The phase-III ENHANCE-2 study was designed to test the efficacy of magrolimab in combination with azacitidine in patients with previously untreated TP53-mutated acute myeloid leukemia (AML). Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, and colleagues provided an update on the trial in a poster presentation (AML-554) during the Society of Hematologic Oncology (SOHO) 2023 Annual Meeting.1
The combination is being studied to test if a hypomethylating agent synergizes with magrolimab, an antibody blocking CD47, a macrophage immune checkpoint and “don’t eat me” signal on cancer cells, that eliminates leukemia stem cells by inducing phagocytosis. By combining magrolimab with azacitidine the hypothesis is that it would induce “eat me” signals on leukemic blasts.
The trial will enroll approximately 346 patients with treatment-naive TP53-mutated disease or biallelic 17p deletions. Patients will be randomly assigned to magrolimab plus azacitidine or physician’s choice of venetoclax plus azacitidine or 7+3 chemotherapy.
However, the trial is currently on a partial clinical hold, Dr. Daver said, noting that patients who are already enrolled can continue treatment, but new patients cannot be enrolled until the data is reviewed and presented to the US Food and Drug Administration.
“It’s not clear right now what the path will be,” Dr. Daver told Blood Cancers Today. “What we’re hoping is that unlike the MDS studies, we will see some benefit in the AML studies and there will be a path forward. But for now, there’s no data yet to make a decision.”
During the first 28-day cycle, patients assigned to the investigational arm will receive magrolimab intravenously at a priming dose of 1 mg/kg on days one and four, 15 mg/kg on day eight, and 30 mg/kg on days 11, 15, and then weekly for five doses, followed by every other week beginning one week after the fifth weekly dose. For patients randomized to venetoclax plus azacitidine, these will be administered per labeled indications. Patients receiving 7+3 chemotherapy will undergo 1−2 induction cycle(s) with IV daunorubicin or idarubicin on days one to three and cytarabine 100 mg/m2 or 200 mg/m2 on days one to seven followed by up to four consolidation cycles with high-dose cytarabine (1500 or 3000 mg/m2).
The primary endpoint is overall survival (OS) in patients appropriate for nonintensive therapy; a secondary endpoint is OS in all patients.
Magrolimab is also being studied in patients with newly diagnosed AML who are unfit for intensive chemotherapy (ENHANCE-3).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, Vyas P, Xing G, et al. A phase III, randomized, open-label study evaluating the safety and efficacy of magrolimab in combination with azacitidine in previously untreated patients with TP53-mutant acute myeloid leukemia. Abstract AML-554. Presented at the Annual Meeting of the Society of Hematologic Oncology. September 6-9, 2023; Houston, Texas.
- Daver NG, Liu K, Kuwahara SB, et al. AML-557. 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). Presented at: Society of Hematologic Oncology (SOHO) 2023 Annual Meeting; September 6-9, 2023. Presented at the Annual Meeting of the Society of Hematologic Oncology. September 6-9, 2023; Houston, Texas.
- Gilead. Gilead to discontinue phase 3 ENHANCE study of magrolimab plus azacitidine in higher-risk MDS. July 21, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/7/gilead-to-discontinue-phase-3-enhance-study-of-magrolimab-plus-azacitidine-in-higher-risk-mds.