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

NCT07492641 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: BGB-43395-3022025-523960-19-00
• Study Type: interventional
• Target: 1,056
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

HR+/HER2- Breast Cancer

Keywords

CDK4 inhibitor; CDK4/6 inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Determined by Blinded Independent Central Review (BICR)

  PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  Up to approximately 4 years

Secondary Outcomes (9)

• Overall Survival (OS)

  Up to approximately 11 years

• Overall Response Rate (ORR)

  Up to approximately 4 years

• Duration of Response (DOR)

  Up to approximately 4 years

• PFS Determined by Investigator

  Up to approximately 4 years

• Clinical Benefit Rate (CBR)

  Up to approximately 4 years

Study Arms (2)

Arm A: BGB-43395 + Letrozole

EXPERIMENTAL

Participants will receive BGB-43395 in combination with letrozole.

Drug: BGB-43395; Drug: Letrozole

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

ACTIVE COMPARATOR

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

Drug: Letrozole; Drug: Abemaciclib; Drug: Palbociclib; Drug: Ribociclib

Interventions

BGB-43395 DRUG

Administered orally.

Arm A: BGB-43395 + Letrozole

Letrozole DRUG

Administered orally.

Arm A: BGB-43395 + Letrozole; Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole

Abemaciclib DRUG

Administered orally.

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

Palbociclib DRUG

Administered orally.

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

Ribociclib DRUG

Administered orally.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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, except for prior investigational or approved SERDs in the adjuvant setting, provided that disease recurrence occurred more than 12 months after the last dose of endocrine-based therapy.
• Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis.

Sponsors & Collaborators

• BeOne Medicines: lead

MeSH Terms

Interventions

Letrozole; abemaciclib; palbociclib; ribociclib

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Study Director

  BeOne Medicines

  STUDY DIRECTOR

Central Study Contacts

Study Director

CONTACT

877-828-5568; clinicaltrials@beonemed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 25, 2026
• Study Start: May 11, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): August 7, 2037
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description