AML-196: The First-in-Class Anti-CD47 Antibody Magrolimab in Combination with Azacitidine Is Well Tolerated and Effective in AML Patients: Phase 1b Results

Abstract

Context: Magrolimab, an anti-CD47 antibody, induces tumor phagocytosis and eliminates leukemia stem cells. Azacitidine (AZA) synergizes with magrolimab by inducing prophagocytic “eat me” signals. Magrolimab + AZA is clinically effective in acute myeloid leukemia (AML) and myelodysplastic syndrome. Objective: To report Phase 1b data of magrolimab + AZA in untreated AML. Design: This is an open-label, nonrandomized, Phase 1b, interventional study. Interventions: Patients received a magrolimab priming/intrapatient dose-escalation regimen (1–30 mg/kg intravenous weekly followed by 30 mg/kg every 2 weeks in cycle 3 and beyond) and AZA (75 mg/m2 on days 1–7 on a 28-day cycle). Patients or Other Participants: Treatment-naive AML patients unfit for intensive chemotherapy. Main Outcomes Measures: Outcome measures included the percentage of patients with adverse events (AEs), objective response (OR), time to response, and duration of response. Results: Fifty-two patients were treated with magrolimab + AZA. Overall, 64% had poor-risk cytogenetics, and 65% had TP53 mutations. Magrolimab + AZA was well tolerated with a safety profile similar to AZA monotherapy. Treatment-related AEs (≥15% of patients) were anemia (31%), fatigue (19%), blood bilirubin increase (19%), neutropenia (19%), thrombocytopenia (17%), and nausea (15%). On-target anemia was generally transient and reversible, and no immune-related AEs associated with magrolimab were observed. Of 34 patients evaluable for efficacy, 22 (65%) achieved an OR, 15 (44%) achieved complete response (CR), 4 (12%) with CR with incomplete count recovery (CRi), 1 (3%) with partial response, 2 (6%) with morphological leukemia-free state (MLFS), 11 (32%) with stable disease (SD), and 1 (3%) with progressive disease (PD). Time to response was 2.04 months. In TP53-mutant patients, 15/21 (71%) achieved an OR, 10 (48%) achieved a CR, 4 (19%) with CRi, 1 (5%) with MLFS, 5 (24%) with SD, and 1 (5%) with PD. The median overall survival for TP53-mutant patients (n=34) and TP53–wild-type patients (n=16) was 12.9 and 18.9 months, respectively, with a median follow-up of 4 and 12 months, respectively. Conclusions: Magrolimab + AZA was well tolerated, with efficacy in both TP53-mutant and TP53–wild-type AML patients. A Phase 3 trial evaluating magrolimab + AZA in untreated TP53-mutant AML patients is planned (NCT04778397). Magrolimab, an anti-CD47 antibody, induces tumor phagocytosis and eliminates leukemia stem cells. Azacitidine (AZA) synergizes with magrolimab by inducing prophagocytic “eat me” signals. Magrolimab + AZA is clinically effective in acute myeloid leukemia (AML) and myelodysplastic syndrome. To report Phase 1b data of magrolimab + AZA in untreated AML. This is an open-label, nonrandomized, Phase 1b, interventional study. Patients received a magrolimab priming/intrapatient dose-escalation regimen (1–30 mg/kg intravenous weekly followed by 30 mg/kg every 2 weeks in cycle 3 and beyond) and AZA (75 mg/m2 on days 1–7 on a 28-day cycle). Treatment-naive AML patients unfit for intensive chemotherapy. Outcome measures included the percentage of patients with adverse events (AEs), objective response (OR), time to response, and duration of response. Fifty-two patients were treated with magrolimab + AZA. Overall, 64% had poor-risk cytogenetics, and 65% had TP53 mutations. Magrolimab + AZA was well tolerated with a safety profile similar to AZA monotherapy. Treatment-related AEs (≥15% of patients) were anemia (31%), fatigue (19%), blood bilirubin increase (19%), neutropenia (19%), thrombocytopenia (17%), and nausea (15%). On-target anemia was generally transient and reversible, and no immune-related AEs associated with magrolimab were observed. Of 34 patients evaluable for efficacy, 22 (65%) achieved an OR, 15 (44%) achieved complete response (CR), 4 (12%) with CR with incomplete count recovery (CRi), 1 (3%) with partial response, 2 (6%) with morphological leukemia-free state (MLFS), 11 (32%) with stable disease (SD), and 1 (3%) with progressive disease (PD). Time to response was 2.04 months. In TP53-mutant patients, 15/21 (71%) achieved an OR, 10 (48%) achieved a CR, 4 (19%) with CRi, 1 (5%) with MLFS, 5 (24%) with SD, and 1 (5%) with PD. The median overall survival for TP53-mutant patients (n=34) and TP53–wild-type patients (n=16) was 12.9 and 18.9 months, respectively, with a median follow-up of 4 and 12 months, respectively. Magrolimab + AZA was well tolerated, with efficacy in both TP53-mutant and TP53–wild-type AML patients. A Phase 3 trial evaluating magrolimab + AZA in untreated TP53-mutant AML patients is planned (NCT04778397).