BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors

BeOne Medicines

Status and phase: Enrolling; Phase 1

Conditions: Hormone-receptor-positive Breast Cancer; Non-small Cell Lung Cancer; Advanced Solid Tumor; Hormone Receptor Positive HER-2 Negative Breast Cancer; Hormone Receptor Positive Malignant Neoplasm of Breast; Metastatic Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor Positive Breast Carcinoma; Advanced Breast Cancer

Treatments: Drug: Fulvestrant; Drug: BGB-43395; Drug: Elacestrant; Drug: Letrozole; Drug: Anti-Diarrheal Agent

Study type: Interventional

Funder types: Industry

Identifiers

NCT06120283

BGB-43395-101

CTR20243370 (Registry Identifier)

2023-506888-34-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 399 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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399 participants in 5 patient groups

Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: Letrozole

Drug: Elacestrant

Drug: BGB-43395

Drug: Fulvestrant

Safety Expansion

Experimental group

Description:

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

Treatment:

Drug: Letrozole

Drug: BGB-43395

Drug: Fulvestrant

Dose Expansion Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: BGB-43395

Drug: Fulvestrant

Dose Expansion Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: Letrozole

Drug: BGB-43395

Dose Expansion Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: Anti-Diarrheal Agent

Drug: Letrozole

Drug: BGB-43395