Uproleselan With Chemo Fails to Improve EFS in Older Patients With AML

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

Findings from a phase 2/3 study (NCT03701308) reveal that combining uproleselan with 7+3 chemotherapy (daunorubicin and cytarabine) did not significantly improve event-free survival (EFS) compared with chemotherapy alone for older patients with newly diagnosed acute myeloid leukemia (AML).¹

The trial, which enrolled patients aged 60 and older eligible for intensive chemotherapy, did not reach its primary end point of EFS in the phase 2 portion.

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

About the Phase 2/3 Study

The trial sought to assess whether adding uproleselan to daunorubicin and cytarabine could benefit older patients with AML undergoing induction chemotherapy.²

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

The primary end points of the trial were EFS in the phase 2 part and overall survival (OS) in phase 3, with secondary goals including disease-free survival, CR rate, overall response, and adverse event monitoring.

Earlier Findings on Uproleselan Plus Chemotherapy

In previous updates, findings from a separate phase 3 trial (NCT03616470) that included patients with relapsed or refractory AML showed a modest OS benefit with uproleselan plus chemotherapy. Among 388 patients in the intent-to-treat population, the median OS was 13.0 months with uproleselan vs 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 with 10.1 months with placebo (HR, 0.58; 95% CI, 0.37-0.91), suggesting a potential benefit in this group.

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

REFERENCES:

1. GlycoMimetics announces National Cancer Institute phase 2/3 study of uproleselan did not meet primary endpoint. News release. October 29, 2024. Accessed October 31, 2024. https://tinyurl.com/s423tjun

2. Daunorubicin and cytarabine with or without uproleselan in treating older 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 comprehensive results from pivotal phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). News release. GlycoMimetics, Inc. June 4, 2024. Accessed October 31, 2024. https://tinyurl.com/ywn49e3t