PIK3CA-Related Overgrowth Spectrum Clinical Trials

• 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.