ASH 2019 round up – Magrolimab

During the American Society of Hematology (ASH) annual meeting in 2019, a phase Ib study (NCT03248479) of magrolimab in combination with azacitidine was featured by the AML Hub Steering Committee as a practice changing abstract, due to the novel mechanism of action and efficacy in patients with TP53 mutations.

Magrolimab is a first-in-class antibody against the macrophage immune checkpoint protein CD47. CD47 facilitates immune evasion and is associated with poor prognosis in patients with acute myeloid leukemia (AML). Therefore, blockade of this protein induces tumor phagocytosis and facilitates the elimination of tumor cells.

During the 25th Congress of the European Hematology Association (EHA, 2020), and the American Society of Clinical Oncology (ASCO) virtual meeting 2020, the AML Hub covered the updated data presented from this ongoing study as a video interview with Naval Daver and a podcast discussion between David Sallman and Naval Daver.

The trial was conducted in two cohorts of patients: those with high-risk myelodysplastic syndrome (MDS), and those with high-risk AML who were older (> 60 years of age) and ineligible for standard induction chemotherapy. Although the number of patients in each cohort was still relatively small (n = 39, MDS; and n = 29, AML), and the follow-up period at the time of data cutoff was relatively short (~9 months), the efficacy data were encouraging, with overall response rates of 91% and 64% (MDS and AML, respectively); median duration of response was not yet reached, and safety and tolerability profiles were good, with the maximum tolerated dose not yet reached, and only one treatment discontinuation for an infusion-site reaction.¹

As initial results of the trial showed higher and more durable responses for patients with TP53 mutations, the study protocol was amended to focus on this subset of patients for AML, and a cohort expansion in both arms is continuing. A written summary of the current trial results can be found here. A phase III randomized study (ENHANCE, NCT04313881) is also planned to compare the combination of magrolimab and azacitidine, with azacitidine alone, in patients with MDS. Another phase Ib/II study will look at the combination of magrolimab, azacitidine, and venetoclax in patients with AML (NCT04435691).

We look forward to further updates on immunotherapeutics at the 62nd ASH annual meeting on December 5–8, 2020. Follow us on twitter, @AML-Hub, for our live coverage of Session 616 ‘Novel therapy, excluding transplantation: Advances in immunotherapeutics for management of AML’, on Saturday, December 5, at 12:00–13:30 Pacific Time, and visit our live event page for summarized articles and video interviews from the meeting.