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Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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. Prior cytotoxic treatment is prohibited. 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

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: BGB-43395
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
  • Drug: Letrozole
    Standard dose administered orally as a tablet.
  • Drug: Elacestrant
    Standard dose administered orally as a tablet.
Experimental
Safety Expansion 		Phase 1a: Cohorts of selected dose levels of BGB-43395 in combination with fulvestrant or letrozole in HR+/HER2 breast cancer.
  • Drug: BGB-43395
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
  • Drug: Letrozole
    Standard dose administered orally as a tablet.
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.
  • Drug: BGB-43395
    Planned doses administered orally.
  • Drug: Fulvestrant
    Standard dose administered via intramuscular injection.
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.
  • Drug: BGB-43395
    Planned doses administered orally.
  • Drug: Letrozole
    Standard dose administered orally as a tablet.
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.
  • Drug: BGB-43395
    Planned doses administered orally.
  • Drug: Letrozole
    Standard dose administered orally as a tablet.
  • Drug: Anti-Diarrheal Agent
    Administered orally as a tablet.

Recruiting Locations

Sarah Cannon Research Institute (Scri) At Health One
Denver, Colorado 80218-1238

Washington University School of Medicine
St Louis, Missouri 63110-1010

Duke Cancer Center
Durham, North Carolina 27710-2000

James Cancer Hospital and Solove Research Institute
Columbus, Ohio 43210-1240

Scri Oncology Partners
Nashville, Tennessee 37203-1503

The University of Texas Md Anderson Cancer Center
Houston, Texas 77030-4009

Next Dallas
Irving, Texas 75039-2743

Next Oncology
San Antonio, Texas 78229-6028

More Details

Status
Recruiting
Sponsor
BeOne Medicines

Study Contact

Study Director
1.877.828.5568
clinicaltrials@beonemed.com

Detailed Description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.