Tests zovegalisib with fulvestrant against capivasertib in PIK3CA-mutant breast cancer
Compares zovegalisib plus fulvestrant with capivasertib plus fulvestrant in adults with breast cancer.
Plain-language title generated from the registry record
Registry title: Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
Key facts
- Where
- Bath, Cardiff, London, Manchester, Nottingham, Swindon, Taunton, and Truro, United KingdomSee the 11 sites
- Phase
- Phase 3
AI summary: who the study is looking for
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with breast cancer that is hormone receptor positive, HER2 negative, advanced or spread, and has a PIK3CA gene change. The cancer must have grown after a CDK4/6 inhibitor.
- Age
- 18 years and older
- Sex
- Women and men can join. Women before menopause need to be on a GnRH agonist, started at least 2 weeks before randomization.
- Disease stage
- HR+/HER2- locally advanced or metastatic breast cancer that came back or grew. Locally advanced disease must not be removable by surgery meant to remove all of the disease. Measurable disease or bone-only disease.
- Earlier treatment
- Must have had 1 or 2 lines of endocrine therapy. Must have had only 1 prior line of CDK4/6 inhibitor, with the cancer growing on or after it.
- Biomarker or test result
- One or more known main cancer-causing PIK3CA mutations.
Main reasons for not taking part
- Earlier treatment with CDK2 inhibitors, PIK3, AKT or mTOR inhibitors, immunotherapy or antibody drug conjugates
- Type 1 diabetes, or type 2 diabetes needing medicine to lower blood sugar, or high blood sugar levels
- Serious uncontrolled heart disease or factors raising the risk of heart rhythm problems
- Active uncontrolled or symptomatic brain or spinal cord metastases
- History of interstitial lung disease or radiation pneumonitis needing steroids
Read by machine on 9 November 2026.
Could this be for you?
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- What did the tests on your tumour show about hormone receptors and the HER2 protein?
- Have you been treated with a CDK4/6 inhibitor (for example palbociclib, ribociclib or abemaciclib)?
Source: NCT06982521, who can take part
Where in United Kingdom
- Royal United Hospitals Bath NHS Foundation TrustBath, United KingdomTaking people
- Velindre University NHS TrustCardiff, United KingdomTaking people
- Guy's and St Thomas' NHS Foundation TrustLondon, United KingdomTaking people
- Sarah Cannon Research Institute UKLondon, United KingdomTaking people
- St. Bartholomew's HospitalLondon, United KingdomTaking people
- University College London Hospitals NHS Foundation TrustLondon, United KingdomTaking people
- The Christie NHS Foundation TrustManchester, United KingdomTaking people
- Nottingham University Hospital NHS TrustNottingham, United KingdomTaking people
- Great Western Hospital NHS Foundation TrustSwindon, United KingdomTaking people
- Musgrove Park Hospital - Somerset Nhs Foundation TrustTaunton, United KingdomTaking people
- Royal Cornwall HospitalTruro, United KingdomTaking people
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Relay Therapeutics, Inc.
- Trial code
- NCT06982521EU 2025-523083-21-00
- Record updated
- 5 November 2026
- Original description
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.Read full original descriptionShow less
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
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.
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 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.
Exclusion: 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; Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control; Clinically significant, uncontrolled cardiovascular disease; 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; 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); Any factors that increase the risk of QTc prolongation or risk of arrhythmic events; Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K.