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NCT07492641PHASE3Recruiting

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

Start Date

5/22/2026

Completion Date

8/7/2037

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

BGB-43395

DRUG

Letrozole

DRUG

Abemaciclib

DRUG

Palbociclib

DRUG

Ribociclib

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Conditions

HR+/HER2- Breast Cancer

Locations

Alabama Oncology Princeton

Birmingham, Alabama 35211

United States

Alaska Oncology and Hematology, Llc

Anchorage, Alaska 99508-2974

United States

Fairbanks Cancer Care Physicians Pc

Fairbanks, Alaska 99701

United States

Pioneer Research Center

Bullhead City, Arizona 86442

United States

Ironwood Cancer and Research Centers Chandler Ii

Chandler, Arizona 85224-5665

United States

Genesis Cancer and Blood Institute Hot Springs (Harmony Park)

Hot Springs, Arkansas 71913

United States

Helios Clinical Research the Oncology Institute Fountain Valley

Fountain Valley, California 92708

United States

California Research Institute

Los Angeles, California 90027

United States

Ventura County Hematology Oncology Specialists

Oxnard, California 93030

United States

Brcr Coral Springs

Coral Springs, Florida 33065

United States

Mid Florida Hematology and Oncology Center

Orange City, Florida 32763-8316

United States

Cancer Care Centers of Brevard Palm Bay

Palm Bay, Florida 32901

United States

Florida Clinical Trials Group Plantation

Plantation, Florida 33322

United States

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida 34952-7596

United States

The Oncology Institute of Hope and Innovation South Miami

South Miami, Florida 33143

United States

Florida Clinical Trials Group Tamarac

Tamarac, Florida 33321

United States

Moffitt Cancer Center McKinley Campus Richard M Shulze Family Foundation Outpatient Center

Tampa, Florida 33612

United States

University Cancer and Blood Center Athens Comprehensive Cancer Center

Athens, Georgia 30607

United States

Central Georgia Cancer Care Macon Office

Macon, Georgia 31210

United States

Hawaii Cancer Care

Honolulu, Hawaii 96813

United States

Hope and Healing Cancer Services

Hinsdale, Illinois 60521-0509

United States

Cancer Care Specialists For Illinois

OFallon, Illinois 62269

United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana 46804

United States

Hematology Oncology of Indiana

Indianapolis, Indiana 46260

United States

Mercy Medical Center

Cedar Rapids, Iowa 52403

United States

Owensboro Health Mitchell Memorial Cancer Center

Owensboro, Kentucky 42303

United States

Karmanos Cancer Institute

Detroit, Michigan 48201-2013

United States

Aspirus St Lukes Hospital

Duluth, Minnesota 55805

United States

Metro Minnesota Community Oncology Research Consortium (Mmcorc)

Saint Paul, Minnesota 55101-2502

United States

Oncology Hematology Associates

Springfield, Missouri 65807-5288

United States

Nebraska Cancer Specialists St Francis Grand Island

Grand Island, Nebraska 68803

United States

Cancer Partners of Nebraska April Sampson Cancer Center

Lincoln, Nebraska 68516

United States

Nebraska Cancer Specialists

Omaha, Nebraska 68130-2042

United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada 89169-3321

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Astera Cancer Care East Brunswick

East Brunswick, New Jersey 08816-4096

United States

Summit Medical Group

Florham Park, New Jersey 07932-1049

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901-1914

United States

Nyu Langone Health Perlmutter Cancer Center Sunset Park

Brooklyn, New York 11220

United States

Nyu Langone Health Perlmutter Cancer Center At Nyu Langone Hospital Long Island

Mineola, New York 11501

United States

Nyu Langone Health Perlmutter Cancer Center 34Th Street

New York, New York 10016

United States

University of Rochester

Rochester, New York 14642-0001

United States

New York Cancer and Blood Specialists

Shirley, New York 11967

United States

Pardee Cancer Center

Hendersonville, North Carolina 28739

United States

Carolina Cancer Research Center

Wilson, North Carolina 27896

United States

Gabrail Cancer Center Research

Canton, Ohio 44718-2566

United States

Dayton Physicians Network

Dayton, Ohio 45409

United States

Oncology Associates of Oregon Willamette Valley Cancer Center

Eugene, Oregon 97401

United States

Oregon Oncology Specialists

Salem, Oregon 97301

United States

Consultants in Medical Oncology and Hematology Cancer Center At Broomall

Broomall, Pennsylvania 19008

United States

McGlinn Cancer Institute

West Reading, Pennsylvania 19611-2143

United States

Ballad Health Cancer Center Kingsport

Kingsport, Tennessee 37660

United States

Texas Oncology Austin Central

Austin, Texas 78731-4214

United States

Utah Cancer Specialists Cancer Center

Salt Lake City, Utah 84107

United States

Oncology and Hematology Associates of Southwest Virginia, Inc (Us Oncology Research)

Blacksburg, Virginia 24060-6325

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031-2171

United States

Virginia Cancer Institute

Richmond, Virginia 23229-8605

United States

Vista Oncology East Olympia

Olympia, Washington 98506

United States

Multicare Cancer Institute Deaconess Medical Office Building 1

Spokane, Washington 99204

United States

Multicare Cancer Institute Tacoma General Hospital

Tacoma, Washington 98405

United States

Northwest Medical Specialties

Tacoma, Washington 98405

United States

Multicare Cancer Institute North Star Lodge

Yakima, Washington 98902

United States

Gundersen Health System

La Crosse, Wisconsin 54601-5467

United States

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales NSW 2148

Australia

Liverpool Hospital

Liverpool, New South Wales NSW 2170

Australia

Wollongong Hospital

Wollongong, New South Wales NSW 2500

Australia

Sunshine Coast University Private Hospital

Birtinya, Queensland QLD 4575

Australia

Townsville University Hospital

Douglas, Queensland QLD 4814

Australia

Peter Maccallum Cancer Centre

Melbourne, Victoria VIC 3000

Australia

Fiona Stanley Hospital

Murdoch, Western Australia WA 6150

Australia

One Clinical Research

Nedlands, Western Australia WA 6009

Australia

Fundacao Pio Xii Hospital de Amor de Barretos

Barretos, 14.784-400

Brazil

Hospital Brasilia

Brasília, 71681-603

Brazil

Instituto de Pesquisa Em Saude Da Universidade de Caxias Do Sul

Caxias do Sul, 95070-560

Brazil

Oncosite Centro de Pesquisa Clinica Em Oncologia

Ijuí, 98700-000

Brazil

Liga Norte Riograndene Contra O Cancer

Natal, 59062-000

Brazil

Hospital Sao Lucas Da Pucrs

Porto Alegre, 90610-000

Brazil

Instituto Sul Mineiro de Oncologia Ltda

Pouso Alegre, 37554-238

Brazil

Hospital Do Cancer de Pernambuco

Recife, 50040-000

Brazil

Instituto Nacional de Cancer

Rio de Janeiro, 20560-120

Brazil

Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira

São Paulo, 01246-000

Brazil

The First Affiliated Hospital of Bengbu Medical University

Bengbu, Anhui 233004

China

Beijing Cancer Hospital

Beijing, Beijing Municipality 100142

China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality 630014

China

Fujian Medical University Union Hospital

Fuzhou, Fujian 350001

China

The Peoples Hospital Affiliated to Fujian University of Traditional Chinese Medicine

Fuzhou, Fujian 350009

China

Fujian Cancer Hospital

Fuzhou, Fujian 350014

China

Sun Yat Sen University Cancer Center

Guangzhou, Guangdong 510060

China

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)

Guangzhou, Guangdong 510245

China

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong 515031

China

Guangxi Medical University Cancer Hospital Wuxiang Branch

Nanning, Guangxi 530201

China

Hainan General Hospital

Haikou, Hainan 570206

China

Affiliated Hospital of Hebei University(North Branch)

Baoding, Hebei 71000

China

The Fourth Hospital of Hebei Medical University East Branch

Shijiazhuang, Hebei 050035

China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan 450052

China

Union Hospital Tongji Medical College Huazhong University of Science and Technologyjinyinhu Branch

Wuhan, Hubei 430048

China

Hubei Cancer Hospital

Wuhan, Hubei 430079

China

The First Peoples Hospital of Changde City

Changde, Hunan 415000

China

Xiangya Hospital of Central South University

Changsha, Hunan 410008

China

Jiangsu Province Hospital Longjiang Branch

Nanjing, Jiangsu 210036

China

Affiliated Hospital of Nantong University

Nantong, Jiangsu 201203

China

Nanchang Peoples Hospitalchaoyang Branch

Nanchang, Jiangxi 330025

China

Jiangxi Cancer Hospital

Nanchang, Jiangxi 330029

China

The Second Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi 710004

China

Weifang Peoples Hospital

Weifang, Shandong 261000

China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality 200000

China

Yuncheng Central Hospital West Branch

Yuncheng, Shanxi 44099

China

Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital

Chengdu, Sichuan 610071

China

Binhai Hospital, Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality 300453

China

Yunnan Cancer Hospital

Kunming, Yunnan 650100

China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang 325000

China

Centre de Lutte Contre Le Cancer Institut Bergonie

Bordeaux, 33076

France

Icm Val Daurelle

Montpellier, 34090

France

Centre Eugene Marquis

Rennes, 35043

France

Institut Gustave Roussy

Villejuif, 94800

France

Invo Institut Fur Versorgungsforschung in Der Onkologie

Koblenz, 56068

Germany

Istituto Europeo Di Oncologia

Milan, 20141

Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168

Italy

Japan Community Healthcare Organization Kurume General Hospital

Kurumeshi, Fukuoka 830-0013

Japan

Gunma Prefectural Cancer Center

Otashi, Gunma 373-8550

Japan

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, Hiroshima 730-8518

Japan

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido 003-0804

Japan

Hyogo Medical University Hospital

Nishinomiyashi, Hyōgo 663-8501

Japan

Social Medical Corporation Hakuaikai Sagara Hospital

Kagoshima, Kagoshima-ken 892-0833

Japan

Tokai University Hospital

Iseharashi, Kanagawa 259-1193

Japan

Nippon Medical School Musashi Kosugi Hospital

Kawasakishi, Kanagawa 211-8533

Japan

Yokohama City University Medical Center

Yokohama, Kanagawa 232-0024

Japan

Kanagawa Cancer Center

Yokohama, Kanagawa 241-8515

Japan

Mie University Hospital

Tsu, Mie-ken 514-8507

Japan

National Hospital Organization Osaka National Hospital

Osakashi, Osaka 540-0006

Japan

The University of Osaka Hospital

Suitashi, Osaka 565-0871

Japan

Tokyo Metropolitan Komagome Hospital

Bunkyoku, Tokyo 113-8677

Japan

Cancer Institute Hospital of Jfcr

Kotoku, Tokyo 135-8550

Japan

Showa Medical University Hospital

Shinagawaku, Tokyo 142-8666

Japan

Tokyo Womens Medical University Hospital

Shinjukuku, Tokyo 162-8666

Japan

Pulau Pinang Hospital

George Town, 10450

Malaysia

Hospital Raja Permaisuri Bainun

Ipoh, 30450

Malaysia

Hospital Raja Perempuan Zainab Ii

Johor Bahru, 15586

Malaysia

Hospital Wanita Dan Kanak Kanak Sabah (Hospital Likas)

Kota Kinabalu Sabah, 88996

Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, 50586

Malaysia

University Malaya Medical Centre

Kuala Lumpur, 59100

Malaysia

Sarawak General Hospital

Kuching, 93586

Malaysia

Hospital Picaso

Petaling Jaya, 46300

Malaysia

National Cancer Institute (Institut Kanser Negara)

Putrajaya, 62250

Malaysia

Bialostockie Centrum Onkologii Im M Sklodowskiej Curie W Bialymstoku

Bialystok, 15-027

Poland

Szpitale Pomorskie Spolka Z Ograniczona Odpowiedzialnoscia

Gdynia, 81-519

Poland

Pratia McM Krakow

Krakow, 30-727

Poland

Szpital Specjalistyczny Im Ludwika Rydygiera W Krakowie

Krakow, 31-826

Poland

Opolskie Centrum Onkologii

Opole, 45-061

Poland

Brcr Global Puerto Rico Hato Rey

San Juan, 00917

Puerto Rico

Inje University Haeundae Paik Hospital

HaeundaeGu, Busan Gwang'Yeogsi 48108

South Korea

Dong A University Hospital

Seogu, Busan Gwang'Yeogsi 49201

South Korea

Chungbuk National University Hospital

Cheongju-si, Chungcheongbukdo 28644

South Korea

Soon Chun Hyang University Cheonan Hospital

Cheonansi, Chungcheongnam-do 31151

South Korea

Keimyung University Dongsan Hospital

Dalseogu, Daegu Gwang'Yeogsi 42601

South Korea

Cha Bundang Medical Center, Cha University

BundangGu SeongnamSi, Gyeonggi-do 13496

South Korea

Korea University Ansan Hospital

DanwonGu AnsanSi, Gyeonggi-do 15355

South Korea

National Cancer Center (Korea)

IlsandongGu GoyangSi, Gyeonggi-do 10408

South Korea

The Catholic University of Korea, St Vincents Hospital

PaldalGu SuwonSi, Gyeonggi-do 16247

South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do 13620

South Korea

Inha University Hospital

Jemulpogu, Incheon Gwang'Yeogsi 22332

South Korea

Gachon University Gil Medical Center

NamdongGu, Incheon Gwang'Yeogsi 21565

South Korea

Chonnam National University Hwasun Hospital

HwasunGun, Jeonnam-Gwangju S.M. City 58128

South Korea

Chung Ang University Hospital

DongjakGu, Seoul Teugbyeolsi 06973

South Korea

Samsung Medical Center

GangnamGu, Seoul Teugbyeolsi 06351

South Korea

Korea University Guro Hospital

GuroGu, Seoul Teugbyeolsi 08308

South Korea

The Catholic University of Korea, Seoul St Marys Hospital

SeochoGu, Seoul Teugbyeolsi 06591

South Korea

Severance Hospital Yonsei University Health System

SeodaemunGu, Seoul Teugbyeolsi 03722

South Korea

Korea University Anam Hospital

SeongbukGu, Seoul Teugbyeolsi 02841

South Korea

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi 03080

South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi 06273

South Korea

Ehwa Womans University Mokdong Hospital

Seoul, Seoul Teugbyeolsi 07985

South Korea

Asan Medical Center

SongpaGu, Seoul Teugbyeolsi 05505

South Korea

Ulsan University Hospital

Ulsan, Ulsan Gwang'Yeogsi 44033

South Korea

Ajou University Hospital

Suwon, 16499

South Korea

Hospital General Universitario de Elche

Elcheelx, 03203

Spain

Hospital Universitario Clinico San Cecilio

Granada, 18016

Spain

Iob Institute of Oncology Madrid

Madrid, 28007

Spain

Complejo Hospitalario Univ de Santiago (Chus)

Santiago de Compostela, 15706

Spain

Hospital Universitario Virgen Del Rocio

Seville, 41013

Spain

Taipei Veterans General Hospital

Beitou Dist, 11217

Taiwan

China Medical University Hospital

Taichung, 40447

Taiwan

National Cheng Kung University Hospital

Tainan, 704

Taiwan

National Taiwan University Hospital

Zhongzheng Dist, 100225

Taiwan

Adana City Education and Research Hospital

Adana, 01060

Turkey (Türkiye)

Hacettepe University

Ankara, 6100

Turkey (Türkiye)

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380

Turkey (Türkiye)

Royal Surrey County Hospital

Guildford, GU27XX

United Kingdom

Maidstone and Tunbridge Wells Nhs Trust Kent Oncology Centre Maidstone Hospital

Maidstone, ME16 9QQ

United Kingdom