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

NCT ID: NCT06756932

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-04

Study Completion Date

2027-07-30

Brief Summary

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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.

Detailed Description

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This new study will check how safe and helpful a potential anticancer drug called BGB-21447 (Bcl-2i) is. This drug will be tested in combination with fulvestrant, with or without BGB-43395 (CDK4i), in adults with metastatic breast cancer.

HR+/HER2- tumors account for approximately 70% of all breast cancers and are responsible for most breast cancer-related deaths. While CDK4/6 inhibitors combined with endocrine therapy have improved outcomes for patients with HR+/HER2- metastatic breast cancer, patients eventually develop progressive disease on these therapies and require new treatments.

BGB-21447 is an oral drug that is highly potent and selectively stops a protein called B-cell lymphoma-2 (Bcl-2). Bcl-2 proteins are often overexpressed in some cancers (like HR+ breast cancer) by keeping the cancer cells from dying. Disrupting this pathway is believed to lead to cell death.

BGB-43395 is an oral drug that selectively stops a protein called cyclin-dependent kinase 4 (CDK4). CDK4 is a type of protein that regulates cell growth and division in your body.

Fulvestrant is a treatment that blocks estrogen receptors and reduces estrogen production. Fulvestrant has been approved to treat hormone receptor positive metastatic breast cancer to help stop the cancer cells from growing.

This combination might be a good way to fight cancer, aiming to give patients the best possible treatment. The study is designed to see if this combination is safe and works well.

Conditions

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Hormone-receptor-positive Breast Cancer HER2-negative Breast Cancer Metastatic Breast Cancer

Keywords

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BGB-21447 BGB-43395 metastatic breast cancer Bcl-2i CDK4i

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1A: BGB-21447 + Fulvestrant

Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant.

Group Type EXPERIMENTAL

BGB-21447

Intervention Type DRUG

Administered orally.

Fulvestrant

Intervention Type DRUG

Administered via intramuscular injection.

Part 1B: BGB-21447 + BGB-43395 + Fulvestrant

Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395.

Group Type EXPERIMENTAL

BGB-21447

Intervention Type DRUG

Administered orally.

Fulvestrant

Intervention Type DRUG

Administered via intramuscular injection.

BGB-43395

Intervention Type DRUG

Administered orally.

BGB-21447 + Fulvestrant Food Effect Substudy

Participants will receive BGB-21447 at the recommended dose with a high-fat meal and under a fasted state in combination with fulvestrant.

Group Type EXPERIMENTAL

BGB-21447

Intervention Type DRUG

Administered orally.

Fulvestrant

Intervention Type DRUG

Administered via intramuscular injection.

Part 2: Dose Expansion, BGB-21447 + Fulvestrant

Participants will receive BGB-21447 at the recommended dose(s) for expansion determined in Part 1A in combination with fulvestrant.

Group Type EXPERIMENTAL

BGB-21447

Intervention Type DRUG

Administered orally.

Fulvestrant

Intervention Type DRUG

Administered via intramuscular injection.

Interventions

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BGB-21447

Administered orally.

Intervention Type DRUG

Fulvestrant

Administered via intramuscular injection.

Intervention Type DRUG

BGB-43395

Administered orally.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeOne Medicines

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeOne Medicines

Locations

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Hoag Memorial Presbyterian

Newport Beach, California, United States

Site Status RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

Md Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status RECRUITING

Saint Vincents Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status RECRUITING

Sunshine Coast University Private Hospital

Birtinya, Queensland, Australia

Site Status RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Western Health Sunshine Hospital

St Albans, Victoria, Australia

Site Status RECRUITING

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status RECRUITING

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)

Guangzhou, Guangdong, China

Site Status RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, China

Site Status RECRUITING

Fudan University Shanghai Cancer Centerpudong

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Site Status RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

Countries

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United States Australia China

Central Contacts

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Study Director

Role: CONTACT

Phone: 1.877.828.5568

Email: [email protected]

Other Identifiers

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CTR20250114

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-21447-102

Identifier Type: -

Identifier Source: org_study_id