Atezolizumab in Combination With Carboplatin Plus Pemetrexed in Chemotherapy-naïve Patients With Asymptomatic Brain Metastasis

Inclusion Criteria:

* Patients aged 18 years or older.
* Signed written informed consent.
* ECOG Performance Status (PS) of 0 to 1.
* Subjects with histologically or cytologically confirmed stage IV non-squamous NSCLC who did not received any prior chemotherapy or brain radiotherapy. Patients with EGFR mutation or ALK fusion will be excluded.
* Patients who received prior neo-adjuvant, adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months since the last dose of chemotherapy and/or radiotherapy.
* Asymptomatic or oligosymptomatic(considered to have alterations in the neurological examination, whether or not they are noted in the anamnesis, that do not prevent appropriate functioning according to the patients' basal state, or that disappear with medical treatment (corticosteroids, analgesics, anticonvulsants) untreated brain metastases.
* Steroids treatment (dexamethasone) is allowed and patients that remained oligosymptomatic or asymptomatic for 2 weeks on steroids will be eligible when they were receiving ≤ 4mg dexamethasone once a day.
* Systemic measurable disease by computed tomography (CT) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria AND brain measurable disease by magnetic resonance imaging (MRI) per RANO-BM criteria.
* Availability of a formalin-fixed paraffin-embedded block (cell blocks will be accepted if tumor biopsy is not available) containing tumor tissue or 10 unstained slides.
* Adequate hematopoietic, hepatic and renal function:

ANC ≥ 1,500 cells/μL o Lymphocyte count ≥ 500 cells/μL o Platelet count ≥ 100,000 cells μL o Hemoglobin ≥ 9.0 g/dL (transfusion are is allowed) o INR or aPTT ≤ 1.5 x upper limit of normal (ULN); patients receiving therapeutic anticoagulation should be on a stable dose o ALT, AST and/or alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions: -patients with known liver metastasis: ALT and/or AST ≤ 5 x ULN -patients with known bone metastasis: alkaline phosphatase ≤ 5 x ULN o Serum bilirubin ≤ 1.5 x ULN; patients with known Gilbert disease who have serum bilirubin ≤ 3 x ULN may be recruited) o Calculated creatinine clearance (CRCL) ≥ 45 mL/min (based on the standard Cockcroft and Gault formula).

* For women of childbearing potential: agreement to remain abstinent or use contraceptive non-hormonal methods with a failure rate of 1% per year during the treatment period and for 3 months after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of non-hormonal contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization and copper intrauterine devices.
* For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 3 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

Exclusion Criteria:

* History of other malignancy within 3 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
* Patients harboring an EGFR mutation or an ALK fusion will be excluded
* Leptomeningeal carcinomatosis or metastases in the brain stem, mid-brain, pons, medulla or lesions causing obstructive hydrocephalus
* Patients with neurological symptoms, including those receiving \> 4mg of dexamethasone will not be eligible for this study
* Spinal or hemorrhagic metastases will be excluded
* Prior surgical resection of brain or spinal lesions in the prior 14 days
* Previous systemic treatment or neo-adjuvant or adjuvant chemotherapy less than 6 months before enrollment
* Clinical significant comorbidities that impaired administration of platinum-based chemotherapy
* History of autoimmune disease, including but not limited to myasthenia gravis, myosistis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré 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 dose of insulin are eligible for this study
  * Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriasic arthritis would be excluded) are permitted provided that they meet the following conditions: rash covers less than 10% of body surface area, disease is well controlled at baseline and only requires lowpotency topical steroids, no acute exacerbations during the last 12 months
* History of idiopathic pulmonary fibrosis, drug-induced pneumonitis or active radiation pneumonitis out of the radiation field
* Previous treatment with immune checkpoint inhibitors or CD137 and OX-40 agonists
* Treatment with investigational therapy within 28 days prior to initiation of study drug - Positive for hepatitis C virus (HCV) antibody or for hepatitis B surface antigen (HBsAg) at screening. Patients with past or resolved hepatitis B virus (HBV) infection (HBcAb positive with absence of HBsAg) would be eligible whether they are negative for HBV DNA. Patients positive for HCV antibody would be eligible whether they are negative for HCV RNA
* Active tuberculosis or HIV infection
* Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment.
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.