A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/​6i and Endocrine Combination Therapy (INAVO121)

• Drug: Inavolisib
• Drug: Fulvestrant
• Drug: Alpelisib

Inclusion Criteria:

• If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1
• Histologically or cytologically confirmed adenocarcinomacancer arising from mucus-producing glands in organs of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells with curative intent
• Documented HR +/ HER2- tumor according to American Society of Clinical Oncologythe study, diagnosis and treatment of cancer/College of American Pathologists (ASCO/CAP) guidelines
• Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test
• Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: <= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based therapy does not need to be the last one received prior study entry; one line of chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells in mBC setting allowed
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Life expectancy of > 6 months
• Adequate hematologic and organ function prior to initiation of study treatment