CD47 monoclonal antibody magrolimab in the treatment of acute myeloid leukemia (AML): a response rate of 63%

Gilead CD47 monoclonal antibody Magrolimab first-line treatment of acute myeloid leukemia (AML): a response rate of 63%.

Gilead Sciences recently announced the latest results of a Phase 1b clinical study evaluating the first-line anti-CD47 monoclonal antibody Magrolimab for the treatment of acute myeloid leukemia (AML) at the 62nd Annual Meeting of the American Society of Hematology (ASH).

The study was carried out in AML patients who had not previously received treatment and were not suitable for intensive chemotherapy, including TP53 mutant AML patients.

The results showed that Magrolimab combined with azacitidine treatment achieved a very high response rate: in the entire study population, the overall response rate (ORR) was 63% (n=27/43), while the ORR in patients with TP53 mutation was 69 %(N=20/29).

The research investigator, H. Lee Moffitt Cancer Center and Research Institute David Sallman, MD, said: “In this ongoing study, the combination of Magrolimab and azacitidine in the treatment of AML patients who are not suitable for first-line chemotherapy continues to show Promising and long-lasting results. These findings are particularly encouraging for patients with TP53 mutations, which are associated with poor prognosis and limited response to existing treatment options.”

In this study, 64 patients received Magrolimab combined with azacitidine, including 47 patients with TP53 mutations, which is a difficult-to-treat population with poor prognosis.

As of November 2020, 63% (n=27/43) of patients with curative effects that can be assessed have reached the objective remission of the European LeukemiaNet 2017 standard (European LeukemiaNet 2017), and 42% (n=18/43) of patients have achieved complete remission.

Remission (CR), 12% (n=5/43) of patients obtained CR (CRi) with incomplete recovery of hematological counts. The median duration of response (DOR) was 9.6 months (range: 0.03+ to 18.7 months), and the median time to remission was 1.95 months (range: 0.95 to 5.6 months).

For patients with TP53 mutation, 69% (n=20/29) got remission, 45% (n=13/29) got CR, and 14% (n=4/29) got CRi. The median DOR was 7.6 months (range: 0.03+ to 15.1+ months), and the minimal residual disease (MRD) negative rate among CR/CRi patients was 29% (n=5/17).

The initial median overall survival (OS) of TP53 wild-type patients (n=16) was 18.9 months (95% CI: 4.34, NE), and the initial median overall survival (OS) of TP53 mutant patients (n=47) ( OS) was 12.9 months (95%CI: 8.21, 17.28).

The median follow-up time of TP53 wild-type and TP53 mutant patients were 12.5 months and 4.7 months, respectively.

More patients and longer follow-up are needed to further determine the survival benefit.

In the study, common treatment-related adverse events observed (incidence> 15%) included anemia, fatigue, elevated blood bilirubin, infusion-related reactions, neutropenia, thrombocytopenia, and elevated ALT.

Most patients had thrombocytopenia at the baseline examination, and no significant increase in thrombocytopenia, infection, or immune-related adverse events (AE) was observed in the study.

The 30-day all-cause mortality rate was 4.7% (n=3/64), and the 60-day mortality rate was 7.8% (n=5/64). 4.7% of patients discontinued treatment due to drug-related adverse events.

CD47 monoclonal antibody magrolimab in the treatment of acute myeloid leukemia (AML): a response rate of 63% — *(Magrolimab mechanism of action)*

Magrolimab is a monoclonal antibody that blocks the CD47 signal obtained by Gilead after purchasing Forty Seven for approximately US$4.9 billion in April this year.

Magrolimab is designed to interfere with the recognition of CD47 by SIRPα receptors on macrophages, thereby blocking cancer cells from using “don’t eat me” signals to avoid being swallowed by macrophages.

Currently, Magrolimab is being developed in some hematology and solid tumor malignancies, including AML and myelodysplastic syndrome (MDS).

Previously, Magrolimab has been granted Fast Track Qualification (FTD) for MDS, AML, Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) by the FDA.

Magrolimab was also granted orphan drug designation (ODD) for the treatment of MDS and AML by the FDA, and was granted the orphan drug designation for the treatment of AML by the European Medicines Agency (EMA).

In September of this year, the FDA granted Magrolimab a breakthrough drug designation (BTD) for the first-line treatment of MDS.

MDS is a type of cancer caused by poorly formed or dysfunctional blood cells in the bone marrow.

In the United States, approximately 15,000 people are diagnosed with MDS each year, and no new treatment has been approved for 14 years.

The average survival time of patients with low-risk MDS is 6 years, and patients with high-risk MDS are about 18 months.

The BTD is based on the positive results of an ongoing Phase 1b study. The study evaluated the combination of Magrolimab and azacitidine in the treatment of previously untreated patients with moderate, high, and very high-risk MDS.

Data published at the European Society of Hematology (EHS) conference in 2020 showed that among evaluable patients (n=33) who received the combination therapy of Magrolimab and azacitidine, the objective response rate (ORR) was as high as 91%, and the complete response rate was (CR) up to 42%.

The combination of Magrolimab and azacitidine is well tolerated. The maximum tolerated dose was not reached, and no patients with MDS discontinued treatment due to treatment-related adverse events.

Currently, Magrolimab is undergoing a double-blind, placebo-controlled, randomized Phase 3 ENHANCE trial for previously untreated patients with high-risk MDS.

The trial will evaluate the safety and effectiveness of Magrolimab combined with azacitidine by CR and CR duration.

CD47 monoclonal antibody Magrolimab in the treatment of acute myeloid leukemia (AML): a response rate of 63%

(source:internet, reference only)

Disclaimer of medicaltrend.org