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

NCT06982521 | Recruiting Phase 3 FDA Drug

• 1 other identifier: RLY-2608-102
• Study Type: interventional
• Target: 540
• Locations: 18 countries
• Sites: 113

Brief 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.

Conditions

Hormone Receptor Positive Tumor; Metastatic Breast Cancer; Advanced Breast Cancer; PIK3CA Mutation; HER2- Negative Breast Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR)

  The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months

Secondary Outcomes (10)

• Overall Survival (OS) within the overall and kinase populations

  The time from randomization to the date of death by any cause, up to approximately 77 months

• PFS by Investigator within the overall and kinase populations

  The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months

• Objective Response Rate (ORR) within the overall and kinase populations

  Up to approximately 77 months

• Duration of Response (DOR) within the overall and kinase populations

  Up to approximately 77 months

• Clinical Benefit Rate (CBR) within the overall and kinase populations

  Up to approximately 77 months

Study Arms (2)

RLY-2608 + fulvestrant

EXPERIMENTAL

RLY-2608 + fulvestrant combination for participants with HR+/HER2- advanced breast cancer

Drug: RLY-2608; Drug: Fulvestrant

capivasertib + fulvestrant

ACTIVE COMPARATOR

capivasertib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer

Drug: Capivasertib; Drug: Fulvestrant

Interventions

RLY-2608 DRUG

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

RLY-2608 + fulvestrant

Capivasertib DRUG

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

Also known as: TRUQAP

capivasertib + fulvestrant

Fulvestrant DRUG

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

Also known as: Faslodex

RLY-2608 + fulvestrant; capivasertib + fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has ECOG performance status of 0-1
• One or more known primary oncogenic PIK3CA mutation(s)
• Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 4 weeks prior to randomization and must be willing to continue on it for the duration of the study.
• Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent
• Measurable disease per RECIST v1.1 or evaluable bone-only disease.
• Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with:
• At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting
• prior line of CDK4/6 inhibitor therapy in one of the following settings:
• CDK4/6 inhibitor + ET in the ABC setting
• CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET
• Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had \>1 prior line of CDK4/6 inhibitor and are not eligible

You may not qualify if:

• Prior treatment with any of the following:
• CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases
• PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
• Immunotherapy
• Antibody drug conjugates
• Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL, or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
• Clinically significant, uncontrolled cardiovascular disease
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
• Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
• Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients
• Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K

Sponsors & Collaborators

• Relay Therapeutics, Inc.: lead

Study Sites (120)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

RECRUITING

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

Stanford University School of Medicine

Palo Alto, California, 94304, United States

RECRUITING

University of California Davis

Sacramento, California, 95817, United States

RECRUITING

University of California San Diego

San Diego, California, 92037, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Kaiser Permanente - Vallejo

Vallejo, California, 94589, United States

RECRUITING

Rocky Mountain Cancer Centers

Longmont, Colorado, 80504, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06511, United States

RECRUITING

Medical Oncology Hematology Consultants

Newark, Delaware, 19713, United States

RECRUITING

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

RECRUITING

Cancer Care Centers of Brevard

Palm Bay, Florida, 32909, United States

RECRUITING

Rush Medical College

Chicago, Illinois, 60607, United States

RECRUITING

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Community Health Network

Indianapolis, Indiana, 46250, United States

RECRUITING

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

RECRUITING

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

RECRUITING

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Profound Research LLC

Royal Oak, Michigan, 48073, United States

RECRUITING

Minnesota Oncology Hematology

Minneapolis, Minnesota, 55404, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39213, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Renown Regional Medical Center

Reno, Nevada, 89502, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

RECRUITING

NYU Langone Cancer Center

New York, New York, 10016, United States

RECRUITING

Mount Sinai

New York, New York, 10029, United States

RECRUITING

Columbia University Herbert Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97210, United States

RECRUITING

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

RECRUITING

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology Central/South

Austin, Texas, 78745, United States

RECRUITING

Texas Oncology DFW

Dallas, Texas, 75246, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Baylor Scott and White Research Institute

Temple, Texas, 76508, United States

RECRUITING

Huntsman Cancer Center, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Sydney Adventist Hospital

Wahroonga, New South Wales, 2076, Australia

RECRUITING

Barwon Health

Geelong, Victoria, 3220, Australia

RECRUITING

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Sunshine Hospital

Saint Albans, Victoria, 3021, Australia

RECRUITING

Ballarat Oncology & Haematology Service

Wendouree, Victoria, 3355, Australia

RECRUITING

Medical University of Graz

Graz, 8010, Austria

RECRUITING

Ordensklinikum Linz GmbH

Linz, 4010, Austria

RECRUITING

LKH Feldkirch, Interne E am LKH Rankweil

Rankweil, 6830, Austria

RECRUITING

Centre Hospitalier de l'Ardenne

Libramont, 6800, Belgium

RECRUITING

CHU-UCL Namur, Site Sainte-Elisabeth

Namur, Belgium

RECRUITING

Vitaz, Campus Sint-Niklaas

Sint-Niklaas, Belgium

RECRUITING

CHR de Verviers site Tourelle

Verviers, 4800, Belgium

RECRUITING

CEON+ Pesquisas

São Caetano do Sul, São Paulo, 09541-270, Brazil

RECRUITING

Centro de Pesquisa Oncoclinica Natal Oncoclinicas

Natal, 59020-505, Brazil

RECRUITING

Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, 90020-090, Brazil

RECRUITING

Centro Gaúcho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, 90110-270, Brazil

RECRUITING

Centro de Pesquisa Clínica da Associação Hospitalar Moinhos de Vento

Porto Alegre, 90560-032, Brazil

RECRUITING

Centro de Pesquisa em Oncologia - PUCRS

Porto Alegre, 90610-000, Brazil

RECRUITING

Oncoclinicas Rio de Janeiro

Rio de Janeiro, 22250-905, Brazil

RECRUITING

Instituto de Educação Pesquisa e Gestão em Saúde

Rio de Janeiro, 22775-001, Brazil

RECRUITING

NOB (Nucleo de Oncologia da Bahia)

Salvador, 40170-110, Brazil

RECRUITING

William Osler Health System- Brampton Civic Hospital

Brampton, Ontario, L6R 3J7, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H8L6, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Masarykuv onkologicky ustav

Brno, 656 33, Czechia

RECRUITING

Aalborg University Hospital

Aalborg, Denmark

RECRUITING

Zealand University Hospital

Næstved, 4700, Denmark

RECRUITING

Sygehus Sønderjylland

Sønderborg, Denmark

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Marienhospital Bottrop gGmbH

Bottrop, 46236, Germany

RECRUITING

Studienzentrale für das MVZ Eggenfelden GbR

Eggenfelden, 84307, Germany

RECRUITING

Praxis fuer Interdisziplinaere Onkologie und Haematologie

Freiburg im Breisgau, 79110, Germany

RECRUITING

Iaso Hospital

Athens, 151 21, Greece

RECRUITING

Interbalkan Hospital of Thessaloniki

Thessaloniki, 570 01, Greece

RECRUITING

Hong Kong United Oncology Centre

Hong Kong, HGK, Hong Kong

RECRUITING

Queen Mary Hospital

Hong Kong, HGK, Hong Kong

RECRUITING

IRCCS Candiolo

Candiolo, 10060, Italy

RECRUITING

AOU Ferrara, Arcispedale Sant'Anna

Cona, 44124, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

RECRUITING

Maastricht University Medical Center

Maastricht, 6229, Netherlands

RECRUITING

Radboud UMC

Nijmegen, 6525, Netherlands

RECRUITING

Haga Ziekenhuis

The Hague, 2545, Netherlands

RECRUITING

Pratia MCM Krakow

Krakow, 30-727, Poland

RECRUITING

Curie Oncology

Singapore, 217562, Singapore

RECRUITING

CHA Bundang Medical Center, CHA University

Seongnam-si, 13496, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

The Catholic University, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seoul, 13620, South Korea

RECRUITING

Hospital Universitario de Badajoz

Badajoz, 06006, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

RECRUITING

Hospital Universitario Juan Ramon Jimenez

Huelva, 21005, Spain

RECRUITING

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

RECRUITING

Hospital Beata Maria Ana/IOB Madrid

Madrid, 28007, Spain

RECRUITING

Clinica Universidad de Navarra

Madrid, 28027, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

RECRUITING

Hospital Universitario de Canarias

San Cristóbal de La Laguna, 38320, Spain

RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Chang Gung Memorial Hospital, Linkou

Taoyuan District, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

capivasertib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Relay Therapeutics, Inc

CONTACT

617-322-0731; ClinicalTrials@relaytx.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 21, 2025
• Study Start: August 26, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: April 2, 2026

Record last verified: 2025-09

Locations

SG (1); HK (2); PL (1); DK (3); DE (3); GR (2); IT (3); BE (4); AU (3); CA (4); TW (5); US (50); FR (1); CZ (1); NL (3); KR (7); ES (11); BR (9)