A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

Inclusion Criteria

• Confirmed diagnosis of HR+/HER2- breast cancer

• Metastatic or locally advanced disease not amenable to curative therapy

• Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen

• Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal

• Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)

• Consent to provide fresh or archival tumor tissue specimen

• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible

• Eastern Cooperative Oncology Group Performance Status of 0 or 1

• Life expectancy of > 6 months

• Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

• Metaplastic breast cancer

• Any history of leptomeningeal disease or carcinomatous meningitis

• Any prior systemic therapy for metastatic breast cancer

• Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months

• Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway

• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes

• Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible

• Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period

• Symptomatic active lung disease, or requiring daily supplemental oxygen

• History of inflammatory bowel disease or active bowel inflammation

• Anti-cancer therapy within 2 weeks before study entry

• Investigational drug(s) within 4 weeks before randomization

• Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation

• Chronic corticosteroid therapy or immunosuppressants

• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 2 weeks after the final dose of study treatment

• Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1