BGB-43395 Plus Letrozole Versus CDK4/6i Plus Letrozole for Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Treatment for Advanced or Metastatic Disease

BeOne Medicines

Status and phase: Begins enrollment this month; Phase 3

Conditions: HR+/HER2- Breast Cancer

Treatments: Drug: Palbociclib; Drug: Letrozole; Drug: Ribociclib; Drug: BGB-43395; Drug: Abemaciclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT07492641

2025-523960-19-00 (EU Trial (CTIS) Number)

BGB-43395-302

Details and patient eligibility

About

The purpose of this study is to investigate the efficacy and safety of BGB-43395 in combination with letrozole compared with investigator's choice of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with letrozole in patients with advanced or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) who have not received prior systemic treatment for advanced or metastatic disease.

Enrollment: 1,056 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the informed consent.
• Participants with histologically confirmed locally advanced or metastatic HR+ HER2- breast cancer.
• Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.
• Adequate organ function.

Exclusion criteria

• Participants who have received prior systemic treatment in the advanced or metastatic setting.
• Participants who have received prior treatment with any selective cyclin-dependent kinase 4 (CDK4) or cyclin-dependent kinase 2 (CDK2) targeting agent, or any other investigational anticancer drug in any disease setting.
• Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis.

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,056 participants in 2 patient groups

Arm A: BGB-43395 + Letrozole

Experimental group

Description:

Participants will receive BGB-43395 in combination with letrozole.

Treatment:

Drug: BGB-43395

Drug: Letrozole

Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole

Active Comparator group

Description:

Participants will receive either abemaciclib, palbociclib, or ribociclib based on the Investigator's choice in combination with letrozole.

Treatment:

Drug: Abemaciclib

Drug: Ribociclib

Drug: Palbociclib

Drug: Letrozole