Phase 3 Study Comparing RLY-2608 + Fulvestrant and Capivasertib + Fulvestrant for Advanced PIK3CA-mutant HR+/HER2- Breast Cancer

Inclusion Criteria

• Adults with a performance status of 0-1, meaning they are fully active or have some restrictions but can carry out light work.
• Have a known PIK3CA mutation in their cancer.
• Women (pre- and post-menopausal) and men can participate. Pre-menopausal women must agree to take a hormone treatment (GnRH agonist) starting at least 4 weeks before joining the study and continue it throughout the study.
• Have a confirmed diagnosis of HR+/HER2- advanced breast cancer that cannot be surgically removed.
• Have measurable cancer or bone-only disease that can be evaluated.
• Have shown cancer progression after previous treatments, including:
  • 1 or 2 lines of hormone therapy, with cancer returning during or within 12 months after treatment.
  • 1 line of CDK4/6 inhibitor therapy, either with hormone therapy for advanced cancer or during adjuvant treatment if cancer progressed during or within 12 months after completion.

Exclusion Criteria

• Previous treatment with certain drugs, including:
  • CDK2 or selective CDK4 inhibitors, or experimental drugs targeting similar pathways.
  • PIK3, AKT, or mTOR inhibitors, or drugs affecting the same pathway.
  • Immunotherapy or antibody drug conjugates.
• Have Type 1 diabetes or Type 2 diabetes requiring medication, or high blood sugar levels.
• Have significant, uncontrolled heart disease.
• Have conditions that increase the risk of heart rhythm problems.
• Have active, uncontrolled brain metastases causing symptoms or requiring ongoing treatment.
• Have a history of lung diseases like interstitial lung disease or radiation pneumonitis needing steroid treatment.
• Have allergies to fulvestrant or similar drugs, RLY-2608, or capivasertib.
• Have certain genetic mutations or loss of gene function that activate cancer pathways.