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)

August 18, 2026 updated by: BeOne Medicines

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1056

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Blacktown, New South Wales, Australia, NSW 2148
        • Recruiting
        • Blacktown Cancer and Haematology Centre
      • Liverpool, New South Wales, Australia, NSW 2170
        • Recruiting
        • Liverpool Hospital
      • Wollongong, New South Wales, Australia, NSW 2500
        • Recruiting
        • Wollongong Hospital
    • Queensland
      • Birtinya, Queensland, Australia, QLD 4575
        • Recruiting
        • Sunshine Coast University Private Hospital
      • Douglas, Queensland, Australia, QLD 4814
        • Recruiting
        • Townsville University Hospital
    • Victoria
      • Melbourne, Victoria, Australia, VIC 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Murdoch, Western Australia, Australia, WA 6150
        • Recruiting
        • Fiona Stanley Hospital
      • Nedlands, Western Australia, Australia, WA 6009
        • Recruiting
        • One Clinical Research
  • Brazil
      • Barretos, Brazil, 14.784-400
        • Recruiting
        • Fundacao Pio Xii Hospital de Amor de Barretos
      • São Paulo, Brazil, 01246-000
        • Recruiting
        • Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
  • China
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 630014
        • Recruiting
        • The First Affiliated Hospital of Chongqing Medical University
    • Fujian
      • Fuzhou, Fujian, China, 350009
        • Recruiting
        • The Peoples Hospital Affiliated to Fujian University of Traditional Chinese Medicine
    • Guangdong
      • Guangzhou, Guangdong, China, 510245
        • Recruiting
        • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
      • Shantou, Guangdong, China, 515031
        • Recruiting
        • Cancer Hospital of Shantou University Medical College
    • Guangxi
      • Nanning, Guangxi, China, 530201
        • Recruiting
        • Guangxi Medical University Cancer Hospital Wuxiang Branch
    • Hainan
      • Haikou, Hainan, China, 570206
        • Recruiting
        • Hainan General Hospital
    • Hubei
      • Wuhan, Hubei, China, 430048
        • Recruiting
        • Union Hospital Tongji Medical College Huazhong University of Science and Technologyjinyinhu Branch
    • Hunan
      • Changde, Hunan, China, 415000
        • Recruiting
        • The First Peoples Hospital of Changde City
    • Jiangxi
      • Nanchang, Jiangxi, China, 330025
        • Recruiting
        • Nanchang Peoples Hospitalchaoyang Branch
    • Shaanxi
      • Xi'an, Shaanxi, China, 710004
        • Recruiting
        • The Second Affiliated Hospital of Xian Jiaotong University
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Fudan University Shanghai Cancer Center
    • Sichuan
      • Chengdu, Sichuan, China, 610071
        • Recruiting
        • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300453
        • Recruiting
        • Binhai Hospital, Tianjin Medical University Cancer Institute and Hospital
  • Japan
    • Fukuoka
      • Kurumeshi, Fukuoka, Japan, 830-0013
        • Recruiting
        • Japan Community Healthcare Organization Kurume General Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 003-0804
        • Recruiting
        • National Hospital Organization Hokkaido Cancer Center
    • Hyōgo
      • Nishinomiyashi, Hyōgo, Japan, 663-8501
        • Recruiting
        • Hyogo Medical University Hospital
    • Kagoshima-ken
      • Kagoshima, Kagoshima-ken, Japan, 892-0833
        • Recruiting
        • Social Medical Corporation Hakuaikai Sagara Hospital
    • Kanagawa
      • Iseharashi, Kanagawa, Japan, 259-1193
        • Recruiting
        • Tokai University Hospital
      • Kawasakishi, Kanagawa, Japan, 211-8533
        • Recruiting
        • Nippon Medical School Musashi Kosugi Hospital
      • Yokohama, Kanagawa, Japan, 232-0024
        • Recruiting
        • Yokohama City University Medical Center
    • Mie-ken
      • Tsu, Mie-ken, Japan, 514-8507
        • Recruiting
        • Mie University Hospital
    • Osaka
      • Osakashi, Osaka, Japan, 540-0006
        • Recruiting
        • National Hospital Organization Osaka National Hospital
      • Suitashi, Osaka, Japan, 565-0871
        • Recruiting
        • The University of Osaka Hospital
    • Tokyo
      • Bunkyoku, Tokyo, Japan, 113-8677
        • Recruiting
        • Tokyo Metropolitan Komagome Hospital
      • Kotoku, Tokyo, Japan, 135-8550
        • Recruiting
        • Cancer Institute Hospital of JFCR
      • Shinagawaku, Tokyo, Japan, 142-8666
        • Recruiting
        • Showa Medical University Hospital
      • Shinjukuku, Tokyo, Japan, 162-8666
        • Recruiting
        • Tokyo Womens Medical University Hospital
  • Malaysia
      • George Town, Malaysia, 10450
        • Recruiting
        • Pulau Pinang Hospital
      • Kota Kinabalu Sabah, Malaysia, 88996
        • Recruiting
        • Hospital Wanita Dan Kanak Kanak Sabah (Hospital Likas)
      • Kuala Lumpur, Malaysia, 59100
        • Recruiting
        • University Malaya Medical Centre
      • Kuala Lumpur, Malaysia, 50586
        • Recruiting
        • Hospital Kuala Lumpur
      • Kuching, Malaysia, 93586
        • Recruiting
        • Sarawak General Hospital
      • Petaling Jaya, Malaysia, 46300
        • Recruiting
        • Hospital Picaso
      • Putrajaya, Malaysia, 62250
        • Recruiting
        • National Cancer Institute (Institut Kanser Negara)
  • Puerto Rico
      • San Juan, Puerto Rico, 00917
        • Recruiting
        • Brcr Global Puerto Rico Hato Rey
  • South Korea
      • Suwon, South Korea, 16499
        • Recruiting
        • Ajou University Hospital
    • Busan Gwang'Yeogsi
      • HaeundaeGu, Busan Gwang'Yeogsi, South Korea, 48108
        • Recruiting
        • Inje University Haeundae Paik Hospital
      • Seogu, Busan Gwang'Yeogsi, South Korea, 49201
        • Recruiting
        • Dong A University Hospital
    • Chungcheongbukdo
      • Cheongju-si, Chungcheongbukdo, South Korea, 28644
        • Recruiting
        • Chungbuk National University Hospital
    • Chungcheongnam-do
      • Cheonansi, Chungcheongnam-do, South Korea, 31151
        • Recruiting
        • Soon Chun Hyang University Cheonan Hospital
    • Daegu Gwang'Yeogsi
      • Dalseogu, Daegu Gwang'Yeogsi, South Korea, 42601
        • Recruiting
        • Keimyung University Dongsan Hospital
    • Gyeonggi-do
      • BundangGu SeongnamSi, Gyeonggi-do, South Korea, 13496
        • Recruiting
        • CHA Bundang Medical Center, CHA University
      • DanwonGu AnsanSi, Gyeonggi-do, South Korea, 15355
        • Recruiting
        • Korea University Ansan Hospital
      • IlsandongGu GoyangSi, Gyeonggi-do, South Korea, 10408
        • Recruiting
        • National Cancer Center (Korea)
      • PaldalGu SuwonSi, Gyeonggi-do, South Korea, 16247
        • Recruiting
        • The Catholic University of Korea, St Vincents Hospital
      • Seongnam-si, Gyeonggi-do, South Korea, 13620
        • Recruiting
        • Seoul National University Bundang Hospital
    • Incheon Gwang'Yeogsi
      • Jemulpogu, Incheon Gwang'Yeogsi, South Korea, 22332
        • Recruiting
        • Inha University Hospital
      • NamdongGu, Incheon Gwang'Yeogsi, South Korea, 21565
        • Recruiting
        • Gachon University Gil Medical Center
    • Jeonnam-Gwangju S.M. City
      • HwasunGun, Jeonnam-Gwangju S.M. City, South Korea, 58128
        • Recruiting
        • Chonnam National University Hwasun Hospital
    • Seoul Teugbyeolsi
      • DongjakGu, Seoul Teugbyeolsi, South Korea, 06973
        • Recruiting
        • Chung Ang University Hospital
      • GangnamGu, Seoul Teugbyeolsi, South Korea, 06351
        • Recruiting
        • Samsung Medical Center
      • GuroGu, Seoul Teugbyeolsi, South Korea, 08308
        • Recruiting
        • Korea University Guro Hospital
      • SeochoGu, Seoul Teugbyeolsi, South Korea, 06591
        • Recruiting
        • The Catholic University of Korea, Seoul St Marys Hospital
      • SeodaemunGu, Seoul Teugbyeolsi, South Korea, 03722
        • Recruiting
        • Severance Hospital Yonsei University Health System
      • SeongbukGu, Seoul Teugbyeolsi, South Korea, 02841
        • Recruiting
        • Korea University Anam Hospital
      • Seoul, Seoul Teugbyeolsi, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, Seoul Teugbyeolsi, South Korea, 06273
        • Recruiting
        • Gangnam Severance Hospital, Yonsei University Health System
      • Seoul, Seoul Teugbyeolsi, South Korea, 07985
        • Recruiting
        • Ehwa Womans University Mokdong Hospital
      • SongpaGu, Seoul Teugbyeolsi, South Korea, 05505
        • Recruiting
        • Asan Medical Center
    • Ulsan Gwang'Yeogsi
      • Ulsan, Ulsan Gwang'Yeogsi, South Korea, 44033
        • Recruiting
        • Ulsan University Hospital
  • Taiwan
      • Taichung, Taiwan, 40447
        • Recruiting
        • China Medical University Hospital
  • United Kingdom
      • Maidstone, United Kingdom, ME16 9QQ
        • Recruiting
        • Maidstone and Tunbridge Wells Nhs Trust Kent Oncology Centre Maidstone Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35211
        • Recruiting
        • Alabama Oncology Princeton
    • Alaska
      • Anchorage, Alaska, United States, 99508-2974
        • Recruiting
        • Alaska Oncology and Hematology, LLC
    • Arizona
      • Chandler, Arizona, United States, 85224-5665
        • Recruiting
        • Ironwood Cancer and Research Centers Chandler Ii
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
        • Recruiting
        • Genesis Cancer and Blood Institute Hot Springs (Harmony Park)
    • California
      • Fountain Valley, California, United States, 92708
        • Recruiting
        • Helios Clinical Research the Oncology Institute Fountain Valley
      • Oxnard, California, United States, 93030
        • Recruiting
        • Ventura County Hematology Oncology Specialists
    • Florida
      • Coral Springs, Florida, United States, 33065
        • Recruiting
        • Brcr Coral Springs
      • Orange City, Florida, United States, 32763-8316
        • Recruiting
        • Mid Florida Hematology and Oncology Center
      • Plantation, Florida, United States, 33322
        • Recruiting
        • Florida Clinical Trials Group Plantation
      • Port Saint Lucie, Florida, United States, 34952-7596
        • Recruiting
        • Hematology Oncology Associates of the Treasure Coast
      • Tamarac, Florida, United States, 33321
        • Recruiting
        • Florida Clinical Trials Group Tamarac
    • Illinois
      • Hinsdale, Illinois, United States, 60521-0509
        • Recruiting
        • Hope and Healing Cancer Services
      • OFallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Specialists For Illinois
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Recruiting
        • Fort Wayne Medical Oncology and Hematology
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403
        • Recruiting
        • Mercy Medical Center
    • Kentucky
      • Owensboro, Kentucky, United States, 42303
        • Recruiting
        • Owensboro Health Mitchell Memorial Cancer Center
    • Minnesota
      • Saint Paul, Minnesota, United States, 55101-2502
        • Recruiting
        • Metro Minnesota Community Oncology Research Consortium (MMCORC)
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • Recruiting
        • Nebraska Cancer Specialists St Francis Grand Island
      • Lincoln, Nebraska, United States, 68516
        • Recruiting
        • Cancer Partners of Nebraska April Sampson Cancer Center
      • Omaha, Nebraska, United States, 68130-2042
        • Recruiting
        • Nebraska Cancer Specialists
    • Nevada
      • Reno, Nevada, United States, 89502
        • Recruiting
        • Renown Regional Medical Center
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816-4096
        • Recruiting
        • Astera Cancer Care East Brunswick
      • Florham Park, New Jersey, United States, 07932-1049
        • Recruiting
        • Summit Medical Group
    • New York
      • Shirley, New York, United States, 11967
        • Recruiting
        • New York Cancer and Blood Specialists
    • North Carolina
      • Hendersonville, North Carolina, United States, 28739
        • Recruiting
        • Pardee Cancer Center
      • Wilson, North Carolina, United States, 27896
        • Recruiting
        • Carolina Cancer Research Center
    • Ohio
      • Canton, Ohio, United States, 44718-2566
        • Recruiting
        • Gabrail Cancer Center Research
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Dayton Physicians Network
    • Oregon
      • Salem, Oregon, United States, 97301
        • Recruiting
        • Oregon Oncology Specialists
    • Pennsylvania
      • West Reading, Pennsylvania, United States, 19611-2143
        • Recruiting
        • McGlinn Cancer Institute
    • Tennessee
      • Kingsport, Tennessee, United States, 37660
        • Recruiting
        • Ballad Health Cancer Center Kingsport
    • Virginia
      • Richmond, Virginia, United States, 23229-8605
        • Recruiting
        • Virginia Cancer Institute
    • Washington
      • Spokane, Washington, United States, 99204
        • Recruiting
        • Multicare Cancer Institute Deaconess Medical Office Building 1
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • Northwest Medical Specialties
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • Multicare Cancer Institute Tacoma General Hospital
      • Yakima, Washington, United States, 98902
        • Recruiting
        • Multicare Cancer Institute North Star Lodge

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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)
Time Frame: Up to approximately 4 years
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)
Time Frame: Up to approximately 11 years
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)
Time Frame: Up to approximately 4 years
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)
Time Frame: Up to approximately 4 years
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
Time Frame: Up to approximately 4 years
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)
Time Frame: Up to approximately 4 years
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)
Time Frame: Up to approximately 4 years
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)
Time Frame: From first dose of study drug up to 30 days after last dose, up to approximately 11 years
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.
Time Frame: Baseline and up to approximately 4 years

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)
Time Frame: Up to approximately 4 years
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

This is where you will find people and organizations involved with this study.

Sponsor

BeOne Medicines

Investigators

  • Study Director: Study Director, BeOne Medicines

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 22, 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)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 18, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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