Acute myeloid leukemia (AML) cells: © LASZLO – stock.adobe.com

Results from a phase 2/3 study (NCT03701308) reveal that the combination of uproleselan with 7+3 chemotherapy (daunorubicin and cytarabine) did not significantly improve event-free survival (EFS) by compared to chemotherapy alone in elderly patients with newly diagnosed acute myeloid leukemia (AML).¹

The trial, which enrolled patients aged 60 and older eligible for intensive chemotherapy, did not meet its primary endpoint of EFS in phase 2.

The National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology plan to further analyze the results, exploring the effectiveness of subgroups that could support additional research. The full results are expected to be presented at an upcoming medical meeting.

About the phase 2/3 study

The trial aimed to evaluate whether adding uproleselan to daunorubicin and cytarabine could benefit older AML patients undergoing induction chemotherapy.²

In the experimental group, patients received uproleselan intravenously on day 1, followed by dosing every 12 hours from day 2 to day 10, in combination with daunorubicin on days 2 to 4 and infusion continuous cytarabine for 7 days on days 2 through 8. For those achieving a complete response (CR) or CR with incomplete blood count recovery, uproleselan was administered during consolidation once on day 1 and then every 12 hours on days 2 to 8, in combination with cytarabine over a course of 5 days, every 28 days for a maximum of 3 days. cycles if there was no progression or excessive toxicity.

The primary endpoints of the trial were EFS in phase 2 and overall survival (OS) in phase 3, with secondary objectives including disease-free survival, CR rate, overall response and monitoring of adverse events.

Previous results on Uproleselan Plus chemotherapy

In previous updates, the results of a separate phase 3 trial (NCT03616470) which included patients with relapsed or refractory AML showed a small OS benefit with uproleselan plus chemotherapy. Among 388 patients in the intention-to-treat population, median OS was 13.0 months with uproleselan versus 12.3 months with placebo, but this difference was not statistically significant (HR: 0.89; 95% CI: 0.69-1.15).³

In a subgroup analysis, patients with primary refractory AML saw a median OS of 31.2 months with uproleselan, compared to 10.1 months with placebo (HR: 0.58; 95% CI, 0.37-0.91), suggesting a potential benefit in this group.

Additional data from subgroups of patients with early relapse showed a median OS of 3.7 months with uproleselan versus 6.4 months with placebo (HR: 1.50; 95% CI: 0.69 -3.27). In patients with late relapse, median OS was 15.4 months with uproleselan versus 18.2 months with placebo (HR: 1.10; 95% CI, 0.77-1.57), highlighting the need for further analysis of treatment timing and outcomes.

REFERENCES:

1. GlycoMimetics announces that the National Cancer Institute’s Phase 2/3 study of uproleselan did not meet the primary endpoint. Press release. October 29, 2024. Accessed October 31, 2024. https://tinyurl.com/s423tjun

2. Daunorubicin and cytarabine with or without uproleselan in the treatment of elderly adult patients with acute myeloid leukemia receiving intensive induction chemotherapy. ClinicalTrials.gov. Updated October 9, 2024. Accessed October 31, 2024. https://clinicaltrials.gov/study/NCT03701308

3. GlycoMimetics announces full results from a pivotal Phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). Press release. GlycoMimetics, Inc. June 4, 2024. Accessed October 31, 2024.