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

Recruiting now · Phase 3

Conditions studied: PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer

In brief

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.

Key facts

Study ID

NCT06982521

Run by

Relay Therapeutics, Inc.

People needed

540

Starts

2025-08-26

Expected to finish

2031-12-31

Last updated by the study team

2026-08-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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 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:
• 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
• Only 1 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 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor
• 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 (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

Where it is running

• Beverly Hills Cancer Center — Beverly Hills, California, United States (enrolling)
• City of Hope National Medical Center — Duarte, California, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)
• Stanford Women's Cancer Center — Palo Alto, California, United States (enrolling)
• University of California, Davis Comprehensive Cancer Center — Sacramento, California, United States (enrolling)
• University of California San Diego Moores Cancer Center — San Diego, California, United States (enrolling)
• University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States (enrolling)
• Kaiser Permanente Medical Center — Vallejo, California, United States (enrolling)
• Rocky Mountain Cancer Centers, LLP — Longmont, Colorado, United States (enrolling)
• Yale-New Haven Hospital-Yale Cancer Center — New Haven, Connecticut, United States (enrolling)
• Medical Oncology Hematology Consultants, P.A. — Newark, Delaware, United States (enrolling)
• Georgetown University Medical Center — Washington D.C., District of Columbia, United States (enrolling)
• AdventHealth — Altamonte Springs, Florida, United States (enrolling)
• Florida Cancer Specialists-South — Fort Myers, Florida, United States (enrolling)
• Cancer Care Centers of Brevard, Inc — Palm Bay, Florida, United States (enrolling)
• Atlanta Cancer Care - Northside Hospital — Atlanta, Georgia, United States (enrolling)
• Rush University Medical Center — Chicago, Illinois, United States (enrolling)
• Robert H. Lurie Comprehensive Cancer Center of Northwestern University — Chicago, Illinois, United States (enrolling)
• Community Health Network, Inc — Indianapolis, Indiana, United States (enrolling)
• University of Kansas Cancer Center — Westwood, Kansas, United States (enrolling)
• Cancer Center of Kansas — Wichita, Kansas, United States (enrolling)
• Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins — Baltimore, Maryland, United States (enrolling)
• Tufts Medical Center — Boston, Massachusetts, United States (enrolling)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.