Conditions: Myelodysplastic Syndromes
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief summary:
The primary purpose of the study is to evaluate the preliminary safety and efficacy of oral decitabine/cedazuridine in combination with magrolimab.

Detailed description:

Arms:
arm 1: Participants will receive 35 milligrams (mg) decitabine/100 mg cedazuridine as a fixed dose combination (FDC) tablet, orally, once daily (QD) on Days 1-5 of each 28-day cycle in combination with magrolimab, intravenous (IV) infusion of 1 milligrams per kilogram (mg/kg) on Days 1 and 4, 15 mg/kg on Day 8, 30 mg/kg on Days 11, 15, 22, 29, 36, 43, and 50, followed by a maintenance dose of 30 mg/kg on Day 57 and every 14 days thereafter until toxicity, progressive disease, withdrawal, death or end of study (approximately 44 months).

Interventions: intervention 1: Decitabine/Cedazuridine intervention 2: Magrolimab
Intervention descriptions: intervention 1: Oral FDC tablets administration intervention 2: IV administration

Protocol document:
Prot_SAP_000.pdf: 
Official Title: 
NCT Number: 
NCT05835011
Document Dates:
 Protocol and SAP Version 2.0: 19 December 2022
A Phase 2 Study of Oral Decitabine/Cedazuridine in Combination With 
Magrolimab for Previously Untreated Subjects With Intermediate- to Very High-
Risk Myelodysplastic Syndromes (MDS) 


Astex Pharmaceuticals. Inc. 
 
ASTX727 
Synoptic Clinical Study Report ASTX727-10 
Confidential Information 
16.1.1 Protocol and Protocol Amendments  
Protocol Amendment 1.0 (19 December 2022) 
• Summary of Changes from Original 


CONFIDENTIAL 
This document is a confidential communication of Astex Pharmaceuticals, Inc. Acceptance of the 
document constitutes agreement by the recipient that the contents will not be disclosed to any 
unauthorized personnel without the prior written authorization of Astex Pharmaceuticals, Inc. 
 
 
Clinical Study Protocol — ASTX727-10 
A Phase 2 Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab for 
Previously Untreated Subjects With Intermediate- to Very High-Risk Myelodysplastic 
Syndromes (MDS) 
Protocol Number: 
ASTX727-10 
Amendment Number: 
1.0 
Compound: 
Oral Decitabine/Cedazuridine + Magrolimab 
Short Title: 
A Study of Oral Decitabine/Cedazuridine in Combination 
With Magrolimab in Subjects With Intermediate- to Very 
High-Risk MDS 
Study Phase: 
Phase 2 
Sponsor Name: 
Astex Pharmaceuticals, Inc. 
Legal Registered Address: 
4420 Rosewood Drive, Suite 200 
Pleasanton, CA 94588 
Medical Monitor Name and  
, MD PhD 
Contact Information: 
Office: 
 
 
IND Number: 
116145 
EU CTR Number: 
2022-501548-14-00 
Version (Date): 
Original (28 September 2022) 
 
Amendment 1.0 (19 December 2022) 
 
 


Astex Pharmaceuticals, Inc. 
 
Oral Decitabine/Cedazuridine 
Clinical Protocol ASTX727-10 
Confidential Information 
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Amendment 1.0, 19 December 2022 
TABLE OF CONTENTS 
LIST OF TABLES .........................................................................................................................5 
LIST OF FIGURES .......................................................................................................................6 
LIST OF ABBREVIATIONS AND DEFINITIONS ..................................................................7 
1.0 
PROTOCOL SUMMARY ..............................................................................................10 
1.1 
Synopsis .............................................................................................................................10 
1.2 
Schema ...............................................................................................................................14 
1.3 
Schedules of Activities (SoA) ............................................................................................15 
2.0 
INTRODUCTION............................................................................................................22 
2.1 
Background ........................................................................................................................22 
2.2 
Study Rationale ..................................................................................................................23 
2.3 
Benefit/Risk Assessment ...................................................................................................25 
2.3.1 
Oral Decitabine/Cedazuridine .......................................................................................25 
2.3.2 
Magrolimab ...................................................................................................................25 
3.0 
OBJECTIVES AND ENDPOINTS ................................................................................26 
4.0 
STUDY DESIGN ..............................................................................................................26 
4.1 
Overall Design ...................................................................................................................26 
4.1.1 
Dose-Limiting Toxicity Cohort .....................................................................................27 
4.2 
Scientific Rationale for Study Design ................................................................................29 
4.3 
Data and Safety Review Committee ..................................................................................30 
4.4 
Recruitment ........................................................................................................................30 
4.5 
Dosing Administration .......................................................................................................31 
4.6 
Justification for Dose .........................................................................................................34 
4.6.1 
Oral Decitabine/Cedazuridine .......................................................................................34 
4.6.2 
Magrolimab ...................................................................................................................34 
4.7 
End of Study Definition .....................................................................................................36 
5.0 
STUDY POPULATION ..................................................................................................37 
5.1 
Inclusion Criteria ...............................................................................................................37 
5.2 
Exclusion Criteria ..............................................................................................................39 
5.3 
Lifestyle Considerations ....................................................................................................40 
5.3.1 
Meals and Dietary Restrictions .....................................................................................40 
5.3.2 
Contraceptive Requirements .........................................................................................41 
5.3.3 
Type and Screen and Direct Antiglobulin Test .............................................................41 
5.4 
Screen Failures ...................................................................................................................41 
6.0 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY .............................42 
6.1 
Description of Study Interventions Administered .............................................................42 


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Clinical Protocol ASTX727-10 
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6.2 
Preparation/Handling/Storage/Accountability ...................................................................42 
6.3 
Measures to Minimize Bias: Randomization and Blinding ...............................................43 
6.4 
Study Intervention Compliance .........................................................................................44 
6.5 
Premedication ....................................................................................................................44 
6.6 
Dose Modification .............................................................................................................44 
6.6.1 
Oral Decitabine/Cedazuridine Dose Modifications ......................................................44 
6.6.2 
Magrolimab Dose Modifications ...................................................................................45 
6.6.3 
Temporary Discontinuation of Oral Decitabine/Cedazuridine .....................................46 
6.7 
Missed or Vomited Doses ..................................................................................................46 
6.8 
Treatment of Overdose ......................................................................................................47 
6.9 
Concomitant Therapy.........................................................................................................48 
6.9.1 
Supportive, Prophylactic, or Other Treatments Allowed ..............................................48 
6.9.2 
Prohibited Medications/Therapies .................................................................................48 
6.9.3 
Rescue Medicine ...........................................................................................................49 
6.9.4 
COVID-19 Vaccine .......................................................................................................49 
6.10 
Study Treatment After the End of the Study .....................................................................49 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................49 
7.1 
Permanent Discontinuation of Study Treatment ................................................................49 
7.2 
Subject Discontinuation/Withdrawal From the Study .......................................................50 
7.3 
Lost to Follow-up ...............................................................................................................50 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ..........................................................51 
8.1 
Demographics, Medical History, and Prior Anticancer Therapy ......................................51 
8.2 
Safety Assessments ............................................................................................................52 
8.2.1 
Physical Examinations ..................................................................................................52 
8.2.2 
Vital Signs .....................................................................................................................52 
8.2.3 
Twelve-lead Electrocardiograms ...................................................................................52 
8.2.4 
Clinical Safety Laboratory Assessments .......................................................................53 
8.2.5 
Pregnancy Testing .........................................................................................................55 
8.2.6 
Eastern Cooperative Oncology Group Performance Status ..........................................55 
8.3 
Efficacy Assessments .........................................................................................................56 
8.3.1 
Disease Response Assessment ......................................................................................56 
8.3.2 
Long-term Follow-up ....................................................................................................57 
8.4 
Pharmacokinetics ...............................................................................................................57 
8.5 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ............................59 
8.5.1 
Time Period and Frequency for Collecting Adverse Events and Serious Adverse 
Event Information .........................................................................................................59 


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Clinical Protocol ASTX727-10 
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8.5.2 
Method of Detecting Adverse Events and Serious Adverse Events .............................59 
8.5.3 
Follow-up of Adverse Events and Serious Adverse Events ..........................................59 
8.5.4 
Regulatory Reporting Requirements for Serious Adverse Events ................................60 
8.5.5 
Pregnancy ......................................................................................................................60 
8.5.6 
Definition of Dose-limiting Toxicities ..........................................................................60 
8.5.7 
Specific Safety Management Guidelines ......................................................................61 
9.0 
STATISTICAL CONSIDERATIONS ...........................................................................63 
9.1 
Sample Size Determination ................................................................................................63 
9.2 
Analyses Sets .....................................................................................................................64 
9.3 
Statistical Analyses ............................................................................................................64 
9.3.1 
General Considerations .................................................................................................64 
9.3.2 
Primary Endpoint(s) ......................................................................................................64 
9.3.3 
Other Analysis ...............................................................................................................65 
9.4 
Interim Analysis .................................................................................................................65 
9.5 
Toxicity Stopping Rule ......................................................................................................66 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS .......................................................................................................67 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............................67 
10.1.1 
Regulatory and Ethical Considerations .........................................................................67 
10.1.2 
Financial Disclosure ......................................................................................................67 
10.1.3 
Informed Consent Process .............................................................................................68 
10.1.4 
Data Protection ..............................................................................................................68 
10.1.5 
Dissemination of Clinical Study Data ...........................................................................68 
10.1.6 
Data Quality Assurance .................................................................................................69 
10.1.7 
Source Documents .........................................................................................................69 
10.1.8 
Study and Site Closure ..................................................................................................70 
10.1.9 
Publication Policy ..........................................................................................................70 
10.1.10 
Clinical Trial Insurance .................................................................................................70 
10.2 
Appendix 2: Contraceptive and Barrier Guidance .............................................................71 
10.2.1 
Definitions .....................................................................................................................71 
10.2.2 
Contraception Guidance ................................................................................................72 
10.2.3 
Collection of Pregnancy Information ............................................................................73 
10.3 
Appendix 3: Revised International Prognostic Scoring System for Myelodysplastic 
Syndromes (IPSS-R) ..........................................................................................................74 
10.4 
Appendix 4: Molecular International Prognostic Scoring System for Myelodysplastic 
Syndromes (IPSS-M) .........................................................................................................75 


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Clinical Protocol ASTX727-10 
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10.5 
Appendix 5: Adverse Events and Serious Adverse Events: Definitions and Procedures 
for Recording, Evaluating, Follow-up, and Reporting ......................................................77 
10.5.1 
Definition of AE ............................................................................................................77 
10.5.2 
Definition of SAE ..........................................................................................................78 
10.5.3 
Recording, Severity, Relationship, and Follow-Up of AEs and/or SAEs, Lost to 
Follow-up and Stopping of AE/SAE Collection ...........................................................79 
10.5.4 
Reporting of Overdose or Other Medication Errors: .....................................................83 
10.5.5 
Reporting of SAEs .........................................................................................................84 
10.6 
Appendix 6: Disease Response Assessment Based on International Working Group 
Criteria ...............................................................................................................................85 
10.7 
Appendix 7: Modifications During a COVID-19 Health Emergency ...............................87 
10.7.1 
General Information ......................................................................................................87 
10.7.2 
Study Status ...................................................................................................................87 
10.7.3 
COVID-19 Benefit/Risk Assessment ............................................................................87 
10.7.4 
Modifications to Study Conduct ....................................................................................88 
10.8 
Appendix 8: Summary of Changes from Original to Amendment 1.0 ..............................89 
11.0 
REFERENCES .................................................................................................................91 
 
LIST OF TABLES 
Table 1: 
Schedule of Activities for Oral Decitabine/Cedazuridine .........................15 
Table 2: 
Schedule of Activities for Magrolimab ......................................................18 
Table 3: 
Dosing Schedule for Oral Decitabine/Cedazuridine ..................................20 
Table 4: 
Dosing Schedule for Magrolimab ..............................................................20 
Table 5: 
Treatment Administration Schedule for Oral Decitabine/Cedazuridine ....31 
Table 6: 
Treatment Administration Schedule for Magrolimab ................................32 
Table 7: 
Alternative Options for Oral Decitabine/Cedazuridine Administration 
on Days 1-5 ................................................................................................32 
Table 8: 
Oral Decitabine/Cedazuridine and Magrolimab Products Used in the 
Study ..........................................................................................................42 
Table 9: 
Dosing Reduction Guidelines for Oral Decitabine/Cedazuridine ..............45 
Table 10: 
Laboratory Analyte Listing (To Be Performed at Screening) ...................54 
Table 11: 
Laboratory Analyte Listing (To Be Performed During the Study) ............55 
Table 12: 
Eastern Cooperative Oncology Group Performance Status .......................56 
Table 13: 
Serum Collection Schedule for Pharmacokinetic Analysis and 
Antidrug Antibodies (ADA) for Serum Magrolimab ................................58 
Table 14: 
Plasma Collection Schedule for Pharmacokinetic Analysis for Oral 
Decitabine/Cedazuridine ............................................................................58 


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Clinical Protocol ASTX727-10 
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Table 15: 
Analysis Populations ..................................................................................64 
Table 16: 
Probabilities of Observing Varying Frequency of Response Under 
Different True Response Rates (40 Subjects) ............................................66 
Table 17: 
Criteria for Excess Toxicity for an Acceptable Dose-limiting Toxicity 
Rate of 20%................................................................................................66 
Table 18: 
Revised International Prognostic Scoring System for Myelodysplastic 
Syndromes Prognostic Score Values .........................................................74 
Table 19: 
Revised International Prognostic Scoring System for Myelodysplastic 
Syndromes Prognostic Risk Categories/Scores .........................................74 
Table 20: 
IPSS-M Risk Score Construction From an Adjusted Cox Multivariable 
Regression for Leukemia-Free Survival ....................................................76 
Table 21: 
Response Criteria in Myelodysplastic Syndromes (IWG 2006 Criteria) ...85 
Table 22: 
Criteria for Hematologic Improvement .....................................................86 
 
LIST OF FIGURES 
Figure 1: 
Schema .......................................................................................................14 
Figure 2: 
Dosing Reduction Process for Oral Decitabine/Cedazuridine-
Associated Dose-Limiting Toxicities ........................................................29 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS  
Abbreviation 
Definition 
ABO 
any of the 4 blood groups (A, B, AB, and O) 
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 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BM 
bone marrow 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CMML 
chronic myelomonocytic leukemia 
CNS 
central nervous system 
CR 
complete response 
CS&RM 
Clinical Safety and Risk Management 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAT 
direct antiglobulin test 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
DSRC 
Data and Safety Review Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
Fc 
fragment crystallizable 
FDC 
fixed-dose combination 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HBV 
hepatitis B virus  
HCV 
hepatitis C virus 
Hgb 
hemoglobin  
HBsAg 
hepatitis B surface antigen 
HI 
hematologic improvement 
HIV 
human immunodeficiency virus 
HMA 
hypomethylating agent 
HRT 
hormonal replacement therapy 
HSCT 
hematopoietic stem cell transplant 
IB 
Investigator Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 


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Clinical Protocol ASTX727-10 
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Abbreviation 
Definition 
IEC 
Independent Ethics Committee 
IMP 
investigational medicinal product (the specific Astex drug product under study) 
IND 
investigational new drug 
INR 
international normalized ratio 
IPSS-M 
Molecular International Prognostic Scoring System for myelodysplastic syndromes 
IPSS-R 
Revised International Prognostic Scoring System for myelodysplastic syndromes 
IRB 
Institutional Review Board 
IV 
intravenous 
IWG 
International Working Group 
LDH 
lactate dehydrogenase 
LFS 
leukemia-free survival 
LTFU 
Long-term follow-up 
M 
Magrolimab 
mAb(s) 
monoclonal antibody(ies) 
mCR 
marrow complete response 
MDS 
myelodysplastic syndromes 
MPN 
myeloproliferative neoplasm 
MRD 
minimal residual disease 
MTD 
maximum tolerated dose 
NA 
not applicable 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin lymphoma 
No. 
number 
ORR 
overall response rate 
OS 
overall survival 
PB 
peripheral blood 
PE 
physical examination 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PO 
by mouth 
PR 
partial response 
PS 
performance status 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QD 
once daily 
RBC 
red blood cell 
Rh 
rhesus factor 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCT 
stem cell transplant 
SGOT 
serum glutamic-oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SIRPα 
signal regulatory protein alpha 
SoA 
schedule of activities 
SOC 
standard of care 


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Clinical Protocol ASTX727-10 
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Abbreviation 
Definition 
ULN 
upper limit of normal 
WBC 
white blood cell 
w/v 
weight by volume 
 
 
 


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Clinical Protocol ASTX727-10 
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1.0 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Study Number and Title: ASTX727-10: A Phase 2 Study of Oral Decitabine/Cedazuridine in 
Combination With Magrolimab for Previously Untreated Subjects With Intermediate- to Very 
High-Risk Myelodysplastic Syndromes (MDS) 
Short Title: A Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab in 
Subjects With Intermediate- to Very High-Risk MDS 
Clinical Phase: 2 
Study Centers Planned/Country: Multicenter; countries in North America, Europe, and Asia 
Pacific  
Rationale: The current study will aim to evaluate oral decitabine/cedazuridine in combination 
with magrolimab for previously untreated subjects with intermediate- to very high-risk MDS, as 
determined by the Revised International Prognostic Scoring System for myelodysplastic 
syndromes (IPSS-R).  
Oral decitabine/cedazuridine is a hypomethylating agent (HMA) that is approved for use in 
subjects with intermediate- to high-risk MDS, as well as in subjects with chronic myelomonocytic 
leukemia (CMML), in the US, Canada, and Australia. Oral decitabine/cedazuridine was approved 
based on clinical studies that determined its pharmacokinetic (PK) area under the concentration-
time curve (AUC) equivalence to intravenous (IV) decitabine administration. Results from Phase 2 
and 3 studies have demonstrated a positive treatment effect of oral decitabine/cedazuridine and 
that the clinical efficacy of oral decitabine/cedazuridine is consistent with efficacy described for 
intravenously administered decitabine in subjects with MDS. At the therapeutic dose of 35 mg 
decitabine and 100 mg cedazuridine (administered concomitantly as separate capsules or as a 
fixed-dose combination [FDC] tablet), overall results from a Phase 2 study of oral 
decitabine/cedazuridine (ASTX727-01) showed complete response (CR) rate of 18%, with 
hematologic improvement (HI) in an additional 16.3% of subjects with MDS or CMML. Among 
the 41 subjects who were dependent on red blood cell (RBC) and/or platelet transfusions at 
baseline, 20 subjects (49%) became independent of RBC and platelet transfusions during any 
consecutive 56-day post-baseline period. Of the 39 subjects who were independent of both RBC 
and platelet transfusions at baseline, 25 subjects (64%) remained transfusion independent during 
any consecutive 56-day post-baseline period. 
Results from a Phase 3, multicenter, randomized, crossover study in subjects with MDS/CMML 
or acute myeloid leukemia (AML) (ASTX727-02) established AUC equivalence of the FDC tablet 
(35 mg decitabine and 100 mg cedazuridine) with IV administered decitabine (20 mg/m2). 
Assessment of efficacy indicated that the best response of CR was observed in 21.8% of all treated 
subjects and in 24.8% of subjects evaluable for response. Marrow CR was achieved in 32.3% of 
all treated subjects and in 36.8% of subjects evaluable for response. The overall response rate 


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Oral Decitabine/Cedazuridine 
Clinical Protocol ASTX727-10 
Confidential Information 
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Amendment 1.0, 19 December 2022 
(ORR; complete response [CR] + partial response [PR] + marrow CR [mCR] + HI) was 61.7% in 
all treated subjects and 70.1% in subjects evaluable for response. In addition, mCR with HI was 
reported in 16.5% of all treated subjects and in 18.8% of subjects evaluable for response. Sixteen 
subjects (12%) were not evaluable for response. With respect to the rate of subjects who were 
transfusion independent for ≥56, ≥84, and ≥112 consecutive days at any time post-baseline for 
subjects who were transfusion dependent at baseline, more than half (51.9%) of the 54 subjects 
who were RBC transfusion dependent at baseline were RBC transfusion independent for any 
consecutive ≥56-day period post-baseline. A similar overall rate of platelet TI (50%) for any 
consecutive ≥56-day period post-baseline was observed for subjects with platelet transfusion 
dependence at baseline. Rates of RBC and platelet TI were 40.7% and 33.3%, respectively, for 
≥84 consecutive days and leveled at 33.3% for ≥112 consecutive days. The overall incidence of 
common adverse events (AEs) of thrombocytopenia, neutropenia, anemia, and febrile neutropenia 
observed in Phase 2 and Phase 3 was generally similar between oral decitabine/cedazuridine and 
IV decitabine. 
The anti CD47 monoclonal antibody (mAb) magrolimab has demonstrated encouraging data in the 
MDS population in combination with the HMA azacitidine (Vidaza®). Clinical studies have 
demonstrated that this combination has meaningful clinical activity that appears to be enhanced 
compared with azacitidine monotherapy in subjects with MDS. In a study investigating the clinical 
activity of magrolimab in combination with azacitidine in subjects with treatment-naïve 
intermediate- to higher-risk MDS (by IPSS-R), 24 subjects were evaluable for efficacy. The ORR 
was 92%, with 50% achieving a CR. Complete cytogenetic response was observed in 26% of 
subjects who had abnormal cytogenetics at baseline. Minimal residual disease negativity was 
achieved in 23% of subjects, as assessed by flow cytometry. With a median follow-up of 
6.4 months, no median duration of response (DOR) had been reached, with several subjects 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 subjects who were evaluated. Magrolimab in combination with 
azacitidine is currently being evaluated for survival and CR (co primary objectives) in a large, 
randomized Phase 3 study (ENHANCE, NCT04313881) comparing the efficacy and safety of 
magrolimab plus azacitidine with that of azacitidine + placebo (PBO) in previously untreated 
subjects with high-risk MDS. Despite its clinical benefit, treatment with azacitidine requires 
chronic parenteral treatment for 5 to 7 days each month for responding subjects; this number of 
clinic/hospital visits is a significant burden for what is primarily an elderly population. 
Furthermore, an online survey that assessed treatment challenges in subjects with MDS determined 
that IV/subcutaneous HMA administration resulted in pain and impacted daily activities, 
suggesting that an oral HMA might reduce treatment challenges for this population. 
This study will assess the safety and efficacy of combining oral decitabine/cedazuridine (oral 
HMA) with magrolimab in subjects with intermediate- to very high-risk MDS. This combination 
with an oral HMA could provide an effective treatment option for this population while 
minimizing the burden of treatment for subjects and caregivers (ie, number of required clinic visits, 
transportation time, and complications of parenteral therapy). 


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Objectives 
Endpoints 
Primary 
• 
To evaluate preliminary safety and efficacy 
of oral decitabine/cedazuridine in 
combination with magrolimab. 
• 
Adverse events graded according to NCI 
CTCAE, Version 5.0 (Section 10.5), DLTs, and 
CR rate. 
Secondary 
• 
To evaluate the PK profile of oral 
decitabine/cedazuridine and magrolimab. 
• 
Concentration versus time and PK parameters. 
• 
To evaluate other clinical efficacy of oral 
decitabine/cedazuridine and magrolimab. 
• 
ORR, rate of HI, duration of PFS, LFS, 
undetectable disease assessed by MRD, DOR, 
and OS. 
• 
To evaluate efficacy and safety by 
prespecified subgroups (eg, IPSS-M, p53 
status). 
• 
Safety and efficacy based on molecular features 
(eg, IPSS-M score, p53 status). 
CR=complete response; DLT=dose-limiting toxicity; DOR=duration of response; HI=hematologic improvement; 
IPSS-M=Molecular International Prognostic Scoring System for myelodysplastic syndromes; LFS=leukemia-free 
survival; MRD=minimal residual disease; NCI CTCAE=National Cancer Institute Common Terminology Criteria 
for Adverse Events; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; 
PK=pharmacokinetic(s) 
 
Study Design and Investigational Plan: This is a Phase 2, open-label, multicenter, 
non-randomized interventional study to evaluate the safety, efficacy, and PK of oral 
decitabine/cedazuridine when given in combination with magrolimab for the treatment of 
previously untreated intermediate- to very high-risk MDS subjects. The goal of this study is to 
assess the safety and efficacy of combining oral decitabine/cedazuridine (oral HMA) with 
magrolimab in subjects with intermediate- to very high-risk MDS. This combination with an oral 
HMA may provide a safe and efficacious alternative to azacitidine in combination with 
magrolimab, while minimizing the burden of treatment for subjects and caregivers (ie, number of 
required clinic visits, transportation time, and complications of parenteral therapy). 
Study Duration: Approximately 44 months. The study length may be adjusted based on 
enrollment rate as well as DOR. 
Number of Subjects: Approximately 135 subjects will be screened to achieve approximately 
100 evaluable subjects (ie, subjects who received one or more dose of study treatment). 
Intervention Groups and Duration: 
Participation will include screening, treatment, and follow-up. 


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• The following magrolimab dosing regimen is proposed for this study (Figure 1): The dose of 
magrolimab is increased over time in a series called priming doses. Priming doses of 
magrolimab: 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, 22, 29, 
36, 43, and 50.  
• Maintenance doses of magrolimab will be 30 mg/kg on Day 57 and every 14 days thereafter. 
If magrolimab is not administered within 28 days or more and then restarted, the resulting 
doses, called repriming doses, follow the same schedule and dose level as the first 22 days of 
the priming doses, then maintenance dosing can start 7 days later. For subjects who have not 
received at least one 30 mg/kg dose of magrolimab (ie, for subjects who have either not 
received their first dose of 30 mg/kg or subjects who have received doses <30 mg/kg), a dose 
delay of only 14 days is allowed until repriming is required. 
Oral decitabine/cedazuridine study treatment will be administered according to the following 
schedule (Figure 1): 
• Oral decitabine/cedazuridine will be administered on Days 1-5 of a cycle. In this protocol, a 
cycle is defined as a cycle of oral decitabine/cedazuridine, which is normally 28 days. 
• Days 1-5: oral decitabine/cedazuridine by mouth daily on an empty stomach (morning before 
breakfast) with no food for 2 hours before and 2 hours after administration. When taking oral 
decitabine/cedazuridine, subjects may have clear liquids such as water, black coffee, or tea. 
The dosing regimen for this study may be modified during the assessment of dose-limiting 
toxicities (DLTs) in the DLT cohort.  
Note: DLTs are defined in Section 8.5.6. 
Alternative options for oral decitabine/cedazuridine administration on Days 1-5 are outlined in 
Section 4.5. 
Systematic dosing reductions of oral decitabine/cedazuridine may be necessary, as detailed in 
Section 4.1.1 and Section 6.6.1. Dose reductions of magrolimab may be considered in rare 
circumstances, as outlined in Section 6.6.2. 
Treatment will continue until disease progression, death, or unacceptable treatment related 
toxicity, the subject withdraws or is withdrawn from the study, the treatment becomes 
commercially available, or the sponsor stops the study. 
Data Safety Review Committee and Safety Monitoring Plan: 
The Data and Safety Review Committee (DSRC) will comprise the principal investigators (or 
designees), and the Astex medical monitor, clinical pharmacologist, lead statistician, and other 
study team members as appropriate. 


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The DSRC will review emerging safety data after the first 6 subjects are enrolled. The first 6 to 
approximately 18 subjects enrolled will be evaluated for DLTs during the first 2 cycles; if present 
(following standard 3+3 design), there will be dosing reductions of oral decitabine/cedazuridine 
which will be applied to all subsequent subjects. In addition, the DSRC will continue to review 
safety data after approximately 20 subjects are enrolled and receive at least 2 cycles of treatment. 
Ad hoc meetings may occur throughout the study.  
1.2 
Schema 
Figure 1: 
Schema 
 
CR=complete response; DOR=duration of response; HI=hematologic improvement; IWG=International Working 
Group; LFS=leukemia-free survival; M=magrolimab; MRD=minimal residual disease; ORR=overall response rate; 
OS=overall survival; PFS=progression-free survival; PK=pharmacokinetic(s). 
Note: Each cycle of oral decitabine/cedazuridine will normally be 28 days. 
 
Assessment of Response by IWG 2006 
Obtain oral decitabin cedazuridine and magrolimab phannacokinetics 
Subjects continue 
until toxicity, 
progressive 
disease. 
withdrawal. or for 
other reasons 


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1.3 
Schedules of Activities (SoA) 
Table 1: 
Schedule of Activities for Oral Decitabine/Cedazuridine 
 
 
In-Clinic Visits 
 
Treatment Cycles (28 Days) 
Screeninga 
Cycle 1 
Cycle 2 
Cycle ≥3b 
Tx Discc 
30-day 
Safety 
follow-up 
(±5)d 
LTFU 
(±14)e 
Cycle Day (Window) 
1 
4 
5 
8 
(±1) 
15 
(±3) 
1 
4 
8 
(±1) 
15 
(±3) 
1 
15 
(±3) 
Study Treatmentf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Oral decitabine/cedazuridine dispensation 
 
× 
 
 
 
 
× 
 
 
 
× 
 
 
 
 
Distribute dosing diaryg 
× 
 
 
 
 
× 
 
 
 
× 
 
 
 
 
Dosing complianceg 
 
 
 
 
 
× 
 
 
 
× 
 
 
 
 
Clinical and Safety Assessments/Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical history 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum or urine pregnancy testh 
× 
× 
 
 
 
 
× 
 
 
 
× 
 
× 
× 
 
Investigator's confirmation of eligibility 
× 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
PEi 
× 
× 
 
 
 
 
 
 
 
 
 
 
× 
 
 
Symptom-directed PEj 
 
 
 
 
 
 
× 
 
 
 
× 
 
 
× 
 
Height  
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weightk 
× 
× 
 
 
 
 
× 
 
 
 
× 
 
× 
 
 
Vital Signsl 
× 
× 
 
 
 
 
× 
 
 
 
× 
 
 
 
 
ECOG performance status 
× 
× 
 
 
 
 
× 
 
 
 
× 
 
× 
× 
 
12-lead ECGm 
× 
× 
 
 
 
 
× 
 
 
 
× 
 
 
 
 
Laboratory Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect blood for PKn 
 
× 
× 
× 
 
 
 
× 
 
 
 
 
 
 
 
Hematology (CBC)o 
 
× 
× 
× 
× 
× 
× 
 
× 
× 
× 
× 
× 
 
 
Chemistriesp 
× 
× 
 
 
 
× 
× 
 
 
× 
× 
× 
× 
 
 
Urinalysis 
× 
× 
 
 
 
 
 
 
 
 
 
 
× 
 
 
Reporting concomitant medications/AEsq 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
 
Reporting transfusionsr 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 


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In-Clinic Visits 
 
Treatment Cycles (28 Days) 
Screeninga 
Cycle 1 
Cycle 2 
Cycle ≥3b 
Tx Discc 
30-day 
Safety 
follow-up 
(±5)d 
LTFU 
(±14)e 
Cycle Day (Window) 
1 
4 
5 
8 
(±1) 
15 
(±3) 
1 
4 
8 
(±1) 
15 
(±3) 
1 
15 
(±3) 
Disease Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BM aspirate/biopsy/MRDs 
× 
 
 
 
 
 
 
 
 
 
× 
 
× 
 
 
Survival follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
× 
AE=adverse event; BM=bone marrow: CBC=complete blood count; CR=complete response; DOR=duration of response; ECG=electrocardiogram; 
ECOG=Eastern Cooperative Oncology Group; LTFU=long-term follow-up; MDS=myelodysplastic syndromes; MRD=minimal residual disease; PB=peripheral 
blood; PE=physical examination; SCT=stem cell transplant; Tx Disc=treatment discontinuation. 
Note: For any given laboratory assessment or clinical/safety assessments/procedures required on a given day for both oral decitabine/cedazuridine and 
magrolimab, one such activity suffices for both drugs. 
a 
Screening: must occur within 21 days before first dose of study drug. 
b 
In Cycle ≥3, pregnancy testing on Day 1 of each cycle (or within a 3-day window prior).  
c 
Treatment Discontinuation: Treatment discontinuation refers to the discontinuation of both oral decitabine/cedazuridine and magrolimab. The treatment 
discontinuation visit should occur within 1 week after the last study treatment or within 3 days before starting a new treatment for MDS/leukemia. If a 
subject discontinues study treatment at a scheduled visit, the assessments at that visit can be used to fulfill the visit requirements. If the subject cannot attend 
the clinic, the visit may be conducted by telephone to collect, at minimum, AE information.  
d 
30-day Safety Follow-up Visit: Safety follow-up visit may occur at the same time as treatment discontinuation if the decision to permanently discontinue 
treatment is made at least 30 days after last dose of study treatment or within 3 days before starting a new anticancer therapy. 
e 
Long-term Follow-up (LTFU) visits: Beginning 3 months after the 30-day Safety Follow-up visit (for subjects who permanently discontinued treatment), 
subjects will be followed in LTFU for health status information, which will be gathered every 3 months (±2 weeks) until death, the subject withdraws 
consent, the subject is lost to follow-up, or the study ends, whichever occurs first. Additionally, disease response assessments, including conversion to acute 
myeloid leukemia (transfusion, hematology, and/or BM aspirate/biopsy) are done only for subjects who discontinued treatment before documented disease 
progression, until peripheral blood or BM assessment shows disease progression or relapse, or the subject starts new anti-leukemia/MDS treatment. Visits 
may be conducted by telephone if appropriate. Women of childbearing potential will be reminded that they should not get pregnant for 250 days after 
discontinuation of study medication and will be asked if they are pregnant during the LTFU either in person or by telephone. Male subjects should be 
reminded to continue contraception for a minimum of 160 days after treatment discontinuation. 
f 
Study treatment: When both study drugs are given on the same visit day, magrolimab will be administered at least 1 hour after oral decitabine/cedazuridine 
administration.  
g 
Distribute dosing diary and dosing compliance: only for oral decitabine/cedazuridine. 
h 
A highly sensitive serum pregnancy test (from whole blood) is required at screening; serum or urine testing may be used at subsequent time points, as 
required by local regulations. 
i 
Physical examination (PE): Complete PE will be performed at screening, predose on Cycle 1 Day 1, and at treatment discontinuation.  
j 
Symptom-directed PE is not required if it is performed within 3 days of Day 1. After Cycle 1 Day 1, symptom-directed PE will be done, unless otherwise 
indicated, at the investigator's discretion.  


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k 
Weight: Weight should be measured at screening, each visit in which oral decitabine/cedazuridine and/or magrolimab is administered, and at treatment 
discontinuation. 
l 
Vital signs: On dosing days, all vital signs will be measured predose per the institutional standard practice. In addition to the vital signs measured predose on 
Cycle 1 Day 1, systolic and diastolic blood pressure and heart rate will also be obtained 2 hours (±30 minutes) postdose on Cycle 1 Day 1. Vital signs are 
resting systolic/diastolic blood pressure, resting respiration rate, resting heart rate, oxygen saturation, and body temperature.  
m 
Twelve-lead ECG: Assessments on dosing days will be obtained predose. Postdose ECGs will also be obtained during PK assessment per Section 8.4. 
n 
Collect blood for PK (oral decitabine/cedazuridine): Central laboratory assessment. Predose assessments will be obtained at Cycle 1 Day 4, Cycle 1 Day 5, 
and Cycle 2 Day 4. The blood collection on Cycle 1 Day 5 must be within 24 ± 1 hour after the blood collection on Cycle 1 Day 4. Postdose assessments 
will be obtained at Cycle 1 Day 1, Cycle 1 Day 4, Cycle 2 Day 4, and ad-hoc throughout the study (if needed). Further details are provided in Table 14. 
o 
CBC: Local laboratory assessment. Day 1 CBC does not need to be drawn if drawn 1 day prior, Day 15 CBC does not need to be drawn if drawn within 
3 days prior. If there is Grade >3 neutropenia or thrombocytopenia present, consider weekly CBCs. 
p 
Chemistries: Perform only if not obtained within the previous 7 days. 
q 
Reporting of concomitant medications starts from 14 days before treatment and ends 30 days after the last dose of study treatment. Reporting of AEs starts at 
the signing of the informed consent form and ends 30 days after the last dose of study treatment. 
r 
Recording transfusions: Record all blood and platelet transfusions from 56 days before the start of study treatment through 30 days after the last dose of 
study treatment and in long-term follow up for subjects who discontinue treatment before documented disease progression until disease progression is 
documented. 
s 
BM aspirate/biopsy: Screening BM will be accepted up to 6 weeks prior to first dose; however, cytogenetics is required. If a subject undergoes SCT, they 
will continue to be followed using BM aspirate/biopsy per SOC for SCT. Cytogenetic data will be collected from the BM aspirate/biopsy sample each time a 
BM aspirate/biopsy is performed. Postdosing BM is to be performed on Day 1 (or within a 3-day window prior to Day 1) of Cycles 3, 5, and 7, and every 
3 cycles thereafter (or within a 7-day window), as well as at the end of treatment or at disease progression, whichever is earlier. If the investigator suspects 
that the development of Grade 4 neutropenia or thrombocytopenia is drug related and the event continues for 7 days in Cycle 1 or 2, a BM assessment (no 
later than the 10th day of Grade 4 cytopenia) may be done, at the discretion of the investigator, to assist with determination of DLT. If hematologic recovery 
is in progress, a repeat CBC may be done no more than 7 days after the BM evaluation for response assessment. BM evaluation may occur as clinically 
indicated to monitor DOR as appropriately guided by PB counts after achieving a confirmed CR but should occur at least every 3 cycles for the first year, 
then as clinically indicated at additional time points. MRD will be obtained per local standard of care. 
 


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Table 2: 
Schedule of Activities for Magrolimab 
 
In-Clinic Visits 
Day 
(Window) Screening 
1 
2 
3 
4 
(±3) 
5 
(±3) 
8  
(±3) 
11 
(±3) 
15 
(±3) 
22 
(±3) 
29 
(±3) 
36 
(±3) 
43 
(±3) 
50 
(±3) 
57 
(±3) 
Every 14 days 
thereafter 
(±3) 
Study Treatmenta 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Magrolimab infusionb 
 
× 
 
 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Laboratory Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood type and screen (ABO, Rh) DAT, and 
extended RBC phenotyping or genotypingc 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology (CBC)c,d 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Coagulationc 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistryc 
× 
× 
 
 
 
 
× 
 
× 
 
× 
 
× 
 
× 
× 
Urinalysisc 
× 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect blood for PK and ADAe 
 
× 
 
 
 
 
 
 
 
 
 
 
 
× 
× 
 
Collect blood for molecular analysisf 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical and Safety Assessments/Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signsg  
× 
× 
 
 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Weighth 
× 
× 
 
 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Reporting concomitant medications/AEsi 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Reporting transfusionsj 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Premedicationk 
 
× 
 
 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Compete PE and Symptom-directed PEl 
× 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ABO=any of the 4 blood groups (A, B, AB, and O); ADA=antidrug antibody; AE=adverse event; CBC=complete blood count; eCRF=electronic case report 
form; MDS=myelodysplastic syndromes; PK=pharmacokinetic(s); Rh=Rhesus factor; Tx Disc=treatment discontinuation. 
Note: For any given laboratory assessment or clinical/safety assessments/procedures required on a given day for both oral decitabine/cedazuridine and 
magrolimab, one such activity suffices for both drugs. 
a 
Study treatment: When both study drugs are given on the same visit day, magrolimab will be administered at least 1 hour after oral decitabine/cedazuridine 
administration. Subjects 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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b 
Magrolimab infusion: If magrolimab is not administered for 28 days or more and restarted, the resulting doses, called repriming doses, follow the same 
schedule and dose level as the first 22 days of the priming doses, then maintenance dosing can start 7 days later. For subjects who have not received at least 
one 30 mg/kg dose of magrolimab, a dose delay of only 14 days is allowed until repriming is required. During the first 2 doses of priming and repriming, 
blood testing of hemoglobin will be required 3 to 6 hours after a magrolimab dose, and the results must be reviewed prior to discharging the subject from 
clinic. The duration of each magrolimab infusion including flush will be 3 hours (±30 minutes) for the first 3 doses of treatment. After the third dose of 
treatment, the magrolimab infusion including flush will be 2 hours (±30 minutes). 
c 
Lab assessment done at a local laboratory. 
d 
No safety window will be permitted for assessments made for the first 2 doses of magrolimab (priming or repriming), otherwise CBC does not need to be 
drawn if done one day prior. CBC for Days 4 and 5 must be on consecutive days.  
e 
Collect blood for PK and ADA (magrolimab): Assessment done at a central lab, and will take place predose at all time points shown, plus on Day 141 and at 
the end of treatment. A sample at the end of infusion for PK only will be collected on Day 57 only. No safety window will be permitted for assessments 
made on the day of the first magrolimab dose (priming or repriming). A time window of ±3 day will be permitted for subsequent assessments starting on 
Day 8 (or Day 8 of repriming).  
f 
Collect peripheral blood to be sent to central lab for molecular analysis. 
g 
Vital signs: Vital signs will be measured with each magrolimab dosing. Vital signs to be measured are heart rate, respiratory rate, oxygen saturation, blood 
pressure, and temperature. Height is recorded only at screening. Vital signs are to be recorded prior to the infusion of magrolimab. All subjects should be 
monitored hourly during infusion and for 1 hour after infusion for doses during the first 28 days and the repriming doses 
h 
Weight: Weight should be measured at screening, each visit in which oral decitabine/cedazuridine and/or magrolimab is administered, and at treatment 
discontinuation. 
i 
Concomitant medications/AE: Concomitant medication can be used throughout study. Concomitant medications/AEs should be reported on the eCRF and 
reviewed at each visit. Reporting of concomitant medications starts from 14 days before treatment and ends 30 days after the last dose of study treatment. 
Reporting of AEs starts at the signing of the informed consent form and ends 30 days after the last dose of study treatment. 
j 
Recording transfusions: Record all blood and platelet transfusions from 56 days before the start of study treatment through 30 days after the last study 
treatment and in long-term follow-up for subjects who discontinue treatment before documented disease progression until disease progression is 
documented. 
k 
Premedication is required prior to the administration of magrolimab through the Day 22 infusion of priming or repriming. Premedications may be continued 
based on the treating physician’s clinical judgment and the presence/severity of prior infusion-related reactions. 
l 
Compete PE at screening and treatment discontinuation; symptom-directed PE at the discretion of the investigator.   
 


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Table 3: 
Dosing Schedule for Oral Decitabine/Cedazuridine 
Day for Dosing Oral Decitabine/Cedazuridine 
1 
2 
3 
4 
5 
6-28 
× 
× 
× 
× 
× 
— 
DLT=dose-limiting toxicity; FDC=fixed-dose combination; "×"= dosing day; "—"= non-dosing day. 
Note: Oral decitabine/cedazuridine will be administered as a single agent or in combination with magrolimab and will follow the same dosing schedule for each 
cycle. Each dose of oral decitabine/cedazuridine is an FDC tablet (35 mg decitabine/100 mg cedazuridine) administered on Days 1-5 of each 28-day cycle. The 
dosing schedule may be altered if DLTs are observed in the DLT cohort; see Section 4.1.1 for further information. 
Table 4: 
Dosing Schedule for Magrolimab 
Day for Dosing Magrolimab During Priming, Maintenance, and Repriming 
Priming Days 1-28a 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13-14 
15 
16 
17 
18 
19 
20 
21 
22 
23-28 
× 
— 
— 
× 
— 
— 
— 
× 
— 
— 
× 
— 
— 
× 
— 
— 
— 
— 
— 
— 
× 
— 
Priming Days 29-56b 
29 
30 
31 
32 
33 
34 
35 
36 
37 
38 
39 
40 
41-42 
43 
44 
45 
46 
47 
48 
49 
50 
51-56 
× 
— 
— 
— 
— 
— 
— 
× 
— 
— 
— 
— 
— 
× 
— 
— 
— 
— 
— 
— 
× 
— 
Maintenance Days 57-84c 
57 
58 
59 
60 
61 
62 
63 
64 
65 
66 
67 
68 
69-70 
71 
72 
73 
74 
75 
76 
77 
78 
79-84 
× 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
— 
× 
— 
— 
— 
— 
— 
— 
— 
— 
Repriming Days 1-28d 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13-14 
15 
16 
17 
18 
19 
20 
21 
22 
23-28 
× 
— 
— 
× 
— 
— 
— 
× 
— 
— 
× 
— 
— 
× 
— 
— 
— 
— 
— 
— 
× 
— 
CBC=complete blood count; DLT=dose-limiting toxicity; FDC=fixed-dose combination; Hgb=hemoglobin; "×"= dosing day; "—"= non-dosing day. 
Note: The dosing schedule may be altered if DLTs are observed in the DLT cohort; see Section 4.1.1 for further information. Magrolimab should not be given on 
consecutive days. 


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a 
Priming doses of magrolimab: 1 mg/kg on Days 1 and 4; 15 mg/kg Day 8; 30 mg/kg Days 11, 15, and 22. All subjects should be monitored for 1 hour after 
infusion for doses during the first 28 days. Within 24 hours prior to each of the first 2 priming doses of magrolimab, all subjects must have a documented 
Hgb ≥9 g/dL. Subjects who do not meet these criteria must be transfused and have their Hgb rechecked to meet the minimum Hgb threshold prior to each of 
the first 2 doses of magrolimab. During the first 2 doses of priming, blood testing of Hgb will be required 3 to 6 hours after a magrolimab dose and the 
results must be reviewed prior to discharging the subject from the clinic. The subject should be transfused as clinically appropriate. Investigators should 
consider additional Hgb monitoring during the first week of treatment in subjects with symptoms of anemia or increased risk for complications of anemia.   
b 
Dosing of magrolimab: 30 mg/kg on Days 29, 36, 43, and 50. 
c 
Maintenance days are the days on which the magrolimab dose remains the same from dose to dose. Dosing of magrolimab: 30 mg/kg on Days 57 and 71. 
Maintenance dosing beyond Day 71 should repeatedly use the dose schedule of Days 57-84. Maintenance days can continue repeatedly after Day 84 
following the same interval of dosing as seen in Maintenance Days 57-84. 
d 
If magrolimab is not administered for 28 days or more and then restarted, the resulting doses, called repriming doses, follow the same schedule and dose 
level as the first 22 days of the priming doses, then maintenance dosing can start 7 days later. For subjects who have not received at least one 30 mg/kg dose 
of magrolimab, a dose delay of only 14 days is allowed until repriming is required. Within 24 hours prior to each of the repriming doses of magrolimab, all 
subjects must have a documented Hgb ≥9 g/dL. Subjects who do not meet these criteria must be transfused and have their Hgb rechecked to meet the 
minimum Hgb threshold prior to each of the first 2 doses of magrolimab. During the first 2 doses of repriming, blood testing of Hgb will be required 3 to 
6 hours after a magrolimab dose and the results must be reviewed prior to discharging the subject from clinic. 
A CBC is needed before each dose during the repriming cycle. Within 24 hours prior to each of the first 2 repriming doses of magrolimab, all subjects must 
have a documented Hgb ≥9 g/dL. Subjects who do not meet these criteria must be transfused and have their Hgb rechecked to meet the minimum Hgb 
threshold prior to each of the first 2 repriming doses of magrolimab. Magrolimab should be infused over 3 hours (±30 minutes) following the repriming dose 
schedule (1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; and 30 mg/kg on Days 11, 15, 22.). Days are adjusted depending on when repriming occurs. During 
the first 2 doses of repriming, blood testing of Hgb will be required 3 to 6 hours after a magrolimab dose and the results must be reviewed prior to 
discharging the subject from the clinic. The subject should be transfused as clinically appropriate. Vital signs, weight, reporting of concomitant 
medications/transfusions/AEs, premedications, chemistries, and urinalysis follow the same schedule as given for priming in Table 2. 
 


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2.0 
INTRODUCTION 
2.1 
Background 
Myelodysplastic syndromes (MDS) are premalignant clonal hematopoietic disorders characterized 
by bone marrow (BM) failure due to the production of dysfunctional, dysplastic BM cells. 
Primarily, these disorders affect individuals ≥60 years of age (Ma 2012). Low- and very low- risk 
subjects, as defined by the Revised International Prognostic Scoring System for myelodysplastic 
syndromes (IPSS-R; Greenberg et al 2012), are often treated with erythroid and myeloid growth 
factor support and carry a low risk of leukemic progression. In contrast, intermediate- to high-risk 
subjects with MDS have up to a 25% chance of leukemic transformation (NCCN 2022).  
Intermediate- to high-risk subjects with MDS and are generally treated with hypomethylating 
agents (HMAs). The HMAs azacitidine (Vidaza®) and decitabine (DACOGEN®) are given as 
standard of care (SOC) for newly diagnosed MDS subjects with specific high-risk subtypes, and 
the approved schedules comprise consecutive daily dosing for 5 or 7 days in 28-day cycles. 
Treatment, which may continue for several months or even years, may engender significant 
hardship due to the 5 to 7 daily visits required each month, and the 1-hour intravenous (IV) infusion 
or large-volume subcutaneous injections. A possible consequence is noncompliance or premature 
discontinuation. In addition, the overall response rate (ORR; complete response [CR] + partial 
response [PR]) is approximately 16%, and overall survival (OS) is approximately 18 months 
(Silverman et al 2002). Thus, novel therapies that replace or augment the efficacy of HMAs or that 
can be formulated as a more convenient oral administration are needed to improve outcomes and 
extend survival for subjects with MDS. 
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 et al 2011). Increased CD47 expression was identified first on leukemic stem 
cells in human acute myeloid leukemia (AML) (Majeti et al 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. The 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. CD47-blocking monoclonal antibodies (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 et al 2010). 
Astex Pharmaceuticals, Inc. (Astex) has developed oral decitabine/cedazuridine, composed of the 
HMA decitabine in combination with cedazuridine. Cedazuridine (Ferraris et al 2014) is a new 
potent cytidine deaminase inhibitor that is pharmaceutically stable. Concomitant administration of 
oral decitabine with cedazuridine has been shown to markedly enhance the bioavailability of 
decitabine in nonclinical animal models (monkeys; Ricerca 031253). In addition, the safety profile 
of oral decitabine/cedazuridine has been evaluated in multiple clinical trials with MDS subjects 
and has been shown to be similar to the established safety profile of IV decitabine (current 


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DACOGEN® US prescribing information) supporting the approval of oral decitabine/cedazuridine 
in patients with MDS/chronic myelomonocytic leukemia (CMML) in the US, Canada, and 
Australia. 
The anti-CD47 mAb magrolimab is a first in class oral investigational anticancer therapeutic agent 
targeting the CD47-SIRPα axis. The activity of magrolimab is primarily dependent on blocking 
CD47 binding to SIRPα and not on the recruitment of fragment crystallizable (Fc)-dependent 
effector functions, although the presence of the immunoglobulin 4 Fc domain is required for its 
full activity. For this reason, magrolimab was engineered with a human immunoglobulin 4 isotype 
that is relatively inefficient at recruiting Fc-dependent effector functions that might enhance toxic 
effects on normal CD47-expressing cells (Liu et al 2015). Binding of magrolimab to human CD47 
on-target malignant cells blocks the “don’t eat me” signal to macrophages and enhances tumor cell 
phagocytosis. In addition, magrolimab has the potential to elicit an antitumor T-cell response. 
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). This 
represents a novel strategy for the treatment of cancer. Magrolimab has demonstrated encouraging 
safety and efficacy in the treatment of previously untreated subjects with intermediate- to very 
high-risk MDS when used in combination with parenteral azacitidine, an HMA (Sallman et al 
2022). 
2.2 
Study Rationale 
The current study will aim to evaluate oral decitabine/cedazuridine in combination with 
magrolimab for previously untreated subjects with intermediate- to very high-risk MDS, as 
determined by IPSS-R.  
Oral decitabine/cedazuridine is an HMA that is approved for use in subjects with intermediate- to 
high-risk MDS, as well as in subjects with CMML, in the US, Canada, and Australia. Oral 
decitabine/cedazuridine was approved based on clinical studies that determined its 
pharmacokinetic (PK) area under the concentration-time curve (AUC) equivalence to 
IV decitabine administration. Results from Phase 2 and 3 studies have demonstrated a positive 
treatment effect of oral decitabine/cedazuridine and that the clinical efficacy of oral 
decitabine/cedazuridine is consistent with efficacy described for intravenously administered 
decitabine in subjects with MDS; further details on the clinical development of oral 
decitabine/cedazuridine can be found in the Investigator Brochure (IB). At the therapeutic dose of 
35 mg decitabine and 100 mg cedazuridine (administered concomitantly as separate capsules or as 
a fixed-dose combination [FDC] tablet), overall results from a Phase 2 study of oral 
decitabine/cedazuridine (ASTX727-01) showed a CR rate of 18%, with hematologic improvement 
(HI) in an additional 16.3% of subjects with MDS or CMML. Among the 41 subjects who were 
dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 20 subjects (49%) 
became independent of RBC and platelet transfusions during any consecutive 56-day post-baseline 
period. Of the 39 subjects who were independent of both RBC and platelet transfusions at baseline, 


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25 subjects (64%) remained transfusion-independent during any consecutive 56-day post-baseline 
period.  
Results from a Phase 3, multicenter, randomized, crossover study in subjects with MDS/CMML 
or AML (ASTX727-02) established AUC equivalence of the FDC tablet (35 mg decitabine and 
100 mg cedazuridine) with IV administered decitabine (20 mg/m2). Assessment of efficacy 
indicated that the best response of CR was observed in 21.8% of all treated subjects and in 24.8% 
of subjects evaluable for response. Marrow CR was achieved in 32.3% of all treated subjects and 
in 36.8% of subjects evaluable for response. The ORR (CR + PR + mCR + HI) was 61.7% in all 
treated subjects and 70.1% in subjects evaluable for response. In addition, mCR with HI was 
reported in 16.5% of all treated subjects and in 18.8% of subjects evaluable for response. Sixteen 
subjects (12%) were not evaluable for response. With respect to the rate of subjects who were 
transfusion independent for ≥56, ≥84, and ≥112 consecutive days at any time post-baseline for 
subjects who were transfusion dependent at baseline, more than half (51.9%) of the 54 subjects 
who were RBC transfusion dependent at baseline were RBC transfusion independent for any 
consecutive ≥56-day period post-baseline. A similar overall rate of platelet TI (50%) for any 
consecutive ≥56-day period post-baseline was observed for subjects with platelet transfusion 
dependence at baseline. Rates of RBC and platelet TI were 40.7% and 33.3%, respectively, for 
≥84 consecutive days and leveled at 33.3% for ≥112 consecutive days. The overall incidence of 
common adverse events (AEs) of thrombocytopenia, neutropenia, anemia, and febrile neutropenia 
observed in Phase 2 and Phase 3 was generally similar between oral decitabine/cedazuridine and 
IV decitabine. Further details can be found in the oral decitabine/cedazuridine IB. 
The anti-CD47 mAb magrolimab has demonstrated encouraging data in the MDS population in 
combination with the HMA azacitidine (Vidaza®). Clinical studies have demonstrated that this 
combination has meaningful clinical activity that appears to be enhanced compared with 
azacitidine monotherapy in subjects with MDS. In a study investigating the clinical activity of 
magrolimab in combination with azacitidine in subjects with treatment-naïve intermediate- to 
higher-risk MDS (by IPSS-R) (Study 5F9005; Sallman et al 2019), 24 subjects were evaluable for 
efficacy. The ORR was 92%, with 50% achieving a CR. Complete cytogenetic response was 
observed in 26% of subjects who had abnormal cytogenetics at baseline. Minimal residual disease 
(MRD) negativity was achieved in 23% of subjects, as assessed by flow cytometry. With a median 
follow-up of 6.4 months, no median duration of response (DOR) had been reached, with several 
subjects 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 subjects who were evaluated. Magrolimab in combination with 
azacitidine is currently being evaluated for survival and CR (co-primary objectives) in a large, 
randomized Phase 3 study (ENHANCE, NCT04313881) comparing the efficacy and safety of 
magrolimab plus azacitidine with that of azacitidine plus placebo (PBO) in previously untreated 
subjects with high-risk MDS; further details can be found in the magrolimab IB. Despite its clinical 
benefit, treatment with azacitidine requires chronic parenteral treatment for 5 to 7 days each month 
for responding subjects; this number of clinic/hospital visits is a significant burden for what is 
primarily an elderly population. Furthermore, an online survey that assessed treatment challenges 


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in subjects with MDS determined that IV/subcutaneous HMA administration resulted in pain and 
impacted daily activities, suggesting that an oral HMA might reduce treatment challenges for this 
population (Zeidan et al 2022). 
This study will assess the safety and efficacy of combining oral decitabine/cedazuridine (oral 
HMA) with magrolimab in subjects with intermediate- to very high-risk MDS. This combination 
with an oral HMA may provide a safe and efficacious alternative to azacitidine in combination 
with magrolimab, while minimizing the burden of treatment for subjects and caregivers (ie, 
number of required clinic visits, transportation time, and complications of parenteral therapy). 
2.3 
Benefit/Risk Assessment 
2.3.1 
Oral Decitabine/Cedazuridine 
It is difficult to separate risks associated with oral decitabine/cedazuridine from those of MDS 
itself, as the AEs that occur with MDS are similar to those that occur with oral 
decitabine/cedazuridine. The safety of oral decitabine/cedazuridine mimics the safety of 
decitabine, which is mainly the risk of myelosuppression and its consequences (pneumonia, sepsis, 
or hemorrhage) with potential gastrointestinal (GI) effects due to oral administration. All safety 
issues that have been identified with oral decitabine/cedazuridine to date are consistent with the 
safety profile of IV decitabine at oral doses/cycle of up to 200 mg decitabine and 500 mg of 
cedazuridine. Blood levels of decitabine (at 35 mg decitabine and 100 mg cedazuridine and) in 
study ASTX727-01 have been shown to be similar to levels seen after 1-hour IV infusion with 
20 mg/m2 
decitabine. 
For 
more 
detailed 
information, 
please 
refer 
to 
the 
oral 
decitabine/cedazuridine IB. 
In addition, most cancer subjects prefer oral to injectable drug formulations (Liu et al 1997); 
benefits of an oral HMA (oral decitabine/cedazuridine) include alleviating the inconvenience of 
potential long-duration parenteral therapy as well as minimizing the hardship involved with the 
frequent hospital/clinic visits associated with a drug that must be administered intravenously. This 
is of particular importance considering the prevalence of this disease in the elderly and the need 
for continued monthly treatment potentially for years, particularly for those subjects who respond 
to treatment and benefit the most. An oral drug may also improve compliance with 5 days/month 
treatment. 
2.3.2 
Magrolimab 
As of 24 July 2021, over 700 participants have been treated with magrolimab monotherapy or 
magrolimab in combination with other agents. Overall, nonclinical and clinical data to date on 
magrolimab in combination with azacitidine show evidence of efficacy in untreated higher-risk 
MDS and also demonstrate the acceptable safety profile of the combination therapy in this patient 
population, with no maximum tolerated dose (MTD) reached and a treatment discontinuation rate 
due to AEs of 1.6%. No significant exacerbation of azacitidine related AEs by magrolimab has 
been observed, as evidenced by the minimally observed myelosuppression from the combination. 
Therefore, based on the available safety data, magrolimab has an acceptable safety profile both as 


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a monotherapy and a combination therapy across multiple hematologic and advanced solid tumor 
malignancies; the clinical study findings are consistent with nonclinical toxicology studies and 
there are no additional expected risks expected in the present study. In addition, while magrolimab 
requires frequent IV dosing in the first 56 days of treatment, subsequent administration is every 14 
days Combining this with an oral HMA (decitabine/cedazuridine) will significantly reduce overall 
requirement for subjects to attend in-person clinic visits. 
3.0 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• 
To evaluate preliminary safety and efficacy 
of oral decitabine/cedazuridine in 
combination with magrolimab. 
• 
Adverse events graded according to NCI 
CTCAE, Version 5.0 (Section 10.5), DLTs, and 
CR rate. 
Secondary 
• 
To evaluate the PK profile of oral 
decitabine/cedazuridine and magrolimab. 
• 
Concentration versus time and PK parameters. 
• 
To evaluate other clinical efficacy of oral 
decitabine/cedazuridine and magrolimab. 
• 
ORR, rate of HI, duration of PFS, LFS, 
undetectable disease assessed by MRD, DOR, 
and OS. 
• 
To evaluate efficacy and safety by 
prespecified subgroups (eg, IPSS-M, p53 
status). 
• 
Safety and efficacy based on molecular features 
(eg, IPSS-M score, p53 status). 
CR=complete response; DLT=dose-limiting toxicity; DOR=duration of response; HI=hematologic improvement; 
IPSS-M=Molecular International Prognostic Scoring System for myelodysplastic syndromes; LFS=leukemia-free 
survival; MRD=minimal residual disease; NCI CTCAE=National Cancer Institute Common Terminology Criteria 
for Adverse Events; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; 
PK=pharmacokinetic(s) 
 
4.0 
STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 2, open-label, multicenter, non-randomized interventional study to evaluate the 
safety, efficacy, and PK of oral decitabine/cedazuridine when given in combination with 
magrolimab for the treatment of subjects with previously untreated intermediate- to very high-risk 
MDS. Subjects with higher-risk MDS (IPSS-R ≥3.5) will be screened for participation with the 
goal of obtaining approximately 100 subjects who are evaluable, those subjects receiving one or 
more dose of study treatment, for the primary study endpoint. The first 6 to approximately 
18 subjects enrolled will be evaluated for dose-limiting toxicities (DLTs) during the first 2 cycles 
of oral decitabine/cedazuridine and will be used to confirm the dosing for oral 
decitabine/cedazuridine in combination with magrolimab. In this protocol, a cycle is defined as a 


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cycle of oral decitabine/cedazuridine, which is normally 28 days. Dose-limiting toxicities are 
defined in Section 8.5.6.  
The primary analysis of the CR rate will be conducted approximately 8 months after enrollment 
of approximately 100 subjects has occurred. Participation will include screening, treatment, and 
follow-up. The screening period will last up to 21 days before the first dose of study treatment, 
during which time the participant’s eligibility and baseline characteristics will be determined. 
Subjects will receive study treatment per the dosing schedule in Table 3 and Table 4. Study 
treatment may be continued until disease progression (including treatment failure by the 
International Working Group [IWG] 2006 criteria or relapse after PR/CR), or unacceptable 
toxicities occur, the subject is withdrawn from study treatment, or the sponsor stops the study. In 
case subjects choose to discontinue the study treatment due to reasons other than disease 
progression, eg, voluntary withdrawal, subjects will be followed up for response assessments until 
documented disease progression occurs. For subjects who stop receiving the study treatment to 
receive a stem cell transplant (SCT), follow-up for response assessment and collection of SOC BM 
biopsy/aspirate results will continue until documented disease progression occurs or start of new 
anticancer therapy, whichever occurs first. Then subjects will be observed for survival until death, 
withdrawal of consent, or the end of the study, whichever occurs first. 
The study duration will be approximately 44 months. This may be adjusted based on enrollment 
rate as well as DOR. 
The Schedules of Activities (SoAs) are detailed in Table 1 and Table 2. 
The COVID-19 pandemic may continue to affect the way clinical studies need to be conducted 
such that alternative measures may need to be implemented to ensure the safety of subjects and 
maintain the integrity of clinical trial data. Section 10.7 details information regarding potential 
modifications to the conduct of the study in the event of a COVID-19 health emergency. 
4.1.1 
Dose-Limiting Toxicity Cohort 
The first 6 to approximately 18 subjects enrolled, the DLT cohort, will be evaluated to confirm 
that the dosing of oral decitabine/cedazuridine in combination with magrolimab is well tolerated 
(Section 8.5.6). Due to the low incidence of magrolimab DLTs (please reference Investigational 
New Drug [IND] 147229 for the magrolimab Investigator Brochure), it is expected that most DLTs 
will be related to oral decitabine/cedazuridine, especially those related to neutropenia, 
thrombocytopenia, GI toxicity, and infection. Thus, a DLT should generally be considered related 
to oral decitabine/cedazuridine unless the investigator feels that a DLT is related to magrolimab. 
The DLT period will last the first 2 cycles of oral decitabine/cedazuridine treatment as defined in 
Section 4.1. Evaluation of the cohort will end when a tolerated dosing is identified, or the study is 
stopped due to toxicity. Oral decitabine/cedazuridine and magrolimab dosing will initiate as 
outlined in Section 4.5. If there are DLTs associated with magrolimab that occur in the DLT 
cohort, the investigator in consultation with the Astex medical monitor and the Data and Safety 


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Review Committee (DSRC) will determine if a dose modification of magrolimab is appropriate 
(see Section 6.6.2 for magrolimab dose modification recommendations).  
The dosing reduction process for oral decitabine/cedazuridine-associated DLTs will follow a 3+3 
design (Figure 2), as follows: 
• The first 6 subjects will be evaluated for myelosuppression and other DLTs (Section 8.5.6). 
• If fewer than 2 subjects among the first 6 (<33%) experience a DLT (Section 8.5.6), the current 
dosing level will be maintained, and no further DLT cohort evaluation will be conducted. 
• If a DLT occurs in 2 or more of the initial 6 subjects, then oral decitabine/cedazuridine dosing 
will be reduced 1 level (Table 9) and 3 more subjects will be enrolled at that dosing level. 
• If no additional DLTs occur, the dosing will be maintained, and no further DLT cohort 
evaluation will be conducted. If any DLT occurs, another 3 subjects will be enrolled. If fewer 
than 2 subjects (<33%) have a DLT out of the 6 subjects, then the dosing will be maintained, 
and no further DLT cohort evaluation will be conducted. If oral decitabine/cedazuridine 
associated DLTs occur in 2 or more out of 6 subjects, dosing of oral decitabine/cedazuridine 
will be reduced one dose level as per Table 9, and 3 more subjects will be enrolled. 
• This process is repeated until a tolerated oral decitabine/cedazuridine dosing is identified and 
the dosing will be maintained with no further DLT cohort evaluation OR the dosing levels falls 
to Level 5 (Table 9) and in consultation with the DSRC, the study will be closed or the protocol 
amended to modify the dosing of oral decitabine/cedazuridine. 
• During the study, a stopping rule for observation of excess toxicity will be implemented, as 
described in Section 9.5.  


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Figure 2: 
Dosing Reduction Process for Oral Decitabine/Cedazuridine-
Associated Dose-Limiting Toxicities 
 
DLT=dose-limiting toxicity 
 
4.2 
Scientific Rationale for Study Design 
Oral decitabine/cedazuridine has been developed by Astex and is an HMA approved for use in 
subjects with intermediate to high-risk MDS, as well as in subjects with CMML. As discussed in 
Section 2.2, results from Phase 2 and 3 studies have demonstrated a positive treatment effect of 
oral decitabine/cedazuridine. This is a Phase 2, open-label, multicenter, non-randomized 
interventional study with no active comparator or control. The goal of this study is to assess the 
safety and efficacy of combining oral decitabine/cedazuridine with magrolimab in subjects with 
intermediate- to very high-risk MDS. This combination with an oral HMA may provide a safe and 
efficacious alternative to azacitidine in combination with magrolimab for this population while 
minimizing the burden of treatment for subjects and caregivers (ie, number of required clinic visits, 
transportation time, and complications of parenteral therapy). 
Complete response was the efficacy endpoint in several Phase 1 studies with magrolimab and it is 
the co-primary endpoint in two Phase 3 studies (ENHANCE [ClinicalTrials.gov Identifier: 
NCT04313881] and VERONA [ClinicalTrials.gov Identifier: NCT04401748]); therefore, 
measurement of CR will form part of the primary endpoint in the proposed study (alongside 
measurement of AEs and DLTs). Other efficacy endpoints, including ORR (including CR, mCR, 
I 
Enter 6 subjects at Level 1 dose 
I 
I 
I 
0-1 subjects with 
~2 subjects with DLT 
I~ 
1:: 
DLT 
l 
l 
I 
Reduce dose by a level 
I 
I 
I 
Maintain dose 
l 
l 
Enroll 3 more 
If 1 DLT, enroll 3 
DLT evaluation 
subjects 
-
more subjects 
period closed 
l 
No additional DLTs 
l 
DLT evaluation 
period closed 


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and any HI), rate of HI, duration of progression-free survival (PFS), leukemia-free survival (LFS), 
undetectable disease assessed by minimal residual disease (MRD), DOR, and OS will also be 
evaluated to better characterize the clinical efficacy of oral decitabine/cedazuridine in combination 
with magrolimab.  
4.3 
Data and Safety Review Committee  
The DSRC will comprise the principal investigators (or designees), and the Astex medical monitor, 
clinical pharmacologist, and lead statistician, and other study team members as appropriate. 
The DSRC will review emerging safety data after the first 6 subjects are enrolled. The first 6 to 
approximately 18 subjects enrolled will be evaluated for DLTs during the first 2 cycles; if present 
(following standard 3+3 design), there will be dosing reductions of oral decitabine/cedazuridine 
which will be applied to all subsequent subjects.  
Further details of the DLT cohort are provided in Section 4.1.1. 
4.4 
Recruitment 
Approximately 58 sites in North America, Europe, and Asia Pacific will be included in this study. 
Approximately 135 subjects will be screened to achieve 100 evaluable subjects. 
All subjects must be provided with an informed consent form (ICF) describing the study with 
sufficient information for subjects to make an informed decision regarding their participation. 
Subjects 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 
timeframe. 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 subjects sign the ICF, they will enter the screening period for the study and receive a unique 
subject identification number before any study procedures are performed. This number will be 
used to identify the subject throughout the clinical study and must be used on all study 
documentation related to that subject, including if a subject is rescreened. 
Screening assessments do not need to be repeated if they were previously performed during 
screening and were within 21 days of Cycle 1 Day 1. Blood samples for determination of 
Molecular International Prognostic Scoring System for myelodysplastic syndromes (IPSS-M) 
score and p53 status do not need to be repeated if they were obtained within 6 weeks (42 days) of 
Cycle 1 Day 1. Subjects who fail screening may undergo up to 2 repeated screenings.  
All subjects who provide informed consent must be registered in the electronic data capture (EDC) 
system and interactive voice/web/mobile response system (IXRS), including screen failures. 


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4.5 
Dosing Administration 
The treatment administration schedule for oral decitabine/cedazuridine and magrolimab is 
presented in Table 5 and Table 6. The detailed PK assessment schedule is presented in Table 13 
and Table 14. 
The following magrolimab dosing regimen is proposed for this study: 
• The dose of magrolimab is increased over time in a series called priming doses. Priming doses 
of magrolimab: 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, 22, 
29, 36, 43, and 50.  
• Maintenance doses of magrolimab: 30 mg/kg on Day 57 and every 14 days thereafter. 
• If magrolimab is not administered for 28 days or more and then restarted, the resulting doses, 
called repriming doses, follow the same schedule and dose level as the first 22 days of the 
priming doses, then maintenance dosing can start 7 days later. For subjects who have not 
received at least one 30 mg/kg dose of magrolimab (ie, for subjects who have either not 
received their first dose of 30 mg/kg or subjects who have received doses <30 mg/kg), a dose 
delay of only 14 days is allowed until repriming is required. 
The duration of each magrolimab infusion including flush will be 3 hours (±30 minutes) for 
the first 3 doses of priming and repriming. Recommended premedications are listed in 
Section 6.5. After the third dose of treatment, the magrolimab infusion including flush will be 
2 hours (±30 minutes). The reduced infusion time to 2 hours is based on prior data 
demonstrating the majority CD47 receptor occupancy (RO) on peripheral blood cells, thus 
mitigating anticipated RBC toxicities from magrolimab. 
Oral decitabine/cedazuridine study treatment is to be administered according to the following 
schedule: 
• Days 1-5: oral decitabine/cedazuridine by mouth daily on an empty stomach (morning before 
breakfast) with no food for 2 hours before and at least 2 hours after administration. When 
taking oral decitabine/cedazuridine, subjects may have clear liquids such as water, black 
coffee, or tea. The dosing regimen may be modified during assessment of DLTs in the DLT 
cohort (Section 4.1.1). 
Table 5: 
Treatment Administration Schedule for Oral 
Decitabine/Cedazuridine 
Day → 
1 
2 
3 
4 
5 
6-28 
All Cycles 
× 
× 
× 
× 
× 
— 
DLT=dose-limiting toxicity; FDC=fixed-dose combination; "×"= dosing day; "—"= non-dosing day  
Note: All treatments are one FDC tablet (35 mg decitabine/100 mg cedazuridine). After evaluation of the DLT 
cohort, the dosing regimen for subsequent subjects may be altered. 
 


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Table 6: 
Treatment Administration Schedule for Magrolimab 
Day → 
1 
2-3 
4 
5-7 
8 
9-10 
11 
12-14 
15 
16-21 
22 
23-28 
Dose 
(mg/kg) 
1 
— 
1 
— 
15 
— 
30 
— 
30 
— 
30 
— 
 
Day → 
29 
30-35 
36 
37-42 
43 
44-49 
50 
51-56 
57 
58-70 
71 
72-84 
Dose 
(mg/kg) 
30 
— 
30 
— 
30 
— 
30 
— 
30 
— 
30 
— 
Note: The dose of magrolimab is increased from 1 mg/kg to 30 mg/kg during priming on Days 1-56. Maintenance 
doses continue after priming at 30 mg/kg, starting at Day 57 and every 14 days thereafter. If magrolimab is not 
administered for 28 days or more and then restarted, the resulting doses, called repriming doses, follow the same 
schedule and dose level as the first 22 days of the priming doses, then maintenance dosing can start 7 days later. 
For subjects who have not received at least one 30 mg/kg dose of magrolimab, a dose delay of only 14 days is 
allowed until repriming is required. 
Alternative options for oral decitabine/cedazuridine administration on Days 1-5 are detailed in 
Table 7.  
Table 7: 
Alternative Options for Oral Decitabine/Cedazuridine Administration 
on Days 1-5 
Oral 
decitabine/cedazuridine 
Last meal 
(≥2 hours before taking oral 
decitabine/cedazuridine) 
Next meal 
(≥2 hours after taking oral 
decitabine/cedazuridine) 
Between breakfast and lunch 
Breakfast 
Lunch 
Between lunch and dinner 
Lunch 
Dinner 
At bedtime 
Dinner 
Breakfast (next day) 
Systematic dosing reductions of oral decitabine/cedazuridine may be necessary, as detailed in 
Section 4.1.1 and Section 6.6.1. Dose reductions of magrolimab may be considered in rare 
circumstances, as outlined in Section 6.6.2. 
Treatment will continue until disease progression, death, or unacceptable treatment-related 
toxicity, the subject withdraws or is withdrawn from the study, the treatment becomes 
commercially available, or the sponsor stops the study. 
Initially, magrolimab will be administered according to the current magrolimab IB and Table 6, 
and oral decitabine/cedazuridine will be administered according to the approved dosing regimen 
(Daily×5); please refer to the latest oral decitabine/cedazuridine IB and magrolimab IB for further 
information. 
This study will follow the dosing schedule as determined in the DLT cohort. The primary objective 
of the study is to evaluate preliminary safety and efficacy of oral decitabine/cedazuridine in 
combination with magrolimab. Efficacy will be determined by CR, which is based on the 


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2006 IWG criteria (Cheson et al 2006), described in Section 10.6. Subjects should be premedicated 
in accordance with Section 6.5. Oral decitabine/cedazuridine and magrolimab should be prepared 
as outlined in the Pharmacy Manual for the study. 
There is no dose modification for oral decitabine/cedazuridine based on weight.  
The dose of each magrolimab study treatment will be calculated based on actual weight at 
enrollment (using weight obtained either at screening or on Day 1) and remains constant 
throughout the study unless there is a >10% change in weight from baseline. Modifications to the 
magrolimab 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. 
When both study drugs are given on the same visit day, magrolimab will be administered at least 
1 hour after oral decitabine/cedazuridine administration. 
Magrolimab doses will be given twice weekly during priming and escalation (2 weeks), with a 
window of ±3 days for each dose; however, magrolimab doses are not to be given on consecutive 
days. If additional delay is needed to ensure a white blood cell (WBC) of ≤20×103/μL, please 
contact the sponsor’s medical monitor. 
During the first 28 days of treatment (Days 1, 4, 8, 11, and 22), WBC count must be ≤20×103/μL 
prior to each magrolimab dose. Subjects with WBC >20×103/μL can be treated with hydroxyurea 
(up to 4 g/day) during the first 56 days to reduce the WBC to ≤20×103/μL.  
Within 24 hours prior to each of the first 2 priming or repriming doses of magrolimab, all subjects 
must have a documented hemoglobin (Hgb) ≥9 g/dL. Subjects who do not meet these criteria must 
be transfused and have their Hgb rechecked to meet the minimum Hgb threshold prior to each of 
the first 2 doses of magrolimab. During the first 2 doses of priming and repriming, blood testing 
of Hgb will be required 3 to 6 hours after a magrolimab dose and the results must be reviewed 
prior to discharging the subject from the clinic. The subject should be transfused as clinically 
appropriate. Investigators should consider additional Hgb monitoring during the first week of 
treatment in subjects with symptoms of anemia or increased risk for complications of anemia.  
All subjects should be monitored hourly during infusion and for 1 hour after infusion for doses 
during the first 28 days and the repriming doses. Subjects 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.  
Postinfusion monitoring is not required for doses after Day 22 of priming or repriming. Subjects 
who experience any treatment-related AEs prior to this point should be further monitored as 


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clinically appropriate. Management of infusion-related reactions is further described in 
Section 8.5.7.2. 
Subjects 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 are described in Section 7.1. 
4.6 
Justification for Dose 
4.6.1 
Oral Decitabine/Cedazuridine 
The recommended dose and regimen of oral decitabine/cedazuridine for initiating the study is 
35 mg decitabine and 100 mg cedazuridine given orally as the FDC tablet once daily (QD) on 
Days 1-5 of each 28-day cycle (Days 1-5 in all cycles). This is the approved dose of oral 
decitabine/cedazuridine for MDS per INQOVI prescribing information in Australia, Canada, and 
the US (Australia, Canada, US) and the selection of this dose and regimen is based on the 
decitabine 5-day AUC from time 0 to 24 hours equivalence of oral decitabine/cedazuridine with 
IV decitabine (20 mg/m2 Daily×5). This dose and regimen were shown in the Phase 2 study 
(ASTX727-01) and confirmed in the Phase 3 study (ASTX727-02) in subjects with MDS/CMML. 
In addition, oral decitabine/cedazuridine treatment at the recommended dose and regimen achieved 
almost identical demethylation to IV decitabine (<1% as measured by percentage of long 
interspersed nucleotide elements-1 demethylation), with clinical response, transfusion 
independence, and survival data consistent with previous results for the approved IV decitabine 
5-day regimen (current DACOGEN US Prescribing Information; Steensma et al 2009). Likewise, 
safety data from the Phase 2 and Phase 3 studies (in MDS/CMML) largely mirrored the safety 
profile of IV decitabine in the same subject population. This dose is expected to yield efficacy 
similar to that of azacitidine. 
4.6.2 
Magrolimab 
The magrolimab dosing regimen for this study is outlined in Section 4.5. 
Rationale for the magrolimab dose proposed in this study originates from safety, efficacy, and 
PK/pharmacodynamic data and modeling and simulation analyses based on data obtained from all 
ongoing and completed clinical trials with magrolimab in subjects with solid tumors, NHL, and 
AML/MDS. In the first-in-human study of magrolimab (SCI-CD47-001) in subjects 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 RBCs that are sensitive to 
CD47 blockade and triggers a reticulocytosis of young RBCs that are not affected by CD47 
blockade (Chen et al 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 et al 2018; Liu et al 2015; Sikic et al 2019). The top dose 
of 45 mg/kg has an acceptable safety profile, and no MTD was identified in this study 


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(SCI-CD47-001). In Studies SCI-CD47-002 and 5F9005, in subjects 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 
DLT 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 intrasubject dose 
escalation approach was followed; after the priming dose, the subjects 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 intrasubject 
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 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 subjects 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 are being tested in an ongoing 
Phase 1b/2 study of magrolimab in combination with rituximab in subjects with 
relapsed/refractory NHL (Study 5F9003). Based on data obtained from this study so far, there was 
no significant difference in efficacy across the dose range tested. For instance, in 
relapsed/refractory diffuse large B-cell lymphoma, the ORR of subjects in the combined 30 mg/kg 
dose arm (N=35) and at 45 mg/kg (N=17) was 34% and 38%, respectively (Advani et al 2019). 
Preliminary PK/PD modeling indicated lack of relationship between exposure and ORR across the 
dose/concentration range. Also, no relationship was observed between concentrations and DOR in 
responders across the tested dose range. Together, these results indicated maximal efficacy at 
30 mg/kg with no further efficacy benefit at higher doses. 
In addition, in Study SCI-CD47-002 and Study 5F9005, CD47 RO was tested at baseline and at 
multiple time points on treatment for both peripheral blood (PB) and BM cells, including leukemic 
blasts. A PK/PD model linking dose exposure and blood and BM RO was developed and described 
these data well. Simulations with the model predicted that >90% RO would be achieved in the BM 
cells at the magrolimab dosing regimen proposed in this study. This level of RO is typically 
associated with maximal efficacy for many immune-oncology antibodies. Therefore, the proposed 
dose regimen is expected to maximize efficacy in the MDS patient population. Exploratory 
analysis of exposure-objective response data from Study 5F9005 also indicated a lack of 
relationship between concentration and likelihood of response in this concentration range, 
indicating that doses in this range are likely to be maximally effective. 
Based on results from the Phase 1b study of magrolimab in MDS and AML (Study 5F9005), this 
study will employ the same intrasubject dose escalation regimen for oral decitabine/cedazuridine 
in combination with magrolimab in treatment-naïve subjects with MDS to mitigate on-target 


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toxicities such as anemia and other toxicities observed in nonclinical AML models. The 
intrasubject dose escalation regimen uses initial twice-weekly dosing at a starting magrolimab dose 
of 1 mg/kg for Week 1 (Days 1 and 4), with escalation to 15 mg/kg on Day 8 and 30 mg/kg on 
Days 11 and 15, followed by 30 mg/kg weekly for 5 doses (Day 22, Day 29, Day 36, Day 43, and 
Day 50). The maintenance dose of magrolimab is 30 mg/kg on Day 57 and every 14 days 
thereafter. Treatment should be continued until disease progression, loss of clinical benefit, or 
unacceptable toxicities occur. The strategy of intrasubject dose escalation was found to result in 
both mitigation of acute toxicities seen in nonclinical models and in expected RBC toxicities that 
were manageable for this subject population. 
In summary, the proposed dose regimen is like the dose regimen being tested in a Phase 3 study in 
higher risk MDS in combination with azacitidine. The combination has been shown to have an 
acceptable safety profile in multiple oncology patient populations, including MDS subjects. Based 
on PK/PD modeling, the proposed dose is predicted to result in optimal efficacy in this population. 
Further increases in dose beyond 30 mg/kg are not predicted to result in increased efficacy. 
4.7 
End of Study Definition 
The study will be considered complete for data reporting purposes when all subjects have died, 
withdrawn from study treatment (Section 7.2), or the sponsor terminates the study, whichever 
occurs first. Astex reserves the right to terminate the study at any time for any reason. 
Upon completion or closure of the study, the sponsor will provide the opportunity to continue 
study drug(s) for those that continue to derive benefit from treatment through expanded access, or 
the local equivalent, and collect, at a minimum, safety information from subjects until disease 
progression, death, or unacceptable treatment-related toxicity, the subject is withdrawn from study 
treatment, or treatment becomes commercially available. 


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5.0 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. Adherence to study eligibility criteria is essential.  
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all the following criteria apply: 
Age 
1) Aged ≥18 years at the time of signing the ICF. 
Type of Participant and Disease Characteristics 
2) Histological confirmation of previously untreated MDS (ie, no HMA, chemotherapy, or 
allogenic SCT) per World Health Organization 2016 classification with <20% BM blasts per 
marrow biopsy/aspirate at screening.  
3) Projected life expectancy of at least 3 months. 
4) Overall IPSS-R score ≥3.5 MDS (intermediate risk or higher). 
5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2. 
6) Hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged HSCT on 
Cycle 1 Day 1, or HSCT ineligible. 
7) Hemoglobin ≥9 g/dL on the first day of drug administration, transfusions allowed. 
8) Blood type and screen (ABO/Rh) along with extended red blood cell phenotyping or 
genotyping completed prior to study drug treatment. 
9) Willing to undergo blood transfusions as per parameters of protocol and clinically necessary. 
10) White blood cell count ≤20×103/μL prior to first dose and throughout study. Hydroxyurea can 
be used to achieve this goal prior to and during the first 56 days of magrolimab administration. 
Sex and Contraceptive/Barrier Requirements 
11) Subject can be male or female. 
a) Male subjects: 
i) Male subjects are eligible to participate if they agree to the following during the 
treatment period and for at least 90 days plus 5 half-lives of magrolimab (70 days), 
totaling 160 days (approximately 5.5 months), after the last dose of study treatment: 
• Refrain from donating sperm. 


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PLUS either: 
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent; 
OR 
• Must agree to use contraception/barrier as detailed below: 
o Agree to use a male condom when having sexual intercourse with a woman of 
childbearing potential who is not currently pregnant.  
o Female partners should be advised of the benefit of using an additional highly 
effective contraceptive method with a failure rate of <1% per year as described 
in Section 10.2 as a condom may break or leak. 
b) Female subjects: 
i) A female subject is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies: 
• Is not a woman of childbearing potential (Section 10.2); 
OR 
• Is a woman of childbearing potential and using a contraceptive method that is 
highly effective with a failure rate of <1% per year), preferably with low user 
dependency, as described in Section 10.2, during the treatment period and for at 
least 180 days plus 5 half-lives of magrolimab (70 days), totaling 250 days 
(approximately 8.5 months), after the last dose of study treatment and agrees not to 
donate eggs (ova, oocytes) for the purpose of reproduction during this period. The 
investigator should evaluate the potential for contraceptive method failure (eg, 
noncompliance, recently initiated) in relationship to the first dose of study 
treatment. 
o A woman of childbearing potential must have a negative serum pregnancy test 
within 24 hours before the first dose of study treatment. 
o Additional requirements for pregnancy testing during and after study treatment 
are located in Section 8.2.5.  
o The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a woman with an 
early undetected pregnancy. 


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Informed Consent 
12) Capable of giving signed informed consent (Section 10.1.3), which includes compliance with 
the requirements and restrictions listed in the ICF and in this protocol, and willing to participate 
in the study. 
5.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply:  
Medical Conditions 
1) Known active hepatitis B (eg, HBsAg reactive), or hepatitis C (eg, HCV RNA [qualitative] is 
detected), or chronic hepatitis B or C infection or human immunodeficiency virus (HIV) 
infection in medical history, with the following exceptions: 
a) Those with a history of hepatitis with a negative polymerase chain reaction (either 
qualitative or quantitative) OR have documentation of stable disease with aspartate 
aminotransferase (AST)/serum glutamic oxaloacetic transaminase 
and 
alanine 
aminotransferase (ALT)/serum glutamic pyruvic transaminase <2.0×upper limit of normal 
(ULN) may be eligible for this study. 
b) Subjects with history of HIV who have an undetectable viral load for the prior 3 months, 
and who agree to maintain antiviral therapy, may be eligible for the study. 
2) 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. 
3) Abnormal biochemical indices as listed below: 
a) Aspartate aminotransferase/serum glutamic oxaloacetic transaminase and ALT/serum 
glutamic pyruvic transaminase >3.0×ULN. 
b) Total or direct bilirubin >1.5×ULN or >3.0×ULN and primarily unconjugated unless the 
participant has a previously documented history of Gilbert's syndrome or genetic 
equivalent. 
c) Serum 
creatinine 
>1.5×ULN, 
calculated 
glomerular 
filtration 
rate 
(GFR) 
<40 mL/min/1.73 m2, or calculated creatinine clearance <50 mL/min by Cockcroft Gault 
formula or other medically acceptable formulas. 
4) Known inherited or acquired bleeding disorders that require medication or medical 
intervention. 


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5) Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized 
prostate cancer, or other malignancies for which subjects are not on active anticancer therapies 
and have had no evidence of active malignancy for at least ≥1 year. 
Prior/Concomitant Therapy 
6) Immediate eligibility for an allogeneic SCT, as determined by the investigator, with an 
available donor. 
7) Prior therapy for MDS with chemotherapy, allogenic SCT, or ≥1 full cycle of treatment with 
any HMA. 
8) History of therapy-related MDS, MDS evolving from a pre-existing myeloproliferative 
neoplasm (MPN), MDS/MPN including CMML, atypical chronic myeloid leukemia, juvenile 
myelomonocytic leukemia, and unclassifiable MDS/MPN. 
9) Prior anti-CD47 treatment. 
10) Previous SCT within 6 months before first dose administration, active graft-versus-host 
disease, or requiring transplant-related immunosuppression. 
Other Exclusions 
11) Known or suspected hypersensitivity to decitabine, cedazuridine, magrolimab, or any of their 
excipients. 
12) Known significant mental illness or other condition such as active alcohol or other substance 
abuse or addiction that, in the opinion of the investigator, predisposes the subject to high-risk 
of noncompliance with the protocol. 
13) Clinical suspicion of active central nervous system (CNS) involvement by MDS. 
14) History of psychiatric illness or substance abuse likely to interfere with the ability to comply 
with protocol requirements or give informed consent. 
15) Pregnant or actively breastfeeding. 
5.3 
Lifestyle Considerations 
Subjects are required to adhere to all guidelines in this section. 
5.3.1 
Meals and Dietary Restrictions 
Oral decitabine/cedazuridine tablets should be taken with water on empty stomach (defined as 
having no food for 2 hours before dosing) with no food for 2 hours after administration 
(Section 4.5). 


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5.3.2 
Contraceptive Requirements 
Lifestyle considerations pertaining to contraceptive requirements while on study are described in 
Section 10.2 for both men and women. Magrolimab has a longer half-life than oral 
decitabine/cedazuridine, which forms the basis of the duration of contraceptive requirements for 
both men and women. 
5.3.3 
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, 
any of the 4 blood groups (A, B, AB, and O)/Rhesus factor (ABO/Rh) type, antibody screen, 
extended phenotyping or genotyping, and DAT need to be performed at screening before exposure 
to magrolimab, as described in Section 8.5.7.  
Red blood cell genotyping (instead of an extended RBC phenotyping) must be performed if a 
subject received any RBC or whole blood transfusion within the previous 3 months (unless the 
laboratory has availability for special techniques for performing phenotyping for subjects with a 
recent transfusion). Extended RBC genotyping instead of extended RBC phenotyping is acceptable 
for any subject. 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 subject was transfused since that time. Results must be 
available before the first dose of magrolimab.  
5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study (ie, sign the 
ICF), but are not subsequently treated. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
screening procedure-related AEs. 
Individuals who do not meet the criteria for participation (screen failure) may be rescreened (no 
minimum time is required before rescreening and the number of times a subject can be rescreened 
is limited to 2). Rescreened subjects should be assigned the same subject number as for the initial 
screening.  


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6.0 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY 
6.1 
Description of Study Interventions Administered 
Descriptions of the study treatments to be administered are shown in Table 8. ASTX727 and oral 
decitabine/cedazuridine are often used interchangeably. 
Table 8: 
Oral Decitabine/Cedazuridine and Magrolimab Products Used in the 
Study 
 
Single Arm 
Oral Decitabine/Cedazuridine (also 
known as ASTX727)a,b 
Magrolimab 
Intervention Name 
Oral decitabine/cedazuridine  
Magrolimab 
Type  
Drug  
Drug 
Dose Formulation 
Tablet 
IV 
Unit Dose Strength(s) 
35 mg decitabine and 
100 mg cedazuridine 
1 mg/kg, 15 mg/kg, and 30 mg/kg 
Dosage Level(s) 
Cycle 1:  
• 
One tablet QD on Days 1-5a 
Cycles ≥2:  
• 
One tablet QD on Days 1-5a  
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 
Day 22, Day 29, Day 36, Day 43, 
and Day 50) 
Maintenance Dose: 
• 
30 mg/kg on Day 57 and 
• 
30 mg/kg every 14 days thereafter 
Route of Administration 
PO 
IV 
Sourcing 
Provided centrally by the sponsor 
Provided centrally by the sponsor 
Packaging and Labeling 
Provided in 5-count opaque 
high-density polyethylene bottle with 
child resistant closure. Each bottle 
labeled per country requirement. 
Single-use, 10 mL vials containing 
200 mg of the antibody in a 
formulation of 10 mM sodium acetate, 
5% (w/v) sorbitol, 0.01% (w/v) 
polysorbate 20, at a pH of 5.0. 
DLT=dose-limiting toxicity; IV=intravenous; PO=by mouth; QD=once daily; w/v=weight by volume 
a. 
ASTX727 and oral decitabine/cedazuridine are often used interchangeably. 
b. 
Dosing may be modified if DLTs are observed in the DLT cohort. 
 
6.2 
Preparation/Handling/Storage/Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained at the study center for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention. 


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Only subjects enrolled in the study may receive study intervention and only authorized site staff 
may supply or administer study intervention. All study intervention must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff. 
Store oral decitabine/cedazuridine tablets at room temperature at 20°C to 25°C (68°F to 77°F); 
excursions from 15°C to 30°C (59°F to 86°F) are permitted. Excursions for ≤7 days at temperatures 
>30°C (86°F) and ≤40°C (104°F) are not expected to affect the strength or stability; however, 
excursions at these temperatures for >7 days may impact investigational medicinal product (IMP) 
quality depending upon severity. Excursion at temperatures <15°C (59°F) or >40°C (104°F) for 
any amount of time will impact IMP quality. For those temperature excursions that impact IMP 
quality, the IMP should be quarantined and stored at the recommended temperature, while the 
Astex staff is contacted for further instructions. 
Instructions regarding transport from pharmacy to home and at-home storage instructions should 
be given to the study subject, as applicable. 
Magrolimab is supplied in single-use, 10 mL vials containing 200 mg of the antibody in a 
formulation of 10 mM sodium acetate, 5% (weight by volume) sorbitol, 0.01% (weight by volume) 
polysorbate 20, at a pH of 5.0. 
The labeling complies with the requirements of the applicable regulatory agencies. Vials 
containing magrolimab should be stored under refrigeration at 2°C to 8°C (36°F to 46°F) in an 
appropriate, locked room and/or locked refrigerator, accessible only to pharmacy personnel or a 
duly designated person. Magrolimab should not be frozen. Protect from light during storage. 
DO NOT SHAKE. 
Additional details about oral decitabine/cedazuridine and magrolimab are provided in the 
Pharmacy Manual. 
The investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study intervention accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Pharmacy Manual. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
This study is not blinded or randomized; therefore, bias may occur. To minimize bias, response 
assessments to determine efficacy will be assessed by the investigator and calculated using a 
pre-specified program based on the 2006 IWG criteria (Section 10.6) and methods to assess CR as 
described in 2006 (Cheson et al 2006), as defined in Table 21 and Table 22. 


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6.4 
Study Intervention Compliance 
Subject compliance with oral decitabine/cedazuridine will be assessed at time points defined in the 
SoA (Table 1). Compliance will be assessed by direct questioning, counting returned tablets, and 
reviewing subject’s dosing diaries. Deviation(s) from the prescribed dosage regimen should be 
recorded in the subject’s dosing diary. 
Treatment start and stop dates, including dates and reasons for treatment interruption and/or dose 
modifications will also be recorded in the electronic case report form (eCRF). 
6.5 
Premedication 
Premedication is required prior to the administration of magrolimab through the Day 22 infusion 
of priming and repriming. Premedications 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 8.5.7.2). 
Premedications are oral acetaminophen 650 mg to 1000 mg and oral or IV diphenhydramine 25 mg 
to 50 mg or comparable regimen. If less than 4 hours have elapsed since a prior dose of 
acetaminophen has been given, the dose of acetaminophen premedication may be omitted. 
These premedications are to be entered as concomitant medications. 
6.6 
Dose Modification 
6.6.1 
Oral Decitabine/Cedazuridine Dose Modifications 
In the event of toxicity that prevents initiation of a subsequent cycle containing oral 
decitabine/cedazuridine, the first intervention is dosing delay rather than dosing reduction. 
Subsequent cycles should be delayed in subjects with an absolute neutrophil count ≤500 cells/µL, 
until recovery to >500 cells/µL. Delays of up to 2 weeks are acceptable without a change in dosing. 
The planned dosing of oral decitabine/cedazuridine may be reduced for individual subjects in the 
event of unacceptable treatment-related toxicity or delay in initiating a treatment cycle (eg, an AE 
that meets the definition of a DLT) as assessed by the investigator (Section 8.5.6), and should be 
reduced based on the guidelines outlined in Table 9.  
When delays are required, the following parameters should be followed: 
• If dosing of oral decitabine/cedazuridine is delayed more than 3 days prior to Day 15, then the 
next dosing of oral decitabine/cedazuridine will be further delayed to align with the next dose 
of magrolimab.  
• If oral decitabine/cedazuridine is delayed to Day 15 of a cycle, then that cycle length will be 
increased to 42 days. The next cycle will start 28 days after Day 15. 


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• If oral decitabine/cedazuridine is delayed beyond 15 days into a cycle, then administration of 
oral decitabine/cedazuridine will be held for that cycle. 
Table 9: 
Dosing Reduction Guidelines for Oral Decitabine/Cedazuridine 
Number of Dose Reductions per 
Individual Subject 
Dose per Cycle 
Level 1 
Oral decitabine/cedazuridine Daily×5 for each 28-day cycle 
Level 2 
Oral decitabine/cedazuridine Daily×4 for each 28-day cycle 
Level 3 
Oral decitabine/cedazuridine Daily×3 for each 28-day cycle 
Level 4 
Oral decitabine/cedazuridine on Days 1, 3, and 5 of each 28-day cycle 
Level 5 
Discontinue oral decitabine/cedazuridine 
DLT=dose-limiting toxicity  
Note: For subjects receiving oral decitabine/cedazuridine outside of the period of DLT assessment in the DLT 
cohort, a maximum of 2 dose reductions are allowed before study treatment must be permanently discontinued. 
 
6.6.2 
Magrolimab Dose Modifications 
In clinical experience with magrolimab, no significant dose-dependent toxicities have been 
identified. Therefore, in general, dose modifications or delays to magrolimab should not be made. 
The dose of magrolimab may be reduced for Grade ≥3 AEs that are deemed clearly related to 
magrolimab and not oral decitabine/cedazuridine and that do not resolve to Grade ≤2 or baseline 
value within 14 days of onset. However, dose delay of magrolimab should occur first, and if the 
AE does not resolve, then a magrolimab dose reduction can be considered (Section 6.6.2.1). If 
there is a delay of dosing of magrolimab during a cycle of oral decitabine/cedazuridine, the cycle 
can be extended by up to 14 days to allow for dosing of the study drug(s) on Day 1 of the 
subsequent oral decitabine/cedazuridine cycle. The Medical Monitor should be notified of any 
planned dose delays. 
If a magrolimab 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 
dose reductions from 20 to 15 mg/kg may be warranted. For persistent BM hypocellularity or 
peripheral cytopenias (where both oral decitabine/cedazuridine and magrolimab may have a 
contribution), the dose of oral decitabine/cedazuridine should be reduced first. Subjects can 
re-escalate to higher doses of magrolimab up to the original 30 mg/kg dose if AEs improve, after 
discussion with the sponsor’s Medical Monitor. 
6.6.2.1 
Repriming for Magrolimab 
Given the large CD47 antigen sink on normal cells, subjects who have a dose delay of magrolimab 
equivalent to 28 days or more are required to be reprimed with magrolimab to resaturate the CD47 
antigen sink. Within 24 hours prior to each of the repriming doses of magrolimab, all subjects must 
have a documented Hgb ≥9 g/dL. Subjects who do not meet these criteria must be transfused and 


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have their Hgb rechecked to meet the minimum Hgb threshold prior to each of the first 2 doses of 
magrolimab. During the first 2 doses of repriming, blood testing of Hgb will be required 3 to 
6 hours after a magrolimab dose and the results must be reviewed prior to discharging the subject 
from clinic. The subject should be transfused as clinically appropriate.  
Repriming differs depending on where the participant is in their treatment period as follows:  
1) For subjects who have not reached Day 57 of magrolimab, up to 14 days between doses is 
permitted.  
2) For subjects who have received Day 57 (or beyond) dose of magrolimab, up to 28 days between 
doses is permitted.  
After Day 22 of repriming, subjects should return to their original maintenance dose schedule.  
Please notify the Medical Monitor of any planned dose delays. 
6.6.3 
Temporary Discontinuation of Oral Decitabine/Cedazuridine 
Study drug dosing should be withheld anytime a toxicity would have qualified as a DLT 
(Section 8.5.6). Dosing may resume, at the investigator’s discretion, if and when the following 
conditions are met: 
• When study treatment-related toxicity has: 
o Completely resolved or returned to baseline (all AEs), or 
o Partially recovered to Grade 2 or less (anemia, fatigue, malaise, alopecia), or 
o Partially recovered to Grade 1 or less (all other toxicities) 
If toxicity, other than cytopenias, has not resolved as described above within 21 days, the 
investigator should consider permanently discontinuing study treatment. 
If cytopenia-related toxicity has not resolved as described above within 42 days, the investigator 
should consider permanently discontinuing study treatment. 
If and when dosing is resumed following an oral decitabine/cedazuridine-associated DLT, the 
individual’s dosing of oral decitabine/cedazuridine should be adjusted to the next lower dose and 
should follow what is outlined in Section 6.6. 
6.7 
Missed or Vomited Doses 
Oral decitabine/cedazuridine 
If a dose is missed within 12 hours of the time it is usually taken, the subject should take the missed 
dose as soon as possible. If a dose is missed by more than 12 hours, the subject should not take the 


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missed dose. In either scenario, the subject should resume the usual dosing schedule the next day 
and proceed with completing the full 5 days (unless previously adjusted) of treatment per cycle. 
If the subject vomits after dosing, the vomiting episode and the time it occurred should be recorded 
in the dosing diary. No additional dose should be taken that day. The next dose should be taken at 
the usual time. Investigators should consider pre-medicating the subject with antiemetics if 
vomiting is anticipated to be a recurring issue. 
Magrolimab 
If a dose of magrolimab is missed, it should be given as soon as possible. If delayed by more than 
3 days (excluding priming or repriming), the timing of subsequent doses needs to be reset so that 
the subsequent dose is offset by the appropriate number of days. If there is a delay of magrolimab 
dosing then oral decitabine/cedazuridine dosing should be delayed to align the 2 study drugs (See 
Section 6.6.2).  
6.8 
Treatment of Overdose 
For this study, any administered dose of magrolimab or oral decitabine/cedazuridine greater than 
the assigned daily dose defined in the treatment administration (Section 6.1) will be considered an 
overdose. A dose given on a day that is not prescribed by the protocol is also considered an 
overdose. Based on the clinical experience of decitabine, an overdosage of oral 
decitabine/cedazuridine may result in more profound or prolonged myelosuppression and its 
consequences such as infection, or bleeding, or GI toxicity, and subjects should be managed 
accordingly. Based on the clinical experience of magrolimab, there is no known or expected effect 
from a single overdose of magrolimab. There is no specific treatment for an overdose with oral 
decitabine/cedazuridine alone or in combination with magrolimab. 
In the event of an overdose: 
• Inform the Astex medical monitor immediately. 
• Closely monitor the subject for AEs/serious adverse events (SAEs) and laboratory 
abnormalities. 
• Obtain a plasma sample for PK analysis. 
• Record the actual dose of study drug administered in the source document and on the Dosing 
eCRF page. 
• Record any adverse clinical signs and symptoms associated with an overdose on the AE 
eCRF page. 
• Report signs and symptoms of an overdose that meet SAE criteria (Section 10.5.2) to Astex 
on the SAE form within 24 hours (Section 10.5.4).  
• Treat any AE (including SAE) based on SOC for the specific signs and symptoms. 


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• Record as a protocol deviation. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Astex medical monitor based on the clinical evaluation of the subject. 
6.9 
Concomitant Therapy 
All medications a subject takes, starting from 14 days before first dose administration and ending 
30 days after the last dose of study treatment, including supportive or palliative treatment (see 
below) whether prescription or over-the-counter, vitamin and mineral supplements, herbs, and 
medications taken for procedures (eg, biopsy) should be reported on the Concomitant Medication 
eCRF. This reporting includes antacids, proton pump inhibitors, H2 antagonists and cold 
medications. The following information is expected: medication name, start/stop dates, and 
indication for use. Medications used for premedication before infusion should be entered and noted 
as premedications. 
6.9.1 
Supportive, Prophylactic, or Other Treatments Allowed 
Premedication is permitted while on study treatment (Section 6.5). Localized non-CNS 
radiotherapy, erythroid and/or myeloid growth factors, hormonal therapy with luteinizing 
hormone-releasing hormone agonists for prostate cancer, and treatment with bisphosphonates 
receptor activator of nuclear factor kappa beta inhibitors are permitted. Blood transfusions are 
permitted during screening or before first dose administration to ensure adequate Hgb levels. 
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 during the first 56 days to reduce the WBC to 
≤20×103/μL. In nonclinical studies, coadministration of magrolimab and hydroxyurea in human 
leukemia engrafted immunodeficient mice did not cause phagocytosis of normal BM cells, 
suggesting limited on-mechanism toxicity in subjects. 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 subjects who have received 
concomitant magrolimab and hydroxyurea. 
6.9.2 
Prohibited Medications/Therapies 
Prohibited concomitant therapies while on study are as follows: CNS or systemic radiation therapy, 
chemotherapy, immunotherapy, or any experimental therapy. Drugs and supplements that are 
metabolized by cytidine deaminase should be used with caution or held on days when oral 
decitabine/cedazuridine is administered. 
Vaccination with live vaccines is prohibited while subjects remain on study treatment. 


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6.9.3 
Rescue Medicine 
There is no specific rescue medication that would be considered standard as this differs by subject 
disease and by regional or institutional standards. If a subject develops progressive disease while 
on treatment or the treatment is not tolerated, subjects should permanently discontinue treatment. 
Any subsequent or rescue therapy will be based on individual case and local site standards of 
management. 
6.9.4 
COVID-19 Vaccine 
COVID-19 vaccines should not be considered investigational agents for the purposes of this study; 
approved and authorized COVID-19 vaccines should be listed as concomitant medication and 
entered in the electronic record as such (Desai et al 2021). 
6.10 
Study Treatment After the End of the Study 
The investigator is responsible for ensuring that consideration is given for poststudy care of the 
subject’s medical condition whether Astex is providing specific poststudy treatment or not. As 
defined in Section 4.7, the sponsor provides the opportunity to continue treatment with the study 
drugs through expanded access, or the local equivalent, and collect, at a minimum, safety 
information from subjects who are still deriving benefit from continued treatment, until the subject 
is withdrawn from study treatment, or the treatment is commercially available for this indication. 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Permanent Discontinuation of Study Treatment 
It may be necessary for a subject to permanently discontinue study treatment. Treatment 
discontinuation refers to the discontinuation of both oral decitabine/cedazuridine and magrolimab. 
If study treatment is permanently discontinued, the subject will remain in the study to be evaluated 
for safety and long-term health status. See the SoA for data to be collected at the time of treatment 
discontinuation (Table 1 and Table 2). 
A subject may choose to permanently discontinue study treatment at any time (described in further 
detail in Section 7.2). In addition, subjects may be required to permanently discontinue study 
treatment at any time for the following reasons: 
• Investigators can discontinue subjects from study treatment in case of unacceptable toxicity, 
non-compliance, disease progression, or if the investigator determines it is in the subject's best 
interest. 
• Astex Pharmaceuticals may require that a subject is discontinued from treatment for safety 
reasons or for noncompliance. 
• Any female participant who becomes pregnant while participating in the study will 
permanently discontinue study treatment. 


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In all cases, the reason(s) for discontinuation from study treatment must be recorded in the source 
document and on the relevant page of the subject's eCRF. 
At the time of permanent discontinuation of treatment, a Treatment Discontinuation Visit should 
be conducted, as detailed in the SoA (Table 1 and Table 2). At minimum, subjects should be 
followed up for safety until 30 days after the last dose of study treatment. 
Every effort must be made to undertake protocol specified follow-up procedures. For subjects 
willing to continue study follow-up procedures, the investigator should review the follow-up 
procedures with the subject, including the number of visits, the specific procedures to be done, and 
the total length of the follow-up period. 
7.2 
Subject Discontinuation/Withdrawal From the Study 
A study subject may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for behavioral, compliance, or 
administrative reasons. This is expected to be uncommon. It is important to distinguish between 
the decision for a subject to permanently discontinue treatment and the decision for a subject to 
withdraw completely from the study. The term study withdrawal/withdrawal of consent should 
only be restricted to those subjects who wish to completely withdraw from the study and stop all 
study follow-up procedures including long-term follow-up that may be conducted remotely. A 
subject’s decision to discontinue treatment or discontinue certain follow-up procedures IS NOT 
considered study withdrawal. 
In all cases, the reason(s) for withdrawal from study must be recorded in the source document and 
on the relevant page of the subject's eCRF. 
• The investigator must also ensure the subject understands that his or her medical records will 
continue to be available for the follow-up period as described in the approved ICF for the entire 
study period.  
• If a subject withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
• Additionally, if a subject withdraws consent from the study, he/she may request destruction of 
any samples taken and not tested, and the investigator must document this in the site study 
records and inform the sponsor within 24 hours. 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 


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• The site must attempt to contact the subject and reschedule the missed visit as soon as possible 
and counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the subject wishes to and/or should continue in the study. 
• Before a study subject is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the subject’s medical record. 
• Should the study subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1. 
8.0 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Table 1 and Table 2). Protocol 
waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the sponsor immediately upon occurrence 
or awareness to determine if the participant should continue or discontinue study intervention. 
• Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The investigator will maintain a screening log to record details of 
all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
• Procedures conducted as part of the subject’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the SoA. 
• Biological samples which are collected as part of routine medical care or as part of protocol 
procedures may be stored and analyzed as part of secondary endpoint analysis (eg, genetic, 
PK) and will follow all applicable local regulatory guidelines. 
8.1 
Demographics, Medical History, and Prior Anticancer Therapy 
Demographic data will be recorded at screening. Investigators will obtain subject’s relevant 
medical and surgical history including date [month (if available) and year], and prior anticancer 
therapies (including best response) at screening, using the investigator’s best judgement, and 
record it on the appropriate medical history eCRF page. 


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8.2 
Safety Assessments 
Planned time points (including the visit windows) for all safety assessments are provided in the 
SoA (Table 1 and Table 2).  
8.2.1 
Physical Examinations 
A complete and/or symptom directed physical examination (PE) will be performed per the SoA 
(Table 1). A complete PE will be performed per the institutional standard practice, and at a 
minimum should include assessment of the cardiovascular, respiratory, GI, lymphatics, skin, and 
neurological systems at screening, predose on Cycle 1 Day 1, and at treatment discontinuation. For 
subjects who had a complete PE performed at screening within 3 days before the first dose of study 
drug(s), it is not necessary to repeat the complete PE on Cycle 1 Day 1; a symptom-directed PE 
on Cycle 1 Day 1 can be done instead. A symptom directed PE will be performed at all other time 
points detailed in the SoA (Table 1). If the subject has no subjective complaints, a symptom- 
directed PE is not necessary and should be noted as such in the eCRF. Height and weight will also 
be measured before study treatment at visits specified in the SoA. The symptom-directed PE can 
be performed the day before the visits if more convenient. 
8.2.2 
Vital Signs 
On magrolimab dosing days and on Day 1 of any cycle of oral decitabine/cedazuridine, all vital 
signs will be measured predose per the institutional standard practice at the time points outlined 
in the SoA (Table 1 and Table 2). On non-dosing days (Table 1 and Table 2), vital signs 
measurements should be conducted per institutional standard practice. Vital signs to be measured 
are resting systolic and diastolic blood pressure, resting heart rate, resting respiration rate, oxygen 
saturation, and body temperature. In addition to the vital signs measured predose on Cycle 1 Day 1, 
systolic and diastolic blood pressure and heart rate will also be obtained 2 hours (±30 minutes) 
postdose on Cycle 1 Day 1.  
The date and time of collection and measurements will be recorded on the appropriate eCRF. 
8.2.3 
Twelve-lead Electrocardiograms 
Twelve-lead electrocardiogram (ECG) will be obtained predose and at the time points indicated in 
the SoA (Table 1) using an ECG machine that automatically calculates the heart rate and measures 
RR interval, PR segment, QRS duration, and QT duration. Postdose ECGs will also be obtained 
during PK assessment per Section 8.4. 
Electrocardiograms will be read locally and ECG parameters including clinical interpretation will 
be recorded in the eCRF. 


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8.2.4 
Clinical Safety Laboratory Assessments 
The list of clinical safety laboratory tests (including serum/plasma chemistry, hematology, and 
urinalysis) to be performed in this study are detailed below.  
Hematology must include complete blood count (CBC) with either manual or automated 
differential and platelet counts. If manual and automated differentials are done, the manual counts 
will be entered into the eCRF. Urinalysis includes dipstick test (if available).  
If sites do not have the capability to perform extended RBC genotyping or phenotyping analysis, 
samples will be sent to the central laboratory for RBC genotyping. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Pregnancy testing should be conducted as detailed in Table 1 (a serum test [from whole blood] is 
required at screening; serum or urine testing may be used at subsequent time points, as required 
by local regulations). Testing should also be conducted at the end of relevant systemic exposure 
plus an additional 30 days and correspond with the time frame for female participant contraception 
in Section 5.1. 
Analytes to be assessed by the local laboratory or specialty laboratories at screening are presented 
in Table 10.  


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Table 10: 
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 
LDHAST (SGOT) 
ALT (SGPT) 
Alkaline phosphatase 
RBC 
Hgb 
Hematocrit 
Platelets 
WBC  
Neutrophils 
Eosinophils 
Basophils 
Lymphocytes 
Monocytes 
Reticulocytes 
Haptoglobin 
PT 
INR aPTT or PTT 
PB smear 
RBC 
Glucose 
Protein  
Urine pH  
Ketones  
Bilirubin  
Urine specific gravity  
Pregnancy test (serum at screening) 
 
Blood phenotyping or blood 
genotyping 
 
Type and screen (ABO/Rh) 
 
DAT 
 
ADA 
 
Hepatitis B and hepatitis C 
assessments: HBsAg, anti-HBc, HCV 
antibody; HBV DNA and HCV RNA 
(as required) 
 
HIV antibody (if clinically indicated) 
Molecular study to determine IPSS-M, 
including p53 statusa 
ABO=any of the 4 blood groups (A, B, AB, and O); ADA=antidrug antibody; 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; Hgb=hemoglobin; HIV=human immunodeficiency 
virus; INR=international normalized ratio; IPSS-M=Molecular International Prognostic Scoring System for 
myelodysplastic syndromes; LDH=lactate dehydrogenase; PB=peripheral blood; 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 cell. 
Note: Refer to the Schedules of Activities (Table 1 and Table 2) for collection time points.  
a 
Please see Section 10.4 for further details on the molecular markers used for IPSS-M. 
Analytes to be assessed by the local laboratory or specialty laboratories during the study are 
presented in Table 11. 


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Table 11: 
Laboratory Analyte Listing (To Be Performed During the Study) 
Chemistry 
(Serum or Plasma)a 
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 
Hgb 
Platelets 
WBC 
Neutrophils 
Lymphocytes 
Reticulocytes 
Haptoglobinb 
PB smear 
Peripheral blasts 
Pregnancy testc 
PKd 
ADAd 
Cytogenetics 
MRDd,e 
ABO=any of the 4 blood groups (A, B, AB, and O); ADA=antidrug antibody; ALT=alanine aminotransferase; 
AST=aspartate aminotransferase; BUN=blood urea nitrogen; DAT=direct antiglobulin test; Hgb=hemoglobin; 
IEC=Independent Ethics Committee; INR=international normalized ratio; IRB=Institutional Review Board; 
LDH=lactate dehydrogenase; MRD=minimal residual disease; PB=peripheral blood; PK=pharmacokinetic(s); 
RBC=red blood cell; Rh=Rhesus factor; SAE=serious adverse event; SGOT=serum glutamic oxaloacetic 
transaminase; SGPT=serum glutamic pyruvic transaminase; SOC=standard of care; ULN=upper limit of normal; 
WBC=white blood cell.  
Note: Refer to the Schedules of Activities (Table 1 and Table 2) for collection time points. 
a 
All events of ALT ≥3×ULN and bilirubin ≥2×ULN (>35% direct bilirubin) or ALT ≥3×ULN and INR >1.5, if 
INR measured which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis). 
b 
Collection of LDH and haptoglobin is not required after Day 29 except during repriming cycles. 
c 
Pregnancy testing after screening can be performed on either urine or serum based on local preferences and 
testing requirements of local regulation or Institutional Review Boards/Independent Ethics Committees. 
d 
This assay will be performed at a central laboratory. 
e 
Information on MRD will be collected from sites per SOC. 
 
8.2.5 
Pregnancy Testing 
Pregnancy testing will be performed at the time points indicated in the SoA (Table 1) for women 
of childbearing potential only. A serum test is required at screening; serum or urine testing may be 
used at subsequent time points, as required by local regulations. Results must be reviewed prior to 
dosing and must be recorded in the eCRF. 
8.2.6 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group PS scores are detailed in Table 12 and will be recorded per 
the SoA (Table 1). The timing and frequency of ECOG performance score assessments are detailed 
in the SoA (Table 1) and can be performed on the day before the visit if more convenient. 


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Table 12: 
Eastern Cooperative Oncology Group Performance Status 
Score 
ECOG Description 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or 
sedentary nature (eg, light house work, office work) 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about 
more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
Source: ECOG Performance Status — https://ecog-acrin.org/resources/ecog-performance-status/ (accessed 
10 August 2022) 
 
8.3 
Efficacy Assessments 
Efficacy (response) assessments should be performed within the prespecified windows indicated 
in the SoA (Table 1). 
8.3.1 
Disease Response Assessment 
Disease assessment will follow IWG 2006 criteria (Section 10.6) and will include CR, HI, and 
ORR (including CR, mCR, or any HI). Other assessments will include duration of PFS, LFS, 
undetectable disease assessed by MRD, DOR, and OS. Disease response assessment will be 
determined based on BM evaluations and a corresponding PB sample along with transfusion 
requirements. Bone marrow evaluations must include aspirate (when feasible), biopsy, and 
cytogenetics. If hematologic recovery is in progress, a repeat CBC may be done no more than 
7 days after the BM evaluation for response assessment. The BM biopsy and aspirate procedure 
will be conducted according to local standard practice at time points shown in the SoA (Table 1). 
BM and PB samples adequate for analysis must be obtained in order to confirm response. BM 
biopsy and aspirate and a CBC must be repeated if the BM and/or PB sample are not interpretable 
by the investigator. A local laboratory will be used to assess BM and PB samples. BM samples 
should be Wright Giemsa or May Grunwald Giemsa stained. Detailed instructions for processing 
BM samples will be provided in the Laboratory Manual.  
BM evaluations should be performed at screening and on Day 1 of every cycle (or within a 3-day 
window prior to Day 1) until an mCR is achieved (BM myeloblasts ≤5% and decrease by ≥50% 
over pretreatment). If an mCR is achieved, without meeting CR criteria, a follow-up BM 
evaluation should occur on Day 1 of the next cycle (or within a 3-day window prior to Day 1) to 
assess or confirm the possibility of CR. Thereafter, BM evaluation may occur as clinically 
indicated to monitor DOR as appropriately guided by PB counts after achieving a confirmed CR 


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but should occur at least every 3 cycles for the first year, then as clinically indicated. Results do 
not have to be fully available to start study treatment for that cycle.  
Response will be assessed by the investigator and derived programmatically based on the 2006 
IWG criteria (Cheson et al 2006). Further details of the IWG criteria can be found in Section 10.6. 
8.3.2 
Long-term Follow-up 
Beginning 3 months after the 30-day Safety Follow-up visit (for subjects who permanently 
discontinued treatment), subjects will be followed in long-term follow-up for health status 
information, which will be gathered every 3 months (±2 weeks) until death, the subject withdraws 
consent, the subject is lost to follow-up, or the study ends, whichever occurs first. Long-term 
follow-up may be accomplished through a telephone call to the subject or next of kin, contact with 
the local treating physician, or medical record review. If the subject did not have disease 
progression prior to treatment discontinuation, the absence of disease progression should be 
monitored according to standard practice during long-term follow-up contact. For subjects who 
discontinued treatment before documented disease progression and have a telephone visit, they 
should be asked if they have had disease progression (bone marrow blast count ≥5% and MDS 
conversion to AML) or any transfusion requirements since last contact. Follow-up contact will 
also permit BM biopsy reports to be obtained from subjects that discontinue treatment to receive 
an SCT, allowing efficacy to be followed at this stage. The investigator or designee should record 
the subject’s survival status in the eCRF. Date of death may be collected and recorded in the EDC 
system from public sources in cases of subjects who withdraw consent or who are lost to follow-
up. In the event of death, a death form detailing the primary cause of death must be completed for 
the subject. 
8.4 
Pharmacokinetics 
PK samples will be collected as described in the SoA (Table 1 and Table 2) and evaluated for 
magrolimab and oral decitabine/cedazuridine concentrations. Serum magrolimab and plasma 
decitabine and cedazuridine assessments will be done using validated assays. This could include 
using leftover serum for alternative PK assay development and analysis. 
Table 13 shows the schedule for PK sample collection for serum magrolimab and Table 14 shows 
assessments for oral decitabine/cedazuridine (for determination of plasma levels of decitabine and 
cedazuridine). PK collections for oral decitabine/cedazuridine require special pretreatment with 
tetrahydrouridine (THU, for stabilization) of blood collection tubes and details for this procedure 
will be included in the Laboratory Manual.  


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Table 13: 
Serum Collection Schedule for Pharmacokinetic Analysis and 
Antidrug Antibodies (ADA) for Serum Magrolimab 
Day 
Dosing Day? 
Predose 
End of Infusiona 
Day 1 
Yes 
 
 
Day 50 
Yes 
 
 
Day 57 
Yes 
 
 (PK Only) 
Day 141 
Yes 
 
 
End of treatment 
NA 
 
 
NA=not applicable; PK=pharmacokinetic(s). 
Note: =PK blood sample is to be collected at the indicated time point. 
a Magrolimab should be infused over 3 hours (±30 minutes). 
 
Table 14: 
Plasma Collection Schedule for Pharmacokinetic Analysis for Oral 
Decitabine/Cedazuridine 
Day 
Dosing Day? 
Predoseb 
Hours Postdose 
Cycle 1 Day 1 
Yes 
NA 
2.0 (±30 minutes)c,d 
Cycle 1 Day 4a,e 
Yes 
c 
0.5 (±5 minutes), 1.0 (±5 minutes)c,d,  
1.5 (±5 minutes), 2.0 (±30 minutes)c,d,  
3.0 (±10 minutes), 4.0 (±10 minutes)c,d,  
6.0 (±20 minutes), 8.0 (±30 minutes) 
Cycle 1 Day 5e 
Yes 
Predose (24 ±1.0 hours 
after Cycle 1 Day 4 dose)c 
 
Cycle 2 Day 4e 
Yes 
c 
1.0 (±30 minutes)b,c, 2.0 (±30 minutes)c,d,  
4.0 (±60 minutes)c,d 
Ad-hoc PK sample 
NA 
NA 
Optional (if needed) 
ECG=electrocardiogram; NA=not applicable; PK=pharmacokinetic(s). 
Notes: =PK blood sample is to be collected at the indicated time point.  
a 
If there are 2 or more dose reductions, then PK should be done on Day 3 and Day 4 instead of Day 4 and 
Day 5. 
b 
On dosing days, predose samples are to be collected within 60 minutes before administration of study 
treatment. 
c 
The PK sample is a time-matched blood sample to be taken immediately following (within 5 minutes) the 
ECG assessment) as described in Section 8.2.3. 
d 
ECG assessment is to be taken postdose at this time point. 
e 
If the oral decitabine/cedazuridine dosing level falls below Level 4 (please refer to Table 9 for further details), 
the timing of PK acquisition at this time point will be adjusted to be 1 day earlier. 
 


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8.5 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of AEs or SAEs can be found in Section 10.5. 
8.5.1 
Time Period and Frequency for Collecting Adverse Events and Serious Adverse 
Event Information 
All AEs and SAEs will be collected from the time the ICF is signed until 30 days after the last 
dose of study treatment. Any clinically significant findings that begin before the start of study 
treatment but after the ICF is signed will be recorded on the Medical History/Current Medical 
Conditions section of the eCRF, not in the AE section. However, if the event is related to a 
screening procedure it will be captured and recorded as an AE in the eCRF. Any clinically 
significant finding(s) observed after the start of study treatment will be recorded as an AE in the 
eCRF. 
If the subject starts a new anti-cancer treatment, including a new investigational treatment, the stop 
date for reporting obligations for this study will be based on whichever occurs earlier (ie, 30 days 
after the last dose of study drug or initiation of a new anticancer therapy). Details for recording 
AEs and SAEs are provided in Section 10.5. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours after the 
investigator is aware of the SAE, as indicated in Section 10.5. The investigator will submit any 
updated SAE data to the sponsor within 24 hours of the data becoming available. 
Investigators are not obligated to actively seek AE or SAE information ≥30 days after the last dose 
of study treatment. However, if the investigator becomes aware of an SAE or of a death at any 
time beyond 30 days after the last dose, and he/she considers the event to be reasonably related to 
the study treatment or study participation, the investigator must promptly notify the sponsor as 
described in Section 10.5.4. 
8.5.2 
Method of Detecting Adverse Events and Serious Adverse Events 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.5. 
Care should be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the study subject is the preferred method to inquire about AE 
occurrences (such as “Have you had any new symptoms, injuries, illnesses since your last visit?”).  
8.5.3 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until clinically relevant information is 
complete and reported to the sponsor; details are provided in Section 10.5.3.  
Additional information for follow-up requirement of AEs/SAEs is provided in Section 10.5.3. 


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8.5.4 
Regulatory Reporting Requirements for Serious Adverse Events 
• The sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB/IEC, and investigators. 
• Investigator safety reports must be prepared by the sponsor or sponsor’s designee for suspected 
unexpected serious adverse reactions according to local regulatory requirements and sponsor 
policy and forwarded to investigators as necessary.  
• An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file 
it along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.5.5 
Pregnancy 
• Details of all pregnancies in female subjects will be collected after the start of study treatment 
and until 180 days plus 5 half-lives of magrolimab (70 days), totaling 250 days (approximately 
8.5 months), after the last dose of either study treatment. Details of pregnancies in female 
partners of male subjects will be collected after the start of study treatment and until 90 days 
plus 5 half-lives of magrolimab (70 days), totaling 160 days (approximately 5 months), after 
the last dose of either study treatment. 
o Magrolimab has a longer half-life than oral decitabine/cedazuridine, which forms the basis 
of the requirements above. 
• If a pregnancy is reported, the investigator should follow the procedures outlined in 
Section 10.2. 
The investigator should counsel any female subject with a positive pregnancy test after the start of 
treatment, discussing any risks of continuing the pregnancy and any possible effects on the fetus. 
The investigator will record any occurrence of pregnancy on the Pregnancy Exposure Report Form 
Part 
I 
and 
email 
to 
Astex 
Clinical 
Safety 
and 
Risk 
Management 
(CS&RM; 
drugsafety@astx.com). After the outcome of the pregnancy, collect information by completing 
the Pregnancy Exposure Report Form Part II.  
8.5.6 
Definition of Dose-limiting Toxicities 
Dose-limiting toxicities are defined as any of the following toxicities at least possibly related to 
the treatment regimen as determined by the DSRC: 
• Drug-related Grade ≥3 non-hematologic events (except nausea, vomiting, or diarrhea if the 
events do not require tube feeding, total parenteral nutrition, or require or prolong 
hospitalization). 
• Grade 4 neutropenia and thrombocytopenia, not present prior to dosing, that last 28 days or 
longer should be considered a DLT unless clearly and solely due to the underlying disease. 


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o If the investigator suspects that the development of Grade 4 neutropenia or 
thrombocytopenia is drug related and the event continues for 7 days in Cycle 1, a BM 
assessment (no later than the 14th day of Grade 4 cytopenia) may be done, at the discretion 
of the investigator, to assist with the determination of DLT. 
• Delay of >2 weeks after Cycle 1 is complete due to drug-related toxicity. That is, if initiation 
of Cycle 2 is delayed for drug-related toxicity, the DLT window will expand accordingly. 
• Establishment of an MTD is not a goal of this study. However, the DSRC will assess the 
occurrence of DLTs in the DLT cohort (Section 4.1.1) to help ensure the study drug 
combination is safe. The DLT period has been defined as the first 2 cycles of oral 
decitabine/cedazuridine (from the start of administration to Cycle 1 Day 28) in the first 6 to 
approximately 18 subjects.  
8.5.7 
Specific Safety Management Guidelines 
8.5.7.1 
Anemia, Blood Cross-matching, and Packed Red Blood Cell Transfusion 
Procedures 
Magrolimab binds to RBCs and leads to erythrophagocytosis. In clinical studies, anemia is the 
most common treatment-related AE and is typically manifested as a decline in Hgb observed in 
the first 1 to 2 weeks of treatment. Subjects with low baseline Hgb level, especially those with 
cardiac history, should be monitored closely after initial administrations of magrolimab as 
preexisting anemia could be exacerbated. In general, a Hgb level of at least 9.5 g/dL or higher for 
subjects with cardiac comorbidities prior to the first magrolimab dose is recommended. Hgb ≥9 is 
required prior to the first two doses in priming and repriming of magrolimab. Red blood cell 
transfusions are permitted prior to study treatment to ensure adequate Hgb level. This, coupled 
with anemia from other causes in participants with cancers, means that care has to be taken with 
RBC cross-matching and packed RBC transfusions. There is a possibility that treatment with 
magrolimab may obscure assessment of RBC phenotyping, although this has not been observed in 
the subjects treated to date. 
Prior to initiation of magrolimab, extended RBC phenotyping or genotyping for minor antigens, 
type and screen (ABO/Rh), and DAT will be performed for each subject as described in 
Section 5.3.3. This, together with using the prior phenotype, will facilitate allocation of properly 
matched blood, should a blood transfusion be warranted. 
8.5.7.2 
Management of Infusion-related Reactions 
Infusion-related reactions are defined by the National Cancer Institute Common Terminology 
Criteria for Adverse Events (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” (Section 10.5). 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. 


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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. 
o 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 (eg, antihistamines, nonsteroidal anti-
inflammatory drugs, narcotics, corticosteroids, IV fluids), and prophylactic medications are 
indicated for ≤24 hours: 
o Stop the magrolimab infusion, begin an IV infusion of normal saline, and consider treating 
the participant with diphenhydramine 50 mg IV (or equivalent) and/or 500 mg to 750 mg 
of oral acetaminophen. 
o Remain at bedside and monitor participant until resolution of symptoms. 
o Corticosteroid therapy may also be given at the discretion of the investigator. 
o If the infusion is interrupted, wait until symptoms resolve, then restart the infusion at 50% 
of the original infusion rate. 
o 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. 
o If symptoms recur, stop infusion and disconnect participant from the infusion apparatus. 
No further magrolimab will be administered at that visit. 
o Premedications should be considered before any future infusions. 
o The amount of magrolimab infused must be recorded on the eCRF. 
o 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 (eg, 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 (eg, renal impairment, pulmonary 
infiltrates) and Grade 4 is described as having life-threatening consequences and where urgent 
intervention is indicated. 
o Immediately discontinue infusion of magrolimab. 
o Begin an IV infusion of normal saline and consider treating the participant as follows: 
Administer bronchodilators, epinephrine 0.2 mg to 1 mg of a 1:1000 solution for 
subcutaneous administration or 0.1 mg to 0.25 mg of a 1:10,000 solution injected slowly 


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for IV administration and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg 
IV (or equivalent), as needed. 
o
The participant should be monitored until the Investigator is comfortable that the symptoms
will not recur.
o
Participants who have Grade 4 infusion-related reactions occurring with the first dose
(priming dose) will be permanently discontinued from study treatment.
o
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 mg to 1000 mg), oral or IV diphenhydramine (25 mg to 50 mg), and
IV dexamethasone (4 mg 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.
o
Participants who receive premedication and still experience a Grade 3 or 4 infusion-related
reaction will be permanently discontinued from the study treatment.
o
For anaphylaxis, investigators should follow their institutional guidelines for treatment.
o
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.
9.0 
STATISTICAL CONSIDERATIONS
9.1 
Sample Size Determination
The CR rate with HMA monotherapy varies between studies and depends on severity of disease 
with an estimated overall range of approximately 10% to 20%. In Study ASTX727-02, for 
higher-risk MDS (IPSS-R >3) subjects, the observed CR rate with oral decitabine/cedazuridine 
was 22% (95% confidence interval [CI] of 14% to 32%). 
The combination of magrolimab plus azacitidine seems promising with better efficacy compared 
to azacitidine monotherapy, including a 50% CR rate, objective response rate of 92%, with an 
acceptable safety profile, suggesting that this combination offers advantages beyond HMA 
monotherapy (Garcia-Manero et al 2020). Assuming treatment of higher-risk MDS subjects with 
HMA oral decitabine and cedazuridine or with azacitidine is similar and that the combination of 
HMA oral decitabine/cedazuridine with magrolimab will result in a CR rate of approximately 40%, 
a sample size of approximately 100 subjects will allow for a greater than 80% power to rule out 
an HMA response rate of 20% (ie, lower bound of the exact 95% CI for the response rate will be 
greater than 20%). In addition, assuming that the response rate for this study will be approximately 
40%, a sample size of approximately 100 subjects will allow for 80% power to estimate a CI with 
half-width of approximately 10%. This sample size represents a preliminary estimate of the study 
size, however, the final sample size for the study may be revised based on the final response rate 
to be observed in the Phase 3 Magrolimab ENHANCE study. 


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9.2 
Analyses Sets 
For purposes of analysis, the following populations are defined: 
Table 15: 
Analysis Populations 
Population 
Description 
Enrolled  
All subjects who sign an ICF and meet all eligibility criteria as assessed by 
the investigator and sponsor. 
Efficacy  
All subjects who receive any study treatment.  
Safety  
All subjects who receive any study treatment.  
PK 
All subjects who have received study treatment and for whom PK samples 
were collected and successfully analyzed. 
ICF=informed consent form; PK=pharmacokinetic 
 
9.3 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to any efficacy assessment (first interim 
analysis for futility), and it will include a technical and detailed description of the statistical 
analyses described in this section. This section is a summary of the planned statistical analyses of 
the most important endpoints including primary and key secondary endpoints. 
9.3.1 
General Considerations 
All efficacy and safety endpoint parameters will be summarized descriptively. Continuous efficacy 
and safety endpoints will be summarized using the mean, standard deviation, median, minimum, 
and maximum, 25 and 75 percentiles). Frequency distributions (counts and percentages) will be 
used to summarize categorical endpoints.  
The primary efficacy analysis will be performed using a 2-sided 0.05 significance level. No 
adjustments for multiple endpoints is planned.  
It is anticipated that statistical summaries will be performed using SAS Version 9.4 or higher (SAS 
Institute, Inc., Cary, NC, USA) or higher. Additional software may be used to produce graphics 
and for statistical methodology not available in SAS.  
9.3.2 
Primary Endpoint(s) 
The primary efficacy endpoint for this study is the proportion of subjects who achieve CR. 
Response rate will be based on the investigator assessment for all treated subjects. Exact Clopper-
Pearson 95% CI will be presented. 
The analysis of duration of CR, ORR, OS, and PFS will be conducted using the Kaplan-Meier 
method based on subjects who achieved CR. Median duration of CR will be estimated with its 
95% CI for each treatment arm based on the Kaplan-Meier method. For the time-to-event 


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endpoints of the duration of CR and DOR will be based on subjects who achieved ORR. The 
median duration will be estimated with its 95% CI for each treatment arm. 
Analysis for all secondary efficacy endpoints will also be performed by pre-specified subgroups. 
Details of this analysis will be presented in the SAP. 
No formal hypothesis testing will be conducted for any key secondary endpoint. 
9.3.3 
Other Analysis 
PK analyses will be described in the SAP finalized before database lock. The population PK 
analysis will be presented separately from the main clinical study report. 
9.4 
Interim Analysis 
This is an open-label study. Ongoing analyses to help manage the study and support the DSRC 
reviews for safety and antitumor activity will be undertaken.  
One formal interim assessment of futility is planned after approximately 40 subjects have been 
treated with the oral decitabine/cedazuridine plus magrolimab and completed a minimum of 
6 cycles of treatment. The number of subjects to include in the interim analysis was chosen to 
minimize the chance of exposing subjects to an ineffective treatment. The expected CR is 
approximately 40%. However, the expected response rate may be revised once the results of the 
Phase 3 magrolimab ENHANCE study are available. If the achievement of the expected CR rate 
is questionable, possible study modification will be discussed with the DSRC. 
The decision to continue enrollment will be informed by the observed number of CRs (ie, CRs) 
and safety of the combination (ie, incidence and severity of adverse events). Table 16 provides the 
probabilities of observing varying frequency of response under different true response rates for a 
sample of approximately 40 subjects. For example, observing 8 or fewer responses out of 
40 treated subjects would suggest a low likelihood (11% chance) that the true response rate is 
>30% and 0.6% chance that the true response rate is >40%. On the other hand, observing 14 or 
more responses out of the 40 treated subjects would suggest a high likelihood (80% chance) that 
the true response is greater than 30%. Therefore, when 40 subjects are treated and evaluable for 
response assessment, if 8 or fewer responses are observed, the study will be discontinued. 
Similarly, if a two-stage Simon design is implemented to test whether the proportion responding 
(P) warrants continuation to the next phase (ie, H0: P ≤0.2 versus H1: P ≥0.3), Type I error rate of 
0.05, 80% power, and a total sample size of approximately 100 subjects, at the first stage 
(n approximately 40) the trial should be discontinued if 8 or fewer subjects respond to the 
treatment. Otherwise, the study will continue to the next stage.  
This calculation will be revised once the results of the Phase 3 magrolimab ENHANCE study are 
available and the true expected response is confirmed. 


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Table 16: 
Probabilities of Observing Varying Frequency of Response Under 
Different True Response Rates (40 Subjects) 
 
Event Rate 
No. Response (r) 
Probability 
20% 
30% 
40% 
50% 
8 
Prob(no. resp <= r| true p) 
0.593 
0.111 
0.006 
0.000 
9 
Prob(no. resp <= r| true p) 
0.732 
0.196 
0.016 
0.000 
10 
Prob(no. resp <= r| true p) 
0.839 
0.309 
0.035 
0.001 
11 
Prob(no. resp <= r| true p) 
0.912 
0.441 
0.071 
0.003 
12 
Prob(no. resp <= r| true p) 
0.957 
0.577 
0.129 
0.008 
13 
Prob(no. resp <= r| true p) 
0.981 
0.703 
0.211 
0.019 
14 
Prob(no. resp <= r| true p) 
0.992 
0.807 
0.317 
0.040 
15 
Prob(no. resp <= r| true p) 
0.997 
0.885 
0.440 
0.077 
16 
Prob(no. resp <= r| true p) 
0.999 
0.937 
0.568 
0.134 
Prob=probability; No.=number. 
 
9.5 
Toxicity Stopping Rule 
Any dosing adjustment made during assessment of DLTs in the DLT cohort will be applied as the 
dosing schedule for remainder of the study. During the study, a stopping rule for observation of 
excess toxicity will be implemented. The rate of AEs that would meet the DLT criteria 
(Section 8.5.6) of the study will be used to establish stopping guidelines for excess toxicity. For 
the duration of therapy, any event that occurs and is at least possibly related to study treatment, 
and that meets the criteria set out for DLT, will be counted. Sequential boundaries will be used to 
monitor the DLT rate (Ivanova et al 2005). Accrual will be halted if excessive numbers of subjects 
with DLTs are observed, that is, if the number of subjects with DLTs is equal to or exceeds bn out 
of n subjects who start Cycle 1. This is a Pocock-type stopping boundary that yields the probability 
of crossing the boundary at most 20% for DLTs when the presumed rate of DLTs is equal to 
approximately 20% (Table 17). In addition to this stopping rule, Astex may stop enrollment and/or 
terminate the study for safety concerns. 
Table 17: 
Criteria for Excess Toxicity for an Acceptable Dose-limiting Toxicity 
Rate of 20% 
Number of Subjects, n 1 
2 
3-4 
5-7  
8-10 
11-14  
15-17 
18-21 
22-25 
26-28 
Boundary, b 
- 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Number of Subjects, n 29-32 33-36 
37-40 
41-44 
45-48 
49-52 
53-56 
57-60 
61-64 
65-69 
Boundary, b 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Number of Subjects, n 70-73 74-77 
78-81 
82-85 
86-90 
91-94 
95-98 
99-100  
 
Boundary, b 
21 
22 
23 
24 
25 
26 
27 
28 
 
 
 
 


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10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines. 
o Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines. 
o Applicable laws and regulations. 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study subjects. 
• The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC. 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures. 
o Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 


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10.1.3 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the prospective 
subject or his/her legally authorized representative and answer all questions regarding the 
study. 
• Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative [defined in 21 CFR 50.3 (L)] will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act requirements, where applicable, and the 
IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was obtained before 
the subject was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
• Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A signed copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative. 
Subjects who are rescreened are required to sign a new ICF. 
10.1.4 
Data Protection 
• Subjects will be assigned a unique identifier by the sponsor. Any subject records or datasets 
that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 
• The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. 
• The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5 
Dissemination of Clinical Study Data 
All data generated in this study required to be publicly available will follow all local and global 
regulations. Requests to delay submission of study results will follow the appropriate regulatory 
procedures, if warranted. 
Peer reviewed publication(s) of the study results will follow the publication policy detailed in 
Section 10.1.9. 


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10.1.6 
Data Quality Assurance 
• All subject data relating to the study will be recorded on printed or eCRF unless transmitted to 
the sponsor or designee electronically (eg, laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues, study 
treatment storage and accountability, and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan.  
• The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
• The sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
• Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
10.1.7 
Source Documents 
• Definition of source data: All information in original records and certified copies of original 
records of clinical findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  
• Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the study center. 


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• The goal is to maximize data transmitted directly from source to the EDC system. For data 
transcribed in the eCRF from source documents, the data must be consistent with the source 
documents or the discrepancies must be explained. The investigator may need to request 
previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
10.1.8 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are not 
limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of subjects by the investigator. 
• Discontinuation of further study intervention development. 
10.1.9 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
• The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
10.1.10 
Clinical Trial Insurance 
Clinical trial insurance has been undertaken according to the laws of the countries where the study 
will be conducted. An insurance certificate will be made available to the participating study centers 
upon request. 
 


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10.2 
Appendix 2: Contraceptive and Barrier Guidance  
10.2.1 
Definitions 
Woman of Childbearing Potential  
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study treatment, additional evaluation should be considered. 
Women in the following categories are considered women of nonchildbearing potential: 
1) Premenarchal 
2) Premenopausal female with 1 of the following: 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
3) Postmenopausal female 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
i) A high follicle stimulating hormone level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, confirmation with more than 1 follicle stimulating hormone measurement 
is required.  
ii) Females on HRT and whose menopausal status is in doubt will be required to use 1 of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 


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10.2.2 
Contraception Guidance 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency  
• Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• Intrauterine device 
• Intrauterine hormone-releasing system (IUS)c 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia a highly effective contraceptive method provided that the partner is the sole sexual 
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. Spermatogenesis 
cycle is approximately 90 days. 
Note: documentation of azoospermia for a male participant can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
o Oral 
o Intravaginal 
o Transdermal 
o Injectable 
• Progestogen-only hormone contraception associated with inhibition of ovulationc 
o Oral 
o Injectable 
• Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
a 
Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for those participating in clinical studies. 
b Failure rate of <1% per year when used consistently and correctly. Typical use failure rates 
differ from those when used consistently and correctly. 
c 
Male condoms must be used in addition to hormonal contraception. If locally required, in 
accordance with Clinical Trial Facilitation Group guidelines, acceptable contraceptive 
methods are limited to those which inhibit ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable 
methods of contraception for this study. Male condom and female condom should not be used 
together (due to risk of failure with friction). 
 


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10.2.3 
Collection of Pregnancy Information 
Male subjects with partners who become pregnant 
• The investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is in this study. This applies only to male 
subjects who receive study treatment. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and submit 
it to the sponsor within 24 hours of learning of the partner’s pregnancy (drugsafety@astx.com). 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. Information 
on any children born will be collected until 1 year of age. Any termination of the pregnancy 
will be reported regardless of fetal status (presence or absence of anomalies) or indication for 
the procedure. 
Female subjects who become pregnant: 
• The investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate form 
and submitted to the sponsor within 24 hours of learning of a subject's pregnancy 
(drugsafety@astx.com).  
• The subject will be followed to determine the outcome of the pregnancy. The investigator will 
collect follow-up information on the subject and the neonate and the information will be 
forwarded to the sponsor. Information on any children born will be collected until 1 year of 
age. Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication, 
abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death [<20 weeks gestation], 
stillbirth [>20 weeks gestation], congenital anomalies, ectopic pregnancy), or elective 
termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is always 
considered to be an SAE and will be reported as such. Any post-study pregnancy related SAE 
considered reasonably related to the study treatment by the investigator will be reported to the 
sponsor as described in Section 10.5.4. While the investigator is not obligated to actively seek 
this information in former study subjects, he or she may learn of an SAE through spontaneous 
reporting. 
o Any subject who becomes pregnant while participating in the study will immediately 
discontinue study treatment. 
 


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10.3 
Appendix 3: Revised International Prognostic Scoring System for Myelodysplastic 
Syndromes (IPSS-R) 
The Revised International Prognostic Scoring System for myelodysplastic syndromes (IPSS-R) 
prognostic score values and prognostic risk categories/scores are presented in Table 18 and 
Table 19, respectively. 
The IPSS-R is an algorithm that uses clinical features of subjects with MDS (percentage BM blasts, 
Hgb, platelets, absolute neutrophil count) and 5 cytogenetic categories (very good, good, 
intermediate, poor, very poor) to stratify subjects into risk categories, which can then be used to 
inform appropriate treatment pathways. 
Table 18: 
Revised International Prognostic Scoring System for Myelodysplastic 
Syndromes Prognostic Score Values 
Prognostic 
Variable 
0 
0.5 
1 
1.5 
2 
3 
4 
Cytogenetics 
Very good 
- 
Good 
- 
Intermediate 
Poor 
Very poor 
BM blast, % 
≤2 
- 
>2% to <5% 
- 
5% to 10% 
>10% 
- 
Hemoglobin 
≥10 
- 
8 to <10 
<8 
- 
- 
- 
Platelets 
≥100 
50 to <100 
<50 
- 
- 
- 
- 
ANC 
≥0.8 
<0.8 
- 
- 
- 
- 
- 
“-”= not applicable; ANC=absolute neutrophil count; BM=bone marrow 
Source: Greenberg et al 2012 
 
Table 19: 
Revised International Prognostic Scoring System for Myelodysplastic 
Syndromes Prognostic Risk Categories/Scores 
Risk Category 
Risk Score 
Very low 
≤1.5 
Low 
>1.5-3 
Intermediate 
>3-4.5 
High 
>4.5-6 
Very high 
>6 
Source: Greenberg et al 2012 
 
 
 


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10.4 
Appendix 4: Molecular International Prognostic Scoring System for 
Myelodysplastic Syndromes (IPSS-M) 
The Molecular International Prognostic Scoring System for myelodysplastic syndromes (IPSS-M) 
is a recently designed and validated scoring system that incorporates molecular diagnostic testing 
into the risk stratification that is described above in Section 10.3 (Bernard et al 2022).  
The model was developed by profiling mutations in 152 genes in pretreatment diagnostic or 
peridiagnostic samples from 2957 subjects with MDS. The IPSS-M score was constructed from 
an adjusted Cox multivariable regression for LFS and used a weighted sum of prognostic variables 
observed for each subject (Table 20). 


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Table 20: 
IPSS-M Risk Score Construction From an Adjusted Cox 
Multivariable Regression for Leukemia-Free Survival 
Category and Variable 
Adjusted Hazard Ratio (95% CI)a 
Model Weightb 
Clinical 
BM blast, % 
1.07 (1.05–1.09) 
0.0704 
Min *platelets,250), ×109/L 
0.998 (0.997–0.999) 
−0.00222 
Hemoglobin, g/dL 
0.84 (0.81–0.88) 
−0.171 
Cytogenetic 
 
 
IPSS-R cytogenetic categoryc 
1.33 (1.21–1.47) 
0.287 
Gene main effects (17 variables, 16 genes)d 
TP53multihit 
3.27 (2.38–4.48) 
1.18 
MLLPTD 
2.22 (1.49–3.32) 
0.798 
FLT3ITD+TKD 
2.22 (1.11–4.45) 
0.798 
SF3B15q 
1.66 (1.03–2.66) 
0.504 
NPM1 
1.54 (0.78–3.02) 
0.430 
RUNX1 
1.53 (1.23–1.89) 
0.423 
NRAS 
1.52 (1.05–2.20) 
0.417 
ETV6 
1.48 (0.98–2.23) 
0.391 
IDH2 
1.46 (1.05–2.02) 
0.379 
CBL 
1.34 (0.99–1.82) 
0.295 
EZH2 
1.31 (0.98–1.75) 
0.270 
U2AF1 
1.28 (1.01–1.61) 
0.247 
SRSF2 
1.27 (1.03–1.56) 
0.239 
DNMT3A 
1.25 (1.02–1.53) 
0.221 
ASXL1 
1.24 (1.02–1.51) 
0.213 
KRAS 
1.22 (0.84–1.77) 
0.202 
SF3Bα 
0.92 (0.74 1.16) 
−0.0794 
Gene residuals (1 variable, 15 genes; possible values of 0, 1, or 2)e 
min(Nres,2) 
1.26 (1.12–1.42) 
0.231 
BM=bone marrow; CI=confidence interval; IPSS-M=International Prognostic Scoring System–Molecular; IPSS-
R=International Prognostic Scoring System–Revised; ITD=internal tandem duplication; min=minimum; 
PTD=partial tandem duplication; TKD=tyrosine kinase domain. 
a 
Hazard ratio is for the risk of leukemic transformation or death, adjusted for age, sex, and secondary/therapy-
related versus primary myelodysplastic syndrome. Cox regression was performed for 2428 subjects with 
available covariables and leukemia-free survival data. 
b 
Model weights were derived from the logarithm of the raw hazard ratios up to three significant digits. The 
following formula applies: IPSS-M score = 1.15467 + (∑variables jwj xj)/log(2), where wj denotes the weight of 
variable j, and xj the value of the variable j observed in a given patient. 
c 
IPSS-R cytogenetic categories were as follows: 0 denotes very good, 1 good, 2 intermediate, 3 poor, and 4 
very poor. 
d 
SF3B15q is the SF3B1 mutation in the presence of isolated del(5q) — that is, del(5q) only or with one 
additional aberration excluding -7/del(7q). SF3B1α is the SF3B1 mutation without comutations in BCOR, 
BCORL1, RUNX1, NRAS, STAG2, SRSF2, and del(5q). 
e 
Nres is defined as the number of mutated genes within the following list: BCOR, BCORL1, CEBPA, ETNK1, 
GATA2, GNB1, IDH1, NF1, PHF6, PPM1D, PRPF8, PTPN11, SETBP1, STAG2, and WT1. The variable 
min(Nres,2) can therefore take the value 0, 1, or 2. 
Source: Bernard et al 2022 
 
 


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10.5 
Appendix 5: Adverse Events and Serious Adverse Events: Definitions and 
Procedures for Recording, Evaluating, Follow-up, and Reporting 
Adverse events and/or adverse drug reactions will be graded according to the Common 
Terminology Criteria for Adverse Events (CTCAE) v5. 
View the National Cancer Institute (NCI) CTCAE electronically at the following web link: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf. 
10.5.1 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a subject or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered related to 
the study intervention. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (ie, not related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• New condition(s) detected or diagnosed after administration of study treatment(s) even 
though condition(s) may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. 
• A complication that occurs as a result of a protocol-specified procedure. 
• “Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported 
as an AE or SAE. Such instances will be captured as progressive disease and recorded on the 
appropriate eCRF. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfill the definition of an AE or SAE. 
 


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Events NOT Meeting the AE Definition 
• The disease being studied, and any symptoms, safety, laboratory, or other diagnostic findings 
due to underlying disease (including disease progression), unless judged by the investigator 
to be more severe than expected for the participant’s condition. See Section 10.5.3 for 
clarification on reporting SAEs in the setting of disease progression.  
• Medical or surgical procedures (eg, endoscopy, appendectomy, or other procedures for 
general health maintenance) are not considered AEs. The condition, excluding general health 
maintenance, that leads to the procedure is the AE and should be recorded on the appropriate 
eCRF. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• Anticipated day-to-day fluctuations (without worsening in intensity) of signs and symptoms 
related to pre-existing disease(s) or condition(s) that were present before first dose and were 
not related to screening procedures. 
 
10.5.2 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE. 
An SAE is defined as any serious adverse event that, at any dose: 
a. Results in death 
b. Is life-threatening 
• The term 'life-threatening' in the definition of 'serious' adverse event refers to an event in 
which the participant was at immediate risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization should be considered AEs if they are 
deemed clinically significant by the investigator. If a complication prolongs hospitalization 
or fulfills any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an SAE or AE. 


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d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. 
Other situations: 
• Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or 
may require medical or surgical intervention to prevent 1 of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
• Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that 
do not result in hospitalization, or development of drug dependency or drug abuse. 
 
10.5.3 
Recording, Severity, Relationship, and Follow-Up of AEs and/or SAEs, Lost to 
Follow-up and Stopping of AE/SAE Collection 
AE and SAE Recording 
• The reporting of AE/SAEs will start at the signing of the informed consent form (ICF) and 
continue through 30 days after the last and final dose of study treatment (see section on 
Stopping of AE/SAE Collection and Section 8.5.1). 
• If the subject starts a new anticancer treatment within those 30 days, including a new 
investigational treatment, the stop date for reporting obligations for this study will be the 
date when the subject started the anticancer therapy, or the 30 days whichever occurs earlier.  
• If an AE/SAE occurs between signing ICF and first dose administered, the AE/SAE will be 
recorded as medical history and not in the AE section. However, if the event is related to a 
screening procedure it will be captured and recorded as an AE in the eCRF. Any clinically 
significant finding(s) observed after the start of study treatment will be recorded as an AE 
in the eCRF (Section 8.5.1). 
• When reporting AE/SAE after one or more doses of study treatment has been administered, 
the AE/SAE will be considered a treatment emergent adverse event.  


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• Death should not be recorded or reported as AE/SAE but should be recorded as an outcome 
of a single event, eg, the cause of death. The condition that resulted in the death should be 
recorded and reported as the AE/SAE. 
• Disease progression as a term should not be reported as AE/SAE. When an SAE occurs in a 
subject and it is presumed to be, but not yet confirmed to be the cause of disease progression, 
the SAE must be reported. When and/or if disease progression is confirmed to be the cause, 
the previously reported SAE WILL NOT be retracted; therefore, the SAE shall remain in the 
database. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
pertaining to the event. 
• The investigator or delegated site staff will then record all relevant AE/SAE information in 
the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Astex CS&RM in lieu of completion of the AE/SAE eCRF page. 
• There may be instances when copies of medical records for certain cases are requested by 
Astex CS&RM. In these cases, all participant identifiers, except for the participant number, 
will be redacted on the copies of the medical records before submission to Astex CS&RM. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
• If there is a change in the serious criteria of an event such that a non-serious event becomes 
serious, an end date of the non-serious event will be entered. Then, the serious event will be 
entered as a separate event with the next day as the starting date.  
• In the example below, hypotension would be listed twice in the eCRF (once for the 
nonserious event and once for the serious event). 
Nonserious event (no serious criteria met): hypotension, Grade 2, onset 01 February 2021, 
end date 07 February 2021.  
Serious event (as hospitalization was added): hypotension, Grade 3, onset 08 February 
2021, end date 10 February 2021.  
Note that the dates do not overlap; the nonserious event must end prior to the serious event 
beginning. 
• If a serious event is downgraded to nonserious, a new entry will be created in the eCRF to 
note that change as described above. 
 


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AE Assessment of Severity 
Use the definitions found in the CTCAE v5 for grading the severity (intensity) of AEs. The 
CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each 
referenced AE. Should a subject experience any AE not listed in the CTCAE, use the following 
grading system to assess severity: 
• Grade 1 – Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
treatment not indicated. 
• Grade 2 – Moderate; minimal, local, or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living, such as preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc. 
• Grade 3 – Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care of 
activities of daily living, such as bathing, dressing, and undressing, feeding self, using the 
toilet, taking medications, and not bedridden. 
• Grade 4 – Life-threatening consequences; urgent intervention indicated. 
• Grade 5 – Death related to AE. 
NOTE: If a nonserious event is continuous, but changes in severity (CTCAE grade) over time, 
the site will have one record of the one unique event (preferred term) with the highest severity 
grade recorded for the entire duration of the event. Only a change from nonserious to serious 
requires a new entry. 
For example: If there is a change in severity, the highest severity should be recorded for the 
entire duration.  
For the AEs: 
Hypertension Grade 1, onset 15 January 2021, end date 20 January 2021.  
• Hypertension Grade 2, onset 21 January 2021, end date 30 January 2021.  
• Hypertension Grade 1, onset 31 January 2021, end date 19 February 2021.  
Record as:  
• Hypertension Grade 2, onset 15 January 2021 end date 19 February 2021. 
 
AE Assessment of Causality 
• The investigator is obligated to assess the relationship between study treatment(s) and each 
occurrence of each AE/SAE as related or not related to study treatment(s). 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment administration 
will be considered and investigated. 


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• The investigator will also consult the IB and/or Product Information (for marketed products) 
to assist in his/her assessment of a causality. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to Astex CS&RM. However, it is very important 
that the investigator always assesses causality for every event before the initial 
transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up information 
by modifying the SAE eCRF with the updated causality assessment. 
• The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated to elucidate the nature and/or 
causality of the AE or SAE as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• After the initial AE/SAE report, the investigator is required to actively follow each subject 
at subsequent visits/contacts. If any information necessary to evaluate the suspected adverse 
reaction/event is missing or unknown, the investigator should seek such information from 
the source of the report when available and without delay forward it to Astex CS&RM, as 
soon as the information is available. 
• It is the investigator’s responsibility to follow all SAEs and any additional information 
pertaining to an SAE, such as, but not limited to clinically relevant information and SAE 
outcomes. This additional information should be reported to Astex CS&RM without delay 
as soon as the information is available. 
• Additionally, the sponsor may request necessary information to evaluate serious adverse 
reaction/event and it is the investigator’s responsibility to report this information without 
delay to Astex CS&RM, as soon as possible. 
• If a subject dies during participation in the study or during a recognized follow-up period, 
the investigator will provide Astex CS&RM with a copy of any post-mortem findings 
including histopathology, if available. 
• New or updated information will be recorded in the eCRF or otherwise communicated to 
Astex CS&RM within 24 hours of receipt of the information. If the new or updated 
information is entered into the EDC system, it will automatically be sent to Astex CS&RM. 
 


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Lost to Follow-up and Stopping of AE/SAE Collection 
• If the investigator has determined that the subject is lost to follow-up, no further collection 
of AE/SAE information is required. Investigator shall document in the appropriate CRF that 
the subject was lost to follow-up.  
• All AE/SAE should be collected and reported to the sponsor (Astex CS&RM), 30 days 
following the last dose of the study treatment (investigational drug or control drug). 
However, if the investigator becomes aware of an SAE or of a death at any time beyond 30 
days after the last dose, and he/she considers the event to be reasonably related to the study 
treatment or study participation, the investigator must promptly notify the sponsor and the 
information should be reported without delay and as soon as the information is available 
(Section 8.5.1). 
• If the subject starts a new anticancer treatment within those 30 days, including a new 
investigational treatment, the stop date for reporting obligations for this study will be the 
date when the subject started the anticancer therapy, or the 30 days whichever occurs earlier.  
• If the subject has withdrawn full informed consent to participate in the study, investigator 
should not collect AE/SAE data beyond the date of withdrawing inform consent.  
• If the sponsor chooses to terminate or end the study, the sponsor will communicate 
expectations for data collection, including AE/SAEs. 
 
10.5.4 
Reporting of Overdose or Other Medication Errors: 
It is the responsibility of the investigator/site personnel to report to Astex CS&RM 
overdose or other medication errors 
If an overdose or other medication error should occur, please proceed as follows: 
• If no AE/SAE occurred as a result of the medication error, document the medication error 
as a protocol deviation according to the Protocol Deviation guidance. 
• If an AE occurred as a result of the medication error, document as an AE in the EDC system 
as well as a protocol deviation according to the Protocol Deviation guidance. 
• If an SAE occurred as a result of the medication error, document as an SAE in the EDC 
system as well as a protocol deviation according to the Protocol Deviation guidance. 


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10.5.5 
Reporting of SAEs 
SAE Reporting to Astex CS&RM via an Electronic Data Capture Tool 
• The primary mechanism for reporting an SAE to Astex CS&RM will be the electronic data 
capture (EDC) tool. 
• Study center staff will enter the SAE data into the EDC system as soon as it becomes 
available, but no longer than 24 hours from receipt of the information. The EDC system will 
automatically send a report to Astex CS&RM. 
• If a causality assessment is not provided, the default assessment will be ‘related’, for safety 
reporting purposes. 
• After the study is completed at a given site, the EDC tool will be taken off-line to prevent 
the entry of new data or changes to existing data. 
• If an investigational site receives a report of a new SAE from a study subject or receives 
updated data on a previously reported SAE after the EDC tool has been taken off-line, then 
the investigational site staff can report this information on a paper SAE report form (see the 
following section). 
 
SAE Reporting to Astex CS&RM when EDC Tool is Unavailable 
• If the EDC tool is unavailable, the site will enter the SAE data via paper SAE report form 
within 24 hours of first becoming aware of the SAE and email to Astex CS&RM.  
• Contact for SAE reporting is as follows: drugsafety@astx.com 
 


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10.6 
Appendix 6: Disease Response Assessment Based on International Working Group 
Criteria 
Response will be assessed in patient with MDS in part by using the 2006 IWG criteria (Cheson et 
al 2006), as defined in Table 21. Criteria for hematologic improvement are defined in Table 22. 
Table 21: 
Response Criteria in Myelodysplastic Syndromes (IWG 2006 Criteria) 
Category 
Response Criteria (responses must last ≥4 weeks) 
CR 
• 
BM ≤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: 
• 
BM blasts decreased by ≥50% over pretreatment but still >5% 
• 
Cellularity and morphology not relevant 
Marrow CR 
BM ≤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 BM 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 BM 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 
BM=bone marrow; CR=complete response; FAB=French-American-British classification; Hgb=hemoglobin; 
HI=hematologic improvement; IWG=International Working Group; MDS=myelodysplastic syndromes; 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 (eg, 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. 
Source: Cheson et al 2006 
 


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Table 22: 
Criteria for Hematologic Improvement 
Hematologic Improvement 
Response Criteria (responses must last ≥8 weeks) 
Erythroid response 
(pretreatment, <11 g/dL) 
1) Hgb increase by ≥1.5 g/dL and/or 
2) Relevant reduction of units of RBC transfusions by an absolute number of at least 
4 RBC transfusions/8 weeks compared with the pretreatment transfusion number 
in the previous 8 weeks. Only RBC transfusions given for a Hgb of ≤9.0 g/dL 
pretreatment will count in the RBC transfusion response evaluation. 
Platelet response 
(pretreatment, <100×109/L) 
1) Absolute increase of ≥30×109/L for subjects starting with >20×109/L platelets 
and/or 
2) Increase from <20×109/L to >20×109/L and by at least 100%. 
Neutrophil response 
(pretreatment, <1.0×109/L) 
At least 100% increase and an absolute increase >0.5×109/L. 
Hgb=hemoglobin; RBC=red blood cell 
Source: Criteria from 2006 MDS criteria (adapted from Cheson et al 2006) 
 
 
 


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10.7 
Appendix 7: Modifications During a COVID-19 Health Emergency 
10.7.1 
General Information 
This section describes modifications to the study protocol which may be implemented to allow 
flexibility in conducting this study during the current COVID-19 public health emergency or 
re-emergence of the same, while maintaining safety of trial participants, maintaining compliance 
with GCP, and minimizing risks to trial integrity. These modifications are intended to remain in 
effect only for the duration of the public health emergency related to COVID-19 and only in 
instances where the study cannot be conducted per the protocol. 
Any modifications to the study protocol must be discussed with the Astex medical monitor before 
implementing. 
10.7.2 
Study Status 
In extenuating circumstances (eg, during the COVID-19 pandemic), Astex may implement all or 
some of the following modifications: 
• Temporarily pause recruitment of new trial subjects. 
• Extend the duration of the study. 
• Postpone activation of study centers that have not been initiated. 
• Transfer study subjects to investigational study centers away from high-risk zones or closer to 
their home. 
• Convert physical visits to phone or video visits. 
• Modify to ensure that only strictly necessary visits are performed at study centers. 
• Allow laboratory tests and/or diagnostic tests to be conducted at a local laboratory/facility 
authorized/certified to perform such tests. 
• Make changes to the per-protocol informed consent process in accordance with IRB/IEC and 
institutional guidelines. 
10.7.3 
COVID-19 Benefit/Risk Assessment 
The safety of each trial participant is of primary importance. Astex will continually reassess the 
risks of conducting this clinical trial against the anticipated benefit for trial participants as the 
COVID-19 situation evolves and implement and document changes accordingly. 
It is possible that local circumstances may lead to a local change in risk assessment (eg, an 
escalation of the pandemic within a certain region); therefore, the need to implement additional 
measures may arise. Investigators may be asked to complete a risk assessment questionnaire 
provided by Astex. This assessment should be documented in the investigator’s site master file 
and communicated to Astex. 


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10.7.4 
Modifications to Study Conduct 
10.7.4.1 
Alternative Methods for IMP Shipment 
In extenuating circumstances (eg, during the COVID-19 pandemic) where standard approaches to 
dispensing study drug to subjects are not possible, alternative methods for dispensing study drug 
to subjects may be used Astex will work with individual sites to find acceptable alternative 
arrangements (eg, shipment of study drug from study center pharmacies to subjects) that assure 
compliant control of study drug and acceptable safety monitoring. Alternative methods for drug 
dispensing must be reviewed by Astex before implementing. 
10.7.4.2 
Study Visits and Procedures 
Study visits and procedures should be conducted as follows:  
• Study subjects may use local laboratories for standard laboratory testing (eg, hematology, 
serum chemistry, and urinalysis). 
• Telemedicine visits (ie, conducted via telephone and/or video calls, or in-person Telehealth 
Visits with a health professional) may be permitted in lieu of in-person visits to monitor AEs 
and subject safety. 
o Telemedicine visits must be approved by Astex and aligned with Institutional practice and 
local regulations. 
o Telemedicine visits must be appropriately documented in source documents. 
o Additional details regarding how to conduct telemedicine visits will be provided by Astex. 
In-person visits are required to assess eligibility, perform baseline assessments, and for primary 
outcome measures. Telemedicine visits would generally not be permitted for the following 
procedures unless approved by Astex: 
• Screening and/or predose Cycle 1 Day 1 assessments to determine eligibility. 
• Visits with blood sample collection for PK analysis. 
• Bone marrow collection. 
• Visits with magrolimab infusions.  
 
 


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10.8 
Appendix 8: Summary of Changes from Original to Amendment 1.0 
Protocol: ASTX727-10 Amendment 1.0; Date: 19 December 2022 
Rationale for Amendment 1.0: In the original protocol the schedule of administration of oral 
decitabine/cedazuridine is linked to the schedule of administration of magrolimab. This 
amendment treats the administration of oral decitabine/cedazuridine independently from the 
administration of magrolimab to allow for a dose delay of either drug. In addition, other minor 
changes were made to add clarification to the protocol. 
Summary of Changes 
Section 1.2 Schema: 
• Figure 1 Schema has been modified to show the administration of magrolimab in days instead 
of cycle-days.  
Section 1.3 Schedule of Activities 
• Table 1 Schedule of Activities for Oral Decitabine/Cedazuridine and Table 2 Schedule of 
Activities for Magrolimab have been created from the original Table 1 Schedule of Activities 
for Oral Decitabine/Cedazuridine. The new tables separate the activities associated with oral 
decitabine/cedazuridine from the activities associated with magrolimab. 
• Table 3 Dosing Schedule for Oral Decitabine/Cedazuridine and Table 4 Dosing Schedule for 
Magrolimab have been created from the original Table 2 Dosing Schedule for Oral 
Decitabine/Cedazuridine and Magrolimab. The new tables separate the dosing schedules 
associated with oral decitabine/cedazuridine from the dosing schedules associated with 
magrolimab. 
Section 2.3.2 Magrolimab 
• Dosing of magrolimab is changed from cycles to days. 
Section 4.1 Overall Design 
• The DLT group has been more clearly defined to be the first 6 to approximately 18 subjects 
enrolled during the first 2 cycles of oral decitabine/cedazuridine. 
• Cycle is newly defined for this protocol to be “a cycle of oral decitabine/cedazuridine, which 
is normally 28 days”. 
Section 4.1.1 Dose-Limiting Toxicity Cohort 
• The DLT group has been more clearly defined to be the first 6 to approximately 18 subjects 
enrolled during the first 2 cycles of oral decitabine/cedazuridine. 


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Section 4.5 Dosing Administration 
• Table 5 Treatment Administration Schedule for Oral Decitabine/Cedazuridine and  Table 6 
Treatment Administration Schedule for Magrolimab have been created from the original Table 
3 Treatment Administration Schedule. 
Section 4.6.1 Oral Decitabine/Cedazuridine 
• References have been added for the justification for the dose of oral decitabine/cedazuridine. 
In addition to the INQOVI US Prescribing Information, prescribing information from Australia 
and Canada have been included. 
Section 6.1 Description of Study Interventions Administered 
• In Table 8 Oral Decitabine/Cedazuridine and Magrolimab Products Used in Study, the 
magrolimab cycle-days have been changed to days. 
Section 6.6.1 Oral Decitabine/Cedazuridine Dose Modifications 
• Bullets have been added to clarify when to start administration of oral decitabine/cedazuridine 
after delays of different numbers of days. 
Section 6.6.2.1 Repriming for Magrolimab 
• The requirement for the repriming for magrolimab has been defined as a dose delay of 
magrolimab equivalent to 28 days or more.  
Section 7.1 Permanent Discontinuation of Study Treatment 
• Treatment 
discontinuation 
has 
been 
defined 
as 
discontinuation 
of 
both 
oral 
decitabine/cedazuridine and magrolimab. 
Section 10.5.4 Reporting of Overdose or Other Medication Errors 
• Section 10.5.4 is a new section that has been added. 
Section 11.0 REFERENCES 
• INQOVI Australia Product Information and INQOVI Canada Product Monograph were added 
as references. 


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11.0 
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