RecruitingPhase 3NCT06982521

Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer

A Phase 3 Open-Label Randomized Study Assessing the Efficacy and Safety of RLY-2608 + Fulvestrant Versus Capivasertib + Fulvestrant as Treatment for PIK3CA-mutant Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Locally Advanced or Metastatic Breast Cancer Following Recurrence or Progression On or After Treatment With a CDK4/6 Inhibitor

Sponsor

Relay Therapeutics, Inc.

Enrollment

540 participants

Start Date

Aug 26, 2025

Study Type

INTERVENTIONAL

Conditions

PIK3CA Mutation

Summary

This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This Phase 3 study is comparing two treatment combinations in people with advanced hormone receptor-positive, HER2-negative breast cancer that has a specific genetic mutation called PIK3CA. The study tests RLY-2608 (a new targeted drug) plus fulvestrant against the current standard combination of capivasertib plus fulvestrant. **You may be eligible if...** - You are an adult (male or female) with HR+/HER2- locally advanced or metastatic breast cancer - Your tumor has been tested and has a known PIK3CA mutation - You have already been treated with at least one hormonal therapy and one CDK4/6 inhibitor, and your cancer has since progressed - Your health status is good enough to participate (ECOG 0-1) - Pre-menopausal women can participate if they are on hormone suppression therapy **You may NOT be eligible if...** - You have already received more than 2 lines of hormonal therapy in the advanced setting - You have certain diabetes-related conditions or are on medications that can't be held safely - Your cancer does not have a PIK3CA mutation - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGRLY-2608

400 mg orally BID administered daily on a 28-day treatment cycle

DRUGCapivasertib

400mg orally BID administered on an intermittent weekly dosing schedule. Patients will dose on Days 1 through 4 each week of a 28-day treatment cycle

DRUGFulvestrant

500 mg intramuscularly administered on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (28-day treatment cycle)

Locations(120)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Beverly Hills Cancer Center

Beverly Hills, California, United States

Cedars-Sinai Medical Center

Beverly Hills, California, United States

City of Hope

Duarte, California, United States

Stanford University School of Medicine

Palo Alto, California, United States

University of California Davis

Sacramento, California, United States

University of California San Diego

San Diego, California, United States

University of California San Francisco

San Francisco, California, United States

Kaiser Permanente - Vallejo

Vallejo, California, United States

Rocky Mountain Cancer Centers

Longmont, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Medical Oncology Hematology Consultants

Newark, Delaware, United States

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Cancer Care Centers of Brevard

Palm Bay, Florida, United States

Rush Medical College

Chicago, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Community Health Network

Indianapolis, Indiana, United States

University of Kansas Medical Center

Westwood, Kansas, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Profound Research LLC

Royal Oak, Michigan, United States

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University

St Louis, Missouri, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Renown Regional Medical Center

Reno, Nevada, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Rutgers Cancer Institute

New Brunswick, New Jersey, United States

NYU Langone Cancer Center

New York, New York, United States

Mount Sinai

New York, New York, United States

Columbia University Herbert Irving Medical Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

Texas Oncology Central/South

Austin, Texas, United States

Texas Oncology DFW

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Baylor Scott and White Research Institute

Temple, Texas, United States

Huntsman Cancer Center, University of Utah

Salt Lake City, Utah, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

University of Wisconsin

Madison, Wisconsin, United States

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Barwon Health

Geelong, Victoria, Australia

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Sunshine Hospital

Saint Albans, Victoria, Australia

Ballarat Oncology & Haematology Service

Wendouree, Victoria, Australia

Medical University of Graz

Graz, Austria

Ordensklinikum Linz GmbH

Linz, Austria

LKH Feldkirch, Interne E am LKH Rankweil

Rankweil, Austria

Centre Hospitalier de l'Ardenne

Libramont, Belgium

CHU-UCL Namur, Site Sainte-Elisabeth

Namur, Belgium

Vitaz, Campus Sint-Niklaas

Sint-Niklaas, Belgium

CHR de Verviers site Tourelle

Verviers, Belgium

CEON+ Pesquisas

São Caetano do Sul, São Paulo, Brazil

Centro de Pesquisa Oncoclinica Natal Oncoclinicas

Natal, Brazil

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Brazil

Centro Gaúcho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, Brazil

Centro de Pesquisa Clínica da Associação Hospitalar Moinhos de Vento

Porto Alegre, Brazil

Centro de Pesquisa em Oncologia - PUCRS

Porto Alegre, Brazil

Oncoclinicas Rio de Janeiro

Rio de Janeiro, Brazil

Instituto de Educação Pesquisa e Gestão em Saúde

Rio de Janeiro, Brazil

NOB (Nucleo de Oncologia da Bahia)

Salvador, Brazil

William Osler Health System- Brampton Civic Hospital

Brampton, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Sunnybrook Research Institute

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Masarykuv onkologicky ustav

Brno, Czechia

Aalborg University Hospital

Aalborg, Denmark

Zealand University Hospital

Næstved, Denmark

Sygehus Sønderjylland

Sønderborg, Denmark

Centre Leon Berard

Lyon, France

Marienhospital Bottrop gGmbH

Bottrop, Germany

Studienzentrale für das MVZ Eggenfelden GbR

Eggenfelden, Germany

Praxis fuer Interdisziplinaere Onkologie und Haematologie

Freiburg im Breisgau, Germany

Iaso Hospital

Athens, Greece

Interbalkan Hospital of Thessaloniki

Thessaloniki, Greece

Hong Kong United Oncology Centre

Hong Kong, Hong Kong

Queen Mary Hospital

Hong Kong, Hong Kong

IRCCS Candiolo

Candiolo, Italy

AOU Ferrara, Arcispedale Sant'Anna

Cona, Italy

Azienda Ospedaliera Universitaria Careggi

Florence, Italy

Maastricht University Medical Center

Maastricht, Netherlands

Radboud UMC

Nijmegen, Netherlands

Haga Ziekenhuis

The Hague, Netherlands

Pratia MCM Krakow

Krakow, Poland

Curie Oncology

Singapore, Singapore

CHA Bundang Medical Center, CHA University

Seongnam-si, South Korea

Seoul National University Hospital

Seoul, South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

The Catholic University, Seoul St. Mary's Hospital

Seoul, South Korea

Korea University Guro Hospital

Seoul, South Korea

Seoul National University Bundang Hospital

Seoul, South Korea

Hospital Universitario de Badajoz

Badajoz, Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Hospital Clinic de Barcelona

Barcelona, Spain

Hospital San Pedro de Alcantara

Cáceres, Spain

Hospital Universitario Juan Ramon Jimenez

Huelva, Spain

Hospital Universitari Arnau de Vilanova

Lleida, Spain

Hospital Beata Maria Ana/IOB Madrid

Madrid, Spain

Clinica Universidad de Navarra

Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

Hospital General Universitario Morales Meseguer

Murcia, Spain

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Spain

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan

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NCT06982521

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