Investigators will submit data from the phase 3 ENHANCE trial evaluating magrolimab plus azacitidine in higher-risk myelodysplastic syndromes for presentation at a future medical meeting.
A version of this article was originally published on Cancer Network. This version has been lightly edited.
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
Imetelstat Offers Benefits for Patients With MDS Who Are Red Blood Cell–Transfusion Dependent
December 5th 2023The past year has offered new hope for patients with lower-risk myelodysplastic syndromes. Besides imetelstat, which has an FDA deadline for action of June 2024, the agency approved luspatercept, which has a different mechanism of action.
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7-Day Dosing of Azacytidine Shows Benefit for Females With High-Risk MDS Not Seen in Males
November 30th 2023Investigators from several medical centers in Japan were surprised to find that women with myelodysplastic syndrome (MDS) had a survival advantage from a 7-day dosing schedule, but that benefit compared with a reduced schedule was not seen in men.
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Allogeneic HCT Provides OS Benefit Independent of TP53 Allelic Status in MDS
November 27th 2023Patients with myelodysplastic syndrome harboring a TP53 mutation experienced a survival benefit with allogeneic hematopoietic cell transplantation compared with non-HCT treatment regardless of TP53 allelic status.
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ESAs Do Not Improve Hb Levels in Lower-Risk Myelodysplastic Syndrome
November 23rd 2023Data from a retrospective study spotlight a need for more effective first-line and second-line clinical management strategies to improve outcomes in patients with lower-risk myelodysplastic syndrome.
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Authors Support Trials of Triplet Therapy in Higher-Risk MDS
November 9th 2023Given the likelihood of MDS to progress to acute myeloid leukemia (AML), the authors state, “There are certain settings where ‘AML-like’ therapies are appropriate in MDS, particularly given our evolving understanding of the overlapping biology of these malignancies.”
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