A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

Inclusion Criteria

• Inclusion Criteria for Both Stages: - Measurable disease per RECIST v1.1 - Adequate hematologic and end organ function - Disease progression during or after first- or second-line hormonal therapy with CDK4/6 inhibitor Inclusion Criteria for Stage 1: - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Metastatic or inoperable, locally advanced, histologically or cytologically confirmed invasive HR-positive HER2-negative breast cancer - Recommended for endocrine therapy, and cytotoxic chemotherapy not indicated at study entry - Recurrence or progression following most recent systemic breast cancer therapy - Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease - Postmenopausal according to protocol-defined criteria - Life expectancy >3 months - Available tumor specimen for determination of PD-L1 status Inclusion Criteria for Stage 2: - ECOG performance status of 0-2 - Ability to initiate treatment within 3 months after disease progression or unacceptable toxicity on a Stage 1 regimen Exclusion Criteria for Both Stages: - Significant or uncontrolled comorbid disease as specified in the protocol - Uncontrolled tumor-related pain - Autoimmune disease except for stable/controlled hypothyroidism, Type 1 diabetes mellitus, or certain dermatologic conditions - Positive human immunodeficiency virus test - Active hepatitis B or C - Active tuberculosis - Severe infection within 4 weeks and/or antibiotics within 2 weeks prior to study treatment - Prior allogeneic stem cell or solid organ transplantation - History of malignancy other than breast cancer within 2 years prior to screening except those with negligible risk of metastasis/death - History of or known hypersensitivity to study drug or excipients - For patients entering Stage 2, recovery from all immunotherapy-related adverse events to Grade 1 or better or to baseline at the time of consent Exclusion Criteria for Stage 1: - Prior fulvestrant or cytotoxic chemotherapy for metastatic breast cancer, or certain other agents as specified in the protocol - Unresolved AEs from prior anti-cancer therapy - Eligibility only for the control arm - Prior treatment with inhibitors as specified in the protocol Exclusion Criteria for Stage 2: - Unacceptable toxicity with atezolizumab during Stage 1 - Uncontrolled cardiovascular disease or coagulation disorder, including use of anticoagulants as specified in the protocol - Significant abdominal or intestinal manifestations within 6 months prior to treatment - Grade 2 or higher proteinuria