Phase III ENHANCE-2 trial of magrolimab + azacitidine in TP53-Mutant AML is discontinued

The decision followed a review conducted by an independent data monitoring committee and was based on data from an ad-hoc analysis. It was concluded that magrolimab is not likely to provide a survival benefit compared with standard of care in this population.

The randomized, open-label trial enrolled patients with treatment-naïve AML whose tumors harbored at least 1 TP53 mutation. To participate, they needed to have an ECOG performance status ranging from 0 to 2 and have acceptable renal and cardiac function. Moreover, they were required to have a white blood cell count of up to 20 x 103/L before randomization and a hemoglobin level of at least 9 g/dL. Those who were candidates for intensive treatment but who had previously received maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones were excluded, as were those who previously received SIRP?-targeted drugs or antileukemic therapy for their disease, a hypomethylating agent, low-dose cytarabine, and/or venetoclax. Those with suspected active central nervous system involvement or those with acute promyelocytic leukemia were also not permitted.

In January 2022, the FDA placed a partial clinical hold on all clinical trials examining magrolimab plus azacitidine after an apparent imbalance in investigator-reported, suspected unexpected serious adverse reactions observed between study arms. At the time, no clear trend in toxicities or new safety signals were reported. The partial hold impacted ENHANCE-2, the phase III ENHANCE trial (NCT04313881) in those with myelodysplastic syndrome, the phase III ENHANCE-3 trial (NCT05079230) in unfit patients with AML, a phase 1b trial (NCT03248479) in those with MDS, and the azacitidine cohorts of the phase II GS-4721 trial (NCT04778410) in those with myeloid malignancies. In April 2022, the partial hold was lifted after a comprehensive safety data review was performed.