Inclusion Criteria:

• Signed Informed Consent Form.
• Male or female, 18 years of age or older.
• ECOG performance status of 0 or 1.
• Histologically or cytologically confirmed, Stage IV non-squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 7th edition; Detterbeck et al. 2009).
  • Patients with tumors of mixed histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous.
• No prior treatment for Stage IV non-squamous NSCLC.
  • Patients with a sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs, such as erlotinib, gefitinib, or another EGFR TKI appropriate for the treatment of EGFR-mutant NSCLC.
  • Patients known to have an ALK fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (e.g., crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene.
  • Patients with unknown EGFR and ALK status require test results at screening.
  • ALK and/or EGFR may be assessed locally or at a central laboratory.
  • Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy cycle.
• Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
  • Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord);
  • No ongoing requirement for corticosteroids as therapy for CNS disease;
  • No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization;
  • No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.
• Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to randomization, if all other criteria are met.
• Known PD-L1 tumor status as determined by an IHC assay performed by a central laboratory on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening.
  • A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or 15 or more unstained, freshly cut, serial sections on slides from an FFPE tumor specimen is required for participation in this study.
  • If fewer than 15 slides are available at baseline (but no fewer than 10), the patient may still be eligible, upon discussion with the Medical Monitor. This specimen must be accompanied by the associated pathology report.
  • Fine-needle aspiration (defined as samples that do not preserve tissue architecture and yield cell suspension and/or cell smears), brushing, cell pellet specimens (e.g., from pleural effusion, and lavage samples) are not acceptable.
  • Tumor tissue from bone metastases that is subject to decalcification is not acceptable.
  • For core-needle biopsy specimens, preferably at least three cores embedded in a single paraffin block, should be submitted for evaluation.
• Measurable disease, as defined by RECIST v1.1
  • Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to randomization:
  • ANC ≥ 1500 cells/µL without granulocyte colony-stimulating factor support;
  • Lymphocyte count ≥ 500/µL;
  • Platelet count ≥ 100,000/µL without transfusion;
  • Hemoglobin ≥ 9.0 g/dL;
  • Patients may be transfused to meet this criterion;
  • INR or aPTT ≤ 1.5 x upper limit of normal (ULN).
    • This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • AST, ALT, and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions:
  • Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN;
  • Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN;
  • Serum bilirubin ≤ 1.25 x ULN;
  • Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled;
  • Serum creatinine ≤ 1.5 x ULN.
• For female patients of childbearing potential agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 5 months after the last dose of atezolizumab or for 30 days after the last dose of nab-paclitaxel, whichever is later. Women must refrain from donating eggs during this same period. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of nab-paclitaxel and/or carboplatin, whichever is later. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence. Male patients should not donate sperm during this study and for at least 6 months after the last dose of nab-paclitaxel and/or carboplatin, whichever is later.
• Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug. The same rules are valid for male patients involved in this clinical study if they have a partner of childbearing potential. Male patients must always use a condom.
• Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.

Exclusion Criteria:

Cancer-Specific Exclusions

• Active or untreated CNS metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments.
• 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.
• Leptomeningeal disease.
• Uncontrolled tumor-related pain.
  • Patients requiring pain medication must be on a stable regimen at study entry.
  • Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
  • Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
  • Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN).
  • Patients who are receiving denosumab prior to randomization must be willing and eligible to receive a bisphosphonate instead while in the study.
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
• Known tumor PD-L1 expression status as determined by an IHC assay from other clinical studies (e.g., patients whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD-L1 antibodies but were not eligible are excluded)

General Medical Exclusions

• Women who are pregnant, lactating, or intending to become pregnant during the study.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions 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, Sjören’s syndrome, Guillain-Barrésyndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 13 for a more comprehensive list of autoimmune diseases)
  • 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 regimen are eligible for this study.
  • Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
    • Rash must cover less than 10% of body surface area;
    • Disease is well controlled at baseline and only requiring low-potency topical steroids;
    • No acute exacerbations of underlying condition within the previous 12 months (not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids).
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, 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.
  • All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the clinical study.
• Patients with active hepatitis B (chronic or acute; 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 the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA;
  • Patients who are positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
• Active tuberculosis.
• Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Received therapeutic oral or IV antibiotics within 2 weeks prior to randomization Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are
• eligible.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Major surgical procedure other than for diagnosis within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study.
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
• Illness or condition that interferes with the patient’s capacity to understand, follow, and/or comply with study procedures.

Exclusion Criteria Related to Medications

• Any approved anti-cancer therapy, including hormonal therapy within 21 days prior to initiation of study treatment; the following exceptions are allowed:
  • TKIs approved for treatment of NSCLC discontinued > 7 days prior to randomization; the baseline scan must be obtained after discontinuation of prior TKIs.
• Treatment with any other investigational agent with therapeutic intent within 28 days prior to randomization.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies:
  • Patients who have had prior anti-CTLA-4 treatment may be enrolled, provided the following requirements are met:
    • Last dose of anti-CTLA-4 at least 6 weeks prior to randomization;
    • No history of severe immune-mediated adverse effects from anti-CTLA-4 (NCI CTCAE Grades 3 and 4).
• Treatment with systemic immunostimulatory agents (including, but not limited to, IFNs, IL-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to randomizatio
  • Prior treatment with cancer vaccines is allowed.
  • Treatment with systemic immunosuppressive medications (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to randomization.
• Patients who have received acute, low-dose (≤ 10 mg oral prednisone or equivalent), systemic immunosuppressant medications may be enrolled in the study.
• The use of corticosteroids (≤ 10 mg oral prednisone or equivalent) for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency is allowed.

Exclusions Related to Chemotherapy

• Known history of severe allergic reactions to platinum-containing compounds or mannitol.
• Known sensitivity to any component of nab-paclitaxel.
• Grade ≥ 2 peripheral neuropathy as defined by NCI CTCAE v4.0.
• Known history of severe hypersensitivity reactions to products containing Cremophor® EL (e.g., cyclosporin for injection concentrate and teniposide for injection concentrate).