLQ-C30: EORTC QLQ-C30 Version 3.0 is the most recent version and is 
used for this study. This questionnaire is collected on Day 1 of each treatment cycle 
(prior to dosing), at EOT and the Safety Follow-up visit. 
• PRO-CTCAE™: The following symptoms from the PRO-CTCAE™ library are 
included in a symptom-specific patient questionnaire: decreased appetite, nausea, 
vomiting, diarrhea, abdominal pain, and fatigue. This questionnaire is collected on 
Days 1, 8 and 15 in the first three treatment cycles (Cycles 1-3), on Days 1 and 15 in 
the last three treatment cycles (Cycles 4-6) and at the EOT and Safety Follow-up 
Visit. 
Surgical Outcomes and Complications: All subjects that undergo surgery within the 
protocol-specified window (at least 4 weeks after the last dose and no longer than 8 weeks after 
the last dose) are followed for surgical outcomes and complications for 90 days after their 
discharge. Surgical safety is assessed by the collection of surgical outcomes measures and 
surgical complications that occur during this timeframe. 
• Surgical Complications: All surgical complications that occur are collected and 
graded in severity according to the Clavien-Dindo Classification (Appendix 4 in 
protocol). 
• Surgical Outcomes: The following surgical outcomes are measured: 
o Type of procedure/resection 
o Resection outcome 
o >10 lymph nodes 
o Operative time >10 hours 
o Length of hospital stay 
o Estimated blood loss (EBL) at time of surgery 


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o Transfusions; units of blood 
o Return to operating room within 30 days 
4. 
STUDY ENDPOINTS AND DEFINITIONS 
4.1. 
Study Endpoints 
4.1.1. 
Primary Endpoint 
The primary endpoint of this trial is Overall Survival (OS), defined as the time from 
randomization to death due to any cause.  
4.1.2. 
Event-Free Survival Endpoint for Accelerated Approval 
The Event-Free Survival (EFS) Endpoint is a composite time-to-event endpoint, the event being 
‘treatment failure’ defined as the earliest occurrence of: 
• Failure to achieve disease-free status locally after completion of neoadjuvant 
treatment and/or after surgery (i.e., resection failure or progression that precludes 
surgery) 
• Local or distant recurrence, or 
• Death 
EFS is also a key secondary endpoint. 
4.1.3. 
Secondary Endpoints 
The secondary endpoints of this trial are: 
• Event-Free Survival (as described above) 
• Progression-Free survival (PFS), defined as the time from randomization until 
objective tumor progression or death (whichever occurs first). 
• RECIST 1.1 – Best Overall Objective Response Rate (ORR), defined as the 
proportion of patients who achieve Complete Response (CR) or Partial Response 
(PR) during treatment period.  
4.1.4. 
Exploratory Endpoints 
• Exploratory endpoints for this trial are: 
• Change in Patient Reported Outcomes (PROs) as measured by: 
o Mean change from baseline during the treatment period in physical function by 
EORTC QLQ-C30 
o Mean change from baseline during the treatment period in abdominal pain by  
o NCI-PRO-CTCAE 


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o Mean change from baseline during the treatment period in fatigue by NCI-PRO-
CTCAE 
• Proportion of all randomized subjects in whom R0 or R1 resection is achieved 
• Difference in OS between resected and non-resected subjects 
• The proportion of subjects considered eligible for surgical exploration per 
protocol-defined criteria 
• Mean change from baseline during the treatment period in CA19-9 
• Change in FDG-PET SUVmax and MTV at EOT when compared to baseline 
• Correlative analyses of baseline CTGF serum levels with clinical outcomes 
• PK exposure-response analysis 
• Histological analysis in tumor tissues collected during resection 
• Evaluation of CTGF as prognostic or predictive biomarker 
• Evaluation of other selected protein and nucleic acid markers in plasma samples 
• Evaluation of number of chemotherapy cycles between the two arms 
5. 
GENERAL STATISTICAL CONSIDERATIONS 
5.1. 
Analysis Populations 
5.1.1. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects regardless of whether or not study 
treatment is received. The primary analysis of efficacy will be based on the ITT population 
(based on treatment randomized).  
5.1.2. 
Per-Protocol (PP) Population 
The Per-Protocol (PP) Population is defined as all subjects who have completed the 6-cycle 
study treatment, had baseline and at least one post-baseline tumor assessments. 
5.1.3. 
Safety Population 
The Safety Population is defined as all randomized subjects who have received study medication. 
All analyses of safety will be based on the Safety population (based on treatment received).  
5.1.4. 
PK Population 
The Pharmacokinetic (PK) population is defined as all randomized subjects who have signed 
informed consent to participate in the study, received at least one dose of study medication, and 
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5.1.5. 
Immunogenicity Analysis Set (IGS) 
The IGS will include all subjects who are in the Safety Population and have a baseline evaluable 
immunogenicity assessment and at least 1 post-baseline evaluable (i.e., positive, negative) 
immunogenicity assessment. 
5.2. 
Multiple Endpoints Hypotheses and Decision Rules 
By design, two-sided 0.01 alpha will be allocated to EFS, the primary endpoint for accelerated 
approval, while two-sided 0.04 will be allocated to OS, the primary endpoint for full approval. 
The alpha designated to EFS will be spent at the time of 161 EFS events (or more depending on 
completion of accrual).   
A hierarchical approach will be implemented.  If the analysis of the effect of pamrevlumab on 
EFS is statistically significant at two-sided p=0.01 at the interim analysis, then that alpha will be 
carried forward to the final analysis of OS, which then would be conducted at the two-sided 
p=0.05 level.  If the effect of pamrevlumab on EFS is not statistically significant at two-sided 
p=0.01 at the interim analysis, then the final analysis of pamrevlumab’s effect on OS would be 
conducted at the two-sided p=0.04 level.  
At the time of 161-event analysis of EFS (or more depending on completion of accrual), an 
interim look of OS will also be conducted at that time by the Data Monitoring Committee 
(DMC) for lack of benefit analysis. The final analysis of OS will occur when 233 OS events have 
occurred, estimated to be approximately 48-54 months into the trial.  
Please refer to the Interim Analysis Plan (IAP Version 1.2, dated of 28 February 2022) for 
detailed description of the interim analysis.  
5.3. 
Handling of Dropouts or Missing Data 
All assessments collected will be considered for analyses regardless of whether such data were 
collected during treatment or after a subject discontinued treatment. All analyses assume the 
missing data are missing at random (MAR), unless stated otherwise. Except for the cases 
described in this section and Section 6.6, only observed data without imputation will be used in 
analyses.  
5.3.1. 
Handling Missing/Incomplete AE Onset Date 
Incomplete Start Date 
The following imputation rules apply to the case where the start date is incomplete (i.e., partially 
missing) for adverse events. 
Missing day and month 
If the year is same as the year of first day on double-blind study medication, then the day and 
month of the start date of double-blind study medication will be assigned to the missing fields. 
If the year is not the same as the year of first day on double-blind study medication, then January 
1 will be assigned to the missing fields. 
 


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Missing month only 
Treat day as missing and replace both month and day according to the above procedure. 
Missing day only  
If the month and year are same as the year and month of first day on double-blind study 
medication, then the start date of double-blind study medication will be assigned to the missing 
day. 
If the month and year are not the same as the year and month of first day on double-blind study 
medication, then the first day of the month will be assigned to the missing day. 
Incomplete Stop Date   
If the stop date is complete and the imputed start date as above is after the stop date, the start 
date will be imputed by the stop date.  
If needed, the following imputation rules apply to the case where the end date is incomplete (i.e., 
partially missing) for adverse events. Other partial end date will not be imputed. 
Missing day and month, or Missing month only 
December 31 will be assigned to the missing fields. 
Missing day only  
The last day of the month will be assigned to the missing day. 
5.3.2. 
Handling Missing/Incomplete CM Start/Stop Dates 
For prior or concomitant medications, including rescue medications, incomplete (i.e., partially 
missing) start date and/or stop date will be imputed. When the start date and the stop date are 
both incomplete for a patient, impute the start date first. 
Incomplete Start Date 
The following rules will be applied to impute the missing start date.  If the stop date is complete 
and the imputed start date is after the stop date, then the start date will be imputed using the stop 
date. 
Missing day and month 
If the year of the incomplete start date is the same as the year of the first dose date of double-
blind study medication, then the day and month of the first dose date will be assigned to the 
missing fields.  
If the year of the incomplete start date is not the same as the first dose date of double-blind study 
medication, then January 1 will be assigned to the missing fields. 
Missing month only 
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Missing day only  
If the month and year of the incomplete start date are the same as the month and year of the first 
dose date of double-blind study medication, then the day of the first dose date will be assigned to 
the missing day.  
If the month and year of the incomplete start date are the same as the first dose date of double-
blind study medication, then the first day of the month will be assigned to the missing day. 
Incomplete Stop Date   
The following rules will be applied to impute the missing stop date, if needed.  If the last dose 
date of double-blind study medication is missing, impute it with the last visit date. If the imputed 
stop date is before the start date (imputed or non-imputed start date), then the imputed stop date 
will be replaced with the start date. 
Missing day and month 
If the year of the incomplete stop date is the same as the year of the last dose date of double-
blind study medication, then the day and month of the last dose date will be assigned to the 
missing fields.  
If the year of the incomplete stop date is not the same as the year of the last dose date of double-
blind study medication, then December 31 will be assigned to the missing fields. 
Missing month only 
Treat day as missing and replace both month and day according to the above procedure. 
Missing day only  
If the month and year of the incomplete stop date are the same as the month and year of the last 
dose date of double-blind study medication, then the day of the last dose date will be assigned to 
the missing day.  
If the month and year of the incomplete stop date are not the same as the month and year of the 
last dose date of double-blind study medication, then the last day of the month will be assigned 
to the missing day. 
5.4. 
Stratification Factors 
Comparisons between treatment arms will be adjusted for the following factors. 
• Chemotherapy treatment regimen (G/NP or FOLFIRINOX) 
• SMA encasement (> or ≤ 180°) 
• Unreconstructible disease (yes or no) 
• Geographic region (North America/Europe or Asia Pacific) 


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5.5. 
Definition of Baseline 
Unless otherwise specified, baseline is defined as the last evaluable observation collected prior to 
the first dose of study drug. 
5.6. 
Study Day Calculation 
The day when a subject receives the first dose of any study drugs (pamrevlumab/placebo, 
gemcitabine, nab-paclitaxel, or FOLFIRINOX) after randomization is designated as Day 1. For 
subjects who have not received any study drug in an ITT analysis, their randomization date will 
be used as Day 1. 
Study day of an assessment/procedure is calculated as following: 
• For assessments or procedures on Day 1 or later,  
Study day = assessment/procedure date – Day 1 date + 1. 
• For assessments or procedures earlier than Day 1,  
Study day = assessment/procedure date – Day 1 date. 
5.7. 
Efficacy Analysis Visit Window 
Efficacy assessments will be summarized by analysis visit based on actual date of assessment. 
Visit windows will have the widths of the corresponding assessments centered at the scheduled 
day as shown in Table 2. 
Table 2: 
Analysis Visit Window 
Study Period 
Assessment 
Interval 
Target Assessment 
Window 
Cycle 1 
Day 1 
1st day of Cycle 1 (Day 1) 
Days=1 ± 4 
Day 8 
8-th day of Cycle 1 (Day 8) 
Days=8 ± 4  
Day 15 
15-th day of Cycle 1 (Day 15) 
Days=15 ± 4 
Cycles 2-6 
Day 1 
k-th day of Cycle x (Day (k + 28 * 
(x-1))) 
Days= (k + 28 * (x-1)) ± 4 
Day 8 
k-th day of Cycle x (Day (k + 28 * 
(x-1))) 
Days=(k + 28 * (x-1)) ± 4 
Day 15 
k-th day of Cycle x (Day (k + 28 * 
(x-1))) 
Days=(k + 28 * (x-1)) ± 4 
End of 
Treatmenta 
Last assessment between Day 2 and EOT visit day, match to the closest scheduled visit in protocol 
if patient had not been off drug for more than 14 days. 
EOT visit should occur within ±2 days of protocol-specified time point.  
Safety 
Follow-up 
Visita 
Around 28 days after the last dose. The Safety Follow-up visit should occur within ±3 days of the 
specified time point.  
 
a: Subjects who discontinue treatment early for any reason will complete End of Treatment (EOT) visit and continue 
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All scheduled and unscheduled assessments are included in analyses. If two assessments are 
available in the same window, the later assessment will be used in analysis. Assessments that do 
not fall in any windows will not be included in analyses. Assessments in follow-up periods will 
be summarized by nominal clinic visit. 
Safety data (lab tests, vital signs, ECG, physical exams) are summarized by nominal clinic visit. 
Data collected during the unscheduled visits are not included in the summary tables, but are 
included in data listings and in evaluations for clinically significant abnormal changes. 
ADA assessment: select in the order of 1) last ADA+ assessment; 2) earlier ADA+ assessment; 
3) last ADA- assessment. 
5.8. 
Interim Analyses and Data Monitoring Committee 
In addition to routine safety monitoring, an independent Data Monitoring Committee (DMC) 
(Ellenberg 2019; Fleming 2018) will be established to review safety data on an ongoing basis. A 
DMC charter will establish the procedures, meeting frequency, and scope of responsibilities of 
the committee.  
The DMC will be comprised of individuals with relevant expertise who are external to the study 
and are not directly involved with the study conduct. The sponsor proposes to convene the DMC 
within 21 days after the first 10 subjects have received at least 3 cycles of investigational drug in 
combination with the FOLFIRINOX regimen to specifically evaluate the safety of this 
combination. After this initial DMC meeting and if no additional signal has been identified in 
addition to what is seen with FOLFIRINOX, the DMC will meet approximately every 6 months 
during the study, in accordance with the DMC Charter.  
At the time of 161 EFS events (or more depending on completion of accrual), a hypothesis of 
equality of EFS between Pamrevlumab and Placebo will be tested at an alpha of 0.01 
(two-sided), while these data will be available only to the DMC and the independent reporting 
statistician who is the liaison between the DMC and the database.  At this time of EFS interim 
analysis, approximately 70 OS events would have occurred, an interim analysis of OS to test for 
lack of benefit will be conducted by the DMC.  
At the interim, a recommendation for early termination of the study for lack of benefit would be 
based on an O’Brien-Fleming monitoring boundary ruling out the final OS hazard ratio being 
< 0.77 (the threshold for benefit at the final analysis of OS at the two-sided 0.05 level). 
This O’Brien-Fleming monitoring boundary for ‘lack of benefit’ for OS will be applied at the 
time of the EFS analysis.  At that time, if 70 of the 233 OS events have occurred at the interim, 
an early termination for lack of benefit would be achieved if the estimated HR is >1.84, while 
early termination would occur at 80 OS events if the estimated HR of OS is >1.65. 
At the time of the Interim Analysis, the DMC will issue the recommendation that these results be 
discussed with the FDA regarding a potential application for Accelerated Approval, if all of the 
following conditions are met: 
• Statistical significance for EFS is achieved at the one-sided p < 0.005; 


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• The O’Brien-Fleming monitoring boundary for ‘lack of benefit’ for OS has not been 
crossed, i.e., the trial has not met the criteria for early termination due to lack of 
benefit on OS (HR>1.84 if 70 OS, or HR>1.65 if 80 OS, etc.);  
• There is no evidence of substantial safety concerns in DMC routine safety review and 
assessment.   
If all of the above conditions are met, the recommendation to discuss this outcome with the FDA 
will be communicated with FibroGen Chief Medical Officer only and the interim data may be 
subsequently released to limited personnel of the sponsor in accordance with the Data Access 
Plan. 
Under all circumstances when the study continues after the interim analysis, to protect the 
integrity of the OS data for the final analysis, confidentiality and blinding of data will be 
maintained (Fleming, et al. 2018). 
For detailed description and computation please refer to the IAP. 
All study sites are pooled in all analyses due to the small number of subjects enrolled at each 
site.  
5.9. 
General Layout 
All study parameters, including baseline characteristics, efficacy, safety, PK, and biomarkers, 
will be summarized descriptively or analytically. Descriptive statistics including the number of 
subjects (n), mean, standard deviation (Std) for baseline variables or standard error (SE) for 
efficacy parameters, median, Q1-Q3, minimum and maximum will be presented for continuous 
variables. For continuous PK parameters, coefficient of variation (CV) and geometric mean may 
also be presented. Number (n) and percentage (%) of subjects in each category will be 
summarized for categorical variables.  
Detailed format requirement will be described in Appendix Section 9.2. Efficacy parameters will 
be summarized analytically. Analytical statistics include least squares (LS) mean and SE, 95% 
confidence interval (CI) for the mean or median, and p-value. Depending on the nature of the 
parameter and statistical model employed, treatment difference will be expressed in absolute or 
percent difference, odds ratio, or HR.  
Summary of baseline tables like demographics will be presented by treatment group as well as a 
combined group (Arm A, Arm B, Overall). Nominal p-values will be presented on the baseline 
table comparing between the two treatment arms for reference only. All other efficacy and safety 
summaries except PK will be presented by treatment group, unless specified otherwise.  
Raw data and derived parameters will be presented in data listings. 
Figures, such as line-chart, bar-chart, boxplot, scatter plot, forest plot, or waterfall plot, are in 
general included to facilitate comparison between treatment arms and evaluation of trend. SE 
(instead of Std) will be used in all figures applicable. 
There will be two sets of analyses, one set for Cohort 1 and the other set for combined China 
patients from both Cohort 1 and Cohort 2. The statistical analysis plan for Cohort 1 is 
summarized in Section 6. The statistical analysis plan for combined China patients is 
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6. 
STATISTICAL ANALYSES 
6.1. 
Subject Enrollment and Disposition 
The number of subjects in each study population (ITT, PP, Safety and PK) will be summarized by 
treatment group. The number (%) of subjects who completed or discontinued the treatment and/or 
study and reasons for early discontinuation are summarized by treatment for subjects in the ITT 
population. 
Subject who discontinued the treatment/study early and the reasons for discontinuation will be 
tabulated and listed. 
The data will be summarized with respect to: 
• number of subjects screened, 
• number (%) of subjects screen-failed, 
• number of subjects randomized (defined as subjects who signed informed consent 
form and received treatment randomization), 
• number (%) of subjects randomized, not treated, 
• number (%) of subjects randomized, treated, 
• number (%) of subjects completed treatment, 
• number of (%) subjects prematurely discontinued from treatment by specific reason   
• number (%) of subjects completed study, 
• number (%) of subjects prematurely discontinued from the study. 
Percent of screen-failed will be based on the number of subjects screened. All other percentages 
for subjects will be based on the number of subjects in the ITT population.  
The number of subjects enrolled at each study site will be summarized by treatment group in a 
separate table.  
6.2. 
Protocol Deviations 
Only important protocol deviations need to be reported for Clinical Study Report.  
Important protocol deviations will be summarized by treatment (in columns) and by study site (in 
rows). COVID-19-related summary table and listing will be provided here. All recorded 
important protocol deviations will be listed by site. Reported items that are not considered as 
important protocol deviations will not be included in summary tables. Minor protocol deviations 
will be presented in listing only. 
6.3. 
Demographics and Baseline Disease Characteristics 
Demographics and baseline characteristics will be summarized descriptively for subjects in both 
ITT and safety populations. Each parameter will be presented in data listings.   


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6.3.1. 
Subject Demographics and Baseline Characteristics 
Subject demographics and baseline characteristics include age, age group (18-64, 65-74, ≥ 75), 
sex, ethnicity, race, height, weight, body mass index (BMI), body surface area (BSA), smoking 
status, number of years that subject smoked, and smoking pack-years. 
BSA and BMI are defined below: 
BSA in m2 = Sqrt (weight in kg * height in cm ÷ 3600)  
BMI = Weight (kg) / (Height (m))2 
Smoking pack-years is defined as average packs per day * duration (years). 
6.3.2. 
Baseline Disease Stage 
Baseline disease and disease stage include the following variables: 
• Time from diagnosis (days) defined as date of first dose ─ date of diagnosis + 1 
• Disease stage (1, 2a, 2b, 3, or 4) 
• Tumor Node Metastasis (TNM) stage 
• Primary location of the tumor in the pancreas (Head, Body or Tail) 
• ECOG performance status 
6.3.3. 
Medical History 
Medical conditions, including allergies and surgeries, are coded in system organ class (SOC) and 
preferred term (PT) using Medical Dictionary for Regulatory Activities (MedDRA) (version 25.0 
or higher).  
The medical conditions will be tabulated by SOC and PT. A subject with multiple medical 
conditions within an SOC is only counted once in this SOC. Similarly, a subject with multiple 
medical conditions within a PT is only counted once in this PT. The tabulation will be sorted 
alphabetically by SOC and by decreasing order of frequency of PT within each SOC in the ITT 
population. 
6.4. 
Prior and Concomitant Medications 
The World Health Organization Drug Dictionary (WHODrug Mar 2022) will be used to classify 
concomitant medications by therapeutic class and generic name.   
Prior and concomitant medications, defined below, are summarized by Anatomic Therapeutic 
Class (ATC) Level 3 and PT.  
1. Prior medications are those that are stopped prior to the first infusion.  
2. Concomitant medications are those that are used concomitantly with the study drug, 
which are defined as medications that are not stopped before the first infusion, excluding 
medications started 60 days after the last dose of study drug.   
Subjects reporting more than one use of the same medication will be counted only once in the 
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Table 3 provides the classification guideline when medication starting or ending dates are missing. 
 
Table 3: 
Classification of Prior and Concomitant Medications 
 
End 
Date 
 
Before start of study 
drug administration 
 
On or after start of 
study drug 
administration 
 
Missing 
Start 
Date 
 
Before start of study 
drug administration 
Prior 
 
Concomitant 
 
Concomitant 
On or after start of 
study drug 
administration and 
before the last dose date 
+60 days.   
 
N/A 
 
 
Concomitant 
 
Concomitant 
Missing 
Prior 
Concomitant 
Concomitant 
Prior cancer therapies including systemic, surgical, and radiation will be summarized 
descriptively and presented in data listing.  
Both prior and concomitant medication usage will be summarized by the number (%) of subjects 
receiving the drug within each therapeutic class and ATC code level 3 PT for Safety population. 
Multiple usage of the same drug by a patient will be counted only once. 
Separate summaries may be provided for prior and concomitant medications of special interest. 
All post neo-adjuvant anticancer medications/procedures/surgeries and non-drug therapies will 
be presented in data listings. 
6.5. 
Study Drug Exposure and Treatment Compliance 
6.5.1. 
Study Drug Exposure 
Study drug exposure will be characterized by the following measures: 
• Duration in days from first dose to last dose of any study drug 
• Number of infusions 
• Average dose amount in mg over the entire treatment period for individual subjects 
Average dose (mg) will be derived using these formulas listed below: 
• Pamrevlumab dose amount in mg = 35 * body weight in kg. 
• Gemcitabine dose amount in mg = 1000 * BSA in m2.  
• Nab-paclitaxel dose amount in mg = 125 * BSA in m2.  


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FOLFIRINOX 
• Oxaliplatin dose amount in mg = 85 * BSA in m2. 
• Folinic Acid or Leucovorin dose amount in mg = 400 * BSA in m2. 
• Irinotecan* dose amount in mg = 135 * BSA in m2. 
• Fluorouracil* dose amount in mg = 400 * BSA in m2. 
• Fluorouracil dose amount in mg = 2400 * BSA in m2. 
NOTE: FOLFIRINOX may be administered at the investigator’s discretion and per their 
institutional guidelines. 
These measures will be summarized descriptively for the Safety population. Study drug 
administration log will be listed. 
Number of treatment cycles will also be summarized.  
6.5.2. 
Treatment Compliance 
Compliance will be calculated as the number of doses the subject received divided by the 
number of doses the subject is scheduled to receive during the participation in treatment. The 
compliance of pamrevlumab, gemcitabine, nab-paclitaxel and FOLFIRINOX will be calculated 
separately.  
Compliance = Actual doses received / Scheduled doses while actively in treatment * 100% 
Scheduled doses of the study drugs are listed in Table 4. 
 
Table 4: 
Scheduled Doses of Study Drugs 
Day within a 
Cycle 
Number of Pamrevlumab (or Placebo) Doses / Number of Gemcitabine/Nab-paclitaxel 
Doses/ Number of FOLFIRINOX 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 5 
Cycle 6 
1 
1/1/1 
4/4/3 
6/7/5 
8/10/7 
10/13/9 
12/16/11 
8 
2/2/1 
4/5/3 
6/8/5 
8/11/7 
10/14/9 
12/17/11 
15 
3/3/2 
5/6/4 
7/9/6 
9/12/8 
11/15/10 
13/18/12 
Compliance of pamrevlumab, gemcitabine, nab-paclitaxel, and FOLFIRINOX will be 
summarized in the following categories: 100%, 90-99%, 80-89%, and less than 80%. 
Early compliance (1-3 cycles) and late compliance (4-6 cycles) will also be summarized. 
 
 


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6.6. 
Efficacy Analyses 
All efficacy analyses described in this section will be based on the ITT population.  
6.6.1. 
Interim Analysis 
Event-Free survival (EFS) will be used as a surrogate endpoint for OS at a pre-planned interim 
analysis. If the interim analysis of the effect of pamrevlumab on EFS is statistically significant at 
two-sided p=0.01, then that alpha will be carried forward to the final analysis of OS, which then 
would be conducted at the two-sided p=0.05 level.  If the effect of pamrevlumab on EFS is not 
statistically significant at two-sided p=0.01, then the final analysis of pamrevlumab’s effect on 
OS would be conducted at the two-sided p=0.04 level.  
At the time of 161 EFS events occur in the trial (or more depending on completion of accrual), an 
assessment of OS will be performed by the DMC. Following the completion of the interim 
analysis for EFS/OS, procedures will be in place to avoid pre-judgment of OS data by properly 
maintaining its confidentiality until final OS analysis is complete or unless there is agreement 
with the Regulatory agency to do otherwise. 
EFS is defined as the time from randomization to death, or objective tumor progression, or 
failure to achieve disease-free status locally after completion of neoadjuvant treatment and/or 
after surgery (i.e., resection failure or progression that precludes surgery), whichever occurs first. 
A more specific algorithm is presented in Table 6. 
6.6.2. 
Multiple Comparison Adjustment 
After approximately 233 deaths are reached, the final analysis for the primary endpoint and 
secondary endpoints will be conducted.  A fixed sequence analysis approach is applied to 
preserve the study-wide error rate of 5%. Under the sequential analysis, the primary and 
secondary efficacy endpoints will be tested in a defined sequence according to the order listed in 
Table 5, each at the usual alpha= 0.05 level of statistical significance. The testing will cease when a 
failure occurs in the pre-determined sequential hypothesis testing and all p-values for the subsequent 
testing will be considered nominal.  
Table 5: 
Fixed Sequence Testing Order of Primary and Secondary Endpoints 
Fixed sequence 
testing order 
Endpoints 
1 (primary 
endpoint) 
Overall Survival (OS), defined as the time from randomization to death due to any cause, as 
defined in Section 4.1.1. 
2 
Event-Free Survival (EFS), as defined in Section 4.1.2. 
3 
Progression-Free Survival (PFS), as defined in Section 4.1.3. 
4 
Best Overall Objective Response Rate (ORR), as defined in Section 4.1.3. 
Following the rejection of the primary efficacy null hypothesis, each secondary hypothesis will 
be tested sequentially.  Each treatment effect testing will be relevant only if the preceding tests 
have been rejected at the same 5% level of significance (two-sided) as for the primary endpoint.  


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6.6.3. 
Primary Endpoint - Overall Survival (OS) 
6.6.3.1. 
Definition of Estimand for Overall Survival 
Overall Survival (OS) is defined as the time from randomization until death from any cause. 
Date of death is recorded on the Death CRF. For subjects who are alive at data cut or at study 
closure, the recorded latest date of last known alive, last contact date, or the date of the last clinic 
visit is defined as the censoring date for OS. 
Handling of intercurrent events:  
Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by subject, 
Physician Decision, Protocol Deviations, etc.). Treatment policy strategy prescribed in ICH E9 
Guidance and Addendum (R1) will be used: the occurrence of the intercurrent event is irrelevant 
here due to censoring at the last date. All observed values will be used regardless of whether the 
intercurrent event occurs. Missing data are assumed to be MAR. 
6.6.3.2. 
Primary Analysis of Overall Survival 
The null hypothesis of the primary endpoint is no treatment difference for OS between the two 
treatment groups.  
Treatment comparison will be performed using the stratified log-rank test stratified by factors: 
chemotherapy treatment regimen (G/NP or FOLFIRINOX), SMA encasement (> or ≤ 180°), 
Unreconstructible disease (yes or no), and Geographic region (North America/Europe or Asia 
Pacific). The p-value from stratified log-rank test will be used for hypothesis testing for the 
primary analysis. 
Sample SAS code: 
PROC LIFETEST;  
  TIME {time-to-event variable} * censor (1); 
  STRATA stratiﬁcation-factors / GROUP=arm; 
RUN; 
The 1-year, 2-year, 3-year, on-treatment, Kaplan-Meier (KM) estimates with 95% CI can be 
obtained and calculated from the KM curve with the corresponding cutoffs.  
Hazard ratio and 95% Confidence Interval (CI) will be derived from Cox Proportional Hazard 
Model with the same stratification factors. Comparisons between the two treatment arms will be 
characterized using the following statistics: 
• Hazard ratio (HR) and its 95% CI 
• Median time-to-event and its 95% CI 
• Proportions of subjects with 1-year, 2-year, and 3-year survival 


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Hazard ratio is based on the assumption that the ratio of the hazard rates at each time interval is 
approximately constant during the study. The null hypothesis that this ratio is 1 (event hazard 
rates are the same between treatment group and placebo).  
The Cox proportional hazards model, with adjustment of the stratification factors: chemotherapy 
treatment regimen, SMA encasement, unreconstructible disease, and geographic region, will be 
used to compare the 2 treatment arms and to estimate the HR and the 95% CI. The key 
assumption of the Cox model is the proportional hazard function assumption. Specifically, the 
model assumes that each covariate has a multiplicative effect in the hazards function that is 
constant over time. If the proportional hazard assumption is rejected then the following stratified 
Cox Model will be used instead. 
Sample SAS code: 
PROC PHREG; 
  MODEL {time-to-event variable} * censor (1) = arm /rl; 
          STRATA stratiﬁcation-factors; 
  HAZARDRATIO arm/CL = PL; 
RUN; 
6.6.3.3. 
Sensitivity Analyses of Primary Endpoint of Overall Survival - Difference in 
Restricted Mean Survival Time (RMST) Method and Per-Protocol Population 
The RMST methodology is applicable free of the proportional hazards (PH) assumption and can 
be used as a sensitivity analysis to explore the robustness of the primary analysis results. In 
particular, as it pertains to the cutoff point (τ) to evaluate the RMST, it is noted that the cutoff 
point should not exceed the minimum of the largest observed time for both treatment arms so 
that the RMST of both treatment arms being evaluated can be adequately estimated and 
comparison between treatments is feasible; τ should be clinically meaningful and closer to the 
end of the study follow-up so that the majority of survival outcomes will be covered by the time 
interval. 
• τ = minimum of (largest observed survival time for Arm A, largest observed survival 
time for Arm B). 
The following statements use PROC LIFETEST to perform analyses of the RMST in addition to 
the standard analyses: 
PROC LIFETEST DATA=xxxx TIMELIM= <τ>;  
  TIME survtime * censor (1); 
  STRATA stratiﬁcation-factors/ GROUP= arm;  
RUN; 
The OS analysis will also be applied to PP Population. 


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6.6.3.4. 
Subgroup Analysis using the Primary Model 
Subgroup analyses will be performed for the following subgroups in the Primary Analysis for the 
primary endpoint of OS by using Log-rank test for comparison: 
• Sex: male, female; 
• Race: White, Black, Asian, American Indian or Other  
• Age: < 65, ≥ 65 years old; 
• FOLFIRINOX, GEMICITABIN 
• Unreconstructible disease: Yes, No 
• SMA encasement: > 180 degrees, ≤ 180 degrees 
• Geographic region: North America/Europe, Asia Pacific 
• Patients with any change from baseline during the treatment period in CA19-9 is 
≥ 50%, Patients with all  change from baseline during the treatment period in CA19-9 
is < 50% 
• Patients with ≥ 30% reduction from baseline in FDG-PET SUVmax at EOT, Patients 
with < 30% reduction from baseline in FDG-PET SUVmax at EOT 
• ADA status (positive, negative, or unknown; details in Section 6.8).  
6.6.4. 
Event-Free Survival for Accelerated Approval 
6.6.4.1. 
Definition of Estimand for Event-Free Survival 
Subjects are considered to have an EFS event (shown in Figure 1) at the earliest time that any of 
the following occurs: 
• Progression that precludes surgery 
• Local or distant recurrence 
• Death 
For subjects who did not have the event at study closure or data cutoff for interim analysis, the 
latest date of the following events is defined as the censoring date: last post-baseline CT, last 
post-baseline PET scan, the last known record of ‘Not progressed’, surgical exploration, date of 
surgery cancellation, and date of safety follow-up visit (Details of censoring rules in Table 6). 


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Figure 1: 
EFS Event Determination Criteria Flowchart 
Did subject experience PD during 
neoadjuvant tx period?
Yes
PD (Radiological – Central Imaging) = 
EFS Event (Imaging data: RSDTC(Date 
of Tumor Identification)
No
Did the independent multi-
disciplinary review board  
recommend surgery?
No
Yes
Does Site Agree?
Does Site Agree?
Yes
No
Yes
No
Eligible for Surgery
Site Agrees – Surgery Planned
Surgery Not 
Performed
Site disagreed due to 
lack of surgical skill/
equipment
Continue to follow 
for EFS
Ineligible for Surgery
Site Disagrees – Surgery Planned
Surgery Not Performed 
 Patient was Ineligible for Surgery per Central Review and 
Site Agreed
EFS Event
(Date of CT Scan if subject was ineligible due to PD @ 
EOT or unreconstructible disease)
(Date of Safety Follow-Up Visit if subject was ineligible 
was to performance score or medical contraindication to 
surgery)
All subjects who do 
not undergo 
surgery continue in 
Follow-Up Period 
(progression/survival/anti-
cancer therapies)
Local or distal reucrrence or Death 
Following ‘Resection Achieved’
EFS Event
(Date of CT Scan or Date of Death)
Surgery 
Outcome
Resection Not 
Achieved/ 
Attempted
EFS Event
(Date of 
Surgery)
Surgery 
Outcome
Resection 
Achieved
Follow for EFS 
Event 
(Recurrence/OS)
Surgery 
Outcome
Resection Not 
Achieved/
Attempted
EFS Event
(Date of 
Surgery)
Surgery 
Outcome
Resection 
Achieved
Follow for EFS 
Event 
(Recurrence/OS)
Surgery Cancelled
Patient 
Decision
Continue 
to follow 
for EFS
Comorbidity
EFS Event 
(Date of Surgery 
Cancellation)
Surgery Cancelled
Patient 
Decision
Continue 
to follow 
for EFS
Comorbidity
EFS Event
 (Date of Surgery 
Cancellation)
Surgery Not 
Performed
Site disagreed as they 
felt patient was not a 
surgical candidate
EFS Event = Date of 
Safety Follow-up Visit
 
Handling of Intercurrent Events:  
• Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by 
subject, Physician Decision, Protocol Deviations, etc.). Treatment policy strategy is 
applied: the occurrence of the intercurrent event is irrelevant. All observed values will 
be used regardless of whether the inter-current event occurs.  
• Death: Composite strategy: death is captured through the endpoint definition. 
The null hypothesis for EFS is the equality of EFS between Arm A and Arm B.  


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Table 6: 
Censoring Rules for EFS Analysis (FDA Censoring Rules) 
Situation 
Event/Censor 
Days to EFS or Censoring 
Incomplete or no baseline tumor assessments  
Censored 
1  
Progression documented between scheduled 
visits  
Event  
Earliest of:  
[Date of response assessment 
showing new lesion (if progression is 
based on new lesion); or  
Date of last response assessment] - 
Date of randomization + 1 
No progression  
Censored 
Date of last response assessment 
with no documented progression - 
Date of randomization + 1 
Treatment discontinuation for undocumented 
progression  
Censored 
New anticancer treatment started  
Censored 
Date of last response assessment 
with documented non-progression 
before start of new treatment - Date 
of randomization + 1 
Death before first PD assessment  
Event  
Death date - Date of randomization + 
1 
Death between adequate assessment visits  
Event  
Death or progression after more than one 
missed assessment  
Censored  
Date of last response assessment 
prior to missing assessments with 
documented non-progression - Date 
of randomization + 1 
Disease progressed or death before surgical 
evaluation  
Event 
Earliest date of CT scan date and 
death date - Date of randomization + 
1 
Surgery not performed (MRB recommend 
surgery, site not agree) 
Event 
Date of safety follow-up visit - Date 
of randomization + 1 
Surgery planned (MRB recommend surgery, 
site agree), but cancelled. 
Event  
Date of surgery cancellation - Date 
of randomization + 1 
Surgery not performed (MRB not recommend 
surgery, site agree) 
Event  
Date of CT scan 
(mets/unreconstructible) - Date of 
randomization + 1 
If not above, Date of safety follow-
up visit - Date of randomization + 1 
Surgery planned (MRB not recommend 
surgery, site not agree), but cancelled. 
Event  
Date of surgery cancellation - Date 
of randomization + 1 
Surgery performed but resection not 
achieved/attempted 
Event  
Date of surgery - Date of 
randomization + 1 
Surgery planned (MRB not recommend 
surgery, site not agree), but resection Achieved 
and Local or distal recurrence or death 
following resection achieved 
Event  
Earliest date of CT scan date and 
death date - Date of randomization + 
1 


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Situation 
Event/Censor 
Days to EFS or Censoring 
No event at data cut or at study closure 
Censored 
Latest date of (last post-baseline CT 
date, last post-baseline PET scan 
date, the last known record of ‘Not 
progressed’ date, surgical 
exploration date, date of surgery 
cancellation) - Date of 
randomization + 1 
MRB: Multidisciplinary Review Board. 
6.6.4.2. 
Analysis of Event-Free Survival 
Event-Free Survival will be summarized using the KM method. Median time-to-event and its 
95% CI will be estimated by KM method using SAS PROC LIFETEST procedure. 
Comparison of EFS between treatment and placebo will be performed using the stratified log-
rank test stratified by factors: chemotherapy treatment regimen (G/NP or FOLFIRINOX), SMA 
encasement (> or ≤ 180°), Unreconstructible disease (yes or no) and Geographic region (North 
America/Europe or Asia Pacific). The p-value from stratified log-rank test will be used for 
hypothesis testing for treatment comparison. 
Sample SAS code: 
PROC LIFETEST;  
  TIME {time-to-event variable} * censor (1); 
  STRATA stratiﬁcation-factors / GROUP=arm; 
RUN; 
The Cox proportional hazard model including treatment and stratification factors: chemotherapy 
treatment regimen, SMA encasement, unreconstructible disease and geographic region will be 
used to estimate the HR and corresponding 95% CI. The key assumption of the Cox model is the 
proportional hazard function assumption. Specifically, the model assumes that each covariate has 
a multiplicative effect in the hazards function that is constant over time.  
If the proportional hazard assumption is rejected then the following stratified Cox Model will be 
used instead. 
Sample SAS code: 
PROC PHREG; 
  MODEL {time-to-event variable} * censor (1) = arm /rl; 
  STRATA stratiﬁcation-factors; 
  HAZARDRATIO arm /CL = PL; 
RUN; 


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Initially, the stratification factors are included in the model one at the time. Finally, all the 
explored adjustment of multiple factors will be included in the model.  Those factors with a 
significant p-value by using likelihood test (or Wald test) will be kept in the stratified Cox 
model. 
6.6.4.3. 
Sensitivity Analyses of EFS  
Sensitivity analysis will be conducted to evaluate the robustness of EFS analysis results. It will 
be carried out for EFS endpoint by implementing different censoring rule in the definition of 
EFS (Table 7). This sensitivity analysis will be conducted in the ITT Population.  
More specifically this sensitivity analysis for EFS analysis will be based on European Medicines 
Agency (EMA) Censoring rule. Note that EMA uses similar rules as FDA (Table 6), except that 
EMA does not differentiate special situations such as new anticancer treatment or missing 
assessments (regardless of these situations) when considering censor/event. 
The EFS (FDA censoring rule) will also be conducted for PP Population as another sensitivity 
analysis.    
Table 7: 
Censoring Rule for EFS Analysis (EMA Censoring Rules) 
Situation 
Event/Censor 
Days to EFS or Censoring 
New anticancer treatment started  
Censored 
Date of last adequate response assessment 
- Date of randomization + 1, regardless of 
new anticancer treatment 
New anticancer treatment started 
Event 
Date of documented progression - Date of 
randomization + 1, regardless of new 
anticancer treatment 
Death or progression after more than 
one missed assessment    
Event 
Date of event - Date of randomization + 1, 
regardless of missing assessments 
6.6.5. 
Secondary Endpoint - Progression-Free Survival (PFS) 
6.6.5.1. 
Definition of Estimand for Progression-Free Survival 
Progression-Free Survival is defined as the time from randomization until disease progression or 
death, whichever occurs first. Date of disease progression is defined as the date of radiological 
progression per RECIST 1.1 criteria recorded the Disease Progression CRF.  
Handling of Intercurrent Events:  
• Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by 
subject, Physician Decision, Protocol Deviations, etc.). Treatment policy strategy will 
be applied: the occurrence of the intercurrent event is irrelevant. All observed values 
will be used regardless of whether the intercurrent event occurs.  
• Death. Composite strategy is applied: death is taken to be a component of the 
variable. 
 


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6.6.5.2. 
Analysis of Progression-Free Survival 
Progression-Free Survival will be summarized using the KM method for the ITT Population and PP 
Population. Median time-to-event and its 95% CI will be estimated by KM method using SAS 
PROC LIFETEST procedure. Comparison of PFS between treatment and placebo will be 
performed using the stratified log-rank test stratified by factors: chemotherapy treatment regimen 
(G/NP or FOLFIRINOX), SMA encasement (> or ≤ 180°), Unreconstructible disease (yes or no) 
and Geographic region (North America/Europe or Asia Pacific). The p-value from stratified log-
rank test will be used for hypothesis testing for treatment comparison. 
Refer to Table 8 for details on PFS event and censoring definitions. 
Table 8:   
PFS Event and Censoring Definitions 
# 
Situation 
Date of event or censoring 
Outcome 
1 
No baseline tumor assessment 
Randomization 
Censored 
2 
No adequate post-baseline tumor assessment 
and no death occurs prior to first scheduled 
post-baseline tumor assessment 
Randomization 
Censored 
3 
Centrally-determined progression  
Date of progression 
PFS Event 
4 
Death  
Date of death 
PFS Event 
5 
Two or more consecutively missed scheduled 
tumor assessments immediately followed by 
centrally-determined progression or death 
Date of last adequate tumor 
assessment prior to the 
consecutively missed tumor 
assessments 
Censored 
6 
Start of new anticancer therapy* without 
centrally-determined progression or death 
 
Date of last adequate tumor 
assessment prior to the new 
anticancer therapy 
Censored 
7 
No centrally-determined progression or death  
Date of last adequate tumor 
assessment 
Censored 
*For calculating PFS, start of protocol-specified surgery after the neoadjuvant will not be considered as initiating a 
new anticancer therapy. 
 
6.6.6. 
Secondary Endpoint – Best Overall Objective Response Rate (ORR) 
Best overall objective response rate (ORR) is the secondary endpoint where Objective response 
is defined as a CR or PR according to RECIST 1.1. Objective response will be based on the best 
overall response recorded from Day 1 until centrally-assessed progressive disease (PD), death, or 
first administration of anti-tumor treatment (other than study medication), whichever occurs first. 
Patients who receive anti-tumor treatment other than the study medication prior to reaching a CR 


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or PR, or who die, progress, or drop out for any reason prior to reaching a CR or PR will be 
counted as non-responders in the assessment of ORR. Patients without a post-baseline tumor 
assessment will be considered to be non-responders. 
6.6.6.1. 
Analysis of Best Overall Objective Response Rate (ORR) 
ORR will be summarized by using the analysis of the difference between two proportions for the 
ITT Population and PP Population. Normal approximation method will be used as the sample 
size is larger than 30. Estimation and 95% CI for the ORR for the two arms will be computed 
and difference of the two proportions and its 95% CI will be estimated by SAS PROC FREQ 
procedure. The p-value for testing the difference of the two proportions will be used for 
hypothesis testing for treatment comparison. 
6.6.7. 
Exploratory Endpoints 
6.6.7.1. 
Physical Functioning 
Definition of Estimand for Physical Functioning by EORTC QLQ-C30 
EORTC QLQ-C30 is a health-related quality of life questionnaire (HRQOL) developed to assess 
the quality of life of cancer patients. EORTC QLQ-C30 Version 3.0 is the most recent version 
and is used for this study. Physical functioning (PF) is assessed using the EORTC QLQ-C30 
instrument on Day 1 of every cycle as well as EOT (2 weeks from the last dose), and at safety 
follow-up (4 weeks from last dose). PF scores will be derived as defined in the EORTC QLQ-
C30 Manual. 
Analysis of Physical Functioning by EORTC QLQ-C30 
PF scores will be derived as defined in the EORTC QLQ-C30 Manual. For functional scale, the 
scoring is not affected if there are at least half of the items from the scale answered. All the items 
that are completed are used to calculate the raw score then through a linear transformation to a 
standardized score for the scale. The standardized score ranges from 0 to 100; a higher score 
represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms. If 
there are more than half of the items from the scale that are missing, then the scale score at the 
visit is set to missing. Missing data will not be imputed. 
Difference between treatment arms in mean change from baseline Physical Functional score at 
selected visits during the treatment period is assessed using a Mixed effect Model Repeat 
Measurement (MMRM) model, with adjustment for randomization stratification factors and 
baseline PF scores. The LS mean and the corresponding 95% confidence intervals for the 
differences between Arm A (pamrevlumab + either G/NP or FOLFIRINOX) and Arm B (placebo + 
either G/NP or FOLFIRINOX) will be presented along with the p-values for the treatment 
differences resulting from the model. The unstructured covariance is applied first. If the 
algorithm for unstructured covariance pattern does not converge then heterogeneous Toeplitz 
structure is used. If this second model does not converge then the (homogeneous) Toeplitz 
structure is tried, and if all the covariance failed to converge then the compound symmetry is 
used. All assessments will be included in the model. 
Sample SAS code – MMRM (PF Scores):  


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PROC MIXED DATA = xxx; 
  CLASS arm subjid; 
  MODEL Δscore = arm stratiﬁcation-factors /SOLUTION COVB; 
  REPEATED  /SUBJECT=subjid TYPE=UN;  
  LSMEANS arm/ DIFF CL ALPHA=0.05; 
  ODS OUTPUT lsmeans=mixlsmeans diﬀs=mixdiﬀs; 
RUN; 
6.6.7.2. 
Abdominal Pain and Fatigue Score 
Definition of Estimand for Abdominal Pain and Fatigue Score by NCI-PRO-CTCAE 
Abdominal pain and fatigue are assessed using the PRO-CTCAE™ Questionnaire. This 
questionnaire is collected on Days 1, 8 and 15 in the first three treatment cycles (Cycles 1-3), on 
Days 1 and 15 in the last three treatment cycles (Cycles 4-6) and at the EOT and Safety Follow-
up Visit. 
Analysis of Abdominal Pain and Fatigue Score by NCI-PRO-CTCAE 
The abdominal pain and fatigue scales are scored according to the scoring manual.  
The difference between treatment arms in mean change from baseline abdominal pain and 
fatigue score at selected visits during the treatment period is assessed using a MMRM model, 
with adjustment for randomization stratification factors and baseline Abdominal score and 
baseline fatigue scores. The stratification factors include chemotherapy treatment regimen, SMA 
encasement, unreconstructible disease, and geographic region. The LS mean and the 
corresponding 95% confidence intervals for the differences between Arm A (pamrevlumab + 
either G/NP or FOLFIRINOX) and Arm B (placebo + either G/NP or FOLFIRINOX) will be 
presented along with the p-values for the treatment differences resulting from the model. The 
unstructured covariance is applied first. If the algorithm for unstructured covariance pattern does 
not converge then heterogeneous Toeplitz structure is used. If this second model does not 
converge then the (homogeneous) Toeplitz structure is tried, and if all of the covariance failed to 
converge then the compound symmetry is used. All assessments will be included in the model. 
6.6.7.3. 
Difference in OS between Resected and Non-Resected Subjects 
Resection rate is defined as proportion of all randomized subjects in whom R0 or R1 resection is 
achieved.  Resection outcome (R0 or R1) is determined by pathological examination of the 
surgical specimen after resection and is recorded on Surgical Outcome CRF. An outcome of R0 
or R1 will be considered a successful resection. An R2 resection or the inability to resect the 
tumor following surgical exploration (Resection Not Achieved) will be considered a resection 
failure. 
Difference in OS will be tested by log-rank test between resected subjects and non-resected 
subjects.  


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6.6.7.4. 
Eligibility for Surgical Exploration 
Subjects are considered eligible for surgical exploration if one or more of the following criteria 
are met and have no contraindications: 
• Reduction in CA19-9 level >50% at EOT when compared to baseline.  
• FDG-PET SUVmax decrease by >30% at EOT when compared to baseline. 
• Partial Response (PR), Complete Response (CR) or Stable Disease (SD) per RECIST 
1.1 at EOT. 
• Resectable or borderline resectable per National Comprehensive Cancer Network 
(NCCN) Version 2.2018 
Contraindications include: 
• Development of distant metastases or local progression per RECIST 1.1 
• Performance status of Karnofsky score ≤ 50 
• Unreconstructible disease as determined by central radiological/surgical review 
• Other conditions that are considered by the PI/surgeon to be contraindications to 
surgery 
The central review board (to include radiologists, surgeons, and oncologists) review information 
provided by the site and determine whether a subject is eligible for surgical exploration per 
protocol. The PI/surgeon ultimately decide whether a subject will undergo surgery. 
The proportion of subjects considered eligible for surgical exploration will be summarized by 
treatment group. 
Exact 95% CIs for the point estimates as well as the treatment difference will be obtained from 
SAS PROC FREQ procedure with EXACT option. The two treatment arms will be compared 
using the Cochran-Mantel-Haenszel (CMH) test controlling for the stratification factors listed in 
Section 5.4. 
6.6.7.5. 
Mean Change from Baseline during Treatment Period in CA19-9 
The CA19-9 endpoint defined only in subjects with baseline CA19-9 value higher than the upper 
limit of normal (ULN). ULN is defined as 37 U/mL in this study (Ballehaninna and 
Chamberlain, 2012). The CA19-9 is performed at Day 1 of each cycle, End of Treatment (EOT), 
Safety Follow-up Visit and Surgical Follow-up Visit. Baseline CA19-9 is defined as the 
assessment on Day 1 prior to study drug dosing. If Day 1 assessment is missing, then the last 
assessment prior to dosing is used.  
Mean change from baseline of CA19-9 values at Day 1 of each cycles, EOT, Safety Follow-up 
Visit and Surgical Follow-up Visit will be used for this endpoint. Comparison between the two 
arms will be evaluated using the two-sample Wilcoxon rank sum test.  


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6.6.7.6. 
Change in PET SUVmax at End of Treatment (EOT) when compared to Baseline 
An FDG-PET scan is performed at baseline and EOT. Maximum standardized uptake value 
(SUVmax) is read by radiologists at each site. Change in FDG-PET SUVmax at EOT when 
compared to baseline is summarized. 
Change from baseline in PET SUVmax is evaluated using the one-sample Wilcoxon signed rank 
test. Comparison between the two arms will be evaluated using the two-sample Wilcoxon rank 
sum test.  
6.6.7.7. 
Correlative analyses of baseline CTGF serum levels with clinical outcomes 
CTGF samples are collected on Day 1 pre-dose and at safety follow-up visit. CTGF data are 
summarized descriptively by scheduled time point.  
The Cox model described in Section 6.6.3.2 will be used to evaluate the correlation of baseline 
CTGF serum levels with clinical outcomes of OS, , EFS and PFS. 
6.6.7.8. 
Histological Analysis in Tumor Tissues Collected during Resection 
Tumor tissue will be collected from all resected subjects for histological analysis. The 
histological analysis data will be listed and summarized descriptively by treatment group.  
6.6.7.9. 
Evaluation of CTGF as Prognostic or Predictive Biomarker 
The subjects were divided into two groups by the median of CTGF levels: lower CTGF levels 
(< median) and higher CTGF levels (≥ median). Proportion of patients with Partial Response 
(PR), Complete Response (CR), Stable Disease (SD) as well as Objective Response (PR+CR) at 
EOT will be summarized by CTGF levels. The two CTGF levels will be compared using the 
Chi-square test controlling for the stratification factors listed in Section 5.4 to evaluate the 
potential of CTGF as prognostic biomarker. 
Additional analysis of relationship between clinical outcomes and CTGF, treatment, and CTGF 
by treatment interaction will be explored. 
6.6.7.10. Evaluation of Other Selected Protein and Nucleic Acid Markers in Plasma 
Samples 
Biomarker data will be presented in a separate report. 
6.6.7.11. ECOG 
Change from baseline in ECOG status will be summarized in a shift table of post-baseline versus 
baseline. 
6.6.7.12. Disease Stage 
Disease TNM stage and cancer staging will be summarized in a shift table of EOT versus 
Screening.  


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6.6.7.13. Number of Treatment Cycles 
Number of cycles will be compared between treatment arms using ANOVA. The impact of 
number of cycles and treatment compliance on OS and EFS will be explored using Cox 
proportional hazard model. 
6.7. 
Safety Analyses 
Safety analyses will include summary of adverse events (AEs), surgical safety parameters, lab 
test results, vital signs, ECGs, and physical exams. In general, safety data will only be 
summarized descriptively and no formal inferential statistical test will be applied. All analyses 
described in this section will be based on the Safety population. 
6.7.1. 
Adverse Events 
The definitions of AEs, serious adverse events (SAEs), severity, and relationship to study 
medication are described in Section 8.2 of the protocol. Adverse events are coded using the 
Medical Dictionary for Regulatory Activities (MedDRA version 25.0 or higher) for system organ 
class (SOC) and preferred term (PT) for summary.   
Treatment-Emergent Adverse Event (TEAE)  
Treatment-emergent adverse events (TEAEs) are defined as new or worsening AEs that occurred 
in the time window of first dose of study drug (Day 1) and within 60 days after the last dose of 
study drug. Detailed definitions are in Table 9. 
 
Table 9: 
Definition of TEAE and Study Period When AE Occurred. 
AE Onset Date Relative to Dosing*  
AEPRIOR Flag 
on CRF 
TEAE  
Study Period 
(EPOCH) 
AE onset date < Day 1 
Any 
No 
Screening 
AE onset date = Day 1 
Yes  
No 
Screening 
No  
Yes 
Treatment 
Day 1 < AE onset date ≤ date of last dose in treatment 
period 
Any 
Yes 
Treatment 
Date of last dose < AE onset date ≤ date of last dose + 60 
Any  
Yes 
60-day follow-up 
AE onset date > date of last dose + 60 
Any 
No 
Additional follow-up 
beyond 60 days 
*First dose refers to first of any study medication; last dose refers to last of any study medication. 
AE Severity Rating 
AEs are rated by the investigators as “mild”, “moderate”, “severe”, “life threatening”, or “fatal” 
based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 grading 
system as described in Section 8.3.3 of the protocol. If a subject reports multiple occurrences of 
an AE within one SOC or PT, the most severe occurrence will be presented in the summary by 
severity rating. Missing severity rating will not be imputed. 


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AEs Related to Pamrevlumab/Placebo, or Gemcitabine, or Nab-paclitaxel, or 
FOLFIRINOX 
Investigators determine the relationship of AEs with the study medications as described in 
Section 8.3.4 of the protocol. If related and unrelated occurrences of an AE within one SOC or 
PT are reported in a subject, the related occurrence will be presented in the summary by 
relationship. Missing relationship will be imputed as “Related”. The pamrevlumab, gemcitabine, 
nab-paclitaxel and FOLFIRINOX-related AEs will be listed and summarized separately. 
Analysis of Adverse Events 
All reported AEs will be presented in listings. Treatment-emergent adverse events (TEAEs) will 
be summarized by treatment arm, SOC and PT. The summary tables will be sorted alphabetically 
by SOC and by decreasing order of frequency of PT within each SOC, based on the rate of both 
treatment arms combined.  A subject with multiple AE within an SOC is only counted once in 
this SOC. Similarly, a subject with multiple AE within a PT is only counted once in this PT. 
In addition to listing of all reported AEs and summary of incidence of all TEAEs, the following 
subgroups of AEs will be summarized: 
• Treatment-emergent serious adverse events (TESAEs) (Table and Listing) and 
relationship to the study drugs (whether related or unrelated) 
• Fatal SAEs  
• TEAEs leading to treatment or study discontinuation 
• TEAEs with incidence ≥ 5% in either arm 
• TEAEs occurred in 2 or more subjects in either arm 
• TEAEs with severity grade ≥ 3  
• TEAEs with severity grade ≥3 that are at least possibly related to 
pamrevlumab/placebo (as assessed by investigators) 
• Most frequent non-serious TEAEs with incidence ≥ 5% in either arm 
• All cause deaths 
All deaths captured on Death CRF will be included in the summary of deaths (within 60 days of 
last dose of study drug and beyond 60 days of last dose of study drug).  
6.7.2. 
Laboratory Data 
The lab tests in Table 10  are evaluated at every clinic visit to assess treatment tolerability.  
Table 10: 
Laboratory Tests 
CBC Panel: 
Chemistry Panel: 
Absolute neutrophil count (ANC) 
Bicarbonate 
Eosinophils 
BUN 
Erythrocyte count (RBC) 
Calcium 


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CBC Panel: 
Chemistry Panel: 
Hematocrit 
Creatinine 
INR 
Chloride 
PTT/PT 
Magnesium 
Hemoglobin 
Glucose 
Leukocyte count (WBC) 
Aspartate aminotransferase (AST) 
Lymphocytes 
Alanine aminotransferase (ALT) 
Mean corpuscular volume 
Alkaline phosphatase (ALP) 
Monocytes 
Bilirubin, total 
Neutrophils 
Albumin 
Platelets 
Phosphorous 
CRP 
Potassium 
Basophils 
Sodium 
Investigators review and determine whether the lab results are normal or abnormal, and if 
abnormal, whether they are clinically significant (CS) or not clinically significant (NCS). 
In addition to investigators’ assessments, CTCAE grading is used to evaluate the lab results. 
CTCAE grade 3 or higher is considered potentially clinically significant (PCS). The CTCAE 
Version 5.0 grading for the study-specific tests is presented in Appendix Section 9.5. 
Analysis of Laboratory Data 
Laboratory test results and change from baseline are summarized descriptively by visit.  
CTCAE grade 3 or higher lab test results will be considered PCS. These results will be presented 
in a data listing. 
Shift tables for selected laboratory data will be used to summarize changes from baseline to each 
visit in CTCAE categories are tabulated. Shift from baseline to most severe CTCAE category 
during the study is also summarized. In addition, shift tables from baseline to most abnormal 
laboratory finding (low, normal, and high) will also be presented. 
Lab data are summarized by nominal clinic visit. Data collected during the unscheduled visits 
outside of a visit window are not included in the summary tables, but are included in data listings 
and in evaluations for PCS abnormal changes. 
Some lab data are collected using local labs (in lieu of the ICON central lab) due to central lab 
kit shortages caused by the COVID-19 pandemic.  In these cases, local lab values and reference 
ranges collected from CRFs will be integrated with central lab data when appropriate and 
feasible. Local lab values will be flagged in datasets and data listings to be differentiated from 
central lab values. Sensitivity analyses may be performed for key analyses of lab parameters 
without local lab values (i.e., set to missing). 


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6.7.3. 
Vital Signs 
Vital sign parameters include heart rate, systolic/diastolic blood pressures (BP), respiration, and 
temperature as well as weight and height (height is collected during screening only).  
Potentially clinically significant vital sign changes are those which meet both criteria in the 
Table 11 below. 
Table 11: 
Potentially Clinically Significant (PCS) Values in Vital Signs 
Vital Sign 
Parameter 
 
Flag 
Criteria 
Observed Value 
Change from Baseline 
Systolic BP (mm Hg) 
High 
≥ 160 mmHg 
Increase of  ≥ 20 mmHg 
Low 
  ≤ 95 mmHg 
Decrease of  ≥ 20 mmHg 
Diastolic BP (mm Hg) 
High 
    ≥ 110 mmHg 
Increase of  ≥ 10 mmHg 
Low 
  ≤ 45 mmHg 
Decrease of  ≥ 10 mmHg 
Heart Rate (bpm) 
High 
≥ 100 bpm 
Increase of  ≥ 20 bpm 
Low 
≤ 50 bpm 
Decrease of  ≥ 20 bpm 
Body temperature (⁰C) 
 
37  
>3  
BP=blood pressure; bpm=beats per minute; ⁰C=Celsius 
* A post-baseline value is considered as a PCS value if it meets both criteria for observed change from baseline. 
Analysis of Vital Signs 
Vital sign observed values and change from baseline will be summarized descriptively by Tables 
and Listings and by visit and by treatment arm.  
In addition, incidence of PCS observed values or changes from baseline, which are defined in 
Table 7, will be tabulated for each visit.  
All measurements and change from baseline will be presented in tables and data listings with 
PCS values or changes from baseline flagged. 
6.7.4. 
Physical Examinations 
At each clinic visit, investigators perform physical examination for the following body systems: 
general appearance, head, eyes, ears, nose, throat (HEENT), lungs, heart, chest, back, abdomen, 
extremities, neurologic, and skin. Investigators determine whether the body systems are normal 
or abnormal. For the abnormal cases, descriptions are provided and clinical significance is 
identified. Baseline is defined as the findings on Day 1 prior to first dose. 
Findings from physical examinations will be summarized in shift tables that include cross-
tabulation of ‘Normal’, ‘Abnormal NCS’, ‘Abnormal CS’ from baseline to worst post-treatment. 
The number and percent of subjects with “Normal”, “Abnormal”, “Not Done”, and “Missing” 
physical examination results will be summarized by body system, treatment arm, and visit.  
The data listing includes abnormal findings. 


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6.7.5. 
ECG Data 
ECG is evaluated at baseline, Day 1 of each treatment cycle, and EOT. 
ECG findings will be summarized in shift tables that include cross-tabulation of investigator 
assessments of ‘Normal’, ‘Abnormal NCS’, ‘Abnormal CS’ at Day 1 of each treatment cycle, 
and EOT versus baseline.  
Detailed findings will be presented in the data listing. 
6.7.6. 
Surgical Safety 
Surgical safety assessed during surgery: 
• Duration of the surgery 
• Estimated blood loss (EBL) during surgery 
• Any blood transfusion 
• Amount of blood transfusion (cc) 
Surgical complication during post-operative follow-up: 
• Return to operating room within 30 days of surgery 
Surgical safety measures described in Section 7.2.10 of the protocol will be summarized 
descriptively for subjects who have undergone a R0 or R1 resection. 
6.8. 
Immunogenicity Analysis and PK 
6.8.1. 
Terms and Definitions 
6.8.1.1. 
Sample ADA Status 
• Baseline ADA-positive sample: ADA is detected in the last sample before initiation 
of treatment. 
• Baseline ADA-negative sample: ADA is not detected in the last sample before 
initiation of treatment. 
• Treatment-emergent ADA-Positive: Meets definition of treatment-induced or 
treatment-boosted ADA: 
− Treatment-induced ADA-Positive: A post-treatment positive ADA is detected in 
a subject for whom pre-treatment ADA assessment is either negative or not 
assessable 
− Treatment-boosted ADA-Positive: Pre-existing ADA was boosted to a higher 
level following study treatment, i.e. pre-treatment positive ADA titer was boosted 
by at least 2 dilution steps (4-fold) following study treatment. 
• ADA-negative sample: After initiation of treatment, ADA is not treatment-emergent 
ADA-positive. 
Next, using the sample ADA status, the subject’s ADA status is defined. 


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6.8.1.2. 
Subject ADA Status 
• Baseline ADA-positive subject: A subject with a baseline ADA-positive sample. 
• Baseline ADA-negative subject: A subject with baseline ADA-negative sample. 
• ADA-positive subject: An evaluable subject with at least one treatment-emergent 
ADA-positive sample at any time during the study. 
• Neutralizing-positive: At least one treatment-emergent ADA-positive sample with 
neutralizing antibodies detected (if available). 
• ADA-negative subject: An evaluable patient without a treatment-emergent ADA 
sample during the study. 
• ADA-unknown: Patients without evaluable baseline and/or post-baseline ADA 
samples will be categorized as “ADA-unknown”. 
6.8.2. 
Statistical Analysis for Characterization of ADA Immune Response 
6.8.2.1. 
Incidence of ADA 
• Percentage of treatment-emergent ADA patients for the defined study period, where 
the denominator is the number of ADA evaluable patients in the respective treatment 
arm and/or subgroup. 
• Number (%) of subjects will be reported for the following parameters based on 
evaluable subjects: 
− Baseline ADA-positive 
− Treatment-emergent ADA-positive (treatment-induced, or treatment-boosted) 
− Neutralizing-positive (if available) 
− ADA-negative 
− ADA-unknown 
• ADA prevalence: Percentage of treatment-emergent ADA patients at any given time 
point, where the denominator is the number of ADA evaluable patients in the 
respective treatment arm and/or subgroup at that time point. 
• A listing of all ADA assessments will be provided. 
• Additionally, a separate listing of ADA assessments for all neutralizing antibody 
(NAb)-positive subjects will be provided (if available). 
6.8.2.2. 
ADA Titer Kinetics 
All ADA-positive subjects will be included in the analysis. 
• Summary statistics of subject-level ADA titers using the maximum titer value post-
baseline within an ADA-positive subject will be presented for baseline ADA-negative 
subjects and baseline ADA-positive subjects. The median, interquartile range, and 


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range of the maximum titers will be reported. For ADA-positive subjects with a 
baseline ADA-positive sample, the median and interquartile range of the fold increase 
from baseline in titer (ratio of maximum post-baseline titer to baseline titer) will also 
be reported. Graphical presentation of the summary data may be provided using 
boxplots, as appropriate. 
• For sample-level ADA titers, boxplots of ADA titers at each assessment time point 
will be provided, as appropriate, to demonstrate whether the ADA levels tend to 
change over time during the treatment, along with ADA incidence at each assessment 
time point. 
• Spider plots may be considered to show the trend of ADA titer over time. 
6.8.3. 
Clinical Implication of ADA Immune Response 
Clinical implication of ADA immune response will only be assessed if there are at least ~10 
subjects with treatment-emergent ADA-positive samples.  Otherwise, individual subject’s safety 
profile will be examined and described based on listings. 
6.8.3.1. 
PK and ADA Immune Response 
• Effect of ADA response on drug exposure will be explored by examining the drug 
exposures using graphical plots of observed drug concentration levels by ADA status 
and sampling time. Corresponding numerical values of geometric mean, arithmetic 
mean, and standard deviation will be displayed under the figures. The observed 
concentration below LLOQ will be presented as zero. 
A listing of drug concentrations will be provided. Time course of observed concentrations by 
study visit with identifiers for antibody response will be plotted for each subject separately. 
6.8.3.2. 
Safety and Efficacy 
Effect of ADA response on safety will be explored by examining the frequency and type of AEs 
of interest, including (1) Total TEAEs, (2) Standardized MedDRA Queries (SMQ) for Drug 
Hypersensitivity, (3) Events Associated with Anaphylaxis as defined by Sampson et al 2006, and 
(4) Infusion-related Reactions. 
For each of the above category of AEs, summary tables for incidence will be provided 
for each of the preferred terms and overall, within a category by ADA status, if the 
number of ADA-positive subjects is of sufficient size (e.g., at least ≈10 subjects). 
Otherwise, individual subject’s safety profile will be examined and described based on a 
listing. Preferred term will be determined prior to the database lock.  
Listing of AEs will be provided. The listing will indicate study day and study period of 
the positive responses. 
Primary endpoint will be summarized by ADA status. A listing for all positive subjects (relative 
to baseline) will be provided. The listing will also indicate study day and study period of the 
positive responses. 


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7. 
VALIDATION AND QUALITY ASSURANCE 
Study Data Tabulation Model (SDTM), Analysis Data Model (ADaM), tables, listings, figures 
(TLF) will be programmed by two programmers independently. The results must be 100% 
matched.  
Both primary and validation programmers will develop programs independently based on the 
specifications and/or SAP. If the outputs are datasets, the final outputs will be compared 
electronically. If the outputs are TLFs, benchmark results will be generated and compared. The 
validation findings and resolutions are documented on a Validation Worksheet. 
The detailed process for validation and quality assurance is documented in the Standard 
Operating Procedures of Q2, Inc.  
8. 
REFERENCES 
Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, 
prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J 
Gastrointest Oncol. 2012; 3(2): 105–119 
Eisenhauera EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
Revised RECIST guideline (version 1.1), Eur J Cancer, 2009; 45 (2), 228 –247. 
Ellenberg, Fleming and DeMets. Data Monitoring Committees in Clinical Trials, Second 
Edition, 2019, Wiley. 
Fleming TR, Ellenberg SS, DeMets DL. Data Monitoring Committees: Current Issues. Clinical 
Trials, 2018;15(4): 321-328 
Hung Man Ngai, Interim Analysis Plan: FG-3019-087 Version 1.2 Dated of Feb 28, 2022 
ICH E9 Guideline: Statistical Principles for Clinical Trials, dated of 5 February 1998. 
ICH-E9 (R1) Guideline: Addendum: Estimands and Sensitivity Analysis in Clinical Trials, dated 
of 16 June 2017. 
NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 
The American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification 
and staging system for pancreatic cancer, AJCC Cancer Staging Manual, 7th Edition, 2010. 


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9. 
APPENDICES 
9.1. 
Appendix 1: Schedule of Assessments 
 


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Table 12: 
Schedule of Assessments 
Assessmentsa 
Screening 
Periodb 
Cycle 1 
Cycles 2-6 
End of 
Treatmentc 
Safety 
Follow-
up 
Visit 
Final 
Safety 
Follow-
up 
Contact 
Surgical 
Resectiond  
Surgical 
Follow-
upe 
Follow-
upf 
30 days 
Day 
1 
Day 
8 
Day 
15 
Day 
1 
Day 
8 
Day 
15 
~2 weeks 
post-last 
dose  
~28 
days 
post-
last 
dose 
~60 
days 
post-
last 
dose 
4-8 weeks 
post-last 
dose 
90 days 
post 
discharge 
Up to  
6 years 
Written Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteriab 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics/Medical 
Historyg 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs/Weighth 
(include height at screening) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Disease Stage (TNM) 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
Performance statusi 
X 
X 
 
 
X 
 
 
X 
X 
 
 
 
 
Physical Examj 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
 
 
12-Lead EKGk 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 
CBC/Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Specialty Labs (PK/PD) 
 
See Appendix 2 of the protocol for details. 
 
 
 
 
Pregnancy Testl 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
 


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Table 12: 
Schedule of Assessments 
Assessmentsa 
Screening 
Periodb 
Cycle 1 
Cycles 2-6 
End of 
Treatmentc 
Safety 
Follow-
up 
Visit 
Final 
Safety 
Follow-
up 
Contact 
Surgical 
Resectiond  
Surgical 
Follow-
upe 
Follow-
upf 
30 days 
Day 
1 
Day 
8 
Day 
15 
Day 
1 
Day 
8 
Day 
15 
~2 weeks 
post-last 
dose  
~28 
days 
post-
last 
dose 
~60 
days 
post-
last 
dose 
4-8 weeks 
post-last 
dose 
90 days 
post 
discharge 
Up to  
6 years 
Chemotherapy Regimen  
(G/NP or FOLFIRINOX) 
 
See Section 6.1.2 
or 6.1.3 of the 
protocol for 
details  
See Section 6.1.2 
or 6.1.3 of the 
protocol for 
details 
 
 
 
 
 
 
FG-3019 or placebom 
 
X 
Xm 
X 
X 
 
X 
 
 
 
 
 
 
CA19-9n 
 
X 
 
 
X 
 
 
X 
X 
 
 
X 
 
FDG-PET 
X 
 
 
 
 
 
 
Xo 
 
 
 
 
 
CTp 
X 
Q8W until PD is detected 
Xp 
 
 
 
 
Xp 
EORTC QLQ-C30q 
 
X 
 
 
X 
 
 
X 
X 
 
 
 
 
PRO-CTCAE 
Questionnaireq 
 
X 
X 
X 
X 
Xq 
X 
X 
X 
 
 
 
 
AEs/CMsr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xr 
 
 
Xr 
Eligibility for Surgical 
Explorations 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Surgery/Outcomest 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Surgical Complications 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Progression/Survival/ 
Follow-on Treatment  
 
 
 
 
 
 
 
 
 
 
 
 
X 
 


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CBC = complete blood count; CT = computer tomography; ECOG = Eastern Cooperative Oncology Group; EKG = electrocardiogram; EOT = end of treatment; 
FDG-PET = [18F]-fluorodeoxyglucose-positron emission tomography. 
a. All visits (including the EOT visit) should occur within ±2 days of protocol-specified time point during the neoadjuvant treatment period. The Safety 
Follow-up and the Surgical Follow-up visit should occur within ±3 days of the specified time point. Visit windows should be calculated based on the 
previous study visit date, NOT Cycle 1 Day 1. 
b. All screening activities should be conducted within 30 days prior to Day 1 Cycle 1.  A diagnostic biopsy, which may be performed per SOC, is 
required for histological or cytological confirmation of PDAC. 
c. Subjects who complete 6 cycles of study treatment or discontinue early will undergo an End of Treatment visit approximately 2 weeks following their 
last dose. All final efficacy assessments will be performed. Subjects who complete 6 cycles of treatment will be evaluated by the central review team 
to determine eligibility for surgical exploration.  
d. All surgeries will occur within 4-8 weeks from the subjects’ last dose. Surgery will be performed in accordance with institutional standards and SOPs. 
Surgeons performing surgery for this study will be trained on the protocol. Tumor tissue will be collected during surgical resection and provided to 
central pathology for determination of surgical outcome. 
e. All subjects who undergo surgical exploration will be followed for surgical safety for 90 days (± 3 days) post discharge, in accordance with the 
institutions’ standard of care. A clinic visit should be scheduled to review surgical complications (if any) and collect CA19-9. 
f. All subjects will be followed in Long-Term Follow-up for progression, survival and any additional anticancer therapy (follow-on treatment for 
pancreatic cancer) until the last subject to complete treatment has been followed for 18 months post-last dose. It is recommended that Long-Term 
Follow-up be conducted approximately every 3 months. 
g. Medical history includes smoking history. 
h. Height is collected during screening only.  
i. 
ECOG to be evaluated at screening, Day 1 of each treatment Cycle, and EOT. Karnofsky scores will be evaluated at EOT only. 
j. 
A full physical exam is required during screening and on Day 1 of each treatment cycle. 
k. A 12-lead EKG will be performed during screening, on Day 1 of each cycle and EOT. 
l. 
A serum pregnancy test is required for all females of childbearing potential during screening. The central lab will provide results for the screening 
serum pregnancy test. Additionally, any female of childbearing potential must have a negative serum or urine pregnancy test confirmed at the site on 
Day 1 of each cycle (prior to study drug administration) and at EOT.  
m. Dosing for pamrevlumab (or placebo) will be based on the weight obtained on Day 1 of each dosing cycle (i.e., Cycle 1 Day 1, Cycle 2 Day 1). An 
additional dose of pamrevlumab or placebo to be administered on Day 8 of Cycle 1 only. Pamrevlumab (or placebo) to be infused over 1 hour (± 15 
minutes) following infusion of chemotherapy agents. 


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n. CA 19-9 to be collected at baseline (Cycle 1 Day 1) prior to dosing, Day 1 of each treatment cycle, EOT and safety follow-up visit for all subjects. 
CA19-9 will also be collected at the surgical follow-up visit (approx. 90 days post-surgery discharge) for those subjects who undergo surgical 
exploration. 
o. If a subject discontinues treatment early, an EOT PET scan is required unless the baseline PET was performed less than 8 weeks from EOT.   
p. A baseline CT scan will be conducted during the screening period and approximately every 8 weeks thereafter until disease progression is detected by 
central imaging review:   
• For subjects who complete 6 cycles of treatment, the EOT scan will be evaluated by the central review board in determination of surgical eligibility.   
• If a subject completes 6 cycles of treatment without evidence of disease progression, but does not undergo surgical exploration, CT scans should 
continue to be collected approximately every 8 weeks and submitted for central review until progression is detected (per RECIST 1.1).   
• If a subject undergoes surgical exploration and resection, CT scans should be conducted approximately every 4 months following for up to 2 years 
post-resection and approximately every 6 months from 2-5 years post-resection.   
• If recurrence of disease is suspected clinically at any time during the post-resection follow-up, a CT scan may be performed “off schedule” and 
submitted to central imaging for review/confirmation of progression/recurrence.    
q. All PROs to be collected prior to dosing where applicable. PRO-CTCAE™ questionnaire will be administered on Days 1, 8 and 15 of Cycles 1-3 and 
Days 1 and 15 of each treatment cycle thereafter and at the EOT and Safety follow-up visits.  
r. Adverse events and concomitant medications are collected from Day 1 of the study through 60 days following a subject’s last dose of study treatment. 
Serious adverse events should be collected/reported from the signing of Informed Consent through 60 days following the subject’s last dose of study 
treatment.  A Safety Follow-up visit must be conducted ~28 days post-last dose and a final safety follow-up contact (via phone) must be conducted 
~60 days post-last dose.  Additionally, pamrevlumab related SAEs (including deaths) that occur after the safety follow-up visit through the end of the 
long-term follow-up will be reported. 
s. Eligibility for surgical exploration per protocol will be determined by a central review board.  However, ultimately, the decision to operate on a 
subject lies with the site PI/surgeon. See Section 4 of the protocol for details. 
t. 
Tumor tissue will only be collected during resection.  Surgical outcomes of R0, R1 and R2 will be determined by central pathological review of tissue 
samples collected per the study-specific pathology protocol during surgical resection. Tissue collected during resection may also be evaluated for 
exploratory analysis (i.e., review of slides or digital images for purposes other than determining resection outcome). 


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9.2. 
Appendix 2: General Specifications for Tables, Listings and Figures 
9.2.1. 
Software Used 
All programming of tables, listings, and figures (TLFs) will be performed using the statistical 
software package SAS version 9.3 or greater. 
9.2.2. 
General 
All TLFs are based on SDTM and/or ADaM datasets. By default, data listings reflect the actual 
values captured in SDTM and ADaM datasets, including date/time variables and missing values. 
Except for concatenation of some variables for compact display purpose, data are presented 
directly with minimum manipulation. In general, the character standard result variables, such as 
–STRESC, are presented in data listings. Date is presented in listings in format yyyy-mm-dd. For 
incomplete date, CDISC presentation convention is followed. 
For continuous variables that are recorded as “<X” or “>X”, the value of “X” will be used in the 
calculation of summary statistics. The value “X” is also captured in the numeric variable in the 
SDTM datasets as well as in the ADaM datasets for consistency, although SDTMIG 
recommends capturing missing values in the numeric variables. 
In general, reported verbatim, such as terms of AE, medical history, medication names, 
specifications to the ‘Other’ fields, findings, etc., are presented in upper case. However, when 
reported fields are long, such as comments and protocol deviation descriptions, listing in lower 
case enhances readability.  
9.2.3. 
Table/Listing/Figure Output File Type and Organization 
In general, the final set of TLFs will include both PDF and RTF files. Outputs are combined in 
several large PDF files, e.g., all tables, all listings, and all figures.  A table of content should be 
included with hyperlinking to individual outputs. True RTF files (in-text format) will be created 
for tables and listings. SAS outputs for statistical procedures used in analysis of primary, 
secondary, and exploratory efficacy endpoints will also be included. 
9.2.4. 
Page Layout 
All column headers (consisting of one or several words) will start with uppercase and thereafter 
only lowercase characters, except for acronyms and abbreviations. In case values from the 
database will be displayed in column headers, they may be displayed as in the database. Pages 
will be numbered as ‘Page x of y’, where ‘y’ is the total number of pages of the corresponding 
table or listing. The page specifications are presented in Table 13. 
 
 


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Table 13: 
Specifications for Page Layout 
Paper Size 
Letter 
Orientation 
Landscape 
Alignment 
Center 
Font size 
9 
Font type 
Courier New (default) 
Margins 
 
   Top 
0.75” 
   Bottom 
0.38” 
   Left 
1.00” 
   Right 
1.00” 
The margin sizes and font size for listings may be flexible to provide sufficient information on a 
single page to facilitate review and comparison. 
When created using SAS, tables and listings will be created using ODS, and output files will be 
produced in RTF. When RTF files are produced, titles and footnotes will appear as document 
headers/footers. 
9.2.5. 
Titles and Footnotes 
All tables and listings will have a header showing “FibroGen, Inc.”, the protocol number (A 
Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in combination with 
either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients 
with Locally Advanced, Unresectable Pancreatic Cancer), database cutoff date, Date of data of 
Extraction or ‘Final Database (database lock date)’, and Page x of y. A footer will show the 
program file path/name, output file path/name, run date and time.  
All titles are written in title format, with uppercase at the beginning of each notional word; 
articles, prepositions, and conjunctions, which are of three characters length or less will start 
with lowercase letters (Mixed Case).  Footnotes are in regular text format. 
Titles 
In total there are up to 10 titles available, deﬁned as following: 
first title 
“FibroGen, Inc.” (left aligned) and “Database extraction date: 
ddMMMyyy” or “Final Database (database lock date)” (right aligned) 
second title 
protocol number (A Phase 3, Randomized, Double-Blind Study of 
Pamrevlumab or Placebo in combination with either Gemcitabine Plus 
Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients 
with Locally Advanced, Unresectable Pancreatic Cancer)  + “Clinical 
Study Report” (left aligned) and “Page x of y” (right aligned) 
third title 
blank 


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fourth title: 
table/listing/figure number 
fifth title: 
table/listing/figure title 
sixth title:  
population names if provided in SAP, or brief definition of specific 
analysis set 
Footnotes 
Up to 10 footnote lines are available for tables, listings, and figures. Footnotes 1, 9 and 10 are 
standard. Footnotes 2 to 8 (left aligned) might be used as needed. They are to be specified in the 
Shell.  
first footnote  
is a separating horizontal line. 
second – eighth 
are free text which can be used for explanations.  
ninth footnote  
left blank; in case needed may also be used as for explanations. 
tenth footnote 
the word “Confidential”, the program name (left aligned); date of 
data cutoff, the date and time in the format ddMMMyyyyThh:mm 
when the output was created; reference Table(s) or Listing(s).  
If footnotes take more than 30% of the space of a long listing, they may be presented only on a 
standalone first page. 
For summary tables, the corresponding listings with the parameters being summarized should be 
footnoted as reference. For figures, the corresponding summary table should be footnoted as 
reference. 
9.2.6. 
Table, Listing, Figure Metadata 
The table, listing, and figure (TLF) metadata will include the TLF numbers, titles, analysis 
populations, program names, and input dataset names. For tables and figures, PARAMCD, 
PARAM, and other conditions will be specified. TLF numbers, titles, and footnotes will be 
imported from this master spreadsheet. In addition, this spreadsheet will record the names of the 
original programmer and the validator/reviewer and the date of validation approval. 
9.2.7. 
Significant Digits of Summary Statistics 
For variables of direct measurements, summary statistics are displayed with the following 
specifications of decimal places in Table 14. 
 
 


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Table 14: 
Significant Digits of Summary Statistics 
Description 
Characteristic 
Number of decimal places 
Count 
N 
0 
Mean 
Mean 
As in source + 1 
Standard deviation 
Std 
As in source + 1 
Standard error of 
the mean 
SEM 
As in source + 2 
Confidence 
Interval 
CI 
As in source + 1 
Minimum 
Min  
As in source 
Median 
Median 
As in source  
Maximum 
Max 
As in source 
Q1  /  Q3 
Q1/Q3 
As in source  
10%  /  90% 
10%/90% 
As in source  
Percentage 
% 
All percentages will be rounded to one decimal place and lined up by the 
decimal place. The percentage will be suppressed when the count is zero 
Coefficient of 
variation 
CV (%) 
1 
p-value 
p-value 
p-values will be rounded to four decimal places and will be presented as 
‘<.0001’ if they are less than 0.0001 after rounding 
N=number; Std=Standard deviation; CI=Confidence Interval; Min=minimum; Max=maximum; CV=Coefficient of 
variation 
As a general guideline for derived parameters, 3 significant digits may be displayed for min and 
max; 4 significant digits for median, mean, Q1/Q3 and CI; and 5 significant digits for Std or SE. 
If a derived parameter is in the same scale as some related measured parameters, such as MAP, 
QTc, the same display format may be used as the measured parameters. 
Summary Statistics are to be displayed in the following order: Count, Mean, Standard Deviation, 
<Coefficient of Variation, Standard Error of the Mean, Confidence Interval>, Minimum, <10%>, 
<Q1>, Median, <Q3>, <90%>, Maximum. 
For categorical variables the categories will be displayed in the TLFs in the same order they 
appear in the CRF. 
9.2.8. 
Figure Specifications 
• In general, figures should include annotation of key summary statistics: n, mean, Std 
or SE, median for continuous variables; n and percent for categorical variables; 
number of subjects at risk and cumulative number of events as well as median and 
95% CI for time-to-event data. Other statistics such as quartiles, ranges may be 
included depending on need and space.  
• P-values should be presented if comparisons are of interest. 


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• For scatter plots, linear or non-linear trend lines should be included if the association 
of the two variables is of interest. Correlation coefficient or regression coefficients as 
well as corresponding p-values should be presented. 
• For line-charts, if space allows, 1-sided or 2-sided standard error bars should be 
presented.  
• For box plots, ‘BOXSTYLE=SCHEMATIC’ should be used. The whiskers are drawn 
to the most extreme points in the group that lie within the fences. The upper fence is 
defined as the third quartile (represented by the upper edge of the box) plus 1.5 times 
the interquartile range. The lower fence is defined as the first quartile (represented by 
the lower edge of the box) minus 1.5 times the interquartile range. Observations 
outside the fences are identified with a special symbol. 
9.2.9. 
Unit Conversion 
Units Presented in TLFs 
Units Reported or Derived 
from CRF 
Conversion Formula 
Kilogram (kg) 
Pound (lb) 
kg = lb/2.2 
Centimeter (cm) 
Inch (in) 
cm = 2.54 * in 
Celsius (C°) 
Fahrenheit (F°) 
C° = (5/9) * (F° – 32) 
Year 
Day 
1 year = 365.25 days 
Months 
Day 
1 month = 30.4375 days 
9.3. 
Appendix 3: RECIST (1.1) Criteria 
Below Table 15 and Table 16 are an outline of the definition of RECIST response categories, 
extracted from Eisenhauera, et al. (2009). 
 
 


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Table 15: 
Time Point Response: Patients with Target and Non-Target Lesions 
Assessment Category 
Response Category 
Response Criteria 
Target lesions 
Complete Response 
(CR) 
Disappearance of all target lesions. Any pathological 
lymph nodes (whether target or non-target) must have 
reduction in short axis to <10 mm. 
 
Partial Response (PR) 
At least a 30% decrease in the sum of diameters of target 
lesions, taking as reference the baseline sum diameters. 
 
Progressive Disease 
(PD) 
At least a 20% increase in the sum of diameters of target 
lesions, taking as reference the smallest sum on study (this 
includes the baseline sum if that is the smallest on study). 
In addition to the relative increase of 20%, the sum must 
also demonstrate an absolute increase of at least 5 mm. 
(Note: the appearance of one or more new lesions is also 
considered progression). 
 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest 
sum diameters while on study. 
 
Non-target Lesions 
Complete Response 
(CR) 
Disappearance of all non-target lesions and normalisation 
of tumor marker level. All lymph nodes must be non-
pathological in size (<10mm short axis). 
 
Non-CR/Non-PD: 
Persistence of one or more non-target lesion(s) and/or 
maintenance of tumour marker level above the normal 
limits. 
 
Progressive Disease 
(PD) 
Unequivocal progression of existing non-target lesions. 
(Note: the appearance of one or more new lesions is also 
considered progression). 
 
Table 16: 
Overall Response:  Patients with Target and Non-Target Lesions 
Target Lesions 
Non-target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/no-PD 
No  
PR 
CR 
Not evaluated 
No  
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
In-evaluable 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 


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9.4. 
Appendix 4: TNM and AJCC Staging Definitions 
The definitions below are extracted from AJCC Cancer Staging Manual, 7th Edition (2010). 
TNM definitions 
Primary tumor (T)  
TX: Primary tumor cannot be assessed  
T0:  No evidence of primary tumor  
Tis: Carcinoma in situ  
T1: Tumor limited to the pancreas, ≤2 cm in greatest dimension  
T2: Tumor limited to the pancreas, >2 cm in greatest dimension  
T3: Tumor extends beyond the pancreas but without involvement of the celiac axis or the 
superior mesenteric artery  
T4: Tumor involves the celiac axis or the superior mesenteric artery (unresectable primary 
tumor)  
Regional lymph nodes (N)  
NX: Regional lymph nodes cannot be assessed  
N0:  No regional lymph node metastasis  
N1:  Regional lymph node metastasis  
Distant metastasis (M)  
MX: Distant metastasis cannot be assessed  
M0:  No distant metastasis  
M1:  Distant metastasis  
AJCC Pancreatic Cancer Staging 
Stage 
TNM Category 
0 
Tis, N0, M0  
IA 
T1, N0, M0  
IB 
T2, N0, M0 
IIA 
T3, N0, M0  
IIB 
T1, N1, M0  
T2, N1, M0  
T3, N1, M0  
III 
T4, any N, M0  
IV 
Any T, any N, M1 


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9.5. 
Appendix 5: CTCAE Toxicity Grading for Laboratory Tests 
The following Table 17 and Table 18 are extracted from NCI Common Terminology Criteria for 
Adverse Events (CTCAE) Version 5.0. 
Table 17: 
CTCAE Toxicity Grading for Chemistry 
  
  
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Bicarbonate 
Decreased 
<LLN and no 
intervention 
initiated 
None 
None 
None 
Creatinine 
Increased 
ULN – 1.5 x 
ULN 
>1.5 – 3.0 x 
baseline[2] 
>1.5 – 3.0 x 
ULN 
>3.0 x baseline[2] 
>3.0 – 6.0 x ULN 
>6.0 x ULN 
Albumin 
Decreased 
3 g/dL – LLN 
2 - <3 g/dL 
<2 g/dL 
  
Alkaline 
phosphatase 
(ALP) 
Increased 
ULN – 2.5 x 
ULN[4]; 2.0 - 
2.5 x baseline[5] 
>2.5 – 5.0 x 
ULN[4]; >2.5 - 
5.0 x baseline[5] 
>5.0 – 20.0 x 
ULN[4]; >5.0 - 
20.0 x baseline[5] 
> 20.0 x ULN[4]; 
>20.0 x baseline[5] 
ALT 
Increased 
ULN – 3.0 x 
ULN[4]; 1.5 - 
3.0 x baseline[5] 
>3.0 – 5.0 x 
ULN[4]; >3.0 - 
5.0 x baseline[5] 
>5.0 – 20.0 x 
ULN[4]; >5.0 - 
20.0 x baseline[5] 
>20.0 x ULN[4]; 
>20.0 x baseline[5] 
AST 
Increased 
ULN – 3.0 x 
ULN[4]; 1.5 - 
3.0 x baseline[5] 
>3.0 – 5.0 x 
ULN[4]; >3.0 - 
5.0 x baseline[5] 
>5.0 – 20.0 x 
ULN[4]; >5.0 - 
20.0 x baseline[5] 
>20.0 x ULN[4]; 
>20.0 x baseline[5] 
Total bilirubin 
Increased 
ULN – 1.5 x 
ULN[4]; > 1.0 - 
1.5 x baseline[5] 
>1.5 – 3.0 x 
ULN[4]; >1.5 - 
3.0 x baseline[5] 
>3.0 – 10.0 x 
ULN[4]; >3.0 - 
10.0 x baseline[5] 
>10.0 x ULN[4]; 
>10.0 x baseline[5] 
Calcium 
(Corrected) 
Decreased 
8.0 mg/dL – 
LLN 
7.0 - <8.0 mg/dL 
6.0 - <7.0 mg/dL 
<6.0 mg/dL 
  
Increased 
ULN – 11.5 
mg/dL 
>11.5 – 12.5 
mg/dL 
>12.5 – 13.5 
mg/dL 
>13.5 mg/dL 
Glucose 
(Random) 
Decreased 
55 mg/dL – 
LLN 
40 - <55 mg/dL 
30 - <40 mg/dL 
<30 mg/dL 
Potassium 
Decreased 
3.0 mmol/L – 
LLN 
3.0 mmol/L – 
LLN[1] 
2.5 - <3.0 mmol/L 
<2.5 mmol/L 
  
Increased 
ULN – 5.5 
mmol/L 
>5.5 – 6.0 
mmol/L[3] 
>6.0 – 7.0 
mmol/L 
>7.0 mmol/L 
Sodium 
Decreased 
130 mmol/L – 
LLN 
125-129 mmol/L 
and 
asymptomatic 
125-129 mmol/L 
symptomatic; 
120-124 mmol/L 
regardless of 
symptoms 
<120 mmol/L 
  
Increased 
ULN – 150 
mmol/L 
>150 – 155 
mmol/L[3] 
>155 – 160 
mmol/L 
>160 mmol/L 


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Grade 1 
Grade 2 
Grade 3 
Grade 4 
Magnesium 
Decreased 
1.2 mg/dL – 
LLN 
0.9 - <1.2 mg/dL 
0.7 - <0.9 mg/dL 
<0.7 mg/dL 
  
Increased 
ULN – 3.0 
mg/dL 
None 
>3.0 – 8.0 mg/dL 
>8.0 mg/dL 
Table 18: 
CTCAE Toxicity Grading for Serum Hematology 
  
  
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
Decreased 
10.0 g/dL – LLN 
8.0 - <10.0 g/dL 
<8.0 g/dL 
  
  
Increase 
from 
baseline 
>0 – 2 g/dL 
>2 – 4 g/dL 
>4 g/dL 
  
Platelet 
Decreased 
75,000 /mm3 – 
LLN 
50,000 – <75,000 
/mm3 
25,000 - <50,000 
/mm3 
<25,000 /mm3 
WBC 
Decreased 
3,000 /mm3 – 
LLN 
2,000 - <3,000 
/mm3 
1,000 - <2,000 
/mm3 
<1,000 /mm3 
  
Increased 
None 
None 
>100,000 /mm3 
  
aPTT 
Increased 
ULN – 1.5 x 
ULN 
>1.5 – 2.5 x 
ULN 
>2.5 x ULN 
  
Lymphocytes 
Decreased 
800 /mm3 – LLN 
500 - <800 /mm3 
200 - <500 /mm3 
<200 /mm3 
  
Increased 
None 
>4,000 – 20,000 
/mm3 
>20,000 /mm3 
  
Neutrophils 
Decreased 
1500 /mm3 - 
LLN 
1000 - <1500 
/mm3 
500 - <1000/mm3 
<500/mm3 
Eosinophils 
Increased 
>ULN and 
>Baseline 
None 
Steroids initiated 
None 
Neutrophils 
Decreased 
1,500 /mm3 – 
LLN 
1,000 - <1,500 
/mm3 
500 - <1,000 
/mm3 
<500 /mm3 
Decreased: below LLN; Otherwise, above ULN; 
[1] Symptomatic, Intervention indicated 
[2] Baseline is used if it is above ULN 
[3] Intervention indicated 
[4] ULN is used if Baseline was normal 
[5] Baseline is used if Baseline was abnormal 
9.6. 
Appendix 6: Terminology Used in This Study 
Tumor Grade 
The grade of the cancer (how abnormal the cells look under the microscope) uses a scale from 
G1 to G3 (or sometimes G1 to G4), with G1 cancers looking the most like normal cells and 
having the best outlook.  
The details of grading are a little different for pancreatic neuroendocrine tumors (NETs), where 
measures of how many of the cells are in the process of dividing is an important part of grading. 
This is determined by counting mitoses (cells that have started to split into two new cells) under 


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a microscope and with a Ki-67 test that recognizes cells that are almost ready to start splitting. 
Based on these tests, NETs are divided into 2 groups: 
• Well-differentiated NETs (which includes low-grade [G1] and intermediate-grade 
[G2] tumors) have 20 or fewer mitoses and a Ki-67 index of 20% or lower. 
• Poorly differentiated tumors (high-grade [G3] tumors) have more than 20 mitoses 
or a Ki-67 index of more than 20%. These are also called neuroendocrine 
carcinomas, and they often grow and spread quickly.  
Extent of Resection 
For patients who have surgery, another important factor is the extent of the resection — whether 
or not all of the tumor is removed:  
• R0: All of the cancer is thought to have been removed. (There are no visible or 
microscopic signs suggesting that cancer was left behind.) 
• R1: All visible tumor was removed, but lab tests of the removed specimen show that 
some small areas of cancer were probably left behind. 
• R2: Some visible tumor could not be removed. 
Resectable versus Unresectable Pancreatic Cancer  
The AJCC staging system gives a detailed summary of how far the cancer has spread. But for 
treatment purposes, doctors use a simpler staging system, which divides cancers into groups 
based on whether or not they can be removed (resected) with surgery: 
Resectable 
If the cancer is only in the pancreas (or has spread just beyond it) and the surgeon believes the 
entire tumor can be removed, it is called resectable (In general, this would include most stage 
IA, IB, and IIA cancers in the TNM system). 
It is important to note that some cancers might appear to be resectable based on imaging tests 
such as CT scans, but once surgery is started it might become clear that not all of the cancer can 
be removed. If this happens, only a sample of the cancer may be removed to confirm the 
diagnosis (if a biopsy has not been done already), and the rest of the planned operation will be 
stopped to help avoid the risk of major side effects. 
Borderline Resectable 
This term is used to describe some cancers that might have just reached nearby blood vessels, but 
which the doctors feel might still be removed completely with surgery. This would include some 
stage III cancers in the TNM system. 
Unresectable 
These cancers cannot be removed entirely by surgery. 
Locally advanced: If the cancer has not yet spread to distant organs but it still cannot be 
removed completely with surgery, it is called locally advanced. Often the reason the cancer 
cannot be removed is because it has grown into or surrounded nearby major blood vessels. (In 
general, this would include stage IIB and most III cancers in the TNM system.) 


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Surgery to try to remove these tumors would be very unlikely to be helpful and could still have 
major side effects. Some type of surgery might still be done, but it would be a less extensive 
operation with the goal of preventing or relieving symptoms or problems like a blocked bile duct 
or intestinal tract, instead of trying to cure the cancer. 
Metastatic: If the cancer has spread to distant organs, it is called metastatic. These cancers 
cannot be removed completely. Surgery might still be done, but the goal would be to prevent or 
relieve symptoms, not to try to cure the cancer. 
9.7. 
Appendix 7: China CDE Requirements 
Efficacy data, mainly including overseas key clinical trial data and clinical trial data conducted 
in China, should not only confirm the efficacy of the study drug as a whole, but also analyze the 
consistency between Chinese subgroups and the overall population.  
Safety data, including all domestic and foreign data used for safety evaluation, should be 
analyzed not only for overall safety, but also for consistency between Chinese subgroup and 
overall population. 
All TLF in China may be provided per China regulatory requirements if regulatory submission in 
China is pursued (NMPA guidance). 
9.8. 
Appendix 8: Analyses of Data from China Patients 
According to protocol Amendment 5.1 (China-Only, Aug 16, 2022), when completion of global 
study enrollment (approximately N=280, Cohort 1) is reached, China sites will continue 
enrollment in Cohort 2 until the planned number of subjects in China is achieved. It is expected 
that data analysis from Chinese patients will be used to support a submission in China, in 
addition to the global study Cohort 1 data analysis described in the main body of this SAP. An 
analysis including all patients recruited in China (Chinese patients from global Cohort 1 and 
China Cohort 2) will be provided. 
Definition of China Analysis Sets 
China patients are patients enrolled in sites located in China and declaring themselves as 
Chinese.  
China-only Full Analysis Set  
The China-only Full Analysis Set will include all China patients randomized in China. This 
included all patients randomized in China as part of the global study in Cohort 1 and all 
additional patients recruited in China Cohort 2. 
The China-only Full Analysis Set will be used for all China-only efficacy analyses and treatment 
groups will be summarized on the basis of randomization, regardless of treatment actually 
received. 
China-only safety analysis set 


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The China-only safety analysis set will consist of China-only Full Analysis Set patients  who 
received at least one dose of study treatment. The China-only Safety Analysis Set will be based 
on the treatment actually received. 
China-only pharmacokinetic analysis set 
The China-only Pharmacokinetic Analysis Set is defined as patients in the China-only FAS who 
received at least one dose of study treatment, and have at least one evaluable PK concentration.  
Analysis methods for China Patients 
All efficacy, safety, PRO and PK variables will be derived in the same way as detailed for the 
global study analysis. The analyses described  for main study will be repeated for the patients 
randomized in China using the China-only analysis sets defined in this Appendix. All statistical 
analyses will be considered exploratory and only performed if sufficient numbers of events or 
patients are available and only descriptive statistics will be presented. Subgroup analysis will not 
be conducted. Statistical analysis will be based on unstratified analysis method due to small 
sample size.  
The China patients’ analyses will be performed using the same data cutoff date as the final OS 
analysis for global main study.