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 for Both Stages:

- Measureable 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