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

NCT ID: NCT06982521

Last Updated: 2025-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-26

Study Completion Date

2031-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RLY-2608 + fulvestrant

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

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

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

Fulvestrant

Intervention Type DRUG

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

capivasertib + fulvestrant

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

Group Type ACTIVE_COMPARATOR

Capivasertib

Intervention Type 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

Fulvestrant

Intervention Type DRUG

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

Interventions

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RLY-2608

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

Intervention Type DRUG

Capivasertib

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

Intervention Type DRUG

Fulvestrant

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

Intervention Type DRUG

Other Intervention Names

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TRUQAP Faslodex

Eligibility Criteria

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Inclusion Criteria

* 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:

1. 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
2. 1 prior line of CDK4/6 inhibitor therapy in one of the following settings:

1. CDK4/6 inhibitor + ET in the ABC setting
2. 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
3. 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

Exclusion Criteria

* Prior treatment with any of the following:

1. CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases
2. PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
3. Immunotherapy
4. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Relay Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Beverly Hills Cancer Center

Beverly Hills, California, United States

Site Status RECRUITING

Cedars-Sinai Medical Center

Beverly Hills, California, United States

Site Status RECRUITING

Stanford University School of Medicine

Palo Alto, California, United States

Site Status RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

Rocky Mountain Cancer Centers

Longmont, Colorado, United States

Site Status RECRUITING

Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

Medical Oncology Hematology Consultants

Newark, Delaware, United States

Site Status RECRUITING

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status RECRUITING

Cancer Care Centers of Brevard

Palm Bay, Florida, United States

Site Status RECRUITING

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Community Health Network

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Kansas Medical Center

Westwood, Kansas, United States

Site Status RECRUITING

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status RECRUITING

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Profound Research LLC

Royal Oak, Michigan, United States

Site Status RECRUITING

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status RECRUITING

Renown Regional Medical Center

Reno, Nevada, United States

Site Status RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, United States

Site Status RECRUITING

NYU Langone Cancer Center

New York, New York, United States

Site Status RECRUITING

Columbia University Herbert Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Site Status RECRUITING

Tennessee Oncology

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Oncology Central/South

Austin, Texas, United States

Site Status RECRUITING

Texas Oncology DFW

Dallas, Texas, United States

Site Status RECRUITING

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Huntsman Cancer Center, University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status RECRUITING

Ballarat Oncology & Haematology Service

Wendouree, Victoria, Australia

Site Status RECRUITING

CHU-UCL Namur, Site Sainte-Elisabeth

Namur, , Belgium

Site Status RECRUITING

Vitaz, Campus Sint-Niklaas

Sint-Niklaas, , Belgium

Site Status RECRUITING

CEON+ Pesquisas

São Caetano do Sul, São Paulo, Brazil

Site Status RECRUITING

Aalborg University Hospital

Aalborg, , Denmark

Site Status RECRUITING

Sygehus Sønderjylland

Sønderborg, , Denmark

Site Status RECRUITING

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Countries

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United States Australia Belgium Brazil Denmark Spain

Central Contacts

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Relay Therapeutics, Inc

Role: CONTACT

Phone: 617-322-0731

Email: [email protected]

Other Identifiers

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RLY-2608-102

Identifier Type: -

Identifier Source: org_study_id