An open‐label, single‐arm, multicenter, phase II trial of bireociclib as monotherapy for heavily pretreated HR‐positive, HER2‐negative advanced breast cancer patients: BRIGHT‐1 trial

作者：Jiayu Wang, Qingyuan Zhang, Tao Sun, Huiping Li, Ying Cheng, Zhongsheng Tong, Huihui Li, Wei Li, Jingfen Wang, Yuee Teng, Xinhong Wu, Jing Cheng, Zhendong Chen, Zhengqiu Zhu, Wang Li, Mingming Liu, Xianghui Duan, Lufan Xu, Binghe Xu · 发表于：癌症：英文版 · 年份：2025 · DOI：10.1002/cac2.70009 · 被引用次数：5 · 研究领域：Advanced Breast Cancer Therapies、Cancer-related Molecular Pathways、HER2/EGFR in Cancer Research

Abstract Background Bireociclib (XZP‐3287) is a novel selective cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor, with a favorable safety profile demonstrated in preclinical and phase I studies. BRIGHT‐1 aimed to further explore the efficacy and safety of bireociclib monotherapy in patients with locally advanced, recurrent or metastatic, hormone receptor‐positive and human epidermal growth factor receptor 2‐negative (HR + /HER2 − ) breast cancer who had progressed on or after prior chemotherapy and endocrine therapy in advanced settings, without previous exposure to CDK4/6 inhibitors. Methods In this open‐label phase II trial, eligible patients received bireociclib 480 mg twice daily (BID) until disease progression or intolerable toxicities. The primary endpoint was the confirmed objective response rate (ORR) assessed by an independent review committee (IRC). The secondary endpoints included progression‐free survival (PFS), investigator‐assessed ORR, disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), overall survival (OS), safety and the pharmacokinetic properties of bireociclib. Results A total of 131 patients were enrolled. At data cutoff (July 31, 2023), the IRC‐assessed ORR was 29.8% (95% confidence interval [CI], 22.1% to 38.4%), with a DCR of 73.3% (95% CI, 64.8% to 80.6%), CBR of 42.0% (95% CI, 33.4% to 50.9%) and a median DoR of 15.2 months (95% CI, 9.5 months to not reached). The median PFS was 11.0 months (95% CI, 7.3 months to 12...