Magrolimab Trial Enrollment Halted for Solid Tumors

Gilead Sciences announced a suspension of patient recruitment for clinical trials that are examining the effects of the experimental anti-CD47 antibody magrolimab on solid tumors. The FDA has issued a partial clinical hold on all solid tumor studies involving magrolimab, which impacts several Phase II ELEVATE trials. This includes trials focused on head and neck squamous cell carcinoma, triple-negative breast cancer, and colorectal cancer. Additionally, enrollment for other investigator-led studies on magrolimab in solid tumors will be put on hold.

While Gilead has not provided explicit reasons for this pause, the company has stated that it is currently evaluating the benefit-risk profile of magrolimab in all ongoing trials and will release an update on this evaluation shortly. Patients who are already participating in these trials and are experiencing clinical benefits may continue to receive magrolimab treatment after a process of reconsent.

This decision follows a previous FDA directive to impose a full clinical hold on all studies of magrolimab related to myelodysplastic syndromes and acute myeloid leukemia. This full hold was recommended by an Independent Data Monitoring Committee after reviewing preliminary data from the ENHANCE-3 study. The committee concluded that the study not only met the criteria for futility but also indicated an increased risk of death due to infections and respiratory failure.

Magrolimab is a monoclonal antibody that targets CD47, a protein on the surface of cancer cells that they use to evade the immune system. By blocking the CD47 pathway, magrolimab can enable macrophages and other cells to destroy cancer cells. Gilead has highlighted this mechanism as a potentially groundbreaking approach.

Despite its potential, magrolimab's development has faced challenges. In July 2023, Gilead discontinued the Phase III ENHANCE trial for magrolimab in myelodysplastic syndromes after an analysis indicated futility. In September 2023, the company also ended the ENHANCE-2 trial for acute myeloid leukemia due to disappointing efficacy signals. An interim review suggested that magrolimab was unlikely to offer a survival benefit compared to standard treatments.

In August 2023, the FDA placed magrolimab under a partial clinical hold, preventing enrollment in acute myeloid leukemia studies and its expanded access program.