The purpose of this study is to evaluate the efficacy and safety of inavolisib in combination with fulvestrant compared with inavolisib in combination with fulvestrant in participants with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer (LA/mBC) in the post-cyclin-dependent kinase inhibitor (CDKi) setting.

Inclusion Criteria:

• Documented ER +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
• Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: <= 1 prior lines of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting
• Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
• Confirmation of biomarker eligibility: presence of >= 1 study-eligible PIK3CA mutation
• Life expectancy of > 6 months
• Ability, in the investigator's judgment, and willingness to comply with all study -related procedures, including completion of patient-reported outcomes

Exclusion Criteria:

• Metaplastic breast cancer
• Prior treatment with chemotherapy in the recurrent locally advanced/metastatic setting
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Prior treatment with PI3K/Akt/mTOR inhibitors in the recurrent locally advanced/metastatic setting
• Requirement for daily supplemental oxygen
• Symptomatic active lung disease, including pneumonitis

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing