BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors
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
- Advanced Solid Tumor
- Advanced Breast Cancer
- Metastatic Breast Cancer
- Hormone-receptor-positive Breast Cancer
- Hormone Receptor Positive Breast Carcinoma
- Hormone Receptor Positive Malignant Neoplasm of Breast
- HER2-negative Breast Cancer
- Hormone Receptor Positive HER-2 Negative Breast Cancer
- Non-small Cell Lung Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Phase 1a (Dose Escalation) and 1b (Dose Expansion): 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. - Phase 1a: Received prior therapy for their condition (if available) and should be refractory to, or intolerant of standard-of-care therapies. In regions where approved and available, participants with HR+ breast cancer must have received at least 2 prior lines of treatment including endocrine therapy and a CDK4/6 inhibitor. 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 1b: Selected tumor cohorts will include HR+/HER2- breast cancer and additional tumor types. - Phase 1b: Participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received at least one line of therapy for advanced disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy 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
- Prior therapy selectively targeting CDK4 (prior CDK4/6 inhibitor therapy is permitted and required in local regions where it is approved and available). - 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
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Dose Escalation and Safety Expansion |
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 Dose Expansion |
Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant or letrozole) from Phase 1a will be evaluated in HR+ breast cancer and selected tumor-specific cohorts. |
|
Recruiting Locations
Sarah Cannon Research Institute (Scri) At Health One
Denver 5419384, Colorado 5417618 80218-1238
Denver 5419384, Colorado 5417618 80218-1238
Florida Cancer Specialists and Research Institute
Lake Mary 4161373, Florida 4155751 32746-2115
Lake Mary 4161373, Florida 4155751 32746-2115
Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110-1010
St Louis 4407066, Missouri 4398678 63110-1010
Duke Cancer Center
Durham 4464368, North Carolina 4482348 27710-2000
Durham 4464368, North Carolina 4482348 27710-2000
James Cancer Hospital and Solove Research Institute
Columbus 4509177, Ohio 5165418 43210-1240
Columbus 4509177, Ohio 5165418 43210-1240
Scri Oncology Partners
Nashville 4644585, Tennessee 4662168 37203-1503
Nashville 4644585, Tennessee 4662168 37203-1503
Next Oncology
Austin 4671654, Texas 4736286 78758
Austin 4671654, Texas 4736286 78758
The University of Texas Md Anderson Cancer Center
Houston 4699066, Texas 4736286 77030-4009
Houston 4699066, Texas 4736286 77030-4009
Next Dallas
Irving 4700168, Texas 4736286 75039-2743
Irving 4700168, Texas 4736286 75039-2743
More Details
- NCT ID
- NCT06120283
- Status
- Recruiting
- Sponsor
- BeiGene