A phase 2/3 clinical trial evaluating the addition of uproleselan to standard daunorubicin and cytarabine chemotherapy did not demonstrate a statistically significant improvement in event-free survival (EFS) compared to chemotherapy alone in older patients with newly diagnosed acute myeloid leukemia (AML). The study, designed to assess the efficacy of the combination in patients 60 years and older eligible for intensive induction chemotherapy, failed to meet its primary endpoint.
The trial involved an induction phase where patients in the experimental arm received intravenous uproleselan in conjunction with daunorubicin and cytarabine. Those achieving complete remission (CR) or CR with incomplete hematologic recovery were eligible for consolidation therapy, which included uproleselan and cytarabine, repeated every 28 days for a maximum of three cycles.
The primary endpoints of the trial were EFS in the phase 2 portion and overall survival (OS) in the phase 3 portion. Secondary endpoints included disease-free survival, CR rate, overall response rate, and incidence of adverse effects. Eligible patients were required to have a diagnosis of AML per 2017 World Health Organization criteria, without activating FLT3 mutations or central nervous system involvement, and no prior chemotherapy for related conditions.
Comprehensive results from a previous phase 3 trial evaluating uproleselan in relapsed/refractory AML, announced in June 2024, showed a median OS of 13.0 months with uproleselan/chemotherapy versus 12.3 months with placebo/chemotherapy (HR, 0.89; 95% CI, 0.69-1.15), which was not statistically significant. However, a subgroup of patients with primary refractory disease showed a notable difference, with median OS of 31.2 months in the uproleselan arm compared to 10.1 months in the placebo arm (HR, 0.58; 95% CI, 0.37-0.91).
According to a press release, investigators from the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology are further evaluating the trial findings, including subgroup analysis, to identify potential efficacy signals that may warrant further study. Topline data from the phase 2/3 trial will be shared at a future medical meeting.
