FDA Halts Several Studies Examining Magrolimab-Onureg Combo Across Multiple Cancer Types Due to Serious Side Effects

The U.S. Food and Drug Administration (FDA) placed a partial clinical hold — meaning a delay or suspension of part of a clinical trial — on several studies that were examining the treatment combination of magrolimab plus Onureg (azacitidine) due to different amounts of unexpected serious side effects between study groups.

The update was announced in a news release from Gilead Sciences Inc., the company assessing the treatment combination. Gilead plans to implement the clinical hold among any ongoing trial using magrolimab and Onureg in combination to address the concerns raised by the FDA.

Magrolimab is a first-in-class anti-CD47 monoclonal antibody under development for several hematologic cancers, including myelodysplastic syndromes (MDS) and solid tumors, while Onureg is a chemotherapy treatment used in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML) and MDS.

"The safety and well-being of people enrolled in our studies is our top priority. We will share more information with the medical and patient community as soon as we can,” said Dr. Merdad Parsey, chief medical officer of Gilead Sciences, in the release.

Screening and enrollment of any new study participants are to be paused in any study involving the combination therapy. For patients who are already enrolled, they may continue to receive the treatment — or placebo, depending on their study group — and will be closely monitored via study protocols.

Other studies or groups which may be studying the effects of magrolimab alone, but not the combination, are able to continue without being affected by the clinical hold.

“Considering the high unmet need for new medicines in (MDS) and (AML), we will work closely with regulatory authorities worldwide to continue the magrolimab development program appropriately,” Parsey added. “We remain confident in the potential of magrolimab across a broad range of tumors, including the other ongoing magrolimab studies.”

Gilead intends to work with regulatory authorities to figure out how to proceed and release the hold for the studies using the combination therapy.

The studies impacted by the partial clinical hold are the following:

• Phase 3 ENHANCE study in MDS (NCT04313881)
• Phase 3 ENHANCE-2 study in AML (TP53 mutated patients; NCT04778397)
• Phase 3 ENHANCE-3 study in unfit AML (NCT05079230)
• Phase 1b study in MDS (NCT03248479)
• Phase 2 study in myeloid malignancies (NCT04778410) for the Onureg combination groups only

The magrolimab studies that are not impacted are:

• Phase 2 study in diffuse large B-cell lymphoma (NCT02953509)
• Phase 2 study in multiple myeloma (NCT04892446)
• Phase 2 study in head and neck squamous cell carcinoma (NCT04854499)
• Phase 2 study in solid tumors (NCT04827576)
• Phase 2 study in triple-negative breast cancer (NCT04958785)
• Phase 2 study in colorectal cancer, planned and not currently recruiting

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