Gilead Discontinues Phase 3 ENHANCE Trial of Magrolimab/Azacitidine in Higher-Risk MDS

The phase 3 ENHANCE trial (NCT04313881) evaluating the first-line combination of magrolimab and azacitidine (Vidaza) vs placebo plus azacitidine in patients with higher-risk myelodysplastic syndrome (MDS) has been discontinued due to futility at a planned analysis, according to an announcement from Gilead Sciences.¹

Trial investigators and the company are evaluating the next steps for patients enrolled on the study, and the company recommended the discontinuation of treatment with magrolimab in patients with MDS. Full data from the analysis will be presented at an upcoming 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 of Gilead Sciences, stated in a news release. “Gilead is deeply grateful to the patients, families, investigators, and the advocacy community who contributed to this research as we learn more about magrolimab and explore its potential in treating other cancers.”

The randomized, double-blind ENHANCE study was evaluating the combination of magrolimab plus azacitidine in patients at least 18 years of age with previously untreated MDS defined by World Health Organization classification with a Revised International Prognostic Scoring System prognostic risk category of intermediate, high, or very high. Patients also needed to have an adequate performance status and hematological, liver, and kidney function.²

Patients were excluded if they were eligible for an immediate allogenic stem cell transplant with an available donor, received prior treatment with CD47- or SIRPα-targeting agents, received any prior antileukemic therapy for intermediate, high, or very-high risk MDS, or had clinical suspicion of active central nervous system involvement from MDS.

The study enrolled more than 500 patients who were randomly assigned to receive magrolimab in combination with azacitidine or placebo plus azacitidine. Magrolimab was given with priming doses of 1 mg/kg on days 1 and 4, then 15 mg/kg on day 8, followed by 30 mg/kg on days 11 and 15. Weekly doses of 30 mg/kg were then given on days 22, 29, 36, 43, 50, and 57, followed by once every 2 weeks thereafter. Azacitidine was administered at 75 mg/m² on days 1 to 7 or days 1 to 5 and 8 to 9 of each 28-day cycle in both arms.

Complete remission (CR) and overall survival served as the trial’s primary end points. Secondary end points included duration of response, duration of CR, transfusion independence, progression-free survival, event-free survival, minimal residual disease–negative response rate, and time to transformation to acute myeloid leukemia (AML).

Regarding safety, data from ENHANCE were consistent with the known toxicity profile of magrolimab, and adverse effects were typical for this patient population.

The phase 3 ENHANCE-2 trial (NCT04778397) evaluating magrolimab plus azacitidine vs venetoclax (Venclexta) plus azacitidine or intensive chemotherapy in previously untreated patients with TP53-mutant AML and the phase 3 ENHANCE-3 trial (NCT05079230) examining magrolimab plus venetoclax and azacitidine vs placebo plus venetoclax and azacitidine in previously untreated patients with AML who are ineligible for chemotherapy are currently ongoing.¹

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 22, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/7/gilead-to-discontinue-phase-3-enhance-study-of-magrolimab-plus-azacitidine-in-higher-risk-mds
2. Magrolimab + azacitidine versus azacitidine + placebo in untreated participants with myelodysplastic syndrome (MDS) (ENHANCE). ClinicalTrials.gov. Updated June 9, 2023. Accessed July 22, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04313881