PIKALO-2: A new drug called tersolisib with other standard treatments as first-line treatment for people with HR+, HER2- advanced breast cancer with PIK3CA mutationA Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY4064809 Combined With a CDK4/6 Inhibitor and Endocrine Therapy in Adults With HR+, HER2-Advanced Breast Cancer With a PIK3CA Mutation Who Received No Prior Treatment for Advanced Breast Cancer (PIKALO-2)

Inclusion

• Are willing to follow contraception requirements. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• If assigned female at birth, pre-/peri- and postmenopausal status is allowed. Those with pre- or peri-menopausal status at study entry must agree to use ovarian function suppression with any locally approved gonadotropin-releasing hormone (GnRH) agonist.
• If assigned male at birth with an estrogen receptor positive (ER+) breast cancer diagnosis, they must agree to use hormone suppression with a GnRH agonist.

• Have histologically or cytologically confirmed breast cancer, defined as individuals with

  • locally advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease, and

  • hormone receptors (HR)+/human epidermal growth factor receptor 2 (HER2)- or HR+/HER low defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines

    • HR status: Documented ER+ and/or progesterone receptor-positive (PR+) tumor according to ASCO/CAP Guidelines, defined as greater than or equal to (≥)1 percent (%) of tumor cells stained positive based on the most recent tumor biopsy and assessed locally
    • HER status: immunohistochemistry score of 1+ or score of 2+ with a negative Fluorescence In Situ Hybridization (FISH) based on local results as defined in the ASCO/CAP Guidelines
• Have evidence of an activating PIK3CA mutation, detected in tumor or blood samples using an appropriate assay.
• Have measurable disease or non-measurable, evaluable bone disease

• Part 1:

  • Received 0-2 prior systemic treatments for advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease.
  • Up to 1 of these prior systemic treatments may contain chemotherapy

• Part 2:

  • Received 0 prior systemic treatment for advanced breast cancer not amenable to curative therapy (for example, surgery) or metastatic disease.

  • Individuals who are eligible are either

    • Population 1 (P1): Endocrine sensitive

      • newly diagnosed with advanced breast cancer (de novo)
      • relapsed with documented evidence of progression greater than (>)12 months from completion of (neo)adjuvant ET ± cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, or

    • Population 2 (P2): Endocrine resistant

      • relapsed with documented evidence of progression less than or equal to (≤)12 months of completing (neo)adjuvant ET ± CDK4/6 inhibitor.
      • if a CDK4/6 inhibitor was included as part of neoadjuvant or adjuvant therapy, progression event must be >12 months since completion of CDK4/6 inhibitor portion of neoadjuvant or adjuvant therapy.