Recruiting
Phase 1

BGB-21447, Fulvestrant, BGB-43395

Sponsor:

BeOne Medicines

Code:

NCT06756932

Conditions

Hormone-receptor-positive Breast Cancer

HER2-negative Breast Cancer

Metastatic Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BGB-21447

Fulvestrant

BGB-43395

Study Details

Brief 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.

Conditions

Hormone-receptor-positive Breast Cancer

HER2-negative Breast Cancer

Metastatic Breast Cancer

Study ID

NCT06756932

Start date

Feb 4, 2025

Status verified date

Nov, 2025

Completion date

Jul 30, 2027

Anticipated

Primary completion date

Jul 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

120 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1A: BGB-21447 + Fulvestrant

Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant.

experimental: Part 1B: BGB-21447 + BGB-43395 + Fulvestrant

Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395.

experimental: BGB-21447 + Fulvestrant Food Effect Substudy

Participants will receive BGB-21447 at the recommended dose with a high-fat meal and under a fasted state in combination with fulvestrant.

experimental: Part 2: Dose Expansion, BGB-21447 + Fulvestrant

Participants will receive BGB-21447 at the recommended dose(s) for expansion determined in Part 1A in combination with fulvestrant.

Interventions

BGB-21447

Administered orally.

Fulvestrant

Administered via intramuscular injection.

BGB-43395

Administered orally.

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 ]
  • Part 1: Recommended Dose for Expansion (RDFE) of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395 [ 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) [ Time Frame: Approximately 12 months ]

Central Contacts and Locations

Central contacts

Study Director

1.877.828.5568clinicaltrials@beonemed.com

Locations

University of Iowa Hospitals and Clinics

Recruiting

Iowa City, Iowa, United States, 52242-1009

Md Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-3907

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109-4433

More Information

Sponsor

BeOne Medicines

Last update posted

Jun 22, 2026

Last verified

Nov, 2025

Keywords

  • BGB-21447
  • BGB-43395
  • metastatic breast cancer
  • Bcl-2i
  • CDK4i

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by BeOne Medicines on 2026-06-22.