Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Context: Patients with newly diagnosed AML who are ineligible for intensive chemotherapy (IC) are incurable, despite progress with azacitidine + venetoclax, whereas patients with relapsed/refractory disease continue to have a poor prognosis. Furthermore, relapse remains frequent for patients in remission receiving oral azacitidine. Magrolimab is a blocking antibody against CD47, a “don't eat me” signal overexpressed on cancer cells. This blockade induces tumor phagocytosis and is synergistic with chemotherapy and hypomethylating agents. Magrolimab + azacitidine has demonstrated encouraging efficacy in newly diagnosed AML (objective response rate [ORR], 63%; complete remission [CR], 42%). Objective: To evaluate the safety/tolerability and efficacy of magrolimab combined with antileukemia therapies in patients with newly diagnosed or relapsed/refractory AML or with AML in maintenance post-IC. Design: This open-label, multi-arm, multicenter study includes 3 safety run-ins with corresponding expansion cohorts (NCT04778410). Safety run-in cohorts will enroll 6 patients for 28 days to determine dose-limiting toxicities and the recommended phase 2 dose prior to enrollment of phase 2 cohorts. Patients: Patients must be aged ≥75 or 18–74 years with comorbidities precluding IC (cohort [C]1), have relapsed/primary refractory disease post-IC (C2), or have CR/CR with incomplete hematologic recovery and measurable residual disease (MRD) post-IC (C3). Interventions: Patients will receive magrolimab + venetoclax + azacitidine (C1), magrolimab + mitoxantrone + etoposide + cytarabine (MEC; C2), or magrolimab + CC-486 (C3). In all cohorts, magrolimab will be administered intravenously with priming and ramp-up doses of 1 (day [D]1, D4), 15 (D8), and 30 mg/kg (D11, D15, then QW [x5], followed by Q2W). Azacitidine, venetoclax, MEC, and CC-486 will be administered per label indications. After completion of the safety run-ins, additional patients will be enrolled into the phase 2 study (C1, n=40; C2, n=30; C3, n=40). Study treatments will follow the dosing schedule until disease progression, unacceptable toxicity, or loss of clinical benefit (C1/C3) or for 2 to 3 cycles for MEC with a maximum 12 months of magrolimab (C2). Main Outcome Measures: Primary efficacy endpoints are CR rate (C1/C2) and MRD-negative CR rate (C3). Secondary endpoints include overall survival, ORR, and MRD negativity (C1/C2).

Original publication




Journal article


Clinical Lymphoma, Myeloma and Leukemia

Publication Date