On May 29, 2020 Gilead Sciences, Inc. (Nasdaq: GILD) reported updated results from a single-arm, open-label Phase 1b trial of magrolimab, an investigational anti-CD47 monoclonal antibody, in combination with azacitidine in previously untreated patients with higher-risk myelodysplastic syndrome (MDS) and previously untreated patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML, a high unmet need population (Press release, Gilead Sciences, MAY 29, 2020, View Source [SID1234558703]). Results continue to support the clinical activity of magrolimab and azacitidine. The data were presented during an oral session at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held from May 29-31 (Abstract #7057).

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At the time of the data cut-off, 68 patients had been treated with magrolimab plus azacitidine, including 39 patients with previously untreated higher-risk MDS and 29 patients with previously untreated AML. Of 33 MDS patients who were evaluable for efficacy, 91 percent (n=30/33) achieved an objective response (response assessments per 2006 IWG MDS criteria) including 42 percent (n=14/33) with a complete response (CR). Responses to magrolimab and azacitidine also deepened over time, as the CR rate with at least six months of follow-up was 56 percent in MDS patients.

In AML, 64 percent (n=16/25) of patients evaluable for efficacy achieved an objective response (response assessments per 2017 AML ELN criteria), including 56 percent (n=14/25) with a CR or a CR with incomplete blood count recovery (CRi). Notably in TP53-mutant AML (n=12), a treatment refractory and poor prognosis population, 75 percent achieved a CR or CRi.

Median duration of response and median overall survival have not yet been reached in MDS, AML or TP53-mutant AML, with a median follow-up of 5.8 (range: 2.0-15.0 months), 9.4 (range: 1.9-16.9 months) and 8.8 months (range: 1.9-16.9 months), respectively.

The safety profile of the combination of magrolimab plus azacitidine was generally consistent with prior reports with no maximum tolerated dose reached. Common all-grade treatment-related adverse events (AEs) among 68 patients with MDS or AML were anemia (38 percent), fatigue (21 percent), neutropenia (19 percent), thrombocytopenia (18 percent) and infusion reaction (16 percent). Treatment-related febrile neutropenia occurred in 1.5 percent of patients. Only one patient (1.5 percent) discontinued the trial due to a treatment-related AE.

"We continue to be encouraged by the response rates observed with magrolimab and azacitidine in first-line, high-risk MDS and AML," said David Sallman, MD, H. Lee Moffitt Cancer Center and Research Institute, an investigator for the clinical trial. "Particularly impressive are the responses in some of the most difficult-to-treat patients, including AML patients with a TP53 mutation. This patient group suffers from a lack of effective treatment options. These results support further study in these patients and provide hope for a potentially meaningful clinical advance."

"Results presented at ASCO (Free ASCO Whitepaper) reinforce the clinical potential of CD47 inhibition with magrolimab in high risk, difficult-to-treat hematologic malignancies," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "We look forward to initiating additional trials in MDS and TP53-mutant AML, which will be a significant step forward for this exciting next-generation cancer immunotherapy."

Magrolimab is investigational and not approved anywhere globally. Its efficacy and safety have not been established. More information about clinical trials with magrolimab is available at www.clinicaltrials.gov (NCT03248479).

About Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

Myelodysplastic syndromes (MDS) are a type of cancer caused by poorly formed or dysfunctional blood cells in the bone marrow. Approximately 15,000 people are diagnosed with MDS in the U.S. each year, and no new treatments have been approved in 14 years.

Acute myeloid leukemia (AML) is a type of cancer which begins in the bone marrow and can quickly move to the blood and other parts of the body. AML most often develops from cells that would turn into white blood cells, but can also develop from other types of blood-forming cells. Cancers such as MDS can also develop into AML. Approximately 20,000 Americans will be diagnosed with AML each year.

About the Phase 1b Trial

The Phase 1b trial, which is being funded in part by the California Institute of Regenerative Medicine (CIRM), is designed to evaluate the safety, tolerability and efficacy of magrolimab in combination with azacitidine in untreated patients with higher-risk MDS or with AML who are ineligible for induction chemotherapy. All patients in the trial received a 1 mg/kg priming dose of magrolimab, coupled with intrapatient dose escalation, to mitigate on-target anemia. Patients were then treated with full doses of azacitidine and a magrolimab maintenance dose of 30 mg/kg once weekly (QW) or every two weeks (Q2W). Based on pharmacokinetics and CD47 receptor occupancy data in the bone marrow from the ongoing trial, Q2W dosing has been selected to optimize patient convenience.

This trial, which is ongoing, aims to enroll up to a total of 257 patients.

About Magrolimab

Magrolimab is an investigational monoclonal antibody against CD47 that is designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, thus blocking the "don’t eat me" signal used by cancer cells to avoid being ingested by macrophages. Forty Seven, Inc. developed magrolimab and was recently acquired by Gilead. Magrolimab is initially being studied in patients with MDS and AML, and additional studies are ongoing in non-Hodgkin lymphoma (NHL) and solid tumors. Magrolimab has been granted Fast Track designation by the FDA for the treatment of MDS and AML, and for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma, two forms of B-cell non-Hodgkin’s lymphoma. Magrolimab has also been granted Orphan Drug designation by the U.S. Food and Drug Administration for AML and MDS and by the European Medicines Agency for the treatment of AML.