A multicenter, single-arm, open-label trial of birociclib, a CDK4/6 inhibitor, as a single agent, in patients with refractory HR+/HER2- metastatic breast cancer.

person Jiayu Wang Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, China info_outline Jiayu Wang, Qingyuan Zhang, Tao Sun, Huiping Li, Ying Cheng, Huihui Li, Zhongsheng Tong, Jingfen Wang, Wei Li, Xinhong Wu, Yuee Teng, Jing Cheng, Zhendong Chen, Zhengqiu Zhu, Chengkong Shi, Li Wang, Mingming Liu, Haiyan Xu, Xianghui Duan, Binghe Xu

Authors person Jiayu Wang Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, China info_outline Jiayu Wang, Qingyuan Zhang, Tao Sun, Huiping Li, Ying Cheng, Huihui Li, Zhongsheng Tong, Jingfen Wang, Wei Li, Xinhong Wu, Yuee Teng, Jing Cheng, Zhendong Chen, Zhengqiu Zhu, Chengkong Shi, Li Wang, Mingming Liu, Haiyan Xu, Xianghui Duan, Binghe Xu Organizations Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, China, Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China, China, Department of Breast Medicine, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, China, China, Department of Breast Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China, China, Department of Oncology, Jilin Cancer Hospital, Changchun, China, Department of Breast Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, China, Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, Department II of breast, Linyi Cancer Hospital, Linyi, China, Cancer Center, the First Hospital of Jilin University, Changchun, China, China, Department of Breast Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology and Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan, China, China, Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China, China, Department of Medical Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun, China, Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China, Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, China, Xuanzhu Biopharmaceutical Co., Ltd., Beijing, China, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Xuanzhu Biopharmaceutical Co., Ltd.,Beijing, China Background: Birociclib is a new molecular entity and selective inhibitor of cyclin‐dependent kinase (CDK) 4 and 6. This phase II study (NCT04539496) was to evaluate the single-agent efficacy and safety of Birociclib in patients with refractory HR+/HER2- metastatic breast cancer (MBC). Methods: This phase II study is a multicenter, single‐arm, open‐label trial in patients with HR + /HER2 - MBC who had progressed after prior endocrine therapy and 1‐2 prior chemotherapy regimens in the metastatic setting. Birociclib 480 mg was administered orally on a continuous schedule twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results: 131 patients were enrolled from 29 hospitals in China between 10/2020 and 8/2021, with a median duration of follow-up of 17.74 months. Among them, 84.7% patients had visceral disease, and 61.1% patients had ≥3 metastatic sites. In the metastatic setting, patients had received a median of 3 (range, 1-6) prior systemic therapies including a median of 1 (1-2) chemotherapy regimen and 2 (1-5) endocrine therapy regimens. The investigator-assessed confirmed ORR was 22.9% (95% CI: 16.0-31.1); DCR was 66.4% (95% CI: 57.6-74.4); CBR was 39.7% (95% CI: 31.3-48.6), among which 1 (0.8%) patient was with confirmed complete response (CR) and 29 (22.1%) patients were with confirmed partial response (PR). Median DoR was 13.1 months (95% CI: 9.4- 16.6). Median PFS was 7.4 months (95% CI: 5.5- 9.2). The OS rates at 12 months and 21 months were 81.8% and 64.6%, respectively. Birociclib demonstrated similar activity in subgroups with visceral disease and liver disease, ORR were 20.7% (95% CI: 13.6-29.5) and 18.5% (95% CI: 9.9-30.0), DCR were 64.9% (95% CI: 55.2-73.7) and 66.6% (95% CI: 51.7-76.9), CBR were 39.6% (95% CI: 30.5-49.4) and 35.4% (95% CI: 23.9-48.2), DoR were 14.8 months (95% CI: 7.6-NA) and 11.2 months (95% CI: 5.5-NA), PFS were 8.2 months (95% CI: 5.5-9.3) and 7.3 months (95% CI: 5.388-9.101), respectively. The most common treatment-emergent adverse events (TEAE) were diarrhea [93.1% (all grades); 18.3% (≥grade 3)], neutropenia [87.0% (all grades); 43.5% (≥grade 3)], and leukocytopenia [86.3% (all grades); 32.8% (≥grade 3)]. Most of AEs were grade 1 or grade 2 and could be alleviated or cured by symptomatic treatment. Conclusions: In patients who have limited treatment options with refractory HR+/HER2- metastatic breast cancer, continuous dosing of single-agent Birociclib exhibited promising and sustaining clinical activity with acceptable safety profile, thus it provided an alternative orally administered therapy option. Clinical trial information: NCT04539496.

Clinical