Uproleselan Plus Chemo Fails to Improve OS in R/R AML in China

The addition of uproleselan (GMI-1271) to chemotherapy did not lead to an improvement in overall survival (OS) compared with chemotherapy alone in patients with relapsed/refractory acute myeloid leukemia (AML), according to topline data from a phase 3 trial (NCT05054543) conducted in China.1

Findings showed that patients treated with uproleselan plus chemotherapy (n = 69) experienced a median OS of 9.3 months (95% CI, 6.1-16.0) compared with 14.3 months (95% CI, 6.2-not applicable) in patients treated with chemotherapy plus placebo (n = 71; P = .48).

The safety profile of uproleselan plus chemotherapy was similar to that of chemotherapy alone. Serious adverse effects (AEs) occurred in 43% of patients in the uproleselan arm vs 39% of patients in the chemotherapy arm. The most common serious AEs in the experimental group included decreased platelet count, infectious pneumonia, and sepsis.

In October 2024, data from a phase 2/3 trial (NCT03701308) conducted in the United States demonstrated that uproleselan plus cytarabine and daunorubicin did not produce a statistically significant improvement in event-free survival (EFS) vs chemotherapy alone in adult patients with newly diagnosed AML who were 60 years of age or older and fit for intensive chemotherapy.2

“While we are disappointed that uproleselan did not show a clinical benefit, the results were expected given that the global phase 3 trial of uproleselan in a similar patient population by our partner, Glycomimetics, did not meet its primary end point earlier this year. Our regulatory and commercial strategy in China has always required a positive global phase 3 trial, and therefore we are currently wrapping up this program,” Guo-Liang Yu, PhD, chairman and chief executive officer of Apollomics, stated in a news release.1 “We extend our thanks and gratitude to all the patients and their families, investigators and clinical team that supported the trial.”

The phase 3 trial conducted in China enrolled patients 18 to 75 years of age with relapsed/refractory AML and myeloid marrow blasts or peripheral blood blasts levels of at least 20%.2 No more than one prior stem cell transplant was allowed prior to enrollment, and patients were not allowed to have prior treatment with the mitoxantrone, etoposide, and cytarabine (MEC) chemotherapy regimen used as induction during the study. Patients needed to medically eligible to receive MEC.

Key exclusion criteria consisted of acute promyelocytic leukemia; acute leukemia of ambiguous lineage; chronic myeloid leukemia with myeloid blast crisis; active signs or symptoms of central nervous system involvement; receipt of a stem cell transplant within 4 months of first study dosing; any treatment with immunotherapy or radiotherapy within 28 days of first dosing; treatment with any other experimental therapy or chemotherapy within 14 days of enrollment; inadequate organ function; abnormal liver function; moderate kidney dysfunction defined as a glomerular filtration rate of less than 45 mL/min; uncontrolled acute life-threatening bacterial, viral, or fungal infections; clinically significant cardiovascular disease; and major surgery within 4 weeks of dosing.

Patients were randomly assigned to receive uproleselan or placebo in combination with chemotherapy. Uproleselan or placebo were first combined with MEC during induction before being paired with intermediate- and high-dose cytarabine as consolidation.

OS served as the trial’s primary end point. Secondary end points included remission rates, duration of remission, EFS, and the rate of severe oral mucositis.

Full results from the phase 3 trial will be submitted for presentation at an upcoming medical conference.1

References

1. Apollomics Announces top-line results for phase 3 bridging trial of uproleselan in China in patients with relapsed or refractory acute myeloid leukemia. News release. Apollomics. December 20, 2024. Accessed December 20, 2024. https://ir.apollomicsinc.com/news-releases/news-release-details/apollomics-announces-top-line-results-phase-3-bridging-trial
2. Study to evaluate the efficacy of uproleselan in combination with chemotherapy in Chinese patients with R/R AML. ClinicalTrials.gov. Updated November 24, 2021. Accessed December 20, 2024. https://clinicaltrials.gov/study/NCT05054543