A Study Evaluating the Safety of Inavolisib and Fulvestrant With or Without Palbociclib in Participants With Advanced Breast Cancer (ABC) and Type 2 Diabetes

• Inavolisib (Drug), also known as RO7113755: Participants will receive oral inavolisib on Days 2-28 of each 28-day cycle.
• Fulvestrant (Drug): Participants will receive intramuscular (IM) fulvestrant on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28-day cycle.
• Palbociclib (Drug): Some participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.

Primary outcomes

• Percentage of Participants With Grade 4 Hyperglycemia Adverse Events (AEs) After Cycle 1 [Up to approximately 21 months]
• Percentage of Participants Hospitalized for Hyperglycemia or its Complications After Cycle 1 [Up to approximately 21 months]
• Percentage of Participants with AEs After Cycle 1 [Up to approximately 21 months]

Secondary outcomes

• Percentage of Particiants With Inavolisib-related Hyperglycemia AEs After Cycle 1 [Up to Cycle 1 (each cycle is 28 days)]
• Percentage of Participants With Inavolisib Discontinuations due to Hyperglycemia and its Complications [Up to approximately 21 months]
• Percentage of Participants With Inavolisib Dose Reduction due to Hyperglycemia [Up to approximately 21 months]
• Percentage of Participants With Return of Hemoglobin A1c or Glycated Hemoglobin (HbA1c) to Within 10% of Baseline Within 90 Days After Inavolisib Discontinuation [Up to approximately 21 months]
• Number of Participants Reporting Presence,Frequency,Severity,&/or Degree of Interference with Daily Function of Selected Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for AEs (PRO-CTCAE) [Up to approximately 21 months]
• Percentage of Participants Reporting Each Response Option at Each Time Point for the Treatment Side-Effect Bother Item (GP5) From the Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire [Up to approximately 21 months]
• Change from Baseline in Symptomatic Treatment-Related Toxicities as Assessed Through use of the PRO-CTCAE [Baseline, Up to approximately 21 months]
• Change from Baseline in Treatment Side-Effect Bother as Assessed Through use of the FACT-G General Population, Question 5 (GP5) Item [Baseline, Up to approximately 21 months]
• Objective Response Rate (ORR) [Up to approximately 21 months]
• Best Overall Response Rate (BOR) [Up to approximately 21 months]
• Duration of Response (DOR) [Up to approximately 21 months]
• Progression-Free Survival (PFS) [Up to approximately 21 months]
• Overall Survival (OS) [Up to approximately 21 months]
• Mean and Mean Change From Baseline in Physical Function Score as Assessed by European Organisation for Research and Treatment of Cancer Item Library 17 (EORTC-IL17) [Baseline, up to approximately 21 months]
• Mean and Mean Change From Baseline in Role Function Score as Assessed by EORTC-IL17 [Baseline, up to approximately 21 months]
• Mean and Mean Change From Baseline in Health-Related Quality of Life (HRQoL) Score as Assessed by EORTC-IL17 [Baseline, up to approximately 21 months]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Type 2 diabetes with laboratory fasting blood glucose < 185 milligrams per deciliter (mg/dL) and HbA1c <= 8% on any stable anti-hyperglycemic regimen excluding insulin short-term insulin dosing
* Eligible for triplet of inavolisib, fulvestrant and palbociclib: no prior systemic therapy for locally advanced unresectable or metastatic disease
* Confirmed diagnosis of HR+/HER2- breast cancer
* Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria:

* Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
* Metaplastic breast cancer
* Any history of Type 1 diabetes
* Severe hyper- or hypoglycemia event within 6 months of initiation of study treatment
* Any history of leptomeningeal disease or carcinomatous meningitis
* Known and untreated, or active central nervous system (CNS) metastases Participants with a history of treated CNS metastases are eligible
* Active inflammatory or conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
* Symptomatic active lung disease
* History of active bowel inflammation or active inflammatory bowel disease

• Clinical Trials, Study director, Hoffmann-La Roche