Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results

Authors

Naval G Daver
Paresh Vyas
Suman Kambhampati
Monzr M Al Malki
Richard A Larson
Adam S Asch
Gabriel Mannis
Wanxing Chai-Ho
Tiffany N Tanaka
Terrence J Bradley
Deepa Jeyakumar
Eunice S Wang
Kendra Sweet
Hagop M Kantarjian
Guillermo Garcia-Manero
Rami Komrokji
Guan Xing
Giridharan Ramsingh
Camille Renard
Joshua F Zeidner
David A Sallman

Publication Date

11-1-2023

Journal

Journal of Clinical Oncology

Abstract

Purpose: Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479).

Patients and methods: Patients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR).

Results: Eighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53-mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was -0.9 g/dL (range, -3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53-mutant and wild-type patients were 9.8 months and 18.9 months, respectively.

Conclusion: Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.

Keywords

Humans, Azacitidine, Antibodies, Monoclonal, Humanized, Remission Induction, Leukemia, Myeloid, Acute, Antineoplastic Combined Chemotherapy Protocols

DOI

10.1200/JCO.22.02604

PMID

37703506

PMCID

PMC10617926

PubMedCentral® Posted Date

9-13-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes