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RecruitingInterventionalPhase 3

An Open-Label, Randomized, Multicenter Phase 3 Study Investigating the Efficacy and Safety of BGB-43395 Plus Letrozole Versus CDK4/6 Inhibitors (Abemaciclib, Palbociclib, Ribociclib) Plus Letrozole in Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Systemic Anticancer Treatment for Advanced or Metastatic Disease

NCT ID: NCT07492641Sponsor: BeOne MedicinesLast updated: 2026-06-18

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.

Arms & interventions

  • DrugBGB-43395

    Administered orally.

  • DrugLetrozole

    Administered orally.

  • DrugAbemaciclib

    Administered orally.

  • DrugPalbociclib

    Administered orally.

  • DrugRibociclib

    Administered orally.

Outcome measures

Primary

  • 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.

    Time frame: Up to approximately 4 years

Secondary

  • Overall Survival (OS)

    Time frame: Up to approximately 11 years

  • Overall Response Rate (ORR)

    Time frame: Up to approximately 4 years

  • Duration of Response (DOR)

    Time frame: Up to approximately 4 years

  • PFS Determined by Investigator

    Time frame: Up to approximately 4 years

  • Clinical Benefit Rate (CBR)

    Time frame: Up to approximately 4 years

  • Time to Response (TTR)

    Time frame: Up to approximately 4 years

  • Number of Participants with Adverse Events (AEs)

    Time frame: From first dose of study drug up to 30 days after last dose, up to approximately 11 years

  • Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC)-Item Library (IL)454.

    Time frame: Baseline and up to approximately 4 years

  • Progression-Free Survival 2 (PFS2)

    Time frame: Up to approximately 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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, 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. Note: Other protocol-defined inclusion/exclusion criteria may apply.

Study locations (11)

Alaska Oncology and Hematology, Llc

Anchorage, Alaska, 99508-2974

Recruiting

Ironwood Cancer and Research Centers Chandler Ii

Chandler, Arizona, 85224-5665

Recruiting

Brcr Coral Springs

Coral Springs, Florida, 33065

Recruiting

Florida Clinical Trials Group Tamarac

Tamarac, Florida, 33321

Recruiting

Cancer Care Specialists For Illinois

O'Fallon, Illinois, 62269

Recruiting

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804

Recruiting

Nebraska Cancer Specialists

Omaha, Nebraska, 68130-2042

Recruiting

Astera Cancer Care East Brunswick

East Brunswick, New Jersey, 08816-4096

Recruiting

Pardee Cancer Center

Hendersonville, North Carolina, 28739

Recruiting

Gabrail Cancer Center Research

Canton, Ohio, 44718-2566

Recruiting

Northwest Medical Specialties

Tacoma, Washington, 98405

Recruiting