这是未经处理的急性髓系白血病患者中，加乐斯替吉布与强化化疗（阿糖胞苷和多柔比星）或非强化化疗（阿扎胞苷）相结合的随机安慰剂对照第3期BRIGHT AML 1019临床试验的主要报告。总体生存率（主要终点）在强化治疗（n = 404; 风险比 [HR] 1.05; 95%置信区间 [CI]: 0.782-1.408; 双侧 P = 0.749）和非强化治疗（n = 325; HR 0.99; 95% CI: 0.768-1.289; 双侧 P = 0.969）研究中，加乐斯替吉布与安慰剂组间相似。加乐斯替吉布与安慰剂组间经历治疗出现不良事件的患者比例相似（强化治疗：99.0% vs. 98.5%; 非强化治疗：99.4% vs. 98.8%）。在强化治疗研究中，最常见的治疗出现不良事件是恶心、发热性粒细胞减少症和贫血；在非强化治疗研究中，最常见的治疗出现不良事件是贫血、便秘和恶心。加乐斯替吉布与阿糖胞苷和多柔比星或阿扎胞苷相结合，未显著改善总体生存率，BRIGHT AML 1019第3期试验的主要疗效终点未达到。临床试验登记：ClinicalTrials.gov：NCT03416179.© 2023. 作者。

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.© 2023. The Author(s).