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 (KANDELA-302)

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

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.

Study Overview

• Status: Recruiting
• Conditions: HR+/HER2- Breast Cancer
• Intervention / Treatment: Drug: Abemaciclib; Drug: Letrozole; Drug: BGB-43395; Drug: Palbociclib; Drug: Ribociclib

• Study Type: Interventional
• Enrollment (Estimated): 1056
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 877-828-5568; Email: clinicaltrials@beonemed.com

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, NSW 2500
      • Recruiting
      • Wollongong Hospital
  • Queensland
    • Birtinya, Queensland, Australia, QLD 4575
      • Recruiting
      • Sunshine Coast University Private Hospital
  • Victoria
    • Melbourne, Victoria, Australia, VIC 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Recruiting
      • One Clinical Research
• Japan
  • Tokyo
    • Kotoku, Tokyo, Japan, 135-8550
      • Recruiting
      • Cancer Institute Hospital of JFCR
    • Shinjukuku, Tokyo, Japan, 162-8666
      • Recruiting
      • Tokyo Womens Medical University Hospital
• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 07985
      • Recruiting
      • Ehwa Womans University Mokdong Hospital
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508-2974
      • Recruiting
      • Alaska Oncology and Hematology, Llc
  • Illinois
    • O'Fallon, Illinois, United States, 62269
      • Recruiting
      • Cancer Care Specialists For Illinois
  • Nebraska
    • Omaha, Nebraska, United States, 68130-2042
      • Recruiting
      • Nebraska Cancer Specialists
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816-4096
      • Recruiting
      • Astera Cancer Care East Brunswick
  • Ohio
    • Canton, Ohio, United States, 44718-2566
      • Recruiting
      • Gabrail Cancer Center Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: BGB-43395 + Letrozole; Participants will receive BGB-43395 in combination with letrozole.	Drug: Letrozole; Administered orally.; Drug: BGB-43395; Administered orally.
Active Comparator: Arm B: Cyclin-Dependent Kinase 4/6 Inhibitor + Letrozole; Participants will receive either abemaciclib, palbociclib, or ribociclib based on the Investigator's choice in combination with letrozole.	Drug: Abemaciclib; Administered orally.; Drug: Letrozole; Administered orally.; Drug: Palbociclib; Administered orally.; Drug: Ribociclib; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death due to any cause.	Up to approximately 11 years
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who had a complete response (CR) or partial response (PR), as assessed by BICR per RECIST v1.1.	Up to approximately 4 years
Duration of Response (DOR)	DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first, as assessed by BICR per RECIST v1.1.	Up to approximately 4 years
PFS Determined by Investigator	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to approximately 4 years
Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants who have a CR, PR, or stable disease maintained for ≥ 24 weeks after randomization (without subsequent anticancer treatment) per RECIST v1.1 .	Up to approximately 4 years
Time to Response (TTR)	TTR is defined as the time from treatment initiation to the first response confirmed by BICR per RECIST v1.1.	Up to approximately 4 years
Number of Participants with Adverse Events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results.	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.	The EORTC-IL454 is a questionnaire that asks participants to rate their breast cancer symptoms and the impact of breast cancer on their quality of life (QoL). The EORTC-IL454 is an EORTC Item Library-derived scale set constructed using items from the validated EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) (a core measure of health-related QoL in cancer patients) and the QLQ-BR23 (its breast cancer-specific module) The EORTC-IL454 contains 26 questions, each answered on a 4-point scale (1 = Not at all; 4 = Very much), and includes 2 functional scales (physical functioning and role functioning), 2 symptom scales (Nausea/Vomiting and Diarrhea), and 1 Global Health Status (GHS)/Quality of Life (QoL) scale, 7 systemic side effects scales, 3 arm symptom scales, and 4 breast-specific symptom scales. The recall period is the past 7 days. Higher scores in GHS and functional scales and lower scores in symptom scales indicate better QoL.	Baseline and up to approximately 4 years
Progression-Free Survival 2 (PFS2)	PFS2 is defined as the time from randomization until progression on the next line of treatment (ie, first subsequent therapy), as assessed by the investigator, or death due to any cause, whichever occurs first.	Up to approximately 4 years

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): August 7, 2037

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CDK4/6 inhibitor; CDK4 inhibitor
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Nitriles; Triazoles; Letrozole; abemaciclib; ribociclib; palbociclib
• Other Study ID Numbers: BGB-43395-302; 2025-523960-19-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No