FDA Puts Clinical Hold on Trials Assessing Magrolimab/Azacitidine Combo in AML/MDS

Due to an imbalance of investigator-reported unexpected adverse reactions, the FDA placed a partial clinical hold on all trials examining the combination of magrolimab and azacitidine in acute myeloid leukemia and myelodysplastic syndrome.

A partial clinical hold has been placed by the FDA on studies assessing the use of magrolimab and azacitidine in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), according to a press release from developer Gilead Sciences.

The hold was implemented because of a notable imbalance of investigator-reported unexpected adverse reactions across different study arms. The partial hold is going into effect globally and will apply to any trials utilizing the combination until further data are gleaned, although no clear patterns in adverse reactions or novel safety signals have been observed.

“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,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in the press release. “Considering the high unmet need for new medicines in myelodysplastic syndrome and acute myeloid leukemia, we will work closely with regulatory authorities worldwide to continue the magrolimab development program appropriately. We remain confident in the potential of magrolimab across a broad range of tumors, including the other, ongoing magrolimab studies. We are grateful to those participating in our studies, their families, and the investigators for their continued contributions to the clinical program for magrolimab.”

The first-in-class monoclonal antibody targeting CD47, magrolimab, is also a macrophage checkpoint inhibitor. It was designed to hinder the recognition of CD47 through the SIRPα receptor on macrophages, potentially blocking a signal used by cancer cells to avoid being consumed by macrophages.

A pause on screening and enrolling patients on relevant clinical trials will take place during the hold, although patients who are already on the studies will continue to receive treatment under close monitoring in the study's protocol. Notably, other studies using magrolimab without the addition of azacitidine will not be impacted by the partial hold.

A number of clinical trials will be impacted by the decision, including the following:

  • Phase 3 ENHANCE study in untreated MDS (NCT04313881)
  • Phase 3 ENHANCE-2 study in untreated, TP53-mutant AML (NCT04778397)
  • Phase 3 ENHANCE-3 study in AML (NCT05079230)
  • A phase 1b study in those with hematologic malignancies in cohorts containing azacitidine (NCT03248479)

Notably, a number of clinical trials in solid cancers and hematologic malignancies will continue during the clinical hold. These include:

  1. Phase 2 study in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NCT02953509)
  2. Phase 2 study in relapsed/refractory multiple myeloma (NCT04892446)
  3. Phase 2 study in head and neck squamous cell carcinoma (NCT04854499)
  4. Phase 2 study in solid malignancies (NCT04827576)
  5. Phase 2 study in previously untreated, metastatic triple-negative breast cancer (NCT04958785)
  6. A planned phase 2 study for colorectal cancer that is not presently recruiting

Reference

Gilead announces partial clinical hold for studies evaluating magrolimab in combination with azacitidine. News release. Gilead Sciences. January 25, 2022. Accessed January 26, 2022. https://bit.ly/3rSSav1