Myeloid Malignancies
Conditions
Brief summary
The goal of this clinical study is to learn more about the safety and dosing of the study drug, magrolimab (Mag), in combination with anti-leukemia therapies in participants with acute myeloid leukemia (AML).
Detailed description
The anti-leukemia therapies are defined as follows: * Venetoclax (Ven) * Azacitidine (Aza) * Mitoxantrone, etoposide, and cytarabine (MEC) This study consists of 3 safety run-in cohorts; * Safety Run-in Cohort 1 (1L Unfit AML Mag + Ven + Aza) * Safety Run-in Cohort 2 (R/R AML Mag + MEC) * Safety Run-in Cohort 3 (Post-chemo Maintenance Mag + CC-486) Participants will receive treatment at the assigned dose level for at least 4 cycles in the Safety Run-in cohorts, after which they may continue at the assigned dose level or switch to the RP2D upon agreement between the investigator and the sponsor. After completion of each safety run-in cohort and identification of the RP2D for that cohort, participants may be enrolled into the corresponding Phase 2 cohorts; * Phase 2 Cohort 1 (1L Unfit AML Mag + Ven + Aza) * Phase 2 Cohort 2 (R/R AML Mag + MEC) * Phase 2 Cohort 3 (Post-chemo Maintenance Mag + CC-486) Cycle length is 28 days for both the Safety Run-in and Phase 2 cohorts. Note: All cohorts are closed to screening and enrollment.
Interventions
DRUGMagrolimab
Administered intravenously
DRUGAzacitidine
Administered either subcutaneously or IV, 75 mg/milligram per square (m\^2) on Days 1 to 7 or Days 1 to 5, 8 and 9 during every cycle
DRUGVenetoclax
Administered orally at a dose of 100 mg on Day 1, 200 mg on Day 2, 400 mg on Days 3-28 during Cycle 1, followed by 400 mg on Days 1-28 during every cycle
DRUGMitoxantrone
Administered intravenously, 8 mg/m\^2 on Days 1-5 during Cycle 1 to Cycle 3
DRUGEtoposide
Administered intravenously, 100 mg/m\^2 on Days 1-5 during Cycle 1 to Cycle 3
DRUGCytarabine
Administered intravenously, 1000 mg/m\^2 on Days 1-5 during Cycle 1 to Cycle 3
DRUGCC-486
Administered orally, 300 mg on Days 1-14 during each cycle
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
After completion of Safety Run-in cohorts and identification of the RP2D for the specific cohorts, participants may be enrolled to the corresponding Phase 2 cohorts.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: All Individuals: * White blood cell (WBC) count ≤ 20 × 10\^3/microliter (μL) prior to first dose of study treatment. If the individual's WBC count is \> 20 × 10\^3/ μL prior to first dose of study treatment, the individual can be enrolled, assuming all other eligibility criteria are met * For individuals with prior cardiac history, the hemoglobin must be ≥ 9 grams per deciliter (g/dL) prior to initial dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility * Adequate liver function * Adequate renal function * Individual has provided informed consent * Individual is willing and able to comply with clinic visits and procedures outlined in the study protocol * Pretreatment blood cross-match completed * Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol- specified method(s) of contraception * Individuals must be willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (trephines), unless not feasible as determined by the investigator and discussed with the sponsor Safety Run-in Cohort 1 and Phase 2 Cohort 1 (Ineligible (1L) Unfit acute myeloid leukemia (AML) Magrolimab + Venetoclax + Azacitidine): * Newly diagnosed, previously untreated individuals with histological confirmation of AML by world health organization (WHO) criteria who are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, comorbidity, or other factors. Individuals must be considered ineligible for induction therapy defined by the following: * ≥ 75 years of age * ≥ 18 to 74 years of age with at least 1 of the following comorbidities: * Diffusing capacity of the lung of carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65% * Left ventricular ejection fraction (LVEF) ≤ 50% * Creatinine clearance (CrCl) \< 45 mL/min calculated by the Cockcroft-Gault formula or measured by 24 hours' urine collection * Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy that must be approved by the sponsor medical monitor before study enrollment * Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 * Individuals who have not received prior anti-leukemia therapy for AML (excluding hydroxyurea or oral etoposide), hypomethylating agent (HMA), low-dose cytarabine, and/or venetoclax. Individuals with prior myelodysplastic syndrome (MDS) cannot have received a prior HMA, venetoclax, or a chemotherapeutic agent. Other prior MDS therapies, including but not limited to lenalidomide, erythroid-stimulating agents, or similar red blood cell (RBC) -direct therapies, are allowed * Individuals who have not received strong and/or moderate cytochrome P450 enzyme (CYP) 3A inducers (such as St. John's Wort) within 7 days prior to the initiation of study treatment * Individuals who have not consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment or are willing to discontinue consumption of these while receiving study drug * Individuals without malabsorption syndrome or other conditions that preclude enteral route of administration Safety Run-in Cohort 2 and Phase 2 Cohort 2 (Relapsed/refractory (R/R) AML Magrolimab+Mitoxantrone + Etoposide + Cytarabine (MEC)): * Individuals with confirmation of AML by WHO criteria who are refractory to or have experienced first relapse after initial intensive chemotherapy. Note: Individuals who are relapsed after or are refractory to more than 1 line of anti-AML treatment are not eligible. Individuals who relapsed after undergoing stem cell transplant may be eligible. * At least 2 weeks must have elapsed since any prior anti-leukemia agents. Note: Localized non-central nervous system (CNS) radiotherapy, hydroxyurea, and erythroid and/or myeloid growth factors are not criteria for exclusion * ECOG performance status of 0 to 2 * Individuals with LVEF \> 50%, lack of symptomatic congestive heart failure, or clinically significant cardiac arrhythmias * Must not have been treated with trastuzumab within 7 months prior to the initiation of study treatment * Individuals who have not previously received maximum cumulative doses of anthracyclines and anthracenediones * Individuals without degenerative or toxic encephalopathies. * Individuals who did not undergo hematopoietic SCT in the past 100 days, are not on immunosuppressive therapy post SCT in the 2 weeks prior to the first dose of study treatment, or have no active clinically significant graft-versus-host disease. Safety Run-in Cohort 3 and Phase 2 Cohort 3 (Post-chemo Maintenance Magrolimab+CC-486): * Individuals with histological confirmation of AML by WHO criteria who achieved a complete remission (CR) or CR with incomplete hematologic recovery (CRi) with presence of MRD (MRD positive by flow cytometry assay, defined as ≥ 0.1% detectable MRD) after intensive induction chemotherapy with or without consolidation therapy, prior to starting maintenance therapy for newly diagnosed AML, and who are not candidates for hematopoietic stem cell transplantation (SCT) within 1 year of achievement of initial remission * ECOG performance status of 0 to 2 * Individuals without malabsorption syndrome or other conditions that preclude enteral route of administration Key
Exclusion criteria
* Positive serum pregnancy test * Breastfeeding female * Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient * Individuals receiving any live virus vaccine within 4 weeks prior to initiation of study treatments * Prior treatment with cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPα) -targeting agents * Current participation in another interventional clinical trial * Known inherited or acquired bleeding disorders * Clinical suspicion of or documented active CNS involvement with AML * Individuals who have acute promyelocytic leukemia * Significant disease or medical conditions, as assessed by the investigator 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 * Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anti-cancer therapies and have had no evidence of active malignancy for over 1 year. Previous hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion * Note: Individuals on maintenance therapy alone who have no evidence of active malignancy for at least ≥ 1 year are eligible. * Known active or chronic hepatitis B or C infection or human immunodeficiency virus Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate (Cohorts 1 and 2) | Up to 2 years | CR rate was the percentage of participants who achieved CR (CR without minimal residual disease (CRMRD-) or complete remission with positive or unknown minimal residual disease (CRMRD+/unk)) as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-cancer therapy. CRMRD- and CRMRD+/unk were defined as neutrophils \>1.0 ×10\^9/L; platelets \>100 × 10\^9/L and \<5% bone marrow blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRMRD- status as determined using multiparameter flow cytometry with a sensitivity of \< 0.1%. Assessment of leukemia response in participants with acute myeloid leukemia (AML) were conducted based on the European Leukemia Net (ELN) recommendations for AML. Percentages were rounded-off. Clopper-Pearson method was used for outcome measure analysis. |
| Minimal Residual Disease Negative Complete Remission Rate (Cohort 3) | Up to 2 years | The minimal residual disease (MRD) negative CR rate was defined as the percentage of participants who maintain CR as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments, as determined using multiparameter flow cytometry with a sensitivity of \< 0.1% while on study prior to initiation of any new anti-AML therapy. Assessment of leukemia response in participants with AML were conducted based on the ELN recommendations for AML. CR was defined in outcome measure #1. |
| Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3) | Up to 28 days | DLTs were defined as any Grade 4 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity (that had worsened in severity from pretreatment baseline) during the 4-week DLT assessment period and was related to magrolimab or magrolimab combination. |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3) | First dose date up to 1.7 years plus 70 days | TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 70 days after the study drug last dosing date or the day before initiation of new anticancer therapy including SCT, whichever comes first. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Percentages were rounded-off. |
| Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3) | First dose date up to 1.7 years plus 70 days | Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 70 days or the day before initiation of any new anticancer therapy including SCT, whichever comes first. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment emergent. Percentages were rounded-off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of CR/CRh (Cohorts 1 and 2) | Up to 2 years | Duration of CR/CRh was measured from the time the assessment criteria are first met for CR (CRMRD- or CRMRD+/unk) or CRh until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. CRh was defined in outcome measure #6. KM estimates were used in outcome measure analysis. |
| Event-Free Survival (EFS) (Cohorts 1 and 2) | Up to 2 years | EFS was defined as the time from the date of the first dose of study treatment to the earliest date of documented relapse from CR, treatment failure (defined as failure to achieve CR during the response assessment window (the first treatment dosing date until before the fifth cycle of magrolimab + venetoclax + azacitidine in Cohort 1 and the first treatment dosing date until before the third cycle of magrolimab + MEC in Cohort 2), or death from any cause within the response assessment window. Response assessments post SCT were included in the analysis. Deaths post SCT or new anti-AML therapies (except SCT and post SCT maintenance) were included. Those who were not observed to have one of these events during the study were censored at the date of their last response assessment during the study. Day 1 of treatment was assigned as the event date for participants with treatment failure. CR was defined in outcome measure #1. KM estimates were used in outcome measure analysis. |
| Relapse-Free Survival (RFS) Rate (Cohort 3) | Up to 2 years | RFS was defined as the time from the first dose of study treatment until the first date of AML relapse or death from any cause, whichever came first. |
| MRD Negative CR/CRi Rate (Cohort 3) | Up to 2 years | MRD negative CR/CRi rate was defined as the percentage of participants who maintained CR/CRi as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments as determined using multiparameter flow cytometry with a sensitivity of \< 0.1% while on study prior to initiation of any new anti-AML therapy. CR was defined in outcome measure #1. CRi was defined in outcome measure #6. |
| Duration of Minimal Residual Disease Negative Complete Remission (Cohort 3) | Up to 2 years | Duration of MRD negative CR was measured from the time the participant achieved MRD-negative status and maintained CR until the first date of AML relapse, loss of MRD negative status, or death (including assessments post SCT). CR was defined in outcome measure #1. |
| Duration of MRD Negative CR/CRi (Cohort 3) | Up to 2 years | Duration of MRD negative CR/CRi was measured from the time the participant achieved MRD-negative status (first of the 2 consecutive MRD negative bone marrow assessments) and maintained CR/CRi until the first date of AML relapse, loss of MRD negative status, or death (including assessments post SCT). CR was defined in outcome measure #1. CRi was defined in outcome measure #6. |
| Overall Response Rate (ORR) | Up to 2 years | ORR was the percentage of participants who achieved CR (CRMRD- or CRMRD+/unk), CRi, CRh, PR, or MLFS as per investigator based on prespecified criteria before starting any new anti-AML therapy (including SCT). CRi and CRh were defined as neutrophils \>0.5 x 10\^9/L, platelets \> 50 x 10\^9/L (except residual neutropenia (\<1.0 × 10\^9/L) or thrombocytopenia (\<100 × 109/L) for CRi) and bone marrow blasts \<5%; Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. PR: Neutrophils \>1.0 x 10\^9/L, platelets \>100 x 10\^9/L, bone marrow blasts reduced to 5%-25%, and a ≥50% reduction from baseline. Blasts \<5% with Auer rods may also be considered a PR. MLFS: Bone marrow blasts \<5%, absence of circulating blasts or Auer rods, no extramedullary disease, marrow should not merely be aplastic; at least 200 cells or 10% cellularity, and no requirement for hematologic recovery. CR was defined in outcome measure #1. Percentages were rounded-off. |
| Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3) | Up to 2 years | RBC transfusion independence rate was the percentage of participants who had a 56-day or longer period with no RBC or whole blood transfusion at any time between the date of the first dose and discontinuation of study treatment among all participants who were RBC transfusion-dependent at baseline. RBC transfusion independence rate was reported as 2 categories: 1. Conversion rate: Participants who received an RBC or whole blood transfusion within the 28 days prior to the first dose of study treatment, and were RBC transfusion-independent post-baseline. 2. Maintenance rate: Participants who were RBC transfusion independent at baseline and maintained it post-baseline. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis. |
| Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3) | Up to 2 years | Platelet transfusion independence rate was the percentage of participants who had a 56-day or longer period with no platelet transfusions at any time between the date of the first dose and discontinuation of study treatment among all participants who were platelet transfusion-dependent at baseline. Platelet transfusion independence rate was reported as 2 categories: 1. Conversion rate: Participants who received an platelet transfusion within 28 days prior to the first dose of study treatment, 2. Maintenance rate: Participants who were platelet transfusion independent at baseline and maintained it post-baseline. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis. |
| Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Cohort 1: Predose: Days 1, 8, 29, 57, 113, 169, 253 and 337; Cohort 2: Days 1, 8, 29 and 57 | — |
| Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2) | Up to 2 years | Percentages were rounded-off. |
| Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2) | Up to 2 years | — |
| Overall Survival (OS) (Cohorts 1, 2 and 3) | Up to 2 years | OS was measured from the date of the first dose of study treatment to the date of death from any cause. Those who were not observed to die during the study were censored at last date they were known to be alive. KM estimates were used in outcome measure analysis. |
| Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2) | Up to 2 years | CR/CRh rate was the percentage of participants who achieved CR (CRMRD- or CRMRD+/unk) or CRh as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-AML therapy (including SCT). CR was defined in outcome measure 1. CRh was defined in outcome measure 6. Percentages were rounded-off. Clopper-Pearson exact method was used in outcome measure analysis. |
| Duration of Response (DOR) (Cohorts 1 and 2) | Up to 2 years | DOR was measured from the time assessment criteria that were met for CR (CRMRD- or CRMRD+/unk), CRi, CRh, PR, or MLFS, whichever was first recorded, until the first date of AML relapse, progressive disease, or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies.CR was defined in outcome measure #1. CRi, CRh, PR, or MLFS were defined in outcome measure #6. Kaplan-Meier (KM) estimates were used in outcome measure analysis. |
| Duration of Complete Remission (DCR) (Cohorts 1 and 2) | Up to 2 years | DCR was measured from the time the assessment criteria were first met for CR (CRMRD- or CRMRD+/unk) until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. KM estimates were used in outcome measure analysis. |
| Duration of CR/CRi (Cohorts 1 and 2) | Up to 2 years | Duration of CR/CRi was measured from the time the assessment criteria were first met for CR (CRMRD- or CRMRD+/unk) or CRi until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. CRi was defined in outcome measure #6. KM estimates were used in outcome measure analysis. |
Countries
Australia, United Kingdom, United States
Participant flow
Recruitment details
77 participants were screened.
Pre-assignment details
Participants were enrolled at study sites in the United States, the United Kingdom and Australia. No participants were enrolled in Cohort 3, so, results are reported only for Cohorts 1 and 2. Due to limited number of participants enrolled, and because all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and Phase 2 Cohorts were combined in outcome measures (OMs) except DLT OM, for which data was collected only in Safety Run-in Cohorts
Participants by arm
| Arm | Count |
|---|---|
| Safety Run-in Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine Participants in Safety Run-in Cohort 1 with untreated AML who were unfit for chemotherapy received magrolimab, 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then every week (QW) x 5 doses; 30 mg/kg over 2 hours every 2 weeks (Q2W) beginning 1 week after the 5 weekly 30 mg/kg dose, intravenously (IV) for 28 days.
Participants also received azacitidine 75 mg/m\^2 on Days 1-7 or Days 1-5, 8 and 9, subcutaneously (SC) or IV, along with venetoclax oral tablets, 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3 to 28 of Cycle 1, 400 mg on Days 1 to 28. | 7 |
| Safety Run-in Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) Participants in Safety Run-in Cohort 2 with R/R AML received magrolimab, 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose, IV for 28 days. Participants also received MEC: mitoxantrone 8 mg/m\^2 IV, etoposide 100 mg/m\^2 IV and cytarabine 1000 mg/m\^2 IV on Days 1 to 5 for 28 days. | 6 |
| Phase 2 Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine Participants in Phase 2 Cohort 1 with untreated AML who were unfit for chemotherapy received the recommended dose of magrolimab, 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg over 2 hours Q2W beginning 1 week after the 5 weekly 30 mg/kg dose, IV in 28-day cycles.
Participants also received azacitidine 75 mg/m\^2 on Days 1-7 or Days 1-5, 8 and 9, SC or IV, along with venetoclax oral tablets, 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3 to 28 of Cycle 1, 400 mg on Days 1 to 28 in Cycle 2 and consecutive cycles for every 28-day cycle. The treatment duration was up to a maximum of 1.7 years. | 11 |
| Phase 2 Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) Participants in Phase 2 Cohort 2 with R/R AML received the recommended dose of magrolimab, 1 mg/kg on Days 1, 4; 15 mg/kg on Day 8; 30 mg/kg on Days 11, 15, and then QW x 5 doses; 30 mg/kg Q2W beginning 1 week after the 5 weekly 30 mg/kg dose, IV up to 1.7 years. Participants also received MEC: mitoxantrone 8 mg/m\^2 IV, etoposide 100 mg/m\^2 IV and cytarabine 1000 mg/m\^2 IV on Days 1 to 5 for three 28-day cycles. | 30 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Phase 2 Period | Death | 0 | 0 | 0 | 5 | 18 | 0 |
| Phase 2 Period | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 |
| Phase 2 Period | Study Terminated By Sponsor | 0 | 0 | 0 | 1 | 0 | 0 |
| Phase 2 Period | Withdrew Consent | 0 | 0 | 0 | 0 | 2 | 0 |
| Safety Run-in Period | Death | 5 | 6 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Safety Run-in Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Safety Run-in Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Phase 2 Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Phase 2 Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 74 years STANDARD_DEVIATION 8.6 | 47 years STANDARD_DEVIATION 14.9 | 72 years STANDARD_DEVIATION 4.3 | 51 years STANDARD_DEVIATION 14 | 58 years STANDARD_DEVIATION 16.1 |
| Age, Customized Age, Categorical >= 50 - < 75 Years | 3 Participants | 3 Participants | 9 Participants | 17 Participants | 32 Participants |
| Age, Customized Age, Categorical < 50 Years | 0 Participants | 3 Participants | 0 Participants | 13 Participants | 16 Participants |
| Age, Customized Age, Categorical >= 75 Years | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 11 Participants | 23 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 2 Participants | 9 Participants | 23 Participants | 41 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 5 Participants | 14 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 6 Participants | 16 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 7 | 6 / 6 | 5 / 11 | 19 / 30 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 11 / 11 | 29 / 30 |
| serious Total, serious adverse events | 7 / 7 | 3 / 6 | 11 / 11 | 18 / 30 |
Outcome results
Primary
Complete Remission (CR) Rate (Cohorts 1 and 2)
CR rate was the percentage of participants who achieved CR (CR without minimal residual disease (CRMRD-) or complete remission with positive or unknown minimal residual disease (CRMRD+/unk)) as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-cancer therapy. CRMRD- and CRMRD+/unk were defined as neutrophils \>1.0 ×10\^9/L; platelets \>100 × 10\^9/L and \<5% bone marrow blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. CRMRD- status as determined using multiparameter flow cytometry with a sensitivity of \< 0.1%. Assessment of leukemia response in participants with acute myeloid leukemia (AML) were conducted based on the European Leukemia Net (ELN) recommendations for AML. Percentages were rounded-off. Clopper-Pearson method was used for outcome measure analysis.
Time frame: Up to 2 years
Population: The Full Analysis Set included all enrolled participants who received at least 1 dose of any study treatment, with treatment group designated according to the assigned treatment.~Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Complete Remission (CR) Rate (Cohorts 1 and 2) | 38.9 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Complete Remission (CR) Rate (Cohorts 1 and 2) | 25 percentage of participants |
p-value: 0.1794One Group Chi-Square test
Primary
Minimal Residual Disease Negative Complete Remission Rate (Cohort 3)
The minimal residual disease (MRD) negative CR rate was defined as the percentage of participants who maintain CR as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments, as determined using multiparameter flow cytometry with a sensitivity of \< 0.1% while on study prior to initiation of any new anti-AML therapy. Assessment of leukemia response in participants with AML were conducted based on the ELN recommendations for AML. CR was defined in outcome measure #1.
Time frame: Up to 2 years
Population: As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
Primary
Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3)
DLTs were defined as any Grade 4 or higher hematologic toxicity or Grade 3 or higher nonhematologic toxicity (that had worsened in severity from pretreatment baseline) during the 4-week DLT assessment period and was related to magrolimab or magrolimab combination.
Time frame: Up to 28 days
Population: The DLT Evaluable Analysis Set included all participants in the Safety Analysis Set who were enrolled in the Safety Run-in cohorts, have safety assessments through the protocol-specified DLT assessment window (first 4 weeks of study dosing, inclusive), and fulfill the criteria for evaluation for DLT specified in the protocol.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3) | 0 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) (Safety Run-in Cohorts 1, 2 and 3) | 0 percentage of participants |
Primary
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3)
TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 70 days after the study drug last dosing date or the day before initiation of new anticancer therapy including SCT, whichever comes first. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Percentages were rounded-off.
Time frame: First dose date up to 1.7 years plus 70 days
Population: The Safety Analysis Set included all participants who received at least 1 dose of study treatment, with treatment assignments designated according to the actual treatment received.~Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3) | 100 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) (Cohorts 1, 2 and 3) | 97.2 percentage of participants |
Primary
Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3)
Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 70 days or the day before initiation of any new anticancer therapy including SCT, whichever comes first. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment emergent. Percentages were rounded-off.
Time frame: First dose date up to 1.7 years plus 70 days
Population: Participants in the Safety Analysis Set were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3) | 100 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities (Cohorts 1, 2 and 3) | 97.2 percentage of participants |
Secondary
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2)
CR/CRh rate was the percentage of participants who achieved CR (CRMRD- or CRMRD+/unk) or CRh as determined by the investigator based on prespecified criteria while on study prior to initiation of any new anti-AML therapy (including SCT). CR was defined in outcome measure 1. CRh was defined in outcome measure 6. Percentages were rounded-off. Clopper-Pearson exact method was used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2) | 44.4 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR/CRh) (Cohorts 1 and 2) | 30.6 percentage of participants |
Secondary
Duration of Complete Remission (DCR) (Cohorts 1 and 2)
DCR was measured from the time the assessment criteria were first met for CR (CRMRD- or CRMRD+/unk) until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. KM estimates were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set who achieved CR were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Duration of Complete Remission (DCR) (Cohorts 1 and 2) | 15.9 months |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Duration of Complete Remission (DCR) (Cohorts 1 and 2) | 8.7 months |
Secondary
Duration of CR/CRh (Cohorts 1 and 2)
Duration of CR/CRh was measured from the time the assessment criteria are first met for CR (CRMRD- or CRMRD+/unk) or CRh until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. CRh was defined in outcome measure #6. KM estimates were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set who achieved CR/CRh were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Duration of CR/CRh (Cohorts 1 and 2) | 15.9 months |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Duration of CR/CRh (Cohorts 1 and 2) | 8.7 months |
Secondary
Duration of CR/CRi (Cohorts 1 and 2)
Duration of CR/CRi was measured from the time the assessment criteria were first met for CR (CRMRD- or CRMRD+/unk) or CRi until the first date of AML relapse or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies. CR was defined in outcome measure #1. CRi was defined in outcome measure #6. KM estimates were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set who achieved CR/CRi were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Duration of CR/CRi (Cohorts 1 and 2) | 15.9 months |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Duration of CR/CRi (Cohorts 1 and 2) | 8.7 months |
Secondary
Duration of Minimal Residual Disease Negative Complete Remission (Cohort 3)
Duration of MRD negative CR was measured from the time the participant achieved MRD-negative status and maintained CR until the first date of AML relapse, loss of MRD negative status, or death (including assessments post SCT). CR was defined in outcome measure #1.
Time frame: Up to 2 years
Population: As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
Secondary
Duration of MRD Negative CR/CRi (Cohort 3)
Duration of MRD negative CR/CRi was measured from the time the participant achieved MRD-negative status (first of the 2 consecutive MRD negative bone marrow assessments) and maintained CR/CRi until the first date of AML relapse, loss of MRD negative status, or death (including assessments post SCT). CR was defined in outcome measure #1. CRi was defined in outcome measure #6.
Time frame: Up to 2 years
Population: As no participants were enrolled in Cohort 3, data were not collected for this outcome measure.
Secondary
Duration of Response (DOR) (Cohorts 1 and 2)
DOR was measured from the time assessment criteria that were met for CR (CRMRD- or CRMRD+/unk), CRi, CRh, PR, or MLFS, whichever was first recorded, until the first date of AML relapse, progressive disease, or death (including assessments post SCT). Participants who were not observed to have a relapse, progressive disease, or death were censored at the date of their last response assessment. For participants who started taking new anti-AML therapies (except SCT and post SCT maintenance treatment) before relapse/PD/death, duration of response were censored at the last response assessment before the initiation of the new anti-AML therapies.CR was defined in outcome measure #1. CRi, CRh, PR, or MLFS were defined in outcome measure #6. Kaplan-Meier (KM) estimates were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set who achieved overall response were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Duration of Response (DOR) (Cohorts 1 and 2) | 15.9 months |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Duration of Response (DOR) (Cohorts 1 and 2) | 8.7 months |
Secondary
Event-Free Survival (EFS) (Cohorts 1 and 2)
EFS was defined as the time from the date of the first dose of study treatment to the earliest date of documented relapse from CR, treatment failure (defined as failure to achieve CR during the response assessment window (the first treatment dosing date until before the fifth cycle of magrolimab + venetoclax + azacitidine in Cohort 1 and the first treatment dosing date until before the third cycle of magrolimab + MEC in Cohort 2), or death from any cause within the response assessment window. Response assessments post SCT were included in the analysis. Deaths post SCT or new anti-AML therapies (except SCT and post SCT maintenance) were included. Those who were not observed to have one of these events during the study were censored at the date of their last response assessment during the study. Day 1 of treatment was assigned as the event date for participants with treatment failure. CR was defined in outcome measure #1. KM estimates were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Event-Free Survival (EFS) (Cohorts 1 and 2) | 3.8 months |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Event-Free Survival (EFS) (Cohorts 1 and 2) | 0.0 months |
Secondary
Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Time frame: Up to 2 years
Population: Participants in the Immunogenicity Analysis Set with post-baseline data were analyzed. Per Specified analysis, the arms for both Cohorts 1 and 2 for Safety Run-in and Phase 2 periods were combined for analysis.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2) | NA titer |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Levels of Anti-Magrolimab Antibodies (Cohorts 1 and 2) | NA titer |
Secondary
MRD Negative CR/CRi Rate (Cohort 3)
MRD negative CR/CRi rate was defined as the percentage of participants who maintained CR/CRi as determined by the investigator based on prespecified criteria and reach MRD negative disease status on 2 consecutive bone marrow assessments as determined using multiparameter flow cytometry with a sensitivity of \< 0.1% while on study prior to initiation of any new anti-AML therapy. CR was defined in outcome measure #1. CRi was defined in outcome measure #6.
Time frame: Up to 2 years
Population: As no participants were enrolled in Cohort 3, data were not collected for this outcome measure.
Secondary
Overall Response Rate (ORR)
ORR was the percentage of participants who achieved CR (CRMRD- or CRMRD+/unk), CRi, CRh, PR, or MLFS as per investigator based on prespecified criteria before starting any new anti-AML therapy (including SCT). CRi and CRh were defined as neutrophils \>0.5 x 10\^9/L, platelets \> 50 x 10\^9/L (except residual neutropenia (\<1.0 × 10\^9/L) or thrombocytopenia (\<100 × 109/L) for CRi) and bone marrow blasts \<5%; Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease. PR: Neutrophils \>1.0 x 10\^9/L, platelets \>100 x 10\^9/L, bone marrow blasts reduced to 5%-25%, and a ≥50% reduction from baseline. Blasts \<5% with Auer rods may also be considered a PR. MLFS: Bone marrow blasts \<5%, absence of circulating blasts or Auer rods, no extramedullary disease, marrow should not merely be aplastic; at least 200 cells or 10% cellularity, and no requirement for hematologic recovery. CR was defined in outcome measure #1. Percentages were rounded-off.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set were analyzed. Clopper-Pearson exact method was used in outcome measure analysis.~Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Overall Response Rate (ORR) | 66.7 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Overall Response Rate (ORR) | 38.9 percentage of participants |
Secondary
Overall Survival (OS) (Cohorts 1, 2 and 3)
OS was measured from the date of the first dose of study treatment to the date of death from any cause. Those who were not observed to die during the study were censored at last date they were known to be alive. KM estimates were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Overall Survival (OS) (Cohorts 1, 2 and 3) | 15.3 months |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Overall Survival (OS) (Cohorts 1, 2 and 3) | 10.5 months |
Secondary
Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2)
Percentages were rounded-off.
Time frame: Up to 2 years
Population: The Immunogenicity Analysis Set included all enrolled participants who received at least 1 dose of magrolimab and have at least 1 reported anti-magrolimab antibody test result. Participants with post-baseline data were analyzed.~Per pre-specified analysis, arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received same dose.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2) | 0 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Percentage of Participants With Anti-Magrolimab Antibodies (Cohorts 1 and 2) | 0 percentage of participants |
Secondary
Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3)
Time frame: Cohort 1: Predose: Days 1, 8, 29, 57, 113, 169, 253 and 337; Cohort 2: Days 1, 8, 29 and 57
Population: The Pharmacokinetic Analysis Set included all enrolled participants who received at least 1 dose of magrolimab and 1 measurable (non-below the limit of quantitation numeric values) post-treatment serum concentration of magrolimab. Participants with available data were analyzed. Per pre-specified analysis, arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 8 | 0.0 μg/mL | Standard Deviation 0 |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 113 | 648 μg/mL | Standard Deviation 314 |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 169 | 592 μg/mL | Standard Deviation 371 |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 253 | 178 μg/mL | Standard Deviation 166 |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 337 | 337 μg/mL | — |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 29 | 376 μg/mL | Standard Deviation 271 |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 57 | 1050 μg/mL | Standard Deviation 925 |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 1 | 0.0 μg/mL | Standard Deviation 0 |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 8 | 0.0 μg/mL | Standard Deviation 0 |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 57 | 824 μg/mL | Standard Deviation 581 |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 29 | 507 μg/mL | Standard Deviation 272 |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Plasma Concentration of Magrolimab in Combination With Anti-leukemia Therapy (Cohorts 1, 2 and 3) | Predose: Day 1 | 0.0 μg/mL | Standard Deviation 0 |
Secondary
Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3)
Platelet transfusion independence rate was the percentage of participants who had a 56-day or longer period with no platelet transfusions at any time between the date of the first dose and discontinuation of study treatment among all participants who were platelet transfusion-dependent at baseline. Platelet transfusion independence rate was reported as 2 categories: 1. Conversion rate: Participants who received an platelet transfusion within 28 days prior to the first dose of study treatment, 2. Maintenance rate: Participants who were platelet transfusion independent at baseline and maintained it post-baseline. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3) | Platelet Transfusion Independence (Conversion) Rate | 0.0 percentage of participants |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3) | Platelet Transfusion Independence (Maintenance) Rate | 60.0 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3) | Platelet Transfusion Independence (Conversion) Rate | 8.7 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Platelet Transfusion Independence Rate (Cohorts 1, 2 and 3) | Platelet Transfusion Independence (Maintenance) Rate | 7.7 percentage of participants |
Secondary
Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3)
RBC transfusion independence rate was the percentage of participants who had a 56-day or longer period with no RBC or whole blood transfusion at any time between the date of the first dose and discontinuation of study treatment among all participants who were RBC transfusion-dependent at baseline. RBC transfusion independence rate was reported as 2 categories: 1. Conversion rate: Participants who received an RBC or whole blood transfusion within the 28 days prior to the first dose of study treatment, and were RBC transfusion-independent post-baseline. 2. Maintenance rate: Participants who were RBC transfusion independent at baseline and maintained it post-baseline. Percentages were rounded-off. Clopper-Pearson method were used in outcome measure analysis.
Time frame: Up to 2 years
Population: Participants in the Full Analysis Set were analyzed. Per pre-specified analysis, the arms for Cohorts 1 and 2 for Safety Run-in and Phase 2 were combined for analysis as participants in Cohorts 1 and 2 received the same dose.~As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3) | RBC Transfusion Independence (Conversion) Rate | 30.8 percentage of participants |
| Cohort 1 (1L, Unfit AML): Magrolimab + Venetoclax + Azacitidine | Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3) | RBC Transfusion Independence (Maintenance) Rate | 60.0 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3) | RBC Transfusion Independence (Maintenance) Rate | 20.0 percentage of participants |
| Cohort 2 (R/R AML): Magrolimab + MEC (Mitoxantrone + Etoposide + Cytarabine) | Red Blood Cell (RBC) Transfusion Independence Rate (Cohorts 1, 2 and 3) | RBC Transfusion Independence (Conversion) Rate | 3.8 percentage of participants |
Secondary
Relapse-Free Survival (RFS) Rate (Cohort 3)
RFS was defined as the time from the first dose of study treatment until the first date of AML relapse or death from any cause, whichever came first.
Time frame: Up to 2 years
Population: As no participants were enrolled in Cohort 3, data for Cohort 3 were not collected for this outcome measure.