KEY TAKEAWAYS
- Phase 3 randomized, double-blind placebo-controlled multicenter trial (ENHANCE-3) evaluating magrolimab + azacitidine + venetoclax in AML patients ineligible for intensive chemotherapy.
- The primary aims are a complete remission rate within 6 treatment cycles and overall survival.
- The method involves administering magrolimab intravenously, venetoclax orally, and azacitidine intravenously or subcutaneously.
- Secondary endpoints include the duration of complete remission, transfusion independence, and event-free survival.
Patients with severe clonal hematological malignancies of myeloid cells, such as acute myeloid leukemia (AML), who cannot undergo intense chemotherapy due to age or other medical conditions, have poor prognoses. Tumor phagocytosis by macrophages is induced by the antibody magrolimab (Hu5F9-G4), which blocks CD47, a “don’t eat me” signal on cancer cells. Patients with AML have benefited from a triplet treatment consisting of magrolimab, azacitidine, and venetoclax. In untreated individuals with AML who are not candidates for aggressive chemotherapy, we sought to determine the effectiveness, safety, and tolerability of magrolimab + azacitidine + venetoclax. This is a third-phase, multicenter, placebo-controlled randomized trial. Around 432 participants will be randomly assigned to either the magrolimab + azacitidine + venetoclax (experimental arm) or the placebo + azacitidine + venetoclax (control arm) groups.
The participants’ ages, cytogenetic risk groups, and regions will be used to determine their random assignment. Individuals must be at least 75, or between 18 and 74 years old, with certain co-morbidities to be considered for enrollment. Prior treatment with antileukemic drugs for AML is prohibited. On days 1 and 4, an intravenous priming dosage of 1 mg/kg of magrolimab will be given to reduce on-target anemia. Starting one week after the fifth weekly 30 mg/kg dose, the dosage will be reduced to 15 mg/kg every other week. This schedule begins one week after the initial 8-day 15-mg/kg dose. At the same intervals as magrolimab, a placebo will be administered. For example, on day 1, you’ll take 100 mg of venetoclax; on day 2, you’ll take 200 mg. And on day 3, and every day after that, you’ll take 400 mg by mouth. Intravenous or subcutaneous azacitidine 75 mg/m2 will be administered on days 1-7 or 1-5 and 8-9 of 28-day cycles. Study participation will continue until the patient experiences disease worsening, relapse, loss of therapeutic benefit, intolerable toxicity, or meets another criterion for study withdrawal.
The two major objectives are the complete remission (CR) rate at 6 cycles of therapy and overall survival. Secondary goals include time in CR, independence from transfusions, and time to the first adverse event.
Source: https://library.ehaweb.org/eha/2022/eha2022-congress/357413/naval.g.daver.a.phase.3.randomized.trial.of.magrolimab.in.combination.with.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26840%2Amarker%3D1769%2Afeatured%3D17676
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT05079230
Daver N, Liu K, Werneke S, Rustia E, Ramsingh G, & Vyas R. A PHASE 3, RANDOMIZED TRIAL OF MAGROLIMAB IN COMBINATION WITH VENETOCLAX AND AZACITIDINE IN PREVIOUSLY UNTREATED PATIENTS WITH ACUTE MYELOID LEUKEMIA INELIGIBLE FOR INTENSIVE CHEMOTHERAPY (ENHANCE-3). (Abstract release date: 05/12/22) EHA Library. G Daver N. 06/10/2022; 357413; P550.
