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Recruiting Phase 1

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer

NCT06756932 · tracked via the Priya Life Science USA tracker
Phase
Phase 1
Started
2025-02-04
Last updated
2026-09-14

Condition(s) studied

Hormone-receptor-positive Breast CancerHER2-negative Breast CancerMetastatic Breast Cancer

Investigational drug(s) / intervention(s)

BGB-21447Fulvestrant →BGB-43395 →

BGB-21447: Administered orally.

Fulvestrant: Administered via intramuscular injection.

BGB-43395: Administered orally.

Study summary

This is a dose escalation and dose expansion study to assess the safety and tolerability of BGB-21447 (a B-cell leukemia/lymphoma 2 inhibitor, Bcl-2i) in combination with fulvestrant, with or without BGB-43395 (cyclin-dependent kinase 4 inhibitor, CDK4i), in adults with HR+/HER2- metastatic breast cancer.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * Histologically or cytologically confirmed HR+/HER2- metastatic breast cancer. Part 1A and 1B: Participants must have received ≥ 1 prior line(s) of treatment for advanced/metastatic disease, including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting. Part 2: Participants must have received 1-3 prior line(s) of treatment for advanced/metastatic disease, including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting. * Female participants will be required (either continue ongoing or initiate as soon as feasible) to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal. * Male participants may be required to use GnRH agonists when being treated with fulvestrant at the discretion of the investigator. * Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1. * Adequate organ function. * Female participants of childbearing potential and nonsterile male participants with female partners of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for 7 days after the last dose of BGB-21447, 6 months after the last dose of BGB-43395, and 2 years after the last dose of fulvestrant. * Food effect substudy only: Participants who are able and willing to fast overnight (≥ 10 hours) and consume a high-fat meal. Exclusion Criteria: * Prior Bcl-2 inhibitor exposure. For triplet combination cohorts only: Prior therapy selectively targeting CDK4. * Known leptomeningeal disease or uncontrolled, untreated brain metastases. * Any malignancy ≤ 3 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, treated papillary thyroid carcinoma, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast). * For Part 1B: Uncontrolled diabetes. * History of hepatitis B or active Hepatitis C infection * China Only: Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA \> 500 IU/ml (or \> 2500 copies/ml) at screening. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcome measure(s)

  • Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) — From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and AEs that meet protocol-defined dose-limiting toxicity criteria.
  • Part 1: Recommended Dose for Expansion (RDFE) of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395 — From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 6 to 9 months
    RDFE of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395 will be determined based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD).
  • Part 2: Objective Response Rate (ORR) — Approximately 12 months
    ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Trial sites (14)

FacilityCityRegionStatus
University of Iowa Hospitals and Clinics Iowa City Iowa Recruiting
Md Anderson Cancer Center Houston Texas Recruiting
Fred Hutchinson Cancer Research Center Seattle Washington Recruiting
Saint Vincents Hospital Sydney Darlinghurst New South Wales Terminated
Calvary Mater Newcastle Waratah New South Wales Recruiting
Sunshine Coast University Private Hospital Birtinya Queensland Recruiting
Peter Maccallum Cancer Centre Melbourne Victoria Recruiting
Western Health Sunshine Hospital St Albans Victoria Recruiting
Linear Clinical Research Nedlands Western Australia Recruiting
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South) Guangzhou Guangdong Recruiting
The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan Recruiting
Fudan University Shanghai Cancer Centerpudong Shanghai Shanghai Municipality Recruiting
Tianjin Medical University Cancer Institute and Hospital Tianjin Tianjin Municipality Recruiting
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou Zhejiang Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06756932 on ClinicalTrials.gov ↗ ← All trials in the USA