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RecruitingLast updated: 7 March 2025

BGB-21447-102: This study is recruiting people with HR+, HER2- metastatic breast cancer to assess how safe and tolerable a targeted drug called BGB-21447 is when given in combination with hormone therapy (called fulvestrant), with or without another targeted drug (called BGB-43395)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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Breast Cancers Breast

Age

People18+

Trial acronym

BGB-21447-102

Clinical summary

Summary

This new study will check how safe and helpful a powerful anticancer drug called BGB-21447 (Bcl-2i) is. This drug will be tested in combination with the hormone therapy Fulvestrant, with or without another targeted drug called BGB-43395 (a CDK4 inhibitor) in adults with metastatic breast cancer.

While CDK4/6 inhibitors combined with hormone (also called endocrine) therapy have improved outcomes for people with HR+/HER2- metastatic breast cancer, people may eventually develop a 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. By disrupting this pathway, anti-tumour effects can be achieved.

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. CDK4 inhibition is believed to have anti-tumour effects.

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

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

The study has two parts. In Part A, sequential cohorts of increasing dose levels of oral BGB-21447 will be evaluated in combination with Fulvestrant (given as an injection into the muscle). In Part B, sequential cohorts of increasing dose levels of oral BGB-21447 will be evaluated in combination with Fulvestrant and oral BGB-43395.

Conditions

This trial is treating people with HR+/HER2- metastatic breast cancer who have had at least 2 prior lines of treatment

Eligibility

Inclusion

  • Histologically or cytologically confirmed HR+/HER2- metastatic breast cancer. Participants must have received at least 2 prior lines of treatment for metastatic disease, including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.
  • Female participants with metastatic breast cancer will be required (either continue ongoing or initiate as soon as feasible) to have ovarian function suppression using GnRH agonists (such as goserelin) or be postmenopausal.
  • Male participants will be required to use gonadotropin-releasing hormone (GnRH) agonists when being treated with aromatase inhibitors and can be treated with 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 90 days after the last dose of BGB-21447, 3 months after the last dose of BGB-43395, and 2 years after the last dose of fulvestrant.

Exclusion

  • Prior Bcl-2 inhibitor exposure.
  • 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).
  • Uncontrolled diabetes.
  • History of hepatitis B or active Hepatitis C infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

BeiGene

Scientific 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

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