BEBT-209, a primary CDK4 selective inhibitor, for the treatment of HR+ / HER2-advanced breast cancer (BECTOP1) - A phase 1, multicentre, open-label study

Sep 23, 2026

Uploaded by Pentious

BEBT-209 is evaluated as a primary CDK4-selective inhibitor for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. The phase 1, multicentre, open-label trial enrolled Chinese patients, with dose-limiting toxicity and maximum tolerated dose as primary endpoints. Secondary outcomes included objective response rate, clinical benefit rate, progression-free survival, and pharmacokinetic parameters. Dose escalation identified DLT at 150 mg twice daily, with MTD at 100 mg twice daily and neutropenia as the most common adverse event.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Purpose

Patients and methods

Results

Conclusion

Introduction

The Breast 83 (2025) 104527 Contents lists available at ScienceDirect The Breast journal [homepage:](homepage: www.journals.elsevier.com/the-breast)[ www.journals.elsevier.com/the-breast](homepage: www.journals.elsevier.com/the-breast) | BEBT-209, a primary CDK4 selective inhibitor, for the treatment of HR+/ HER2-advanced breast cancer (BECTOP1): a phase 1, multicentre,
open-label study
Zhe-Yu Hua,b, Kegang Jiang c, Can Tiana,b, Fan Zhang c, Yehui Shid, Ying Wang e, Wei Lif, Biao Wug, Boni Dingh, Liping Liu a,b, Huawu Xiao a,b, Xiaohong Yanga,b, Jing Lia,b, Ning Xiea,b, Binliang Liu a,b, Shouman Wangi,*, Quchang Ouyanga,b,**
a Medical Department of Breast Cancer, Hunan Cancer Hospital, Changsha, China
b Medical Department of Breast Cancer, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China c BeBetter Med Inc., Guangzhou, China
d Tianjin Medical University Cancer Institute & Hospital, Tianjin, China e Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China f The First Hospital of Jilin University, Changchun, China
g Department of Breast, The First Affiliated Hospital of Nanchang University, Nanchang, China h Department of Breast, The Third Xiangya Hospital of Central South University, Changsha, China i Department of Breast, Xiangya Hospital, Central South University, Changsha, China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords:
Advanced breast cancer HR+
HER2-
Endocrine therapy
A primary CDK4 selective inhibitor BEBT-209 | | Purpose: Several cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Despite the side effects that affect patients’ quality of life, most patients still opt for CDK4/6 inhibitors due to their significant benefits. However, to further enhance treatment efficacy and safety, new approaches are still needed.
Patients and methods: This multicentre, open-label, Phase 1 trial enrolled Chinese patients with HR+, HER2-advanced breast cancers. The primary endpoints were dose-limiting toxicity (DLT), maximum tolerated dose (MTD). Secondary endpoints included the objective response rate (ORR), clinical benefit rate (CBR), progressionfree survival (PFS), and pharmacokinetic parameters.
Results: During the dose-escalation phase, a DLT was observed in the 150 mg bid dose cohort, specifically, 2 patients experienced grade 4 neutropenia. MTD of BEBT-209 was 100 mg bid, and the most common adverse event (AE) was neutropenia. In Phase 1b, the median PFS of patients with BEBT-209 alone, BEBT-209 plus letrozole, and BEBT-209 plus fulvestrant was 10.38 months, 24.94 months, and not reached, respectively. At doses of 25 mg qd–150 mg bid, steady state areas under the concentration–time curve and peak concentration increased proportionally with dose. The most common grade 3 or 4 AEs were neutropenia (65.4 %), lymphocytopenia (7.4 %), and anaemia (4.9 %).
Conclusion: BEBT-209 was a primary CDK4 selective inhibitor and showed an acceptable safety profile and dosedependent plasma exposure. The results highlight the potential of combination treatments as compelling options, particularly in combination with fulvestrant. | 1. Introduction Cyclin-dependent kinases 4/6 (CDK4/6) are key regulators ofthe cell cycle [1]. . CDK4/6 inhibitors reportedly inhibit tumour cell progression during the G1 phase [2,3]. In hormone receptor-positive (HR+ ) breast cancer, the overexpression of CDK4/6 leads to unchecked cell * Corresponding author. Department of Breast, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 41000, China. ** Corresponding author. Medical Department of Breast Cancer, Hunan Cancer Hospital, No. 283, Tongzipo Road, Changsha, 410013, China. E-mail [addresses:](addresses: wangshouman@126.

FAQs

What is the purpose of this phase 1 study of BEBT-209?

To assess a new CDK4-selective approach that could improve efficacy and safety for HR+/HER2- advanced breast cancer, given the benefits and side effects of existing CDK4/6 inhibitors.

What were the primary endpoints and how were they measured?

Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) were used as the primary endpoints during the dose-escalation phases.

What dosing and safety results were reported for BEBT-209?

DLT occurred in the 150 mg twice-daily cohort, with grade 4 neutropenia in 2 patients. The MTD was 100 mg twice daily, and neutropenia was the most common adverse event.

Sep 23, 2026

Uploaded by Pentious