Recruiting
Phase 3

RLY-2608 & Capivasertib

Sponsor:

Relay Therapeutics, Inc.

Code:

NCT06982521

Conditions

PIK3CA Mutation

HER2- Negative Breast Cancer

Hormone Receptor Positive Tumor

Breast Cancer

Metastatic Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zovegalisib

Capivasertib

Fulvestrant

Study Details

Brief summary:

This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 (zovegalisib) + 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

PIK3CA Mutation

HER2- Negative Breast Cancer

Hormone Receptor Positive Tumor

Breast Cancer

Metastatic Breast Cancer

Study ID

NCT06982521

Start date

Aug 26, 2025

Status verified date

Jul, 2026

Completion date

Dec 31, 2031

Anticipated

Primary completion date

Apr 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 2 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. Only 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 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor
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 (7.8 mmol/L), 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, zovegalisib, 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

Study Design

Enrollment

540 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Zovegalisib + fulvestrant

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

active comparator: capivasertib + fulvestrant

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

Interventions

Zovegalisib

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

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

Fulvestrant

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

Primary outcome measure

  • Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR) [ Time Frame: The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months ]

Central Contacts and Locations

Central contacts

Relay Therapeutics, Inc

617-322-0731ClinicalTrials@relaytx.com

Locations

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

Beverly Hills Cancer Center

Recruiting

Beverly Hills, California, United States, 90211

City of Hope National Medical Center

Recruiting

Duarte, California, United States, 91010

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Stanford Women's Cancer Center

Recruiting

Palo Alto, California, United States, 94304

University of California, Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

University of California San Diego Moores Cancer Center

Recruiting

San Diego, California, United States, 92037

University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center

Recruiting

San Francisco, California, United States, 94158

Kaiser Permanente Medical Center

Recruiting

Vallejo, California, United States, 94589

Rocky Mountain Cancer Centers, LLP

Recruiting

Longmont, Colorado, United States, 80504

Yale-New Haven Hospital-Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06510

Medical Oncology Hematology Consultants, P.A.

Recruiting

Newark, Delaware, United States, 19713

Georgetown University Medical Center

Recruiting

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

AdventHealth

Recruiting

Altamonte Springs, Florida, United States, 32701

Florida Cancer Specialists-South

Recruiting

Fort Myers, Florida, United States, 33901

Cancer Care Centers of Brevard, Inc

Recruiting

Palm Bay, Florida, United States, 32909

Atlanta Cancer Care - Northside Hospital

Recruiting

Atlanta, Georgia, United States, 30342

Rush University Medical Center

Recruiting

Chicago, Illinois, United States, 60607

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Community Health Network, Inc

Recruiting

Indianapolis, Indiana, United States, 46250

University of Kansas Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Cancer Center of Kansas

Recruiting

Wichita, Kansas, United States, 67214

Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins

Recruiting

Baltimore, Maryland, United States, 21287

Tufts Medical Center

Recruiting

Boston, Massachusetts, United States, 02111

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Profound Research LLC

Recruiting

Royal Oak, Michigan, United States, 48073

Minnesota Oncology Hematology, P.A.

Recruiting

Minneapolis, Minnesota, United States, 55404

University of Mississippi Medical Center

Recruiting

Jackson, Mississippi, United States, 39213

Washington University School of Medicine- Siteman Cancer Center

Recruiting

St Louis, Missouri, United States, 63108

Nebraska Cancer Specialists

Recruiting

Omaha, Nebraska, United States, 68130

Renown Health Medical Oncology

Recruiting

Reno, Nevada, United States, 89502

John Theurer Cancer Center at Hackensack University Medical Center

Recruiting

Hackensack, New Jersey, United States, 07601

Rutgers Cancer Institute

Recruiting

New Brunswick, New Jersey, United States, 08901

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

Recruiting

New York, New York, United States, 10016

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Columbia University Irving Medical Center

Recruiting

New York, New York, United States, 10032

Memorial Sloan-Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Oregon Health & Science University, Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97210

Avera Cancer Institute

Recruiting

Sioux Falls, South Dakota, United States, 57105

Tennessee Cancer Specialists

Recruiting

Knoxville, Tennessee, United States, 37909

Tennessee Oncology, PLLC

Recruiting

Nashville, Tennessee, United States, 37203

Texas Oncology Central/South

Recruiting

Austin, Texas, United States, 78731

Texas Oncology DFW

Recruiting

Dallas, Texas, United States, 75246

University of Texas Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Houston Methodist Hospital Cancer Center

Recruiting

Houston, Texas, United States, 77030

The University of Texas M.D. Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Baylor Scott and White Medical Center

Recruiting

Temple, Texas, United States, 76508

Huntsman Cancer Institute, University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Virginia Cancer Specialists, PC

Recruiting

Fairfax, Virginia, United States, 22031

Virginia Oncology Associates

Recruiting

Norfolk, Virginia, United States, 23502

University of Wisconsin Carbone Cancer Center- University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

William Osler Health System- Brampton Civic Hospital

Recruiting

Brampton, Ontario, Canada, L6R 3J7

The Ottawa Hospital Cancer Centre

Recruiting

Ottawa, Ontario, Canada, K1H8L6

Sunnybrook Research Institute

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

Saskatoon Cancer Centre

Recruiting

Saskatoon, Saskatchewan, Canada, S7N 4H4

More Information

Sponsor

Relay Therapeutics, Inc.

Last update posted

Sep 3, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Relay Therapeutics, Inc. on 2026-09-03.