Inclusion Criteria
Clinical stage IV ER, PR, HER2 negative invasive mammary carcinoma, previously documented by histological analysis
Willing to undergo biopsy of a metastatic lesion (in patients with reasonably accessible metastatic lesions such as chest wall, skin, subcutaneous tissue, lymph nodes, bones, peripheral lung, and liver metastases)
Measurable disease
Zero or one prior chemotherapy regimens for metastatic disease
No prior treatment with carboplatin in the metastatic setting
Patients must have adequate hematologic, hepatic, and renal function
For patients who are not postmenopausal (women) or surgically sterile (absence of ovaries and/or uterus or vasectomy), agreement to remain abstinent or to use two adequate methods of contraception (e.g., condoms, diaphragm, vasectomy/vasectomized partner, tubal ligation), during the treatment period and for at least 30 days after the last dose of study treatment. Hormone based oral contraceptives are not allowed on study
Exclusion Criteria
Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization
Known CNS disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: measurable disease outside the CNS, only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla, or spinal cord), no evidence of progression or hemorrhage after completion of CNS- directed therapy, no ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed), no stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
Leptomeningeal disease
Uncontrolled tumor-related pain: patients requiring narcotic pain medication must be on a stable regimen at registration
Uncontrolled hypercalcemia
Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biological therapy) other than the ones specified in the protocol. Any other investigational drugs should be discontinued 2 weeks prior to the first dose of study medication.
Women only: pregnancy or lactation
Evidence of significant uncontrolled concomitant disease that in the opinion of the investigator could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
Significant cardiovascular disease
Severe infection requiring systemic treatment within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis. Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.
History of severe reactions (e.g. allergic, anaphylactic, or other hypersensitivity) to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener?s granulomatosis, Sj?gren?s syndrome, Guillain-Barr? syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible for this study.
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Positive test for HIV (testing required prior to registration)
Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study drug (C1D1) or anticipation that such a live, attenuated vaccine will be required during the study
Prior treatment with CD137 agonists, anti?PD-1, or anti?PD-L1 therapeutic antibody or pathway-targeting agents
Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to cycle 1, day 1, or anticipated requirement for systemic immunosuppressive medications during the trial