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

Open to females ages 18 years and up

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

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