Recruiting
Phase 1

BGB-43395

Sponsor:

BeOne Medicines

Code:

NCT06120283

Conditions

Advanced Solid Tumor

Advanced Breast Cancer

Metastatic Breast Cancer

Hormone-receptor-positive Breast Cancer

Hormone Receptor Positive Breast Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BGB-43395

Fulvestrant

Letrozole

Elacestrant

Anti-Diarrheal Agent

Study Details

Brief summary:

This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy or in combination with fulvestrant, letrozole, or elacestrant in participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-43395.

Conditions

Advanced Solid Tumor

Advanced Breast Cancer

Metastatic Breast Cancer

Hormone-receptor-positive Breast Cancer

Hormone Receptor Positive Breast Carcinoma

Study ID

NCT06120283

Start date

Dec 1, 2023

Status verified date

Aug, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors associated with dependency on CDK4, including HR+ breast cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer, and others. For combination with elacestrant, participants must have received at least 1 prior line of treatment for advanced/metastatic disease including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.
  • Phase 1a Safety Expansion: For combination with fulvestrant in regions where approved and available, participants with HR+ breast cancer must have received at least 1 prior line of treatment including endocrine therapy and a CDK4/6 inhibitor. For combination with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
  • Phase 1b: Participants with HR+/HER2- breast cancer.
  • Phase 1b: For combination with fulvestrant, participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received 1-2 lines of therapy for advanced/metastatic disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy for advanced disease. For combination cohorts with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
  • Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
  • Female participants with metastatic HR+/HER2- breast cancer must be postmenopausal or receiving ovarian function suppression treatment.
  • Adequate organ function without symptomatic visceral disease.

Exclusion Criteria:

  • 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, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
  • Uncontrolled diabetes.
  • Infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection.
  • Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening.
  • Participants with active hepatitis C infection.
  • Prior allogeneic stem cell transplantation, or organ transplantation.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Enrollment

433 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation

Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant, letrozole, or elacestrant to assess for safety and tolerability.

experimental: Safety Expansion

Phase 1a: Cohorts of selected dose levels of BGB-43395 in combination with fulvestrant or letrozole in HR+/HER2 breast cancer.

experimental: Dose Expansion Cohort 1

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant) from Phase 1a will be evaluated in HR+ breast cancer.

experimental: Dose Expansion Cohort 2

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 in combination with letrozole from Phase 1a will be evaluated in HR+ breast cancer.

experimental: Dose Expansion Cohort 3

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 in combination with letrozole from Phase 1a will be evaluated in HR+ breast cancer. Participants will also receive an anti-diarrheal agent for prophylaxis.

Interventions

BGB-43395

Planned doses administered orally.

Fulvestrant

Standard dose administered via intramuscular injection.

Letrozole

Standard dose administered orally as a tablet.

Elacestrant

Standard dose administered orally as a tablet.

Anti-Diarrheal Agent

Administered orally as a tablet.

Primary outcome measure

  • Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 60 months ]
  • Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395 [ Time Frame: Up to approximately 60 months ]
  • Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395 [ Time Frame: Up to approximately 60 months ]
  • Phase 1b: Objective Response Rate (ORR) [ Time Frame: Up to approximately 60 months ]

Central Contacts and Locations

Central contacts

Study Director

1.877.828.5568clinicaltrials@beonemed.com

Locations

Sarah Cannon Research Institute (Scri) At Health One

Recruiting

Denver, Colorado, United States, 80218-1238

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110-1010

Duke Cancer Center

Recruiting

Durham, North Carolina, United States, 27710-2000

James Cancer Hospital and Solove Research Institute

Recruiting

Columbus, Ohio, United States, 43210-1240

Scri Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203-1503

The University of Texas Md Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4009

Next Dallas

Recruiting

Irving, Texas, United States, 75039-2743

Next Oncology

Recruiting

San Antonio, Texas, United States, 78229-6028

More Information

Sponsor

BeOne Medicines

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Keywords

  • breast cancer
  • advanced solid tumor
  • advanced breast cancer
  • hormone receptor positive breast cancer
  • HER2-negative breast cancer
  • Hormone Receptor Positive HER-2 Negative Breast Cancer
  • BGB-43395

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 2026-08-28.