An independent data monitoring committee has recommended that a phase 3 trial evaluating uproleselan plus chemotherapy for patients with relapsed/refractory acute myeloid leukemia should continue to the planned overall survival event trigger.
An independent data monitoring committee (IDMC) has recommended that a phase 3 trial (NCT03616470) evaluating uproleselan (GMI-1271) plus chemotherapy for patients with relapsed/refractory acute myeloid leukemia (AML) should continue to the planned overall survival (OS) event trigger.1
The IDMC conducted an interim utility analysis using a very high statistical threshold to preserve the integrity of the originally planned final analysis and expressed no concerns about the E-selectin antagonist’s safety. A review of blinded pooled data shows that patients in the experimental arm continue to live longer than historical benchmarks. The biotechnology firm GlycoMimetics now expects the final survival event trigger to occur in first half of 2024.
“Going forward, survival duration for new events in the study will be greater than 14 months since the last patient was randomized, giving us confidence in the potential for uproleselan to improve outcomes for people living with R/R AML,” Harout Semerjian, chief executive officer of GlycoMimetics, said in a news release. “We are proud to be advancing a novel treatment with significant potential to address the urgent unmet medical need in this acute leukemia.”
The company amended the protocol to create the opportunity to achieve unblinding around 80% of survival events while maintaining the integrity of the final analysis if the IDMC recommend the study continue to the final overall events trigger. The interim analysis plan required a high statistical threshold to be met for the IDMC to recommend unblinding, reserving approximately 95% of the study’s statistical power for the final analysis.
The phase 3 trial is evaluating chemotherapy with mitoxantrone, etoposide, and cytarabine, or fludarabine, cytarabine, and idarubicin, with or without Uproleselan in patients with relapsed/refractory AML. OS is serving as the trial’s primary end point, and secondary end points include severe oral mucositis, overall response rate (ORR), event-free survival, duration of remission, safety, and pharmacokinetics.2
Data from a phase 1/2 study (NCT02306291) published in Blood showed uproleselan plus mitoxantrone, etoposide, and cytarabine chemotherapy demonstrated promising results. Patients in the relapsed/refractory AML cohort (n = 66) experienced an ORR of 39%, including a 33% complete response (CR) rate. Patients with newly diagnosed AML (n = 25) experienced an ORR of 72% with a 52% CR rate.3
Uproleselan also induced a minimal residual disease (MRD)–negativity rate of 69% in the relapsed/refractory arm and 56% in the newly diagnosed arm. At a median follow-up of 9.7 months, patients who received the recommended phase 2 dose of uproleselan (10 mg/kg; n = 54) in the relapsed/refractory cohort had a median OS was 8.8 months (95% CI, 5.7-11.4). Median OS was 12.6 months (95% CI, 9.9-not reached) in the newly diagnosed cohort.
Brian A. Jonas, MD, PhD, an associate professor of medicine at UC Davis Health in Sacramento, California, discussed future uses for uproleselan plus chemotherapy in patients with relapsed/refractory AML with OncLive® in November 2022. “Uproleselan seemed to enhance the efficacy of the chemotherapy, [and] it seemed to have a favorable safety profile,” he said.
“Uproleselan has a potential role with any treatment of AML,” Jonas added. “It has a potential role with any stage of disease and any disease population. Indeed, preclinical data support its use in combination with other regimens like azacitidine. The uses of uproleselan could certainly expand, so a combination with venetoclax [Venclexta] is a reasonable idea.”