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
- Brampton, Montreal, Ottawa, Saskatoon, and Toronto, CanadaSee the 5 sites
- Phase
- Phase 3
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 Canada
- William Osler Health System - Brampton Civic HospitalBrampton, CanadaTaking people
- Jewish General HospitalMontreal, CanadaTaking people
- The Ottawa Hospital Cancer CentreOttawa, CanadaTaking people
- Saskatoon Cancer CentreSaskatoon, CanadaTaking people
- Sunnybrook Research InstituteToronto, CanadaTaking 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.