This is the primary report of the randomized, placebo-controlled phase 3 BRIGHT AML 1019 clinical trial of glasdegib in combination with intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated acute myeloid leukemia. Overall survival (primary endpoint) was similar between the glasdegib and placebo arms in the intensive (n = 404; hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.782-1.408; two-sided p = 0.749) and non-intensive (n = 325; HR 0.99; 95% CI: 0.768-1.289; two-sided p = 0.969) studies. The proportion of patients who experienced treatment-emergent adverse events was similar for glasdegib versus placebo (intensive: 99.0% vs. 98.5%; non-intensive: 99.4% vs. 98.8%). The most common treatment-emergent adverse events were nausea, febrile neutropenia, and anemia in the intensive study and anemia, constipation, and nausea in the non-intensive study. The addition of glasdegib to either cytarabine and daunorubicin or azacitidine did not significantly improve overall survival and the primary efficacy endpoint for the BRIGHT AML 1019 phase 3 trial was not met. Clinical trial registration: ClinicalTrials.gov: NCT03416179.

CIBERONC Instituto Carlos 3 Madrid Spain

Department of Clinical Hematology Institute of Hematology and Blood Diseases Hospital Tianjin China

Department of Haematology 3rd Faculty of Medicine Charles University and Faculty Hospital Kralovske Vinohrady Prague Czech Republic

Department of Hematology Medical University of Lodz Lodz Poland

Department of Hematology Oncology Donald and Barbara Zucker School of Medicine at Hofstra Northwell Manhasset NY USA

Department of Internal Medicine and Hematology University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Masaryk University Brno Czech Republic

Division of Hematology and Cellular Therapy Cedars Sinai Cancer Los Angeles CA USA

Division of Hematology Sylvester Comprehensive Cancer Center University of Miami Miami FL USA

Division of Hematology University Hospitals of Cleveland Seidman Cancer Center Case Western Reserve University Cleveland OH USA

Georgia Cancer Center Augusta GA USA

Hospital Universitari i Politècnic La Fe Valencia Spain

Institut de Recherche Saint Louis Hôpital Saint Louis Assistance Publique Hôpitaux de Paris Université Paris Cité Paris France

Pfizer Inc Collegeville PA USA

Pfizer Oncology Pfizer Inc San Diego CA USA

The Royal Marsden Hospital London UK

University of California Irvine Chao Family Comprehensive Cancer Center Orange CA USA

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ClinicalTrials.gov
NCT03416179