BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer

NCT06756932 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: BGB-21447-102CTR20250114
• Study Type: interventional
• Target: 120
• Locations: 3 countries
• Sites: 16

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

  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.

  Approximately 12 months

Secondary Outcomes (13)

• Part 1: ORR

  Approximately 12 months

• Parts 1 and 2: Duration of Response (DOR)

  Approximately 12 months

• Part 1:Time to Response (TTR)

  Approximately 12 months

• Part 2: Disease Control Rate (DCR)

  Approximately 12 months

• Part 2: Clinical Benefit Rate (CBR)

  Approximately 12 months

Study Arms (4)

Part 1A: BGB-21447 + Fulvestrant

EXPERIMENTAL

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

Drug: BGB-21447; Drug: Fulvestrant

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

EXPERIMENTAL

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

Drug: BGB-21447; Drug: Fulvestrant; Drug: BGB-43395

BGB-21447 + Fulvestrant Food Effect Substudy

EXPERIMENTAL

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

Drug: BGB-21447; Drug: Fulvestrant

Part 2: Dose Expansion, BGB-21447 + Fulvestrant

EXPERIMENTAL

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

Drug: BGB-21447; Drug: Fulvestrant

Interventions

BGB-21447 DRUG

Administered orally.

BGB-21447 + Fulvestrant Food Effect Substudy; Part 1A: BGB-21447 + Fulvestrant; Part 1B: BGB-21447 + BGB-43395 + Fulvestrant; Part 2: Dose Expansion, BGB-21447 + Fulvestrant

Fulvestrant DRUG

Administered via intramuscular injection.

BGB-21447 + Fulvestrant Food Effect Substudy; Part 1A: BGB-21447 + Fulvestrant; Part 1B: BGB-21447 + BGB-43395 + Fulvestrant; Part 2: Dose Expansion, BGB-21447 + Fulvestrant

BGB-43395 DRUG

Administered orally.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeOne Medicines: lead

Study Sites (16)

Hoag Memorial Presbyterian

Newport Beach, California, 92663-4162, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242-1009, United States

RECRUITING

Md Anderson Cancer Center

Houston, Texas, 77030-3907, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-4433, United States

RECRUITING

Saint Vincents Hospital Sydney

Darlinghurst, New South Wales, NSW 2010, Australia

RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, NSW 2298, Australia

RECRUITING

Sunshine Coast University Private Hospital

Birtinya, Queensland, QLD 4575, Australia

RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, VIC 3000, Australia

RECRUITING

Western Health Sunshine Hospital

St Albans, Victoria, VIC 3021, Australia

RECRUITING

Linear Clinical Research

Nedlands, Western Australia, WA 6009, Australia

RECRUITING

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)

Guangzhou, Guangdong, 510245, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

RECRUITING

Fudan University Shanghai Cancer Centerpudong

Shanghai, Shanghai Municipality, 201321, China

RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Study Director

  BeOne Medicines

  STUDY DIRECTOR

Central Study Contacts

Study Director

CONTACT

1.877.828.5568; clinicaltrials@beonemed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: January 3, 2025
• Study Start: February 4, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

US (4); CN (6); AU (6)