Testing a new combination of drugs for advanced breast cancer

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 study is testing a new combination of drugs to see if they can help adults with advanced breast cancer that hasn't responded to previous treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BeOne Medicines (industry)
• Locations: 16 sites (Newport Beach, California and 15 other locations)
• Trial ID: NCT06756932 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of BGB-21447, a Bcl-2 inhibitor, in combination with fulvestrant, with or without BGB-43395, a CDK4 inhibitor, for adults with hormone-receptor positive and HER2-negative metastatic breast cancer. The trial aims to determine how well these drugs work together to combat cancer cells that often resist standard treatments. Participants must have previously received at least two lines of treatment for their metastatic disease. The study is designed to provide insights into new therapeutic options for patients who have limited treatment choices.

Who should consider this trial

Good fit: Ideal candidates are adults with HR+/HER2- metastatic breast cancer who have received at least two prior lines of treatment.

Not a fit: Patients with non-HR+/HER2- breast cancer or those who have not received prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new effective treatment option for patients with advanced hormone-receptor positive breast cancer.

How similar studies have performed: Other studies have shown promise with similar drug combinations in treating metastatic breast cancer, indicating potential for success.

Eligibility criteria

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.

Where this trial is running

Newport Beach, California and 15 other locations

• Hoag Memorial Presbyterian — Newport Beach, California, United States (RECRUITING)
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States (RECRUITING)
• Md Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• Fred Hutchinson Cancer Research Center — Seattle, Washington, United States (RECRUITING)
• Saint Vincents Hospital Sydney — Darlinghurst, New South Wales, Australia (RECRUITING)
• Calvary Mater Newcastle — Waratah, New South Wales, Australia (RECRUITING)
• Sunshine Coast University Private Hospital — Birtinya, Queensland, Australia (RECRUITING)
• Peter Maccallum Cancer Centre — Melbourne, Victoria, Australia (RECRUITING)
• Western Health Sunshine Hospital — St Albans, Victoria, Australia (RECRUITING)
• Linear Clinical Research — Nedlands, Western Australia, Australia (RECRUITING)
• Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South) — Guangzhou, Guangdong, China (RECRUITING)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (RECRUITING)
• The First Affiliated Hospital of Nanchang University Branch Donghu — Nanchang, Jiangxi, China (RECRUITING)
• Fudan University Shanghai Cancer Centerpudong — Shanghai, Shanghai Municipality, China (RECRUITING)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Study Director

Conditions: Hormone-receptor-positive Breast Cancer, HER2-negative Breast Cancer, Metastatic Breast Cancer, BGB-21447, BGB-43395, metastatic breast cancer, Bcl-2i, CDK4i