PIK3CA-Related Overgrowth Spectrum Clinical Trials

• 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 4 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

⁃ 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