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, Advanced Breast Cancer
Eligibility Criteria
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:
- 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 Criteria
- 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
Eligibility criteria are kept as the original English records from ClinicalTrials.gov; actual eligibility is determined by the research team's formal assessment and the informed consent form. Source: ClinicalTrials.gov, updated automatically every two weeks. Last synced: 2026年10月8日.