BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer
Hormone-receptor-positive Breast CancerHER2-negative Breast CancerMetastatic Breast Cancer
Investigational drug(s) / intervention(s)
BGB-21447FulvestrantBGB-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)
Facility
City
Region
Status
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.
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