Investigators Discontinue Trial Assessing Magrolimab Combo in Higher-Risk MDS

The FDA granted breakthrough therapy designation to magrolimab for managing newly diagnosed MDS in September 2020.

The phase 3 ENHANCE study (NCT04313881), assessing magrolimab and azacitidine combination therapy in patients with higher-risk myelodysplastic syndromes (MDS), will be discontinued after investigators reported futility in a planned analysis, according to a press release from Gilead Sciences, Inc.¹

The safety data of the ENHANCE study were comparable with the previously established profile of magrolimab and the types of adverse effects (AEs) that typically occur in those with higher-risk MDS. Developers advise that all patients receiving magrolimab for MDS discontinue treatment with the agent. Investigators will determine suitable next steps for those enrolled on the ENHANCE study and submit their data for presentation at a later medical meeting.

“The health and well-being of patients are our top priorities and while this is disappointing news, it confirms the challenges of treating [higher-risk] MDS, where no new class of treatments have been approved in nearly 20 years,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in the press release.

In the phase 3 ENHANCE study, more than 500 patients with higher-risk MDS were randomly assigned to receive one of 2 regimens. Patients received magrolimab or matched placebo at 1 mg/kg on days 1 and 4, 15 mg/kg on day 8, and 30 mg/kg on days 11 and 15, and then once weekly for 5 doses. Maintenance doses with magrolimab or placebo were administered at 30 mg/kg on day 57 and every 2 weeks thereafter. All patients also received 75 mg/m2 of azacitidine on days 1 to 7 of each 28-day cycle.

The study’s primary end points were complete remission (CR) rate and overall survival. Secondary end points included the duration of CR, objective response rate (ORR), duration of response, and progression-free survival.

Patients 18 years and older with MDS based on World Health Organization classification and a Revised International Prognostic Scoring System prognostic risk category of intermediate-, high-, or very high-risk disease were eligible for enrollment on the ENHANCE study. Patients also needed to have adequate hematological, liver, and kidney function to enroll.

The FDA granted breakthrough therapy designation to magrolimab for managing newly diagnosed MDS in September 2020.² Supporting data for this designation came from a phase 1b trial in which the agent elicited an ORR of 91% in 33 evaluable patients and a CR rate of 42%.

The FDA previously put a partial clinical hold on magrolimab and azacitidine trials in MDS and acute myeloid leukemia (AML) in February 2022.³ The regulatory agency put this hold into effect based on a notable imbalance of investigator-reported AEs across treatment arms. The hold impacted all trials evaluating this combination therapy around the world until investigators could provide additional data.

The FDA lifted its hold on the magrolimab and azacitidine trials in April 2022 after a comprehensive safety data review indicated that investigators could continue to assess the combination therapy in the previously described patient population.⁴

“Our confidence in the risk-benefit profile of magrolimab has been unwavering, and we continue to believe in the potential for this treatment to address the unmet medical needs faced by people living with MDS and AML,” Parsey said at the time the hold was lifted. “This is a significant milestone for Gilead and, more importantly, for patients diagnosed with these cancers.”

References

1. Gilead to discontinue phase 3 ENHANCE study of magrolimab plus azacitidine in higher-risk MDS. News release. Gilead Sciences, Inc. July 21, 2023. Accessed July 24, 2023. bit.ly/3Qd0xzk
2. Gilead’s Magrolimab, an investigational anti-CD47 monoclonal antibody, receives FDA breakthrough therapy designation for treatment of myelodysplastic syndrome. News release. Gilead Sciences, Inc. September 15, 2020. Accessed July 24, 2023. bit.ly/43C2EQs
3. Gilead announces partial clinical hold for studies evaluating magrolimab in combination with azacitidine. News release. Gilead Sciences, Inc. January 25, 2022. Accessed July 24, 2023. bit.ly/3Ycu3ar
4. FDA lifts partial clinical hold on MDS and AML magrolimab studies. News release. Gilead Sciences, Inc. April 11, 2022. Accessed July 24. 2023. bit.ly/44BYM3f