BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer
- Conditions
- Hormone-receptor-positive Breast CancerHER2-negative Breast CancerMetastatic Breast Cancer
- Interventions
- Registration Number
- NCT06756932
- Lead Sponsor
- BeiGene
- Brief Summary
The purpose of this study is 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
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. By disrupting this pathway, antitumor 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 antitumor effects.
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 92
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: BGB-21447 + Fulvestrant BGB-21447 Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant. Part A: BGB-21447 + Fulvestrant Fulvestrant Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant. Part B: BGB-21447 + BGB-43395 + Fulvestrant Fulvestrant Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395. Part B: BGB-21447 + BGB-43395 + Fulvestrant BGB-43395 Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395. Part B: BGB-21447 + BGB-43395 + Fulvestrant BGB-21447 Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395.
- Primary Outcome Measures
Name Time Method Recommended Dose for Expansion (RDFE) of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395 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).
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.
- Secondary Outcome Measures
Name Time Method 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.
Duration of Response (DOR) Approximately 12 months 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.
Time to Response (TTR) Approximately 12 months 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.
Maximum observed plasma concentration (Cmax) of BGB-21447, BGB-43395, and BGB-43395 metabolite Up to approximately 2 months Time to reach maximum observed plasma concentration (Tmax) of BGB-21447, BGB-43395, and BGB-43395 metabolite Up to approximately 2 months Area under the concentration-time curve (AUC) of BGB-21447, BGB-43395, and BGB-43395 metabolite Up to approximately 2 months Apparent terminal elimination half-life (t1/2) of BGB-21447, BGB-43395, and BGB-43395 metabolite Up to approximately 2 months
Related Research Topics
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Trial Locations
- Locations (15)
Hoag Memorial Presbyterian
🇺🇸Newport Beach, California, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Saint Vincents Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Sunshine Coast University Private Hospital
🇦🇺Birtinya, Queensland, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Western Health Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Fudan University Shanghai Cancer Centerpudong
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China