Uproleselan Plus Chemotherapy Fails to Improve EFS in Older Patients With AML

Harout Semerjian, CEO of GlycoMimetics

The combination of uproleselan and standard cytarabine plus daunorubicin (7+3) chemotherapy failed to elicit a statistically significant improvement in event-free survival (EFS) vs 7+3 chemotherapy alone in adult patients with newly diagnosed acute myeloid leukemia (AML) who are 60 years or older and fit for intensive chemotherapy, according to an announcement from GlycoMimetics regarding the phase 2 analysis of the adaptive phase 2/3 trial (NCT03701308) being conducted by the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology.¹

GlycoMimetics is working with the Alliance group to receive the full trial data for further analysis, including subgroup analysis to determine whether there are efficacy signals in other patient populations that may warrant additional study in future clinical trials.

Topline data from the trial are anticipated to be presented by the NCI at an upcoming medical meeting.

Earlier in May 2024, GlycoMimetics announced that uproleselan plus chemotherapy failed to achieve a statistically significant improvement in overall survival (OS) vs chemotherapy alone in the intention-to-treat population of patients with relapsed/refractory AML (n = 388) enrolled in a global phase 3 trial (NCT03616470). Topline results indicated that the median OS was 13 months with the combination vs 12.3 months with chemotherapy alone. In terms of safety, adverse effects were consistent with the known toxicity profiles of the chemotherapy agents that were used in the trial.2 The study has since been terminated.³

The randomized, double-blind, placebo-controlled phase 3 study evaluated uproleselan in combination with MEC (mitoxantrone, etoposide and cytarabine) or FAI (fludarabine, cytarabine, and idarubicin) in patients with relapsed/refractory AML. Eligible patients were between the ages of 18 and 75 and considered candidates for intensive induction chemotherapy. In addition to having relapsed/refractory disease patients could not have undergone more than 1 prior stem cell transplant or received the chemotherapy regimen intended for induction in the trial’s protocol.^2,3

Patients received either uproleselan or placebo for 1, 8-day cycle for induction and, if applicable, up to 3 cycles of consolidation.²

The primary end point of the study was OS without censoring for transplant. Secondary end points included incidence of severe oral mucositis, complete remission rate, and remission rate. Patients enrolled across 70 sites in 9 countries were randomly assigned 1:1 to either treatment arm.²

In December 2021, GlycoMimetics announced that it had completed enrollment of the 267 patients in the phase 2 portion of the adaptive phase 2/3 trial, allowing for the planned evaluation of the phase 2 portion of the trial to determine whether the prespecified threshold for continuing to phase 3 had been met based on EFS.⁴

At the time, Harout Semerjian, chief executive officer of GlycoMimetics said, “I would like to thank the Alliance for completing the enrollment of the phase 2 portion despite all the logistical challenges associated with the pandemic. If the EFS analysis meets the preplanned metric, the data will be transferred confidentially to GlycoMimetics to support regulatory filings for uproleselan in AML, and enrollment will continue in the phase 3 portion of the trial. Together, the GlycoMimetics- and NCI-sponsored programs will constitute a large dataset of 650 patients with AML. We would anticipate filing with regulatory agencies for approval for treatment of patients in both the frontline and relapsed/refractory AML settings should both trials achieve positive readouts.”4

References

1. GlycoMimetics announces national cancer institute phase 2/3 study of uproleselan did not meet primary end point. News release. GlycoMimetics. October 29, 2024. Accessed October 29, 2024. https://ir.glycomimetics.com/news-releases/news-release-details/glycomimetics-announces-national-cancer-institute-phase-23-study
2. GlycoMimetics announces results of pivotal phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). News release. GlycoMimetics. May 6, 2024. Accessed October 29, 2024. https://ir.glycomimetics.com/news-releases/news-release-details/glycomimetics-announces-results-pivotal-phase-3-study
3. Study to determine the efficacy of uproleselan (GMI-1271) in combination with chemotherapy to treat relapsed/refractory acute myeloid leukemia. ClinicalTrials.gov. Updated July 29, 2024. Accessed October 29, 2024. https://clinicaltrials.gov/study/NCT03616470
4. NCI-sponsored trial of uproleselan in older, newly diagnosed AML patients fit for intensive chemotherapy completes enrollment of phase 2 portion ahead of schedule. News release. GlycoMimetics. December 6, 2021. Accessed October 29, 2024. https://glycomimeticsinc.gcs-web.com/news-releases/news-release-details/nci-sponsored-trial-uproleselan-older-newly-diagnosed-aml