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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Administered orally.
Administered via intramuscular injection.
Administered orally.
Hoag Memorial Presbyterian
Newport Beach, California, United States
RECRUITINGUniversity of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
RECRUITINGMd Anderson Cancer Center
Houston, Texas, United States
RECRUITINGFred Hutchinson Cancer Research Center
Seattle, Washington, United States
RECRUITINGSaint Vincents Hospital Sydney
Darlinghurst, New South Wales, Australia
RECRUITINGCalvary Mater Newcastle
Waratah, New South Wales, Australia
RECRUITINGSunshine Coast University Private Hospital
Birtinya, Queensland, Australia
RECRUITINGPeter Maccallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGWestern Health Sunshine Hospital
St Albans, Victoria, Australia
RECRUITINGLinear Clinical Research
Nedlands, Western Australia, Australia
RECRUITING...and 6 more locations
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.
Time frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
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).
Time frame: 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
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.
Time frame: Approximately 12 months
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.
Time frame: Approximately 12 months
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.
Time frame: Approximately 12 months
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.
Time frame: Approximately 12 months
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.
Time frame: Approximately 12 months
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).
Time frame: Approximately 12 months
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.
Time frame: Approximately 12 months
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.
Time frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
Maximum observed plasma concentration (Cmax) of BGB-21447 and BGB-43395
Time frame: Up to approximately 2 months
Time to reach maximum observed plasma concentration (Tmax) of BGB-21447 and BGB-43395
Time frame: Up to approximately 2 months
Area under the concentration-time curve (AUC) of BGB-21447 and BGB-43395
Time frame: Up to approximately 2 months
Apparent terminal elimination half-life (t1/2) of BGB-21447 and BGB-43395
Time frame: Up to approximately 2 months
Food Effect Substudy: AUC of BGB-21447 under fasted and fed state
Time frame: Up to approximately 2 months
Food Effect Substudy: Cmax of BGB-21447 under fasted and fed state
Time frame: Up to approximately 2 months
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