404P - 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

Background

Birociclib is a selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. This phase II study (NCT04539496) was to evaluate the efficacy and safety of birociclib as single-agent in patients with refractory HR+/HER2- metastatic breast cancer (MBC).

Methods

The patients with HR⁺/HER2^- MBC who had progressed after prior endocrine therapy and 1-2 prior chemotherapy regimens in the metastatic setting were eligible. 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) assessed by Independent Reivew Committee (IRC) per RECIST v1.1. Other endpoints included investigator-assessed ORR,duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety,etc.

Results

131 patients were enrolled from 29 hospitals in China between 10/2020 and 08/2021. As of Nov 30, 2022, the median duration of follow-up was 19.0 months. Median duration of treatment was 6 months. The majority (84.7%) patients had visceral metastasis, 60.3% of patients had ≥3 metastatic organs. In the metastatic setting, patients had received a median of 3 prior systemic therapies including a median of 1 chemotherapy regimen and 2 endocrine therapy regimens. The main results are shown in the table. Table: 404P

Responses according to RECIST v1.1

The most common treatment-emergent adverse events (TEAEs) were gastrointestinal and hematological toxicity, common to CDK4/6 inhibitors. Most of these AEs were grade 1-2, and manageable with supportive treatments.

Conclusions

In patients with refractory HR+/HER2- MBC who have previously received chemotherapy and endocrine therapy, continuous dosing of single-agent birociclib exhibited promising and sustaining clinical activity with manageable toxicities, thus it provides an alternative orally single-agent therapy.

Clinical trial identification

NCT04539496.

Editorial acknowledgement

Legal entity responsible for the study

Xuanzhu Biopharmaceutical Co., Ltd.

Funding

Xuanzhu Biopharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.