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RecruitingLast updated: 18 May 2026

ReDiscover-2: Comparing two targeted therapies when given with hormone therapy for the treatment of HR+, HER2- breast cancer that is locally advanced or metastatic, and has PIK3CA mutationA 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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Breast Cancers Breast

Age

People18+

Trial acronym

ReDiscover-2

Clinical summary

Summary

This clinical trial is evaluating how safe and effective treatment with a targeted drug called RLY-2608 + fulvestrant hormone therapy is compared to treatment with capivasertib targeted therapy + fulvestrant. 

The study is recruiting people with HR+, HER-, locally advanced or metastatic breast cancer that has a PIK3CA mutation, and has come back (recurrent) or progressed after treatment with a CDK4/6 inhibitor.

Eligible participants will be randomly allocated (by chance) to one of two treatment arms.

Experimental Arm
Participants will receive RLY-2608 given as an oral tablet twice daily, plus Fulvestrant given as an injection into the muscle (intramuscularly) on Cycle 1, Day 1 and Day 15, and then Day 1 of each following cycle. Treatment cycles are 28-days.

Active Comparator Arm
Participants will receive Capivasertib orally twice daily on an intermittent weekly dosing schedule. This means participants will dose Days 1-4 each week of a 28-day treatment cycle. Participants will also receive fulvestrant as an injection into the muscle on Cycle 1, Day 1 and Day 15, and then Day 1 of each following cycle. 

Conditions

This trial is treating people with locally advanced or metastatic HR+, HER2- breast cancer with PIK3CA mutation

Eligibility

Inclusion

  • 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

  • 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

Inclusion

  • You have had treatment, but your cancer has come back (relapsed or recurrent).
  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Relay Therapeutics, Inc.

Scientific Title

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

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