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.
Authors: Wang Jiayu , Zhang Qingyuan , Sun Tao , Li Huiping , Cheng Ying , Li Huihui , Tong Zhongsheng , Wang Jingfen , Li Wei , Wu Xinhong , Teng Yuee , Cheng Jing , Chen Zhendong , Zhu Zhengqiu , Shi Chengkong , Wang Li , Liu Mingming , Xu Haiyan , Duan Xianghui , Xu Binghe 
Published: June 2023

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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 .