Clinical trial NCT04313881
Conditions: Myelodysplastic Syndromes
Sponsor: Gilead Sciences
Start date: 2020-09-09; Completion date: 2023-09-13
Enrollment: 539 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of magrolimab in combination with azacitidine compared to that of azacitidine plus placebo in previously untreated participants with intermediate/high/very high risk myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R) as measured by complete remission (CR) and overall survival (OS).

Detailed description:

Arms: arm 1: Participants will receive the following magrolimab and azacitidine dosing regimens:

Magrolimab:

Magrolimab Priming Dose:

* 1 mg/kg on Days 1 and 4
* 15 mg/kg on Day 8
* 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50)

Magrolimab Maintenance Dose:

* 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter.

Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. arm 2: Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine:

Placebo: On Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter.

Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle.
Interventions: intervention 1: Magrolimab intervention 2: Azacitidine intervention 3: Placebo
Intervention descriptions: intervention 1: Administered intravenously intervention 2: Administered either subcutaneously (SC) or intravenously (IV) according to region-specific drug labeling intervention 3: Placebo to match magrolimab administered intravenously

Protocol documents:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
ENHANCE: A Randomized, Double-blind, Multicenter Study 
Comparing Magrolimab in Combination with Azacitidine 
versus Azacitidine Plus Placebo in Treatment-naïve Patients 
with Higher Risk Myelodysplastic Syndrome
Name of Test Drug:
Magrolimab (Hu5F9-G4) (GS-4721) 
Study Number:
5F9009
Protocol Version (Date):
Amendment 8 (11 October 2022)
Analysis Type:
2nd Interim and Final Analyses
Analysis Plan Version:
1.0
Analysis Plan Date:
06 March 2023
Analysis Plan Authors:
Jiang Shao, PhD
CONFIDENTIAL AND PROPRIETARY INFORMATION


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................4
LIST OF ABBREVIATIONS.........................................................................................................................................5
1.
INTRODUCTION..................................................................................................................................................7
1.1.
Study Objectives........................................................................................................................................7
1.2.
Study Design .............................................................................................................................................8
1.3.
Sample Size and Power ...........................................................................................................................10
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................12
2.1.
DMC Interim Analyses............................................................................................................................12
2.2.
Optional Interim Analysis Performed by Sponsor ..................................................................................15
2.3.
Final Analysis..........................................................................................................................................15
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................16
3.1.
Analysis Sets ...........................................................................................................................................16
3.1.1.
Intent-to-Treat (ITT) Analysis Set.........................................................................................16
3.1.2.
Safety Analysis Set................................................................................................................16
3.1.3.
Pharmacokinetic Analysis Set ...............................................................................................16
3.1.4.
Immunogenicity Analysis Set................................................................................................16
3.2.
Subject Grouping.....................................................................................................................................17
3.3.
Strata and Covariates...............................................................................................................................17
3.4.
Examination of Subject Subgroups .........................................................................................................17
3.5.
Multiple Comparisons .............................................................................................................................18
3.6.
Missing Data and Outliers.......................................................................................................................18
3.6.1.
Missing Data..........................................................................................................................18
3.6.2.
Outliers ..................................................................................................................................18
3.7.
Data Handling Conventions and Transformations ..................................................................................18
3.8.
Analysis Visit Windows..........................................................................................................................19
3.8.1.
Definition of Study Day ........................................................................................................19
3.8.2.
Analysis Visit Windows........................................................................................................20
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window .................................................................................................................................21
4.
SUBJECT DISPOSITION ...................................................................................................................................22
4.1.
Subject Enrollment and Disposition........................................................................................................22
4.2.
Extent of Study Drug Exposure...............................................................................................................23
4.2.1.
Duration of Exposure to Study Drug.....................................................................................23
4.2.2.
Relative Dose Intensity..........................................................................................................23
4.3.
Protocol Deviations .................................................................................................................................24
4.4.
Assessment of COVID-19 Impact...........................................................................................................24
4.4.1.
Study Drug Discontinuation Due to COVID-19 ...................................................................24
4.4.2.
Protocol Deviations Due to COVID-19 ................................................................................25
4.4.3.
Missed and Virtual Visits due to COVID-19 ........................................................................25
4.4.4.
Adverse Events Due to COVID-19 .......................................................................................25
5.
BASELINE CHARACTERISTICS .....................................................................................................................26
5.1.
Demographics and Baseline Characteristics ...........................................................................................26
5.2.
Other Baseline Characteristics ................................................................................................................26
5.3.
Medical History.......................................................................................................................................26


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6.
EFFICACY ANALYSES.....................................................................................................................................27
6.1.
Primary Efficacy Endpoints ....................................................................................................................27
6.1.1.
Definition of Primary Efficacy Endpoints.............................................................................27
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoints ...................................................28
6.1.3.
Analysis of the Primary Efficacy Endpoints .........................................................................28
6.1.4.
Follow-up Time.....................................................................................................................29
6.1.5.
Sensitivity Analysis of the Primary Efficacy Endpoint.........................................................29
6.1.6.
Exploratory Analysis of the Primary Efficacy Endpoint.......................................................29
6.2.
Secondary Efficacy Endpoints ................................................................................................................30
6.2.1.
Definition of Secondary Efficacy Endpoints.........................................................................30
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints...........................................................31
6.3.
Exploratory Efficacy Endpoints ..............................................................................................................33
6.3.1.
Definition of Exploratory Efficacy Endpoints ......................................................................33
6.3.2.
Analysis Methods for Exploratory Efficacy Endpoints.........................................................34
6.4.
Patient-Reported Outcome ......................................................................................................................34
6.4.1.
Definition of Patient-Reported Outcome Data......................................................................34
6.4.2.
Analysis of Patient-Reported Outcome Data ........................................................................35
7.
SAFETY ANALYSES.........................................................................................................................................37
7.1.
Adverse Events and Deaths.....................................................................................................................37
7.1.1.
Adverse Event Dictionary .....................................................................................................37
7.1.2.
Adverse Event Severity .........................................................................................................37
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................37
7.1.4.
Serious Adverse Events.........................................................................................................37
7.1.5.
Treatment-Emergent Adverse Events....................................................................................37
7.1.6.
Summaries of Adverse Events and Deaths............................................................................38
7.1.7.
Additional Analysis of Adverse Events ................................................................................40
7.2.
Laboratory Evaluations ...........................................................................................................................41
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................41
7.2.2.
Graded Laboratory Values ....................................................................................................42
7.2.3.
Liver-related Laboratory Evaluations....................................................................................43
7.2.4.
Shifts Relative to the Baseline Value ....................................................................................43
7.3.
Body Weight and Vital Signs..................................................................................................................44
7.4.
Prior and Concomitant Medications........................................................................................................44
7.4.1.
Prior Medications ..................................................................................................................44
7.4.2.
Concomitant Medications......................................................................................................45
7.5.
Premedication..........................................................................................................................................45
7.6.
Electrocardiogram Results.......................................................................................................................46
7.7.
Other Safety Measures ............................................................................................................................46
8.
PHARMACOKINETIC (PK) AND IMMUNOGENECITY ANALYSES.........................................................47
8.1.
PK Sample Collection .............................................................................................................................47
8.2.
PK Analyses ............................................................................................................................................47
8.3.
Immunogenicity Analysis........................................................................................................................47
9.
PHARMACODYNAMIC ANALYSES ..............................................................................................................49
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES..............................................................................50
11.
REFERENCES.....................................................................................................................................................51
12.
SOFTWARE.........................................................................................................................................................52
13.
SAP REVISION...................................................................................................................................................53
14.
APPENDICES......................................................................................................................................................54


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Appendix 1.
Schedule of Assessments.........................................................................................................55
Appendix 2.
Disease Response Assessment Based on International Working Group Criteria....................63
LIST OF IN-TEXT TABLES
Table 1-1.
Dose Level and Schedule ........................................................................................................10
Table 2-1.
Stopping Boundaries for Efficacy Superiority Analyses.........................................................13
Table 2-2.
Non-Binding Futility Boundaries ............................................................................................13
Table 2-3.
Definition of Information Fraction..........................................................................................14
Table 3-1.
Analysis Visit Windows for Lab By-visit Summaries ............................................................20
Table 3-2.
Analysis Visit Windows for By-visit Summaries of PRO assessments ..................................20
Table 6-1.
Censoring Rules for DCR, DOR, and Duration of RBC Transfusion Independence..............33
Table 6-2.
Censoring Rules for EFS, Time to Transformation to AML, and PFS ...................................33


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AML
acute myeloid leukemia
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
BLQ
below the limit of quantitation
BMI
body mass index
BSA
body surface area
CI
confidence interval
CR
complete remission
CRF
case report form
CRh
complete remission with partial hematologic recovery
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DCR
duration of complete remission
DMC
Data Monitoring Committee
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EFS
event-free survival
EQ-5D-5L
5-Level EuroQol 5 Dimensions
EQ VAS
EQ visual analogue scale
EOT
end of treatment
ET
early termination
FACT-Anemia
Functional Assessment of Cancer Therapy – Anemia
HLT
high-level term
HLGT
high-level group term
HRQoL
health-related quality of life
IA
Interim analysis
ICH
International Conference on Harmonization
ID
identification
ITT
Intent-to-Treat
IPSS-R
Revised International Prognostic Scoring System
IWG
International Working Group
IXRS
interactive voice/web/mobile response system (IXRS) 


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LLT
lower-level term
LOQ
limit of quantitation
MDS
myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Activities
MRD
minimal residual disease
MST
MedDRA Search Term 
ORR
objective response rate
OS
overall survival
PFS
progression-free survival
PR
partial remission
PRO
patient-reported outcome
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetics
PT
preferred term
Q1, Q3
first quartile, third quartile
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SCT
stem cell transplant
StD
standard deviation
SE
standard error
SI (units) 
international system of units
SMQ
Standardised MedDRA Queries
SOC
system organ class
TE
treatment-emergent
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) of the second interim efficacy 
analysis and final analysis specified in the study protocol. 
This SAP is based on the study protocol amendment 8 dated 11 October 2022 and the electronic 
case report form (eCRF). The SAP will be finalized prior to data finalization for the second 
interim and final analysis. Any changes made after the finalization of the SAP will be 
documented in the clinical study report (CSR). 
1.1.
Study Objectives
The 2 primary objectives of this study are as follows:

To evaluate the efficacy of magrolimab + azacitidine compared with that of azacitidine + 
placebo in previously untreated patients with intermediate/high/very high risk 
myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System 
(IPSS-R) as measured by complete remission (CR) rate

To evaluate the survival benefit of magrolimab + azacitidine compared with that of 
azacitidine + placebo
The secondary objectives of this study are as follows:

To evaluate the duration of CR (DCR) of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To evaluate the objective response rate (ORR) and duration of response (DOR) of 
magrolimab + azacitidine compared with that of azacitidine + placebo 

To evaluate red blood cell (RBC) transfusion independence rate of magrolimab + azacitidine 
compared with that of azacitidine + placebo

To evaluate the efficacy of magrolimab + azacitidine compared with that of azacitidine + 
placebo as measured by event-free survival (EFS)

To evaluate the CR of magrolimab + azacitidine compared with that of azacitidine + placebo 
in TP53 mutant population

To assess the level of minimal residual disease (MRD) negativity of magrolimab + 
azacitidine compared with that of azacitidine + placebo

To assess time to transformation to acute myeloid leukemia (AML) of magrolimab + 
azacitidine compared with that of azacitidine + placebo


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
To evaluate the efficacy of magrolimab + azacitidine compared with that of azacitidine + 
placebo, as measured by progression free survival (PFS)

To assess the safety and tolerability of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To evaluate pharmacokinetics (PK) of magrolimab

To evaluate the immunogenicity of magrolimab

To evaluate the health-related quality of life (HRQoL) of magrolimab + azacitidine compared 
with that of azacitidine + placebo, as measured by Functional Assessment of Cancer Therapy 
– Anemia (FACT-Anemia) response rate
The exploratory objectives of this study are as follows:

To evaluate transplantation rate of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To assess time to first transplant of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To evaluate the duration of RBC transfusion independence of magrolimab + azacitidine 
compared with that of azacitidine + placebo

To evaluate RBC transfusion independence of magrolimab + azacitidine compared with that 
of azacitidine + placebo  among all patients irrespective of RBC transfusion-dependence at 
baseline

To evaluate the HRQoL of magrolimab + azacitidine compared with that of azacitidine + 
placebo, as measured by score change from baseline in FACT-Anemia, Patient Global 
Impression of Severity/Patient Global Impression of Change (PGIS/PGIC), and 5-level 
EuroQol 5 dimensions (EQ-5D-5L) questionnaires 

To assess biomarkers including but not limited to, immune cell recruitment, immune cell 
signaling, and bone marrow penetration of magrolimab
1.2.
Study Design
This is a Phase 3, randomized, double-blind, placebo-controlled multicenter study investigating 
magrolimab + azacitidine compared with azacitidine + placebo in previously untreated patients 
with intermediate/high/very high risk MDS by IPSS-R. The primary endpoints are CR rate and 
OS. Patients will be randomized in 1:1 ratio to receive either magrolimab + azacitidine 
(experimental arm) or azacitidine + placebo (control arm). Randomization will be stratified by 
3 factors: 1) geographic region (US versus ex-US sites); 2) cytogenetic risk status (very 
good/good/intermediate versus poor/very poor versus unknown) according to IPSS-R 
{Greenberg 2012}; and 3) percentage of bone marrow blasts (≥ 10% versus < 10% blasts). 


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The primary analysis of CR rate will be conducted 8 months after 348 patients are randomized. 
Patient participation will include screening, treatment, and follow-up. Screening will last up to 
30 days before the first dose of study treatment, during which time the patient’s eligibility and 
baseline characteristics will be determined. Patients will receive study treatment per the dose 
schedule in Table 1-1. No cross-over between arms is allowed. Study treatment may be 
continued until disease progression (including treatment failure by International Working Group 
[IWG] 2006 criteria or relapse after partial/complete remission [PR/CR]), loss of clinical benefit, 
or unacceptable toxicities occur. In case patients discontinue the study treatment due to reasons 
other than disease progression, patients will be followed up for response assessments until 
documented disease progression occurs. For patients who come off the study treatment to receive 
a stem cell transplant (SCT), follow-up for response assessment and collection of SOC bone 
marrow biopsy/aspirate results will continue until documented disease progression occurs or start 
of new anticancer therapy (excluding SCT), whichever occurs first. All participants will be 
followed for survival until death, withdrawal of consent, or the end of the study, whichever 
occurs first. For participants who are lost to follow-up or withdraw consent, study staff may use 
public records (eg, public health records) to obtain information about survival status where 
allowable by local regulation.
The study treatments within each arm are described in Table 1-1:


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Table 1-1.
Dose Level and Schedule
Dose Schedule (Day per 28-day Cycle)
Treatment Arms
Drug/Dose/Route
Cycle 1
Cycle 2
Cycle 3+
Experimental arm 
(Magrolimab+ azacitidine) 
And
Control arm
(azacitidine + placebo)
Azacitidine 75 mg/m2 SC or 
IVa
Days 1–7
or
Days 1–5 and 
8-9
Days 1–7
or
Days 1–5 
and 8–9
Days 1–7
or
Days 1–5 and 8–9
Dose Schedule
Treatment Arms
Drug/Dose/Route
Priming Dose 
Magrolimab 1 mg/kg IV
Days 1, 4
Magrolimab 15 mg/kg IV
Day 8
Maintenance Dose 
Experimental arm 
(Magrolimab+ azacitidine) 
Magrolimab 30 mg/kg IV
Days 11, 15, followed by 
weekly administration for 
5 doses (Days 22, 29, 36, 43, 
50) 
Day 57 and every 
2 weeks thereafter
Control arm 
(azacitidine + placebo)
Placebo
to mirror the magrolimab 
dosing schedule above
to mirror the 
magrolimab dosing 
schedule above
Abbreviations:  IV = intravenous; SC = subcutaneous.
a
Azacitidine administered per region-specific labeling.
Treatment with azacitidine as standard of care is recommended for a minimum of 6 cycles. 
Therefore, in this study, patients without evidence of disease progression (including treatment 
failure by IWG 2006 criteria or relapse after PR/CR), loss of clinical benefit, or unacceptable 
toxicity should continue azacitidine for at least 6 cycles. Patients may be discontinued from the 
treatment per Investigator’s discretion prior to reaching the recommended minimum cycles for 
any of these reasons detailed in Protocol Section 5.7.
The schedules of assessments are provided in Protocol Section 4.3.
1.3.
Sample Size and Power
The study will randomize approximately 520 patients in total into 2 treatment arms at a 1:1 ratio, 
determined by formal hypothesis testing performed on 2 primary efficacy endpoints: CR rate and 
OS, with family-wise Type I error controlled at a 2-sided significance level of 0.05. The primary 
analysis of the CR rate will be conducted at 8 months after 348 patients are randomized. Based 
on the first 348 randomized patients, the study has 95% power to reject the null hypothesis that 
the CR rates in the 2 treatment arms are the same at the 2-sided 0.03 significance level, assuming 
the true CR rate is 20% in the control arm and 39% in the experimental arm (i.e., a 19% 
improvement).


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If the null hypothesis has been rejected for CR rate, the hypothesis test on OS will be conducted 
at a 2-sided significance level of 0.05; otherwise, it will be conducted at a 2-sided significance 
level of 0.02 for the superiority test together with a futility test. Approximately 364 OS events 
(70% of 520 patients) in the ITT Analysis Set will allow 90% power to reject the null hypothesis 
that medians in OS in the 2 treatment arms are the same, assuming 18 months in the control arm 
and 25.4 months in the experimental arm (i.e., hazard ratio [HR] = 0.71), at a 2-sided 
significance level of 0.05, or at least 80% power at a 2-sided significance level of 0.02.
The sample size is determined according to the group sequential design. Assuming an enrollment 
rate of approximately 0.22 patients/site/month and 1% annual loss to follow-up of survival 
status, accrual is projected to occur over 22 months for 520 patients. The primary CR rate 
analysis is expected approximately 26 months after the first patient is randomized. The first 
interim analysis of OS will be conducted at the same time. The second interim analysis of OS 
will be conducted when approximately 257 deaths (71% of 364 deaths) have occurred. The final 
OS analysis is expected approximately 4.4 years after the first patient is randomized. The actual 
length of the study and the time for analyses will depend on the actual enrollment rate and the 
number of events that occur.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
DMC Interim Analyses
An external multidisciplinary data monitoring committee (DMC) reviewed the progress of the 
study, performed interim reviews of safety data at regular intervals, and provided 
recommendation to Gilead on whether the nature, frequency, and severity of AEs associated with 
study treatment warrant the early termination (ET) of the study in the best interests of the patient, 
whether the study should continue as planned, or whether the study should continue with 
modifications. 
In addition, the DMC has reviewed the results from the 1st planned interim efficacy analysis and 
will review the results from the 2nd  planned interim efficacy analysis. Based on the pre-specified 
superiority and futility rules, the DMC may make recommendations to Gilead on whether the 
study should be stopped early due to overwhelming efficacy, be terminated for futility, or 
continue as planned. Efficacy superiority boundaries are specified in Table 2-1 and non-binding 
futility rules are specified in Table 2-2. 
The DMC’s specific activities were defined by a mutually agreed unpon charter, which defined 
the DMC’s membership, conduct, and meeting schedule.
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, the ultimate decision on whether to implement or act based 
upon the recommendations of the DMC will be made by Gilead.
The study protocol specified 2 interim efficacy analyses conducted and evaluated by the DMC.
The first DMC interim efficacy analysis was conducted at 8 months after 348 patients had been 
randomized (data cut date: 12Aug2022).  At that time, 144 deaths (39.6% of 364 deaths) were 
observed. 
The second planned interim efficacy analysis will be conducted when approximately 257 deaths 
(71% of 364 deaths) have occurred, outstanding data queries have been resolved or adjudicated 
as unresolvable, and the data have been cleaned and finalized. In the case that the null hypothesis 
on CR rate was not rejected based on the first 348 randomized patients in the first interim 
analysis at a 2‑sided significance level of 0.03, a non-binding futility analysis with a futility 
boundary of HR = 0.95 will be performed at the second planned interim analysis.

If the null hypothesis on CR based on the first 348 randomized patients was rejected in the 
first interim analysis at a 2-sided significance level of 0.03, α = 0.05 (2-sided) will be 
allocated to the analysis of OS and key secondary endpoints in the first interim, second 
interim, and final analyses 

If the null hypothesis on CR rate based on the first 348 randomized patients was not rejected 
in the first interim analysis at a 2-sided significance level of 0.03, α = 0.02 (2-sided) will be 
allocated to the analysis of OS and key secondary endpoints in the first interim, second 
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The Lan-DeMets approach with O’Brien-Fleming type alpha spending function are used for the 
first and second interim analyses, and final analysis for OS. The stopping boundaries at each 
analysis time are provided in Table 2-1. 
Table 2-1.
Stopping Boundaries for Efficacy Superiority Analyses
Stopping Boundary
Planned Analyses
Efficacy 
Analysis
Events (%)
HRa 
Two-sided p-value 
First IA
CR
-
-
0.03
First IA
OS
144b (40%)
0.570
0.000732
Second 
IA
OS
257 (71%)
0.738
0.0150*
If the test of CR 
is rejected in 
first IA
Final 
Analysis
OS
364 (100%)
0.811
0.0453*
First IA
OS
144 (40%)
0.519
0.000084
Second 
IA
OS
257 (71%)
0.700
0.0043*
If the test of CR 
fails to be 
rejected in first 
IA
Final 
Analysis
OS
364 (100%)
0.781
0.0186*
HR = hazard ratio, IA = interim analysis, OS = overall survival, CR = complete remission
a
HR presented in the table is 1-sided (lower) efficacy boundary.
b
144 deaths were observed at first interim efficacy analysis (data cut date: 12Aug2022).
*
The boundary p-values at each analysis timepoint will be based on the actual observed events and adjusted by using the Lan 
DeMets approach with O’Brien-Fleming type alpha spending function.
Table 2-2.
Non-Binding Futility Boundaries 
Non-Binding Futility Boundary
Planned Analyses
Efficacy Analysis
HR 
First IA
OS
0.99
If the test of CR fails to 
be rejected in first IA
Second IA
OS
0.95
HR = hazard ratio, IA = interim analysis, OS = overall survival
The primary efficacy endpoint of OS will be tested for superiority first at the significance level 
specified in Table 2-1. If the superiority of OS is established, key secondary efficacy endpoints 
listed in Table 2-3 will be tested for superiority. To strongly control the overall type I error 
across the testing of the key secondary efficacy endpoints, a hierarchical testing strategy will be 
performed with a predefined order as listed below. For each key secondary endpoint, an O'Brien-
Fleming boundary will be derived based on the information fraction at each interim analysis and 
the remaining type I error respectively per Table 2-3.


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Table 2-3.
Definition of Information Fraction
Endpoint
Information Fraction at the Interim Analysis
ORR 
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
RBC transfusion independence rate
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
EFS
40% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)*
CR in TP53 mutant population
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
MRD-negative response
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
Time to transformation to AML
40% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)*
PFS
40% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)*
FACT-Anemia response rate
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
AML = acute myeloid leukemia; EFS = event-free survival; FACT-Anemia = Functional Assessment of Cancer Therapy-
Anemia; MRD = minimal residual disease; ORR = objective response rate; OS = overall survival, PFS = progression free 
survival
*The information fraction at each analysis timepoint will be based on the actual observed OS events
The key secondary endpoints will be tested in the following order: 

ORR

RBC transfusion independence rate

EFS

CR in TP53 mutant population

MRD-negative response

Time to transformation to AML

PFS

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A given hypothesis can only be tested and declared statistically significant if all previous 
hypotheses tested in the hierarchy are also statistically significant. 
2.2.
Optional Interim Analysis Performed by Sponsor
At the time of the second interim efficacy analysis, if the efficacy superiority boundary of OS 
has been crossed, the Sponsor study team may be unblinded for the entire ITT Analysis Set by 
the data cutoff date and will conduct the efficacy and safety analyses. Gilead Oversight 
Committee will make the decision on whether study team will be unblinded.   
2.3.
Final Analysis
If the null hypothesis on OS is not rejected in either of the 2 planned interim analyses, the final 
unblinded efficacy analysis will be conducted when approximately 364 OS events have occurred, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
been cleaned and finalized. 
If the null hypothesis on OS is rejected in any planned interim analyses, the timing of the final 
analysis may be driven by the data maturity of all efficacy data and the need of the safety 
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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of patients in each category will be presented; for continuous variables, 
the number of patients (n), mean, standard deviation (StD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all patients in the Intent-to-Treat (ITT) Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable). Data collected on log forms, 
such as AEs, will be presented in chronological order within the subject. Age, sex at birth, race, 
and ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the patients to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing.
For each analysis set, the number and percentage of patients eligible for inclusion will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
Intent-to-Treat (ITT) Analysis Set
The ITT Analysis Set includes all patients who were randomized in the study, with treatment 
assignment designated according to the treatment to which the subject is randomized. This is the 
primary analysis set for efficacy analyses. 
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all randomized patients who took at least 1 dose of any study 
treatment, with treatment assignment designated according to the actual treatment received. This 
is the primary analysis set for safety analyses.
3.1.3.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all patients who took at least 1 dose of 
Magrolimab, and have at least 1 measurable post-treatment serum concentration of magrolimab. 
This is the primary analysis set for all PK analyses. 
3.1.4.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all patients who took at least 1 dose of 
Magrolimab, and have at least 1 reported anti-drug antibody (ADA) result. 


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3.2.
Subject Grouping
For analyses based on the ITT Analysis Set, patients will be grouped according to the treatment 
to which they were randomized. For analyses based on the Safety Analysis Set, patients will be 
grouped according to the actual treatment received. The actual treatment received will differ 
from the randomized treatment only when their actual treatment differs from randomized 
treatment for the entire treatment duration.
For the PK Analysis Set and the Immunogenicity Analysis Set, patients will be grouped 
according to the actual treatment they received.
3.3.
Strata and Covariates
Patients will be randomized in a 1:1 ratio to treatment arms using an interactive 
voice/web/mobile response system (IXRS) with a stratified randomization schedule. 
Stratification will be based on the following variables: 

geographic region (US versus ex-US sites)

cytogenetic risk status (very good/good/intermediate versus poor/very poor versus unknown) 
according to IPSS-R

percentage of baseline bone marrow blasts (≥ 10% versus < 10% blasts) 
If bone marrow blasts stratification factor value is not recorded in the clinical database, the value 
recorded in the IXRS will be used for analyses. If there are discrepancies in stratification factor 
values between the IXRS and the clinical database, the values recorded in the clinical database 
will be used for analyses. Additionally, stratification discrepancies will be reviewed and 
assessed. Based on the assessment of stratification discrepancies, a sensitivity analysis of the 
primary endpoint may be performed.
Efficacy endpoints will be evaluated using stratification factors as covariates or stratification 
variables for analyses when applicable, as specified in Section 6. If there is an imbalance in 
presumed prognostic baseline characteristics between treatment groups, efficacy evaluations may 
be performed that include these baseline values in efficacy analysis models as covariates; these 
evaluations will be considered as sensitivity analyses.
In the situation where there is insufficient information in a stratum, pooling of the stratum with 
the smallest adjacent stratum for stratified analyses will be considered.
3.4.
Examination of Subject Subgroups
The primary efficacy endpoints will be examined using the following subgroups:

geographic region (US versus ex-US sites)


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
cytogenetic risk status (very good/good/intermediate versus poor/very poor versus unknown) 
according to IPSS-R

percentage of baseline bone marrow blasts (≥ 10% versus < 10% blasts) 
The analysis may also be conducted in the subgroups by TP53 mutational status (mutant and 
wild type), age (< 65 years and ≥ 65 years; < 75 years and ≥ 75 years), sex at birth (male and 
female), race (White, Asian, Black, Other), IPSS-R (Intermediate, High, Very high), baseline 
ECOG (0, 1, and 2), disease type (non-therapy related vs therapy-related).
If the number of subjects in one or more subgroups is too small to conduct the analysis, some 
subgroups will be pooled for the analysis. 
3.5.
Multiple Comparisons
The Multiple Comparisons are provided in Section 2.1.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
The handling of missing or incomplete dates for disease diagnosis is described in Section 5.3, for 
the death date and the start date of new anticancer therapy in Section 6.1.1, for AE onset in 
Section 7.1.5.2, and for prior and concomitant medications in Section 7.4. 
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed


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In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, then age derived based on date of birth and the Day 1 
visit date will be used instead. If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (eg, estimates of creatinine clearance, age at 
date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
If methods based on the assumption that the data are normally distributed are not adequate, 
analyses may be performed on transformed data or nonparametric analysis methods may be used, 
as appropriate.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of any study drug, which is the date of the 
first dose of magrolimab/placebo, or azacitidine, whichever occurs first and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date 
Therefore, study day 1 is the day of first dose of study drug administration. If the subject is 
randomized but not dosed, the randomization date will be study day 1. 


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3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows. The analysis windows for lab are provided in 
Table 3-1.
Table 3-1.
Analysis Visit Windows for Lab By-visit Summaries
Visit Window Study Day
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1a
Week 1
8
1b
11
Week 2
15
12
18
Week 3
22
19
25
Week 4
29
26
32
Week 5
36
33
39
Week 6
43
40
46
Week 7
50
47
53
Week 8
57
54
63
Week 10
71
64
77
Week xx
xx*7+1
(xx-1)*7+1
(xx+1)*7
a
Prior to first dose date time.
b
Post first dose date time.
The analysis windows for PRO are provided in Table 3-2.
Table 3-2.
Analysis Visit Windows for By-visit Summaries of PRO assessments
Visit Window Study Day
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
Week 4
29
2
42
Week 8
57
43
70
Week 12
85
71
98
Week xx
xx*7+1
xx*7-13
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For any data relating to unscheduled visits, the following will be made:

An unscheduled visit prior to the first dosing of any study drug will be included in the 
calculation of the baseline value, if applicable.

Unscheduled visits after the first dosing of any study drug will be included in determining the 
maximum postbaseline toxicity grade and anti-magrolimab antibody status.

Response assessments and PRO assessments performed at unscheduled visits after the date of 
randomization will be included in the analyses of the efficacy endpoints and the PRO related 
endpoints, respectively.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window 
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date of study drug (and 
prior to first dosing time) will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
the arithmetic average of the measurements for continuous data, or the measurement with the 
lowest severity for categorical data.

For postbaseline values:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the arithmetic average will be taken for 
continuous data and the worse severity will be taken for categorical data, unless 
otherwise specified.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group for each country, 
investigator and overall. The summary will present the number and percentage of patients 
enrolled. For each column, the denominator for the percentage calculation will be the total 
number of patients analyzed for that column.
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of patients in the stratum will be the total number of enrolled patients. If there are 
discrepancies in the value used for stratification assignment between the IXRS and the clinical 
database, the value collected in the clinical database will be used for the summary. A listing of 
patients with discrepancies in the value used for stratification assignment between the IXRS and 
the clinical database at the time of data finalization will be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group. This summary will 
present the number of patients screened and the number of patients who met all eligibility criteria 
but were not randomized with reasons patients not randomized in total; and the number of 
patients in each of the categories listed below by treatment group:

ITT Analysis Set

Safety Analysis Set 

Continuing study treatment (magrolimab/placebo, azacitidine)

Discontinued study treatment (magrolimab/placebo, azacitidine) with reasons for 
discontinuation

On-going in study (including long-term follow-up and survival follow-up)

Discontinued study with reasons for discontinuation
For the status of study drug and study completion and reasons for discontinuation, the number 
and percentage of patients in each category will be provided. The denominator for the percentage 
calculation will be the total number of patients in the ITT Analysis Set corresponding to that 
column. In addition, a CONSORT flow diagram will be provided to depict the disposition.
A by-subject listing with reasons for study drug or study discontinuation will be provided by 
subject identification (ID) number in ascending order to support the above summary table.


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4.2.
Extent of Study Drug Exposure 
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and relative dose intensity. Each summary statistic will be calculated for 
magrolimab/placebo, and azacitidine separately.  No formal statistical testing between treatment 
group is planned. 
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to each study drug (magrolimab/placebo, and azacitidine) will be 
defined for a subject as last dosing date minus first dosing date plus 1 day, regardless of any 
temporary interruptions in study drug administration, and will be expressed in weeks using up to 
1 decimal place (eg, 4.5 weeks). 
The total duration of exposure to each study drug will be summarized using descriptive statistics 
for continuous variables, as well as using the number (i.e., cumulative counts) and percentage of 
patients exposed for at least the following time periods: 1 day, 4 weeks, 8 weeks, 12 weeks, 
16 weeks, 20 weeks, and 24 weeks, etc. 
For azacitidine, the number of cycles patients are exposed will be summarized using descriptive 
statistics, and the number and percentage of patients who received at least 1, 2 …, 6 cycles will 
be presented.
The number and percentage of patients who have dose reduction for azacitidine or delay for each 
drug and the reasons will be summarized. 
4.2.2.
Relative Dose Intensity
Relative dose intensity is the percentage of the total amount of study drug administered relative 
to the total amount of study drug expected to be administered during a subject’s actual 
on-treatment period based on the study drug regimen. 
For magrolimab/placebo:
The relative dose intensity is the percentage of the total amount of study drug administered 
relative to the total amount of study drug expected to be administered, expressed as a percentage 
using the following formula:
Relative dose intensity  (%) =  
Cumulative Dosage Received (in mg/kg)
 Magrolimab/Placebo Dosage to be Administered 
on Treatment (in mg/kg) 
 x 100
Cumulative dosage (mg/kg) received for each subject is defined as the sum of all delivered 
dosages (mg/kg) of all infusions the subject received.
Magrolimab/placebo dosage to be administered on treatment (mg/kg) for each subject is defined 
as the total amount of magrolimab/placebo the subject was expected to receive during the 
subject’s treatment period.


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For azacitidine:
Relative dose intensity (%) =  
Total Amount of Azacitidine Administered
Azacitidine Expected to be Administered on Treatment  x 100
For each study drug, descriptive statistics for the relative dose intensity with the number and 
percentage of patients belonging to relative dose intensity categories (eg, < 75%, ≥ 75 to < 90%, 
≥ 90%) will be provided by treatment group for the Safety Analysis Set.
A by-subject listing of each study drug administration will be provided by treatment group, 
subject ID number (in ascending order) and visit (in chronological order).
4.3.
Protocol Deviations 
Patients who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized. The summary will present the number and percentage of patients who did not meet 
at least 1 eligibility criterion and the number of patients who did not meet specific criteria by 
treatment group based on the ITT Analysis Set. A by-subject listing will be provided for those 
patients who did not meet at least 1 eligibility (inclusion or exclusion) criterion. The listing will 
present the eligibility criterion (or criteria if more than 1 deviation) that patients did not meet and 
related comments, if collected.
Protocol deviations occurring after patients entered the study are documented during routine 
monitoring. The number and percentage of patients with important protocol deviations by 
deviation reason (eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) 
will be summarized by treatment group for the ITT Analysis Set. A by-subject listing will be 
provided for those patients with important protocol deviation.
4.4.
Assessment of COVID-19 Impact
This study was ongoing during the novel coronavirus (COVID-19) pandemic which has an 
impact on the study conduct. Some subjects were unable to attend onsite visits due to shelter in 
place guidelines, site closures, or other reasons. This section describes how special situations due 
to COVID-19 will be handled in the analysis.
4.4.1.
Study Drug Discontinuation Due to COVID-19
A summary of reasons for discontinuing study drug due to COVID-19 will be provided by 
treatment group and overall, similar to the summary described in the subject enrollment and 
disposition section (see Section 4.1). 
A by-subject listing of reasons for study drug discontinuation due to COVID-19 will be provided 
if applicable.


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4.4.2.
Protocol Deviations Due to COVID-19
A summary of important protocol deviations due to COVID-19 will be provided, similar to the 
summary described in the protocol deviations section (Section 4.3).
The number and percentage of subjects with non-important protocol deviations related to 
COVID-19 will be summarized by treatment group.
A by-subject listing will be provided for subjects with important protocol deviations related to 
COVID-19 if applicable. 
4.4.3.
Missed and Virtual Visits due to COVID-19
An overall summary of the number and percentage of subjects with at least 1 missed scheduled 
or virtual visits due to COVID-19 will be provided by treatment group and overall. The 
denominator for the percentage calculation will be the total number of subjects in the safety 
population for that column.
4.4.4.
Adverse Events Due to COVID-19
A by-subject listing of AEs of COVID-19 will be provided if applicable.


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5.
BASELINE CHARACTERISTICS  
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (ie, age, sex at birth, race, ethnicity, geographic region) and 
baseline characteristics (body weight [in kg], height [in cm], body mass index [BMI; in kg/m2], 
Body Surface Area [BSA; in m2]) will be summarized by treatment group and overall using 
descriptive statistics for continuous variables and using number and percentage of patients for 
categorical variables. The summary of demographic data will be provided for the ITT Analysis 
Set.
A by-subject demographic listing, including the informed consent date, will be provided by 
treatment group and subject ID number.
5.2.
Other Baseline Characteristics
Other baseline characteristics include but are not limited to: ECOG, BM blast, Cytogenetic Risk 
Status, and TP53 mutational status. These baseline characteristics will be summarized by 
treatment group and overall using descriptive statistics for continuous variables and using 
number and percentage of patients for categorical variables. The summary of these baseline 
characteristics will be provided for the ITT Analysis Set. No formal statistical testing is planned.
A by-subject listing of other baseline characteristics will be provided.
5.3.
Medical History
Medical history will be collected at screening for disease-specific and general conditions 
(ie, conditions not specific to the disease being studied).
MDS Diagnosis history will be summarized by treatment group and overall, by the number and 
percentage of patients with each prepopulated categories including but not limited to: IPSS-R, 
WHO Classification of MDS, Therapy-related MDS, RBC Transfusion Independence. The 
summary will be provided for the ITT Analysis Set. Time since diagnosis (months) will be 
calculated by (date of randomization – date of diagnosis) / 30.4375. Time since diagnosis will be 
summarized using summary statistics for a continuous variable. No formal statistical testing is 
planned. A by-subject listing of disease-specific medical history will be provided. In deriving the 
time since disease diagnosis, all partial dates of diagnosis and last regimen will be identified, and 
the partial dates will be imputed as follows:

If day and month are missing but year is available, then the imputed day and month will be 
01 Jan.

If day is missing but the month and year are available, then the imputed day will be the first 
day of the month.

Partial date will not be imputed if the year is missing.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoints
6.1.1.
Definition of Primary Efficacy Endpoints
The two primary efficacy endpoints of this study are CR rate and OS. 
CR Rate: The CR rate is the proportion of patients who reach morphologic CR (morphological 
blast of ≤ 5% and recovery of ANC, platelets, and hemoglobin from complete blood counts as 
well as peripheral blast) based on Investigator-assessed IWG 2006 MDS criteria {Cheson 2006} 
on or prior to initiation of any new anticancer therapy, including SCT.
Overall Survival: The OS is measured from the date of randomization to the date of death from 
any cause. Those who are not observed to die during the study will be censored at their last 
known alive date.
The date of the last known alive will be determined by selecting the last available visit date 
across all datasets. 
For participants who come off the study, study staff may use public records (eg, public health 
records) to obtain information about survival status where allowable by local regulation.
Every attempt will be made to ensure that complete death dates are recorded. In those rare 
instances where complete death dates are not recorded, the following algorithm will be used:

If day is missing but the month and year are available, then the imputed date will be the 1st 
day of the month or the last known alive date + 1, whichever is later.

If day and month are missing but year is available, then the imputed date will be 01Jan of 
that year or the last known alive date + 1, whichever is later.
When the date of initiation of a new anticancer therapy other than the study treatment or the date 
of SCT is incomplete or missing, the following algorithm will be followed:

If the day is missing but the month and year are available, then the imputed day will be the 
first day of the month or the day of last dose + 1 if the month and year of new anti-cancer 
therapy and the month and year of last dose are the same.

If day and month are missing but year is available, then the imputed day and month will be 
01Jan or the date of last dose + 1 if the year of new anti-cancer therapy and the year of last 
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6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoints 
The first primary efficacy hypothesis was tested on CR rate difference between magrolimab + 
azacitidine (experimental arm) and placebo + azacitidine (control arm) based on the first 
348 randomized patients at the 1st planned interim efficacy analysis. Using CR rateexp and CR 
ratectrl to denote the CR rates for the experimental arm and control arm, respectively, the 
statistical hypotheses tested in this study is:
𝐻0: CR rateexp = CR ratectrl
𝐻1: CR rateexp ≠ CR ratectrl (experimental arm is not equal to control arm in terms of CR rate)
The second primary efficacy hypothesis to be tested is that there is no difference between 
magrolimab + azacitidine (experimental arm) and placebo + azacitidine (control arm) in OS for 
patients. Using Sexp(t) and Sctrl(t) to denote the OS distribution functions of the experimental arm 
and control arm, respectively, the statistical hypotheses to be tested in this study will be:
𝐻0: Sexp(t) = Sctrl(t) at all time points t
𝐻1: Sexp(t) ≠ Sctrl(t) (experimental arm is not equal to control arm in terms of OS for some 
t > 0)
6.1.3.
Analysis of the Primary Efficacy Endpoints
The primary analysis of CR rates was done at the 1st interim efficacy analysis (data cut date: 
12Aug2022) based on the first 348 randomized patients in the ITT Analysis Set using the 
Cochran-Mantel-Haenszel (CMH) test, stratified by the stratification factors at randomization. 
The odds ratio comparing the 2 arms adjusted for the stratification factors was presented along 
with 95% confidence interval (CI).  
The point estimate of the CR rate and the corresponding 2-sided exact 95% CI based on the 
Clopper-Pearson method was provided for each arm. Patients, who are randomized but have no 
on-study response assessment or receive any new anticancer therapy including SCT prior to 
achieving CR, are considered as non-responders.
If the CR rate of experimental arm is higher than that of control arm and 2-sided p-value from 
the stratified CMH test using SAS procedure freq is less than 0.03, the null hypothesis of CR rate 
in Section 6.1.2 would be rejected and the superiority of experimental arm to control arm in 
terms of CR rate is established.
The primary analysis of OS will compare the OS distributions of two treatment groups using the 
stratified log-rank test, stratified by the stratification factors at randomization for the ITT 
Analysis Set. Medians, Q1, Q3 of the OS distributions, and the proportion of patients who are 
alive at 6, 12, 18 and 24 months from randomization will be estimated along with corresponding 
95% CIs using the Kaplan-Meier method. Kaplan-Meier curves will be provided by treatment 
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If the median survival time of experimental arm is longer than that of control arm and two-sided 
p-value from the stratified log-rank test using SAS procedure Lifetest is less than the cutoff 
p-values based on observed number of OS events by the data cutoff date as mentioned in 
Section 2.1, the null hypothesis of OS in Section 6.1.2 will be rejected and the superiority of 
experimental arm to control arm in terms of OS is established.
In addition, the HR between the 2 treatment groups and its 95% CI will be estimated using the 
Cox proportional hazards regression model stratified by the stratification factors. For 
pre-specified non-binding futility analysis boundary of HR=0.95 at the second interim analysis if 
CR was not statistically significant, the HR from the Cox model will be used to check whether 
the futility boundary has been crossed or not.
6.1.4.
Follow-up Time
The follow-up time for OS is defined as the interval from date of randomization to the death date 
for patients who died on or prior to the data cutoff, or from the date of randomization to the last 
known alive date for patients who are alive up to the data cutoff. The follow-up time will be 
summarized by treatment groups using descriptive statistics including median and range 
(minimum and maximum). It will also be summarized by treatment groups using statistics such 
as median, Q1, Q3 with corresponding 95% CIs estimated with the reverse Kaplan-Meier (K-M) 
method. The reverse K-M model switches the event/censoring indicators of patients in the 
original OS analysis with Kaplan-Meier method. It considers patients lost to follow-up or 
administratively censored due to analysis data cut as achieving the full follow up, and the full 
follow up time of those patients who died could not be observed as it is ‘censored’ by death. 
6.1.5.
Sensitivity Analysis of the Primary Efficacy Endpoint
To assess the robustness of the primary CR results, the following sensitivity analysis will be 
performed at the second interim and final analysis: 

CR will be analyzed  based on all randomized patients who have at least 8 months follow-up 
since randomization in the ITT Analysis Set for the Cochran-Mantel-Haenszel (CMH) test.
To assess the robustness of the primary OS results, the following sensitivity analysis will be 
performed: 

OS will be analyzed using the stratified log-rank test, stratified by the stratification factors in 
IXRS. In addition, the HR between the 2 treatment groups and its 95% CI will be estimated using 
the Cox proportional hazards regression model stratified by the stratification factors in IXRS.
6.1.6.
Exploratory Analysis of the Primary Efficacy Endpoint
An exploratory analysis may be performed to investigate the potential prognostic factors 
influencing the primary efficacy endpoint OS using the Cox regression model approach. The 
variables with prognostic potential will be included in the model as covariates to identify 
plausible significant factors on OS, such as age, gender, percentage of bone marrow blast, 
ECOG, etc. In addition, the Max-Combo test may be performed to compare the OS distributions 
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6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of Secondary Efficacy Endpoints
Duration of CR: The DCR is measured from the time measurement criteria are first met for CR 
to the first date of relapse, disease progression or death, whichever occurs earlier. Those who are 
not observed to relapse, disease progression or die will be censored at their last response 
assessment date with evidence of no relapse/no disease progression. Patients who achieve a CR 
and then proceed to SCT will continue to be followed for the response assessment posttransplant, 
will be included in the analysis of DCR, and will not be censored at the time of transplant. If 
patients start taking new anticancer therapies (excluding SCT) before relapse, disease 
progression or death, DCR will be censored at the last response assessment on or before the 
initiation of the new anticancer therapies.
Objective Response Rate (ORR): The ORR is the proportion of patients who reach objective 
response including CR, PR, marrow CR, or hematologic improvement per IWG 2006 MDS 
criteria on or prior to initiation of any new anticancer therapy, including SCT.
Duration of Response (DOR): The DOR is measured from the time measurement criteria are 
first met for objective response to the first date of relapse, disease progression after the initial 
objective response or death, whichever occurs earlier. Those who are not observed to relapse, 
disease progress after the initial objective response or die will be censored at their last response 
assessment date with evidence of no relapse/no disease progression. Patients who achieve a 
response and then proceed to SCT will continue to be followed for the DOR posttransplant, will 
be included in the analysis of DOR, and will not be censored at the time of transplant. If patients 
start taking new anticancer therapies (excluding SCT) before relapse, disease progression or 
death, DOR will be censored at the last response assessment on or before the initiation of the 
new anticancer therapies.
RBC Transfusion Independence Rate: The RBC transfusion independence rate is the 
proportion of patients who have a 56-day or longer period with no RBC transfusions at any time 
between randomization and initiation of any new anticancer therapy, including SCT, among all 
patients who are RBC transfusion-dependent at baseline.
Event-free Survival: The EFS is defined as the time from randomization to transformation to 
AML or death from any cause, whichever occurs first. Transformation assessments and deaths 
post SCT will be included in the analysis. Patients who are not observed to have one of these 
events during the study will be censored at their last response assessment date with evidence of 
no transformation to AML. If patients start taking new anticancer therapies (excluding SCT) 
before transformation to AML or death, EFS will be censored at the last response assessment on 
or before the initiation of the new anticancer therapies. Patients will be censored at the date of 
randomization if no response assessment performed after randomization and the patients didn’t 
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CR in TP53 Mutant Population: CR in TP53 Mutant Population is defined as the proportion of 
patients who achieve a morphologic CR based on Investigator assessments using IWG criteria 
{Cheson 2006} on or prior to initiation of any new anticancer therapy, including SCT in TP53 
mutant population.
MRD-negative Response Rate: The MRD-negative response rate is defined as the proportion of 
patients who achieve a morphologic CR or marrow CR based on Investigator assessments using 
IWG criteria {Cheson 2006} and reach MRD-negative disease status on or prior to initiation of 
any new anticancer therapy, including SCT. MRD-negative disease status will be assessed using 
a multiparameter flow cytometry-based assay performed by a central laboratory.
Time to Transformation to AML: Time to transformation to AML is defined as the time from 
randomization to transformation to AML. Patients who are not observed to have transformation 
to AML will be censored at their last response assessment date with evidence of no AML 
diagnosis. Transformation assessments post SCT will be included in the analysis. If patients start 
taking new anticancer therapies (excluding SCT) before documented AML diagnosis, Time to 
Transformation to AML will be censored at the last response assessment on or before the 
initiation of the new anticancer therapies. Patients will be censored at the date of randomization 
if no response assessment performed after randomization.
Progression-free Survival: PFS is defined as the time from randomization to the date of 
documented disease progression (including treatment failure by IWG criteria or relapse after 
PR/CR), or death from any cause, whichever occurs first. Response assessments and deaths post 
SCT will be included in the analysis. Those who are not observed to have one of these events 
will be censored at their last response assessment date with evidence of no disease 
progression/relapse. If patients start taking new anticancer therapies (excluding SCT) before 
disease progression (including treatment failure by IWG criteria or relapse after PR/CR) or 
death, PFS will be censored at the last response assessment on or before the initiation of the new 
anticancer therapies. Patients will be censored at the date of randomization if no response 
assessment performed after randomization and the patients didn’t die.
FACT-Anemia Response Rate: The FACT-Anemia response rate is defined as the proportion 
of patients who showed clinically meaningful improvement in health-related quality of life 
(HRQoL) based on the score from the FACT-Anemia instrument on or prior to initiation of any 
new anticancer therapy, including SCT {Cella 2002}. The minimal clinically meaningful 
difference of 7.0 as suggested in the referenced literature will be used as cutoff for clinically 
meaningful improvement. Patients, who are randomized but have no baseline or no postbaseline 
FACT-Anemia questionnaire assessment or receive any new anticancer therapy including SCT 
prior to achieving the FACT-Anemia response, will be considered as non-responders.
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints
Key secondary efficacy endpoints will be tested according to the order specified in Section 2.1, 
after the superiority for the primary efficacy endpoint OS is established. 


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6.2.2.1.
Objective Response Rate, CR in TP53 Mutant Population, MRD-negative 
Response Rate, and FACT-Anemia Response Rate 
The ORR, CR in TP53 mutant population, MRD-negative response rate, and FACT-Anemia 
response rate will be evaluated in a similar manner as the CR rate. 
6.2.2.2.
Duration of CR, and Durations of Response
For the time-to-event endpoints of DCR and DOR, analyses will be conducted based on the 
subsets on which the outcome measures are defined. Specifically, DCR will be based on patients 
who achieve CR, and DOR will be based on patients who achieve objective response. The 
Kaplan-Meier method will be used to estimate median duration with its 95% CI, and 
Kaplan-Meier plots will be provided. The censoring rules for DCR and DOR are summarized in 
Table 6-1.
6.2.2.3.
Event-Free Survival, Time to Transformation to AML, and Progression-Free 
Survival
The distribution of EFS, time to transformation to AML, and PFS will be estimated for each 
treatment arm using Kaplan-Meier method and compared between treatment arms using the 
stratified log-rank test, stratified by the stratification factors at randomization for the ITT 
Analysis Set. Medians, Q1, Q3 of the distributions, and the proportion of patients who are event-
free at 6, 12, 18 and 24 months from randomization will be estimated along with corresponding 
95% CIs using the Kaplan-Meier method. Kaplan-Meier curves will be provided by treatment 
group. The hazard ratio between treatment arms will be estimated using the Cox proportional 
hazards regression model stratified by the stratification factors. The censoring rules for EFS, 
Transformation to AML, and PFS are summarized in Table 6-2.
6.2.2.4.
RBC Transfusion Independence Rate 
The point estimates of RBC transfusion independence rate as well as the corresponding 2-sided 
exact 95% CIs based on Clopper-Pearson method will be provided by treatment arm 
respectively. Estimation will be based on a subset of all randomized patients who are RBC 
transfusion dependent at baseline. Difference in transfusion independence rate between treatment 
groups will be tested using the Cochran-Mantel-Haenszel test, stratified by the randomization 
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Table 6-1.
Censoring Rules for DCR, DOR, and Duration of RBC Transfusion 
Independence
Situation
Date of Censoring
No subsequent response assessments and no death after 
the first date CR/OR/RBC transfusion independence met 
Date of first time meet CR/OR/RBC transfusion 
independence
No corresponding events or no subsequent response 
assessments on or prior to initiation of any new 
anticancer therapy (excluding SCT)
Date of the last response assessment on or before the 
initiation of the new anticancer therapies (excluding 
SCT) or Date of first time meet CR/OR/RBC 
transfusion independence
No corresponding events and no any new anticancer 
therapy (excluding SCT)
Date of the last response assessment
Table 6-2.
Censoring Rules for EFS, Time to Transformation to AML, and PFS 
Situation
Date of Censoring
No postbaseline response assessment (for Time to 
Transformation to AML);
No postbaseline response assessment and no death (for 
EFS and PFS) 
Date of randomization 
No corresponding events or no postbaseline response 
assessment on or prior to initiation of any new anticancer 
therapy (excluding SCT)
Date of the last response assessment on or before the 
initiation of the new anticancer therapies (excluding 
SCT) or date of randomization
No corresponding events and no any new anticancer 
therapy (excluding SCT)
Date of the last response assessment
6.3.
Exploratory Efficacy Endpoints
6.3.1.
Definition of Exploratory Efficacy Endpoints
Duration of RBC Transfusion Independence: The duration of RBC transfusion independence 
is measured from the time the assessment criteria are first met for RBC transfusion independence 
until RBC transfusion dependence again (including assessments post SCT) or death,  whichever 
occurs first. Those who are not observed to have RBC transfusion dependence again or death 
will be censored at the date of their last response assessment. If patients start taking new 
anticancer therapies (excluding SCT) before becoming RBC transfusion dependent again or 
death, duration of RBC transfusion independence will be censored at the last response 
assessment on or before the initiation of the new anticancer therapies (excluding SCT).
Transplantation Rate: The transplantation rate is the proportion of patients who initiated 
transplant type subsequent anti-cancer therapy for MDS.


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Time to First Transplant: Time to first transplant is defined as the time from randomization to 
the initiation of first transplant type subsequent anti-cancer therapy for MDS. The definition has 
been changed from protocol definition. Specifically, time to first transplant will just be based on 
participants who had initiated transplant. Participants who are not observed to initiate transplant 
will be excluded.
RBC Transfusion Independence Rate Irrespective of RBC Transfusion Status at Baseline: 
The RBC transfusion independence rate irrespective of RBC transfusion status at baseline is the 
proportion of patients who have a 56-day or longer period with no RBC transfusions at any time 
between randomization and initiation of any new anticancer therapy, including SCT, among all 
randomized patients.
6.3.2.
Analysis Methods for Exploratory Efficacy Endpoints
Time to first transplant will be summarized using descriptive statistics by treatment group for 
patients who are observed to initiate transplant in the ITT Analysis Set. 
The duration of RBC transfusion independence will be analyzed in a similar manner as the 
analysis of DCR, as specified in Section 6.2.2.2. The censoring rule for duration of RBC 
transfusion independence is summarized in Table 6-1.
The transplantation rate will be analyzed in a similar manner as the analysis of ORR, as specified 
in Section 6.2.2.1. 
A by-subject listing for RBC transfusions required throughout the study will be provided by 
treatment group and subject ID in chronological order. Date of transfusion, transfusion type, and 
the number of units transfused will be presented. 
6.4.
Patient-Reported Outcome
6.4.1.
Definition of Patient-Reported Outcome Data
Four PRO instruments will be administered in this study: the Functional Assessment of Cancer 
Therapy-Anemia (FACT-Anemia), the 5-level EuroQol 5 dimensions (EQ-5D-5L), the Patient 
Global Impression of Severity (PGIS), and the Patient Global Impression of Change (PGIC). 
Functional Assessment of Cancer Therapy-Anemia  is described in Section 6.2.1.
The EQ-5D-5L is an instrument for use as a measure of health outcome and consists of 
2 sections: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The 
questionnaire is provided in the protocol Appendix D. 
The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems, and extreme problems. The patient is asked to 
indicate his/her health state by ticking the box next to the most appropriate statement in each of 
the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for 


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that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that 
describes the patient’s health state. The VAS records the subject’s self-rated health on a vertical 
VAS in which the endpoints are labeled “best imaginable health state” on the top and “worst 
imaginable health state” on the bottom. Higher EQ VAS indicates better health.
The PGIS and PGIC assessments are both single-item assessments used to demonstrate 
sensitivity and meaningful change thresholds and bolster the validity of selected PRO 
assessments for health-related quality of life and the physical function. The questionnaires are 
provided in the protocol Appendix E.
6.4.2.
Analysis of Patient-Reported Outcome Data
In addition to the analyses specified in Section 6.2 for the secondary PRO endpoint, exploratory 
analyses comparing the effects of magrolimab + azacitidine versus placebo + azacitidine on 
health-related quality of life will be performed on the 4 PRO measures: FACT-Anemia, 
EQ-5D-5L, PGIS, and the PGIC. Analyses will be based on the ITT Analysis Set.
FACT-Anemia

FACT-G: Mean total score and subscale scores at baseline and all follow-up timepoints will 
be summarized by treatment arm. The FACT-G consisits of the physical, social/family, 
emotional, functional subscales.

FACT TOI-An: Mean total score and subscale scores at baseline and all follow-up timepoints 
will be summarized by treatment arm. The FACT TOI-An consists of the physical, functional 
and anemia symptoms subscales.

FACT TOI-F: Mean total score and subscale scores at baseline and all follow-up timepoints 
will be summarized by treatment arm. The FACT TOI-F consists of the physical, functional 
and fatigue subscales.

FACT-F: Mean total score and subscale scores at baseline and all follow-up timepoints will 
be summarized by treatment arm. The FACT-F consisits of the physical, social/family, 
emotional, functional and fatigue subscales.
EQ-5D-5L
The EQ-5D-5L data will be summarized by treatment group and visit as the following:

A health profile: summary statistics will be provided, including number and percentage of 
patients who report each response category for the 5 dimensions (mobility, self-care, usual 
activity, pain/discomfort, and anxiety/depression).

A self-perceived current health score: calculated from patient level EQ VAS responses 
(continuous variable). Descriptive statistics will be provided.


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PGIC/PGIS
The proportion of patients who report each response category on the PGIC and PGIS at 
scheduled time-point will be summarized by treatment group. Descriptive statistics will be 
calculated for PGIC and PGIS at scheduled time-point. The mean and change from baseline on 
the PGIS to each subsequent assessment may be summarized.
Additional exploratory analyses may be conducted and documented in a separate PRO SAP.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to CTCAE 
Version 5.0. The severity grade of events for which the investigator did not record severity will 
be categorized as “missing” for tabular summaries and data listings. The missing category will 
be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” for a drug on the AE CRF to 
the question of “Related to Study Treatment.” Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and reported as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. Serious adverse events captured 
and stored in the clinical database will be reconciled with the SAE database from the Gilead 
Global Patient Safety before data finalization.
7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any AEs with an onset date on or 
after the study drug start date and no later than 70 days after the study drug last dose date or the 
day before initiation of new anticancer therapy including SCT (whichever is earlier). If the AE 
onset date is on or before the last dose date, the AE is considered as TEAE regardless of the start 
of new anticancer therapy.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to the cutoff date of TEAE period, which is defined as the 70 days after the 
study drug last dose date or the day before initiation of new anticancer therapy including 
SCT (whichever is earlier)
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
In case when the AE onset date is incomplete and needs to be imputed, the following algorithm 
will be followed:

If the day is missing but the month and year are available, then the imputed day will be the 
first dosing date if they have the same month and year, or the first day of the month 
otherwise.

If the day and month are missing but year is available, then the imputed day and month will 
be the first dosing date if they have the same year, or 01Jan otherwise.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE incidence in Combined Severity Grade Subsets 
A brief, high-level summary of the number and percentage of patients who experienced at least 
1 TEAE in the categories described below will be provided by treatment group. 
The number and percentage of patients who experienced at least 1 TEAE will be provided and 
summarized by SOC, PT, and treatment group. 


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For the AE categories described below, summaries will be provided by SOC, PT, and treatment 
group:

TEAEs 

TEAEs with Grade 3 or higher

TE treatment-related AEs for any study drug and for each study drug

TE treatment-related AEs with Grade 3 or higher for any study drug and for each study drug

TE SAEs

TE treatment-related SAEs for any study drug and for each study drug

TEAEs leading to dose reduction of azacitidine

TEAEs leading to discontinuation of any study drug and for each study drug 

TEAEs leading to death 
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and then by PT in descending order of 
frequencies in magrolimab + azacitidine treatment arm within each SOC. For summaries by 
severity, the most severe grade will be used for those AEs that occurred more than once in a 
given subject during the study.
In addition to the above summary tables, all TEAEs, TEAEs of Grade 3 or higher, TE SAEs and 
TEAEs leading to death will be summarized by PT only in descending order of frequencies in 
magrolimab + azacitidine treatment arm.
In addition, data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

All SAEs

All Deaths

All SAEs leading to death 

All AEs with severity of Grade 3 or higher

All AEs leading to discontinuation of study drug

All AEs leading to dose reduction of azacitidine 

TEAEs leading to dose delay or interruption of study drug


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A summary (number and percentage of patients) of deaths will be provided by treatment group. 
Summary will include the following categories:

All deaths

Deaths within 30 days of the first dosing of study drug

Deaths within 30 days of the last dosing of study drug

Deaths within 60 days of the first dosing of study drug

Deaths within 70 days of the last dosing of study drug

Deaths beyond 30 days of the last dosing of study drug

Deaths beyond 70 days of the last dosing of study drug
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Treatment-Emergent Adverse Events (TEAE) of Special Interest
Number and percentage of subjects with the following AEs of special interest will be 
summarized by PT: 

Anaemia (MST Anemia Extravascular Transient Hemolysis)

Infusion Related Reaction (IRR) (SMQ-Hypersensitivity Narrow Terms) + within one day of 
latest infusion

Transfusion reactions due to magrolimab interference with RBC typing (Gilead’s MST)

Thromboembolic Events (SMQ- Embolic and Thrombotic Events Broad Terms)

Pneumonitis (SMQ- Interstitial Lung Disease Broad Terms)
Number and percentage of subjects with the following AEs of special interest will also be 
summarized by first AE onset time within 2 weeks, >2 weeks to 2 months, >2 months to 6 
months, >6 months to 12 months, and >12 months of first dosing of any study drug:

Anaemia 

IRR

Transfusion reactions due to magrolimab interference with RBC typing 

Thromboembolic Events

Pneumonitis


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7.1.7.2.
Other Important Safety Topics
Number and percentage of subjects with the following AEs of important safety topics will be 
summarized by PT: 

Infections and infestations (SOC)

Immune-Mediated Events (SMQ-Immune-mediate and autoimmune disorder Narrow Terms)

Hemorrhages (SMQ- Haemorrhages Broad Terms)
Number and percentage of subjects with the following AEs of important safety topics will also 
be summarized by first AE onset time within 2 weeks, >2 weeks to 2 months, >2 months to 
6 months, >6 months to 12 months, and >12 months of first dosing of any study drug:

Immune-Mediated Events (SMQ-Immune-mediate and autoimmune disorder Narrow Terms)
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days 
or the day before initiation of new anticancer therapy including SCT (whichever is earlier). The 
analysis will be based on values reported in conventional units. When values are below the LOQ, 
they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7. 
A by-subject listing for laboratory test results will be provided by treatment group, subject ID 
and visit in chronological order for hematology and serum chemistry separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
CTCAE severity grade will be flagged in the data listings, as appropriate.
Plots of lab parameters will include (but not limit to) hemoglobin, platelet, and absolute 
neutrophil counts across time.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values

Values at each postbaseline time point visit 

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
Postbaseline minimum value

Change and percentage change from baseline at each postbaseline time point visit

Change and percentage change from baseline to postbaseline maximum value

Change and percentage change from baseline to postbaseline minimum value
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of any study drug. Change from baseline to a postbaseline visit will be 
defined as the postbaseline value minus the baseline value. The mean, median, Q1, Q3, 
minimum, and maximum values will be displayed to the reported number of digits; StD values 
will be displayed to the reported number of digits plus 1.
Median (Q1, Q3) of the observed values will be plotted using a line plot by treatment group and 
visit for the laboratory tests including but not limited to hemoglobin, platelet, and absolute 
neutrophil counts.
In the case of multiple values associated with a visit, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The CTCAE Version 5.0 will be used to assign toxicity grades (0 to 4) to laboratory results for 
analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of at least 
Grade 1. For laboratory tests with criteria for both increased and decreased levels, analyses for 
each direction (ie, increased, decreased) will be presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days or the day before initiation of new anticancer therapy including 
SCT (whichever is earlier). If the relevant baseline laboratory value is missing, any abnormality 
of at least Grade 1 observed within the time frame specified above will be considered treatment 
emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
patients in the study with the given response at baseline and each scheduled postbaseline time 
point.
The following summaries (number and percentage of patients) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; patients will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

TE laboratory abnormalities

TE Grade 3 or 4 laboratory abnormalities


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For all summaries of laboratory abnormalities, the denominator is the number of patients with 
nonmissing postbaseline values up to 30 days after the last dosing date or the day before 
initiation of new anticancer therapy including SCT (whichever is earlier).
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and visit in chronological order. This listing will include all test 
results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades displayed.
7.2.3.
Liver-related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of patients who were reported to have the following laboratory 
test values for postbaseline measurements:

Aspartate aminotransferase (AST): > 3 times of the upper limit of reference range (ULN)

Alanine aminotransferase (ALT): > 3 x ULN

AST or ALT: > 3 x ULN

Total bilirubin: > 2 x ULN

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN and alkaline phosphatase (ALP) < 2 x 
ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
study drug. For individual laboratory tests, patients will be counted once based on the most 
severe postbaseline values. For the composite endpoints of AST or ALT and total bilirubin and 
ALP, patients will be counted once when the criteria are met at the same postbaseline visit date. 
The denominator is the number of patients in the Safety Analysis Set who have nonmissing 
postbaseline values of all relevant tests at the same postbaseline visit date. 
A listing of patients who met at least 1 of the above criteria will be provided.
7.2.4.
Shifts Relative to the Baseline Value
Shift tables will be presented by showing change in severity grade from baseline to the worst 
grade postbaseline for hematology and chemistry laboratory tests.


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7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI, and vital signs 
as follows:

Baseline value

Postbaseline maximum value

Postbaseline minimum value

Change and percentage change from baseline to postbaseline maximum value

Change and percentage change from baseline to postbaseline minimum value. 
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of any study drug. Change from baseline to a postbaseline visit will be defined as 
the postbaseline value minus the baseline value. 
In the case of multiple values for the same visit, data will be selected for analysis as described in 
Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and time point in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
Prior medications are defined as any medications taken before a subject takes the first study 
drug.
Prior medications will be summarized by Anatomical Therapeutic Chemical (ATC) drug class 
Level 2 preferred name using the number and percentage of patients for each treatment group 
and overall. A subject reporting the same medication more than once will be counted only once 
when calculating the number and percentage of patients who received that medication. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
order of descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
For the purposes of analysis, any medication with a start date prior to the first dosing date of 
study drug will be included in the prior medication summary regardless of when the stop date is. 
If a partial start date is entered the medication will be considered prior unless the month and year 
(if day is missing) or year (if day and month are missing) of the start date are after the first 
dosing date. Medications with a completely missing start date will be included in the prior 
medication summary, unless otherwise specified.


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Summaries will be based on the Safety Analysis Set. No formal statistical testing is planned.
7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a subject took study drug. Use 
of concomitant medications will be summarized by ATC drug class Level 2 preferred name 
using the number and percentage of patients for each treatment group. A subject reporting the 
same medication more than once will be counted only once when calculating the number and 
percentage of patients who received that medication. The summary will be ordered 
alphabetically by ATC medical class and then by preferred term in descending overall frequency 
within each ATC medical class. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on 70 days after last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or 70 days 
after the last dosing date of study drug will also be considered concomitant. Medications with a 
stop date prior to the date of first dosing date of study drug or a start date after the last dosing 
date of study drug plus 70 days will be excluded from the concomitant medication summary. If a 
partial stop date is entered, any medication with the month and year (if day is missing) or year (if 
day and month are missing) prior to the date of first study drug administration will be excluded 
from the concomitant medication summary. If a partial start date is entered, any medication with 
the month and year (if day is missing) or year (if day and month are missing) after the study drug 
stop date plus 70 days will be excluded from the concomitant medication summary. Medications 
with completely missing start and stop dates will be included in the concomitant medication 
summary, unless otherwise specified. Summaries will be based on the Safety Analysis Set. No 
formal statistical testing is planned.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.
7.5.
Premedication
Premedication is required prior to the administration of the first 4 doses of magrolimab/placebo 
and in case of repriming. Premedication during subsequent infusions may be continued based on 
the treating physician’s clinical judgment and the presence/severity of prior infusion-related 
reactions. In the case of a Grade 3 infusion-related reaction, a premedication regimen for 
subsequent infusions is required.
Premedications will be summarized by Anatomical Therapeutic Chemical (ATC) drug class 
Level 2 preferred name using the number and percentage of patients for each treatment group 
and overall. A subject reporting the same medication more than once will be counted only once 
when calculating the number and percentage of patients who received that medication. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
order of descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.


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7.6.
Electrocardiogram Results
A by-subject listing of ECG results will be provided by subject ID number in ascending order.
7.7.
Other Safety Measures
A by-subject listing of ECOG performance status will be provided by subject ID number in 
ascending order.


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8.
PHARMACOKINETIC (PK) AND IMMUNOGENECITY 
ANALYSES
8.1.
PK Sample Collection
Blood samples for evaluating magrolimab serum concentrations will be collected at pre-dose at 
Day 1, Day 8, Day 29, Day 57, Day 113, Day 169, Day 253, Day 337, and EOT.  
8.2.
PK Analyses 
Magrolimab concentration will be summarized for the PK Analysis Set. The individual subject’s 
concentration data for magrolimab will be listed based on the sampling time point. Magrolimab 
PK data will be summarized per nominal time point using descriptive statistics. Summary 
statistics (n, mean, SD, coefficient of variation [%CV], median, min, max, Q1, Q3, and 
geometric mean) will be presented for magrolimab serum concentration data at each time point. 
The sample size (number of patients) at each time point will be based on the number of patients 
with nonmissing concentration data at that time point. Missing concentration values will be 
reported as is in data listings. Values that are BLQ will be treated as 0 at predose and postdose 
time points for summary purposes, and reported as-is in data listings.
Descriptive graphical plots of individual serum concentration versus time profiles and mean 
(StD) concentration versus nominal time profiles will be generated.
Due to the sparse nature of PK collection, PK parameters will not be calculated.
Data from this study may be combined with PK data from other magrolimab clinical studies and 
analyzed using a population PK model. Such an analysis will be reported separately.
8.3.
Immunogenicity Analysis
The rate and magnitude of antimagrolimab antibody prevalence, incidence, persistence, and 
transience will be summarized for the Immunogenicity Analysis Set. Neutralizing antibody 
incidence will also be summarized. 
ADA Prevalence: the proportion of subjects who had at least one positive ADA sample 
(baseline or post-baseline) based on the Immunogenicity Analysis Set.
Treatment-Induced ADA Rate: the proportion of subjects who had negative baseline ADA 
sample and at least one positive post-treatment ADA sample based on subjects who had both 
non-missing baseline and at least one post-treatment ADA result reported (i.e. ADA Incidence 
Analysis Set).
Treatment-Boosted ADA Rate: the proportion of subjects who had positive baseline ADA 
sample and at least one positive post-treatment ADA sample and the (max titer of the post-
treatment ADA) / (titer of baseline ADA) >= 4 based on the ADA Incidence Analysis Set


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ADA Incidence (treatment-emergent ADA): the proportion of subjects who had treatment-
induced or treatment-boosted ADA based on subjects who had non-missing baseline ADA 
sample and at least one post-treatment ADA result reported in Immunogenicity Analysis Set.
Persistent ADA is defined as:
a) Treatment-Induced ADA detected at two or more sampling time points during the 
treatment (including follow-up period if any), where the first and last ADA-positive 
sample (irrespective of any negative samples in between) are separated by a period of 16 
weeks or longer. 
or
b) Treatment-Induced ADA detected in the last sampling time point of the treatment study 
period.
ADA Persistence Rate: the proportion of subjects who had persistent ADA based on the ADA 
Incidence Analysis Set.
Transient ADA is defined as: 
Treatment-Induced ADA that does not meet the definition of persistent ADA. The proportion of 
subjects who had transient ADA is based on the subjects evaluable for ADA incidence.
Neutralizing antibody (NAb) Incidence: the proportion of subjects who had at least one 
positive neutralizing antibody result reported based on the treatment-emergent ADA (treatment-
induced or treatment-boosted ADA) among the subjects evaluable for ADA incidence.
Titer summaries may also be generated, if relevant. Exploratory evaluations may be conducted to 
determine the relationship between anti-magrolimab antibody positivity and safety, PK, or 
efficacy parameters (eg, drug concentrations, AEs, or disease response) using graphical, and/or 
tabular approaches.  


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9.
PHARMACODYNAMIC ANALYSES
Exploratory analyses may be performed to evaluate the association of each biomarker or 
combination of biomarkers with clinical outcomes. Additional details will be provided separately 
by the biomarker sciences group.


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10.
Changes From Protocol-Specified Analyses
There are no deviations from the protocol-specified analyses.


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11.
REFERENCES
Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in Cancer Patients Compared with 
Fatigue in the General United States Population. Cancer 2002;94 (2):528-38.
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised 
recommendations of the International Working Group for Diagnosis, 
Standardization of Response Criteria, Treatment Outcomes, and Reporting 
Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 
2003;21 (24):4642-9.
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical 
application and proposal for modification of the International Working Group 
(IWG) response criteria in myelodysplasia. Blood 2006;108 (2):419-25.
Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised 
International Prognostic Scoring System for Myelodysplastic Syndromes. Blood 
2012;120 (12):2454-65.


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12.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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13.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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14.
APPENDICES
Appendix 1.
Schedule of Assessments
Appendix 2.
Disease Response Assessment Based on International Working Group Criteria


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Appendix 1.
Schedule of Assessments
Appendix Table 1.
Schedule of Assessments – Screening
Study 5F9009
Assessment
Day -30 to --1
Informed consent
Xa
Demographics
X
Medical and cancer history
X
Pregnancy test 
Xb
Serum or plasma chemistry
X
Serum uric acid, phosphorus
X
Hematologyd 
X
Blood phenotyping or genotyping,  type, and screen (ABO/Rh), DATe
X
Urinalysis
X
Bone marrow biopsy and aspirate for blast evaluation, biomarker 
studies, cytogenetics, and MRD assessmentc
X
ECOG
X
Vital signs, height, and weight
X
Complete physical examination
X
ECG (single)
X
Hepatitis B, hepatitis C, and HIVf 
X
Adverse events related to protocol-mandated procedures
X
Concomitant medications
X
Entry criteria
X
Randomization 
Xa
Abbreviations:  ABO = any of the 4 blood groups A, B, AB, and O comprising the ABO system; DAT = direct antiglobulin test; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FSH = follicle-stimulating hormone; MRD = minimal 
residual disease; Rh = Rhesus factor; SOC = standard of care.
a
Screening must be completed before randomization.  Randomization must occur within 30 days of signing informed 
consent.  The first dose of study treatment (Protocol Table 3 and Protocol Table 4) must be given within 72 hours after 
randomization.
b
Screening pregnancy test may be used as the Day 1 test if performed within 72 hours of first dose; additional guidance is 
provided in Protocol Section 5.1.1.  FSH test is required for female patients who are < 54 years old who are not on hormonal 
contraception and who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal 
failure.
c
A trephine (biopsy) is to be collected for baseline. A bone marrow biopsy collected per SOC within 30 days of 
randomization can be considered the screening sample, and shipped to central laboratory.  This procedure must be 
performed prior to the first dose of study treatment at the latest.  An aspirate sample must be collected at the screening visit 
for blast evaluation, MRD assessment, biomarker studies, baseline for response assessment and biobanking.  It is preferred 
that bone marrow aspirate samples are obtained at the time of bone marrow (trephine) biopsy.  Conventional cytogenetics to 
be tested per institutional standards.
d
Hematology analytes to be assessed at screening are provided in Protocol Table 7
e
RBC genotyping (instead of an extended RBC phenotyping) must be performed if a patient received any RBC or whole 
blood transfusion within the previous 3 months (unless laboratory has availability for special techniques for performing 
phenotyping for patients with recent transfusion). Results must be available before the first dose of magrolimab.
f
Refer to Exclusion Criteria 13 and Other Laboratory Measurements in Protocol Table 7 


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Appendix Table 2.
Schedule of Assessments - Treatment Period-Azacitidine Dosing and Study Assessments
Cycle (28-day Cycles)
1
2
3+
Visit Window (Days)
None
± 3
± 3
± 3
Cycle Day
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
PRO assessmenta
X
X
X
CBC with differential, platelets, reticulocytesb
X
X
X
Serum or plasma chemistryb
X
X
X
Bone marrow biopsy and aspirate for biomarker studies c
Xd,e
Bone marrow aspirate biopsy for MRD monitoring, 
cytogenetics, and response assessmentd,f
X
Q2C, Q3Ce
Vital signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed physical examinationb
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Azacitidineh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations:  CBC = complete blood count; EQ-5D-5L = 5-level EuroQol 5 dimensions; FACT-Anemia = Functional Assessment of Cancer Therapy-Anemia; MRD = minimal 
residual disease; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PRO = patient-reported outcome; Q2C = every 2 cycles; 
Q3C = every 3 cycles.
a
Four PRO questionnaires will be administered in this study:  the FACT-Anemia questionnaire, the EQ-5D-5L, the PGIS, and the PGIC.  The patient should complete these 
questionnaires before other study procedures at required visits.  No PGIC assessment at Cycle 1 Day 1.  FACT‑Anemia and EQ-5D-5L should be implemented prior to 
PGIS/PGIC.
b
If magrolimab and azacitidine are administered on the same day, only one such study assessment is needed.  Assessments should be performed prior to study treatment 
administration. Pretreatment assessments for the initial dose (Cycle 1 Day 1) may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment 
assessments are to be collected within 24 hours prior to study treatment administration. 
c
Bone marrow biopsy samples will be collected at Day 1 of Cycles 3 and 10.
d
An aspirate sample will be collected for response assessment, biomarker studies, and MRD assessment.  Conventional cytogenetics to be tested per institutional standards.  
Response assessments may be adjusted by ± 1 week for Cycle 3 Day 1.  After Cycle 3 Day 1, the window is ± 14 days.
e
An aspirate sample will be collected for biomarker studies at Day 1 of Cycles 3, 5, 7, 10, and 13.  
f
Samples will be collected at Day 1 of Cycles 3, 5, and 7 and then every 3 cycles thereafter during study treatment.  Bone marrow aspirate biopsies for response assessments 
may be adjusted by ± 1 week for Cycle 3 Day 1.  After Cycle 3 Day 1, the window is ± 14 days. 
g
Vital signs will be assessed prior to infusion/injection of each study treatment.  Weight will be assessed on Day 1 of each cycle.  Details are provided in Protocol Section 5.1.5.
h
If Azacitidine and magrolimab/placebo are administered on the same day, azacitidine administration should be completed at least 1 hour before magrolimab/placebo 
administration.  Azacitidine may be administered on an alternative schedule of Days 1 to 5, Day 8, and Day 9 of a 28-day cycle for flexibility and convenience.  


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Appendix Table 3.
Schedule of Assessments - Treatment Period-Magrolimab or Placebo Dosing and Study Assessments
Dose Schedule
Priming Dosing 
Maintenance Dosing
Visit Window (Days)
None
± 3
± 3
Day
1
2 
4
8
11
15
22
29
36
43
50
57
every 2 Weeks thereafter 
Pregnancy testa
X
X
X Q4W
CBC with differential, platelets, 
reticulocytesb,c,d
Xe
X
Xe
X
X
X
X
X
X
X
X
X
X
Haptoglobin and LDHc
X
X
X
Serum or plasma chemistryb,c
X
X
X
X
X
X
X
X
Peripheral smearc,f
X
X
X
Peripheral blood sample for biomarker 
studiesg
X
X
X
Xh
PKg
X
X
X
Xi 
Antidrug antibodiesc,j
X
X
Xi
Vital signsk
X
 
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed physical examinationb,c
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X 
X
X
X
X
X
X
X
X
X
X
X
X
Premedicationl
X
X
X
X
Magrolimab or placebom
Xn
Xn 
X
X
X
X
X
X
X
X
X
X
Abbreviations:  CBC = complete blood count; D = day; EOT = end of treatment; LDH = lactate dehydrogenase; MRD = minimal residual disease; PK = pharmacokinetic(s); PRO = 
patient-reported outcome; Q4W = every 4 weeks; WBC = white blood cell.
a
Screening pregnancy test may be used if performed within 72 hours of first dose; pregnancy tests will be conducted once every month; additional guidance is provided in 
Protocol Section 5.1.1.
b
If magrolimab and azacitidine are administered on the same day, only one such study assessment is needed Assessments should be performed prior to study treatment 
administration. For monitoring of infusion-related reactions, please refer to Protocol Section 6.5


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c
Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected 
within 24 hours prior to study treatment administration.
d
Additional samples for CBC may be collected outside of the protocol-specified time points to ensure a WBC level ≤ 20 × 103/µL prior to each magrolimab/placebo dose 
during the first 28 days of magrolimab priming dose.  Peripheral blasts should be included in the CBC assessments.
e
An additional hemoglobin check must be performed 3 to 6 hours after the initiation of the first and second doses of magrolimab/placebo during initial treatment. The patient 
should be transfused as clinically appropriate. Investigators should consider additional hemoglobin monitoring during the first week of treatment in patients with symptoms of 
anemia or increased risk for complications of anemia.
f
Peripheral smears will be collected predose and assessed locally.
g
Samples for PK and biomarker studies will be collected predose within 12 hours prior to study treatment administration.
h
Samples will be collected prior to first maintenance dose (Day 57), ninth (Day 169) maintenance dose, and EOT.
i
Samples will be collected predose on Day 57, Day 113, Day 169, Day 253, Day 337, and EOT.
j
When collected on the day of study treatment dosing, the blood sample for antidrug antibodies must be collected at the same time as the predose PK sample.
k
Vital signs will be assessed prior to infusion/injection of each study treatment.  Weight will be assessed every 4 weeks.  Details are provided in Protocol Section 5.1.5.
l
Premedication is required prior to the administration of the first 4 doses of study treatment and in case of reintroduction with repriming.  Premedication for subsequent 
treatment periods may be continued based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions.  In the case of a Grade 3 
infusion-related reaction, a premedication regimen for subsequent treatment periods is required (Protocol Section 6.5).
m
Magrolimab or saline placebo should not be given on consecutive days.  The duration of each magrolimab/placebo infusion including flush will be 3 hours (± 30 minutes) for 
the first dose of treatment. After the first dose of treatment, the magrolimab/placebo infusion including flush will be 2 hours (± 30 minutes).  All patients should be monitored for 
1 hour after infusion for doses during the first 28 days and the repriming doses.
n
Within 24 hours prior to each of the first 2 doses of magrolimab/placebo infusion during initial treatment, all subjects must have a documented hemoglobin  9.0 g/dL. 
Patients who do not meet these criteria must be transfused and have their hemoglobin rechecked to meet 9.0 g/dL prior to each of the first 2 doses of magrolimab. 


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Appendix Table 4.
Schedule of Assessments – Post Treatment
End-of-
treatment Visit
Safety Follow-up Visit/Call
(Telephone)a
Long-term 
Follow-up
Survival 
Follow-up
Within 7 Days 
after Last Dose 
or EOT Decision
30 Days
after Last 
Dose
70 Days 
after Last 
Dosek
Until Start of New 
Anticancer Therapy 
or Transformation 
to AMLb
Every 2 Months 
Until Death or 
End of Study
Visit Window
± 7 Days
± 7 Days
± 7 Days
+4 Weeks
Serum or urine pregnancy test
X
Q4Wc
Q4Wc
CBC with differential, platelet count, reticulocytes
X
Q8Wd
Serum or plasma chemistry
X
Peripheral blood for biomarker studies
X
Pharmacokinetics
X
Antidrug antibodies 
X
Bone marrow biopsy and aspirate for MRD monitoring and 
cytogeneticsd,e
X
Q8Wd
Response assessmente,f
X
Q8Wd
ECOG
X
Vital signs
X
Symptom-directed physical examination
X
PRO assessmentg
X
X
Adverse eventsh
X
X
X
Concomitant medications
X
X
X
Blood transfusioni
X
X
New anticancer therapyj
X
X
Survival follow-up
Q2M
Abbreviations:  AE = adverse event; AML =  acute myeloid leukemia; CBC = complete blood count; CR = complete remission; eCRF = electronic case report form; EOT = end of 
treatment; EQ-5D-5L = 5-level EuroQol 5 dimensions; FACT-Anemia = Functional Assessment of Cancer Therapy-Anemia; IWG = International Working Group; 
MDS = myelodysplastic syndrome; MRD = minimal residual disease; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PR = partial 
remission; PRO = patient-reported outcome; QxM = every x months; QxW = every x weeks; SAE = serious adverse event.


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a
If the patient experiences a treatment-related AE or an SAE (regardless of attribution), the patient must be asked to come to the site.
b
Until start of new anticancer therapy or transformation to AML, whichever comes first.
c
Collect until the end of the contraception requirement.
d
Bone marrow assessment, MRD, CBC, and response assessment should be performed until start of new anticancer therapy or transformation to AML, whichever comes first.  
Conventional cytogenetic testing (per institutional standards) is required for all patients.
e
For patients who come off the study treatment to undergo a stem cell transplant, response assessments for relapse/remission status and bone marrow aspirate results are 
required to be obtained locally and entered into the eCRF. 
f
Response assessment at EOT visit not required if performed within the last 30 days or progressive disease has been documented.  After disease progression (including 
treatment failure by IWG criteria and relapse after CR or PR), response assessment will focus on evaluation of transformation to AML.
g
Paper PROs will be administered in this study:  The FACT-Anemia questionnaire, the EQ-5D-5L, the PGIS, and the PGIC will be administered.  The patient should complete 
these questionnaires before other study procedures at required visits.  FACT-Anemia and EQ-5D-5L should be implemented prior to PGIS/PGIC. FACT-Anemia, EQ-5D-5L 
the PGIS, and the PGIC should also be collected during long-term follow-up prior to initiation disease progression or initiation of a new anticancer therapy.
h
Report all AEs through the Safety Follow-up Visit/Call and any treatment-related SAEs thereafter.
i
Collect blood transfusions until start of new anticancer therapy.
j
Collect new anticancer therapy data following the last dose of study treatment.
k
For patients who do not initiate new anticancer therapy after the last dose. See Protocol Sections 5.1.10 for adverse event reporting details.


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Appendix Table 5.
Schedule of Assessments – Repriming (Required After > 4 Weeks Have Lapsed Since the Last Dose of 
Magrolimab/Placebo Delays)
Day
1
2
3
4
5
6
7
8
11
15
22
Visit Window (Days)
-
-
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
Pregnancy test
X
CBC with differential, platelets, and 
reticulocytesa,b
X
X
X
X
X
X
X
Haptoglobin and LDH
X
X
Serum or plasma chemistrya
X
X
X
X
Peripheral smeara,c
X
X
X
Peripheral blood for biomarker studiesd
X
X
PKd
X
X
Antidrug antibodiesa
X
Vital signse
X
X
X
X
X
Symptom-directed physical examinationa
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
Blood transfusions
X
X
X
X
X
X
X
X
X
X
X
Premedicationf
X
X
X
X
Magrolimab/placebo: reprimingg
X
X
X
X
X
X
Abbreviations: CBC = complete blood count; ECOG = Eastern Cooperative Oncology Group; LDH = lactate dehydrogenase; PK = pharmacokinetic(s); PRO = patient-reported 
outcome; WBC = white blood cell.
a
Pretreatment assessments are to be collected within 24 hours prior to study treatment administration.
b
Additional samples for CBC may be collected outside of the protocol-specified time points to ensure a WBC level ≤ 20 × 103/μL for the repriming cycle.
c
Peripheral smears will be collected and assessed locally.
d
Samples for PK and biomarker studies will be collected predose within 12 hours prior to study treatment administration.


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e
Vital signs prior to infusion/injection of study treatment. Weight at Day 1. Details are provided in Protocol Section 5.1.5.
f
Premedication is required prior to the administration of the first 4 doses of study treatment and in case of reintroduction with repriming. Premedication for subsequent cycles 
may be continued based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions. In the case of a Grade 3 infusion-related 
reaction, a premedication regimen for subsequent cycles is required (Protocol Section 6.5).
g
Magrolimab or saline placebo should not be given on consecutive days. During repriming, the duration of each magrolimab/placebo infusion including flush will be 3 hours 
(± 30 minutes) for the first 3 doses of treatment and 2 hours (± 30 minutes) for infusions beyond the first 3 doses. All participants should be monitored for 1 hour after 
infusion for doses during the first 28 days and the repriming doses. After Day 22, participants should return to their original dose schedule.


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Appendix 2.
Disease Response Assessment Based on International Working Group 
Criteria 
Response will be assessed in myelodysplastic syndrome (MDS) patients using the 2006 
International Working Group (IWG) criteria {Cheson 2006} with modifications as shown in 
Appendix Table 6.  In addition, complete remission (CR) with partial hematologic recovery 
(CRh) will be assessed for MDS, defined as patients who achieve a CR per IWG 2006 MDS 
criteria {Cheson 2006}, with the exception of requiring partial hematologic recovery as defined 
by a platelet count of > 50 × 109/L and an absolute neutrophil count of > 500/µL.
In addition, HI will be assessed by 2006 IWG criteria {Cheson 2006}; Appendix Table 8) and 
cytogenetic/molecular response by 2003 IWG criteria {Cheson 2003}; Appendix Table 7).
Appendix Table 6.
Response Criteria in MDS (IWG 2006 Criteria)
Category
Response Criteria 
CR
Bone marrow ≤ 5% myeloblasts with normal maturation of all cell linesa
Persistent dysplasia will be noteda,b
Peripheral bloodc
Hgb ≥ 11 g/dL
Platelets ≥ 100 × 109/L
Neutrophils ≥ 1.0 × 109/Lb
Blasts 0%
PR
All CR criteria if abnormal before treatment except:
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%
Cellularity and morphology not relevant
Marrow CRb
Bone marrow ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatmentb
Peripheral blood:  if HI responses, they will be noted in addition to marrow CRb
Stable Disease
Failure to achieve at least PR, but no evidence of progression for > 8 weeks
Failure
Death during treatment or disease progression characterized by worsening cytopenias, 
increase in percentage of bone marrow blasts, or progression to a more advanced MDS 
FAB subtype than pretreatment
Relapse after CR 
or PR
At least 1 of the following:
Return to pretreatment bone marrow blast percentage
Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets
Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependenced
Cytogenetic 
Response
Complete:  Disappearance of chromosomal abnormality without appearance of new ones
Partial:  At least 50% reduction of the chromosomal abnormality


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Category
Response Criteria 
Disease 
Progression
For patients with:
Less than 5% blasts:  ≥ 50 increase in blasts to > 5% blasts
5%-10% blasts:  ≥ 50% increase in blasts to > 10% blasts
10%-20% blasts:  ≥ 50% increase in blasts to > 20% blasts
20%-30% blasts:  ≥ 50% increase in blasts to > 30% blasts
Any of the following:
At least 50% decrement from maximum remission/response in granulocytes or platelets
Reduction in Hgb by ≥ 2 g/dLd
Transfusion dependenced
Source: {Cheson 2006}
Abbreviations:  CR = complete remission; FAB = French-American-British classification; Hgb = hemoglobin; HI = hematologic 
improvement; IWG = International Working Group; MDS = myelodysplastic syndrome; PR = partial remission.
a
Dysplastic changes should consider the normal range of dysplastic changes.
b
Modification to IWG response criteria
c
In some circumstances, protocol therapy may require the initiation of further treatment (e.g., consolidation, maintenance) 
before the 4-week period.  Such patients can be included in the response category into which they fit at the time the therapy 
is started.  Transient cytopenias during repeated chemotherapy courses should not be considered as interrupting durability of 
response, as long as they recover to the improved counts of the previous course.
d
Impact of anemia must be deemed disease-related and not due to study treatment.
Appendix Table 7.
Additional Response Definitions Used in This Study 
(2003 IWG Criteria)
Definitions
Response Criteria
Neutrophils
Platelets
Bone Marrow 
Blasts
Other
cCR
≥ 1.0 × 109/L
≥ 100 × 
109/L
< 5%
Cytogenetics normal and no 
evidence of extramedullary disease 
mCR
≥ 1.0 × 109/L
≥ 100 × 
109/L
< 5%
Molecular investigations normal 
and no evidence of extramedullary 
disease 
Treatment Failurea
Lack of response/Progressive Disease + loss of clinical benefit
Source:  {Cheson 2003}
Abbreviations:  cCR = cytogenetic complete remission; IWG = International Working Group; mCR = molecular complete 
remission.
a
Treatment failure defined for this protocol


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Appendix Table 8.
Response Criteria for Hematologic Improvement
Hematologic Improvement (HI) 
Categorya
Response Criteria (all responses must last ≥ 8 weeks)
Erythroid Response (HI-E)
(pretreatment < 110 g/L)
Pretransfusion increase in hemoglobin by 15 g/L
or
Compared to an 8-week pretreatment period, a reduction in 
transfusion requirements by 4 units in an 8-week posttreatment 
period 
Platelet Response (HI-P)
(pretreatment < 100 × 109/L)
Absolute increase of ≥ 30 × 109/L for patient starting with a 
platelet count > 20 × 109/L pretreatment
or
Increase from < 20  × 109/L pretreatment to > 20  × 109/L 
posttreatment and by at least 100%
Neutrophil Response (HI-N)
(pretreatment < 1.0 × 109/L)
At least 100% increase and an absolute increase of > 0.5 × 109/L
Progression/relapse after Hematological 
Improvementb
One or more of the following
≥ 50% decrement from maximum response in neutrophils or 
platelets
Reduction in hemoglobin by ≥ 15 g/L
Transfusion dependence
Source:  {Cheson 2006}
a
Pretreatment counts should be an average of at least 2 measurements (not influenced by transfusions) performed ≥ 1 week 
apart.
b
In the absence of another explanation.  For example, including, but not restricted to, acute infection, gastrointestinal 
bleeding and hemolysis.


5F9009 SAP – 2nd Interim and Final Analyses
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Bill Grossman
Clinical eSigned
08-Mar-2023
00:38:33
Jenny Huang10
Biostatistics eSigned
09-Mar-2023
01:01:41

Prot_000.pdf: 
ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in 
Combination with Azacitidine versus Azacitidine Plus Placebo in Treatment-naïve Patients 
with Higher Risk Myelodysplastic Syndrome
Short title: Magrolimab + Azacitidine versus Azacitidine + Placebo in 
Untreated MDS
Investigational Product(s)
Magrolimab (Hu5F9-G4) (GS-4721)
Protocol Number
5F9009
Version Date
Original protocol: 26 February 2020
Protocol Amendment 1: 18 September 2020
Protocol Amendment 2: 09 October 2020
Protocol Amendment 2.1 (UK): 23 December 2020
Protocol Amendment 3: 07 January 2021 
Protocol Amendment 4: 04 February 2021
Protocol Amendment 5: 18 August 2021
Protocol Amendment 6: 01 April 2022
Protocol Amendment 7: 27 July 2022
Protocol Amendment 8: 11 October 2022
EudraCT Number
NCT Number
2020-004287-26
NCT04313881
Sponsor
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Confidentiality Statement
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Science, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff and an applicable institutional 
review board and independent ethics committee. The information is only to be used by you in 
connection with authorized clinical studies of the investigational drug described in the protocol. 
You will not disclose any of the information to others without written authorization from Gilead 
Sciences, Inc., except to the extent necessary to obtain informed consent from those persons to 
whom the drug may be administered.
This study will be conducted under United States Food and Drug Administration investigational 
new drug (IND) regulations (21 Code of Federal Regulations Part 312); however, sites located in 
the European Economic Area, the United Kingdom, and Switzerland are not included under the 
IND and are considered non-IND sites.
 


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Protocol 5F9009
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Gilead Sciences, Inc.
Amendment 8
CONFIDENTIAL
Page 2
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STATEMENT OF COMPLIANCE
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practices (GCP) as outlined by International Council for Harmonisation (ICH) E6(R2), and all 
applicable country and regional (local) regulatory requirements. Enrollment at any clinical study 
site may not begin prior to that site receiving approval from the ethics committee of record for 
the protocol and all materials provided to potential participants.
Any amendments to the protocol or changes to the consent document will be approved before 
implementation of that amendment. Re-consent of previously enrolled participants may be 
necessary depending on the nature of the amendment.
The Principal Investigator will ensure that changes to the study plan as defined by this protocol 
will not be made without prior agreement from the Sponsor and documented approval from the 
ethics committee of record, unless such a change is necessary to eliminate an immediate hazard 
to the study participants.
All personnel involved in the conduct of this study have completed Human Subjects Protection 
and GCP Training as outlined by their governing institution.


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Protocol 5F9009
Final
Gilead Sciences, Inc.
Amendment 8
CONFIDENTIAL
Page 3
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SPONSOR’S APPROVAL
Title
ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab 
in Combination with Azacitidine versus Azacitidine Plus Placebo in Treatment-naïve 
Patients with Higher Risk Myelodysplastic Syndrome
Protocol Number
5F9009
Version Date
Amendment 8: 11 October 2022
The design of this study as outlined by this protocol has been reviewed and approved by the 
Sponsor’s responsible personnel as indicated in the signature table below.
Name:
Title:
Signature:
Date:
Medical Monitor,
Senior Director, 
Clinical Development, 
Oncology
[See appended electronic 
signature]
[See appended electronic 
signature]
PPD


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Protocol 5F9009
Final
Gilead Sciences, Inc.
Amendment 8
CONFIDENTIAL
Page 4
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PRINCIPAL INVESTIGATOR’S AGREEMENT
I have read the protocol, appendices, and accessory materials related to Study 5F9009 and agree 
to the following:
To conduct this study as described by the protocol and any accessory materials
To protect the rights, safety, and welfare of the participants under my care
To provide oversight to all personnel to whom study activities have been delegated
To control all investigational products provided by the Sponsor and maintain records of the 
disposition of those products
To conduct the study in accordance with all applicable local and national regulations, the 
requirements of the ethics committee of record for my clinical site, and GCP as outlined by ICH 
E6(R2)
To obtain institutional review board (IRB)/independent ethics committee (IEC) and other 
committee approval as required for the protocol and all written materials provided to participants 
prior to initiating the study at my site
To obtain informed consent – and updated consent in the event of new information or 
amendments – from all participants enrolled at my study site prior to initiating any study-specific 
procedures or administering investigational products to those participants
To maintain records of each participant’s participation and all data required by the protocol
Name
Title
Site Number
Signature
Date


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Protocol 5F9009
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Gilead Sciences, Inc.
Amendment 8
CONFIDENTIAL
Page 5
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SUMMARY OF CHANGES, PROTOCOL 5F9009 AMENDMENT 8
In Amendment 8, Protocol 5F9009 has been updated to clarify current language that does not 
specifically include the use of publicly available records as part of survival data in the case of 
withdrawal of consent.
The major updates to the protocol and related rationale are as follows:

Sections 4 and 5.7: Text is clarified to explicitly include withdrawal of consent as a 
circumstance in which sites may use public records in order to obtain information about 
survival status.

Section 5.7.2: Text is removed that limits data analysis to data collected up until withdrawal 
of consent, in order to allow analysis of survival data collected from the search of public 
records. 
Additional changes to the protocol include the correction of typographical and formatting errors, 
where appropriate.


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Gilead Sciences, Inc.
Amendment 8
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TABLE OF CONTENTS
STATEMENT OF COMPLIANCE................................................................................................................................2
SPONSOR’S APPROVAL.............................................................................................................................................3
PRINCIPAL INVESTIGATOR’S AGREEMENT ........................................................................................................4
SUMMARY OF CHANGES, PROTOCOL 5F9009 AMENDMENT 8........................................................................5
TABLE OF CONTENTS................................................................................................................................................6
LIST OF IN TEXT TABLES..........................................................................................................................................9
LIST OF IN TEXT FIGURES........................................................................................................................................9
LIST OF APPENDICES...............................................................................................................................................10
LIST OF ABBREVIATIONS.......................................................................................................................................11
1.
SYNOPSIS ...........................................................................................................................................................14
2.
INTRODUCTION................................................................................................................................................17
2.1.
Background..............................................................................................................................................17
2.1.1.
Target Indication and Population ..........................................................................................18
2.1.2.
Description of Magrolimab ...................................................................................................18
2.1.3.
Description of Azacitidine.....................................................................................................20
2.1.4.
Supportive Nonclinical Data .................................................................................................21
2.1.5.
Supportive Clinical Data .......................................................................................................22
2.1.6.
Benefit-risk Assessment ........................................................................................................26
2.2.
Study Rationale .......................................................................................................................................27
3.
OBJECTIVES AND ENDPOINTS......................................................................................................................28
4.
STUDY PLAN .....................................................................................................................................................31
4.1.
Study Design ...........................................................................................................................................31
4.2.
Study Schematic ......................................................................................................................................32
4.3.
Schedule of Assessments.........................................................................................................................34
4.4.
Design Rationale .....................................................................................................................................43
4.5.
Recruitment .............................................................................................................................................43
4.6.
Definitions of Enrollment and Screen Failure.........................................................................................44
4.7.
Inclusion Criteria.....................................................................................................................................44
4.8.
Exclusion Criteria....................................................................................................................................45
4.9.
Lifestyle Restrictions...............................................................................................................................47
4.9.1.
Female Participants ...............................................................................................................47
4.9.2.
Male Participants...................................................................................................................47
5.
STUDY CONDUCT ............................................................................................................................................48
5.1.
Study Procedures.....................................................................................................................................48
5.1.1.
Pregnancy Test ......................................................................................................................48
5.1.2.
Complete Blood Counts ........................................................................................................48
5.1.3.
Peripheral Blood Smear Assessment.....................................................................................49
5.1.4.
Type and Screen and Direct Antiglobulin Test .....................................................................49
5.1.5.
Vital Signs .............................................................................................................................49
5.1.6.
Physical Examination ............................................................................................................49
5.1.7.
Electrocardiogram .................................................................................................................49
5.1.8.
Bone Marrow Assessments ...................................................................................................50
5.1.9.
Patient-reported Outcomes ....................................................................................................50




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Amendment 8
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7.7.1.
Requirements for Collection Prior to Study Drug Initiation: ................................................83
7.7.2.
Adverse Events......................................................................................................................83
7.7.3.
Serious Adverse Events.........................................................................................................83
7.7.4.
Study Drug Special Situation Reports...................................................................................84
7.7.5.
Concomitant Therapy Reports...............................................................................................84
7.8.
Reporting Process for Serious Adverse Events and Special Situation Reports.......................................85
7.8.1.
Serious Adverse Event Reporting Process ............................................................................85
7.8.2.
Special Situations Reporting Process ....................................................................................85
7.9.
Gilead Reporting Requirements ..............................................................................................................87
7.10.
Specific Safety Management Guidelines.................................................................................................87
7.10.1.
Magrolimab/Placebo..............................................................................................................87
7.10.2.
Azacitidine.............................................................................................................................92
8.
STATISTICAL CONSIDERATIONS.................................................................................................................93
8.1.
Sample Size Determination .....................................................................................................................93
8.2.
Analysis Sets ...........................................................................................................................................93
8.3.
Planned Analyses.....................................................................................................................................94
8.3.1.
DMC Interim Analyses..........................................................................................................94
8.3.3.
Final Analysis........................................................................................................................97
8.4.
Endpoint Definitions ...............................................................................................................................97
8.5.
Efficacy Analysis.....................................................................................................................................99
8.5.1.
Analysis of Primary Efficacy Endpoints ...............................................................................99
8.5.2.
Analysis of Secondary Efficacy Endpoint(s) ......................................................................100
8.6.
Safety Analysis......................................................................................................................................100
8.6.1.
Extent of Exposure ..............................................................................................................100
8.6.2.
Adverse Events....................................................................................................................100
8.6.3.
Laboratory Evaluations .......................................................................................................101
8.6.4.
Other Safety Analyses .........................................................................................................101
8.7.
Analysis of PRO Data ...........................................................................................................................101
8.8.
Pharmacokinetics Analysis....................................................................................................................101
8.9.
Immunogenicity Analysis......................................................................................................................102
9.
ETHICAL CONSIDERATIONS .......................................................................................................................103
9.1.
Investigator Responsibilities .................................................................................................................103
9.2.
Sponsor Responsibilities .......................................................................................................................104
9.2.1.
Protocol Modifications ........................................................................................................104
9.2.2.
Study Reports and Publications...........................................................................................104
9.3.
Ethics Review........................................................................................................................................104
9.4.
Informed Consent ..................................................................................................................................104
9.5.
Data Privacy and Confidentiality ..........................................................................................................105
9.6.
Urgent Safety Measures ........................................................................................................................106
9.7.
Disclosure..............................................................................................................................................106
9.8.
Biological Specimens and Data.............................................................................................................106
9.8.1.
Payment Reporting ..............................................................................................................107
10.
OVERSIGHT .....................................................................................................................................................108
10.1.
Independent Monitoring ........................................................................................................................108
10.1.1.
DMC....................................................................................................................................108
10.2.
Quality Control and Assurance .............................................................................................................108
10.2.1.
Monitoring...........................................................................................................................108
10.2.2.
Audits ..................................................................................................................................108
10.2.3.
Records................................................................................................................................108
10.3.
Serious Breaches or Fraud.....................................................................................................................110
CCI


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10.4.
Study Termination or Study Site Closure..............................................................................................110
11.
FINANCIAL DISCLOSURE AND INSURANCE ...........................................................................................111
12.
REFERENCES...................................................................................................................................................112
13.
APPENDICES....................................................................................................................................................117
LIST OF IN TEXT TABLES
Table 1.
Dose Level and Schedule ........................................................................................................32
Table 2.
Schedule of Assessments - Screening .....................................................................................35
Table 3.
Schedule of Assessments - Treatment Period-Azacitidine Dosing and Study 
Assessments.............................................................................................................................36
Table 4.
Schedule of Assessments - Treatment Period-Magrolimab or Placebo Dosing and 
Study Assessments ..................................................................................................................37
Table 5.
Schedule of Assessments - Posttreatment ...............................................................................39
Table 6.
Schedule of Assessments - Repriming (Required After > 4 Weeks Have Lapsed 
Since the Last Dose of Magrolimab/Placebo Delays).............................................................41
Table 7.
Laboratory Analyte Listing (To Be Performed at Screening) .................................................53
Table 8.
Laboratory Analyte Listing (To Be Performed During the Study)..........................................54
Table 9.
Investigational Interventions Used in This Study....................................................................62
Table 10.
Magrolimab/Placebo Dosing Guidance for Surgical Procedures on Study.............................67
Table 11.
Azacitidine Dose Modification for Participants With and Without Cytopenia in the 
Absence of MDS .....................................................................................................................70
Table 12.
Azacitidine Dose Modification: Participants with Reduced Bone Marrow Cellularity 
and Reduced Peripheral Blood Counts in the Absence of MDS .............................................71
Table 13.
Azacitidine Dose Modification: Nonhematologic Toxicities..................................................72
Table 14.
Adverse Event Grade (Severity) Scale ....................................................................................78
Table 15.
Causal Attribution Guidance ...................................................................................................79
Table 16.
Pneumonitis Management Algorithm......................................................................................92
Table 17.
Stopping Boundaries for Efficacy Superiority Analyses.........................................................95
Table 18.
Definition of Information Fraction for Key Secondary Endpoints..........................................96
Table 19.
Response Criteria in MDS (IWG 2006 Criteria With Modifications)...................................118
Table 20.
Additional Response Definitions Used in This Study (2003 IWG Criteria) .........................119
Table 21.
Response Criteria for Hematologic Improvement.................................................................119
LIST OF IN TEXT FIGURES
Figure 1.
Treatment-related and Treatment-emergent Adverse Events in AML/MDS Patients 
Treated with Magrolimab in Combination with Azacitidine in Study 5F9005.......................24
Figure 2.
Magrolimab Priming/Maintenance Dose Regimen Alleviates Anemia in AML/MDS 
Patients Treated with Magrolimab in Combination with Azacitidine in Study 
5F9005.....................................................................................................................................25
Figure 3.
Neutrophil and Platelet Counts in MDS/AML Patients Treated with Magrolimab in 
Combination with Azacitidine in Study 5F9005 .....................................................................25
Figure 4.
Study 5F9009 Schematic.........................................................................................................33


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Gilead Sciences, Inc.
Amendment 8
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LIST OF APPENDICES
Appendix A.
National Cancer Institute Common Terminology Criteria for Adverse Events ....................117
Appendix B.
Disease Response Assessment Based on International Working Group Criteria..................118
Appendix C.
Functional Assessment of Cancer Therapy – Anemia...........................................................120
Appendix D.
5-Level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L).................................................121
Appendix E.
Patient Global Impression of Severity and Patient Global Impression of Change................122
Appendix F.
Eastern Cooperative Oncology Group Performance Status...................................................123
Appendix G.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements..................................................................................................124
Appendix H.
Pandemic Risk Assessment and Mitigation Plan ..................................................................127


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LIST OF ABBREVIATIONS
ABO
any of the 4 blood groups A, B, AB, and O comprising the ABO system
ADA
antidrug antibody
AE
adverse event
ALT
alanine aminotransferase
AML
acute myeloid leukemia
ANC
absolute neutrophil count
anti-HBc
antibody against hepatitis B core antigen
AST
aspartate aminotransferase
CBC
complete blood count
CFR
Code of Federal Regulations
CI
confidence interval
CMV
cytomegalovirus
CNS
central nervous system
COVID-19
coronavirus disease 2019
CR
complete remission
CRh
complete remission with partial hematologic recovery
CRO
contract research organization
CSR
clinical study report
CT
computed tomography
DAT
direct antiglobulin test
DLBCL
diffuse large B-cell lymphoma 
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EFS
event-free survival
EQ-5D-5L
5-level EuroQol 5 dimensions
EQ VAS
EuroQol visual analogue scale
EOT
end of treatment
EU
European Union
FACT-Anemia
Functional Assessment of Cancer Therapy – Anemia
FACT-G
Functional Assessment of Cancer Therapy-General
FACT TOI-An
Functional Assessment of Cancer Therapy Trial Outcome Index-Anemia scale
FACT TOI-F
Functional Assessment of Cancer Therapy Trial Outcome Index-Fatigue scale
FDA
Food and Drug Administration


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FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GLPS
Global Patient Safety
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
Hgb
hemoglobin
HI
hematologic improvement
HIV
human immunodeficiency virus
HR
hazard ratio
HRQoL
health-related quality of life
Hu5F9-G4 (GS-4721)
humanized monoclonal antibody that blocks the antiphagocytic signal CD47 
(5F9; magrolimab)
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IDCC
independent data coordinating center
IEC
independent ethics committee
IgG
immunoglobulin
IHC
immunohistochemistry
IPSS
International Prognostic Scoring System
IPSS-R
Revised International Prognostic Scoring System
IRB
institutional review board
ITT
intent-to-treat
IV
intravenous
IWG
International Working Group
IXRS
interactive voice/web/mobile response system
KM
Kaplan-Meier
LDH
lactate dehydrogenase
LHRH
luteinizing hormone-releasing hormone
mAb
monoclonal antibody
MDS
myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Activities
MNS
a human blood group system based upon 2 genes (glycophorin A and glycophorin 
B) on chromosome 4
MOA
mechanism of action
MRD
minimal residual disease
MTD
maximum tolerated dose
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events


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NHL
non-Hodgkin lymphoma
ORR
objective response rate
OS
overall survival
PCR
polymerase chain reaction
PFS
progression-free survival
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetic(s)
PR 
partial remission
PR/CR
partial/complete remission
PRO
patient-reported outcome
Q2W
every 2 weeks
RANKL
receptor activator of nuclear factor kappa-B ligand
RBC
red blood cell
RFS
relapse-free survival
Rh
Rhesus factor
RNA
ribonucleic acid
RO 
receptor occupancy
R/R
relapsed/refractory 
SADR
serious adverse drug reaction
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SCT
stem cell transplant
SIRPα
signal regulatory protein alpha
SOC
standard of care
SOP
standard operating procedure
SSR
special situation report
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment emergent adverse event
UK
United Kingdom
ULN
upper limit of normal
US
United States
WBC
white blood cell


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1.
SYNOPSIS
Title
A Randomized, Double-blind, Multicenter Study Comparing 
Magrolimab in Combination with Azacitidine versus Azacitidine 
Plus Placebo in Treatment-naïve Patients with Higher Risk 
Myelodysplastic Syndrome
Short Title
Magrolimab + Azacitidine versus Azacitidine + Placebo in 
Untreated MDS
Acronym
ENHANCE: Efficacy of a Novel Hu5F9-G4 + Azacitidine 
Therapy in Treatment-Naïve Patients with MyelodysplastiC 
SyndromE
Phase
3
Study Design
This is a randomized, double-blind, placebo-controlled, 
multicenter study investigating magrolimab + azacitidine 
compared with azacitidine + placebo in previously untreated 
participants with intermediate/high/very high risk myelodysplastic 
syndrome (MDS) by Revised International Prognostic Scoring 
System (IPSS-R).
Rationale
Novel therapies that can be combined with hypomethylating 
agents while maintaining an acceptable safety profile and 
improving durable complete remissions or survival probability are 
needed for individuals with higher risk MDS. No new therapies 
have been approved in MDS for over a decade, which underscores 
a high unmet medical need in this population. Patients with MDS 
experience frequent comorbidities and mortalities as a result of 
cytopenias due to the disease and to hypomethylating agents. The 
need for combination therapies that can induce hematologic 
improvement and disease remission leading to a clear clinical 
benefit is quite evident. Magrolimab in combination with 
azacitidine is being developed in previously untreated participants 
with intermediate/high/very high risk MDS by IPSS-R to improve 
clinical activity and maintain an acceptable safety profile.
Target Population
Previously untreated participants ≥ 18 years of age with MDS 
defined according to World Health Organization classification 
with an IPSS-R risk category of intermediate, high, or very high 
risk.
Number of Participants
Total: Approximately 520 participants globally


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Length of Participation
On treatment: Until disease progression, loss of clinical benefit, or 
unacceptable toxicities occur
On study (including screening and follow-up): Up to 4 years after 
the last participant is randomized
Intervention
Magrolimab + azacitidine, or azacitidine + placebo as follows:
Magrolimab

Priming doses of magrolimab: 1 mg/kg on Days 1 and 4; 
15 mg/kg on Day 8; 30 mg/kg on Days 11 and 15; and then 
30 mg/kg weekly for a total of 5 doses (on Days 22, 29, 36, 
43, and 50).

Maintenance doses of magrolimab: 30 mg/kg on Day 57, 
and 30 mg/kg every 2 weeks thereafter.
Placebo

Saline placebo to mirror the magrolimab dosing schedule 
above.
Azacitidine

75 mg/m2 on Days 1 to 7 of a 28-day cycle

Alternative schedule: 75 mg/m2 on Days 1 to 5, Day 8, and 
Day 9 of a 28-day cycle for flexibility and convenience
Primary Objectives and 
Primary Endpoints
Synopsis Table 1.
Primary Objectives and Endpoints
Objective
Endpoint
To evaluate the efficacy of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo in 
previously untreated participants 
with intermediate/high/very high risk 
MDS by IPSS-R as measured by CR 
rate
CR rate as assessed by Investigators
To evaluate the survival benefit of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo
OS
Abbreviations: CR = complete remission; IPSS-R = Revised International Prognostic 
Scoring System; MDS = myelodysplastic syndrome; OS = overall survival.
Number of Sites
Approximately 200 sites in the United States, Australia, Europe, 
and other countries as required, based on enrollment and study 
timelines


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Study Duration
Estimated study duration: up to 4 years after the last participant is 
randomized
Data Monitoring 
Committee
The data monitoring committee (DMC) will review the unblinded 
data generated during the clinical study. The mandate of the DMC 
is to serve as an independent committee with pertinent clinical and 
trial conduct expertise to monitor and ensure the safety of the 
therapies for participants on trial. Prior to the final overall survival 
(OS) analysis, 2 planned interim efficacy analyses will be 
conducted by the DMC. The composition, structure, and function 
of the DMC and the scope of data for review are defined in the 
DMC Charter. The timing of such data review will be predefined 
in the DMC Charter.


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2.
INTRODUCTION
2.1.
Background
Myelodysplastic syndrome (MDS) is a premalignant clonal hematopoietic disorder characterized 
by bone marrow failure due to production of dysfunctional, dysplastic bone marrow cells. Low 
and very low risk patients, as defined by the Revised International Prognostic Scoring System 
(IPSS-R;{Greenberg 2012}), are often treated with erythroid and myeloid growth factor support 
and carry a low risk of leukemic progression. In contrast, intermediate, high, and very high risk 
patients with MDS are generally treated with hypomethylating agents and carry an elevated risk 
of leukemic progression. Azacitidine (Vidaza®) is standard of care (SOC) for newly diagnosed 
MDS patients with specific high risk subtypes. However, complete remission (CR) rates are low, 
and overall survival (OS) is only around 18 months {Silverman 2002}. Thus, novel therapies that 
replace or augment the efficacy of azacitidine are needed to extend survival for patients with 
MDS.
CD47 is a key molecule mediating cancer cell evasion of phagocytosis by the innate immune 
system. CD47 appears to be an indispensable means by which cancer cells, including cancer 
stem cells, overcome intrinsic expression of their prophagocytic “eat me” signals ({Jaiswal 2009, 
Majeti 2009}). The progression from normal cell to cancer cell involves changes in genes and 
gene expression that trigger programmed cell death and programmed cell removal {Chao 2012} 
Many of the steps in cancer progression subvert the multiple mechanisms of programmed cell 
death, and the expression of the dominant antiphagocytic signal, CD47, may represent an 
important checkpoint {Chao 2012}. Increased CD47 expression was identified first on leukemic 
stem cells in human acute myeloid leukemia (AML; {Majeti 2009}), and since then, it has been 
found that CD47 expression is increased on the surface of cancer cells from a large number of 
diverse human tumor types.
In mouse xenograft models, CD47-blocking monoclonal antibodies (mAbs) inhibit human 
xenograft tumor growth and metastasis by enabling the phagocytosis and elimination of cancer 
cells from various hematologic malignancies and solid tumors {Chao 2011a, Chao 2010a, Chao 
2011b, Edris 2012, Kim 2012, Majeti 2009, Willingham 2012}. Binding of CD47 on cancer cells 
to its ligand signal regulatory protein alpha (SIRPα) expressed on phagocytes leads to inhibition 
of tumor phagocytosis. Thus, blockade of the CD47 SIRPα-signaling pathway by an anti-CD47 
antibody leads to phagocytosis and elimination of tumor cells. Selective targeting of tumor cells 
by an anti-CD47 antibody is due to the presence of prophagocytic signals expressed mainly on 
tumor cells and not on normal cell counterparts{Chao 2010b}. In addition, the anti-CD47 
antibody induces an anticancer T-cell response through cross-presentation of tumor antigens by 
macrophage and antigen-presenting cells after tumor cell phagocytosis {Liu 2015b, Tseng 
2013}. Furthermore, CD47-blocking mAbs have shown synergistic efficacious activity with 
cancer-specific targeting antibodies, including anti-CD20 antibody rituximab in a nonclinical 
model of non-Hodgkin lymphoma (NHL; {Chao 2010a}).


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Magrolimab (also known as Hu5F9-G4 or 5F9 [GS-4721]), a humanized anti-CD47 mAb, has 
been investigated in a Phase 1 AML study (Study SCI-CD47-002; EudraCT No. 
2015-000720-29) conducted in the United Kingdom (UK) and has been further investigated in an 
ongoing Phase 1b study (Study 5F9005; EudraCT No. 2017-000678-12) in multiple subtypes of 
AML and intermediate/high/very high risk MDS, both as monotherapy and in combination with 
azacitidine.
2.1.1.
Target Indication and Population
Myelodysplastic syndrome is a premalignant clonal hematopoietic disorder characterized by 
peripheral blood cytopenias, dyspoiesis, and increased risk of AML development. The disorder 
affects primarily individuals in their seventh decade of life ({Ma 2012}), and treatment strategies 
are based on standard prognostic scoring. Patients classified as low or very low risk categories, 
as defined by the IPSS-R {Greenberg 2012}, are normally treated with erythroid and myeloid 
growth factor support. These individuals also have a low risk of progression to acute leukemia. 
In contrast, patients with intermediate, high, or very high risk MDS have a 25% chance of 
leukemic transformation and are generally treated with hypomethylating agents {(NCCN) 2018}. 
Specifically, azacitidine is the standard of care for newly diagnosed MDS categorized as 
intermediate, high, or very high risk. However, the overall response rate (CR + partial remission 
[PR]) was only about 16% (azacitidine prescribing information), and median OS is 
approximately 18 months {Silverman 2002}. Thus, new therapies that may replace or augment 
the efficacy of azacitidine are needed to improve outcomes for these patients. 
Magrolimab + azacitidine (compared with azacitidine + placebo) is being investigated for the 
treatment of previously untreated patients with intermediate/high/very high risk MDS by IPSS-R.
2.1.2.
Description of Magrolimab
Magrolimab is a humanized anti-CD47 mAb that blocks the interaction of CD47 with its receptor 
and enables phagocytosis of human cancer cells {Liu 2015a}. The activity of magrolimab is 
primarily dependent on blocking CD47 binding to SIRPα and not on the recruitment of 
Fc-dependent effector functions, although the presence of the immunoglobulin 4 (IgG4) Fc 
domain is required for its full activity. For this reason, magrolimab was engineered with a human 
IgG4 isotype that is relatively inefficient at recruiting Fc-dependent effector functions that might 
enhance toxic effects on normal CD47-expressing cells {Liu 2015a}. Nonclinical studies using 
xenograft cancer models provide compelling evidence that magrolimab triggers phagocytosis and 
elimination of cancer cells from human solid tumors and hematologic malignancies. Based on 
this mechanism of action (MOA) and its potent nonclinical activity, magrolimab is being 
developed as a novel therapeutic candidate for solid tumors and hematologic malignancies.
The magrolimab program represents a novel strategy for the treatment of cancer and is the first 
therapeutic agent to target the CD47-SIRPα axis. Extensive nonclinical studies have 
demonstrated activity against both human solid tumors (breast, ovarian, pancreas, colon, 
leiomyosarcoma, bladder, prostate, and others) and hematologic malignancies (AML, acute 
lymphoblastic leukemia, NHL, myeloma, MDS, and others).


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2.1.2.1.
Justification for Dosing Strategy
The following magrolimab dosing regimen is proposed for this study:

Priming doses of magrolimab: 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on 
Days 11 and 15; and then 30 mg/kg weekly for a total of 5 doses (Days 22, 29, 36, 43, and 
50).

Maintenance doses of magrolimab: 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks 
thereafter.
Rationale for the magrolimab dose proposed in this study originates from safety, efficacy, and 
pharmacokinetic (PK)/pharmacodynamic data and modeling and simulation analyses based on 
data obtained from all ongoing and completed clinical trials with magrolimab in participants with 
solid tumors, NHL, and AML/MDS.
In the first-in-human study of magrolimab (SCI-CD47-001) in participants with solid tumors and 
lymphomas, after an initial priming dose of 1 mg/kg on the first day, magrolimab was tested as a 
monotherapy at weekly doses of up to 45 mg/kg. The use of an initial 1 mg/kg priming dose was 
integrated to the dosing regimen based on mitigation of the on-target anemia induced by CD47 
blockade. An initial priming dose leads to elimination of aged red blood cells (RBCs) that are 
sensitive to CD47 blockade and triggers a reticulocytosis of young RBCs that are not affected by 
CD47 blockade {Chen 2018}. Utilizing a priming dose leads to an initial, transient, and mild 
anemia that generally normalizes back to baseline over several weeks even in the presence of 
repeated therapeutic doses of magrolimab ({Advani 2018, Liu 2015a, Sikic 2019}. The top dose 
of 45 mg/kg has an acceptable safety profile, and no maximum tolerated dose (MTD) was 
identified in this study. In Studies SCI-CD47-002 and 5F9005, in participants with AML/MDS, 
magrolimab was administered as a monotherapy at doses of up to 30 mg/kg twice weekly and in 
combination with azacitidine at doses of up to 30 mg/kg weekly. In these studies, no significant 
dose-limiting toxicity was observed, and magrolimab has an acceptable safety profile over the 
tested dose range up to a maximum of 30 mg/kg twice a week. Furthermore, in these 2 studies, 
an intrapatient dose escalation approach was followed; after the priming dose, the participants 
received doses of 15 mg/kg on Day 8 during Week 2, after which the dose was escalated to 
30 mg/kg on Day 11 and then weekly thereafter. This was based on nonclinical data indicating 
enhanced safety of intrapatient dose escalation. In Studies 5F9003 and 5F9004, magrolimab in 
combination with rituximab and cetuximab, respectively, was found to have an acceptable safety 
profile at doses up to 45 mg/kg every other week. Based on the entirety of safety data in multiple 
oncology populations, including the proposed study population, both as a monotherapy and in 
combination with other tumor targeted antibodies and chemotherapeutics, the proposed dosing 
regimen of magrolimab is expected to have an acceptable safety profile.
Currently, there are limited data on dose/exposure-response in the treatment-naïve MDS 
population, but available dose-ranging data in patients with NHL also support the proposed 
dosing regimen. After a priming dose of 1 mg/kg in the first week, maintenance doses in the 
range of 10 to 45 mg/kg every week and 30 to 45 mg/kg every 2 weeks (Q2W) are being tested 
in an ongoing Phase 1b/2 study of magrolimab in combination with rituximab in participants 




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Azacitidine is SOC and approved in the United States (US) for treatment of subtypes of MDS 
including, but not limited to, MDS with refractory with anemia excess blasts, a subtype that is 
mostly composed of patients with intermediate to very high risk MDS by IPSS-R criteria. 
Azacitidine is also an SOC therapy for newly diagnosed patients with AML who are ineligible 
for induction chemotherapy or stem cell transplant (SCT) based on age, comorbidities, or other 
factors. In Europe, azacitidine is approved for patients with intermediate-2 and high risk MDS 
according to the International Prognostic Scoring System (IPSS) criteria and for patients with 
AML who are ineligible for SCT.
The adverse event (AE) profile of azacitidine primarily includes myelosuppression (anemia, 
leukopenia, and thrombocytopenia) and clinical sequelae of myelosuppression (neutropenic 
fever, infections, bleeding, and fatigue). Common nonhematologic AEs include gastrointestinal 
events (diarrhea, nausea, constipation, and decreased appetite), skin disorders (rash, pruritus, 
petechiae, and ecchymosis), injection site/infusion-related reactions (injection site erythema 
and/or pain for subcutaneous [SC] administration), and fever. Generally, these toxicities can be 
managed with supportive care interventions, pharmacologic treatment, or dose delays and/or 
adjustments. Further information on the safety profile of azacitidine is outlined in the summary 
of product characteristics for SC and the prescribing information for SC or intravenous (IV) use. 
2.1.3.1.
Justification for Dosing Strategy
Azacitidine will be dosed according to region-specific drug labeling, either SC or IV, at the 
standard clinical dose of 75 mg/m2 on Days 1 to 7 of a 28-day cycle in combination with 
magrolimab/placebo. Azacitidine may be administered on an alternative schedule of Days 1 to 5, 
Day 8, and Day 9 of a 28-day cycle for flexibility and convenience. In accordance with the 
azacitidine drug label, it is recommended that patients be treated for a minimum of 6 cycles. 
Treatment should be continued until disease progression, loss of clinical benefit, or unacceptable 
toxicities occur, as described in the azacitidine prescribing information references. Participants 
with MDS enrolled on this study will consist of participants in both the US, Australia, and other 
relevant country-specific-based azacitidine approval indications.
2.1.4.
Supportive Nonclinical Data
The nonclinical studies referred to in the publications referenced in this section have been 
conducted with a commercially available CD47-blocking mAb (clone B6H12, mouse IgG1), and 
additional nonclinical studies have been conducted with the humanized CD47-blocking mAb 
magrolimab.
An anti-CD47 antibody has demonstrated therapeutic efficacy in MDS in nonclinical models. 
Blockade of CD47 may be therapeutic in patients with higher risk MDS as CD47 expression 
increases with progression from low risk to high risk MDS to AML. In nonclinical models, 
dysplastic cells from high risk MDS patients were eliminated by phagocytosis with an anti-CD47 
antibody {Pang 2013}.


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Since MDS is pathophysiologically considered a spectrum of disease sharing many 
characteristics to AML, nonclinical studies evaluating magrolimab in AML have relevance to 
MDS and are reported here. Magrolimab treatment eliminated both circulating leukemic and 
bone marrow disease in nonclinical mouse models engrafted with human patient AML cells as 
monotherapy {Liu 2015a}.
The combination of magrolimab + azacitidine was evaluated in leukemic nonclinical models. 
Nonclinical synergy was observed based on the upregulation of prophagocytic signals (including 
calreticulin) on leukemic cells by azacitidine combined with blockade of the antiphagocytic 
signal CD47 with magrolimab {Feng 2018}. Magrolimab + azacitidine led to synergistic 
phagocytosis of leukemic cells in vitro and near 100% long-term durable remissions in an 
aggressive nonclinical leukemia mouse model compared with modest effects with monotherapy. 
These data serve as the mechanistic and nonclinical rationale for combining magrolimab with 
azacitidine in MDS. Further nonclinical data including efficacy, toxicology, and pharmacology 
can be found in the investigator’s brochure (IB).
2.1.5.
Supportive Clinical Data
2.1.5.1.
Clinical Pharmacology and Pharmacokinetics
Clinical PK data have been collected in all ongoing trials of magrolimab conducted to date. PK 
data have been analyzed for participants in the solid tumor Phase 1 study (SCI-CD47-001). In 
this study, participants have been treated with weekly magrolimab doses ranging from 0.1 to 
45 mg/kg, with increasing plasma concentrations associated with increasing dose. Nonlinear PK 
consistent with target-mediated clearance has been observed over this dose range. However, at 
maintenance doses of 10 mg/kg and above, target-mediated clearance was saturated within the 
dosing regimen, and trough levels associated with magrolimab efficacy in nonclinical studies 
have been achieved. Evidence of sustained target trough levels has been observed at doses of 
10 mg/kg weekly and higher. Nine of 88 (10%) evaluable participants tested positive for antidrug 
antibody (ADA) against magrolimab at any time point including baseline; ADA positivity had no 
impact on PK or clinical safety in these participants.
For the Phase 1 AML study (SCI-CD47-002), PK data have been analyzed for all cohorts (dose 
range from 0.1 to 30 mg/kg twice weekly). Similar to the solid tumor Phase 1 study, nonlinear 
PK consistent with target-mediated clearance has been observed. Pharmacokinetics sampling is 
continuing in other ongoing magrolimab trials. Three of 20 (15%) evaluable participants tested 
positive for ADA against magrolimab at any time point including baseline; ADA positivity had 
no impact on PK. ADA positivity in either study was not associated with increased AEs.
Preliminary PK data of magrolimab from other ongoing studies (5F9003, 5F9004, and 5F9005) 
of magrolimab indicate similar PK properties across all tumor populations and in the presence of 
coadministered drugs. Across all studies, 21 out of 264 (8%) participants tested positive for ADA 
against magrolimab at any time point including baseline. ADA positivity was not associated with 
changes in PK or AE profile.


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A preliminary population PK analysis of combined magrolimab PK data indicated that results for 
magrolimab population PK were typical of other nonlinear antibodies {Dirks 2010}. No 
clinically significant covariates of PK variability were identified.
2.1.5.2.
Clinical Safety
Magrolimab is administered as an IV infusion, and it is currently being studied in 6 clinical trials. 
Two single-agent Phase 1 studies include Study SCI-CD47-001 in participants with advanced 
solid tumors and lymphomas and Study SCI-CD47-002 in participants with R/R AML. 
Four combination trials include the following: Study 5F9003, a Phase 1b/2 study of magrolimab 
with rituximab in participants with R/R NHL; Study 5F9004, a Phase 1b/2 study of magrolimab 
with cetuximab in solid tumor and colorectal cancer participants; Study 5F9005, a Phase 1b 
study of magrolimab with azacitidine in AML and MDS participants; and Study 5F9006, a 
Phase 1b study of magrolimab with avelumab in solid tumor and ovarian cancer participants. As 
of July 2019, approximately 400 participants have been treated with magrolimab. Overall, the 
safety profile has been acceptable with magrolimab as monotherapy or in combination, with no 
MTD reached in any study with dosing up to 45 mg/kg.
As of November 2019, 62 participants (35 untreated higher risk MDS participants and 
27 untreated induction chemotherapy-ineligible AML participants) have been enrolled in 
Study 5F9005 with the combination of magrolimab + azacitidine {Sallman 2019}. The safety 
profile of magrolimab in combination with azacitidine was acceptable and consistent with 
azacitidine monotherapy, with no apparent increased toxicities in combination. No MTD was 
reached with magrolimab dosing of 30 mg/kg weekly. The most common treatment-related AEs 
with magrolimab were anemia (39%), neutropenia/neutrophil count decreased (23%), and 
thrombocytopenia/platelet count decreased (18%) (Figure 1). Treatment discontinuation due to 
any AE occurred in only 1 of 62 (1.6%) participants, with no MDS participants discontinuing 
treatment due to any AE.






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2.1.5.3.
Clinical Efficacy
As of November 2019 in Study 5F9005, clinical activity was assessed for 
magrolimab + azacitidine in participants with treatment-naïve/unfit AML and treatment-naïve 
intermediate to higher risk (by IPSS-R) MDS {Sallman 2019}. Forty-six (24 MDS and 22 AML) 
participants were evaluable for efficacy. In MDS, the ORR was 92%, with 50% achieving a CR. 
In AML, the ORR was 64%, with 41% achieving a CR and 14% achieving complete remission 
with incomplete hematologic recovery (Cri). Time to response was rapid at 1.9 months. 
Complete cytogenetic responses were observed in 26% of MDS participants and 60% of AML 
participants of whom had abnormal cytogenetics at baseline. Twenty-three percent of MDS and 
57% of responding AML participants achieved minimal residual disease (MRD) negativity, as 
assessed by flow cytometry. With a median follow-up of 6.4 months and 8.8 months for MDS 
and AML, respectively, no median DOR had been reached, with several participants in response 
over 14 months on therapy. In addition, putative CD34+CD48− leukemia stem cell progenitors 
were substantially reduced or eradicated by magrolimab in combination with azacitidine in 
responding participants who were evaluated. In summary, magrolimab in combination with 
azacitidine has meaningful clinical activity that appears to be enhanced compared with 
azacitidine monotherapy in both MDS and AML participants.
For further clinical efficacy information, please refer to the magrolimab IB.
2.1.6.
Benefit-risk Assessment
Overall, nonclinical and clinical data to date on magrolimab in combination with azacitidine 
show the therapy to have evidence of efficacy in untreated higher risk MDS and show the 
therapy to have an acceptable safety profile in this patient population. This encouraging activity 
is based on a 92% ORR and 50% CR rate observed with no median DOR reached throughout a 
median follow-up of 6.4 months. The safety profile of the combination is acceptable, with no 
MTD reached and a treatment discontinuation rate due to AEs of 1.6%. No significant 
exacerbation of azacitidine AEs by magrolimab has been observed, as evidenced by the 
minimally observed myelosuppression from the combination. The efficacy of 
magrolimab + azacitidine compares favorably to azacitidine monotherapy in higher risk MDS. 
To this point, based on large historical studies, the ORR for azacitidine monotherapy ranges from 
40% to 50%, and the CR rate ranges from 6% to 17% (azacitidine US package insert,{Fenaux 
2009, Silverman 2006}. One additional study evaluating azacitidine demonstrated a CR rate of 
24%; however, this study also included lower risk MDS by IPSS-R and chronic myelomonocytic 
leukemia participants with the CR rate specifically in higher risk MDS participants not reported 
{Sekeres 2017}.
The potential risks and mitigations associated with participants being unable to attend study 
visits as a result of a pandemic have been identified for this study and are described in 
Appendix H. Given the risk-mitigation measures that are being implemented, the expected 
benefit-risk assessment to the participant remains unchanged. 


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Overall, based on the scientific rationale, nonclinical data, and acceptable safety profile and 
encouraging clinical activity data obtained for magrolimab in combination with azacitidine, the 
risk-benefit ratio is acceptable for proceeding forward with this study in untreated higher risk 
MDS.
2.2.
Study Rationale
Azacitidine upregulates prophagocytic signals in leukemia cells and results in increased 
phagocytosis when combined with magrolimab’s blockade of CD47, a major antiphagocytic 
signal. Nonclinical data have demonstrated enhanced phagocytosis of leukemia cells in vitro and 
long-term remissions in AML-engrafted mice with magrolimab in combination with azacitidine 
compared with either single agent alone. Magrolimab in combination with azacitidine is being 
developed in multiple indications within MDS and AML, specifically in a potential pivotal 
single-arm study in untreated intermediate to very high risk MDS participants as assessed by 
IPSS-R criteria. Data reported from December 2019 demonstrated an ORR of 92% and a CR rate 
of 50% in 24 MDS participants, an acceptable safety profile, and a treatment discontinuation rate 
due to AEs of only 1.6% {Sallman 2019}. The SOC therapy for this population is 
hypomethylating agents (azacitidine and decitabine); however, efficacy is limited, with CR rates 
of approximately 6% to 17% and a median OS of approximately 18 months (azacitidine US 
package insert,{Fenaux 2009, Silverman 2006}). For higher risk MDS, azacitidine is in general 
more widely used than decitabine, given azacitidine’s approval for MDS in the US, Europe, and 
other regions. Novel effective therapies that can be combined with hypomethylating agents while 
maintaining an acceptable safety profile are needed for individuals with higher risk MDS. As of 
December 2019, no new therapies have been approved in MDS for over a decade, which 
underscores a high unmet medical need in this population. Participants with MDS experience 
frequent comorbidities and mortalities as a result of cytopenias due to both the disease and to 
hypomethylating agents. The need for combination therapies that can induce hematologic 
improvement and disease remission leading to a clear clinical benefit is quite evident. 
Magrolimab in combination with azacitidine is being developed in previously untreated 
participants with intermediate/high/very high risk MDS by IPSS-R to improve clinical activity 
and maintain an acceptable safety profile. This study will compare the efficacy and safety of 
magrolimab + azacitidine with that of azacitidine + placebo.


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Amendment 8
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3.
OBJECTIVES AND ENDPOINTS
The aim of this study is to evaluate the efficacy and safety of magrolimab + azacitidine 
compared with azacitidine + placebo in previously untreated participants with 
intermediate/high/very high risk MDS by IPSS-R prognostic risk categories.
Tier
Objectives
Endpoints
Primary: Efficacy
To evaluate the efficacy of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo in 
previously untreated participants with 
intermediate/high/very high risk MDS 
by IPSS-R as measured by CR rate
CR rate as assessed by 
Investigators
Primary: Efficacy
To evaluate the survival benefit of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo
OS
Secondary: Efficacy
To evaluate the duration of CR of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo
Duration of CR
Secondary: Efficacy
To evaluate ORR and DOR of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo
ORR and DOR
Secondary: Efficacy
To evaluate RBC transfusion 
independence rate of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo 
among all participants who are RBC 
transfusion-dependent at baseline
RBC transfusion independence rate
Secondary: Efficacy
To evaluate the efficacy of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo as 
measured by EFS
EFS
Secondary: Efficacy
To evaluate CR of 
magrolimab + azacitidine compared 
with that of azacitidine + placebo in 
TP53 mutant population
CR rate in TP53 mutant population
Secondary: Efficacy
To assess the level of MRD negativity 
of magrolimab + azacitidine compared 
with that of azacitidine + placebo
MRD-negative response rate
Secondary: Efficacy
To assess time to transformation to 
AML of magrolimab + azacitidine 
compared with that of 
azacitidine + placebo
Time to transformation to AML






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Amendment 8
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4.
STUDY PLAN
4.1.
Study Design
This is a Phase 3, randomized, double-blind, placebo-controlled multicenter study investigating 
magrolimab + azacitidine compared with azacitidine + placebo in previously untreated 
participants with intermediate/high/very high risk MDS by IPSS-R. The primary endpoints are 
CR rate and OS. Participants will be randomized in 1:1 ratio to receive either 
magrolimab + azacitidine (experimental arm) or azacitidine + placebo (control arm). 
Randomization will be stratified by 3 factors: 1) geographic region (US versus ex-US sites); 
2) cytogenetic risk status (very good/good/intermediate versus poor/very poor versus unknown) 
according to IPSS-R {Greenberg 2012}); and 3) percentage of bone marrow blasts 
(≥ 10% versus < 10% blasts). The primary analysis of CR rate will be conducted 8 months after 
348 participants are randomized.
Participant participation will include screening, treatment, and follow-up. Screening will last up 
to 30 days before first dose of study treatment, during which time the participant’s eligibility and 
baseline characteristics will be determined. Participants will receive study treatment per the dose 
schedule in Table 1. No cross-over between arms is allowed. Study treatment may be continued 
until disease progression (including treatment failure by International Working Group [IWG] 
2006 criteria or relapse after partial/complete remission [PR/CR]), loss of clinical benefit, or 
unacceptable toxicities occur. In case participants discontinue the study treatment due to reasons 
other than disease progression, participants will be followed up for response assessments until 
documented disease progression occurs. For participants who come off the study treatment to 
receive an SCT, follow-up for response assessment and collection of SOC bone marrow 
biopsy/aspirate results will continue until documented disease progression occurs or start of new 
anticancer therapy, whichever occurs first. The participants will be followed for survival, unless 
the participant explicitly indicates a desire to forego survival follow-up in writing to their study 
investigator, until death, withdrawal of consent, loss to follow-up, or study termination, 
whichever occurs first. For any participant who dies during this follow-up period, the immediate 
cause of death must be reported to the Sponsor. For participants who are lost to follow-up or 
withdraw consent, study staff may use public records (eg, public health records) to obtain 
information about survival status where allowable by local regulation.


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Amendment 8
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Table 1.
Dose Level and Schedule 
Dose Schedule (Day per 28-day Cycle)
Treatment Arms
Drug/Dose/Route
Cycle 1
Cycle 2
Cycle 3+
Experimental arm 
(Magrolimab+ azacitidine)
And Control arm 
(azacitidine + placebo)
Azacitidine 75 mg/m2 SC or 
IVa
Days 1–7
or
Days 1–5 and 
8-9
Days 1–7
or
Days 1–5 
and 8–9
Days 1–7
or
Days 1–5 and 8-9
Dose Schedule
Treatment Arms
Drug/Dose/Route
Priming Dose
Magrolimab 1 mg/kg IV
Days 1, 4
Magrolimab 15 mg/kg IV
Day 8
Maintenance Dose
Experimental arm 
(Magrolimab+ azacitidine) 
Magrolimab 30 mg/kg IV
Days 11, 15, followed by 
weekly administration for 
5 doses (Days 22, 29, 36, 43, 
50)
Day 57 and every 
2 weeks thereafter
Control arm 
(azacitidine + placebo)
Placebo
to mirror the magrolimab 
dosing schedule above
to mirror the 
magrolimab dosing 
schedule above
Abbreviations: IV = intravenous; SC = subcutaneous.
a
Azacitidine administered per region-specific labeling.
Treatment with azacitidine as standard of care is recommended for a minimum of 6 cycles. 
Therefore, in this study, participants without evidence of disease progression (including 
treatment failure by IWG 2006 criteria or relapse after PR/CR), loss of clinical benefit, or 
unacceptable toxicity should continue azacitidine for at least 6 cycles. Participants may be 
discontinued from the treatment per Investigator’s discretion prior to reaching the recommended 
minimum cycles for any of these reasons detailed in Section 5.7.
The schedules of assessments are provided in Section 4.3.
4.2.
Study Schematic
The study schematic is presented in Figure 4.


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Protocol 5F9009
Final
Gilead Sciences, Inc.
Amendment 8
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Figure 4.
Study 5F9009 Schematic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
   
 
 
 
 
 
 
 
 
  
  
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 


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Protocol 5F9009
Final
Gilead Sciences, Inc.
Amendment 8
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4.3.
Schedule of Assessments
The schedule of assessments is presented in a separate table for each study period: screening 
(Table 2), treatment period- azacitidine dosing and study assessments (Table 3), treatment 
period-magrolimab or placebo dosing and study assessments (Table 4), posttreatment (Table 5), 
and repriming (Table 6). A cycle is 28 days long.


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Final
Gilead Sciences, Inc.
Amendment 8
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Table 2.
Schedule of Assessments - Screening
Study 5F9009
Assessment
Day -30 to –1
Informed consent
Xa
Demographics
X
Medical and cancer history
X
Pregnancy test 
Xb
Serum or plasma chemistry
X
Serum uric acid, phosphorus
X
Hematologyd 
X
Blood phenotyping or genotyping, type, screen (ABO/Rh), DATe
X
Urinalysis
X
Bone marrow biopsy and aspirate for blast evaluation, biomarker studies, cytogenetics, and MRD assessmentc
X
ECOG
X
Vital signs, height, and weight
X
Complete physical examination
X
ECG (single)
X
Hepatitis B, hepatitis C, and HIVf 
X
Adverse events related to protocol-mandated procedures
X
Concomitant medications
X
Entry criteria
X
Randomization 
Xa
Abbreviations: ABO = any of the 4 blood groups A, B, AB, and O comprising the ABO system; DAT = direct antiglobulin test; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FSH = follicle-stimulating hormone; MRD = minimal 
residual disease; RBC = red blood cell; Rh = Rhesus factor; SOC = standard of care.
a
Screening must be completed before randomization. Randomization must occur within 30 days of signing informed consent. 
The first dose of study treatment (Table 3 and Table 4) must be given within 72 hours after randomization.
b
Screening pregnancy test may be used as the Day 1 test if performed within 72 hours of first dose; additional guidance is 
provided in Section 5.1.1. FSH test is required for female participants who are < 54 years old who are not on hormonal 
contraception and who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal 
failure.
c
A trephine (biopsy) is to be collected for baseline. A bone marrow biopsy collected per SOC within 30 days of 
randomization can be considered the screening sample, and shipped to central laboratory. This procedure must be performed 
prior to the first dose of study treatment at the latest. An aspirate sample must be collected at the screening visit for blast 
evaluation, MRD assessment, biomarker studies, baseline for response assessment and biobanking. It is preferred that bone 
marrow aspirate samples are obtained at the time of bone marrow (trephine) biopsy. Conventional cytogenetics to be tested 
per institutional standards.
d
Hematology analytes to be assessed at screening are provided in Table 7.
e
ABO/Rh type, antibody screen, DAT, and extended RBC phenotyping (including minor antigens such as CcDEe, Cw, 
MNSs, Kk, FyaFyb, and JkaJkb) must be performed for each participant. Red blood cell genotyping instead of extended 
RBC phenotyping is acceptable for any patient. Red blood cell genotyping (instead of an extended RBC phenotyping) must 
be performed if a participant received any RBC or whole blood transfusion within the previous 3 months (unless the 
laboratory has availability for special techniques for performing phenotyping for participants with a recent transfusion). 
Results must be available before the first dose of magrolimab.
f
Refer to Exclusion Criteria 13 and Other Laboratory Measurements in Table 7.


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Final
Gilead Sciences, Inc
Amendment 8
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Table 3.
Schedule of Assessments - Treatment Period-Azacitidine Dosing and Study Assessments
Cycle (28-day Cycles)
1
2
3+
Visit Window (Days)
None
± 3
± 3
± 3
Cycle Day
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
PRO assessmenta
X
X
X
CBC with differential, platelets, reticulocytesb
X
X
X
Serum or plasma chemistryb
X
X
X
Bone marrow biopsy and aspirate for biomarker studiesc
Xd,e
Bone marrow aspirate biopsy for MRD monitoring, 
cytogenetics, and response assessmentd,f
X
Q2C, Q3Ce
Vital signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed physical examinationb
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Azacitidineh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: CBC = complete blood count; EQ-5D-5L = 5-level EuroQol 5 dimensions; FACT-Anemia = Functional Assessment of Cancer Therapy-Anemia; MRD = minimal 
residual disease; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PRO = patient-reported outcome; Q2C = every 2 cycles; 
Q3C = every 3 cycles.
a
Four PRO questionnaires will be administered in this study: the FACT-Anemia questionnaire, the EQ-5D-5L, the PGIS, and the PGIC. The participant should complete these 
questionnaires before other study procedures at required visits. No PGIC assessment at Cycle 1 Day 1. FACT‑Anemia and EQ-5D-5L should be implemented prior to 
PGIS/PGIC.
b
If magrolimab and azacitidine are administered on the same day, only one such study assessment is needed. Assessments should be performed prior to study treatment 
administration. Pretreatment assessments for the initial dose (Cycle 1 Day 1) may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment 
assessments are to be collected within 24 hours prior to study treatment administration. 
c
Bone marrow biopsy samples will be collected at Day 1 of Cycles 3 and 10.
d
An aspirate sample will be collected for response assessment, biomarker studies, and MRD assessment. Conventional cytogenetics to be tested per institutional standards. 
Response assessments may be adjusted by ± 1 week for Cycle 3 Day 1. After Cycle 3 Day 1, the window is ± 14 days.
e
An aspirate sample will be collected for biomarker studies at Day 1 of Cycles 3, 5, 7, 10, and 13. 
f
Samples will be collected at Day 1 of Cycles 3, 5, and 7 and then every 3 cycles thereafter during study treatment. Bone marrow aspirate biopsies for response assessments 
may be adjusted by ± 1 week for Cycle 3 Day 1. After Cycle 3 Day 1, the window is ± 14 days. 
g
Vital signs will be assessed prior to infusion/injection of each study treatment. Weight will be assessed on Day 1 of each cycle. Details are provided in Section 5.1.5.
h
If azacitidine and magrolimab/placebo are administered on the same day, azacitidine administration should be completed at least 1 hour before magrolimab/placebo 
administration. Azacitidine may be administered on an alternative schedule of Days 1 to 5, Day 8, and Day 9 of a 28-day cycle for flexibility and convenience. 


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Final
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Amendment 8
CONFIDENTIAL
Page 37
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Table 4.
Schedule of Assessments - Treatment Period-Magrolimab or Placebo Dosing and Study Assessments
Dose Schedule
Priming Dosing
Maintenance Dosing
Visit Window (Days)
None
± 3
± 3
Day
1
2
4
8
11
15
22
29
36
43
50
57
every 2 Weeks 
thereafter
Pregnancy testa
X
X
X Q4W
CBC with differential, platelets, reticulocytesb,c,d
Xe
X
Xe
X
X
X
X
X
X
X
X
X
X
Haptoglobin and LDHc
X
X
X
Serum or plasma chemistryb,c
X
X
X
X
X
X
X
X
Peripheral smearc,f
X
X
X
Peripheral blood sample for biomarker studiesg
X
X
X
Xh
PKg
X
X
X
Xi
Antidrug antibodiesc,j
X
X
Xi
Vital signsk
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed physical examinationb,c
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
Premedicationl
X
X
X
X
Magrolimab or placebom
Xn
Xn
X
X
X
X
X
X
X
X
X
X
Abbreviations: CBC = complete blood count; D = day; EOT = end of treatment; LDH = lactate dehydrogenase; MRD = minimal residual disease; PK = pharmacokinetic(s); 
PRO = patient-reported outcome; Q4W = every 4 weeks; WBC = white blood cell.
a
Screening pregnancy test may be used if performed within 72 hours of first dose; pregnancy tests will be conducted once every month; additional guidance is provided in 
Section  5.1.1.
b
If magrolimab and azacitidine are administered on the same day, only one such study assessment is needed. Assessments should be performed prior to study treatment 
administration. For monitoring of infusion-related reactions, please refer to Section 6.5


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c
Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected 
within 24 hours prior to study treatment administration.
d
Additional samples for CBC may be collected outside of the protocol-specified time points to ensure a WBC level ≤ 20 × 103/μL prior to each magrolimab/placebo dose 
during the first 28 days of magrolimab priming dose. Peripheral blasts should be included in the CBC assessments.
e
Hemoglobin must be checked again 3 to 6 hours after the initiation of the first and second doses of magrolimab/placebo during initial treatment. The participant should be 
transfused as clinically appropriate. Investigators should consider additional hemoglobin monitoring during the first week of treatment in participants with symptoms of 
anemia or increased risk for complications of anemia.
f
Peripheral smears will be collected predose and assessed locally.
g
Samples for PK and biomarker studies will be collected predose within 12 hours prior to study treatment administration.
h
Samples will be collected prior to first maintenance dose (Day 57), ninth (Day 169) maintenance dose, and EOT.
i
Samples will be collected predose on Day 57, Day 113, Day 169, Day 253, Day 337, and EOT.
j
When collected on the day of study treatment dosing, the blood sample for antidrug antibodies must be collected at the same time as the predose PK sample.
k
Vital signs will be assessed prior to infusion/injection of each study treatment. Weight will be assessed every 4 weeks. Details are provided in Section 5.1.5.
l
Premedication is required prior to the administration of the first 4 doses of study treatment and in case of reintroduction with repriming. Premedication for subsequent 
treatment periods may be continued based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions. In the case of a Grade 3 
infusion-related reaction, a premedication regimen for subsequent treatment periods is required (Section 6.5).
m
Magrolimab or saline placebo should not be given on consecutive days. The duration of each magrolimab/placebo infusion including flush will be 3 hours (± 30 minutes) for the 
first 3 doses of treatment, and then 2 hours (± 30 minutes) for infusions beyond the first 3 doses. All participants should be monitored for 1 hour after infusion for doses during 
the first 28 days and the repriming doses.
n
Within 24 hours prior to each of the first 2 doses of magrolimab/placebo infusion, all participants must have a documented hemoglobin  9 g/dL. Participants who do not meet 
these criteria must be transfused and have their hemoglobin rechecked to meet the minimum hemoglobin threshold prior to administering each of the first 2 doses of 
magrolimab/placebo. 


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Protocol 5F9009
Final
Gilead Sciences, Inc
Amendment 8
CONFIDENTIAL
Page 39
11 October 2022
Table 5.
Schedule of Assessments - Posttreatment
End-of-
treatment Visit
Safety Follow-up Visit/Call
(Telephone)a
Long-term 
Follow-up
Survival 
Follow-up
Within 7 Days 
after Last Dose 
or EOT Decision
30 Days
after Last 
Dose
70 Days 
after Last 
Dosek
Until Start of New 
Anticancer Therapy 
or Transformation 
to AMLb
Every 2 Months 
Until Death or 
End of Study
Visit Window
± 7 Days
± 7 Days
± 7 Days
+4 Weeks
Serum or urine pregnancy test
X
Q4Wc
Q4Wc
CBC with differential, platelet count, reticulocytes
X
Q8Wd
Serum or plasma chemistry
X
Peripheral blood for biomarker studies
X
Pharmacokinetics
X
Antidrug antibodies 
X
Bone marrow biopsy and aspirate for MRD monitoring and 
cytogeneticsd,e
X
Q8Wd
Response assessmente,f
X
Q8Wd
ECOG
X
Vital signs
X
Symptom-directed physical examination
X
PRO assessmentg
X
X
Adverse eventsh
X
X
X
Concomitant medications
X
X
X
Blood transfusioni
X
X
New anticancer therapyj
X
X
Survival follow-up
Q2M
Abbreviations: AE = adverse event; AML = acute myeloid leukemia; CBC = complete blood count; CR = complete remission; eCRF = electronic case report form; EOT = end of 
treatment; EQ-5D-5L = 5-level EuroQol 5 dimensions; FACT-Anemia = Functional Assessment of Cancer Therapy-Anemia; IWG = International Working Group; 


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Gilead Sciences, Inc
Amendment 8
CONFIDENTIAL
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MDS = myelodysplastic syndrome; MRD = minimal residual disease; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PR = partial 
remission; PRO = patient-reported outcome; QxM = every x months; QxW = every x weeks; SAE = serious adverse event.
a
If the participant experiences a treatment-related AE or an SAE (regardless of attribution), the participant must be asked to come to the site.
b
Until start of new anticancer therapy or transformation to AML, whichever comes first.
c
Collect until the end of the contraception requirement.
d
Bone marrow assessment, MRD, CBC, and response assessment should be performed until start of new anticancer therapy or transformation to AML, whichever comes first. 
Conventional cytogenetic testing (per institutional standards) is required for all participants.
e
For participants who come off the study treatment to undergo a stem cell transplant, response assessments for relapse/remission status and bone marrow aspirate results are 
required to be obtained locally and entered into the eCRF. 
f
Response assessment at EOT visit not required if performed within the last 30 days or progressive disease has been documented. After disease progression (including 
treatment failure by IWG criteria and relapse after CR or PR), response assessment will focus on evaluation of transformation to AML.
g
Paper PROs will be administered in this study: The FACT-Anemia questionnaire, the EQ-5D-5L, the PGIS, and the PGIC will be administered. The participant should 
complete these questionnaires before other study procedures at required visits. FACT-Anemia and EQ-5D-5L should be implemented prior to PGIS/PGIC. FACT-Anemia, 
EQ-5D-5L, the PGIS, and the PGIC should also be collected during long-term follow-up prior to initiation disease progression or initiation of a new anticancer therapy.
h
Report all AEs through the Safety Follow-up Visit/Call and any treatment-related SAEs thereafter.
i
Collect blood transfusions until start of new anticancer therapy.
j
Collect new anticancer therapy data following the last dose of study treatment.
k
For participants who do not initiate new anticancer therapy after the last dose. See Section 5.1.10 for adverse event reporting details.


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Final
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Table 6.
Schedule of Assessments - Repriming (Required After > 4 Weeks Have Lapsed Since the Last Dose of 
Magrolimab/Placebo Delays)
Day
1
2
3
4
5
6
7
8
11
15
22
Visit Window (Days)
-
-
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
Pregnancy test
X
CBC with differential, platelets, and 
reticulocytesa,b
X
X
X
X
X
X
X
Haptoglobin and LDH
X
X
Serum or plasma chemistrya
X
X
X
X
Peripheral smeara,c
X
X
X
Peripheral blood for biomarker studiesd
X
X
PKd
X
X
Antidrug antibodiesa
X
Vital signse
X
X
X
X
X
Symptom-directed physical examinationa
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
Blood transfusions
X
X
X
X
X
X
X
X
X
X
X
Premedicationf
X
X
X
X
Magrolimab/placebo: reprimingg
X
X
X
X
X
X
Abbreviations: CBC = complete blood count; ECOG = Eastern Cooperative Oncology Group; LDH = lactate dehydrogenase; PK = pharmacokinetic(s); PRO = patient-reported 
outcome; WBC = white blood cell.
a
Pretreatment assessments are to be collected within 24 hours prior to study treatment administration.
b
Additional samples for CBC may be collected outside of the protocol-specified time points to ensure a WBC level ≤ 20 × 103/μL for the repriming cycle.
c
Peripheral smears will be collected and assessed locally.
d
Samples for PK and biomarker studies will be collected predose within 12 hours prior to study treatment administration.


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e
Vital signs prior to infusion/injection of study treatment. Weight at Day 1. Details are provided in Section 5.1.5.
f
Premedication is required prior to the administration of the first 4 doses of study treatment and in case of reintroduction with repriming. Premedication for subsequent cycles 
may be continued based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions. In the case of a Grade 3 infusion-related 
reaction, a premedication regimen for subsequent cycles is required (Section 6.5).
g
Magrolimab or saline placebo should not be given on consecutive days. During repriming, the duration of each magrolimab/placebo infusion including flush will be 3 hours 
(± 30 minutes) for the first 3 doses of treatment and 2 hours (± 30 minutes) for infusions beyond the first 3 doses. All participants should be monitored for 1 hour after 
infusion for doses during the first 28 days and the repriming doses. After Day 22, participants should return to their original dose schedule.


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4.4.
Design Rationale
This study is a randomized, double-blind, placebo-controlled, multicenter study designed to 
evaluate the efficacy and safety of magrolimab + azacitidine compared with that of 
azacitidine + placebo in previously untreated participants with intermediate/high/very high risk 
MDS by IPSS-R. The primary efficacy endpoints of this study are CR rate and OS. This trial is 
designed to adequately determine the efficacy of magrolimab + azacitidine compared with 
azacitidine + placebo based on CR rate and OS, which are both standard approvable endpoints 
for this participant population. The CR rate of azacitidine monotherapy is well benchmarked in 
several prospective studies in higher risk MDS. Based on large historical studies, the CR rate of 
azacitidine monotherapy ranges from 6% to 17%, accounting for analysis under the IWG criteria 
(azacitidine US package insert,{Fenaux 2009, Silverman 2006}. One additional study evaluating 
azacitidine demonstrated a CR rate of 24%; however, this study also included lower risk MDS by 
IPSS-R and chronic myelomonocytic leukemia participants; the CR rate specifically in higher 
risk MDS participants was not reported {Sekeres 2017}. Given the range of CR rates and median 
OS data for azacitidine reported in large historical studies, with approximately 520 participants 
randomized in a 1:1 ratio, this study is adequately powered to show a superior CR rate or OS for 
the experimental arm compared with the control arm, assuming a CR rate of 20% in the control 
arm and a CR rate of 39% in the experimental arm, and an OS of 18 months in the control arm 
and 25.4 months in the experimental arm. Randomization will be stratified by 3 factors: 
1) geographic region (US versus ex-US sites), 2) cytogenetic risk status, and 3) bone marrow 
blast percentage. The second and third stratification factors are reported as determinants of 
response and duration for azacitidine monotherapy based on a large retrospective analysis in 
higher risk MDS {Itzykson 2011}.
4.5.
Recruitment
Approximately 200 sites in the US, Australia, Europe, and other countries as required, based on 
enrollment and study timelines, will be included in this study. A total of approximately 
520 participants will be enrolled for the 2 primary analyses of CR rate and OS.
All participants must be provided an informed consent form (ICF) describing the study with 
sufficient information for participants to make an informed decision regarding their participation. 
Participants must sign the institutional review board (IRB)/independent ethics committee (IEC) 
approved ICF prior to participation in any study-specific procedure. Data from assessments 
performed as part of SOC prior to ICF signature may be used if they are within the required 
Screening period. The participant must receive a copy of the signed and dated consent 
documents. A signed copy of the consent documents must be retained in the site file.
Once participants sign the ICF, they enter the Screening Period for the study and receive a 
unique patient identification number before any study procedures are performed. This number is 
used to identify the participant throughout the clinical study and must be used on all study 
documentation related to that participant, including if a participant is rescreened.


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Participant screening laboratory assessments may be repeated beyond the initial screening 
assessments within the 30-day Screening Period. Participants who fail screening may undergo 
repeated screening if the participant’s medical condition has changed. However, once a 
participant has been randomized, that participant cannot be rerandomized.
All participants who provide informed consent must be registered in the electronic data capture 
(EDC) and interactive voice/web/mobile response system (IXRS) systems, including any screen 
failures.
4.6.
Definitions of Enrollment and Screen Failure
Participants officially enter the Screening Period following provision of informed consent. After 
signing the ICF, eligible participants must be randomized within 30 days. Treatment will start 
within 72 hours after randomization.
A participant is defined as enrolled in the study when that participant has been randomized.
A screen failure is a consented participant who has been deemed ineligible on the basis of 1 or 
more eligibility criteria or who has withdrawn consent prior to randomization. Screen failures 
may be rescreened if the participant’s medical condition has changed.
4.7.
Inclusion Criteria
To be included in this study, each individual must satisfy all the following criteria:
1) Participants with MDS defined according to World Health Organization classification, with 
an IPSS-R {Greenberg 2012} prognostic risk category of intermediate, high, or very high 
risk. Note: participants who require AML-like therapy are not eligible. 
2) White blood cell (WBC) count ≤ 20 × 103/μL prior to randomization. If the participant’s 
WBC is > 20 × 103/μL prior to randomization, the participant can be randomized, assuming 
all other eligibility criteria are met. Of note, while this does not impact eligibility, please 
ensure that the WBC is ≤ 20 × 103/μL prior to the first dose of study treatment and prior to 
each magrolimab/placebo dose for priming doses of magrolimab.
a) Participants can be treated with hydroxyurea (up to 4 g/day) throughout the study or prior 
to randomization to reduce the WBC to ≤ 20 × 103/μL to enable eligibility and 
magrolimab dosing. Oral etoposide (up to 200 mg orally per day) may be given as an 
alternative to hydroxyurea for participants who are intolerant to hydroxyurea or cannot 
achieve sufficient WBC lowering on hydroxyurea.
3) Participant has provided informed consent.
4) Participant is willing and able to comply with clinic visits and procedures outlined in the 
study protocol.
5) Male or female, age ≥ 18 years.
6) Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.


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7) Willing to undergo blood transfusions as deemed clinically necessary.
8) Pretreatment blood cross-match including ABO (any of the 4 blood groups A, B, AB, and O 
comprising the ABO system)/Rh (Rhesus factor), DAT (direct antiglobulin test), and 
phenotyping or genotyping completed (as detailed in Section 5.1.4).
9) Biochemical indices within the ranges shown below:
b) Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine 
aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper limit of 
normal (ULN)
c) Total bilirubin ≤ 1.5 × ULN or 3.0 × ULN and primarily unconjugated if participant has a 
documented history of Gilbert's syndrome or genetic equivalent
d) Serum creatinine ≤ 1.5 × ULN or calculated glomerular filtration rate (GFR) 
≥ 40 mL/min/1.73 m2
10) All participants must have a documented hemoglobin ≥ 9 g/dL within 24 hours prior to the 
first 2 doses of magrolimab/placebo infusion. Participants who do not meet these criteria 
must be transfused and have their hemoglobin rechecked to meet the minimum hemoglobin 
threshold prior to administering each of the first 2 doses of magrolimab/placebo. 
Transfusions are allowed in order to meet hemoglobin eligibility (see Section 7.10.1.1).
11) Female participants of childbearing potential must not be nursing or planning to be pregnant 
and must have a negative urine or serum pregnancy test within 30 days before randomization 
and within 72 hours before the first administration of study treatment.
12) Male participants and female participants of childbearing potential who engage in 
heterosexual intercourse must agree to use protocol-specified method(s) of contraception as 
described in Appendix G. 
13) Willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies 
(trephines), unless not feasible as determined by the Investigator and discussed with the 
Sponsor. 
4.8.
Exclusion Criteria
If an individual meets any of the following criteria, he or she is ineligible for this study:
1) Prior treatment with CD47 or SIRPα-targeting agents.
2) Prior therapy for the treatment of MDS with an IPSS-R prognostic risk category of 
intermediate, high or very high risk (excluding hydroxyurea or oral etoposide), prior 
treatment with hypomethylating agents and/or low dose cytarabine. NOTE: Localized 
noncentral nervous system (CNS) radiotherapy, erythroid and/or myeloid growth factors, 
previous hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists for 
prostate cancer, and treatment with bisphosphonates and receptor activator of nuclear factor 
kappa-B ligand (RANKL) inhibitors are not criteria for exclusion. Prior lenalidomide is also 
not exclusionary.


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3) Immediately eligible for an allogeneic SCT, as determined by the Investigator, with an 
available donor.
4) Contraindications to azacitidine, including advanced malignant hepatic tumors or known 
hypersensitivity to azacitidine or mannitol.
5) Known inherited or acquired bleeding disorders.
6) Previous SCT within 6 months prior to randomization, active graft-versus-host disease, or 
requiring transplant-related immunosuppression.
7) Clinical suspicion of active CNS involvement by MDS.
8) Significant medical diseases or conditions, as assessed by the Investigators and Sponsor, that 
would substantially increase the risk benefit ratio of participating in the study. This includes, 
but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, 
uncontrolled diabetes mellitus, significant active infections, and congestive heart failure 
New York Heart Association Class III-IV.
9) Second malignancy, except treated basal cell or localized squamous skin carcinomas, 
localized prostate cancer, or other malignancies for which participants are not on active 
anticancer therapies and have had no evidence of active malignancy for at least ≥ 1 year.
10) History of psychiatric illness or substance abuse likely to interfere with the ability to comply 
with protocol requirements or give informed consent.
11) Pregnancy or active breastfeeding.
12) Known active or chronic hepatitis B or C infection or HIV infection in medical history. 
13) Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV), and/or HIV following 
testing at Screening:
a) Participants who test positive for hepatitis B surface antigen (HBsAg). Participants who 
test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by 
quantitative polymerase chain reaction (PCR) for confirmation of active disease.
b) Participants who test positive for HCV antibody. These participants will require HCV 
RNA by quantitative PCR for confirmation of active disease.
c) Participants who test positive for HIV antibody.
d) Participants not currently on antiviral therapy and who have an undetectable viral load in 
the prior 3 months may be eligible for the study.


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4.9.
Lifestyle Restrictions
4.9.1.
Female Participants
Female participants of childbearing potential who have a negative serum or urine pregnancy test 
before enrollment must agree to use one of the highly effective forms of contraception described 
in Appendix G.
4.9.2.
Male Participants
A male participant who is sexually active with a woman of childbearing potential and has not 
had a vasectomy must agree to use contraception described in Appendix G during the study 
treatment period.


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5.
STUDY CONDUCT
It is anticipated that this study will take up to 6 years to complete, assuming 22 months for 
enrollment, plus 1 month screening, 6 or more cycles of study treatment, 30 day and 70 day (or 
until administration of novel anticancer therapy, whichever is earlier) safety follow-ups for each 
participant, and up to 4 years of follow-up after the last participant is randomized.
During the study, study assessments will be performed as listed by study visit in Section 4.3 and 
described in the current section.
5.1.
Study Procedures
5.1.1.
Pregnancy Test
Pregnancy tests are required only for female participants of childbearing potential. Note that a 
woman is considered to be of childbearing potential, ie, fertile, following menarche and until 
becoming postmenopausal (defined as no menses for 12 months without an alternative medical 
cause) unless permanently sterile. Permanent sterilization methods include hysterectomy, 
bilateral salpingectomy, and bilateral oophorectomy. A high follicle-stimulating hormone (FSH) 
level in the postmenopausal range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy. However, in the absence of 
12 months of amenorrhea, a single follicle-stimulating hormone measurement is insufficient. A 
urine or serum pregnancy test is required at Screening and within 72 hours before study 
treatment administration on Cycle 1 Day 1. The Cycle 1 Day 1 pregnancy test does not need to 
be repeated if the Screening pregnancy test was performed within the 72 hours before study 
treatment administration. Pregnancy tests will also be required monthly and posttreatment until 
the end of the contraception requirement.
5.1.2.
Complete Blood Counts
Samples for complete blood counts (CBCs) should be collected per the schedules of assessments 
in Section 4.3. WBC count needs to be ≤ 20 × 103/μL prior to randomization and prior to each 
magrolimab/placebo dose for the first 28 days of magrolimab/placebo dosing and Repriming 
Cycle (see Section 4.7, Inclusion Criterion 2), for details). Additional samples for CBC may be 
collected outside of the protocol-specified time points to ensure WBC level ≤ 20 × 103/μL for the 
first cycle and Repriming Cycle.
All participants must have a documented hemoglobin ≥ 9 g/dL within 24 hours prior to the first 
2 doses of magrolimab/placebo infusion. Participants who do not meet these criteria must be 
transfused and have their hemoglobin rechecked to meet the minimum hemoglobin threshold 
prior to administering each of the first 2 doses of magrolimab/placebo.


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5.1.3.
Peripheral Blood Smear Assessment
Peripheral smears should be collected per the schedules of assessments and assessed for standard 
cell morphology. These samples should be collected from the arm contralateral to the arm being 
used for drug infusion/injection, if possible. All other observed findings should be reported 
according to local laboratory hematopathology standard procedures. Peripheral smears will be 
assessed locally (see also Section 7.10.1.3).
5.1.4.
Type and Screen and Direct Antiglobulin Test
Magrolimab may interfere with RBC phenotyping due to expected coating of the RBC 
membrane. Due to the risk of developing anemia, and because magrolimab may make 
phenotyping difficult, ABO/Rh type, antibody screen, blood phenotyping or genotyping, and 
DAT need to be performed at screening before exposure to magrolimab, as described in 
Section 7.10.1.1. 
Red blood cell genotyping (instead of an extended RBC phenotyping) must be performed if a 
participant received any RBC or whole blood transfusion within the previous 3 months (unless 
the laboratory has availability for special techniques for performing phenotyping for participants 
with a recent transfusion). RBC genotyping instead of extended RBC phenotyping is acceptable 
for any participant. Red blood cell phenotyping/genotyping, ABO type, and DAT need not be 
repeated if results dated before screening are available. Antibody screen need not be repeated if 
results dated before screening are available, unless the participant was transfused since that time. 
Results must be available before the first dose of magrolimab.
5.1.5.
Vital Signs
Vital signs should include heart rate, respiratory rate, oxygen saturation, blood pressure, 
temperature, and weight. Height should be recorded during Screening only. Weight should be 
recorded during Screening and on Day 1 of each cycle. Vital signs are to be recorded prior to 
infusion/injection of each study treatment at the visits specified in the schedules of assessments 
in Section 4.3.
5.1.6.
Physical Examination
Complete physical examination should be performed at Screening. Thereafter, symptom-directed 
physical examinations are acceptable and may also include routine examination of the skin 
(including fingers, toes, and ears) and neurologic system. Symptom-related physical examination 
should be completed on Day 1 of each cycle or as clinically indicated.
5.1.7.
Electrocardiogram
A single electrocardiogram (ECG) will be performed at Screening.


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5.1.8.
Bone Marrow Assessments
Bone marrow assessments (including aspirate and core/trephine biopsy) are required for response 
assessments (refer to Section 5.3 and Appendix B), including conventional cytogenetic analysis 
per institutional standards. In addition, bone marrow specimens may be used for biomarker 
studies, MRD monitoring, 
, and biobanking. Minimal residual disease 
testing will be performed by a central laboratory. Bone marrow aspirate slides for response 
assessment will also be sent to a central laboratory. Details for preparation and distribution of 
aspirate and biopsy/trephine specimens to the testing laboratories will be provided in the 
Laboratory Manual for this study.
Bone marrow assessments include collection of both aspirate and core biopsy (trephine) 
specimens at each time point according to the schedules of assessments in Section 4.3.
Bone marrow biopsies for response assessments may be adjusted by ± 1 week for Cycle 3 Day 1. 
After Cycle 3 Day 1, the window is ± 14 days.
Response assessment at End-of-Treatment (EOT) Visit is not required if performed within the 
last 30 days or progressive disease has been documented. Bone marrow response assessments 
should continue during long-term follow-up approximately every 8 weeks until transformation to 
AML is documented or start of new anticancer therapy, whichever comes first. For participants 
who come off the study treatment to receive an SCT, follow-up for response assessment and 
collection of SOC bone marrow biopsy/aspirate results will continue until documented relapse or 
progressive disease occurs. After documented relapse or progressive disease, follow-up for 
response assessment and collection of SOC bone marrow biopsy/aspirate results will continue 
until transformation to AML occurs or start of new anticancer therapy, whichever comes first.
5.1.9.
Patient-reported Outcomes
Four patient-reported outcome (PRO) instruments will be administered in this study: the 
Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia), the 5-level EuroQol 
5 dimensions (EQ-5D-5L), the Patient Global Impression of Severity (PGIS), and the Patient 
Global Impression of Change (PGIC). The participant should complete these questionnaires 
before any other study procedures at required visits.
5.1.9.1.
FACT-Anemia
The FACT-Anemia questionnaire is a 47-item instrument used to assess anemia- and 
fatigue-related quality of life for patients with cancer and chronic disease. A sample is provided 
in Appendix C. This instrument consists of 5 subscales, including physical well-being, emotional 
well-being, functional well-being, social well-being, and anemia symptoms. Each subscale 
measures items on a 5-point Likert scale from 0 to 4, where 0 = not at all and 4 = very much. The 
FACT-Anemia instrument has demonstrated good validity and reliability in the general 
population as well as in patients with cancer {Cella 2012, Revicki 2013}.
CCI


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5.1.9.2.
EQ-5D-5L
The EQ-5D-5L is an instrument for use as a measure of health outcome {EuroQol Research 
Foundation 2017, Janssen 2013}. The EQ-5D-5L consists of 2 sections: the EQ-5D descriptive 
system and the EuroQol visual analogue scale (EQ VAS). A sample is provided in Appendix D.
The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight 
problems, moderate problems, severe problems, and extreme problems. The participant is asked 
to indicate his/her health state by ticking the box next to the most appropriate statement in each 
of the 5 dimensions. This decision results in a 1-digit number that expresses the level selected for 
that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that 
describes the participant’s health state.
The EQ VAS records the participant’s self-rated health on a vertical visual analogue scale, where 
the endpoints are labeled “The best health you can imagine” and “The worst health you can 
imagine.” The EQ VAS can be used as a quantitative measure of health outcome that reflects the 
participant’s own judgment.
5.1.9.3.
PGIS/PGIC
The PGIS and PGIC assessments are both single-item assessments used to demonstrate 
sensitivity and meaningful change thresholds and bolster the validity of selected PRO 
assessments {Department for Health and Human Services (DHHS) 2018}. A sample of these 
questionnaires is provided in Appendix E.
5.1.10.
Adverse Events
At each visit, the following AEs are to be reported using the applicable electronic case report 
form (eCRF; Section 10.2.3.1): 

After informed consent, but prior to initiation of study treatment, all AEs related to 
protocol-mandated procedures. 

After the first dose of study treatment, all AEs observed by the Investigator or reported by 
the participant that occur through 30 days after last dose of study treatment. Adverse events 
occurring after 30 days of last dose of study treatment will be reported until either 70 days 
after the last dose or until the initiation of new anticancer therapy (including SCT), 
whichever is earlier.
Details of adverse event reporting can be found in Section 7.2.


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5.1.11.
Concomitant Medications
All concomitant medications, including all prescription medications, over-the-counter 
medications, herbal supplements, and IV medications and fluids, taken by a participant within 
30 days before the first dose of study treatment and while on study are to be documented. 
Changes in baseline concomitant medication information is to be collected after informed 
consent through the end of 70-day Safety Follow-up Period or until the initiation of new 
anticancer therapy (including SCT), whichever is earlier. Concomitant medication associated 
with procedure-related AEs will be captured from the time of informed consent and onward. 
Information to be collected includes therapy name, indication, dose, unit, frequency, route, start 
date, and stop date and must be reported using the applicable eCRF.
5.1.11.1
COVID-19 Vaccine
There are no substantial safety data regarding the concomitant administration of the COVID-19 
vaccines and magrolimab. There is no contraindication to the COVID-19 vaccine with 
magrolimab. Participants are allowed to receive the COVID‑19 vaccine, and study visits should 
continue as planned if vaccination occurs while the participant is on the study. Given that 
immunocompromised individuals on myelosuppressive treatment may have attenuated responses 
to vaccines, Investigators should, after consultation with local guidelines, consider delay of 
COVID-19 vaccination for participants (receiving magrolimab/placebo + azacitidine therapy) 
until recovery of a neutropenic individual’s absolute neutrophil count (ANC) and determine the 
ideal timing of the subsequent dose of vaccine based on count recovery. If participants are 
neutropenic, Investigators may use clinical judgment in determining the timing of the COVID-19 
vaccine. Investigators should document vaccinations. Investigators should notify participants of 
the risks of delaying the COVID-19 vaccination and document this along with any mitigation 
strategies for preventing COVID-19 infection in the source. Investigators should follow local 
guidelines for concomitant administration of the COVID-19 vaccines with the study drug(s).
5.2.
Safety Assessments
Analytes to be assessed by the local laboratory or specialty laboratories at Screening are 
presented in Table 7. See Appendix F for ECOG assessment information.


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Table 7.
Laboratory Analyte Listing (To Be Performed at Screening)
Chemistry 
(Serum or Plasma)
Hematology
Urinalysis
Other Laboratory 
Measurements
Sodium
Potassium
Chloride
Bicarbonate
Total protein
Albumin
Calcium
Magnesium
Phosphorus
Glucose
BUN or urea
Creatinine
Uric acid
Total bilirubin
Direct bilirubin
Indirect bilirubin
LDH
AST (SGOT)
ALT (SGPT)
Alkaline phosphatase
RBC
Hemoglobin
Hematocrit
Platelets
WBC
Neutrophils
Eosinophils
Basophils
Lymphocytes
Monocytes
Reticulocytes
Haptoglobin
PT
INR
aPTT or PTT
Peripheral blood smear
RBC
Glucose
Protein
Urine pH
Ketones
Bilirubin
Urine specific gravity
Pregnancy
Biomarker studiesa
Blood phenotyping or 
genotyping
Type and screen (ABO/Rh), 
DAT
Cytogenetics
MRDa
Hepatitis B and hepatitis C 
assessments: HBsAg, 
anti-HBc, HCV antibody; 
HBV DNA and HCV RNA 
as required
HIV antibody
Abbreviations: ABO = any of the 4 blood groups A, B, AB, and O comprising the ABO system; ALT = alanine aminotransferase; 
anti-HBc = antibody against hepatitis B core antigen; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; DAT = direct antiglobulin test; HBV = hepatitis B virus; HCV = hepatitis C virus; 
HBsAg = hepatitis B surface antigen; INR = international normalized ratio; LDH = lactate dehydrogenase; MRD = minimal 
residual disease; PT = prothrombin time; PTT = partial thromboplastin time; RBC = red blood cell; Rh = Rhesus factor; 
SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase; WBC = white blood cells.
Note: Refer to Section 4.3 for collection time points.
a
These assays will be performed at a central laboratory.
Analytes to be assessed by the local laboratory or specialty laboratories during the study are 
presented in Table 8.


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Table 8.
Laboratory Analyte Listing (To Be Performed During the Study)
Chemistry 
(Serum or Plasma)
Hematology
Other Laboratory Measurements
Sodium
Potassium
Chloride
Bicarbonate
Albumin
Glucose
BUN or urea
Creatinine
Total bilirubin
Direct bilirubin
Indirect bilirubin
LDHb
AST (SGOT)
ALT (SGPT)
Alkaline phosphatase
RBC
Hemoglobin
Platelets
WBC
Neutrophils
Lymphocytes
Reticulocytes
Haptoglobinb
Peripheral blood smear
Peripheral blasts
Pregnancy
Biomarker studiesa
Pharmacokineticsa
Antidrug antibodiesa
Cytogenetics
MRDa
Abbreviations: ABO = any of the 4 blood groups A, B, AB, and O comprising the ABO system; ALT = alanine aminotransferase; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; C2D1 = Cycle 2 Day 1; DAT = direct antiglobulin test; 
LDH = lactate dehydrogenase; MRD = minimal residual disease; RBC = red blood cell; Rh = Rhesus factor; SGOT = serum 
glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase; WBC = white blood cell.
Note: Refer to Section 4.3 for collection time points.
a
These assays will be performed at a central laboratory.
b
Please refer to Table 3 for LDH and Haptoglobin collection time points during treatment. Collection is not required after 
C2D1 unless participant is repriming.
5.3.
Efficacy Assessments
Clinical response will be assessed using the guidelines in Appendix B, which are based primarily 
on IWG criteria {Cheson 2003, Cheson 2006}, as described in Appendix B.
Response assessments will be done in conjunction with bone marrow assessments, according to 
the Schedule of Assessments (Section 4.3). Accompanying laboratory results ± 2 weeks from the 
protocol-specified bone marrow efficacy assessment can be used to support an efficacy 
assessment of CR. Response assessments are scheduled on Day 1 of Cycles 3, 5, and 7 and then 
every 3 cycles thereafter during study treatment. These supporting laboratory results will be 
entered into the clinical database. Absolute neutrophil count, platelets, and hemoglobin, that 
reflect CR or PR per IWG 2006 criteria (hemoglobin ≥ 11 g/dL, platelets ≥ 100  109/L, 
neutrophil ≥ 1.0  109/L, peripheral blast = 0%; Appendix B) must be from CBCs collected on 
the same day. If a participant achieves a CR, subsequent bone marrow biopsies and response 
assessments are still required to be performed as per the Schedule of Assessments (Section 4.3). 
Per Schedule of Assessments during the treatment period (Table 3, and Table 4), treatment 
cycles are associated with azacitidine dosing. Therefore if azacitidine is delayed, all assessments 
per Table 3 (e.g., bone marrow aspirate biopsy and MDS disease assessment) will also be 
delayed until resumption of azacitidine dosing.


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Slides used for MDS disease response assessments may be collected by the Sponsor for 
 
independent pathology review.
Response assessment will be obtained at the EOT Visit, unless a prior response assessment has 
been performed within the last 30 days or progressive disease has been documented. Response 
assessments should continue during long-term follow-up approximately every 8 weeks until 
transformation to AML is documented or start of new anticancer therapy, whichever comes first. 
For participants who come off the study treatment to receive an SCT, follow-up for response 
assessment and collection of SOC bone marrow biopsy/aspirate and CBC results will continue 
until documented relapse or progressive disease occurs. After documented relapse or progressive 
disease, follow-up for response assessment and collection of SOC bone marrow biopsy/aspirate 
results will continue until transformation to AML occurs or start of new anticancer therapy, 
whichever comes first.
5.4.
Pharmacokinetics
PK samples will be collected as described in Section 4.3, and evaluated for magrolimab 
concentrations. Serum magrolimab assessment will be done using a validated assay.
Azacitidine PK assessment may be conducted using residual samples used for magrolimab PK 
and ADA analysis. These samples may also be used for pharmacodynamics analyses related to 
magrolimab in combination with azacitidine. This could include using leftover serum for 
 alternative PK assay development and analysis.
5.5.
Immunogenicity (Antidrug Antibodies)
Peripheral blood for immunogenicity assessments for ADA against magrolimab will be collected 
as described in Section 4.3. When collected on the day of magrolimab/placebo dosing, the blood 
sample must be collected at the same time as the predose PK specimen. Neutralizing antibodies 
to magrolimab will also be assessed for samples that test positive for ADA.
5.6.
Pharmacodynamics and Biomarker Assessments
5.6.1.
Biomarker Blood Samples
Biomarker studies will be performed on peripheral blood samples to study the biological activity 
of magrolimab in combination with azacitidine. These studies may include, but are not limited 
to, investigations of plasma cytokine levels, characterization of circulating immune cells, 
quantification of circulating normal and tumor DNA levels, and other studies. Samples for 
biomarker studies in the peripheral blood will be collected per Section 4.3.
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5.6.1.1.
Measurement of Plasma Cytokines
Cytokine release by immune cells is one surrogate measure of immune cell activation (including 
T cells and macrophages). Since magrolimab activates both macrophages and T cells, it is 
hypothesized that a specific cytokine profile relating to immune cell activation will correlate 
with clinical response to therapy. Fluorescence-based platforms allow for a high-throughput 
analysis of a multitude of cytokines and chemokines with high sensitivity {Swartzman 1999}. A 
predefined multiplex panel of human cytokines will be measured from a small thawed vial of 
plasma, detecting and quantifying the soluble proteins and peptides that help control cellular 
function. The observed systemic biochemical changes in the blood may provide a further 
correlate with tumor progression and therapeutic response and help provide a much broader 
understanding of disease. Cytokines involved in macrophage, dendritic cell, and T-cell 
activation/repression will be specifically interrogated.
5.6.1.2.
Characterization of Circulating Immune Cells
In nonclinical studies, macrophage-mediated phagocytosis of tumor cells by an anti-CD47 
antibody leads to cross-presentation of antigens and subsequent T-cell activation {Tseng 2013}. 
It is therefore predicted that magrolimab administration may lead to T-cell activation in 
participants. Peripheral blood samples will be collected, and T-cell activation/repression 
markers/studies may be performed by flow cytometry, mass cytometry, in vitro T-cell activation 
assays, and/or T-cell receptor sequencing. Additional peripheral blood mononuclear cells, serum, 
and plasma at the specified time points will also be cryopreserved and biobanked for 
 
analyses.
5.6.2.
Minimal Residual Disease Monitoring
Minimum residual disease monitoring has become a powerful prognostic factor that is beginning 
to play a central role in the treatment of participants with MDS and AML both in the 
pretransplant and posttransplant settings. In multiple large studies of newly diagnosed 
participants with MDS and AML, as well as in advanced MDS participants who achieved CR, 
MRD positivity posttherapy was an independent poor prognostic factor and a predictor of relapse 
{Buccisano 2012, Freeman 2013, Platzbecker 2018, Sievers 2003}. In a large prospective study 
of MRD monitoring in both MDS and AML who achieved CR and received postremission 
azacitidine, the 12-month relapse-free survival (RFS) for those who were MRD positive was 
46% compared with 88% in participants who were MRD-negative. In another study of MDS 
participants who received hematopoietic SCT, participants who were MRD positive had a 1-year 
relapse rate of 35% compared with just 5% in the MRD-negative group {Pavlu 2019}. Several 
methods for MRD monitoring have been utilized in MDS, including 1) multiparameter flow 
cytometry for detection of aberrant hematopoietic surface antigens, 2) molecular monitoring of 
leukemia-specific mutational burden, and 3) cytogenetic monitoring of leukemia-associated 
chromosomal abnormalities.
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5.7.
Discontinuation or Withdrawal
5.7.1.
Permanent Discontinuation of Treatment
The participant’s health and welfare are the primary consideration in any determination to 
discontinue study treatment. In general, participants are expected to remain on study treatment 
until at least completion of Cycle 6, but participants may decline to continue receiving study 
treatment at any time during the study, although they will continue follow-up study visits unless 
they withdraw completely from the study (Section 5.7.2).
Reasons for discontinuation of study treatment may include, but are not limited to, the following:

Disease progression (including treatment failure by IWG criteria or relapse after PR/CR), 
with confirmation in subsequent assessment at least 4 weeks apart (i.e., disease worsening 
compared with the previous assessment)

Unacceptable toxicity

Loss of clinical benefit

Clinically significant change in the participant’s status that precludes further treatment 
(e.g., pregnancy or other AEs)

Participant request, with or without a stated reason

SCT

Investigator or treating physician decision in the absence of any of the above
This decision to discontinue study treatment would not require approval from the 
Sponsor/Medical Monitor. Participants who discontinue both magrolimab/placebo and 
azacitidine but continue in a response or are achieving clinical benefit will continue to be 
followed on study for response assessments to ascertain relapse and for long-term survival. If 
magrolimab/placebo is discontinued for reasons other than disease progression, treatment with 
azacitidine may continue with corresponding assessments until progression, toxicity, or death.
Although disease progression (including treatment failure by IWG criteria or relapse after 
PR/CR) is considered a sufficient reason for discontinuing a participant from study treatment, 
given the delayed treatment benefit commonly seen in immune therapies, the Investigator is 
advised to continue to treat the participant until the confirmation of disease progression through a 
subsequent response assessment at least 4 weeks apart (i.e., disease worsening compared with the 
previous assessment), or until the Investigator considers the study treatment to be no longer 
clinically beneficial to the participant or the change of disease state renders the participant 
unacceptable for further treatment in the judgment of the Investigator. All participants must be 
followed through completion of all study treatment.


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Participants who discontinue study treatment are to return for an EOT Visit for evaluation of 
safety within 7 days of their last dose or the decision to end study treatment. In addition, 
participants are to have Safety Follow-up telephone calls 30 days (± 7 days) after their last dose 
of study treatment. Participants are also to have Safety Follow-up telephone calls 70 days 
(± 7 days) after their last dose of study treatment or initiation of new anticancer therapy, 
whichever is earlier. When a serious AE (SAE) or treatment-related AE is reported during the 
telephone call, the participant should come to the clinic for physical examination and blood tests, 
if clinically needed. Follow-up for ongoing SAEs or treatment-related AEs after the Safety 
Follow-up Visit/Call will stop if a participant begins another anticancer therapy.
All participants who discontinue study treatment will participate in long-term follow-up for 
disease response until documented transformation to AML or start of new anticancer therapy, 
whichever occurs first, unless the participant withdraws consent for such follow-up or withdraws 
completely from the study (Section 5.7.2). 
For participants who come off the study treatment to receive an SCT, follow-up for response 
assessment and collection of SOC bone marrow biopsy/aspirate and CBC results will continue 
until documented relapse or progressive disease occurs. After documented relapse or progressive 
disease, follow-up for response assessment and collection of SOC bone marrow biopsy/aspirate 
results will continue until transformation to AML occurs or start of new anticancer therapy, 
whichever occurs first. When considering SCT, note that no significant magrolimab-related 
transplant complications have been observed in participants who have achieved a response and 
undergone SCT in an ongoing magrolimab study in AML and MDS (Study 5F9005). However, a 
4-week washout period for magrolimab is recommended prior to start of conditioning treatment 
for SCT. 
All participants will be followed for survival, unless the participant explicitly indicates a desire 
to forego survival follow-up in writing to their study investigator, until death, withdrawal of 
consent, loss to follow-up, or study termination, whichever occurs first. For any participant who 
dies during this follow-up period, the immediate cause of death must be reported to the Sponsor. 
For participants who are lost to follow-up or withdraw consent, study staff may use public 
records (eg, public health records) to obtain information about survival status where allowable by 
local regulation.
The assessments to be performed at each of the posttreatment visits are listed in Table 5 and 
Table 6. 
5.7.2.
Withdrawal from Study
Participants have the right to withdraw completely from the study and end study data collection 
at any time and for any reason without prejudice to their future medical care. Participants may 
decline to continue receiving study treatment and/or other protocol-required therapies or 
procedures at any time during the study but are encouraged to continue follow-up study visits 
and study data collection per Section 4.3, if possible. The Investigator is to discuss with the 
participant the appropriate procedures for withdrawal from the study. The Investigator or 
Sponsor has the right to discontinue any participant from study participation.


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Reasons for participant withdrawal from study participation may include, but are not limited to, 
the following:

Death

Withdrawal of consent

Lost to follow-up

Study termination
For participants who are lost to follow-up or withdraw consent, study staff may use public 
records (eg, public health records) to obtain information about survival status where allowable by 
local regulation.
5.7.3.
Replacement of Participants
Given that the primary analysis will be conducted in an intent-to-treat (ITT) population, 
participants who are randomized will not be replaced.
5.7.4.
Participants Lost to Follow-up
If the participant is lost to follow-up, efforts to obtain follow-up should be appropriately 
documented as such in the participant’s source documentation. If repeated attempts (at least 3) to 
obtain follow-up for the participant by telephone are unsuccessful, then a certified letter should 
be mailed to the permanent home address informing the participant of the need for follow-up. If 
the participant does not respond after delivery of the certified letter, no further attempts to obtain 
follow-up will occur. For participants who discontinue from the study prior to completion of all 
protocol-required visits for study assessment or survival follow-up as described in Section 4.3, 
the Investigator may search publicly available records (where permitted by local laws and 
regulations) to ascertain survival status.
5.8.
Poststudy Care
Upon withdrawal from study treatment, participants will receive the care upon which they and 
their physicians agree. Participants will be followed for survival and AEs as specified in Table 5 
and Table 6.
5.9.
End of Study
All Participants: The end of the entire study for all participants is defined as the date on which 
the last participant remaining on study completes the last study visit/call or when the Sponsor 
decides to end the study. Gilead Sciences, Inc. reserves the right to terminate the study at any 
time for any reason (including safety).
Individual Participants: Participants are considered to have completed study participation 
altogether when they are no longer followed for disease progression (including treatment failure 
by IWG criteria or relapse after PR/CR), transformation to AML, or survival.


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6.
STUDY TREATMENT
6.1.
Description of Products
The active pharmaceutical ingredient of magrolimab is Hu5F9-G4 (GS-4721), a humanized IgG4 
monoclonal antibody of the IgG4 kappa isotype containing a Ser Pro substitution in the hinge 
region (position 228) of the heavy chain to reduce Fab-arm exchange. It comprises a disulfide 
linked glycosylated tetramer consisting of 2 identical 444 amino acid heavy gamma chains and 
2 identical 219 amino acid kappa light chains. Magrolimab targets the human CD47 antigen. 
Magrolimab drug product is a sterile, clear, colorless, preservative-free liquid intended for IV 
infusion.
Azacitidine is a nucleoside metabolic inhibitor. Azacitidine is a white to off-white solid supplied 
in a sterile form for reconstitution as a suspension for SC injection or (in the US only) 
reconstitution as a solution with further dilution for IV infusion.
Table 9 provides a summary of the study treatment in this study.
Table 9.
Investigational Interventions Used in This Study
Product
Section
Dose and Frequency
Route
Duration
Manufacturer
Magrolimab 
(Hu5F9-G4) 
(GS-4721)
6.2
Priming Dose:

1 mg/kg on Days 1 and 4

15 mg/kg on Day 8

30 mg/kg on Days 11, 15, 
followed by weekly 
administration for 5 doses (on 
Days 22, 29, 36, 43, and 50)
Maintenance Dose:

30 mg/kg on Day 57 and 
30 mg/kg every 2 weeks thereafter
IV
Until 
progression, 
relapse, loss of 
clinical benefit, 
or unacceptable 
toxicities
Gilead 
Sciences, Inc.
Placebo 
(saline)
NA
Mirrors magrolimab dosing schedule
IV
Until 
progression, 
relapse, loss of 
clinical benefit, 
or unacceptable 
toxicities
Provided by 
site
Azacitidine
6.3
28-day cycles:
75 mg/m2 IV or SCa on Days 1–7 (or 
Days 1–5, 8, and 9)
SC or 
IVa
At least 6 cycles 
and until 
progression, 
relapse, loss of 
clinical benefit, 
or unacceptable 
toxicities
Marketing 
Authorization 
Holder, NDA
Abbreviations: IV = intravenous; NA = not applicable; NDA = new drug application; SC = subcutaneous.
a
Azacitidine will be administered according to region-specific drug labeling.




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The dose of each study treatment will be calculated based on actual weight at enrollment (using 
weight obtained either at Screening or on Cycle 1 Day 1) and remains constant throughout the 
study unless there is a > 10% change in weight from baseline. Dose modifications for changes in 
body weight ≤ 10% may be made according to local institutional guidelines. In the event that a 
dose is modified due to a > 10% weight change, the weight on which the new dose is based, will 
become the new baseline weight.
When both study drugs are given on the same visit day, magrolimab/placebo will be 
administered at least 1 hour after the completion of azacitidine administration.
When administered IV, the total dose of azacitidine (diluted in a 50 to 100 mL infusion bag of 
either 0.9% sodium chloride injection or lactated Ringer’s injection solution) is infused over a 
period of 10 to 40 minutes (refer to the azacitidine prescribing information references for 
detailed instructions for preparation and administration).
The duration of each magrolimab/placebo infusion including flush will be 3 hours (± 30 minutes) 
for the 3 doses of treatment, and then 2 hours (± 30 minutes) for infusions beyond the first 
3 doses. The reduced infusion time to 2 hours is utilized based on prior data demonstrating 
majority CD47 RO on peripheral blood cells, thus mitigating anticipated RBC toxicities from 
magrolimab.
The first dose of magrolimab/placebo should be administered within 72 hours after 
randomization. Magrolimab/placebo doses will be given twice weekly during priming and 
escalation (2 weeks), with a window of ± 3 days for each dose; however, magrolimab/placebo 
doses are not to be given on consecutive days. If additional delay is needed to ensure a WBC of 
≤ 20 × 103/μL, please contact the Sponsor’s Medical Monitor.
During the first 28 days of treatment (Day 1, Day 4, Day 8, Day 11, Day 15, and Day 22), WBC 
count must be ≤ 20 × 103/μL prior to each magrolimab dose. Participants with WBC 
> 20 × 103/μL can be treated with hydroxyurea (up to 4 g/day) throughout the study to reduce the 
WBC to ≤ 20 × 103/μL. Oral etoposide (up to 200 mg orally per day) may be given as an 
alternative to hydroxyurea for participants who are intolerant to hydroxyurea or cannot achieve 
sufficient WBC lowering on hydroxyurea. 
Within 24 hours prior to each of the first 2 doses of magrolimab/placebo infusion, all participants 
must have a documented hemoglobin  9 g/dL. Participants who do not meet these criteria must 
be transfused and have their hemoglobin rechecked to meet the minimum hemoglobin threshold 
prior to each of the first 2 doses of magrolimab/placebo. Hemoglobin must be checked again 3 to 
6 hours after the initiation of the first and second doses of magrolimab/placebo during initial 
treatment. The participant should be transfused as clinically appropriate. Investigators should 
consider additional hemoglobin monitoring during the first week of treatment in participants with 
symptoms of anemia or increased risk for complications of anemia.
All participants should be monitored hourly during infusion and for 1 hour after infusion for 
doses during the first 28 days and the repriming doses. Participants should be monitored 
(including measurement of vital signs, as clinically appropriate) for signs and symptoms of 
infusion-related reactions, which have been observed in previous magrolimab studies.


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Postinfusion monitoring is not required for doses after Day 22. Participants who experience any 
treatment-related AEs during the observation period should be further monitored as clinically 
appropriate. Management of infusion-related reactions is further described in Section 7.10.1.2.
Participants may continue study treatment until they show evidence of disease progression 
(including treatment failure by IWG criteria or relapse after PR/CR), loss of clinical benefit, or 
unacceptable toxicity (further details about treatment discontinuation in Section 5.7.1). 
Repriming for Magrolimab 
Given the large CD47 antigen sink on normal cells, participants who have a long dose delay of 
magrolimab are required to be reprimed with magrolimab dosing to resaturate the CD47 antigen 
sink.
Repriming differs depending on where the participant is in their treatment period as follows: 
1) For participants who have not reached Day 57 of magrolimab/placebo, a 2-week dose delay 
is permitted.
2) For participants who have received Day 57 (or beyond) of magrolimab/placebo, a 4-week 
dose delay is permitted.
The repriming cycles are stand-alone cycles. After Day 22 of the repriming cycle, participants 
should return to their original dose schedule. Table 6 illustrates the repriming magrolimab dosing 
regimen and schedule of assessments.
Modifications to the study treatment doses administered should be made for a > 10% change in 
body weight from baseline and according to local and regional prescribing standards. Dose 
modifications for changes in body weight ≤ 10% may be made according to local institutional 
guidelines. In the event that a dose is modified due to a > 10%, weight change, the weight on 
which the new dose is based, will become the new baseline weight.
Please notify the blinded Medical Monitor of any planned dose delays. If either magrolimab or 
azacitidine is dose delayed for > 8 weeks for any reason, the Investigator must consult with the 
Sponsor’s Medical Monitor prior to reinitiating study treatment.
6.5.
Premedication
Premedication is required prior to the administration of the first 4 doses of magrolimab/placebo 
and in case of repriming. Premedication during subsequent infusions may be continued based on 
the treating physician’s clinical judgment and the presence/severity of prior infusion-related 
reactions. In the case of a Grade 3 infusion-related reaction, a premedication regimen for 
subsequent infusions is required (Section 7.10.1).
Recommended premedications are oral acetaminophen 650 to 1000 mg and oral or IV 
diphenhydramine 25 to 50 mg or comparable regimen. If less than 4 hours has elapsed since a 
prior dose of acetaminophen has been given, the dose of acetaminophen premedication may be 
omitted.


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6.6.
Neutropenic Fever Prophylaxis
Prophylactic antibiotics for the prevention of neutropenic fever are not required on study but may 
be administered per local institutional guidelines or Investigator discretion.
6.7.
Dose Modification and Delays
6.7.1.
Magrolimab/Placebo
6.7.1.1.
Dose Modifications
In clinical experience with magrolimab, no significant dose-dependent toxicities have been 
identified. Therefore, in general, dose modifications to magrolimab/placebo should not be made. 
In rare circumstances, the dose of magrolimab/placebo may be reduced for ≥ Grade 3 AEs that 
are deemed clearly related to magrolimab/placebo and not azacitidine and that do not resolve to 
≤ Grade 2 or baseline value within 14 days of onset. However, dose delay of magrolimab/placebo 
should occur first, and if the AE does not resolve, then a magrolimab/placebo dose reduction can 
be considered. Please notify the blinded Medical Monitor of any planned dose delays. If a 
magrolimab/placebo dose reduction is considered, an initial 33% dose reduction (from 30 to 
20 mg/kg) should be done first. If no improvement is observed within at least 28 days, further 
magrolimab/placebo dose reductions from 20 to 15 mg/kg may be warranted. For persistent bone 
marrow hypocellularity or peripheral cytopenias (where both azacitidine and 
magrolimab/placebo may have a contribution), the dose of azacitidine should be reduced (see 
Section 6.7.2.2). Participants can re-escalate to higher doses of magrolimab/placebo up to the 
original 30 mg/kg dose if AEs improve, after discussion with the Sponsor’s Medical Monitor. 
For dose modification for > 10% change in body weight, see Section 6.4.
6.7.1.2.
Treatment Delays
A treatment delay is defined as a non–protocol-specified interruption from treatment.
Treatment with magrolimab/placebo may be withheld if a ≥ Grade 3 magrolimab/placebo-related 
AE occurs that does not resolve to ≤ Grade 2 or baseline value within 14 days of onset. 
Magrolimab/placebo dosing may also be delayed for participants who experience hospitalization 
due to an AE that may preclude safe administration of magrolimab/placebo (e.g., intensive care 
unit admissions, significant bleeding events, severe infections, or other such events). In general, 
magrolimab/placebo should be continued/restarted without dose reduction. A dose delay for up 
to 3 days during the first 28 days may be permissible if the participant’s WBC count is 
> 20 × 103/μL (applicable to each dose in the first 28 days: Day 1, Day 4, Day 8, Day 11, 
Day 15, and Day 22), to allow for oral hydroxyurea or etoposide treatment to reduce the WBC 
count. Magrolimab/placebo dosing may be delayed for AEs; however, starting at maintenance 
dose, dose delays of up to 4 weeks for other reasons may be allowed at the discretion of the 
Investigator and Sponsor. Participants with a treatment delay of longer than 4 weeks must 
undergo intraparticipant dose escalation (repriming; see Table 6 and Section 6.4) again.


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Ongoing data analysis across magrolimab + azacitidine trials show that Q2W dosing of 
magrolimab without significant dose delays is important to yield optimal efficacy. In the event 
that dose delay is considered due to azacitidine related-toxicities (e.g., cytopenias) or other 
scenarios, magrolimab/placebo dosing should proceed as per Schedule of Assessment for 
treatment period - Magrolimab dosing (Table 4). Magrolimab/placebo dose may be delayed in 
case of serious adverse events or adverse events clearly related to magrolimab/placebo; in the 
event of magrolimab/placebo delay, dosing should resume as soon as it is clinically appropriate 
and logistically possible, without waiting to align with the participants’ original Q2W schedule. 
Magrolimab dosing is anticipated to coincide with azacitidine dosing. However, in the event that 
magrolimab dosing is decoupled from azacitidine dosing, please refer to Table 4 for assessments 
to be performed during the treatment visit with magrolimab dosing. Of note, in addition to 
assessments such as vital signs and symptom-directed physical examinations, collection of PK, 
ADA and peripheral blood samples for biomarker studies, in addition to other assessments 
specified in the Schedule of Assessments should always coincide with magrolimab dosing at 
time points specified in Table 4.
If either magrolimab or azacitidine is dose delayed for > 8 weeks for any reason, the Investigator 
must consult with the Sponsor’s Medical Monitor prior to reinitiating study treatment.
If nonemergency surgical procedures are needed for participants on study treatment, 
magrolimab/placebo will be delayed and restarted in accordance with Table 10.
Table 10.
Magrolimab/Placebo Dosing Guidance for Surgical Procedures on 
Study
Surgical Procedure
Magrolimab/Placebo Dose Guidance
Minimally invasive procedure
(Examples: biopsies (excluding lung/liver), skin/subcutaneous 
lesion removal, cataract/glaucoma/eye surgery, cystoscopy)
Hold magrolimab/placebo dose 3 days prior to 
procedure and restart 3 days after.
Moderately invasive procedure
(Examples: lung/liver biopsy, hysterectomy, 
cholecystectomy, hip/knee replacement, minor laparoscopic 
procedures, stent/angioplasty)
Hold magrolimab/placebo dose 5 days prior to 
procedure and restart 5 days after.
Highly invasive procedure
(Examples: CNS/spine surgery, major vascular surgery, 
cardiothoracic surgery, major laparoscopic surgery)
Hold magrolimab/placebo dose 7 days prior to 
procedure and restart 7 days after.
Abbreviations: CNS = central nervous system
Finally, please notify the blinded Medical Monitor of any planned dose delays for magrolimab.
6.7.2.
Azacitidine
Treatment delay of azacitidine may not occur for participants in the initial 28-day period 
(Cycle 1).


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6.7.2.1.
Treatment Delays
After the initial 28-day period, in the absence of MDS disease (as defined in Section 6.7.2.2.1), if 
hematologic toxicity is observed following azacitidine treatment, the next cycle of treatment 
should be delayed until platelets are  50 × 109/L and neutrophils are 1.0 × 109/L or if blood 
counts are improving from nadir or baseline. If recovery is achieved within 14 days, no dose 
adjustment is needed. However, if recovery is not achieved within 14 days, the dose should be 
reduced according to the azacitidine dose modification guidelines in Section 6.7.2.2.1.2. For 
nonhematologic AEs ≥ Grade 3 that do not resolve to ≤ Grade 2 or baseline value, dosing will be 
delayed up to 14 days from onset. If recovery is achieved within 14 days, no dose adjustment is 
needed. However, if recovery is not achieved within 14 days, the dose should be reduced 
according to the azacitidine dose modification guidelines in Section 6.7.2.2.3. Following dose 
modifications, the cycle duration should return to 28 days. Azacitidine dosing may also be 
delayed for participants who experience hospitalization due to an AE that may preclude safe 
administration of azacitidine (e.g., intensive care unit admissions, significant bleeding events, 
severe infections, or other such events).
If  2 doses of azacitidine are missed during the 7-day dosing period, dosing should continue so 
that the participant receives the full 7 days of treatment, as long as these additional doses are 
given within 1 week of the previous dose. If ≥ 3 doses of azacitidine are missed during the 7-day 
dosing period, the Investigator should contact the Sponsor, and a dosing decision should be made 
on an individual case basis.
6.7.2.2.
Dose Modifications
Dose modification of azacitidine may not occur for participants in the initial 28-day period 
(Cycle 1).
Dose modifications described below are in accordance with the azacitidine prescribing 
information references, with 1 notable exception: while the US prescribing information allows 
for dose escalation to 100 mg/m2 after the first 2 cycles, an azacitidine dose of 75 mg/m2 is 
planned throughout this study for both treatment arms. Azacitidine dose increases above 
75 mg/m2 are not allowed. Dose modification guidance for azacitidine should be followed 
identically for both the experimental and control arms.
6.7.2.2.1.
Dose Modification due to Hematologic Toxicity
6.7.2.2.1.1.
Dose Modification in the Presence of MDS Disease
Treatment with azacitidine is associated with anemia, neutropenia, and thrombocytopenia. Thus, 
CBCs will be performed as described in the schedules of assessments and as needed to monitor 
toxicity. Importantly, these cytopenias are often a result of underlying hematological disease. It 
is thus critical to distinguish between cytopenias due to azacitidine compared to underlying 
disease, so as to not limit potential treatment benefit. Hematologic cytopenias in the presence of 
MDS disease are not defined as hematologic toxicities.


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In accordance with this distinction, the dose of azacitidine will not be reduced if hematologic 
cytopenias are observed in the presence of MDS disease, defined by any of the criteria below: 

> 5% blasts in the bone marrow 

circulating blasts
Nonhematologic toxicities may require dose modifications independent of the presence of MDS 
disease, given the clearer distinction of these toxicities relating to azacitidine as opposed to 
effects of MDS. Dose modifications for hematologic toxicity, decreased bone marrow cellularity, 
and nonhematologic toxicities are described in the sections below.
6.7.2.2.1.2.
Dose Modifications Due to Hematologic Toxicity in the Absence of MDS Disease
Azacitidine should be dose modified or delayed for hematologic toxicities without evidence of 
MDS disease (defined in Section 6.7.2.2.1).
If hematologic toxicity is observed following azacitidine treatment, the next cycle of therapy 
should be delayed for up to 14 days until the platelet count and the ANC have improved. 
If recovery is achieved within 14 days, no dose adjustment is necessary. However, if recovery is 
not achieved within 14 days (Day 42 of the cycle), the dose should be reduced according to 
Table 11 and Table 12. Following dose modifications, the cycle duration should return to 
28 days. Participants with a dose reduction will be reassessed after 2 additional cycles per 
protocol. For participants with persistent cytopenia (as defined in Table 11 and Table 12), 
treatment should be delayed for up to 14 days (Day 42 of the cycle); if counts have recovered, no 
further dose modification is needed. If counts have not recovered, then a further dose reduction is 
recommended, in accordance with Table 11. The reduced dose should be maintained during 
subsequent cycles unless further toxicity develops (defined in Table 11 as further occurrences). 
Azacitidine may be re-escalated back to a higher dose if toxicities have improved.
Separate dose modifications for hematologic toxicity are provided in Table 11 for participants who 
do not have reduced blood counts at baseline (ANC ≥ 1.5 × 109/L and platelets ≥ 75 × 109/L) and 
who have reduced baseline blood counts (ANC < 1.5 × 109/L or platelets < 75 × 109/L).


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Table 11.
Azacitidine Dose Modification for Participants With and Without 
Cytopenia in the Absence of MDS
Nadir Counts
ANC (× 109/L)
Platelets (× 109/L)
% Dose in the Next Cycle if Recoverya Is Not 
Achieved Within 14 Days
Dose Modification for Participants Without Reduced Blood Counts (ANC ≥ 1.5 × 109/L and Platelets 
 75 × 109/L)
First occurrence
≤ 1.0                              or
≤ 50.0
67% (50 mg/m2)
Second occurrenceb
≤ 1.0                              or
≤ 50.0
50% (37.5 mg/m2)
Third occurrenceb
≤ 1.0                              or
≤ 50.0
33% (25 mg/m2)
Dose Modification for Participants with Reduced Blood Counts (ANC < 1.5 × 109/L or Platelets 
< 75 × 109/L)
First occurrence
< 0.5c                            or
< 25c
67% (50 mg/m2)
Second occurrenceb
< 0.5c                            or
< 25c
50% (37.5 mg/m2)
Third occurrenceb
< 0.5c                            or
< 25c
33% (25 mg/m2)
Abbreviation: ANC = absolute neutrophil count; MDS = myelodysplastic syndrome.
a
Recovery is defined as a ≥ 25% recovery in the nadir count.
b
After initial dose reduction, participants will be reassessed after 2 additional cycles per protocol, and if persistent cytopenias 
are observed, a further dose reduction of azacitidine should be considered as outlined.
c
No dose adjustment is needed if the baseline blood counts are below an ANC < 0.5 × 109/L and/or platelets < 25 × 109/L.
Following dose modifications, the cycle duration should return to 28 days.
6.7.2.2.2.
Dose Modifications Due to Decreased Bone Marrow Cellularity in the Absence of 
MDS Disease
Azacitidine alone or in combination with magrolimab may result in a decrease in bone marrow 
cellularity. No dose modification is required if a decrease in bone marrow cellularity is observed 
without reduced peripheral blood counts or if MDS disease is still observed (as defined in 
Section 6.7.2.2.1). If hypocellularity AND reduced peripheral blood counts are observed, then 
the azacitidine dose should be modified in accordance with the instructions in Table 12.


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Table 12.
Azacitidine Dose Modification: Participants with Reduced Bone 
Marrow Cellularity and Reduced Peripheral Blood Counts in the 
Absence of MDS
Azacitidine Dose Instruction if Recoveryb Is Not Achieved Within 14 Days
Bone Marrow 
Cellularity
First Occurrence
Second Occurrence
Third Occurrence
Recoveryb 
 50% decrease 
from baseline 
with a cellularity 
< 30% in the 
presence of 
reduced 
peripheral blood 
countsa
OR
Decrease to 
< 15% cellularity 
with a baseline 
cellularity > 20% 
in the presence 
of reduced 
peripheral blood 
countsa
Dose reduce 
azacitidine to 
50 mg/m2 
administered Days 
1–7 per cycle
AND
Repeat bone 
marrow biopsy to 
assess bone 
marrow cellularity 
after 2 cycles.
Dose reduce 
azacitidine to 
37.5 mg/m2 
administered 
Days 1–7 per cycle
AND
Repeat bone 
marrow biopsy to 
assess bone marrow 
cellularity after 
2 cycles.
Dose reduce 
azacitidine to 
25 mg/m2 
administered Days 
1–7 per cycle
AND
Repeat bone marrow 
biopsy to assess 
bone marrow 
cellularity within 2 
cycles.
Upon reassessment 
after 2 cycles, if 
reduced cellularity 
persists, then 
decrease azacitidine 
dose to 25 mg/m2 on 
Days 1–5 per cycle 
and reassess bone 
marrow cellularity 
after 2 cycles.
Continue at current 
azacitidine dose. For 
subsequent cycles, the 
azacitidine dose can be 
escalated up to the next 
highest dose 
(i.e., escalate to 
75 mg/m2 if initially 
dose reduced to 
50 mg/m2; escalate to 
50 mg/m2 if previously 
dose reduced to 
37.5 mg/m2; or escalate 
to 37.5 mg/m2 if 
previously dose 
reduced to 25 mg/m2).
AND
Repeat bone marrow 
biopsy to assess bone 
marrow cellularity at 
the next protocol-
defined bone marrow 
assessment.
Abbreviation: ANC = absolute neutrophil count; MDS = myelodysplastic syndrome
a
Reduced peripheral blood counts are defined as ANC < 0.5 × 109/L and platelets < 25 × 109/L in the absence of MDS 
disease (i.e., < 5% bone marrow blasts).
b
Recovery in bone marrow cellularity is defined as an increase in bone marrow cellularity  25% from the nadir, increase in 
bone marrow cellularity to  15%, or improvement of peripheral blood counts to ANC > 0.5 × 109/L and platelets > 25 × 109/L.
Following dose modifications, the cycle duration should return to 28 days.
6.7.2.2.3.
Dose Modifications Due to Nonhematologic Toxicity Irrespective of Presence of 
MDS Disease
Renal abnormalities ranging from elevated serum creatinine to renal failure have been reported 
with rare frequency in participants treated with azacitidine. In addition, renal tubular acidosis, 
defined as a decrease in serum bicarbonate to < 20 mmol/L in association with an alkaline urine 
and hypokalemia (serum potassium < 3 mmol/L), has been rarely observed. If unexplained 
reductions in serum bicarbonate (< 20 mmol/L) occur, the azacitidine dose should be reduced by 
50% on the next cycle. Similarly, if unexplained elevations in serum creatinine or blood urea 
nitrogen to ≥ 2-fold above baseline values and above the ULN occur, the next cycle should be 
delayed until values return to normal or baseline, and the azacitidine dose should be reduced by 
50%. The reduced dose should be maintained during subsequent cycles unless toxicity develops.


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For other azacitidine-related nonhematologic toxicities that are ≥ Grade 3 that do not resolve to 
≤ Grade 2 or baseline levels, azacitidine dosing should be delayed up to 14 days until resolution 
to ≤ Grade 2 or baseline levels. If ≥ Grade 3 toxicities continue despite this dose delay, dose 
modification of azacitidine should be performed in accordance with Table 13.
Table 13.
Azacitidine Dose Modification: Nonhematologic Toxicities
Azacitidine Dose Instruction if Recoverya is Not Achieved within 14 Days
Toxicity
First Occurrenceb
Second Occurrenceb
Third Occurrenceb
Grade 3 or 
higher 
nonhematologic 
adverse event
Dose reduce azacitidine 
to 50 mg/m2 
administered Days 1–7 
per cycle
AND
Reassess toxicity on 
subsequent cycle; if still 
persistent despite dose 
delay, proceed to second 
occurrence.
Dose reduce azacitidine 
to 37.5 mg/m2 
administered Days 1–7 
per cycle
AND
Reassess toxicity on 
subsequent cycle; if still 
persistent despite dose 
delay, proceed to third 
occurrence.
Dose reduce azacitidine to 25 mg/m2 
administered Days 1–7 per cycle
AND
Reassess toxicity on subsequent 
cycle; if still persistent despite dose 
delay, then administer azacitidine at 
25 mg/m2 on Days 1–5 per cycle. 
Reassess toxicity on subsequent 
cycle.
Fourth occurrence and beyond: If 
toxicity still persists, then contact the 
Medical Monitor for azacitidine 
dosing instructions.
a
Recovery is defined as improvement of nonhematologic toxicity to  Grade 2 or baseline value within 14 days of dose 
delay.
b
Azacitidine may be dose-escalated back to the original dose or next higher dose level if there is resolution of the toxicity to 
≤ Grade 2 or back to baseline level.
Following dose modifications, the cycle duration should return to 28 days. Please notify the 
blinded Medical Monitor of any planned dose delays.
6.8.
Treatment Assignment and Bias Minimization
This is a multicenter, randomized, double-blind study. Participants who successfully complete 
screening will be randomized and receive either magrolimab + azacitidine (experimental arm) or 
azacitidine + placebo (control arm).
6.8.1.
Treatment Allocation
Treatment allocation/randomization will occur centrally using an IXRS. Participants will be 
assigned randomly in a 1:1 ratio to either the experimental arm or the control arm.


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6.8.2.
Randomization Strategy and Procedure
To achieve balance between treatment arms, randomization will be stratified according to the 
following factors:
Geographic region (US versus ex-US sites)
Baseline cytogenetic risk (very good/good/intermediate versus poor/very poor versus unknown) 
according to IPSS-R {Greenberg 2012} 
Baseline bone marrow blast percentage (≥ 10% versus < 10%)
6.8.3.
Extent and Maintenance of Blinding
This is a double-blind study. Azacitidine will be administered in both treatment arms. 
Magrolimab and azacitidine will be administered in the experimental arm. For the control arm, 
azacitidine + placebo will be administered. During the study, the Investigators, treatment teams, 
the participants, study management team, and all personnel directly involved in the conduct of 
the study or data cleaning will remain blinded to treatment assignment unless the criteria for 
unblinding at the interim analyses are met (see Section 8.3.1 and Section 8.3.2), with the 
exception of specified personnel who may be unblinded based on their study role as described 
below:

The pharmacists at each site who prepare magrolimab or saline placebo will be unblinded to 
the treatment assignment and will keep this information confidential from the participants, 
Investigators, treatment teams, and the Sponsor’s study team members or their designees 
(excluding the designated unblinded site monitors for investigational product accountability).

An unblinded Medical Monitor is available to provide consultation on protocol deviations 
with respect to magrolimab dosing.

Designated members of Gilead Clinical Operations who serve as liaison in communication 
between the Sponsor study team and the designated unblinded contract research organization 
(CRO) personnel (unblinded site monitors and unblinded trial managers) with respect to 
investigational drug management and Gilead oversight of CRO activities will be unblinded.

The Pharmacokinetics File Administrator, or designee, in Bioanalytical Operations and/or 
Clinical Data Management who facilitates the data transfer of PK files between Gilead and 
vendors will remain unblinded. The personnel handling RO data will also be unblinded.

Individuals in Pharmaceutical Development and Manufacturing who have an Unblinded 
Inventory Manager role in the IXRS for purposes of study drug inventory management will 
remain unblinded.


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
Individuals in Global Patient Safety who are responsible for safety signal detection, 
investigational new drug safety reporting, and/or expedited reporting of suspected 
unexpected serious adverse reactions (SUSARs) may be unblinded to individual case data 
and/or group level summaries.

The data monitoring committee (DMC) and the independent biostatistician and statistical 
programmers from an independent data coordinating center (IDCC) who are responsible for 
preparing interim tables, listings, and graphs for DMC review remain unblinded. Controlled 
access to the unblinded data are described in the DMC Charter.

The laboratories that will store and/or analyze blood samples for conducting PK, ADA, and 
RO analysis will be unblinded.

The external vendor who conducts the PK/ADA merge with clinical data will be unblinded. 
In addition, the vendor who performs the population PK and exposure response analysis may 
be unblinded, if needed.

Regulatory Quality and Compliance personnel in Research and Development may also be 
unblinded for purposes of supporting quality assurance activities and/or regulatory agency 
inspections.
In the event of a medical emergency that requires breaking the blind to provide medical care to 
the participant, the Investigator may obtain treatment assignment directly from the IXRS for that 
participant. Gilead recommends, but does not require, that the Investigator contact the 
Gilead Medical Monitor before breaking the blind. Treatment assignment should remain blinded 
unless that knowledge is necessary to determine the participant’s emergency medical care. The 
rationale for unblinding must be clearly explained in source documentation along with the date 
on which the treatment assignment was obtained. The Investigator is requested to contact the 
Gilead Medical Monitor promptly if any treatment unblinding occurs. 
Data that may potentially unblind the treatment assignment (e.g., study drug plasma 
concentrations) will be handled with special care to ensure that integrity of the blind is 
maintained and the potential for bias is minimized. This may include making special provisions, 
such as segregating the data in question from view by the Investigators, study team, or their 
designees as appropriate until the study unblinding for the primary analysis.
6.9.
Prior and Concomitant Medications and Therapies
6.9.1.
Prohibited Therapies
Antileukemic therapies, including chemotherapy (with the exception of hydroxyurea or oral 
etoposide), targeted therapies, and immunotherapy, are not permitted while participants are on 
study treatment.


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6.9.2.
Permitted Therapies
Premedication, as described in Section 6.5, is permitted while on study treatment. Localized 
non-CNS radiotherapy, erythroid and/or myeloid growth factors, hormonal therapy with LHRH 
agonists for prostate cancer, and treatment with bisphosphonates RANKL inhibitors are 
permitted. Red blood cell and platelet transfusions are permitted during Screening and prior to 
randomization to ensure adequate hemoglobin level. Blood transfusions are also permitted during 
the study as clinically indicated for management of cytopenias. On-study blood transfusion 
should be reported in the dedicated transfusion eCRF. Hydroxyurea (up to 4 g/day) can be used 
throughout the study to reduce the WBC to ≤ 20 × 103/μL. Oral etoposide (up to 200 mg orally 
per day) may be given as an alternative to hydroxyurea for participants who are intolerant to 
hydroxyurea or cannot achieve sufficient WBC lowering on hydroxyurea. In nonclinical studies, 
coadministration of magrolimab and hydroxyurea in human leukemia engrafted immunodeficient 
mice did not cause phagocytosis of normal bone marrow cells, suggesting limited on-mechanism 
toxicity in participants. No gross safety abnormalities were observed in these nonclinical studies. 
While no formal analyses have been performed, in clinical studies no significant safety concerns 
have been observed in participants who have received concomitant magrolimab and hydroxyurea 
or magrolimab, azacitidine, and hydroxyurea.
Concomitant medications, including all prescription medications, over-the-counter medications, 
herbal supplements, IV medications, and fluids received within 30 days before the first dose of 
study treatment through the 70-day safety follow-up visit should be recorded in the eCRF.
6.10.
Accountability for Investigational Medicinal Product 
The unblinded pharmacists at each site are responsible for ensuring adequate accountability of all 
used and unused study drug (vials, etc.). This includes acknowledgment of receipt of each 
shipment of study drug (quantity and condition). All used and unused study drug dispensed to 
participants must be returned to the site.
Each study site must keep accountability records that capture the following:

The date received and quantity of study drug (vials, etc.)

The date, participant number, and the study lot number dispensed

The date, quantity of used and unused study drug returned, along with the initials of the 
person recording the information
6.10.1.
Investigational Medicinal Product Return or Disposal
Gilead recommends that used and unused study drug supplies be destroyed at the site. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead, the site may destroy used (empty or partially empty) and unused study drug supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for the electronic Trial Master File. If study drug is destroyed on site, the Investigator must 


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maintain accurate records for all study drugs destroyed. Records must show the identification 
and quantity of each unit destroyed, the method of destruction, and the person who disposed of 
the study drug. Upon study completion, copies of the study drug accountability records must be 
filed at the site. Another copy will be returned to Gilead. 
If the site does not have an appropriate SOP for drug destruction, used and unused study drug 
supplies are to be sent to the designated disposal facility for destruction. The study monitor will 
provide instructions for return.
The designated unblinded site monitors will review study drug supplies and associated records at 
periodic intervals as per the unblinded Study Monitoring Plan.


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7.
SAFETY MONITORING
7.1.
Definitions

Adverse event – An AE is any unfavorable and unintended sign, symptom, or disease 
temporally associated with the use of an investigational product or other protocol imposed 
intervention, regardless of attribution. This includes the following:
Adverse events not previously observed in the participant that emerge during the 
protocol-specified AE reporting period.
Complications that occur as a result of protocol-mandated interventions (e.g., invasive 
procedures, such as biopsies) that are assessed as related to protocol-mandated 
interventions. These include events that occur prior to administration of study treatment, 
which would otherwise be considered non-AEs.
Preexisting medical conditions, judged by the Investigator to have worsened in severity 
or frequency or changed in character during the protocol-specified AE reporting period.

Serious adverse event – An event is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
Death (For deaths attributed solely to MDS disease progression, please refer to 
Section 7.2.5.)
A life-threatening AE (An event is considered “life-threatening” if, in the view of either 
the Investigator or Sponsor, its occurrence places the participant at immediate risk of 
death. It does not include an AE that, had it occurred in a more severe form, might have 
caused death.)
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/birth defect in a neonate/infant born to a mother exposed to study 
treatment
Important medical events that may not result in death, be life-threatening, or require 
hospitalization but may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.


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The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
(as in mild, moderate, or severe according to National Cancer Institute Common Terminology 
Criteria for Adverse Events [NCI CTCAE], Version 5.0); the event itself may be of relatively 
minor medical significance (such as severe headache). “Serious” is a regulatory definition and is 
based on event outcome or action criteria usually associated with events that pose a threat to a 
participant’s life or vital functions. Seriousness (not severity) serves as the guide for defining 
regulatory reporting obligations.
Severity and seriousness should be independently assessed when recording AEs and SAEs on the 
eCRF.
Table 14.
Adverse Event Grade (Severity) Scale
Grade
Severity
Alternate Description a
1
Mild (apply event-specific NCI CTCAE 
grading criteria)
Mild; asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not indicated.
2
Moderate (apply event-specific 
NCI CTCAE grading criteria)
Moderate; minimal, local or noninvasive intervention 
indicated; limiting age-appropriate instrumental ADL.
3
Severe (apply event-specific 
NCI CTCAE grading criteria)
Severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self-care 
ADL.
4
Very severe, life threatening, or 
disabling (apply event-specific 
NCI CTCAE grading criteria)
Life-threatening consequences; urgent intervention 
indicated.
5
Death related to adverse event
Death related to adverse event.
Source: NCI CTCAE, Version 5.0 (Appendix A)
Abbreviations: ADL = activities of daily life; NCI CTCAE = National Cancer Institute Common Terminology Criteria for 
Adverse Events.
a
Use the alternative descriptions for Grade 1, 2, 3, and 4 events when the observed or reported AE does not appear in the NCI 
CTCAE listing.
7.2.
Documenting Adverse Events
A consistent methodology of nondirective questioning for eliciting AEs at all participant 
evaluation time points should be adopted. Examples of nondirective questions include the 
following:

“How have you felt since your last clinic visit?”

“Have you had any new or changed health problems since you were last here?”
Investigators should use correct medical terminology/concepts when recording AEs and SAEs. 
Avoid colloquialisms and abbreviations.
A separate log line in the Adverse Event eCRF should be used for each medical concept that 
needs to be recorded. Causal relationship of AEs and SAEs attributed to study treatment should 
be recorded individually.


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The Investigator is responsible for ensuring that all AEs (including SAEs) are recorded on the 
Adverse Event eCRF and reported to the Sponsor in accordance with protocol instructions. 
Serious adverse events must be reported to the Sponsor or designee within 24 hours of the 
Investigator becoming aware of the event.
7.2.1.
Classification of Adverse Events
Seriousness, causality, and severity – Investigators will seek information on AEs and SAEs at 
each participant contact. All AEs and SAEs, whether reported by the participant or noted by 
authorized study personnel, will be recorded in the participant’s medical record and on the 
Adverse Event eCRF. For each AE and SAE, the Investigator will make an assessment of 
seriousness, severity (Table 14), and causality (Table 15). For each AE and SAE, causal 
relationship to magrolimab/placebo and azacitidine will be assessed, as applicable. The AE 
grading (severity) scale NCI CTCAE, Version 5.0 (Appendix A) will be used for AE reporting as 
shown in Table 14. Regardless of severity, some events may also meet regulatory serious criteria 
(Section 7.1).
To ensure consistency of causality assessments for either study drug, Investigators should apply 
the following general guidelines:
Table 15.
Causal Attribution Guidance
Is the AE/SAE suspected to be caused by the investigational product based on facts, evidence, 
science-based rationales, and clinical judgment?
YES
/Related
The temporal relationship of the AE/SAE to investigational product administration makes a 
causal relationship possible, AND other drugs, therapeutic interventions or underlying 
conditions do not provide sufficient explanation for the AE/SAE.
NO 
/Not Related
The temporal relationship of the AE/SAE to investigational product administration makes a 
causal relationship unlikely, OR other drugs, therapeutic interventions or underlying conditions 
provide a sufficient explanation for the AE/SAE.
Abbreviations: AE = adverse event; SAE = serious adverse event.
Note: The Investigator’s assessment of causality for individual AE reports is part of the study documentation process. Regardless 
of the “Yes” or “No” causality assessment for individual AE reports, Gilead Sciences, Inc. will promptly evaluate all reported 
SAEs against cumulative product experience to identify and expeditiously communicate possible new safety findings to 
Investigators and applicable regulatory authorities.
7.2.2.
Diagnosis Versus Signs and Symptoms
If known, a diagnosis should be recorded as the AE term on the Adverse Event eCRF rather than 
individual signs and symptoms (e.g., record only liver failure or hepatitis rather than jaundice, 
asterixis, and elevated transaminases). However, if a constellation of signs and/or symptoms 
cannot be medically characterized as a single diagnosis or syndrome at the time of reporting, 
each individual event should be recorded as a separate AE on the Adverse Event eCRF. If a 
diagnosis is subsequently established, all previously reported AEs based on signs and symptoms 
should be nullified and replaced by 1 AE report based on the single diagnosis, with a starting 
date that corresponds to the starting date of the first symptom of the eventual diagnosis.


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7.2.3.
Adverse Events Occurring Secondary to Other Events
In general, AEs occurring secondary to other events (e.g., cascade events or clinical sequelae) 
should be identified by their primary cause. For example, if severe diarrhea is known to have 
resulted in dehydration, it is sufficient to record only diarrhea as an AE on the Adverse Event 
eCRF. However, medically significant AEs occurring secondary to an initiating event that are 
separated in time should be recorded as independent events on the Adverse Event eCRF. For 
example, if a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
recorded separately on the Adverse Event eCRF.
7.2.4.
Persistent or Recurrent Adverse Events
A persistent AE is one that extends continuously, without resolution between participant 
evaluation time points. Such events should only be recorded once in the Adverse Event eCRF 
unless their severity changes. If a persistent AE increases or decreases in severity, it should be 
recorded again on the Adverse Event eCRF with each change in CTCAE grade.
A recurrent AE is one that occurs and resolves between participant evaluation time points and 
subsequently recurs. All recurrent AEs should be recorded on Adverse Event eCRF each time 
they recur.
7.2.5.
Deaths
Death that is attributed by the Investigator as solely due to progression of MDS, and that occurs 
during the protocol-specified AE reporting period (Section 7.7) should be recorded only on the 
Death eCRF (i.e., not collected as an SAE on the Adverse Event eCRF). All other deaths 
(i.e., deaths that are not due to MDS progression) occurring during the protocol-specified AE 
reporting period, regardless of attribution, will be recorded on the Adverse Event eCRF and 
reported within 24 hours of awareness and no later than the next business day.
When recording a death on the Adverse Event eCRF, the event or condition that is considered 
the primary cause of death should be the AE term, and the outcome should be death. A 
participant can only have 1 AE (SAE) with outcome of death and severity of CTCAE Grade 5.
7.2.6.
Worsening of Disease
Events that are considered to represent the expected pattern of worsening or progression of the 
underlying MDS should not be recorded as AE/SAEs. These data will be captured as efficacy 
assessment data only. If there is any uncertainty as to whether an event is due to disease 
progression, it must be reported as an AE/SAE.


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7.2.7.
Hospitalization, Prolonged Hospitalization, or Surgery
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as an SAE unless specifically instructed otherwise in this protocol.
The following hospitalization scenarios do not require reporting as an SAE unless there is the 
occurrence of an AE meeting a seriousness criterion other than “hospitalization/prolonged 
hospitalization”:

Hospitalization to perform an efficacy measurement for the study

Hospitalization to undergo a diagnostic or elective surgical procedure for a preexisting 
medical condition that has not changed

Hospitalization to receive scheduled therapy for the target disease of the study

Hospitalization for social reason (e.g., respite care, waiting for insurance authorization)
7.3.
Study Drugs and Gilead Concomitant Therapy Special Situations Reports
Special situation reports (SSRs) include all reports of medication error, abuse, misuse, overdose, 
occupational exposure, drug interactions, exposure via breastfeeding, unexpected benefit, 
transmission of infectious agents via the product, counterfeit of falsified medicine, and 
pregnancy regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration or administration of a study drug while the medication is in the control of a health 
care professional, participant, or consumer. Medication errors may be classified as a medication 
error without an AE, which includes situations of missed dose, medication error with an AE, 
intercepted medication error, or potential medication error.
Abuse is defined as persistent or sporadic intentional excessive use of a study drug by a 
participant.
Misuse is defined as any intentional and inappropriate use of a study drug that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of a study 
drug given per administration or cumulatively which is above the maximum recommended dose 
as per protocol or in the product labeling (as it applies to the daily dose of the participant in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the participant has taken the excess dose(s). Overdose cannot be established 
when the participant cannot account for the discrepancy, except in cases in which the 
Investigator has reason to suspect that the participant has taken the additional dose(s).


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Occupational exposure is defined as exposure to a study drug as a result of one’s professional or 
nonprofessional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial.
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a Gilead study drug.
Counterfeit or falsified medicine: Any study drug with a false representation of (a) its identity, 
(b) its source, or (c) its history.
7.4.
Clinical Laboratory Findings
Only clinically significant laboratory abnormalities that require active management will be 
recorded as AEs on the Adverse Event eCRF (e.g., laboratory abnormalities that require study 
treatment dose modification, discontinuation of study treatment, more frequent follow-up 
assessments, further diagnostic investigation, etc.).
If the clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5 × ULN associated with cholecystitis), only the 
diagnosis (e.g., cholecystitis) needs to be recorded on the Adverse Event eCRF.
If the clinically significant laboratory abnormality is not a sign of a disease or syndrome, the 
abnormality itself should be recorded as an AE on the Adverse Event eCRF. If the laboratory 
abnormality can be characterized by a precise clinical term, the clinical term should be recorded 
as the AE. For example, an elevated serum potassium level of 7.0 mEq/L should be recorded as 
“hyperkalaemia.”
Observations of the same clinically significant laboratory abnormality that require active 
management from visit to visit should not be repeatedly recorded as AEs or SAEs on the 
Adverse Event eCRF, unless their severity, seriousness, or etiology changes.
7.5.
Abnormal Liver Function Tests
Liver toxicity will be evaluated for all participants.
In the absence of an explanation for increased liver function tests, such as viral hepatitis, 
preexisting or acute liver disease, or exposure to other agents associated with liver injury, the 
participant may be discontinued from the study treatment if the Investigator determines that it is 
not in the participant’s best interest to continue. Discontinuation of treatment should be 
considered if there is an indication of severe liver injury according to Hy’s Law, defined by Food 
and Drug Administration (FDA) Guidance for Industry, Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation {U.S. Department of Health and Human Services 2009} as:


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
Treatment-emergent ALT or AST elevation (≥ 3 × ULN), AND 

Treatment-emergent total bilirubin elevation (> 2 × ULN), and absence of cholestasis 
(defined as alkaline phosphatase < 2 × ULN), AND 

No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, 
alcohol ingestion, congestive heart failure, worsening liver metastases).
7.6.
Pregnancy
Female participants who become pregnant during the treatment period must stop the study 
treatment and inform the Investigator immediately.
Any pregnancy occurring in a participant during treatment with either study treatment or within 
6 months of last study treatment administration must be reported to the Sponsor or designee per 
Section 7.8.2.3 by the Investigator or designee within 24 hours of the Investigator/site staff 
becoming aware of it. 
7.7.
Investigator Requirements and Instructions
7.7.1.
Requirements for Collection Prior to Study Drug Initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
must be reported on the applicable eCRFs: all SAEs regardless of cause or relationship and any 
adverse events related to protocol-mandated procedures.
7.7.2.
Adverse Events
Following initiation of study medication, all AEs, regardless of cause or relationship, will be 
collected until 30 days after last administration of study drug and reported on the eCRFs as 
instructed. Adverse events occurring more than 30 days after the last dose of study drug will be 
reported until 70 days after the last dose of study drug or until the initiation of new anticancer 
therapy (including SCT), whichever is earlier.
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol-defined follow-up period.
7.7.3.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occur after the participant first consents to 
participate in the study (i.e., signing the informed consent) and throughout the duration of the 
study, including the posttreatment follow-up visit, must be reported on the applicable eCRFs and 
Global Participant Safety (GLPS) as instructed below in this section. This also includes any 
SAEs resulting from protocol-associated procedures performed after informed consent is signed.


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Any SAEs and deaths that occur after the posttreatment follow-up visit but within 70 days of the 
last dose of study drug or until the initiation of new anticancer therapy (including SCT), 
whichever is earlier, regardless of causality, should also be reported (Refer to Section 7.2.5 for 
death attributed to progression of MDS).
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period; 
however, if the Investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug, the Investigator 
should promptly document and report the event to Gilead GLPS.
Instructions for reporting SAEs are described in Section 7.8.1.
7.7.4.
Study Drug Special Situation Reports
All study drug SSRs that occur from study drug initiation and throughout the duration of the 
study, including the posttreatment follow-up visit, must be reported to GLPS (Section 7.8.2) 
Adverse events and SAEs resulting from SSRs must be reported in accordance to the AE and 
SAE reporting guidance (Section 7.8.1).
7.7.5.
Concomitant Therapy Reports
7.7.5.1.
Gilead Concomitant Therapy Special Situations Report
Special situation reports involving a Gilead concomitant therapy (not considered study drug) that 
occurs after the participant first consents to participate in the study (i.e., signing the informed 
consent) and throughout the duration of the study, including the posttreatment follow-up visit, 
must be reported to Gilead GLPS utilizing the paper SSR (Section 7.8.2.1).
7.7.5.2.
Non-Gilead Concomitant Therapy Report
Special situations involving non-Gilead concomitant medications do not need to be reported on 
the SSR form; however, for special situations that result in AEs due to a non-Gilead concomitant 
medication, the AE should be reported on the AE form. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse” but may be more appropriately documented as a protocol deviation.
All clinical sequelae in relation to these SSRs will be reported as AEs or SAEs at the same time 
using the AE eCRF and/or the SAE report form. Details of the symptoms and signs, clinical 
management, and outcome will be reported when available.


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7.8.
Reporting Process for Serious Adverse Events and Special Situation Reports
7.8.1.
Serious Adverse Event Reporting Process

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be transmitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal participant identification, 
maintaining the traceability of a document to the participant identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded on the concomitant 
medication section of the participant’s eCRF and the SAE narrative section of the SAE 
Report Form eCRF.
7.8.1.1.
Electronic Serious Adverse Event Reporting Process 

Site personnel will record all SAE data on the applicable eCRFs and from there transmit the 
SAE information to Gilead GLPS within 24 hours of the Investigator’s knowledge of the 
event from ICF signature throughout the duration of the study, including the 
protocol-required posttreatment follow-up period. 

If it is not possible to record and transmit the SAE information electronically, record the SAE 
on the paper SAE reporting form and transmit within 24 hours:
Gilead GLPS
Email: Safety_fc@gilead.com 
or
Fax: 1-650-522-5477

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary. If the database is not locked, any SAE reported via paper must be 
transcribed as soon as possible on the applicable eCRFs and transmitted to GLPS.
7.8.2.
Special Situations Reporting Process 
7.8.2.1.
Paper Special Situations Reporting Process for Study Drug 

All SSRs will be recorded on the special situations report form and transmitted by emailing 
or faxing the report form within 24 hours of the Investigator’s knowledge of the event to the 
attention of Gilead GLPS from study drug initiation throughout the duration of the study, 
including the protocol required posttreatment follow-up period.
Gilead GLPS
Email: Safety_fc@gilead.com 
or
Fax: 1-650-522-5477


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7.8.2.2.
Reporting Process for Gilead Concomitant Medications

Special situations that involve Gilead concomitant medications that are not considered study 
drug must be reported within 24 hours of the Investigator’s knowledge of the event to Gilead 
GLPS utilizing the paper special situations report form to:
Gilead GLPS
Email: Safety_fc@gilead.com 
or
Fax: 1-650-522-5477

Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.

Special situations involving non-Gilead concomitant medications do not need to be reported 
on the SSR form; however, special situations that result in AEs due to a non-Gilead 
concomitant medication, must be reported as an AE.
7.8.2.3.
Pregnancy Reporting Process

The Investigator should report pregnancies in female participants that are identified after 
initiation of study drug and throughout the study, including the follow-up period, to Gilead 
GLPS using the pregnancy report form within 24 hours of becoming aware of the pregnancy. 
Contact details for transmitting the pregnancy report form are as follows:
Gilead GLPS
Email: Safety_fc@gilead.com 
or
Fax: 1-650-522-5477

The pregnancy itself is not considered an AE, nor is an induced elective abortion to terminate 
a pregnancy without medical reasons.

All other premature terminations of pregnancy (e.g., a spontaneous abortion, an induced 
therapeutic abortion due to complications, or other medical reasons) must be reported within 
24 hours as an SAE, as described in Section 7.8.1. The underlying medical reason for this 
procedure should be recorded as the AE term.

A spontaneous abortion is always considered to be an SAE and will be reported as described 
in Section 7.8.1. Furthermore, any SAE occurring as an adverse pregnancy outcome after 
study must be reported to the Gilead GLPS.

The participant should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome of the pregnancy should be reported to Gilead GLPS using the 
pregnancy outcome report form. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead GLPS. Gilead GLPS contact 
information is as follows: 
Email: Safety_FC@gilead.com and fax: +1 (650) 522-5477. 


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
Refer to Appendix G for Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements.
7.9.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the European Union (EU) Clinical Trials Directive (2001/20/EC) and 
relevant updates, and other country-specific legislation or regulations, Gilead may be required to 
expedite to worldwide regulatory agencies reports of SAEs, which may be in the form of 
line-listings, serious adverse drug reactions (SADRs), or SUSARs. In accordance with the 
EU Clinical Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide 
regulatory agencies and the relevant IEC in concerned Member States of applicable SUSARs as 
outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable.
All Investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The Investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
To minimize the possibility of exposing study participants to unusual risk, the safety information 
from this study will also be reviewed periodically by the DMC. The DMC may have access to 
partially blinded or unblinded data and will make recommendations regarding the study 
according to the DMC charter (Section 10.1.1).
7.10.
Specific Safety Management Guidelines
7.10.1.
Magrolimab/Placebo
7.10.1.1.
Anemia, Blood Cross-matching, and Packed Red Blood Cell Transfusion 
Procedures
Magrolimab binds to RBCs and leads to erythrophagocytosis. CD47 is a member of the Rh 
complex in the RBC membrane. Therefore, when magrolimab binds to CD47, it is likely to 
interfere with routine blood bank tests needed in case of transfusion. Notify blood transfusion 
centers/blood banks of this interference with blood bank testing, and inform them that a 
participant will receive magrolimab.
In clinical studies, anemia is the most common treatment-related AE and is typically manifested 
as a decline in hemoglobin of about 0.5 g/dL to 1.5 g/dL that is observed in the first 1 to 2 weeks 
of treatment. This decrease in hemoglobin level is acceptable in participants with no other 
significant diseases or medical conditions. However, for participants with significant diseases or 
medical conditions, such as unstable angina, ischemic heart disease, or uncontrolled diabetes 
mellitus, complications from treatment‑related anemia could be life‑threatening or fatal. 
Significant drops (2 to 3 g/dL or higher) have been observed in early doses.


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Within 24 hours prior to each of the 2 first doses of magrolimab/placebo infusion during initial 
treatment, all participants must have a documented hemoglobin ≥ 9 g/dL. Participants who do 
not meet these criteria must be transfused and have their hemoglobin rechecked to meet the 
minimum hemoglobin threshold prior to each of the first 2 doses of magrolimab/placebo 
infusion.
Participants with a low baseline hemoglobin level, especially those with cardiac history or risk 
factors, must be monitored closely after initial administrations of magrolimab as preexisting 
anemia could be exacerbated. Red blood cell transfusions are permitted prior to study treatment 
to ensure adequate hemoglobin level as per the investigator’s clinical judgment. 
Prior to initiation of magrolimab/placebo, ABO/Rh type, antibody screen, DAT, and extended 
RBC phenotyping (including minor antigens such as CcDEe, Cw, MNSs, Kk, FyaFyb, and 
JkaJkb) must be performed for each participant. Red blood cell genotyping instead of extended 
RBC phenotyping is acceptable for any participant. Red blood cell genotyping (instead of an 
extended RBC phenotyping) must be performed if a participant received any RBC or whole 
blood transfusion within the previous 3 months (unless the laboratory has availability for special 
techniques for performing phenotyping for participants with a recent transfusion). Results must 
be available before the first dose of magrolimab/placebo.
For Participants After Exposure to Magrolimab
Hemoglobin must be checked again 3 to 6 hours after the initiation of the first and second doses 
of magrolimab during initial treatment. The participant should be transfused as clinically 
appropriate. Investigators should consider additional hemoglobin monitoring during the first 
week of treatment in participants with symptoms of anemia or increased risk for complications of 
anemia.
For all elective RBC and platelet transfusions, use leukocyte-reduced and gamma-irradiated units 
per institutional guidelines. For RBC, phenotype/genotype matched units are preferred. 
However, CMV-seronegative units for CMV-seronegative participants will not be required for 
this study.
For instances where the ABO/Rh type cannot be resolved, use pretreatment (historical) 
phenotype/genotype matched units for minor RBC antigens (CcDEe and Kk, to the extent 
feasible). Regarding the ABO type, historical blood group or O type can be used as per the 
institutional guidelines.
For emergency transfusions, the blood transfusion centers may consider using emergency Group 
O RBCs if phenotype/genotype matched units are not available. 
Whenever possible, blood plasma therapy should be blood type specific. Platelets should be 
blood type compatible whenever possible and, if not, should have been tested and found not to 
have high titer anti-A or anti-B. Otherwise, plasma and platelet products can be provided as per 
the institutional policy. 


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A recent report has suggested that cross-match interference by RBCs due to treatment with 
magrolimab may be resolved by use of gamma-clone anti-IgG and multiple alloadsorptions with 
papain-treated RBC samples, pooled single donor apheresis platelets, or commercial human 
platelet concentrate product if required {Troughton 2018, Velliquette 2019}.
7.10.1.2.
Management of Infusion-related Reactions
Infusion-related reactions are defined by the NCI CTCAE, Version 5.0 (under the category 
“General disorders and administration site conditions”) as “a disorder characterized by adverse 
reaction to the infusion of pharmacological or biological substances” (Appendix A). For the 
purposes of this study, the time frame for infusion-related reaction assessment is the 24-hour 
period beginning from the start of the infusion. Premedication use described in Section 6.5 will 
be used to manage infusion-related reactions preemptively.
Recommendations for the management of infusion-related reactions are provided below.

For Grade 1 infusion-related reactions, described as mild transient reaction, infusion 
interruption is not indicated and intervention not indicated:
Remain at bedside and monitor participant until recovery from symptoms.

For Grade 2 infusion-related reaction, infusion interruption is indicated, but participant 
responds promptly to symptomatic treatment (e.g., antihistamines, nonsteroidal 
anti-inflammatory drugs, narcotics, corticosteroids, IV fluids), and prophylactic medications 
are indicated for ≤ 24 hours:
Stop the magrolimab/placebo infusion, begin an IV infusion of normal saline, and consider 
treating the participant with diphenhydramine 50 mg IV (or equivalent) and/or 500 to 750 mg 
of oral acetaminophen.
Remain at bedside and monitor participant until resolution of symptoms.
Corticosteroid therapy may also be given at the discretion of the Investigator.
If the infusion is interrupted, wait until symptoms resolve, then restart the infusion at 50% of 
the original infusion rate.
If no further complications occur after 1 hour (± 10 minutes), the rate may be increased to 
100% of the original infusion rate. Monitor the participant closely.
If symptoms recur, stop infusion and disconnect participant from the infusion apparatus. No 
further magrolimab will be administered at that visit.
Premedications should be considered before any future infusions.
The amount of magrolimab infused must be recorded on the eCRF.


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Participants who experience a Grade 2 infusion-related reaction during the postinfusion 
observation period that does not resolve to ≤ Grade 1 during that time should be observed 
until the AE resolves or stabilizes, with vital sign measurements as medically indicated for 
the management of the AE.

For Grade 3 or Grade 4 infusion-related reaction, where Grade 3 is described as prolonged 
infusion-related reactions (e.g., not rapidly responsive to symptomatic medication and/or 
brief interruption of infusion), or recurrence of symptoms following initial improvement, or 
where hospitalization is indicated for other clinical sequelae (e.g., renal impairment, 
pulmonary infiltrates) and Grade 4 is described as having life-threatening consequences and 
where urgent intervention is indicated.
Immediately discontinue infusion of magrolimab.
Begin an IV infusion of normal saline, and consider treating the participant as follows: 
Administer bronchodilators, epinephrine 0.2 to 1 mg of a 1:1000 solution for SC 
administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly for IV 
administration and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV 
(or equivalent), as needed.
The participant should be monitored until the Investigator is comfortable that the 
symptoms will not recur.
Participants who have Grade 4 infusion-related reactions occurring with the first dose 
(priming dose) will be permanently discontinued from study treatment.
Participants who experience Grade 3 or 4 infusion-related reactions must be given 
premedication prior to subsequent doses. In this setting, premedication with oral 
acetaminophen (650 to 1000 mg), oral or IV diphenhydramine (25 to 50 mg), and IV 
dexamethasone (4 to 20 mg), or a comparable regimen, is recommended for the 
subsequent 2 doses. Continued premedication with corticosteroids beyond these 2 doses 
may be administered at the discretion of the treating physician.
Participants who receive premedication and still experience a Grade 3 or 4 
infusion-related reaction will be permanently discontinued from the study treatment.
For anaphylaxis, Investigators should follow their institutional guidelines for treatment.
All participants with Grade 3 or greater infusion-related reactions will be observed until 
the AE resolves or stabilizes, with vital sign measurements and additional evaluations as 
medically indicated for the management of the AEs.


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7.10.1.3.
Thromboembolic Events
Thromboembolic events, including deep vein thromboses and pulmonary embolisms, have been 
reported in some patients receiving magrolimab, sometimes early in therapy. Available data for 
magrolimab do not support a clear or consistent relationship between clinical thromboembolic 
events and magrolimab use. Patients should be closely monitored for the symptoms of 
thromboembolic events and treated accordingly.
7.10.1.4.
Management of Pneumonitis
Pneumonitis has been infrequently observed in participants receiving magrolimab. Generally, 
immune-related AEs have not been observed in clinical use with magrolimab. In contrast to 
T-cell checkpoint inhibitors, magrolimab primarily exerts its antitumor efficacy through 
macrophage-mediated phagocytosis of tumor cells. Nonspecific T-cell or other host immune 
responses that are seen with T-cell checkpoint inhibitors have not been observed with 
magrolimab in nonclinical studies. Additionally, no events of macrophage activation syndrome 
or hemophagocytic lymphohistiocytosis have been reported in clinical studies. 
In instances of suspected pneumonitis, first rule out noninflammatory causes (e.g., infections, 
etc.). If a noninflammatory cause is identified, treat accordingly and continue therapy per 
protocol. Evaluate with imaging, e.g. chest x-ray or computed tomography, and pulmonary 
consultation.

Management of potential pneumonitis is detailed in Table 16 and follows American Society 
of Clinical Oncology guidelines for immune-related adverse events {Brahmer 2018}. 
Participants who experience Grade 3-4 pneumonitis will be permanently discontinued from 
study treatment.


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Table 16.
Pneumonitis Management Algorithm
Pneumonitis
CTCAE Grade of Pneumonitis
Management
Follow-Up
Grade 1
Radiographic changes (CXR or 
CT) only.
Monitor for signs and symptoms 
weekly and consider monitoring with 
CXR.
Consider pulmonary and infectious 
disease consults.
Consider reimaging with CT in 3-4 
weeks as clinically indicated.
May resume magrolimab with 
radiographic evidence of 
improvement or resolution.
If no clinical improvement or 
worsening, treat as Grade 2.
Grade 2
Mild to moderate new 
symptoms.
Interrupt magrolimab therapy per 
protocol.
Pulmonary and infectious disease 
consults.
Consider empirical antibiotics.
Monitor signs and symptoms every 
2-3 days; consider hospitalization.
1 mg/kg/day oral prednisone or IV 
equivalent.
Consider bronchoscopy, lung biopsy.
Reimage every 1-3 days.
If improving to baseline, taper 
corticosteroids over 4-6 weeks and 
resume magrolimab therapy per 
protocol.
If no clinical improvement after 
48-72 hours or worsening, treat as 
Grade 3-4.
Grade 3-4
Severe new symptoms; new/ 
worsening hypoxia; life-
threatening.
Discontinue magrolimab therapy.
Hospitalize.
Pulmonary and infectious disease 
consults.
1-2 mg/kg/day methylprednisolone 
IV or IV equivalent.
Add empirical antibiotics and 
consider prophylactic antibiotics for 
opportunistic infections.
Consider bronchoscopy, lung biopsy.
If improving to baseline, taper 
corticosteroids over 4-6 weeks.
If no clinical improvement after 
48 hours or worsening, consider 
additional immunosuppression 
(e.g., infliximab, 
cyclophosphamide, IV 
immunoglobulin, mycophenolate 
mofetil).
CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; CXR = chest x-ray; IV = intravenous.
7.10.2.
Azacitidine
Safety management guidelines for azacitidine are described in Section 6.7.2. Additional safety 
guidelines are provided in the azacitidine prescribing information references.


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8.
STATISTICAL CONSIDERATIONS
8.1.
Sample Size Determination
The study will randomize approximately 520 participants in total into 2 treatment arms at a 
1:1 ratio, determined by formal hypothesis testing performed on 2 primary efficacy endpoints: 
CR rate and OS, with family-wise Type I error controlled at a 2-sided significance level of 0.05.
The primary analysis of the CR rate will be conducted at 8 months after 348 participants are 
randomized. Based on the first 348 randomized participants, the study has 95% power to reject 
the null hypothesis that the CR rates in the 2 treatment arms are the same at the 2-sided 
0.03 significance level, assuming the true CR rate is 20% in the control arm and 39% in the 
experimental arm (i.e., a 19% improvement). 
If the null hypothesis has been rejected for CR rate, the hypothesis test on OS will be conducted 
at a 2-sided significance level of 0.05; otherwise, it will be conducted at a 2-sided significance 
level of 0.02 for the superiority test together with a futility test. Approximately 364 OS events 
(70% of 520 participants) in the ITT Analysis Set will allow 90% power to reject the null 
hypothesis that medians in OS in the 2 treatment arms are the same, assuming 18 months in the 
control arm and 25.4 months in the experimental arm (i.e., hazard ratio [HR] = 0.71), at a 2-sided 
significance level of 0.05, or at least 80% power at a 2-sided significance level of 0.02. 
The sample size is determined according to the group sequential design. Assuming an enrollment 
rate of approximately 0.22 participants/site/month and 1% annual loss to follow-up of survival 
status, accrual is projected to occur over 22 months for 520 participants. The primary CR rate 
analysis is expected approximately 26 months after the first participant is randomized. The first 
interim analysis of OS will be conducted at the same time. The second interim analysis of OS 
will be conducted when approximately 257 deaths (71% of 364 deaths) have occurred. The final 
OS analysis is expected approximately 4.4 years after the first participant is randomized. The 
actual length of the study and the time for analyses will depend on the actual enrollment rate and 
the number of events that occur.
8.2.
Analysis Sets
ITT Analysis Set: The efficacy analyses will be conducted on all randomized participants 
according to the treatment arm to which the participants are randomized, unless otherwise 
specified.
Safety Analysis Set: The safety analyses will be conducted on all randomized participants who 
receive at least 1 dose of any study treatment, with treatment assignments designated according 
to the actual treatment received.


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PK Analysis Set: The PK analysis will be conducted on all participants who received at least 
1 dose of magrolimab and have at least 1 measurable posttreatment serum concentration of 
magrolimab. If azacitidine PK analysis is conducted, a separate azacitidine PK analysis set will 
consist of all participants who received any amount of azacitidine and have at least 1 measurable 
posttreatment serum concentration of azacitidine. 
Immunogenicity Analysis Set: The immunogenicity analysis will be conducted on all 
participants who received at least 1 dose of magrolimab and with at least 1 reported ADA result.
8.3.
Planned Analyses
8.3.1.
DMC Interim Analyses
There will be 2 planned interim efficacy analyses conducted and evaluated by the DMC. 
The first one will be conducted at 8 months after 348 participants have been randomized 
(i.e., data cutoff date), outstanding data queries have been resolved or adjudicated as 
unresolvable, and the data have been cleaned and finalized. First, the primary analysis of CR rate 
will be conducted based on the first 348 randomized participants. Second, an interim analysis of 
OS will be conducted based on all randomized participants by the data cutoff date. The interim 
analysis boundary for statistical significance will be determined based on the Lan-DeMets 
approach of the O’Brien-Fleming function according to the α allocated to the comparison of OS. 
Specifically, if the null hypothesis on CR rate is rejected at a 2-sided significance level of 0.03, 
α = 0.05 (2-sided) will be allocated for OS, and there will be no formal futility testing for OS. 
Otherwise, if the null hypothesis on CR rate is not rejected at a 2-sided significance level of 0.03, 
α = 0.02 (2-sided) will be allocated for OS and the first non-binding futility analysis with a 
futility boundary of HR = 0.99 will be performed. Allocation of α is applied to all subsequent 
interim analyses of OS (as well as the final analysis of OS). It is projected that 158 deaths (43% 
of 364 deaths) would have occurred at this time.
The second planned interim efficacy analyses will be conducted when approximately 257 deaths 
(71% of 364 deaths) have occurred in the ITT Analysis Set, outstanding data queries have been 
resolved or adjudicated as unresolvable, and the data have been cleaned and finalized. In the case 
that the null hypothesis on CR rate is not rejected at a 2‑sided significance level of 0.03, a non-
binding futility analysis with a futility boundary of HR = 0.95 will be performed.

If the null hypothesis on CR is rejected in the first interim analysis at a 2-sided significance 
level of 0.03, α = 0.05 (2-sided) will be allocated to the analysis of OS and key secondary 
endpoints in the first and second interim analyses, and final analysis. 

If the null hypothesis on CR rate is not rejected in the first interim analysis at a 2-sided 
significance level of 0.03, α = 0.02 (2-sided) will be allocated to the analysis of OS and key 
secondary endpoints in the first and second interim analyses, and final analysis.
In addition to the 2 planned interim efficacy analyses, the DMC will convene to review interim 
safety analysis results periodically.


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The Lan-DeMets approach with O’Brien-Fleming type alpha spending function will be used for 
the first and second interim analyses and final analysis for OS. The stopping boundaries at each 
analysis time are provided in Table 17.
Table 17.
Stopping Boundaries for Efficacy Superiority Analyses
Stopping Boundary
Planned Analyses
Efficacy 
Analysis
Events (%)
HRa
Two-sided p-value
first IA
CR
-
-
0.03
first IA
OS
158 (43%)
0.600
0.0013b
second 
IA
OS
257 (71%)
0.738
0.0148 b
If the test of CR 
is rejected in 
first IA
Final 
Analysis
OS
364 (100%)
0.811
0.0453 b
first IA
OS
158 (43%)
0.552
0.0002 b
second 
IA
OS
257 (71%)
0.700
0.0043 b
If the test of CR 
fails to be 
rejected in first 
IA
Final 
Analysis
OS
364 (100%)
0.781
0.0186 b
HR = hazard ratio, IA = interim analysis, OS = overall survival, CR = complete remission
a
HR presented in the table is the 1-sided (lower) efficacy boundary.
b
The boundary p-values at each analysis timepoint will be based on the actual observed events and adjusted by using the 
Lan-DeMets approach with O’Brien-Fleming type alpha spending function.
The primary efficacy endpoint of OS will be tested for superiority first at the significance level 
specified in Table 17. If the superiority of OS is established, key secondary efficacy endpoints 
listed in Table 18 will be tested for superiority. To strongly control the overall type I error across 
the testing of the primary and key secondary efficacy endpoints, a hierarchical testing strategy 
will be performed with a predefined order as listed below. For each key secondary endpoint, an 
O'Brien-Fleming boundary will be derived based on the information fraction at each interim 
analysis and the remaining type I error respectively per Table 18. 


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Table 18.
Definition of Information Fraction for Key Secondary Endpoints
Endpoint
Information Fraction at the First and Second Interim Analysis
ORR
Proportion of participants who have at least 8 months follow-up 
since randomization (including participants who have early 
discontinued, are lost to follow-up, or have died)
RBC transfusion independence rate
Proportion of participants who have at least 8 months follow-up 
since randomization (including participants who have early 
discontinued, are lost to follow-up, or have died)
EFS
43% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)a
CR rate in TP53 mutant population
Proportion of participants who have at least 8 months follow-up 
since randomization (including participants who have early 
discontinued, are lost to follow-up, or have died)
MRD-negative response rate
Proportion of participants who have at least 8 months follow-up 
since randomization (including participants who have early 
discontinued, are lost to follow-up, or have died)
Time to transformation to AML
43% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)a
PFS
43% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)a
FACT-Anemia response rate
Proportion of participants who have at least 8 months follow-up 
since randomization (including participants who have early 
discontinued, are lost to follow-up, or have died)
AML = acute myeloid leukemia; CR = complete remission; EFS = event-free survival; FACT-Anemia = Functional Assessment 
of Cancer Therapy-Anemia; MRD = minimal residual disease; ORR = objective response rate; OS = overall survival; 
PFS = progression-free survival; RBC = red blood cell
a
The actual information fraction at each interim analysis for time to event endpoints will be based on actual observed OS 
events by the time of analysis.
The key secondary endpoints will be tested in the following order: 

ORR

RBC transfusion independence rate

Event-free survival (EFS)

CR in TP53 mutant population

MRD-negative response rate

Time to transformation to AML 

Progression-free survival (PFS)

FACT-Anemia response rate




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The following summary measures for endpoints will be evaluated:
CR Rate: The CR rate is the proportion of participants who reach morphologic CR 
(morphological blast of ≤ 5% and recovery of ANC, platelets, and hemoglobin from CBCs as 
well as peripheral blast collected on the same day) based on Investigator-assessed IWG 2006 
MDS criteria {Cheson 2006} prior to initiation of any new anticancer therapy, including SCT.
Duration of CR: The duration of CR is measured from the time measurement criteria are first 
met for CR to the first date of relapse or death, whichever occurs earlier. Those who are not 
observed to relapse or die will be censored at their last response assessment date with evidence 
of no relapse. Participants who achieve a CR and then proceed to an allogeneic SCT will 
continue to be followed for the response assessment posttransplant, will be included in the 
analysis of duration of CR, and will not be censored at the time of transplant. 
Overall Survival (OS): The length of OS is measured from randomization to the date of death 
from any cause. Those who are not observed to die during the study will be censored at their last 
known alive date.
Objective Response Rate (ORR): The ORR is the proportion of participants who reach 
objective response including CR, PR, marrow CR, or hematologic improvement per IWG 2006 
MDS criteria prior to initiation of any new anticancer therapy, including SCT.
Duration of Response (DOR): The DOR is measured from the time measurement criteria are 
first met for objective response to the first date of relapse, disease progression or death, 
whichever occurs earlier. Those who are not observed to relapse, disease progress or die will be 
censored at their last response assessment date with evidence of no relapse/no disease 
progression. Participants who achieve a response and then proceed to an allogeneic SCT will 
continue to be followed for the DOR posttransplant, will be included in the analysis of DOR, and 
will not be censored at the time of transplant. 
RBC Transfusion Independence Rate: The RBC transfusion independence rate is the 
proportion of participants who have a 56-day or longer period with no RBC transfusions at any 
time between randomization and initiation of any new anticancer therapy, including SCT, among 
all participants who are RBC transfusion-dependent at baseline.
Progression-free Survival (PFS): The length of PFS is defined as the time from randomization 
to the date of documented disease progression (including treatment failure by IWG criteria or 
relapse after PR/CR), or death from any cause, whichever occurs first. Those who are not 
observed to have one of these events will be censored at their last response assessment date with 
evidence of no disease progression/relapse. 
Event-free Survival (EFS): The length of EFS is defined as the time from randomization to 
transformation to AML or death from any cause, whichever occurs first. Participants who are not 
observed to have one of these events during the study will be censored at their last response 
assessment date with evidence of no transformation to AML. 


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MRD-negative Response Rate: The MRD-negative response rate is defined as the proportion of 
participants who achieve a morphologic CR or marrow CR based on Investigator-assessed IWG 
criteria {Cheson 2006} and reach MRD-negative disease status prior to initiation of any new 
anticancer therapy, including SCT. MRD-negative disease status will be assessed using a 
multiparameter flow cytometry-based assay performed by a central laboratory.
Time to Transformation to AML: Time to transformation to AML is defined as the time from 
randomization to the collection date of bone marrow sample leading to documented AML 
diagnosis. Participants who are not observed to have transformation to AML will be censored at 
their last response assessment date with evidence of no AML diagnosis.
FACT-Anemia Response Rate: The FACT-Anemia response rate is defined as the proportion 
of participants who showed clinically meaningful improvement in health-related quality of life 
(HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new 
anticancer therapy, including SCT.
Duration of RBC Transfusion Independence: The duration of RBC transfusion independence 
is measured from the time the assessment criteria are first met for RBC transfusion independence 
until RBC transfusion dependence again (including assessments post SCT) or death. Those who 
are not observed to have one of these events will be censored at the date of their last response 
assessment with evidence of no RBC transfusion dependence again.
Transplantation Rate: The transplantation rate is defined as the proportion of participants who 
initiate transplant therapy for MDS after randomization.
Time to First Transplant: Time to first transplant is defined as the time from randomization to 
the initiation of first transplant therapy for MDS. Participants who are not observed to initiate 
transplant therapy will be censored at their last known alive date or death date if the patient died.
RBC Transfusion Independence Irrespective of RBC Transfusion-Dependence at Baseline: 
The RBC transfusion independence irrespective of RBC transfusion-dependence at baseline is 
the proportion of participants who have a 56-day or longer period with no RBC transfusions at 
any time between randomization and initiation of any new anticancer therapy, including SCT, 
among all participants irrespective of RBC transfusion-dependence at baseline.
8.5.
Efficacy Analysis
8.5.1.
Analysis of Primary Efficacy Endpoints
The primary efficacy endpoints are CR rate as assessed by Investigators and OS. The analysis of 
CR rate will be conducted on the first 348 randomized participants in the ITT Analysis Set. The 
analysis of OS will be conducted on the ITT Analysis Set. 
The difference in CR rates between the 2 arms will be tested using the Cochran-Mantel-Haenszel 
test, stratified by the randomization stratification factors including region, baseline cytogenetic 
risk, and bone marrow blast percentage. The point estimate of the CR rate and the corresponding 
2-sided exact 95% CI based on Clopper-Pearson method will be provided for each treatment 
arm.


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Log-rank test, stratified by the randomization stratification factors including region, baseline 
cytogenetic risk, and bone marrow blast percentage, is the primary analysis comparing treatment 
differences in OS. A stratified Cox regression model will be used to estimate HR and its 2-sided 
95% CI. In addition, the KM method will be used to estimate median OS with its 95% CI, and 
the KM plots may also be provided. 
8.5.2.
Analysis of Secondary Efficacy Endpoint(s)
Analysis of EFS, PFS, and time to transformation to AML will be similar to that of OS.
ORR, RBC transfusion independence rate, CR rate in the TP53 mutant population, and 
MRD-negative response rate will be evaluated in a similar manner as the primary efficacy 
endpoint of CR, except that RBC transfusion independence rate will be based on a subset of all 
randomized participants who are RBC transfusion-dependent at baseline and CR rate in the TP53 
mutant population will be based on subset of all randomized participants who have the TP53 
mutation.
For the time-to-event endpoints of duration of CR and DOR, analysis will be conducted using the 
KM method based on the subsets on which the outcome measures are defined. Specifically, 
duration of CR will be based on participants who achieved CR, DOR will be based on 
participants who achieved OR. Median duration will be estimated with its 95% CI for each 
treatment arm. 
Hypothesis testing of key secondary endpoints will be performed under the testing procedure 
described in Section 8.3 to control family-wise Type I error. No formal hypothesis testing will be 
conducted for any key secondary endpoint, unless the null hypothesis of OS is rejected. 
8.6.
Safety Analysis
The statistical analysis of safety data will be conducted in the Safety Analysis Set. Safety 
variables may include, but are not limited to, treatment-emergent adverse events (TEAEs; AEs 
occurring during or after a participant’s first exposure to study treatment and up to 70 days after 
the last day of study treatment or initiation of new anticancer therapy, including SCT [whichever 
is earlier]), vital signs, physical examinations, and laboratory tests.
Data may be graphed, summarized, or listed, depending on the amount of data to be reported.
8.6.1.
Extent of Exposure
A participant’s extent of exposure to study drug data will be generated from the study drug 
administration data. Exposure data will be summarized by treatment.
8.6.2.
Adverse Events
Adverse events will be coded using MedDRA Version 22.1 or later, and the NCI CTCAE, 
Version 5.0 (Appendix A) will be used to grade severity of AEs and clinically significant 
laboratory abnormalities. Participant incidence of TEAEs and treatment-related TEAEs will be 
summarized by system organ class and preferred term. TEAEs will also be summarized using 


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Investigator assessment of the relationship to study treatment (related or not related). Serious 
adverse events, including deaths, will be summarized and/or listed for all participants. TEAEs 
resulting in withdrawal from study treatment will be summarized and/or listed.
Adverse events that occurred before exposure to study treatment will be reported in the AE data 
listings and appropriately identified as non-TEAEs.
Adverse events and SAEs that are not treatment emergent will be reported separately in data 
listings for the Safety Analysis Set.
8.6.3.
Laboratory Evaluations
For select laboratory parameters, changes of laboratory values over time, grade shifts in 
laboratory value from baseline to worst on study value, and Grade 3 or higher laboratory 
abnormalities will be summarized. Incidence of treatment-emergent laboratory abnormalities, 
defined as values that increase at least 1 toxicity grade from baseline at any time point 
postbaseline up to last day of treatment + 30 days, will be summarized by treatment group. If 
baseline data are missing, any graded abnormality (ie, at least a Grade 1) will be considered 
treatment emergent.
8.6.4.
Other Safety Analyses
The number and incidence of participants developing ADAs at any time will be summarized. 
Vital signs and physical examination findings will be summarized at select time points. Details 
will be provided in the statistical analysis plan (SAP).
8.7.
Analysis of PRO Data
A key PRO endpoint, FACT-Anemia response rate, is defined based on the ITT Analysis Set 
(see Section 8.3.1). The analysis method is similar to that of the CR rate. Other indices, such as 
the Functional Assessment of Cancer Therapy-General (FACT-G), FACT Trial Outcome 
Index-Anemia scale (FACT TOI-An), and FACT Trial Outcome Index-Fatigue (FACT TOI-F), 
which can be derived from FACT-Anemia with published minimally clinically meaningful 
difference, will also be analyzed {Cella 2002, Revicki 2013}.
Additional analyses will be conducted on all PRO data, including absolute scores and changes 
from baseline for all items and subscales of the FACT-Anemia instrument, EQ-5D-5L 
instrument, and PGIS/PGIC at each assessment time point for each arm.
8.8.
Pharmacokinetics Analysis
Pharmacokinetic analysis will be conducted for magrolimab on the PK Analysis Set. 
The PK Analysis Set will be used for summaries of PK concentration-versus-time data. Due to 
the sparse nature of PK collection, PK parameters will not be calculated. 




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9.
ETHICAL CONSIDERATIONS
This study will be conducted in accordance with the protocol and with the International Council 
for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, the Declaration of Helsinki, 
and any applicable local health authority and IRB/IEC requirements.
To the extent applicable, all references to the ICH, GCP, and the like shall be interpreted as also 
referring to any corresponding requirements of local regulatory agencies, regulations, and laws. 
If there is any discrepancy between ICH and local requirements, the most stringent standard shall 
apply.
9.1.
Investigator Responsibilities
As required by FDA regulation (21 CFR Part 56) and ICH guidelines for GCP, the Investigator 
at each study site must obtain IRB/IEC review and approval of the study protocol, ICFs, 
participant recruitment materials, and any other pertinent documents before any study-related 
activities involving participants are performed.
As required in 21 CFR Part 50 and ICH guidelines for GCP, the Investigator or designee must 
comply with the informed consent process and ensure that each participant enrolled in this 
clinical study understands the information presented in the IRB/IEC-approved ICF and agrees 
voluntarily to participate in the clinical study.
The Investigator or designee must submit to the IRB/IEC any written safety report or update 
(e.g., amended IB or safety amendments and updates) provided by the Sponsor or representative, 
according to the IRB/IEC-specific reporting requirements.
The Investigator must inform the IRB/IEC of the progress of the clinical study and report any 
nonadministrative changes made to the protocol; in any case, the Investigator must provide an 
update to the IRB/IEC at least once a year or in accordance with IRB/IEC continuing approval 
requirements.
The Investigator must maintain a list of appropriately qualified persons to whom he/she has 
delegated study duties and supervise the delegates. All persons authorized to make entries and/or 
corrections on eCRFs will be included on the Gilead Sciences, Inc. Delegation of Authority 
Form.
The clinical study report must be signed by the Investigator or, in the case of multicenter studies, 
the Coordinating Investigator. The Coordinating Investigator, identified by Gilead Sciences, Inc., 
will be any or all of the following:

A recognized expert in the therapeutic area

An Investigator who provided significant contributions to either the design or interpretation 
of the study

An Investigator contributing a high number of eligible participants


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications may be made only by Gilead.
9.2.2.
Study Reports and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency when 
applicable and in accordance with local regulatory requirements. Gilead will ensure that the 
report meets the standards set out in the ICH Guideline for Structure and Content of Clinical 
Study Reports (ICH E3). For studies with sites in countries following the EU Regulation 
No. 536/2014, a CSR will be submitted within 1 year (6 months for pediatric studies, in 
accordance with Regulation [EC] No. 1901/2006) after the global end of study (as defined in 
Section 5.9).
Investigators in this study may communicate, orally present, or publish study data in scientific 
journals or other scholarly media in accordance with the Gilead clinical trial agreement.
9.3.
Ethics Review 
A copy of the protocol, ICF, other written participant information, and any proposed advertising 
material must be submitted to the IRB/IEC for written approval. A copy of the written approval 
of the protocol and ICF must be received by Gilead Sciences, Inc. or designee before 
randomization of participants in the study and shipment of magrolimab.
The Investigator must submit and, where necessary, obtain approval from the IRB/IEC for all 
subsequent protocol amendments and changes to the ICF. The Investigator is to notify the 
IRB/IEC of important deviations from the protocol or SAEs occurring at the site and other AE 
reports received from Gilead Sciences, Inc., in accordance with local procedures.
The Investigator is responsible for obtaining annual IRB/IEC approval/renewal as per 
country-specific requirements throughout the duration of the study. Copies of the Investigator’s 
reports and the IRB/IEC continuance of approval must be sent to Gilead Sciences, Inc.
9.4.
Informed Consent
A final country level master template ICF will be provided for the Investigator to prepare the site 
specific ICF to be used at his or her site. However, the site level adaptation may be delegated to a 
clinical research organization. Updates to the template are to be communicated formally in 
writing from the Gilead Sciences, Inc. study monitor to the Investigator. The written ICF is to be 
prepared in the language(s) of the potential participant population.
Before a participant’s participation in the clinical study, the Investigator is responsible for 
obtaining written informed consent from the participant after adequate explanation of the aims, 
methods, anticipated benefits, and potential hazards of the study and before any protocol-specific 
screening procedures or any investigational products are administered. 


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The Investigator is also responsible for asking the participant if the participant has a primary care 
physician and if the participant agrees to have his/her primary care physician informed of the 
participant’s participation in the clinical study. If the participant agrees to such notification, the 
Investigator is to inform the participant’s primary care physician of the participant’s participation 
in the clinical study. If the participant does not have a primary care physician and the 
Investigator will be acting in that capacity, the Investigator is to document such in the 
participant’s medical record. The acquisition of informed consent and the participant’s 
agreement or refusal of his/her notification of the primary care physician is to be documented in 
the participant’s medical records, and the ICF is to be signed and personally dated by the 
participant, and by the person who conducted the informed consent discussion. The original 
signed ICF is to be retained in accordance with institutional policy, and a copy of the signed 
consent form is to be provided to the participant.
If a potential participant is illiterate or visually impaired, the Investigator must provide an 
impartial witness to read the ICF to the participant and must allow adequate time for questions. 
Thereafter, both the participant and the witness must sign the ICF to attest that informed consent 
was freely given and understood. If a participant has questions during the conduct of the study, 
the Investigator or site staff must provide assistance.
The informed consent form will inform participants about genomic testing and/or planned 
sample retention. Genomic testing is not optional and is a requirement for study participation. In 
addition to the study-specific informed consent form to be signed by each participant 
participating in the study, participants will be required to document agreement to allow the use of 
the remainder of their already-collected specimens for optional future research, in accordance 
with applicable regulations. The results of the tests done on the samples will not be given to the 
participant or the Investigator.
9.5.
Data Privacy and Confidentiality 
The Investigator must ensure that the participant’s confidentiality is maintained for documents 
submitted to Gilead Sciences, Inc., including the following:

Participants are to be identified by a unique patient identification number.

Where permitted, birth year is to be documented and formatted in accordance with local laws 
and regulations.

On the eCRF demographics page, in addition to the unique patient identification number, the 
age at time of randomization is to be included.

For SAEs reported to Gilead Sciences, Inc., participants are to be identified by their unique 
patient identification number, and birth year (in accordance with local laws and regulations).
Participant medical information obtained by this study is confidential and may be disclosed to 
third parties only as permitted by the ICF (or separate authorization for use and disclosure of 
personal health information) signed by the participant, unless permitted or required by law.


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Documents that are not submitted to Gilead Sciences, Inc. (e.g., signed ICFs) are to be kept in 
confidence by the Investigator, except as described below.
In compliance with the CFR/ICH GCP Guidelines, it is required that the Investigator and 
institution permit authorized representatives of the company, of the regulatory agency(ies), and 
the IRB/IEC direct access to review the participant’s original medical records for verification of 
study-related procedures and data. 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 participant to permit such 
individuals to have access to his/her study-related records, including personal information.
9.6.
Urgent Safety Measures
The Sponsor or Investigator may take appropriate urgent safety measures to protect study 
participants from any immediate hazard to their health or safety. Urgent safety measures may be 
taken without prior authorization. The study may continue with the urgent safety measures in 
place. The Investigator must inform the IRB/IEC and Gilead Sciences, Inc. immediately if 
the study site initiates an urgent safety measure.
The notification must include:

date of the urgent safety measure;

who made the decision; and

why the action was taken.
The Investigator will provide any other information that may be required to enable 
Gilead Sciences, Inc. to report and manage the urgent safety measure in accordance with the 
current regulatory and ethical requirements for expedited reporting and closeout.
9.7.
Disclosure
A description of this clinical study will be available on http://www.ClinicalTrials.gov, as well as 
other country-specific registries, as required by US law and/or other country laws.
9.8.
Biological Specimens and Data
Blood and bone marrow specimens will be cryopreserved and biobanked for additional analyses. 
These samples will be retained for long-term storage by the Sponsor and described in the 
informed consent.
Any blood, tissue, or biomarker sample collected according to the Schedule of Assessments 
(Section 4.3) may be analyzed prior to or after study unblinding for any tests outlined in the 
protocol. This includes testing to ensure that analytical methods produce reliable and valid data 
throughout the course of the study. It may also include, but is not limited to, investigation of 
unexpected results, incurred sample reanalysis, and analyses for method transfer comparability.


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All samples and associated results will be coded prior to being shipped from the site for analysis 
or storage. Samples will be tracked using a unique identifier that is assigned to the samples for 
the study. Results are stored in a secure database to ensure data integrity and control. Samples 
may be retained for up to 15 years.
If permitted by local law and if informed consent is provided by the participant, Gilead 
Sciences, Inc. may do additional testing on remaining samples (i.e., residual and back-up) to 
investigate and better understand MDS and the dose response and/or prediction of response to 
magrolimab, to characterize antibody response, and to characterize aspects of the molecule 
(e.g., MOA/target, metabolites). Results from this analysis are to be documented and maintained 
but are not necessarily reported as part of this study.
Since the evaluations are not expected to benefit the participant directly or to alter the 
participant’s treatment course, the results of these exploratory studies are not placed in the 
participant’s medical record and are not to be made available to the participant, members of the 
participant’s family, the participant’s personal physician, or other third parties, except as 
specified in the ICF.
The participant retains the right to request that the sample material be destroyed by contacting 
the Investigator. Following the request from the participant, the Investigator is to provide the 
Sponsor with the required study and patient number so that any remaining blood samples and 
any other components from the cells can be located and destroyed. Samples will be destroyed 
once all protocol-defined procedures have been completed.
Information collected from samples prior to the request for destruction will be retained by the 
Sponsor. The Sponsor is the exclusive owner of any data, discoveries, and derivative materials 
from the sample materials and is responsible for the destruction of the sample(s) at the request of 
the participant through the Investigator, at the end of the storage period or as appropriate (e.g., 
the scientific rationale for experimentation with a certain sample type no longer justifies keeping 
the sample). If a commercial product is developed from this research project, the Sponsor owns 
the commercial product. The participant has no commercial rights to such product and has no 
commercial rights to the data, information, discoveries, or derivative materials gained or 
produced from the sample.
9.8.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol (e.g., attendance at Investigator meetings). If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to federal and state agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.


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10.
OVERSIGHT
10.1.
Independent Monitoring 
10.1.1.
DMC
The DMC will review the unblinded data generated during the clinical study. The mandate of the 
DMC is to serve as an independent committee with pertinent clinical and study conduct expertise 
to monitor and ensure the safety of the therapies for participants on study. The composition, 
structure, and function of the DMC and the scope of data for review are defined in the 
DMC Charter. The timing of such data review will be predefined in the DMC Charter.
10.2.
Quality Control and Assurance
10.2.1.
Monitoring
The Gilead Sciences, Inc. representative(s) are responsible for contacting and visiting the 
Investigator for the purpose of inspecting the facilities and, upon request, inspecting the various 
records of the clinical study (e.g., eCRFs and other pertinent data) provided that participant 
confidentiality is respected.
The Gilead Sciences, Inc. representative(s) are responsible for verifying the eCRFs at regular 
intervals throughout the study to verify adherence to the protocol; completeness, accuracy, and 
consistency of the data; and adherence to local regulations on the conduct of clinical research. 
The Gilead Sciences, Inc. representative(s) are to have access to participant medical records and 
other study-related records needed to verify the entries on the eCRFs.
The Investigator agrees to cooperate with the Gilead Sciences, Inc. representative(s) to ensure 
that any problems detected in the course of these monitoring visits, including delays in 
completing eCRFs, are resolved.
10.2.2.
Audits
As stipulated by 21 CFR §312.58 and ICH guidelines for GCP, a representative of the Sponsor or 
regulatory agency may conduct periodic site audits or inspections. The Investigator or designee 
will provide these representatives with access to all requested materials, including eCRFs and 
supporting source documents. In addition, the Investigator or other qualified study site personnel 
are to be available to answer questions, hold interviews, and provide facility tours if requested.
10.2.3.
Records 
10.2.3.1.
Data Capture and Management
The Investigator is responsible for complying with the requirements for all assessments and data 
collection (including participants not receiving protocol-required therapies), as stipulated in the 
protocol for each participant in the study. For participants who discontinue from the study prior 


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to completion of all protocol-required visits for study assessments or survival follow-up as 
described in Section 4.3, the Investigator may search publicly available records (where permitted 
by local laws and regulations) to ascertain survival status. This ensures reduced risk of missing 
critical efficacy data.
The Investigator agrees to maintain adequate case histories for the participants treated as part of 
the research under this protocol. Data collection will involve the use of the EDC system, to 
which only authorized personnel will have access. The Investigator agrees to maintain accurate 
eCRFs and source documentation as part of the case histories.
The Investigator or designee must enter all results collected during the clinical study into eCRFs. 
Guidelines for completion of eCRFs will be reviewed with study site personnel at the site 
initiation visits. Investigators are responsible for approval of the entered/corrected data. At a 
minimum, prior to any interim time points or database lock (as instructed by Gilead), the 
Investigator will use his/her log-in credentials to confirm that the forms have been reviewed, and 
that the entries accurately reflect the information in the source documents. Detailed instructions 
are provided in the other study-specific documents.
All entries made on the eCRF may require verification against source documents. In addition to 
periodic monitoring occurring within the system by study monitors, programmatic edit checks 
and data listings will be used to review the data for completeness, logic, and adherence to study 
protocol. As a result of this monitoring and these checks, queries may be electronically issued to 
the clinical study sites and electronically resolved by those sites.
All data collected in the context of this study will be stored and evaluated according to regulatory 
requirements and applicable guidance for electronic records. Also, data will be stored and 
evaluated in such a way as to assure participant confidentiality in accordance with the legal and 
regulatory requirements applying to protected health information. Study records (e.g., copies of 
eCRFs, regulatory documents) will be retained at the study site, along with adequate source 
documentation. The study file and all source data must be retained for the time period required 
by applicable regulatory requirements and will not be destroyed until written notification is given 
by the Sponsor or designee for destruction.
10.2.3.2.
Source Documentation
As stipulated by 21 CFR §312.57 and ICH E6 GCP Consolidated Guidance Section 8, 
the Investigator or designee will maintain source documentation for this clinical study that 
documents the treatment and study course of participants.
The source data for this study may be obtained from EDC and central or local laboratory reports. 
Source documents are original documents, data, and records from which the participant’s eCRF 
data are obtained. These include, but are not limited to, hospital records, clinical and office 
charts, laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence.


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10.2.3.3.
Study Files 
The Investigator and study staff are responsible for maintaining a comprehensive and centralized 
filing system of all study-related (essential) documentation, suitable for inspection at any time by 
representatives from Gilead Sciences, Inc. and/or applicable regulatory authorities.
10.2.3.4.
Records Retention
The Investigator must retain all essential documents for this clinical study until 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 magrolimab. 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 the Sponsor. A Sponsor representative will be 
responsible for informing the Investigator and study site regarding when they no longer need to 
retain these documents. Before destroying any records, the Investigator must notify the Sponsor 
and reach agreement on record destruction, or the Sponsor may request an additional retention 
period.
10.3.
Serious Breaches or Fraud
A serious breach is defined as “A breach of GCP or the study protocol which is likely to effect to 
a significant degree:

the safety or physical or mental integrity of the participants of the study; or

the scientific value of the study”
Investigators or designee must notify Gilead Sciences, Inc. immediately if any serious breach of 
GCP is suspected and prior to notifying IRB/IECs.
If there is any proof of fraud, this must also be reported to Gilead Sciences, Inc. If any additional 
local or national reporting is required, this must also be done.
10.4.
Study Termination or Study Site Closure
Gilead Sciences, Inc. reserves the right to terminate the study at any time. Both Gilead 
Sciences, Inc. and the Investigator reserve the right to terminate the Investigator’s participation 
in the study according to the study contract. The Investigator is to notify the IRB/IEC in writing 
of the study’s completion or early termination and send a copy of the notification to Gilead 
Sciences, Inc.
The study may also be terminated for safety reasons.


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11.
FINANCIAL DISCLOSURE AND INSURANCE
The Sponsor maintains clinical study insurance coverage for this study in accordance with the 
laws and regulations of the country in which the study is performed.
The Investigator and Subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead or proprietary interests in the study drug during 
the course of a clinical study. This documentation must be provided prior to the Investigator’s 
(and any Subinvestigator’s) participation in the study. The Investigator and Subinvestigator agree 
to notify Gilead of any change in reportable interests during the study and for 1 year following 
completion of the study. Study completion is defined as the date when the last participant 
completes the protocol-defined activities.


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12.
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Pavlu J, Labopin M, Niittyvuopio R, Socie G, Yakoub-Agha I, Wu D, et al. Measurable residual 
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[IGT46]. Transfusion 2018;58 (S2):179A-80A.
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13.
APPENDICES
Appendix A.
National Cancer Institute Common Terminology Criteria for Adverse 
Events
Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute 
(NCI), Version 5.0
Publication date: 27 November 2017 (v5.0) 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf
Accessed 18 February 2020


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Appendix B.
Disease Response Assessment Based on International Working Group 
Criteria
Response will be assessed in myelodysplastic syndrome (MDS) patients using the 
2006 International Working Group (IWG) criteria {Cheson 2006} as shown in Table 19. In 
addition, complete remission (CR) with partial hematologic recovery (CRh) will be assessed for 
MDS, defined as patients who achieve a CR per IWG 2006 MDS criteria {Cheson 2006}, with 
the exception of requiring partial hematologic recovery as defined by a platelet count of 
> 50 × 109/L and an absolute neutrophil count of > 500/μL.
In addition, HI will be assessed by 2006 IWG criteria {Cheson 2006} (Table 21) and 
cytogenetic/molecular response by 2003 IWG criteria {Cheson 2003} (Table 20).
Table 19.
Response Criteria in MDS (IWG 2006 Criteria With Modifications)
Category
Response Criteria
CR
Bone marrow ≤ 5% myeloblasts with normal maturation of all cell linesa
Persistent dysplasia will be noteda,b
Peripheral bloodc
Hgb ≥ 11 g/dL
Platelets ≥ 100 × 109/L
Neutrophils ≥ 1.0 × 109/Lb
Blasts 0%
PR
All CR criteria if abnormal before treatment except:
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%
Cellularity and morphology not relevant
Marrow CRb
Bone marrow ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatmentb
Peripheral blood: if HI responses, they will be noted in addition to marrow CRb
Stable Disease
Failure to achieve at least PR, but no evidence of progression for > 8 weeks
Failure
Death during treatment or disease progression characterized by worsening cytopenias, increase in 
percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than 
pretreatment
Relapse after CR or 
PR
At least 1 of the following:
Return to pretreatment bone marrow blast percentage
Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets
Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependenced
Cytogenetic 
Response
Complete: Disappearance of chromosomal abnormality without appearance of new ones
Partial: At least 50% reduction of the chromosomal abnormality
Disease Progression
For patients with:
Less than 5% blasts: ≥ 50 increase in blasts to > 5% blasts
5%-10% blasts: ≥ 50% increase in blasts to > 10% blasts
10%-20% blasts: ≥ 50% increase in blasts to > 20% blasts
20%-30% blasts: ≥ 50% increase in blasts to > 30% blasts
Any of the following:
At least 50% decrement from maximum remission/response in granulocytes or platelets
Reduction in Hgb by ≥ 2 g/dLd
Transfusion dependenced
Source: {Cheson 2006}
Abbreviations: CR = complete remission; FAB = French-American-British classification; Hgb = hemoglobin; HI = hematologic 
improvement; IWG = International Working Group; MDS = myelodysplastic syndrome; PR = partial remission.
a
Dysplastic changes should consider the normal range of dysplastic changes.
b
Modification to IWG response criteria.
c
Transient cytopenias during repeated chemotherapy courses should not be considered as interrupting durability of response, 
as long as they recover to the improved counts of the previous course.
d
Impact of anemia must be deemed disease-related and not due to study treatment.


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Table 20.
Additional Response Definitions Used in This Study 
(2003 IWG Criteria)
Definitions
Response Criteria
Neutrophils
Platelets
Bone Marrow 
Blasts
Other
cCR
≥ 1.0 × 109/L
≥ 100 × 
109/L
< 5%
Cytogenetics normal and no 
evidence of extramedullary disease
mCR
≥ 1.0 × 109/L
≥ 100 × 
109/L
< 5%
Molecular investigations normal 
and no evidence of extramedullary 
disease
Treatment Failurea
Lack of response/Progressive Disease + loss of clinical benefit
Source: {Cheson 2003}
Abbreviations: cCR = cytogenetic complete remission; IWG = International Working Group; mCR = molecular complete 
remission.
a
Treatment failure defined for this protocol
Table 21.
Response Criteria for Hematologic Improvement
Hematologic Improvement (HI) 
Categorya
Response Criteria (all responses must last ≥ 8 weeks)
Erythroid Response (HI-E)
(pretreatment < 110 g/L)
Pretransfusion increase in hemoglobin by 15 g/L
or
Compared to an 8-week pretreatment period, a reduction in 
transfusion requirements by 4 units in an 8-week posttreatment 
period 
Platelet Response (HI-P)
(pretreatment < 100 × 109/L)
Absolute increase of ≥ 30 × 109/L for patient starting with a 
platelet count > 20 × 109/L pretreatment
or
Increase from < 20 × 109/L pretreatment to > 20 × 109/L 
posttreatment and by at least 100%
Neutrophil Response (HI-N)
(pretreatment < 1.0 × 109/L)
At least 100% increase and an absolute increase of > 0.5 × 109/L
Progression/relapse after Hematological 
Improvementb
One or more of the following
≥ 50% decrement from maximum response in neutrophils or 
platelets
Reduction in hemoglobin by ≥ 15 g/L
Transfusion dependence
Source: {Cheson 2006}
a
Pretreatment counts should be an average of at least 2 measurements (not influenced by transfusions) performed ≥ 1 week 
apart.
b
In the absence of another explanation. For example, including, but not restricted to, acute infection, gastrointestinal bleeding 
and hemolysis.


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Appendix C.
Functional Assessment of Cancer Therapy – Anemia
Available online:
FACT-An (facit.org)


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Appendix D.
5-Level EuroQol 5 Dimensions Questionnaire (EQ-5D-5L)
Available online:
EQ-5D-5L – EQ-5D (euroqol.org)Sample_UK-English-EQ-5D-5L-Paper-Self-Complete-v1.2-
ID-24700.pdf


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Appendix E.
Patient Global Impression of Severity and Patient Global Impression 
of Change 
Publication:
Guy W (ed). ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US 
Department of Health, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and 
Mental Health Administration, 1976
Available online:
PGI-C, PGI-I, PGI-S - Patient Global Impressions scale - Change, Improvement, Severity (mapi-
trust.org)
PGI-C_TS1.0_eng-USori_review copy (1).pdf


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Appendix F.
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group Scale of Performance Status
Publication:
Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-655.
Available online:
http://ecog-acrin.org/resources/ecog-performance-status
Accessed 18 February 2020


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Appendix G.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1.
Definitions
a.
Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming postmenopausal, unless 
permanently sterile or with medically documented ovarian failure.
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause. In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female participant of any age.
b.
Definition of Male Fertility
For the purposes of this study, a male born participant is considered fertile after the initiation of 
puberty, unless permanently sterile by bilateral orchidectomy or medical documentation.
2.
Contraception Requirements for Female Participants
a.
Study Drug Effects on Pregnancy and Hormonal Contraception
Magrolimab is contraindicated in pregnancy as a malformative effect has been 
demonstrated/suspected or is unknown taking into consideration class effect and/or strong 
suspicion of human teratogenicity/fetotoxicity in early pregnancy based on nonclinical data. For 
magrolimab, there is no anticipated PK interaction with progestin or other steroids based on the 
distinct clearance pathways. 
Based on the mechanism of action and findings in animals, azacitidine may cause fetal harm 
when administered to a pregnant woman. Advise females with reproductive potential to avoid 
pregnancy during treatment with azacitidine. Studies in vitro have demonstrated that CYP 
enzyme induction or inhibition by azacitidine at clinically achievable plasma concentrations is 
unlikely. 
Refer to the latest version of the magrolimab IB for additional information. Refer to the regional 
prescribing information regarding the potential risks of treatment with azacitidine. 


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b.
Contraception Requirements for Female Participants of Childbearing Potential
The inclusion of female participants of childbearing potential requires the use of highly effective 
contraceptive measures with a failure rate of < 1% per year. They must have a negative serum 
pregnancy test at Screening, and a negative pregnancy test is required prior to study treatment 
administration on Cycle 1 Day 1. Pregnancy tests will be performed at the beginning of each 
cycle thereafter (described in the protocol) until the end of the contraception requirement. 
The duration of required contraception for female participants in this clinical trial should start 
from the Screening Visit until 6 months after the last dose of azacitidine or magrolimab/placebo, 
whichever is later.
Female participants must agree to one of the following contraceptive methods: 
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the participant’s preferred and usual 
lifestyle. 
Or
Consistent and correct use of 1 of the following methods of birth control listed below: 

Hormonal or non-hormonal intrauterine device (IUD) 

Subdermal contraceptive implant

Bilateral tubal occlusion (upon medical assessment of surgical success)

Vasectomy in the male partner (upon medical assessment of surgical success)
Or 
Female participants who wish to use a hormonally based method must use it in conjunction with 
a barrier method, preferably a male condom. Hormonal methods are restricted to those associated 
with the inhibition of ovulation. Hormonally based contraceptives and barrier methods permitted 
for use in this protocol are as follows:

Hormonal methods (each method must be used with a barrier method, preferably male 
condom)
Oral contraceptives (either combined or progesterone only)
Injectable progesterone
Transdermal contraceptive patch
Contraceptive vaginal ring


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
Barrier methods (each method must be used with a hormonal method)
Male condom (with or without spermicide)
Female condom (with or without spermicide)
Diaphragm with spermicide
Cervical cap with spermicide
Sponge with spermicide
Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved. 
Female participants must also refrain from egg donation, cryopreservation of cells, and in vitro 
fertilization during treatment and until the end of contraception requirement. If needed, female 
participants should be advised to seek advice about egg donation and cryopreservation prior to 
treatment. 
3.
Contraception Requirements for Male Participants
Male participants with female partners of childbearing potential must use condoms during 
treatment and until 3 months after the last dose of azacitidine or magrolimab/placebo, whichever 
is later. If the female partner of childbearing potential is not pregnant, use of any locally 
approved contraceptive method should also be considered.
Male participants must also refrain from sperm donation and cryopreservation of cells during 
treatment and until the end of contraception requirement. If needed, male participants should be 
advised to seek advice about sperm donation and cryopreservation prior to treatment. 
4.
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (e.g., calendar, 
ovulation, symptothermal, and postovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM). A female condom and a male 
condom should not be used together.
5.
Procedures to be Followed in the Event of Pregnancy
Participants will be instructed to notify the Investigator immediately if they become pregnant at 
any time during the study or if they become pregnant within 6 months of last study drug dose. 
Participants who become pregnant or who suspect that they are pregnant during the study must 
report the information to the Investigator and discontinue study drug immediately. Participants 
whose partner has become pregnant or suspects she is pregnant during the study must report the 
information to the Investigator. Instructions for reporting pregnancy and pregnancy outcome are 
outlined in Section 7.8.2.3.


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Appendix H.
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with participants being unable to attend 
study visits have been identified for this study. 
These potential risks & mitigation plans can be summarized as follows:
1) Schedule of assessments:
a) Physical Exam: 
i)
For all assessments where a physical exam is indicated, this portion of the visit can be 
conducted virtually. While samples will need to be collected, and dosing will need to 
occur on dosing days in clinic.
ii) If a virtual visit is conducted for the physical exam assessment portion, in order to 
limit a participant’s time in the clinic, vital signs may be omitted.
b) Dosing:
i)
For the priming and repriming period, magrolimab/placebo can be administered on 
Day 7 with azacitidine with collection of Day 8 assessments (i.e. labs, PK) on Day 7 
in order to minimize an extra participant visit.
ii) Dosing with azacitidine:
(1) If needed under specific circumstances, sites can allow for administration of 
azacitidine locally nearer to participant’s residence, with proper documentation 
(i.e., name of site, name of MD overseeing transfusion, name of laboratory used 
including accreditation certificate, etc.)
(2) If treatment administration is given locally, then the participant should be 
evaluated by a local hematologist on Day 1 of that treatment cycle and have all 
labs required on Day 1 treatment cycle performed as per the protocol. The site 
should procure the clinical notes and lab reports for the PI review and signature. 
Site to ensure all these documents are filed in the participant’s source. 
(3) The treating MD at the study site should speak to the local hematologist and go 
over protocol guidelines/dosing of Aza/reporting of reactions and document this 
information in the medical records.
(4) This should be reserved only in cases where participants will not be able to get 
azacitidine dosing otherwise.


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c) Sample Collection:
i)
While it is preferred to collect all protocol specified lab samples, if resources are 
limited, PK/ADA samples may be collected and stored (frozen) and not shipped real 
time if staff are not available to do so.
ii) MRD testing should be collected and shipped. If real time shipping is not possible 
then add RPMI no more than 1:1 ratio if shipment is delayed more than 24 hours but 
not exceed 48 hours and store at room temperature.
iii)  For correlative peripheral blood or bone marrow aspirate samples, if they cannot be 
shipped according to their corresponding standard procedures same day, or 
refrigerated overnight for shipment the next day, please isolate mononuclear cells 
(e.g. by Ficoll gradient) and cryopreserve according to local best practices. If it is not 
possible to either ship samples or preserve and store according to the guidance above, 
then collection of these samples may be omitted until normal operations can resume.
d) General participant selection guidance:
i)
To minimize participants receiving RBC transfusions given the current transfusion 
product shortage, we recommend selecting participants with higher hemoglobin 
thresholds at baseline and use IV iron and/or erythropoietin where clinically 
indicated.
2) Participant safety monitoring and follow-up:
a) Participants may be unable or unwilling to come to the study site for their scheduled 
study visits as required per protocol.
Mitigation plan: For participants who may be unable or unwilling to visit the study site 
for their scheduled study visits as required per protocol, the PI or qualified delegate will 
conduct a virtual study visit, via phone or video conferencing, to assess the participant 
within the target visit window date whenever possible. During the virtual study visit, the 
following information at minimum will be reviewed: 
i)
Confirm if participant has experienced any adverse events (AEs)/serious adverse 
events (SAEs)/special situations (including pregnancy) and follow-up on any 
unresolved AE/SAEs.
ii) Review current list of concomitant medications and document any new concomitant 
medications.
iii) If applicable, confirm that patient-reported outcome questionnaires have been 
completed and transmitted.


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b) Participants may be unable or unwilling to travel to the site for planned assessments 
(e.g., safety blood draws); hence, samples may not be sent for central laboratory analyses.
Mitigation plan: Local laboratories may be utilized as appropriate to monitor participant 
safety until the participant can return to the site for their regular follow-up per protocol. 
Any laboratory assessments conducted at a local laboratory due to the pandemic will be 
documented accordingly. Pregnancy testing may be performed using a home urine 
pregnancy test if local laboratory pregnancy testing is not feasible.
c) Participants may be unable or unwilling to attend the study visit to sign an updated 
informed consent form (ICF) version.
Mitigation plan: The site staff will follow their approved consent process and remain in 
compliance with local EC/IRB and national laws and regulations. Remote consent will be 
allowed if it has been approved by the local EC/IRB. The consent process will be 
documented and confirmed by normal consent procedure at the earliest opportunity. 
d) The safety of trial participants is important and testing of COVID-19 infection will be 
based on local clinical guidelines for testing based on signs/symptoms and or suspected 
exposure to COVID-19. 
Mitigation Plan: If participant has a diagnosis of COVID-19 while on this clinical study, 
study drugs may be held until clinical improvement or resolution in accordance with the 
treating physician’s judgment and general magrolimab/azacitidine dose delay guidance in 
the protocol. Additional supportive care and treatment measures for COVID-19 infection 
on the study will be performed in accordance with local institutional guidelines. 
Participants with a COVID-19 infection while participating in a clinical trial will have 
this event documented as an adverse event in the clinical database. 
3) Protocol and monitoring compliance:
a) Protocol deviations may occur, in case scheduled visits cannot occur as planned per 
protocol.
Mitigation plan: If it is not possible to complete a required procedure, an unscheduled 
visit should be conducted as soon as possible when conditions allow. The situation should 
be recorded and explained as a protocol deviation. Any missed participant visits or 
deviation to the protocol due to the pandemic must be reported in the eCRF and described 
in the clinical study report. Any virtual study visits that are conducted in lieu of clinic 
visits due to the pandemic will be documented as a protocol deviation related to the 
pandemic.
b) Monitors may be unable to carry out source data review (SDR), source data verification 
(SDV), or study drug accountability or assess protocol and GCP compliance. This may 
lead to delays in SDV, an increase in protocol deviations, or under reporting of AEs.


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Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure data entry and query resolution. Remote SDV may be arranged if allowed. The 
study monitor is to reference the Study Monitoring Plan for guidance on how to conduct 
a remote monitoring visit. The study staff is to save and document all relevant 
communication in the study files. The status of sites that cannot accept monitoring visits 
and/or participants on site must be tracked centrally and updated on a regular basis.
4) Missing data and data integrity:
a) There may be an increased amount of missing data due to participants missing 
visits/assessments. This could have an impact on the analysis and the interpretation of 
clinical trial data. 
Mitigation plan: Implications of a pandemic on methodological aspects for the study will 
be thoroughly assessed and documented, and relevant actions will be taken as appropriate 
(i.e., modification of the statistical analysis plan) and in compliance with Regulatory 
Authorities’ guidance. Overall, the clinical study report will describe the impact of the 
pandemic on the interpretability of study data. 
Risks will be assessed continuously, and temporary measures will be implemented to mitigate 
these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide alternative 
methods that will ensure the evaluation and assessment of the safety of participants who are 
enrolled in this study.
Since these potential risks are considered mitigated with the implementation of these measures, 
the expected benefit-risk assessment of the study drugs in study participants remains unchanged. 
In case these potential risks cannot be mitigated due to the escalation of a pandemic, 
randomization of new participants will be placed on hold until the pandemic outbreak is under 
control by following local regulatory guidelines.


amd-8-prot 5F9009
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical Research eSigned
PPD
PPD

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
ENHANCE: A Randomized, Double-blind, Multicenter Study 
Comparing Magrolimab in Combination with Azacitidine 
versus Azacitidine Plus Placebo in Treatment-naïve Patients 
with Higher Risk Myelodysplastic Syndrome
Name of Test Drug:
Magrolimab (Hu5F9-G4) (GS-4721) 
Study Number:
5F9009
Protocol Version (Date):
Amendment 7 (27 July 2022)
Analysis Type:
Interim Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
29 July 2022
Analysis Plan Authors:
Jiang Shao, PhD
CONFIDENTIAL AND PROPRIETARY INFORMATION


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................4
LIST OF ABBREVIATIONS.........................................................................................................................................5
1.
INTRODUCTION..................................................................................................................................................7
1.1.
Study Objectives........................................................................................................................................7
1.2.
Study Design .............................................................................................................................................9
1.3.
Sample Size and Power ...........................................................................................................................10
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................12
2.1.
DMC Interim Analyses............................................................................................................................12
2.2.
Optional Interim Analysis Performed by Sponsor ..................................................................................15
2.3.
Final Analysis..........................................................................................................................................15
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................16
3.1.
Analysis Sets ...........................................................................................................................................16
3.1.1.
Intent-to-Treat (ITT) Analysis Set.........................................................................................16
3.1.2.
Safety Analysis Set................................................................................................................16
3.1.3.
Pharmacokinetic Analysis Set ...............................................................................................16
3.1.4.
Immunogenicity Analysis Set................................................................................................16
3.2.
Subject Grouping.....................................................................................................................................17
3.3.
Strata and Covariates...............................................................................................................................17
3.4.
Examination of Subject Subgroups .........................................................................................................17
3.5.
Multiple Comparisons .............................................................................................................................18
3.6.
Missing Data and Outliers.......................................................................................................................18
3.6.1.
Missing Data..........................................................................................................................18
3.6.2.
Outliers ..................................................................................................................................18
3.7.
Data Handling Conventions and Transformations ..................................................................................18
3.8.
Analysis Visit Windows..........................................................................................................................19
3.8.1.
Definition of Study Day ........................................................................................................19
3.8.2.
Analysis Visit Windows........................................................................................................19
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window .................................................................................................................................21
4.
SUBJECT DISPOSITION ...................................................................................................................................22
4.1.
Subject Enrollment and Disposition........................................................................................................22
4.2.
Extent of Study Drug Exposure...............................................................................................................23
4.2.1.
Duration of Exposure to Study Drug.....................................................................................23
4.2.2.
Relative Dose Intensity..........................................................................................................23
4.3.
Protocol Deviations .................................................................................................................................24
4.4.
Assessment of COVID-19 Impact...........................................................................................................24
4.4.1.
Study Drug or Study Discontinuation Due to COVID-19.....................................................24
4.4.2.
Protocol Deviations Due to COVID-19 ................................................................................25
4.4.3.
Missed and Virtual Visits due to COVID-19 ........................................................................25
4.4.4.
Adverse Events Due to COVID-19 .......................................................................................25
5.
BASELINE CHARACTERISTICS .....................................................................................................................26
5.1.
Demographics and Baseline Characteristics ...........................................................................................26
5.2.
Other Baseline Characteristics ................................................................................................................26
5.3.
Medical History.......................................................................................................................................26


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6.
EFFICACY ANALYSES.....................................................................................................................................27
6.1.
Primary Efficacy Endpoints ....................................................................................................................27
6.1.1.
Definition of Primary Efficacy Endpoints.............................................................................27
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoints ...................................................27
6.1.3.
Analysis of the Primary Efficacy Endpoints .........................................................................28
6.1.4.
Follow-up Time.....................................................................................................................28
6.1.5.
Sensitivity Analysis of the Primary Efficacy Endpoint.........................................................29
6.1.6.
Exploratory Analysis of the Primary Efficacy Endpoint.......................................................29
6.2.
Secondary Efficacy Endpoints ................................................................................................................29
6.2.1.
Definition of Secondary Efficacy Endpoints.........................................................................29
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints...........................................................31
6.3.
Exploratory Efficacy Endpoints ..............................................................................................................33
6.3.1.
Definition of Exploratory Efficacy Endpoints ......................................................................33
6.3.2.
Analysis Methods for Exploratory Efficacy Endpoints.........................................................33
6.4.
Patient-Reported Outcome ......................................................................................................................34
6.4.1.
Definition of Patient-Reported Outcome Data......................................................................34
6.4.2.
Analysis of Patient-Reported Outcome Data ........................................................................34
7.
SAFETY ANALYSES.........................................................................................................................................35
7.1.
Adverse Events and Deaths.....................................................................................................................35
7.1.1.
Adverse Event Dictionary .....................................................................................................35
7.1.2.
Adverse Event Severity .........................................................................................................35
7.1.3.
Relationship of Adverse Events to Study Drug.....................................................................35
7.1.4.
Serious Adverse Events.........................................................................................................35
7.1.5.
Treatment-Emergent Adverse Events....................................................................................35
7.1.6.
Summaries of Adverse Events and Deaths............................................................................36
7.1.7.
Additional Analysis of Adverse Events ................................................................................38
7.2.
Laboratory Evaluations ...........................................................................................................................39
7.2.1.
Summaries of Numeric Laboratory Results ..........................................................................40
7.2.2.
Graded Laboratory Values ....................................................................................................40
7.2.3.
Liver-related Laboratory Evaluations....................................................................................41
7.2.4.
Shifts Relative to the Baseline Value ....................................................................................41
7.3.
Body Weight and Vital Signs..................................................................................................................42
7.4.
Prior and Concomitant Medications........................................................................................................42
7.4.1.
Prior Medications ..................................................................................................................42
7.4.2.
Concomitant Medications......................................................................................................43
7.5.
Premedication..........................................................................................................................................43
7.6.
Electrocardiogram Results.......................................................................................................................44
7.7.
Other Safety Measures ............................................................................................................................44
8.
PHARMACOKINETIC (PK) AND IMMUNOGENECITY ANALYSES.........................................................45
8.1.
PK Sample Collection .............................................................................................................................45
8.2.
PK Analyses ............................................................................................................................................45
8.3.
Immunogenicity Analysis........................................................................................................................46
9.
PHARMACODYNAMIC ANALYSES ..............................................................................................................47
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES..............................................................................48
11.
REFERENCES.....................................................................................................................................................49
12.
SOFTWARE.........................................................................................................................................................50
13.
SAP REVISION...................................................................................................................................................51
14.
APPENDICES......................................................................................................................................................52


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Appendix 1.
Schedule of Assessments.........................................................................................................53
Appendix 2.
Disease Response Assessment Based on International Working Group Criteria....................61
LIST OF IN-TEXT TABLES
Table 1-1.
Dose Level and Schedule ........................................................................................................10
Table 2-1.
Stopping Boundaries for Efficacy Superiority Analyses.........................................................13
Table 2-2.
Definition of Information Fraction..........................................................................................14
Table 3-1.
Analysis Visit Windows for Lab By-visit Summaries ............................................................20
Table 3-2.
Analysis Visit Windows for By-visit Summaries of PRO assessments ..................................20
Table 6-1.
Censoring Rules for DCR, DOR, and Duration of RBC Transfusion Independence..............32
Table 6-2.
Censoring Rules for EFS, Time to Transformation to AML, and PFS ...................................32


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LIST OF ABBREVIATIONS
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AML
acute myeloid leukemia
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
BLQ
below the limit of quantitation
BMI
body mass index
BSA
body surface area
CI
confidence interval
CR
complete remission
CRF
case report form
CRh
complete remission with partial hematologic recovery
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DCR
duration of complete remission
DMC
Data Monitoring Committee
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EFS
event-free survival
EQ-5D-5L
5-Level EuroQol 5 Dimensions
EQ VAS
EQ visual analogue scale
EOT
end of treatment
ET
early termination
FACT-Anemia
Functional Assessment of Cancer Therapy – Anemia
HLT
high-level term
HLGT
high-level group term
HRQoL
health-related quality of life
IA
Interim analysis
ICH
International Conference on Harmonization
ID
identification
ITT
Intent-to-Treat
IPSS-R
Revised International Prognostic Scoring System
IWG
International Working Group
IXRS
interactive voice/web/mobile response system (IXRS) 


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LLT
lower-level term
LOQ
limit of quantitation
MDS
myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Activities
MRD
minimal residual disease
MST
MedDRA Search Term 
ORR
objective response rate
OS
overall survival
PFS
progression-free survival
PR
partial remission
PRO
patient-reported outcome
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetics
PT
preferred term
Q1, Q3
first quartile, third quartile
RBC
red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SCT
stem cell transplant
StD
standard deviation
SE
standard error
SI (units) 
international system of units
SMQ
Standardised MedDRA Queries
SOC
system organ class
TE
treatment-emergent
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) of the first interim efficacy 
analysis for Study 5F9009, which is to be performed 8 months after 348 patients are randomized. 
The purpose of this interim analysis is to evaluate the efficacy of magrolimab in combination 
with azacitidine versus azacitidine plus placebo, based on the analyses of primary endpoints 
complete remission (CR) rate as well as overall survival (OS). The stopping criteria for the 
interim analysis may be found in Section 2 of this SAP. 
This SAP is based on the study protocol amendment 7 dated 27 July 2022 and the electronic case 
report form (eCRF). The SAP will be finalized prior to data finalization for the interim analysis. 
Any changes made after the finalization of the SAP will be documented in the clinical study 
report (CSR). 
1.1.
Study Objectives
The 2 primary objectives of this study are as follows:

To evaluate the efficacy of magrolimab + azacitidine compared with that of azacitidine + 
placebo in previously untreated patients with intermediate/high/very high risk 
myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System 
(IPSS-R) as measured by CR rate

To evaluate the survival benefit of magrolimab + azacitidine compared with that of 
azacitidine + placebo
The secondary objectives of this study are as follows:

To evaluate the duration of CR (DCR) of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To evaluate the objective response rate (ORR) and duration of response (DOR) of 
magrolimab + azacitidine compared with that of azacitidine + placebo 

To evaluate red blood cell (RBC) transfusion independence rate of magrolimab + azacitidine 
compared with that of azacitidine + placebo

To evaluate the efficacy of magrolimab + azacitidine compared with that of azacitidine + 
placebo as measured by event-free survival (EFS)

To evaluate the CR of magrolimab + azacitidine compared with that of azacitidine + placebo 
in TP53 mutant population


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
To assess the level of minimal residual disease (MRD) negativity of magrolimab + 
azacitidine compared with that of azacitidine + placebo

To assess time to transformation to acute myeloid leukemia (AML) of magrolimab + 
azacitidine compared with that of azacitidine + placebo

To evaluate the efficacy of magrolimab + azacitidine compared with that of azacitidine + 
placebo, as measured by progression free survival (PFS)

To assess the safety and tolerability of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To evaluate pharmacokinetics (PK) of magrolimab

To evaluate the immunogenicity of magrolimab

To evaluate the health-related quality of life (HRQoL) of magrolimab + azacitidine compared 
with that of azacitidine + placebo, as measured by Functional Assessment of Cancer Therapy 
– Anemia (FACT-Anemia) response rate
The exploratory objectives of this study are as follows:

To evaluate transplantation rate of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To assess time to first transplant of magrolimab + azacitidine compared with that of 
azacitidine + placebo

To evaluate the duration of RBC transfusion independence of magrolimab + azacitidine 
compared with that of azacitidine + placebo

To evaluate RBC transfusion independence of magrolimab + azacitidine compared with that 
of azacitidine + placebo  among all patients irrespective of RBC transfusion-dependence at 
baseline

To evaluate the HRQoL of magrolimab + azacitidine compared with that of azacitidine + 
placebo, as measured by score change from baseline in FACT-Anemia, Patient Global 
Impression of Severity/Patient Global Impression of Change (PGIS/PGIC), and 5-level 
EuroQol 5 dimensions (EQ-5D-5L) questionnaires 

To assess biomarkers including but not limited to, immune cell recruitment, immune cell 
signaling, and bone marrow penetration of magrolimab


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1.2.
Study Design
This is a Phase 3, randomized, double-blind, placebo-controlled multicenter study investigating 
magrolimab + azacitidine compared with azacitidine + placebo in previously untreated patients 
with intermediate/high/very high risk MDS by IPSS-R. The primary endpoints are CR rate and 
OS. Patients will be randomized in 1:1 ratio to receive either magrolimab + azacitidine 
(experimental arm) or azacitidine + placebo (control arm). Randomization will be stratified by 
3 factors: 1) geographic region (US versus ex-US sites); 2) cytogenetic risk status (very 
good/good/intermediate versus poor/very poor versus unknown) according to IPSS-R 
{Greenberg 2012}; and 3) percentage of bone marrow blasts (≥ 10% versus < 10% blasts). 
The primary analysis of CR rate will be conducted 8 months after 348 patients are randomized. 
Patient participation will include screening, treatment, and follow-up. Screening will last up to 
30 days before the first dose of study treatment, during which time the patient’s eligibility and 
baseline characteristics will be determined. Patients will receive study treatment per the dose 
schedule in Table 1-1. No cross-over between arms is allowed. Study treatment may be 
continued until disease progression (including treatment failure by International Working Group 
[IWG] 2006 criteria or relapse after partial/complete remission [PR/CR]), loss of clinical benefit, 
or unacceptable toxicities occur. In case patients discontinue the study treatment due to reasons 
other than disease progression, patients will be followed up for response assessments until 
documented disease progression occurs. For patients who come off the study treatment to receive 
a stem cell transplant (SCT), follow-up for response assessment and collection of SOC bone 
marrow biopsy/aspirate results will continue until documented disease progression occurs or start 
of new anticancer therapy, whichever occurs first. Then patients will be observed for survival 
until death, withdrawal of consent, or the end of the study, whichever occurs first.
The study treatments within each arm are described in Table 1-1:


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Table 1-1.
Dose Level and Schedule
Dose Schedule (Day per 28-day Cycle)
Treatment Arms
Drug/Dose/Route
Cycle 1
Cycle 2
Cycle 3+
Experimental arm 
(Magrolimab+ azacitidine) 
And
Control arm
(azacitidine + placebo)
Azacitidine 75 mg/m2 SC or 
IVa
Days 1–7
or
Days 1–5 and 
8-9
Days 1–7
or
Days 1–5 
and 8–9
Days 1–7
or
Days 1–5 and 8–9
Dose Schedule
Treatment Arms
Drug/Dose/Route
Priming Dose 
Magrolimab 1 mg/kg IV
Days 1, 4
Magrolimab 15 mg/kg IV
Day 8
Maintenance Dose 
Experimental arm 
(Magrolimab+ azacitidine) 
Magrolimab 30 mg/kg IV
Days 11, 15, followed by 
weekly administration for 
5 doses (Days 22, 29, 36, 43, 
50) 
Day 57 and every 
2 weeks thereafter
Control arm 
(azacitidine + placebo)
Placebo
to mirror the magrolimab 
dosing schedule above
to mirror the 
magrolimab dosing 
schedule above
Abbreviations:  IV = intravenous; SC = subcutaneous.
a
Azacitidine administered per region-specific labeling.
Treatment with azacitidine as standard of care is recommended for a minimum of 6 cycles. 
Therefore, in this study, patients without evidence of disease progression (including treatment 
failure by IWG 2006 criteria or relapse after PR/CR), loss of clinical benefit, or unacceptable 
toxicity should continue azacitidine for at least 6 cycles. Patients may be discontinued from the 
treatment per Investigator’s discretion prior to reaching the recommended minimum cycles for 
any of these reasons detailed in Protocol Section 5.7.
The schedules of assessments are provided in Protocol Section 4.3.
1.3.
Sample Size and Power
The study will randomize approximately 520 patients in total into 2 treatment arms at a 1:1 ratio, 
determined by formal hypothesis testing performed on 2 primary efficacy endpoints: CR rate and 
OS, with family-wise Type I error controlled at a 2-sided significance level of 0.05. The primary 
analysis of the CR rate will be conducted at 8 months after 348 patients are randomized. Based 
on the first 348 randomized patients, the study has 95% power to reject the null hypothesis that 
the CR rates in the 2 treatment arms are the same at the 2-sided 0.03 significance level, assuming 
the true CR rate is 20% in the control arm and 39% in the experimental arm (i.e., a 19% 
improvement).


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If the null hypothesis has been rejected for CR rate, the hypothesis test on OS will be conducted 
at a 2-sided significance level of 0.05; otherwise, it will be conducted at a 2-sided significance 
level of 0.02 for the superiority test together with a futility test. Approximately 364 OS events 
(70% of 520 patients) in the ITT Analysis Set will allow 90% power to reject the null hypothesis 
that medians in OS in the 2 treatment arms are the same, assuming 18 months in the control arm 
and 25.4 months in the experimental arm (i.e., hazard ratio [HR] = 0.71), at a 2-sided 
significance level of 0.05, or at least 80% power at a 2-sided significance level of 0.02.
The sample size is determined according to the group sequential design. Assuming an enrollment 
rate of approximately 0.22 patients/site/month and 1% annual loss to follow-up of survival 
status, accrual is projected to occur over 22 months for 520 patients. The primary CR rate 
analysis is expected approximately 26 months after the first patient is randomized. The first 
interim analysis of OS will be conducted at the same time. The second interim analysis of OS 
will be conducted when approximately 257 deaths (71% of 364 deaths) have occurred. The final 
OS analysis is expected approximately 4.4 years after the first patient is randomized. The actual 
length of the study and the time for analyses will depend on the actual enrollment rate and the 
number of events that occur.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
DMC Interim Analyses
An external multidisciplinary data monitoring committee (DMC) will review the progress of the 
study, perform interim reviews of safety data at regular intervals, and provide recommendation 
to Gilead on whether the nature, frequency, and severity of AEs associated with study treatment 
warrant the early termination (ET) of the study in the best interests of the patient, whether the 
study should continue as planned, or whether the study should continue with modifications. 
In addition, the DMC will review the results from the 2 planned interim efficacy analyses. Based 
on the pre-specified superiority and futility rules, the DMC may make recommendations to 
Gilead on whether the study should be stopped early due to overwhelming efficacy, be 
terminated for futility, or continue as planned. Efficacy superiority boundaries are specified 
below. 
The DMC’s specific activities will be defined by a mutually agreed charter, which will define the 
DMC’s membership, conduct, and meeting schedule.
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, the ultimate decision on whether to implement or act based 
upon the recommendations of the DMC will be made by Gilead.
There will be 2 planned interim efficacy analyses conducted and evaluated by the DMC.
The first DMC interim efficacy analysis will be conducted at 8 months after 348 patients have 
been randomized (i.e., data cutoff date), outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized. First, the primary 
analysis of CR rate will be conducted based on the first 348 randomized patients. Second, an 
interim analysis of OS will be conducted based on all randomized patients by the data cutoff 
date. Specifically, if the null hypothesis on CR rate is rejected at a 2-sided significance level of 
0.03, α = 0.05 (2-sided) will be allocated for OS, and there will be no formal futility testing for 
OS. Otherwise, if the null hypothesis on CR rate is not rejected at a 2-sided significance level of 
0.03, α = 0.02 (2-sided) will be allocated for OS and the first non-binding futility analysis with a 
futility boundary of HR = 0.99 will be performed. Allocation of α is applied to all subsequent 
interim analyses of OS (as well as the final analysis of OS).  It is projected that 158 deaths (43% 
of 364 deaths) will have occurred at the first interim analysis of OS. The actual interim analysis 
boundary for statistical significance will be determined based on the Lan-DeMets approach of 
the O’Brien-Fleming function according to the α allocated to the comparison of OS and the 
observed number of OS events by the data cutoff date.


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The second planned interim efficacy analysis will be conducted when approximately 257 deaths 
(71% of 364 deaths) have occurred in the ITT Analysis Set, outstanding data queries have been 
resolved or adjudicated as unresolvable, and the data have been cleaned and finalized. In the case 
that the null hypothesis on CR rate is not rejected at a 2‑sided significance level of 0.03, a non-
binding futility analysis with a futility boundary of HR = 0.95 will be performed.

If the null hypothesis on CR is rejected in the first interim analysis at a 2-sided significance 
level of 0.03, α = 0.05 (2-sided) will be allocated to the analysis of OS and key secondary 
endpoints in the first and second interim analyses, and final analysis 

If the null hypothesis on CR rate is not rejected in the first interim analysis at a 2-sided 
significance level of 0.03, α = 0.02 (2-sided) will be allocated to the analysis of OS and key 
secondary endpoints in the first and second interim analyses, and final analysis
In addition to the 2 planned interim efficacy analyses, the DMC will convene to review interim 
safety analysis results periodically, or convene for any ad hoc data review meeting, if deemed 
necessary. 
The Lan-DeMets approach with O’Brien-Fleming type alpha spending function will be used for 
the first and second interim analyses, and final analysis for OS. The stopping boundaries at each 
analysis time are provided in Table 2-1.
Table 2-1.
Stopping Boundaries for Efficacy Superiority Analyses
Stopping Boundary
Planned Analyses
Efficacy 
Analysis
Events (%)
HRa 
Two-sided p-value 
First IA
CR
-
-
0.03
First IA
OS
158 (43%)
0.600
0.0013*
Second 
IA
OS
257 (71%)
0.738
0.0148*
If the test of CR 
is rejected in 1st 
IA
Final 
Analysis
OS
364 (100%)
0.811
0.0453*
First IA
OS
158 (43%)
0.552
0.0002*
Second 
IA
OS
257 (71%)
0.700
0.0043*
If the test of CR 
fails to be 
rejected in first 
IA
Final 
Analysis
OS
364 (100%)
0.781
0.0186*
HR = hazard ratio, IA = interim analysis, OS = overall survival, CR = complete remission
a
HR presented in the table is 1-sided (lower) efficacy boundary.
*
The boundary p-values at each analysis timepoint will be based on the actual observed events and adjusted by using the Lan 
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The primary efficacy endpoint of OS will be tested for superiority first at the significance level 
specified in Table 2-1. If the superiority of OS is established, key secondary efficacy endpoints 
listed in Table 2-2 will be tested for superiority. To strongly control the overall type I error 
across the testing of the key secondary efficacy endpoints, a hierarchical testing strategy will be 
performed with a predefined order as listed below. For each key secondary endpoint, an O'Brien-
Fleming boundary will be derived based on the information fraction at each interim analysis and 
the remaining type I error respectively per Table 2-2.
Table 2-2.
Definition of Information Fraction
Endpoint
Information Fraction at the Interim Analysis
ORR 
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
RBC transfusion independence rate
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
EFS
43% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)*
CR in TP53 mutant population
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
MRD-negative response
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
Time to transformation to AML
43% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)*
PFS
43% at the first interim analysis, 71% at the second interim analysis 
(same with those of OS)*
FACT-Anemia response rate
Proportion of patients who have at least 8 months follow-up since 
randomization (including patients who have early discontinued, are lost 
to follow-up, or have died)
AML = acute myeloid leukemia; EFS = event-free survival; FACT-Anemia = Functional Assessment of Cancer Therapy-
Anemia; MRD = minimal residual disease; ORR = objective response rate; OS = overall survival, PFS = progressionfree survival
*The information fraction at each analysis timepoint will be based on the actual observed OS events
The key secondary endpoints will be tested in the following order: 

ORR

RBC transfusion independence rate

EFS

CR in TP53 mutant population


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
MRD-negative response

Time to transformation to AML

PFS

FACT-Anemia response rate
A given hypothesis can only be tested and declared statistically significant if all previous 
hypotheses tested in the hierarchy are also statistically significant. 
At the time of the second DMC interim efficacy analysis, if the efficacy boundary of OS has 
been crossed, the Sponsor study team may be unblinded for the entire ITT Analysis Set and will 
conduct the efficacy and safety analyses. 
2.2.
Optional Interim Analysis Performed by Sponsor
At the time of the first DMC interim efficacy analysis, if the null hypothesis on CR rate is 
rejected at a 2‑sided significance level of 0.03, or if the null hypothesis on CR rate is not rejected 
at a 2‑sided significance level of 0.03 but the null hypothesis on OS is rejected at the allocated 
significance level at the interim analysis, the Sponsor study team may be unblinded for all 
randomized patients by the data cutoff date and conduct additional interim analyses. Gilead 
Oversight Committee will make the decision on whether study team will be unblinded. Duration 
of CR will be estimated for each arm using Kaplan-Meier (KM) estimates, including median 
duration with 2-sided 95% CIs. Safety analysis will be conducted. Other secondary endpoints 
may be included in the analysis scope. However, no formal hypothesis testing will be conducted 
for any key secondary endpoint at the first interim analysis, unless the testing on OS is rejected.  
2.3.
Final Analysis
If the null hypothesis on OS is not rejected in either of the 2 planned interim analyses, the final 
unblinded efficacy analyses will be conducted by the Sponsor when approximately 364 OS 
events (70% of 520 patients) have occurred in the ITT Analysis Set, outstanding data queries 
have been resolved or adjudicated as unresolvable, and the data have been cleaned and finalized. 
Comparison of OS between the 2 treatment arms will be conducted after study unblinding.
If the null hypothesis on OS is rejected in any planned interim analyses, the timing of the final 
analysis may be driven by the data maturity of all required efficacy data and the need of the 
safety evaluation update.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of patients in each category will be presented; for continuous variables, 
the number of patients (n), mean, standard deviation (StD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all patients in the Intent-to-Treat (ITT) Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable). Data collected on log forms, 
such as AEs, will be presented in chronological order within the subject. Age, sex at birth, race, 
and ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the patients to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing.
For each analysis set, the number and percentage of patients eligible for inclusion will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by subject.
3.1.1.
Intent-to-Treat (ITT) Analysis Set
The ITT Analysis Set includes all patients who were randomized in the study, with treatment 
assignment designated according to the treatment to which the subject is randomized. This is the 
primary analysis set for efficacy analyses. 
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all randomized patients who took at least 1 dose of any study 
treatment, with treatment assignment designated according to the actual treatment received. This 
is the primary analysis set for safety analyses.
3.1.3.
Pharmacokinetic Analysis Set
The Pharmacokinetic (PK) Analysis Set will include all patients who took at least 1 dose of 
Magrolimab, and have at least 1 measurable post-treatment serum concentration of magrolimab. 
This is the primary analysis set for all PK analyses. 
3.1.4.
Immunogenicity Analysis Set
The Immunogenicity Analysis Set will include all patients who took at least 1 dose of 
Magrolimab, and have at least 1 reported anti-drug antibody (ADA) result. 


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3.2.
Subject Grouping
For analyses based on the ITT Analysis Set, patients will be grouped according to the treatment 
to which they were randomized. For analyses based on the Safety Analysis Set, patients will be 
grouped according to the actual treatment received. The actual treatment received will differ 
from the randomized treatment only when their actual treatment differs from randomized 
treatment for the entire treatment duration.
For the PK Analysis Set and the Immunogenicity Analysis Set, patients will be grouped 
according to the actual treatment they received.
3.3.
Strata and Covariates
Patients will be randomized in a 1:1 ratio to treatment arms using an interactive 
voice/web/mobile response system (IXRS) with a stratified randomization schedule. 
Stratification will be based on the following variables: 

geographic region (US versus ex-US sites)

cytogenetic risk status (very good/good/intermediate versus poor/very poor versus unknown) 
according to IPSS-R

percentage of bone marrow blasts (≥ 10% versus < 10% blasts) 
If bone marrow blasts stratification factor value is not recorded in the clinical database, the value 
recorded in the IXRS will be used for analyses. If there are discrepancies in stratification factor 
values between the IXRS and the clinical database, the values recorded in the clinical database 
will be used for analyses. Additionally, stratification discrepancies will be reviewed and 
assessed. Based on the assessment of stratification discrepancies, a sensitivity analysis of the 
primary endpoint may be performed.
Efficacy endpoints will be evaluated using stratification factors as covariates or stratification 
variables for analyses when applicable, as specified in Section 6. If there is an imbalance in 
presumed prognostic baseline characteristics between treatment groups, efficacy evaluations may 
be performed that include these baseline values in efficacy analysis models as covariates; these 
evaluations will be considered as sensitivity analyses.
In the situation where there is insufficient information in a stratum, pooling of the stratum with 
the smallest adjacent stratum for stratified analyses will be considered.
3.4.
Examination of Subject Subgroups
The primary efficacy endpoints  will be examined using the following subgroups:

geographic region (US versus ex-US sites)


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
cytogenetic risk status (very good/good/intermediate versus poor/very poor versus unknown) 
according to IPSS-R

percentage of bone marrow blasts (≥ 10% versus < 10% blasts) 
The analysis may also be conducted in the subgroups by TP53 mutational status (mutant and 
wild type), age (< 65 years and ≥ 65 years; < 75 years and ≥ 75 years), sex at birth (male and 
female), race (White, Asian, Black, Other), IPSS-R (Intermediate, High, Very high), baseline 
ECOG (0, 1, and 2), disease type (non therapy related vs therapy related), peripheral blood, 
hemoglobin, and platelet count.
If the number of subjects in one or more subgroups is too small to conduct the analysis, some 
subgroups will be pooled for the analysis. 
3.5.
Multiple Comparisons
The Multiple Comparisons are provided in Section 2.1.
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dosing date of study drug, imputation rules are described in Section 4.2.1. The 
handling of missing or incomplete dates for disease diagnosis is described in Section 5.3, for the 
start date of new MDS therapy in Section 6.1.1, for AE onset in Section 7.1.5.2, and for prior and 
concomitant medications in Section 7.4. Imputation rules adopted in the efficacy analyses are 
specified in Section 6.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed


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In general, age collected at the randomization (in years) will be used for analyses and presented 
in listings. If age at randomization is not available for a subject, then age derived based on date 
of birth and the randomization visit date will be used instead. For screen failures or 
unrandomized patients, the date the first informed consent was signed will be used for the age 
derivation. Age required for longitudinal and temporal calculations and analyses (eg, estimates of 
creatinine clearance, age at date of AE) will be based on age derived from date of birth and the 
date of the measurement or event, unless otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
If methods based on the assumption that the data are normally distributed are not adequate, 
analyses may be performed on transformed data or nonparametric analysis methods may be used, 
as appropriate.
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of any study drug, which is the date of the 
first dose of magrolimab/placebo, or azacitidine, whichever occurs first and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date 
Therefore, study day 1 is the day of first dose of study drug administration. If the subject is 
randomized but not dosed, the randomization date will be study day 1. 
3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows. The analysis windows for lab are provided in 
Table 3-1.


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Table 3-1.
Analysis Visit Windows for Lab By-visit Summaries
Visit Window Study Day
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1a
Week 1
7
1b
10
Week 2
14
11
17
Week 3
21
18
24
Week 4
28
25
31
Week 5
35
32
38
Week 6
42
39
45
Week 7
49
46
52
Week 8
56
53
62
Week 10
70
63
76
Week xx
xx*7
(xx-1)*7
xx*7+6
a
Prior to first dose date time.
b
Post first dose date time.
The analysis windows for PRO are provided in Table 3-2.
Table 3-2.
Analysis Visit Windows for By-visit Summaries of PRO assessments
Visit Window Study Day
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
Week 4
28
2
42
Week 8
56
43
70
Week 12
84
71
98
Week xx
xx*7
xx*7-13
xx*7+14
Any data relating to unscheduled visits will not be assigned to a particular visit or time point. 
However, the following exceptions will be made:

An unscheduled visit prior to the first dosing of any study drug will be included in the 
calculation of the baseline value, if applicable.

Unscheduled visits after the first dosing of any study drug will be included in determining the 
maximum postbaseline toxicity grade and anti-magrolimab antibody status.

Response assessments and PRO assessments performed at unscheduled visits after the date of 
randomization will be included in the analyses of the efficacy endpoints and the PRO related 
endpoints, respectively.


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3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window 
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date of study drug (and 
prior to first dosing time) will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
the arithmetic average of the measurements for continuous data, or the measurement with the 
lowest severity for categorical data.

For postbaseline values:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the arithmetic average will be taken for 
continuous data and the worse severity will be taken for categorical data, unless 
otherwise specified.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group for each country, 
investigator and overall. The summary will present the number and percentage of patients 
enrolled. For each column, the denominator for the percentage calculation will be the total 
number of patients analyzed for that column.
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of patients in the stratum will be the total number of enrolled patients. If there are 
discrepancies in the value used for stratification assignment between the IXRS and the clinical 
database, the value collected in the clinical database will be used for the summary. A listing of 
patients with discrepancies in the value used for stratification assignment between the IXRS and 
the clinical database at the time of data finalization will be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group. This summary will 
present the number of patients screened and the number of patients who met all eligibility criteria 
but were not randomized with reasons patients not randomized in total; and the number of 
patients in each of the categories listed below by treatment group:

ITT Analysis Set

Safety Analysis Set 

Continuing study treatment (magrolimab/placebo, azacitidine)

Discontinued study treatment (magrolimab/placebo, azacitidine) with reasons for 
discontinuation

On-going in study (including long-term follow-up and survival follow-up)

Discontinued study with reasons for discontinuation
For the status of study drug and study completion and reasons for discontinuation, the number 
and percentage of patients in each category will be provided. The denominator for the percentage 
calculation will be the total number of patients in the ITT Analysis Set corresponding to that 
column. In addition, a CONSORT flow diagram will be provided to depict the disposition.
The following by-subject listings will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:

Reasons for study drug discontinuation

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4.2.
Extent of Study Drug Exposure 
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and relative dose intensity. Each variable will be calculated for magrolimab/placebo, 
and azacitidine separately.  No formal statistical testing between treatment group is planned. 
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to each study drug (magrolimab/placebo, and azacitidine) will be 
defined for a subject as last dosing date minus first dosing date plus 1 day, regardless of any 
temporary interruptions in study drug administration, and will be expressed in weeks using up to 
1 decimal place (eg, 4.5 weeks). 
The total duration of exposure to each study drug will be summarized using descriptive statistics 
for continuous variables, as well as using the number (i.e., cumulative counts) and percentage of 
patients exposed for at least the following time periods: 1 day, 4 weeks, 8 weeks, 12 weeks, 
16 weeks, 20 weeks, and 24 weeks, etc. 
For azacitidine, the number of cycles patients are exposed will be summarized using descriptive 
statistics, and the number and percentage of patients who received at least 1, 2 …, 6 cycles will 
be presented.
The number and percentage of patients who have dose reduction for azacitidine or delay for each 
drug and the reasons will be summarized. 
4.2.2.
Relative Dose Intensity
Relative dose intensity is the percentage of the total amount of study drug administered relative 
to the total amount of study drug expected to be administered during a subject’s actual 
on-treatment period based on the study drug regimen. 
For magrolimab/placebo:
The relative dose intensity is the percentage of the total amount of study drug administered 
relative to the total amount of study drug expected to be administered. For doses administered 
from Day 11 (at 30 mg/kg IV) and onward will be expressed as a percentage using the following 
formula:
Relative dose intensity  (%) =  
Cumulative dosage received (in mg/kg)
 Total assigned Magrolimab/Placebo dosage (in mg/kg)  x 100
Cumulative dosage (mg/kg) received for each subject is defined as the sum of all delivered 
dosages (mg/kg) of all infusions the subject received from Day 11 and onward.
Total assigned dosage (mg/kg) for each subject is defined as the product of the assigned dose of 
magrolimab/placebo (30 mg/kg) and number of doses the subject was scheduled to receive 
during the subject’s treatment period (number of infusions administered plus the number of 
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A separate summary for the relative dose intensity of magrolimab/placebo administered for 
Day 1/Day 4 (at 1 mg/kg IV) and re-priming visits of Day 1/Day 4, Day 8 (at 15 mg/kg IV) and 
re-priming visits of Day 8 will be provided, respectively. The calculation will be similar to that 
of from Day 11 and onward (at 30 mg/kg IV).
For azacitidine:
Relative dose intensity (%) =  
Total Amount of Azacitidine Administered
Azacitidine Expected to be Administered on Treatment  x 100
For each study drug, descriptive statistics for the relative dose intensity with the number and 
percentage of patients belonging to relative dose intensity categories (eg, < 75%, ≥ 75 to < 90%, 
≥ 90%) will be provided by treatment group for the Safety Analysis Set.
A by-subject listing of each study drug administration will be provided by treatment group, 
subject ID number (in ascending order) and visit (in chronological order).
4.3.
Protocol Deviations 
Patients who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized. The summary will present the number and percentage of patients who did not meet 
at least 1 eligibility criterion and the number of patients who did not meet specific criteria by 
treatment group based on the ITT Analysis Set. A by-subject listing will be provided for those 
patients who did not meet at least 1 eligibility (inclusion or exclusion) criterion. The listing will 
present the eligibility criterion (or criteria if more than 1 deviation) that patients did not meet and 
related comments, if collected.
Protocol deviations occurring after patients entered the study are documented during routine 
monitoring. The number and percentage of patients with important protocol deviations by 
deviation reason (eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) 
will be summarized by treatment group for the ITT Analysis Set. A by-subject listing will be 
provided for those patients with important protocol deviation.
4.4.
Assessment of COVID-19 Impact
This study was ongoing during the novel coronavirus (COVID-19) pandemic which has an 
impact on the study conduct. Some subjects were unable to attend onsite visits due to shelter in 
place guidelines, site closures, or other reasons. This section describes how special situations due 
to COVID-19 will be handled in the analysis.
4.4.1.
Study Drug or Study Discontinuation Due to COVID-19
A summary of reasons for discontinuing study drug or study due to COVID-19 will be provided 
by treatment group and overall, similar to the summary described in the subject enrollment and 
disposition section (see Section 4.1). 


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A by-subject listing of reasons for premature study drug or study discontinuation due to 
COVID-19 will be provided if applicable.
4.4.2.
Protocol Deviations Due to COVID-19
A summary of important protocol deviations due to COVID-19 will be provided, similar to the 
summary described in the protocol deviations section (Section 4.3).
The number and percentage of subjects with non-important protocol deviations related to 
COVID-19 will be summarized by treatment group.
A by-subject listing will be provided for subjects with important protocol deviations related to 
COVID-19 if applicable. 
4.4.3.
Missed and Virtual Visits due to COVID-19
An overall summary of the number and percentage of subjects with at least 1 missed scheduled 
or virtual visits due to COVID-19 will be provided by treatment group and overall. The 
denominator for the percentage calculation will be the total number of subjects in the safety 
population for that column.
4.4.4.
Adverse Events Due to COVID-19
A by-subject listing of AEs of COVID-19 will be provided if applicable.


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5.
BASELINE CHARACTERISTICS  
5.1.
Demographics and Baseline Characteristics
Subject demographic variables (ie, age, sex at birth, race, ethnicity, geographic region) and 
baseline characteristics (body weight [in kg], height [in cm], body mass index [BMI; in kg/m2], 
Body Surface Area [BSA; in m2]) will be summarized by treatment group and overall using 
descriptive statistics for continuous variables and using number and percentage of patients for 
categorical variables. The summary of demographic data will be provided for the ITT Analysis 
Set.
A by-subject demographic listing, including the informed consent date, will be provided by 
treatment group and subject ID number.
5.2.
Other Baseline Characteristics
Other baseline characteristics include but are not limited to: ECOG,  BM blast, Cytogenetic Risk 
Status,  and TP53 mutational status. These baseline characteristics will be summarized by 
treatment group and overall using descriptive statistics for continuous variables and using 
number and percentage of patients for categorical variables. The summary of these baseline 
characteristics will be provided for the ITT Analysis Set. No formal statistical testing is planned.
A by-subject listing of other baseline characteristics will be provided.
5.3.
Medical History
Medical history will be collected at screening for disease-specific and general conditions 
(ie, conditions not specific to the disease being studied).
MDS Diagnosis history will be summarized by treatment group and overall by the number and 
percentage of patients with each prepopulated categories including but not limited to: IPSS-R, 
WHO Classification of MDS, Therapy-related MDS, RBC Transfusion Independence. The 
summary will be provided for the ITT Analysis Set. Time since diagnosis (months) will be 
calculated by (date of randomization – date of diagnosis) / 30.4375. Time since diagnosis will be 
summarized using summary statistics for a continuous variable. No formal statistical testing is 
planned. A by-subject listing of disease-specific medical history will be provided. In deriving the 
time since disease diagnosis, all partial dates of diagnosis and last regimen will be identified, and 
the partial dates will be imputed as follows:

If day and month are missing but year is available, then the imputed day and month will be 
01 Jan.

If day is missing but the month and year are available, then the imputed day will be the first 
day of the month.

Partial date will not be imputed if the year is missing.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoints
6.1.1.
Definition of Primary Efficacy Endpoints
The two primary efficacy endpoints of this study are CR rate and OS. 
CR Rate: The CR rate is the proportion of patients who reach morphologic CR (morphological 
blast of ≤ 5% and recovery of ANC, platelets, and hemoglobin from CBCs as well as peripheral 
blast collected on the same day) based on Investigator-assessed IWG 2006 MDS criteria 
{Cheson 2006} prior to initiation of any new anticancer therapy, including SCT.
Overall Survival: The OS is measured from the date of randomization to the date of death from 
any cause. Those who are not observed to die during the study will be censored at their last 
known alive date.
The date of the last known alive will be determined by selecting the last available visit date 
across all datasets.
When the date of initiation of a new anticancer therapy other than the study treatment or the date 
of SCT is incomplete or missing, the following algorithm will be followed:

If the day is missing but the month and year are available, then the imputed day will be the 
first day of the month.

If day and month are missing but year is available, then the imputed day and month will be 
01Jan or the last day of the month for the last adequate disease assessment if the year of new 
anticancer therapy and the year of last adequate disease assessment are the same.
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoints 
The first primary efficacy hypothesis to be tested is that there is no difference between 
magrolimab + azacitidine (experimental arm) and placebo + azacitidine (control arm) in CR rate 
for the first 348 randomized patients. Using CR rateexp and CR ratectrl to denote the CR rates for 
the experimental arm and control arm, respectively, the statistical hypotheses to be tested in this 
study will be:
𝐻0: CR rateexp = CR ratectrl
𝐻1: CR rateexp ≠ CR ratectrl (experimental arm is not equal to control arm in terms of CR rate)
The second primary efficacy hypothesis to be tested is that there is no difference between 
magrolimab + azacitidine (experimental arm) and placebo + azacitidine (control arm) in OS for 
patients. Using Sexp(t) and Sctrl(t) to denote the OS distribution functions of the experimental arm 
and control arm, respectively, the statistical hypotheses to be tested in this study will be:


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𝐻0: Sexp(t) = Sctrl(t) at all time points t
𝐻1: Sexp(t) ≠ Sctrl(t) (experimental arm is not equal to control arm in terms of OS for some 
t > 0)
6.1.3.
Analysis of the Primary Efficacy Endpoints
The primary analysis of CR rates will compare the CR rates of two treatment groups in the first 
348 randomized patients in the ITT Analysis Set using the Cochran-Mantel-Haenszel (CMH) 
test, stratified by the stratification factors at randomization. The odds ratio comparing the 2 arms 
adjusted for the stratification factors will be presented along with 95% confidence interval (CI).  
The point estimate of the CR rate and the corresponding 2-sided exact 95% CI based on the 
Clopper-Pearson method will be provided for each arm. Patients, who are randomized but have 
no on-study response assessment or receive any new anticancer therapy including SCT prior to 
achieving CR, will be considered as non-responders.
If the CR rate of experimental arm is higher than that of control arm and 2-sided p-value from 
the stratified CMH test using SAS procedure freq is less than 0.03, the null hypothesis of CR rate 
in Section 6.1.2 will be rejected and the superiority of experimental arm to control arm in terms 
of CR rate is established.
The primary analysis of OS will compare the OS distributions of two treatment groups using the 
stratified log-rank test, stratified by the stratification factors at randomization for the ITT 
Analysis Set. Medians, Q1, Q3 of the OS distributions, and the proportion of patients who are 
alive at 6, 12, 18 and 24 months from randomization will be estimated along with corresponding 
95% CIs using the Kaplan-Meier method. Kaplan-Meier curves will be provided by treatment 
group. 
If the median survival time of experimental arm is longer than that of control arm and two-sided 
p-value from the stratified log-rank test using SAS procedure Lifetest is less than the cutoff 
p-values based on observed number of OS events by the data cutoff date as mentioned in 
Section 2.1, the null hypothesis of OS in Section 6.1.2 will be rejected and the superiority of 
experimental arm to control arm in terms of OS is established.
In addition, the HR between the 2 treatment groups and its 95% CI will be estimated using the 
Cox proportional hazards regression model stratified by the stratification factors. For 
pre-specified non-binding futility analysis boundary of HR=0.99 at the first interim analysis if 
CR is not statistically significant, the HR from the Cox model will be used to check whether the 
futility boundary has been crossed or not.
6.1.4.
Follow-up Time
The follow-up time for OS is defined as the interval from date of randomization to the death date 
for patients who died on or prior to the data cutoff, or from the date of randomization to the last 
known alive date for patients who are alive up to the data cutoff. The follow-up time will be 
summarized by treatment groups using descriptive statistics including median and range 


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(minimum and maximum). It will also be summarized by treatment groups using statistics such 
as median, Q1, Q3 with corresponding 95% CIs estimated with the reverse Kaplan-Meier (K-M) 
method. The reverse K-M model switches the event/censoring indicators of patients in the 
original OS analysis with Kaplan-Meier method. It considers patients lost to follow-up or 
administratively censored due to analysis data cut as achieving the full follow up, and the full 
follow up time of those patients who died could not be observed as it is ‘censored’ by death. 
6.1.5.
Sensitivity Analysis of the Primary Efficacy Endpoint
To assess the robustness of the primary CR results, the following sensitivity analysis will be 
performed: 

CR will be analyzed using stratification factors in IXRS for the Cochran-Mantel-Haenszel 
(CMH) test.
To assess the robustness of the primary OS results, the following sensitivity analysis will be 
performed: 

OS will be analyzed on the same population as CR analysis (ie, the first randomized 
348 patients in the ITT Analysis Set).

OS will be analyzed using the stratified log-rank test, stratified by the stratification factors in 
IXRS. In addition, the HR between the 2 treatment groups and its 95% CI will be estimated 
using the Cox proportional hazards regression model stratified by the stratification factors in 
IXRS.
6.1.6.
Exploratory Analysis of the Primary Efficacy Endpoint
An exploratory analysis may be performed to investigate the potential prognostic factors 
influencing the primary efficacy endpoint OS using the Cox regression model approach. The 
variables with prognostic potential will be included in the model as covariates to identify 
plausible significant factors on OS, such as age, gender, percentage of bone marrow blast, 
ECOG, etc.
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of Secondary Efficacy Endpoints
Duration of CR: The DCR is measured from the time measurement criteria are first met for CR 
to the first date of relapse or death, whichever occurs earlier. Those who are not observed to 
relapse or die will be censored at their last response assessment date with evidence of no relapse. 
Patients who achieve a CR and then proceed to SCT will continue to be followed for the 
response assessment posttransplant, will be included in the analysis of DCR, and will not be 
censored at the time of transplant. If patients start taking new anticancer therapies (excluding 
SCT) before relapse or death, DCR will be censored at the last response assessment before the 
initiation of the new anticancer therapies.


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Objective Response Rate (ORR): The ORR is the proportion of patients who reach objective 
response including CR, PR, marrow CR, or hematologic improvement per IWG 2006 MDS 
criteria prior to initiation of any new anticancer therapy, including SCT.
Duration of Response (DOR): The DOR is measured from the time measurement criteria are 
first met for objective response to the first date of relapse, disease progression after the initial 
objective response or death, whichever occurs earlier. Those who are not observed to relapse, 
disease progress after the initial objective response or die will be censored at their last response 
assessment date with evidence of no relapse/no disease progression. Patients who achieve a 
response and then proceed to SCT will continue to be followed for the DOR posttransplant, will 
be included in the analysis of DOR, and will not be censored at the time of transplant. If patients 
start taking new anticancer therapies (excluding SCT) before relapse, disease progression or 
death, DOR will be censored at the last response assessment before the initiation of the new 
anticancer therapies.
RBC Transfusion Independence Rate: The RBC transfusion independence rate is the 
proportion of patients who have a 56-day or longer period with no RBC transfusions at any time 
between randomization and initiation of any new anticancer therapy, including SCT, among all 
patients who are RBC transfusion-dependent at baseline.
Event-free Survival: The EFS is defined as the time from randomization to transformation to 
AML or death from any cause, whichever occurs first. Response assessments and deaths post 
SCT will be included in the analysis. Patients who are not observed to have one of these events 
during the study will be censored at their last response assessment date with evidence of no 
transformation to AML. If patients start taking new anticancer therapies (excluding SCT) before 
transformation to AML or death, EFS will be censored at the last response assessment before the 
initiation of the new anticancer therapies. Patients will be censored at the date of randomization 
if no response assessment performed after randomization and the patients didn’t die.
CR in TP53 Mutant Population: CR in TP53 Mutant Population is defined as the proportion of 
patients who achieve a morphologic CR based on Investigator-assessed IWG criteria {Cheson 
2006} prior to initiation of any new anticancer therapy, including SCT in TP53 mutant population.
MRD-negative Response Rate: The MRD-negative response rate is defined as the proportion of 
patients who achieve a morphologic CR or marrow CR based on Investigator-assessed IWG 
criteria {Cheson 2006} and reach MRD-negative disease status prior to initiation of any new 
anticancer therapy, including SCT. MRD-negative disease status will be assessed using a 
multiparameter flow cytometry-based assay performed by a central laboratory.
Time to Transformation to AML: Time to transformation to AML is defined as the time from 
randomization to transformation to AML. Patients who are not observed to have transformation 
to AML will be censored at their last response assessment date with evidence of no AML 
diagnosis. Response assessments post SCT will be included in the analysis. If patients start 
taking new anticancer therapies (excluding SCT) before documented AML diagnosis, Time to 
Transformation to AML will be censored at the last response assessment before the initiation of 
the new anticancer therapies. Patients will be censored at the date of randomization if no 
response assessment performed after randomization.


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Progression-free Survival: PFS is defined as the time from randomization to the date of 
documented disease progression (including treatment failure by IWG criteria or relapse after 
PR/CR), or death from any cause, whichever occurs first. Response assessments and deaths post 
SCT will be included in the analysis. Those who are not observed to have one of these events 
will be censored at their last response assessment date with evidence of no disease 
progression/relapse. If patients start taking new anticancer therapies (excluding SCT) before 
disease progression (including treatment failure by IWG criteria or relapse after PR/CR) or 
death, PFS will be censored at the last response assessment before the initiation of the new 
anticancer therapies. Patients will be censored at the date of randomization if no response 
assessment performed after randomization and the patients didn’t die.
FACT-Anemia Response Rate: The FACT-Anemia response rate is defined as the proportion 
of patients who showed clinically meaningful improvement in health-related quality of life 
(HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new 
anticancer therapy, including SCT {Cella 2002}. The minimal clinically meaningful difference 
of 7.0 as suggested in the referenced literature will be used as cutoff for clinically meaningful 
improvement. Patients, who are randomized but have no baseline or no postbaseline FACT-
Anemia questionnaire assessment or receive any new anticancer therapy including SCT prior to 
achieving the FACT-Anemia response, will be considered as non-responders.
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints
Key secondary efficacy endpoints will be tested according to the order specified in Section 2.1, 
after the superiority for the primary efficacy endpoint OS is established. 
6.2.2.1.
Objective Response Rate, CR in TP53 Mutant Population, MRD-negative 
Response Rate, and FACT-Anemia Response Rate 
The ORR, CR in TP53 mutant population, MRD-negative response rate, and FACT-Anemia 
response rate will be evaluated in a similar manner as the CR rate. 
6.2.2.2.
Duration of CR, and Durations of Response
For the time-to-event endpoints of DCR and DOR, analyses will be conducted based on the 
subsets on which the outcome measures are defined. Specifically, DCR will be based on patients 
who achieve CR, and DOR will be based on patients who achieve objective response. The 
Kaplan-Meier method will be used to estimate median duration with its 95% CI, and 
Kaplan-Meier plots will be provided. The censoring rules for DCR and DOR are summarized in 
Table 6-1.
6.2.2.3.
Event-Free Survival, Time to Transformation to AML, and Progression-Free 
Survival
The distribution of EFS, time to transformation to AML, and PFS will be estimated for each 
treatment arm using Kaplan-Meier method and compared between treatment arms using the 
stratified log-rank test, stratified by the stratification factors at randomization for the ITT 
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free at 6, 12, 18 and 24 months from randomization will be estimated along with corresponding 
95% CIs using the Kaplan-Meier method. Kaplan-Meier curves will be provided by treatment 
group. The hazard ratio between treatment arms will be estimated using the Cox proportional 
hazards regression model stratified by the stratification factors. The censoring rules for EFS, 
Transformation to AML, and PFS are summarized in Table 6-2.
6.2.2.4.
RBC Transfusion Independence Rate 
The point estimates of RBC transfusion independence rate as well as the corresponding 2-sided 
exact 95% CIs based on Clopper-Pearson method will be provided by treatment arm 
respectively. Estimation will be based on a subset of all randomized patients who are RBC 
transfusion dependent at baseline. Difference in transfusion independence rate between treatment 
group will be tested using the Cochran-Mantel-Haenszel test, stratified by the randomization 
stratification factors.  
Table 6-1.
Censoring Rules for DCR, DOR, and Duration of RBC Transfusion 
Independence
Situation
Date of Censoring
No subsequent response assessments and no death after 
the first date CR/OR/RBC transfusion independence met 
Date of first time meet CR/OR/RBC transfusion 
independence
No corresponding events or no subsequent response 
assessments prior to initiation of any new anticancer 
therapy (excluding SCT)
Date of the last response assessment before the 
initiation of the new anticancer therapies (excluding 
SCT) or Date of first time meet CR/OR/RBC 
transfusion independence
No corresponding events and no any new anticancer 
therapy (excluding SCT)
Date of the last response assessment
Table 6-2.
Censoring Rules for EFS, Time to Transformation to AML, and PFS 
Situation
Date of Censoring
No postbaseline response assessment (for Time to 
Transformation to AML);
No postbaseline response assessment and no death (for 
EFS and PFS) 
Date of randomization 
No corresponding events or no postbaseline response 
assessment prior to initiation of any new anticancer 
therapy (excluding SCT)
Date of the last response assessment before the 
initiation of the new anticancer therapies (excluding 
SCT) or date of randomization
No corresponding events and no any new anticancer 
therapy (excluding SCT)
Date of the last response assessment


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6.3.
Exploratory Efficacy Endpoints
6.3.1.
Definition of Exploratory Efficacy Endpoints
Duration of RBC Transfusion Independence: The duration of RBC transfusion independence 
is measured from the time the assessment criteria are first met for RBC transfusion independence 
until RBC transfusion dependence again (including assessments post SCT) or death,  whichever 
occurs first. Those who are not observed to have RBC transfusion dependence again or death 
will be censored at the date of their last response assessment. If patients start taking new 
anticancer therapies (excluding SCT) before becoming RBC transfusion dependent again or 
death, duration of RBC transfusion independence will be censored at the last response 
assessment before the initiation of the new anticancer therapies (excluding SCT).
Transplantation Rate: The transplantation rate is the proportion of patients who initiated 
transplant type subsequent anti-cancer therapy for MDS.
Time to First Transplant: Time to first transplant is defined as the time from randomization to 
the initiation of first transplant type subsequent anti-cancer therapy for MDS. Patients who are 
not observed to initiate transplant type subsequent anti-cancer therapy will be censored at their 
last known alive date or death date if the patient died.
RBC Transfusion Independence Rate Irrespective of RBC Transfusion Status at Baseline: 
The RBC transfusion independence rate irrespective of RBC transfusion status at baseline is the 
proportion of patients who have a 56-day or longer period with no RBC transfusions at any time 
between randomization and initiation of any new anticancer therapy, including SCT, among all 
randomized patients.
6.3.2.
Analysis Methods for Exploratory Efficacy Endpoints
Time to first transplant will be analyzed in a similar manner as the analysis of EFS, as specified 
in Section 6.2.2.3. Patients who are not observed to initiate transplant type subsequent anti-
cancer therapy will be censored at their last known alive date or death date if the patient died.
The duration of RBC transfusion independence will be analyzed in a similar manner as the 
analysis of DCR, as specified in Section 6.2.2.2. The censoring rule for duration of RBC 
transfusion independence is summarized in Table 6-1.
The transplantation rate will be analyzed in a similar manner as the analysis of ORR, as specified 
in Section 6.2.2.1. 
A by-subject listing for RBC transfusions required throughout the study will be provided by 
treatment group and subject ID in chronological order. Date of transfusion, transfusion type, and 
the number of units transfused will be presented. 


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6.4.
Patient-Reported Outcome
6.4.1.
Definition of Patient-Reported Outcome Data
Four PRO instruments will be administered in this study: the Functional Assessment of Cancer 
Therapy-Anemia (FACT-Anemia), the 5-level EuroQol 5 dimensions (EQ-5D-5L), the Patient 
Global Impression of Severity (PGIS), and the Patient Global Impression of Change (PGIC). 
Functional Assessment of Cancer Therapy-Anemia  is described in Section 6.2.1.
6.4.2.
Analysis of Patient-Reported Outcome Data
In addition to the analyses specified in Section 6.2 for the secondary PRO endpoint, exploratory 
analyses comparing the effects of magrolimab + azacitidine versus placebo + azacitidine on 
health-related quality of life will be performed on the 4 PRO measures: FACT-Anemia, 
EQ-5D-5L, PGIS, and the PGIC. Analyses will be based on the ITT Analysis Set.
FACT-Anemia

FACT-G: Mean total score and subscale scores at baseline and all follow-up timepoints by 
treatment arm. The FACT-G consisits of the physical, social/family, emotional, functional 
subscales.

FACT TOI-An: Mean total score at baseline and all follow-up timepoints by treatment arm. 
The FACT TOI-An consists of the physical, functional and anemia symptoms subscales.

FACT TOI-F: Mean total score at baseline and all follow-up timepoints by treatment arm. 
The FACT TOI-F consists of the physical, functional and fatigue subscales.

FACT-F: Mean total score at baseline and all follow-up timepoints by treatment arm. The 
FACT-F consisits of the physical, social/family, emotional, functional and fatigue subscales.
EQ-5D-5L
The EQ-5D-5L questionnaire data will be scored, processed, and standardized according to the 
user manual. Missing values will not be imputed and will be left as missing.
Descriptive statistics will be calculated for the EQ-5D-5L dimensional score, the EQ-5D VAS 
score, and PGIS/PGIC response score at scheduled assessments. The mean and change from 
baseline to each subsequent assessment will be summarized by treatment group. 
PGIC/PGIS
The proportion of patients who report each response category on the PGIC and PGIS at 
scheduled time-point will be summarized by treatment group. The mean and change from 
baseline on the PGIS to each subsequent assessment may be summarized.
Additional exploratory analyses may be conducted and documented in a separate PRO SAP.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to CTCAE 
Version 5.0. The severity grade of events for which the investigator did not record severity will 
be categorized as “missing” for tabular summaries and data listings. The missing category will 
be listed last in summary presentation.
Severity of adverse events will be determined by the investigator as mild, moderate, or severe. 
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” for a drug on the AE CRF to 
the question of “Related to Study Treatment.” Relatedness will always default to the 
investigator’s choice, not that of the medical monitor. Events for which the investigator did not 
record relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and reported as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. Serious adverse events captured 
and stored in the clinical database will be reconciled with the SAE database from the Gilead 
Global Patient Safety before data finalization.
7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any AEs with an onset date on or 
after the study drug start date and no later than 70 days after the study drug last dose date or 
initiation of new anticancer therapy including SCT (whichever is earlier).


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to the cutoff date of TEAE period, which is defined as the 70 days after the 
study drug last dose date or initiation of new anticancer therapy including SCT (whichever is 
earlier)
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
In case when the AE onset date is incomplete and needs to be imputed, the following algorithm 
will be followed:

If the day is missing but the month and year are available, then the imputed day will be the 
first dosing date if they have the same month and year, or the first day of the month 
otherwise.

If the day and month are missing but year is available, then the imputed day and month will 
be the first dosing date if they have the same year, or 01Jan otherwise.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE incidence in Combined Severity Grade Subsets 
A brief, high-level summary of the number of percentage of patients who experienced at least 
1 TEAE in the categories described below will be provided by treatment group. 
The number and percentage of patients who experienced at least 1 TEAE will be provided and 
summarized by SOC, PT, and treatment group. 


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For the AE categories described below, summaries will be provided by SOC, PT, and treatment 
group:

TEAEs 

TEAEs with Grade 3 or higher

TE treatment-related AEs for any study drug and for each study drug

TE treatment-related AEs with Grade 3 or higher for any study drug and for each study drug

TE SAEs

TE treatment-related SAEs for any study drug and for each study drug

TEAEs leading to dose reduction of azacitidine

TEAEs leading to discontinuation of any study drug and for each study drug 

TEAEs leading to death 
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and then by PT in descending order of 
frequencies in magrolimab + azacitidine treatment arm within each SOC. For summaries by 
severity, the most severe severity will be used for those AEs that occurred more than once in a 
given subject during the study.
In addition to the above summary tables, all TEAEs, TEAEs of Grade 3 or higher, TE SAEs and 
TEAEs leading to death will be summarized by PT only in descending order of frequencies in 
magrolimab + azacitidine treatment arm.
In addition, data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

All SAEs

All Deaths

All SAEs leading to death 

All AEs with severity of Grade 3 or higher

All AEs leading to discontinuation of study drug

All AEs leading to dose reduction of azacitidine 

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A summary (number and percentage of patients) of deaths will be provided by treatment group. 
Summary will include the following categories:

All deaths

Deaths within 30 days of the first dosing of study drug

Deaths within 30 days of the last dosing of study drug

Deaths within 60 days of the first dosing of study drug

Deaths within 70 days of the last dosing of study drug

Deaths beyond 30 days of the last dosing of study drug

Deaths beyond 70 days of the last dosing of study drug
7.1.7.
Additional Analysis of Adverse Events
The incidence of infusion reaction AEs and Treatment-Emergent AEs will be examined. 
7.1.7.1.
Infusion Reaction Adverse Events (IRAE)
The incidence of infusion reaction AEs will be examined. Infusion reaction AEs are defined by 
the NCI CTCAE (under the category “General disorders and administration site conditions”) as 
“a disorder characterized by adverse reaction to the infusion of pharmacological or biological 
substances”. For the purpose of this study, they are defined as AEs described in Protocol 
Amendment 7 that occur within the 24-hour period beginning from the start of the infusion.  
The number and percentage of subjects who experienced any of the infusion reaction AEs events 
will be summarized by PT.
7.1.7.2.
Treatment-Emergent Adverse Events (TEAE) of Clinical Significance
Number and percentage of subjects with the following AEs of clinical significance will be 
summarized by PT: 

Anaemia/Hemolytic Anemia (MST Anemia Extravascular Transient Hemolysis)

Infusion Related Reaction (IRR) (SMQ-Hypersensitivity Narrow Terms)

Interference with blood cross match or packed RBC transfusion outcomes (Gilead’s MST)

Thromboembolic Events (SMQ- Embolic and Thrombotic Events Broad Terms)

Pneumonitis (SMQ- Interstitial Lung Disease Broad Terms)


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Number and percentage of subjects with the following AEs of clinical significance will also be 
summarized by AE onset time within 2 weeks, >2weeks to 2 months, >2 months to 6 months, 
>6 months to 12 months, and >12 months of first dosing of any study drug:

Anaemia/Hemolytic Anemia 

IRR

Interference with Blood Cross Match or Packed RBC Transfusion Outcomes

Thromboembolic Events

Pneumonitis
7.1.7.3.
Other Important Safety Topics
Number and percentage of subjects with the following AEs of important safety topics will be 
summarized by PT: 

Infections and infestations (SOC)

Immune-Mediated Events (SMQ-Immune-mediate and autoimmune disorder Narrow Terms)
Number and percentage of subjects with the following AEs of important safety topics will also 
be summarized by AE onset time within 2 weeks, >2weeks to 2 months, >2 months to 6 months, 
>6 months to 12 months, and >12 months of first dosing of any study drug:

Immune-Mediated Events (SMQ-Immune-mediate and autoimmune disorder Narrow Terms)
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7. 
A by-subject listing for laboratory test results will be provided by treatment group, subject ID 
and visit in chronological order for hematology and serum chemistry separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
CTCAE severity grade will be flagged in the data listings, as appropriate.
Plots of lab parameters will include (but not limit to) hemoglobin, platelet, and absolute 
neutrophil counts across time.
No formal statistical testing is planned.


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7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Postbaseline maximum value

Postbaseline minimum value

Change and percentage change from baseline to postbaseline maximum value

Change and percentage change from baseline to postbaseline minimum value
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date/time of first dose of any study drug. Change from baseline to a postbaseline visit will be 
defined as the postbaseline value minus the baseline value. The mean, median, Q1, Q3, 
minimum, and maximum values will be displayed to the reported number of digits; StD values 
will be displayed to the reported number of digits plus 1.
Median (Q1, Q3) of the observed values will be plotted using a line plot by treatment group and 
visit for the laboratory tests including but not limited to hemoglobin, platelet, and absolute 
neutrophil counts.
In the case of multiple values associated with a visit, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The CTCAE Version 5.0 will be used to assign toxicity grades (0 to 4) to laboratory results for 
analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of at least 
Grade 1. For laboratory tests with criteria for both increased and decreased levels, analyses for 
each direction (ie, increased, decreased) will be presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days or initiation of new anticancer therapy including SCT 
(whichever is earlier). If the relevant baseline laboratory value is missing, any abnormality of at 
least Grade 1 observed within the time frame specified above will be considered treatment 
emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
patients in the study with the given response at baseline and each scheduled postbaseline time 
point.


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The following summaries (number and percentage of patients) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; patients will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:

TE laboratory abnormalities

TE Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of patients with 
nonmissing postbaseline values up to 30 days after the last dosing date or initiation of new 
anticancer therapy including SCT (whichever is earlier).
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and visit in chronological order. This listing will include all test 
results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades displayed.
7.2.3.
Liver-related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of patients who were reported to have the following laboratory 
test values for postbaseline measurements:

Aspartate aminotransferase (AST): > 3 times of the upper limit of reference range (ULN)

Alanine aminotransferase (ALT): > 3 x ULN

AST or ALT: > 3 x ULN

Total bilirubin: > 2 x ULN

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN and alkaline phosphatase (ALP) < 2 x 
ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
study drug. For individual laboratory tests, patients will be counted once based on the most 
severe postbaseline values. For the composite endpoints of AST or ALT and total bilirubin and 
ALP, patients will be counted once when the criteria are met at the same postbaseline visit date. 
The denominator is the number of patients in the Safety Analysis Set who have nonmissing 
postbaseline values of all relevant tests at the same postbaseline visit date. 
A listing of patients who met at least 1 of the above criteria will be provided.
7.2.4.
Shifts Relative to the Baseline Value
Shift tables will be presented by showing change in severity grade from baseline to the worst 
grade postbaseline for hematology and chemistry laboratory tests.


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7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI, and vital signs 
as follows:

Baseline value

Postbaseline maximum value

Postbaseline minimum value

Change and percentage change from baseline to postbaseline maximum value

Change and percentage change from baseline to postbaseline minimum value. 
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of any study drug. Change from baseline to a postbaseline visit will be defined as 
the postbaseline value minus the baseline value. 
In the case of multiple values for the same visit, data will be selected for analysis as described in 
Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and time point in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
Prior medications are defined as any medications taken before a subject takes the first study 
drug.
Prior medications will be summarized by Anatomical Therapeutic Chemical (ATC) drug class 
Level 2 preferred name using the number and percentage of patients for each treatment group 
and overall. A subject reporting the same medication more than once will be counted only once 
when calculating the number and percentage of patients who received that medication. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
order of descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
For the purposes of analysis, any medication with a start date prior to the first dosing date of 
study drug will be included in the prior medication summary regardless of when the stop date is. 
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(if day is missing) or year (if day and month are missing) of the start date are after the first 
dosing date. Medications with a completely missing start date will be included in the prior 
medication summary, unless otherwise specified.
Summaries will be based on the Safety Analysis Set. No formal statistical testing is planned.
7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a subject took study drug. Use 
of concomitant medications will be summarized by ATC drug class Level 2 preferred name 
using the number and percentage of patients for each treatment group. A subject reporting the 
same medication more than once will be counted only once when calculating the number and 
percentage of patients who received that medication. The summary will be ordered 
alphabetically by ATC medical class and then by preferred term in descending overall frequency 
within each ATC medical class. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to 70 days after last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or 70 days 
after the last dosing date of study drug will also be considered concomitant. Medications with a 
stop date prior to the date of first dosing date of study drug or a start date after the last dosing 
date of study drug plus 70 days will be excluded from the concomitant medication summary. If a 
partial stop date is entered, any medication with the month and year (if day is missing) or year (if 
day and month are missing) prior to the date of first study drug administration will be excluded 
from the concomitant medication summary. If a partial start date is entered, any medication with 
the month and year (if day is missing) or year (if day and month are missing) after the study drug 
stop date plus 70 days will be excluded from the concomitant medication summary. Medications 
with completely missing start and stop dates will be included in the concomitant medication 
summary, unless otherwise specified. Summaries will be based on the Safety Analysis Set. No 
formal statistical testing is planned.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.
7.5.
Premedication
Premedication is required prior to the administration of the first 4 doses of magrolimab/placebo 
and in case of repriming. Premedication during subsequent infusions may be continued based on 
the treating physician’s clinical judgment and the presence/severity of prior infusion-related 
reactions. In the case of a Grade 3 infusion-related reaction, a premedication regimen for 
subsequent infusions is required.


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Premedications will be summarized by Anatomical Therapeutic Chemical (ATC) drug class 
Level 2 preferred name using the number and percentage of patients for each treatment group 
and overall. A subject reporting the same medication more than once will be counted only once 
when calculating the number and percentage of patients who received that medication. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
order of descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
7.6.
Electrocardiogram Results
A by-subject listing of ECG results will be provided by subject ID number in ascending order.
7.7.
Other Safety Measures
A by-subject listing of ECOG performance status will be provided by subject ID number in 
ascending order.


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8.
PHARMACOKINETIC (PK) AND IMMUNOGENECITY 
ANALYSES
8.1.
PK Sample Collection
Blood samples for evaluating magrolimab serum concentrations will be collected at pre-dose at 
Day 1, Day 8, Day 29, Day 57, Day 113, Day 169, Day 253, Day 337, and EOT.  
8.2.
PK Analyses 
Magrolimab concentration will be summarized for the PK Analysis Set. The individual subject’s 
concentration data for magrolimab will be listed based on the sampling time point. Magrolimab 
PK data will be summarized per nominal time point using descriptive statistics. Summary 
statistics (n, mean, SD, coefficient of variation [%CV], median, min, max, Q1, and Q3) will be 
presented for magrolimab serum concentration data at each time point. 
The sample size (number of patients) at each time point will be based on the number of patients 
with nonmissing concentration data at that time point. Missing concentration values will be 
reported as is in data listings. The number of patients with concentration below the limit of 
quantitation (BLQ) will be presented for each time point. 
Concentration values that are BLQ will be presented as “BLQ” in the concentration data listing. 
Values that are BLQ will be treated as 0 at predose and postdose time points for summary 
purposes.
If more than one-third of the subjects have a concentration value of BLQ for a given time point, 
then only the number of samples and order statistics (minimum, Q1, median, Q3, and maximum) 
will be displayed; otherwise, order statistics and summary statistics will be displayed.
The following conventions will be used for the presentation of summary and order statistics: 

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.” 

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.” 

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.” 

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) and summary statistics will be 
displayed as “BLQ.”


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Descriptive graphical plots of individual serum concentration versus time profiles and mean 
(StD) concentration versus nominal time profiles will be generated.
Due to the sparse nature of PK collection, PK parameters will not be calculated.
Data from this study may be combined with PK data from other magrolimab clinical studies and 
analyzed using a population PK model. Such an analysis will be reported separately.
8.3.
Immunogenicity Analysis
The rate and magnitude of anti-magrolimab antibody prevalence, incidence, persistence, and 
transience will be summarized for the Immunogenicity Analysis Set. Neutralizing antibody 
occurrence rate will also be summarized. 
Titer summaries may also be generated, if relevant. Exploratory evaluations may be conducted to 
determine the relationship between anti-magrolimab antibody positivity and safety, PK, or 
efficacy parameters (eg, drug concentrations, AEs, or disease response) using graphical, and/or 
tabular approaches.  


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9.
PHARMACODYNAMIC ANALYSES
Exploratory analyses may be performed to evaluate the association of each biomarker or 
combination of biomarkers with clinical outcomes. Additional details will be provided separately 
by the biomarker sciences group.


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10.
Changes From Protocol-Specified Analyses
There are no deviations from the protocol-specified analyses.


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11.
REFERENCES
Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in Cancer Patients Compared with 
Fatigue in the General United States Population. Cancer 2002;94 (2):528-38.
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised 
recommendations of the International Working Group for Diagnosis, 
Standardization of Response Criteria, Treatment Outcomes, and Reporting 
Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 
2003;21 (24):4642-9.
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical 
application and proposal for modification of the International Working Group 
(IWG) response criteria in myelodysplasia. Blood 2006;108 (2):419-25.
Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised 
International Prognostic Scoring System for Myelodysplastic Syndromes. Blood 
2012;120 (12):2454-65.


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12.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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13.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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14.
APPENDICES
Appendix 1.
Schedule of Assessments
Appendix 2.
Disease Response Assessment Based on International Working Group Criteria


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Appendix 1.
Schedule of Assessments
Appendix Table 1.
Schedule of Assessments – Screening
Study 5F9009
Assessment
Day -30 to --1
Informed consent
Xa
Demographics
X
Medical and cancer history
X
Pregnancy test 
Xb
Serum or plasma chemistry
X
Serum uric acid, phosphorus
X
Hematologyd 
X
Blood phenotyping or genotyping,  type, and screen (ABO/Rh), DATe
X
Urinalysis
X
Bone marrow biopsy and aspirate for blast evaluation, biomarker 
studies, cytogenetics, and MRD assessmentc
X
ECOG
X
Vital signs, height, and weight
X
Complete physical examination
X
ECG (single)
X
Hepatitis B, hepatitis C, and HIVf 
X
Adverse events related to protocol-mandated procedures
X
Concomitant medications
X
Entry criteria
X
Randomization 
Xa
Abbreviations:  ABO = any of the 4 blood groups A, B, AB, and O comprising the ABO system; DAT = direct antiglobulin test; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; FSH = follicle-stimulating hormone; MRD = minimal 
residual disease; Rh = Rhesus factor; SOC = standard of care.
a
Screening must be completed before randomization.  Randomization must occur within 30 days of signing informed 
consent.  The first dose of study treatment (Protocol Table 3 and Protocol Table 4) must be given within 72 hours after 
randomization.
b
Screening pregnancy test may be used as the Day 1 test if performed within 72 hours of first dose; additional guidance is 
provided in Protocol Section 5.1.1.  FSH test is required for female patients who are < 54 years old who are not on hormonal 
contraception and who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal 
failure.
c
A trephine (biopsy) is to be collected for baseline. A bone marrow biopsy collected per SOC within 30 days of 
randomization can be considered the screening sample, and shipped to central laboratory.  This procedure must be 
performed prior to the first dose of study treatment at the latest.  An aspirate sample must be collected at the screening visit 
for blast evaluation, MRD assessment, biomarker studies, baseline for response assessment and biobanking.  It is preferred 
that bone marrow aspirate samples are obtained at the time of bone marrow (trephine) biopsy.  Conventional cytogenetics to 
be tested per institutional standards.
d
Hematology analytes to be assessed at screening are provided in Protocol Table 7
e
RBC genotyping (instead of an extended RBC phenotyping) must be performed if a patient received any RBC or whole 
blood transfusion within the previous 3 months (unless laboratory has availability for special techniques for performing 
phenotyping for patients with recent transfusion). Results must be available before the first dose of magrolimab.
f
Refer to Exclusion Criteria 13 and Other Laboratory Measurements in Protocol Table 7 


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Appendix Table 2.
Schedule of Assessments - Treatment Period-Azacitidine Dosing and Study Assessments
Cycle (28-day Cycles)
1
2
3+
Visit Window (Days)
None
± 3
± 3
± 3
Cycle Day
1
2
3
4
5
6
7
1
2
3
4
5
6
7
1
2
3
4
5
6
7
PRO assessmenta
X
X
X
CBC with differential, platelets, reticulocytesb
X
X
X
Serum or plasma chemistryb
X
X
X
Bone marrow biopsy and aspirate for biomarker studies c
Xd,e
Bone marrow aspirate biopsy for MRD monitoring, 
cytogenetics, and response assessmentd,f
X
Q2C, Q3Ce
Vital signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed physical examinationb
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Azacitidineh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations:  CBC = complete blood count; EQ-5D-5L = 5-level EuroQol 5 dimensions; FACT-Anemia = Functional Assessment of Cancer Therapy-Anemia; MRD = minimal 
residual disease; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PRO = patient-reported outcome; Q2C = every 2 cycles; 
Q3C = every 3 cycles.
a
Four PRO questionnaires will be administered in this study:  the FACT-Anemia questionnaire, the EQ-5D-5L, the PGIS, and the PGIC.  The patient should complete these 
questionnaires before other study procedures at required visits.  No PGIC assessment at Cycle 1 Day 1.  FACT‑Anemia and EQ-5D-5L should be implemented prior to 
PGIS/PGIC.
b
If magrolimab and azacitidine are administered on the same day, only one such study assessment is needed.  Assessments should be performed prior to study treatment 
administration. Pretreatment assessments for the initial dose (Cycle 1 Day 1) may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment 
assessments are to be collected within 24 hours prior to study treatment administration. 
c
Bone marrow biopsy samples will be collected at Day 1 of Cycles 3 and 10.
d
An aspirate sample will be collected for response assessment, biomarker studies, and MRD assessment.  Conventional cytogenetics to be tested per institutional standards.  
Response assessments may be adjusted by ± 1 week for Cycle 3 Day 1.  After Cycle 3 Day 1, the window is ± 14 days.
e
An aspirate sample will be collected for biomarker studies at Day 1 of Cycles 3, 5, 7, 10, and 13.  
f
Samples will be collected at Day 1 of Cycles 3, 5, and 7 and then every 3 cycles thereafter during study treatment.  Bone marrow aspirate biopsies for response assessments 
may be adjusted by ± 1 week for Cycle 3 Day 1.  After Cycle 3 Day 1, the window is ± 14 days. 
g
Vital signs will be assessed prior to infusion/injection of each study treatment.  Weight will be assessed on Day 1 of each cycle.  Details are provided in Protocol Section 5.1.5.
h
If Azacitidine and magrolimab/placebo are administered on the same day, azacitidine administration should be completed at least 1 hour before magrolimab/placebo 
administration.  Azacitidine may be administered on an alternative schedule of Days 1 to 5, Day 8, and Day 9 of a 28-day cycle for flexibility and convenience.  


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Appendix Table 3.
Schedule of Assessments - Treatment Period-Magrolimab or Placebo Dosing and Study Assessments
Dose Schedule
Priming Dosing 
Maintenance Dosing
Visit Window (Days)
None
± 3
± 3
Day
1
2 
4
8
11
15
22
29
36
43
50
57
every 2 Weeks thereafter 
Pregnancy testa
X
X
X Q4W
CBC with differential, platelets, 
reticulocytesb,c,d
Xe
X
Xe
X
X
X
X
X
X
X
X
X
X
Haptoglobin and LDHc
X
X
X
Serum or plasma chemistryb,c
X
X
X
X
X
X
X
X
Peripheral smearc,f
X
X
X
Peripheral blood sample for biomarker 
studiesg
X
X
X
Xh
PKg
X
X
X
Xi 
Antidrug antibodiesc,j
X
X
Xi
Vital signsk
X
 
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed physical examinationb,c
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X 
X
X
X
X
X
X
X
X
X
X
X
X
Premedicationl
X
X
X
X
Magrolimab or placebom
Xn
Xn 
X
X
X
X
X
X
X
X
X
X
Abbreviations:  CBC = complete blood count; D = day; EOT = end of treatment; LDH = lactate dehydrogenase; MRD = minimal residual disease; PK = pharmacokinetic(s); PRO = 
patient-reported outcome; Q4W = every 4 weeks; WBC = white blood cell.
a
Screening pregnancy test may be used if performed within 72 hours of first dose; pregnancy tests will be conducted once every month; additional guidance is provided in 
Protocol Section 5.1.1.
b
If magrolimab and azacitidine are administered on the same day, only one such study assessment is needed Assessments should be performed prior to study treatment 
administration. For monitoring of infusion-related reactions, please refer to Protocol Section 6.5


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c
Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected 
within 24 hours prior to study treatment administration.
d
Additional samples for CBC may be collected outside of the protocol-specified time points to ensure a WBC level ≤ 20 × 103/µL prior to each magrolimab/placebo dose 
during the first 28 days of magrolimab priming dose.  Peripheral blasts should be included in the CBC assessments.
e
An additional hemoglobin check must be performed 3 to 6 hours after the initiation of the first and second doses of magrolimab/placebo during initial treatment. The patient 
should be transfused as clinically appropriate. Investigators should consider additional hemoglobin monitoring during the first week of treatment in patients with symptoms of 
anemia or increased risk for complications of anemia.
f
Peripheral smears will be collected predose and assessed locally.
g
Samples for PK and biomarker studies will be collected predose within 12 hours prior to study treatment administration.
h
Samples will be collected prior to first maintenance dose (Day 57), ninth (Day 169) maintenance dose, and EOT.
i
Samples will be collected predose on Day 57, Day 113, Day 169, Day 253, Day 337, and EOT.
j
When collected on the day of study treatment dosing, the blood sample for antidrug antibodies must be collected at the same time as the predose PK sample.
k
Vital signs will be assessed prior to infusion/injection of each study treatment.  Weight will be assessed every 4 weeks.  Details are provided in Protocol Section 5.1.5.
l
Premedication is required prior to the administration of the first 4 doses of study treatment and in case of reintroduction with repriming.  Premedication for subsequent 
treatment periods may be continued based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions.  In the case of a Grade 3 
infusion-related reaction, a premedication regimen for subsequent treatment periods is required (Protocol Section 6.5).
m
Magrolimab or saline placebo should not be given on consecutive days.  The duration of each magrolimab/placebo infusion including flush will be 3 hours (± 30 minutes) for 
the first dose of treatment. After the first dose of treatment, the magrolimab/placebo infusion including flush will be 2 hours (± 30 minutes).  All patients should be monitored for 
1 hour after infusion for doses during the first 28 days and the repriming doses.
n
Within 24 hours prior to each of the first 2 doses of magrolimab/placebo infusion during initial treatment, all subjects must have a documented hemoglobin  9.0 g/dL. 
Patients who do not meet these criteria must be transfused and have their hemoglobin rechecked to meet 9.0 g/dL prior to each of the first 2 doses of magrolimab. 


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Appendix Table 4.
Schedule of Assessments – Post Treatment
End-of-
treatment Visit
Safety Follow-up Visit/Call
(Telephone)a
Long-term 
Follow-up
Survival 
Follow-up
Within 7 Days 
after Last Dose 
or EOT Decision
30 Days
after Last 
Dose
70 Days 
after Last 
Dosek
Until Start of New 
Anticancer Therapy 
or Transformation 
to AMLb
Every 2 Months 
Until Death or 
End of Study
Visit Window
± 7 Days
± 7 Days
± 7 Days
+4 Weeks
Serum or urine pregnancy test
X
Q4Wc
Q4Wc
CBC with differential, platelet count, reticulocytes
X
Q8Wd
Serum or plasma chemistry
X
Peripheral blood for biomarker studies
X
Pharmacokinetics
X
Antidrug antibodies 
X
Bone marrow biopsy and aspirate for MRD monitoring and 
cytogeneticsd,e
X
Q8Wd
Response assessmente,f
X
Q8Wd
ECOG
X
Vital signs
X
Symptom-directed physical examination
X
PRO assessmentg
X
X
Adverse eventsh
X
X
X
Concomitant medications
X
X
X
Blood transfusioni
X
X
New anticancer therapyj
X
X
Survival follow-up
Q2M
Abbreviations:  AE = adverse event; AML =  acute myeloid leukemia; CBC = complete blood count; CR = complete remission; eCRF = electronic case report form; EOT = end of 
treatment; EQ-5D-5L = 5-level EuroQol 5 dimensions; FACT-Anemia = Functional Assessment of Cancer Therapy-Anemia; IWG = International Working Group; 
MDS = myelodysplastic syndrome; MRD = minimal residual disease; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PR = partial 
remission; PRO = patient-reported outcome; QxM = every x months; QxW = every x weeks; SAE = serious adverse event.


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a
If the patient experiences a treatment-related AE or an SAE (regardless of attribution), the patient must be asked to come to the site.
b
Until start of new anticancer therapy or transformation to AML, whichever comes first.
c
Collect until the end of the contraception requirement.
d
Bone marrow assessment, MRD, CBC, and response assessment should be performed until start of new anticancer therapy or transformation to AML, whichever comes first.  
Conventional cytogenetic testing (per institutional standards) is required for all patients.
e
For patients who come off the study treatment to undergo a stem cell transplant, response assessments for relapse/remission status and bone marrow aspirate results are 
required to be obtained locally and entered into the eCRF. 
f
Response assessment at EOT visit not required if performed within the last 30 days or progressive disease has been documented.  After disease progression (including 
treatment failure by IWG criteria and relapse after CR or PR), response assessment will focus on evaluation of transformation to AML.
g
Paper PROs will be administered in this study:  The FACT-Anemia questionnaire, the EQ-5D-5L, the PGIS, and the PGIC will be administered.  The patient should complete 
these questionnaires before other study procedures at required visits.  FACT-Anemia and EQ-5D-5L should be implemented prior to PGIS/PGIC. FACT-Anemia, EQ-5D-5L 
the PGIS, and the PGIC should also be collected during long-term follow-up prior to initiation disease progression or initiation of a new anticancer therapy.
h
Report all AEs through the Safety Follow-up Visit/Call and any treatment-related SAEs thereafter.
i
Collect blood transfusions until start of new anticancer therapy.
j
Collect new anticancer therapy data following the last dose of study treatment.
k
For patients who do not initiate new anticancer therapy after the last dose. See Protocol Sections 5.1.10 for adverse event reporting details.


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Appendix Table 5.
Schedule of Assessments – Repriming (Required After > 4 Weeks Have Lapsed Since the Last Dose of 
Magrolimab/Placebo Delays)
Day
1
2
3
4
5
6
7
8
11
15
22
Visit Window (Days)
-
-
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
Pregnancy test
X
CBC with differential, platelets, and 
reticulocytesa,b
X
X
X
X
X
X
X
Haptoglobin and LDH
X
X
Serum or plasma chemistrya
X
X
X
X
Peripheral smeara,c
X
X
X
Peripheral blood for biomarker studiesd
X
X
PKd
X
X
Antidrug antibodiesa
X
Vital signse
X
X
X
X
X
Symptom-directed physical examinationa
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
Blood transfusions
X
X
X
X
X
X
X
X
X
X
X
Premedicationf
X
X
X
X
Magrolimab/placebo: reprimingg
X
X
X
X
X
X
Abbreviations: CBC = complete blood count; ECOG = Eastern Cooperative Oncology Group; LDH = lactate dehydrogenase; PK = pharmacokinetic(s); PRO = patient-reported 
outcome; WBC = white blood cell.
a
Pretreatment assessments are to be collected within 24 hours prior to study treatment administration.
b
Additional samples for CBC may be collected outside of the protocol-specified time points to ensure a WBC level ≤ 20 × 103/μL for the repriming cycle.
c
Peripheral smears will be collected and assessed locally.
d
Samples for PK and biomarker studies will be collected predose within 12 hours prior to study treatment administration.


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e
Vital signs prior to infusion/injection of study treatment. Weight at Day 1. Details are provided in Protocol Section 5.1.5.
f
Premedication is required prior to the administration of the first 4 doses of study treatment and in case of reintroduction with repriming. Premedication for subsequent cycles 
may be continued based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions. In the case of a Grade 3 infusion-related 
reaction, a premedication regimen for subsequent cycles is required (Protocol Section 6.5).
g
Magrolimab or saline placebo should not be given on consecutive days. During repriming, the duration of each magrolimab/placebo infusion including flush will be 3 hours 
(± 30 minutes) for the first 3 doses of treatment and 2 hours (± 30 minutes) for infusions beyond the first 3 doses. All participants should be monitored for 1 hour after 
infusion for doses during the first 28 days and the repriming doses. After Day 22, participants should return to their original dose schedule.


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Appendix 2.
Disease Response Assessment Based on International Working Group 
Criteria 
Response will be assessed in myelodysplastic syndrome (MDS) patients using the 2006 
International Working Group (IWG) criteria {Cheson 2006} with modifications as shown in 
Appendix Table 6.  In addition, complete remission (CR) with partial hematologic recovery 
(CRh) will be assessed for MDS, defined as patients who achieve a CR per IWG 2006 MDS 
criteria {Cheson 2006}, with the exception of requiring partial hematologic recovery as defined 
by a platelet count of > 50 × 109/L and an absolute neutrophil count of > 500/µL.
In addition, HI will be assessed by 2006 IWG criteria {Cheson 2006}; Appendix Table 8) and 
cytogenetic/molecular response by 2003 IWG criteria {Cheson 2003}; Appendix Table 7).
Appendix Table 6.
Response Criteria in MDS (IWG 2006 Criteria)
Category
Response Criteria 
CR
Bone marrow ≤ 5% myeloblasts with normal maturation of all cell linesa
Persistent dysplasia will be noteda,b
Peripheral bloodc
Hgb ≥ 11 g/dL
Platelets ≥ 100 × 109/L
Neutrophils ≥ 1.0 × 109/Lb
Blasts 0%
PR
All CR criteria if abnormal before treatment except:
Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%
Cellularity and morphology not relevant
Marrow CRb
Bone marrow ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatmentb
Peripheral blood:  if HI responses, they will be noted in addition to marrow CRb
Stable Disease
Failure to achieve at least PR, but no evidence of progression for > 8 weeks
Failure
Death during treatment or disease progression characterized by worsening cytopenias, 
increase in percentage of bone marrow blasts, or progression to a more advanced MDS 
FAB subtype than pretreatment
Relapse after CR 
or PR
At least 1 of the following:
Return to pretreatment bone marrow blast percentage
Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets
Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependenced
Cytogenetic 
Response
Complete:  Disappearance of chromosomal abnormality without appearance of new ones
Partial:  At least 50% reduction of the chromosomal abnormality


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Category
Response Criteria 
Disease 
Progression
For patients with:
Less than 5% blasts:  ≥ 50 increase in blasts to > 5% blasts
5%-10% blasts:  ≥ 50% increase in blasts to > 10% blasts
10%-20% blasts:  ≥ 50% increase in blasts to > 20% blasts
20%-30% blasts:  ≥ 50% increase in blasts to > 30% blasts
Any of the following:
At least 50% decrement from maximum remission/response in granulocytes or platelets
Reduction in Hgb by ≥ 2 g/dLd
Transfusion dependenced
Source: {Cheson 2006}
Abbreviations:  CR = complete remission; FAB = French-American-British classification; Hgb = hemoglobin; HI = hematologic 
improvement; IWG = International Working Group; MDS = myelodysplastic syndrome; PR = partial remission.
a
Dysplastic changes should consider the normal range of dysplastic changes.
b
Modification to IWG response criteria
c
In some circumstances, protocol therapy may require the initiation of further treatment (e.g., consolidation, maintenance) 
before the 4-week period.  Such patients can be included in the response category into which they fit at the time the therapy 
is started.  Transient cytopenias during repeated chemotherapy courses should not be considered as interrupting durability of 
response, as long as they recover to the improved counts of the previous course.
d
Impact of anemia must be deemed disease-related and not due to study treatment.
Appendix Table 7.
Additional Response Definitions Used in This Study 
(2003 IWG Criteria)
Definitions
Response Criteria
Neutrophils
Platelets
Bone Marrow 
Blasts
Other
cCR
≥ 1.0 × 109/L
≥ 100 × 
109/L
< 5%
Cytogenetics normal and no 
evidence of extramedullary disease 
mCR
≥ 1.0 × 109/L
≥ 100 × 
109/L
< 5%
Molecular investigations normal 
and no evidence of extramedullary 
disease 
Treatment Failurea
Lack of response/Progressive Disease + loss of clinical benefit
Source:  {Cheson 2003}
Abbreviations:  cCR = cytogenetic complete remission; IWG = International Working Group; mCR = molecular complete 
remission.
a
Treatment failure defined for this protocol


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Appendix Table 8.
Response Criteria for Hematologic Improvement
Hematologic Improvement (HI) 
Categorya
Response Criteria (all responses must last ≥ 8 weeks)
Erythroid Response (HI-E)
(pretreatment < 110 g/L)
Pretransfusion increase in hemoglobin by 15 g/L
or
Compared to an 8-week pretreatment period, a reduction in 
transfusion requirements by 4 units in an 8-week posttreatment 
period 
Platelet Response (HI-P)
(pretreatment < 100 × 109/L)
Absolute increase of ≥ 30 × 109/L for patient starting with a 
platelet count > 20 × 109/L pretreatment
or
Increase from < 20  × 109/L pretreatment to > 20  × 109/L 
posttreatment and by at least 100%
Neutrophil Response (HI-N)
(pretreatment < 1.0 × 109/L)
At least 100% increase and an absolute increase of > 0.5 × 109/L
Progression/relapse after Hematological 
Improvementb
One or more of the following
≥ 50% decrement from maximum response in neutrophils or 
platelets
Reduction in hemoglobin by ≥ 15 g/L
Transfusion dependence
Source:  {Cheson 2006}
a
Pretreatment counts should be an average of at least 2 measurements (not influenced by transfusions) performed ≥ 1 week 
apart.
b
In the absence of another explanation.  For example, including, but not restricted to, acute infection, gastrointestinal 
bleeding and hemolysis.


5F9009 SAP – Primary CR and 1st OS Interim Analyses
ELECTRONIC SIGNATURES
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Server Date
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Bill Grossman
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Jenny Huang10
Biostatistics eSigned
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05:02:48