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Hormone-receptor-positive Breast CancerPhase 1NCT06756932

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

A Phase 1 study testing BGB-21447, Fulvestrant and BGB-43395 in people with Hormone-receptor-positive Breast Cancer and HER2-negative Breast Cancer, run by BeOne Medicines at 14 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BGB-21447, Fulvestrant and BGB-43395
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
14 sitesin 3 countries
Study dates
4 Feb 2025to 30 Jul 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Study Director contact

1.877.828.5568

clinicaltrials@beonemed.com

14 sites in 3 countries

Australia6 sites, 5 recruiting

  • Sunshine Coast University Private Hospital

    Birtinya, Queensland, QLD 4575

    Recruiting

  • Saint Vincents Hospital Sydney

    Darlinghurst, New South Wales, NSW 2010

    Terminated

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, VIC 3000

    Recruiting

  • Linear Clinical Research

    Nedlands, Western Australia, WA 6009

    Recruiting

  • Western Health Sunshine Hospital

    St Albans, Victoria, VIC 3021

    Recruiting

  • Calvary Mater Newcastle

    Waratah, New South Wales, NSW 2298

    Recruiting

Other trials in Australia

China5 sites, 5 recruiting

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

    Guangzhou, Guangdong, 510245

    Recruiting

  • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310016

    Recruiting

  • Fudan University Shanghai Cancer Centerpudong

    Shanghai, Shanghai Municipality, 201321

    Recruiting

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, Tianjin Municipality, 300060

    Recruiting

  • The First Affiliated Hospital of Zhengzhou University

    Zhengzhou, Henan, 450052

    Recruiting

Other trials in China

United States3 sites, 3 recruiting

  • Md Anderson Cancer Center

    Houston, Texas, 77030-3907

    Recruiting

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242-1009

    Recruiting

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109-4433

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-21447 (a Bcl-2 Inhibitor) Combinations for Patients With HR+/HER2- Metastatic Breast Cancer

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.

Read the detailed description

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.

Being tested
BGB-21447, Fulvestrant, BGB-43395
Keywords
BGB-21447, BGB-43395, metastatic breast cancer, Bcl-2i, CDK4i
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BGB-21447Drug

    Administered orally.

  • FulvestrantDrug

    Administered via intramuscular injection.

  • BGB-43395Drug

    Administered orally.

Study groups in NCT06756932
Study groupRoleWhat they receive
Part 1A: BGB-21447 + FulvestrantExperimentalSequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant.
Receives: Drug: BGB-21447; Drug: Fulvestrant
Part 1B: BGB-21447 + BGB-43395 + FulvestrantExperimentalSequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395.
Receives: Drug: BGB-21447; Drug: Fulvestrant; Drug: BGB-43395
BGB-21447 + Fulvestrant Food Effect SubstudyExperimentalParticipants will receive BGB-21447 at the recommended dose with a high-fat meal and under a fasted state in combination with fulvestrant.
Receives: Drug: BGB-21447; Drug: Fulvestrant
Part 2: Dose Expansion, BGB-21447 + FulvestrantExperimentalParticipants will receive BGB-21447 at the recommended dose(s) for expansion determined in Part 1A in combination with fulvestrant.
Receives: Drug: BGB-21447; Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Measured: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months

  2. Part 1: Recommended Dose for Expansion (RDFE) of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395

    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).

    Measured: 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

  3. Part 2: Objective Response Rate (ORR)

    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.

    Measured: Approximately 12 months

Secondary outcomes (13)

  1. Part 1: ORR

    ORR is defined as the percentage of participants who had confirmed CR or PR as assessed by the investigator per RECIST v1.1.

    Measured: Approximately 12 months

  2. Parts 1 and 2: Duration of Response (DOR)

    DOR is defined as the time from the first determination of an objective response until the first documentation of progression or death, whichever comes first, as assessed by the investigator per RECIST v1.1.

    Measured: Approximately 12 months

  3. Part 1:Time to Response (TTR)

    TTR is defined as the time from the date of the first dose of study drug to the date of the first CR or PR, as assessed by the investigator per RECIST v1.1.

    Measured: Approximately 12 months

  4. Part 2: Disease Control Rate (DCR)

    DCR is defined as the percentage of participants with best overall response of a CR, PR, and stable disease.

    Measured: Approximately 12 months

  5. Part 2: Clinical Benefit Rate (CBR)

    CBR is defined as the percentage of participants who achieve CR, PR, or durable stable disease (stable disease ≥ 24 weeks).

    Measured: Approximately 12 months

  6. Part 2: Progression-Free Survival (PFS)

    PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of progressive disease as assessed by the investigator, or death, whichever occurs first. The progressive disease assessment is based on RECIST v1.1.

    Measured: Approximately 12 months

  7. Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.

    Measured: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months

  8. Maximum observed plasma concentration (Cmax) of BGB-21447 and BGB-43395

    Measured: Up to approximately 2 months

  9. Time to reach maximum observed plasma concentration (Tmax) of BGB-21447 and BGB-43395

    Measured: Up to approximately 2 months

  10. Area under the concentration-time curve (AUC) of BGB-21447 and BGB-43395

    Measured: Up to approximately 2 months

  11. Apparent terminal elimination half-life (t1/2) of BGB-21447 and BGB-43395

    Measured: Up to approximately 2 months

  12. Food Effect Substudy: AUC of BGB-21447 under fasted and fed state

    Measured: Up to approximately 2 months

  13. Food Effect Substudy: Cmax of BGB-21447 under fasted and fed state

    Measured: Up to approximately 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2025
  2. Study start4 Feb 2025
  3. Primary completion30 Jul 2027 (estimated)
  4. Study completion30 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06756932
Sponsor's protocol ID
BGB-21447-102
Other IDs
CTR20250114
Status last verified
Nov 2025
First submitted
24 Dec 2024
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BGB-21447, Fulvestrant and BGB-43395 in people with Hormone-receptor-positive Breast Cancer and HER2-negative Breast Cancer, run by BeOne Medicines at 14 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Australia, China, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Study Director (1.877.828.5568, clinicaltrials@beonemed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06756932.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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