The phase III ENHANCE study was designed to assess the combination of venetoclax and azacitidine with the CD47-blocking magrolimab in previously untreated patients with acute myeloid leukemia (AML) who were unfit for intensive chemotherapy.
Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, and colleagues provided an update on the trial in a poster presentation during the Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO).1
The combination of azacitidine with venetoclax and magrolimab showed early promise in a phase I/II study of patients with newly diagnosed, high-risk AML. The study of the combination included a small number of patients with newly diagnosed disease; the complete response (CR)/CR with incomplete hematologic recovery rate was 94%.
This phase-III trial is planned to enroll approximately 432 patients with treatment-naive disease. There are currently about 130 active sites. Patients will be randomly assigned to magrolimab plus azacitidine and venetoclax or placebo plus azacitidine plus venetoclax. Enrolled patients must be aged 75 years or older or aged 18-74 years with specific comorbidities.
However, the trial is on a partial clinical hold, Dr. Daver said.
“The patients who are already enrolled are allowed to continue treatment, but no new patients can be enrolled until the data is reviewed and presented to the [US Food and Drug Administration],” he told Blood Cancers Today.
To mitigate on-target anemia, magrolimab will be given intravenously at 1 mg/kg priming dose on days one to four. The dose will be escalated to 15 mg/kg on day eight, and again to 30 mg/kg on days 11 to 15, and then weekly for five doses, followed by every other week beginning one week after the fifth weekly 30 mg/kg dose. Venetoclax will be given orally at 100 mg on day one, 200 mg on day one, and 400 mg daily starting on day three and given in 28-day cycles. Azacitidine will be given intravenously or subcutaneously at 75 mg/m2 on days one to seven, or days one to five and eight to nine.
The dual primary endpoints are CR rate within six treatment cycles and overall survival.
Magrolimab is also being studied in patients with AML with TP53 mutations (ENHANCE-2). The phase-III ENHANCE study of magrolimab plus azacitidine in higher-risk myelodysplastic syndromes (MDS) was discontinued earlier this year due to futility based on a planned analysis.3
This trial is sponsored by Gilead Sciences, Inc.
Daver NG, Liu K, Kuwahara SB, Caldwell K, Vyas P. A phase III, randomized trial of magrolimab in combination with venetoclax and azacitidine in previously untreated patients with acute myeloid leukemia who are ineligible for intensive chemotherapy (ENHANCE-3). Abstract AML-557. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology. September 6-9, 2023; Houston, Texas.