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)

Introduction:
Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy of myeloid cells associated with limited outcomes for patients who are ineligible for intensive chemotherapy due to age or comorbidities. Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a “don’t eat me” signal on cancer cells, resulting in tumor phagocytosis by macrophages. A triplet regimen of magrolimab + azacitidine + venetoclax has shown promising activity in patients with AML. We aim to evaluate the efficacy, safety, and tolerability of magrolimab + azacitidine + venetoclax in previously untreated patients with AML who are ineligible for intensive chemotherapy.
Methods:
This is a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Approximately 432 patients will be randomized 1:1 to receive magrolimab + azacitidine + venetoclax (experimental arm) or placebo + azacitidine + venetoclax (control arm). Randomization will be stratified by age, cytogenetic risk group, and geographic region. Patients are eligible if they are ‚â•75‚Äâyears of age or 18 to 74‚Äâyears of age with specific comorbidities. Receipt of prior antileukemic therapy for AML is not allowed. Magrolimab will be administered intravenously with an initial 1 mg/kg priming dose on days 1 and 4 to mitigate on target anemia. The dose will then be escalated to 15 mg/kg on day 8, then to 30 mg/kg on days 11 and 15, then weekly for 5 doses, followed by every other week beginning 1 week after the fifth weekly 30 mg/kg dose. Placebo will be dosed at the same frequency as magrolimab. Venetoclax will be administered orally at 100 mg on day 1, 200 mg on day 2, and 400 mg daily starting on day 3 and thereafter. Azacitidine will be given intravenously or subcutaneously at 75 mg/m on days 1 to 7, or days 1 to 5 and 8 to 9 of 28-day cycles. Patients will remain on study until disease progression, relapse, loss of clinical benefit, or unacceptable toxicities, or until other discontinuation criteria are met. The dual primary endpoints are complete remission (CR) rate within 6 treatment cycles and overall survival. Secondary endpoints include duration of CR, transfusion independence, and event-free survival.
Results:
Trial in progress.
Discussion:
As of July 2022, patient enrollment is ongoing at 2 active sites. Clinical trial information: NCT05079230.