Gilead Sciences’ investigational therapy magrolimab was well-tolerated and effective in untreated acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, according to data from a Phase 1b trial.
These results were presented recently in an oral presentation, titled “The First-in-Class Anti-CD47 Antibody Magrolimab Combined with Azacitidine Is Well-Tolerated and Effective in AML Patients: Phase 1b Results,” at the 62nd American Society of Hematology Annual Meeting and Exposition.
“In this ongoing study, treatment with magrolimab and azacitidine continues to achieve promising, durable responses in patients with AML who are ineligible for first-line chemotherapy,” David Sallman, MD, of the H. Lee Moffitt Cancer Center and Research Institute, and an investigator in the clinical trial, said in a press release.
Magrolimab (Hu5F9-G4) is an investigational monoclonal antibody that blocks CD47, a macrophage immune checkpoint and “don’t eat me” signal on cancers. Macrophages are a type of immune cell that can digest and clear cellular debris, microbes, or cancer cells (a process called phagocytosis). By blocking CD47, magrolimab is designed to induce tumor clearance by macrophages, thereby eliminating leukemia stem cells.
Azacitidine (brand name Vidaza, among others) works together with magrolimab by inducing “eat me” signals on leukemic blasts and enhancing phagocytosis. Magrolimab in combination with Vidaza has been shown to be clinically effective in both AML and myelodysplastic syndrome.
Gilead’s ongoing Phase 1b trial (NCT03248479) is evaluating the safety, tolerability, and efficacy of treatment with magrolimab in combination with azacitidine in untreated patients with AML who are ineligible for induction chemotherapy.
The clinical trial is still recruiting and plans to enroll a total of 287 participants in several clinical sites across the U.S. and in the U.K.
In the study, 64 AML patients were treated with magrolimab (1–30 mg/kg twice weekly, and 30 mg/kg weekly in cycle 3 and beyond) plus azacitidine (75 milligrams per square meter, mg/m2, on days 1–7 for 28 days), including 47 patients with TP53 mutations, which are associated with poor disease prognosis.
Clinical responses were assessed using the European LeukemiaNet 2017 criteria.
As of November 2020, from the 43 AML patients included in the efficacy analysis, 27 (63%) achieved an objective response, 18 (42%) achieved complete remission — or no signs of cancer — and 5 (12%) achieved complete remission with incomplete count recovery. This means that cancer was eradicated, but other blood parameters were not within a normal range.
The median duration of response was 9.6 months, and the median time to response was 1.95 months.
From the 29 patients with a TP53 mutation, 20 (69%) achieved a response, 13 (45%) achieved complete remission, and 4 (14%) achieved complete remission with incomplete count recovery. The median duration of response was 7.6 months.
The preliminary median overall survival was 18.9 months for AML patients with a TP53 mutation, and 12.9 months for patients without the mutation.
“These findings are especially encouraging for patients with TP53 mutations, which are associated with poor outcomes and limited response to existing treatment options,” Sallman said.
Treatment was well-tolerated. Common side effects included anemia, fatigue, blood bilirubin (a product of the breakdown of red blood cells) increase, neutropenia (low levels of a type of white blood cells called neutrophils), thrombocytopenia (low levels of platelets), and nausea.
From all 64 patients, 3 (4.7%) died 30 days after treatment and 5 (7.8%) died after 60 days. Treatment discontinuation related to side effects occurred in 4.7% of patients.
The U.S. Food and Drug Administration and European Medicines Agency have granted fast track and orphan drug designation for magrolimab to treat AML and myelodysplastic syndrome.
“We continue to be encouraged by the response rates seen in this study and are rapidly advancing the development of magrolimab based on its potential to help address significant unmet medical needs,” Daejin Abidoye, MD, senior vice president, head of oncology of Gilead Sciences, said.