Trial Outcomes & Findings for Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) (NCT NCT04313881)

Last Updated: 2024-06-27

Results Overview

The percentage of participants (CR rate) are participants who reach morphologic CR (morphological blast of ≤ 5% and recovery of absolute neutrophil count (ANC), platelets, and hemoglobin from complete blood counts as well as peripheral blast) based on Investigator-assessed International Working Group (IWG) myelodysplastic syndrome (MDS) criteria on or prior to initiation of any new anticancer therapy, including stem cell therapy (SCT). Percentages were rounded off.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

539 participants

Primary outcome timeframe

From randomization up to 31.01 months

Results posted on

2024-06-27

Participant Flow

Participants were enrolled at study sites in North America, Asia-Pacific Region, and Europe.

854 participants were screened.

Participant milestones

Participant milestones
Measure	Magrolimab + Azacitidine Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Overall Study STARTED	268	271
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	268	271

Reasons for withdrawal

Reasons for withdrawal
Measure	Magrolimab + Azacitidine Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Overall Study Death	138	126
Overall Study Study terminated by sponsor	108	129
Overall Study Consent withdrawn	19	15
Overall Study Reason not Specified	3	1

Baseline Characteristics

Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.	Total n=539 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	64 Participants n=5 Participants	81 Participants n=7 Participants	145 Participants n=5 Participants
Age, Categorical >=65 years	204 Participants n=5 Participants	190 Participants n=7 Participants	394 Participants n=5 Participants
Age, Continuous	70 years STANDARD_DEVIATION 9.2 • n=5 Participants	68 years STANDARD_DEVIATION 9.8 • n=7 Participants	69 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants	94 Participants n=7 Participants	181 Participants n=5 Participants
Sex: Female, Male Male	181 Participants n=5 Participants	177 Participants n=7 Participants	358 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants n=5 Participants	21 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Non Hispanic or Latino	227 Participants n=5 Participants	219 Participants n=7 Participants	446 Participants n=5 Participants
Region of Enrollment Portugal	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Spain	11 Participants n=5 Participants	16 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported / Missing	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized American Indian Or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	209 Participants n=5 Participants	207 Participants n=7 Participants	416 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not reported / Missing	33 Participants n=5 Participants	41 Participants n=7 Participants	74 Participants n=5 Participants
Region of Enrollment Hong Kong	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Hungary	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	175 Participants n=5 Participants	177 Participants n=7 Participants	352 Participants n=5 Participants
Region of Enrollment United Kingdom	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment Switzerland	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment New Zealand	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Turkey	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Belgium	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Norway	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Finland	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Poland	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Italy	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment France	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Australia	40 Participants n=5 Participants	35 Participants n=7 Participants	75 Participants n=5 Participants
Region of Enrollment Germany	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Percentage of Participants With Complete Remission (CR)	21.3 percentage of participants Interval 16.5 to 26.7	23.6 percentage of participants Interval 18.7 to 29.1

PRIMARY outcome

Timeframe: From randomization up to 32.62 months

Population: Participants from intent-to-treat analysis set were analyzed.

OS is defined as the number of months measured from the date of randomization to the date of death from any cause. Kaplan Meier (KM) estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Overall Survival (OS)	15.9 months Interval 13.3 to 19.5	18.6 months Interval 14.9 to 26.2

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set who achieved CR were analyzed.

DOCR=Time from first CR date to the first date of relapse, disease progression (PD) or death, prior to initiation of any new anticancer therapy excluding SCT whichever occurs earlier. PD is defined as: \<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/dL / Transfusion dependence. Relapse is defined as return to pretreatment bone marrow blast percentage / decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets/ reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence. CR is defined in outcome measure 1. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=57 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=64 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Duration of CR (DOCR)	10.9 months Interval 8.9 to 16.7	11.1 months Interval 8.1 to Upper limit of CI was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

ORR is defined as the percentage of participants who reach objective response including CR, partial remission (PR), marrow CR or hematological improvement prior to initiation of any new anticancer therapy including SCT for MDS per IWG 2006 criteria per investigator's evaluation. CR is defined in outcome measure 1. PR is defined as all CR criteria if abnormal before treatment except, one marrow blasts decreased by ≥ 50% over pretreatment but still \> 5% cellularity and morphology not relevant. Marrow CR is defined as bone marrow ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment, stable disease with any hematological improvement, peripheral blood: if hematological improvement responses, they were noted in addition to marrow CR. Stable Disease: Failure to achieve at least PR, but no evidence of progression for \> 8 weeks. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Objective Response Rate (ORR)	53.7 percentage of participants Interval 47.6 to 59.8	58.7 percentage of participants Interval 52.6 to 64.6

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set with objective response were analyzed.

DOR is measured from time measurement criteria are first met for objective response to first date of relapse, disease progression (PD) /death, prior to initiation of any new anticancer therapy excluding SCT whichever occurs earlier. Disease progression and relapse have been defined in outcome measure number 3. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=144 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=159 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Duration of Response (DOR)	10.1 months Interval 8.1 to 12.5	10.2 months Interval 7.6 to 12.9

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set who were RBC transfusion-dependent at baseline were analyzed.

RBC transfusion independence rate is defined as the percentage of participants who have a 56-day or longer period with no RBC transfusions at any time between randomization and initiation of any new anticancer therapy, including SCT, among all participants who were RBC transfusion-dependent at Baseline. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=140 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=125 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Red Blood Cell (RBC) Transfusion Independence Rate	27.9 percentage of participants Interval 20.6 to 36.1	35.2 percentage of participants Interval 26.9 to 44.2

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

EFS is defined as the time from randomization to transformation to acute myeloid leukemia (AML) or death from any cause, whichever occurs first. Transformation assessments and deaths post SCT were included in the analysis. KM estimates were used for analysis

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Event Free Survival (EFS)	13.0 months Interval 10.2 to 15.9	12.9 months Interval 10.8 to 14.6

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set with TP53 mutation were analyzed.

CR in TP53 mutant population is defined as the percentage of participants who achieve a morphologic CR based on investigator assessments using IWG criteria on or prior to initiation of any new anticancer therapy, including SCT in TP53 mutant population. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=79 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=64 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Percentage of Participants With CR in Participants With TP53 Mutation	17.7 percentage of participants Interval 10.0 to 27.9	32.8 percentage of participants Interval 21.6 to 45.7

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

The MRD-negative response rate is defined as the percentage of participants who achieved a morphologic CR or marrow CR based on Investigator-assessed IWG criteria and reached MRD-negative disease status prior to initiation of any new anticancer therapy, including SCT. MRD-negative disease status was assessed using a multiparameter flow cytometry-based assay performed by a central laboratory. Morphologic CR and marrow CR are defined in outcome measures 1 and 4, respectively. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Minimal Residual Disease (MRD)-Negative Response Rate	21.6 percentage of participants Interval 16.9 to 27.1	22.5 percentage of participants Interval 17.7 to 28.0

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

Time to transformation to AML is defined as the time from randomization to the collection date of bone marrow sample leading to documented AML diagnosis. Transformation assessments post SCT were included in the analysis.KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Time to Transformation to AML	NA months Interval 21.2 to Median and upper limit of CI was not estimable due to low number of participants with events.	25.5 months Interval 25.5 to Upper limit of CI was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From randomization up to 31.01 months

Population: Participants from intent-to-treat analysis set were analyzed.

PFS is defined as the time from randomization to the date of documented DP (including treatment failure by IWG criteria or relapse after PR/CR), or death from any cause, whichever occurs first. Response assessments and deaths post SCT were included in the analysis. Treatment failure is defined as, Death during treatment or disease progression characterized by worsening cytopenia, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment. Relapse after CR or PR = Return to pretreatment bone marrow blast percentage / Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets / Reduction in Hgb concentration by ≥ 1.5 g/dL or transfusion dependence. CR, PR and PD are defined in outcome measures 1, 4 and 5 respectively. KM estimates were used for analysis.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Progression Free Survival (PFS)	9.0 months Interval 8.3 to 10.9	9.4 months Interval 8.6 to 11.4

SECONDARY outcome

Timeframe: Up to week 136

Population: Participants from intent-to-treat analysis set were analyzed.

The FACT-Anemia response rate is defined as the percentage of participants who showed clinically meaningful improvement in health-related quality of life (HRQoL) based on the score from the FACT-Anemia instrument prior to initiation of any new anticancer therapy, including SCT. The minimal clinically meaningful difference of 7.0 was used as cutoff for clinically meaningful improvement. The FACT-Anemia instrument consists of 5 subscales, including physical well-being, emotional well-being, functional well-being, social well-being, and anemia symptoms. Each subscale measures items on a 5-point Likert scale from 0 to 4, where 0 = not at all and 4 = very much. The subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest quality of life (QOL) and 100 denotes the highest QOL. Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=268 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=271 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate	37.7 percentage of participants Interval 31.9 to 43.8	49.8 percentage of participants Interval 43.7 to 55.9

SECONDARY outcome

Timeframe: First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years)

Population: Participants from safety analysis set with data available were analyzed. The safety analysis set included all randomized participants who took at least 1 dose of any study treatment, with treatment assignment designated according to the actual treatment received.

TEAE's are defined as any AEs with an onset date on or after the study drug start date, no later than 70 days after study drug last dose date or day before initiation of new anticancer therapy including SCT. If AE onset date is on or before last dose date, it is considered as TEAE regardless of start of new anticancer therapy. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product or other protocol imposed intervention, regardless of attribution. An event is considered "serious", if it results death, life-threatening, inpatient or prolongation hospitalization, incapacity or substantial disruption of the ability to conduct normal functions, a congenital anomaly/birth defect, and important medical events.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=263 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine n=264 Participants Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) TEAE	100 percentage of participants	99.6 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) Serious TEAE	71.9 percentage of participants	51.5 percentage of participants

SECONDARY outcome

Timeframe: Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336

Population: Pharmacokinetic (PK) analysis set included all participants who took at least 1 dose of magrolimab and had at least 1 measurable post-treatment serum concentration of magrolimab. Participants with data available at the given timepoint were analyzed.

Pretreatment assessments for the initial dose may be collected up to 72 hours before administration of study treatment; thereafter, pretreatment assessments are to be collected within 24 hours prior to study treatment administration.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=218 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Serum Concentration of Magrolimab Preinfusion Day 0	0 μg/mL Standard Deviation 0	—
Serum Concentration of Magrolimab Preinfusion Day 7	1.09 μg/mL Standard Deviation 15.575	—
Serum Concentration of Magrolimab Preinfusion Day 28	500.13 μg/mL Standard Deviation 256.129	—
Serum Concentration of Magrolimab Preinfusion Day 56	612.53 μg/mL Standard Deviation 315.037	—
Serum Concentration of Magrolimab Preinfusion Day 112	295.64 μg/mL Standard Deviation 178.952	—
Serum Concentration of Magrolimab Preinfusion Day 168	258.70 μg/mL Standard Deviation 150.259	—
Serum Concentration of Magrolimab Preinfusion Day 252	299.63 μg/mL Standard Deviation 168.944	—
Serum Concentration of Magrolimab Preinfusion Day 336	336.57 μg/mL Standard Deviation 241.789	—

SECONDARY outcome

Timeframe: Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days

Population: Participants in Immunogenicity Analysis Set with at least 1 baseline anti-drug antibody (ADA) sample and at least post-treatment ADA Sample were analyzed. Immunogenicity Analysis Set includes participants who took at least 1 dose of magrolimab and have at least 1 reported ADA result.

Percentages were rounded off.

Outcome measures

Outcome measures
Measure	Magrolimab + Azacitidine n=230 Participants Participants received the following magrolimab and azacitidine dosing regimens: Magrolimab was administered as an intravenous (IV) priming dose of 1 mg/kg on Days 1 and 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Following priming dose, magrolimab maintenance dose of 30 mg/kg was administered on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.6 years.	Placebo + Azacitidine Participants received the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo was administered as an IV on Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine 75 mg/m\^2 was administered either subcutaneously (SC) or IV on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle. The maximum duration of treatment was up to approximately 2.5 years.
Percentage of Participants With Positive Anti-magrolimab Antibodies	3.5 percentage of participants	—

Adverse Events

Magrolimab + Azacitidine

Serious events: 189 serious events

Other events: 246 other events

Deaths: 145 deaths

Placebo + Azacitidine

Serious events: 136 serious events

Other events: 256 other events

Deaths: 132 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER