A Phase II Study of Atezolizumab in Combination With Bevacizumab, Carboplatin or Cisplatin, and Pemetrexed for EGFR-mutant Metastatic Non-small Cell Lung Cancer Patients After Failure of EGFR Tyrosine Kinase Inhibitors.

Exclusion Criteria

• •Previous exposure to platinum-based palliative chemotherapy. The treatment-free interval of neoadjuvant or adjuvant platinum-based chemotherapy should be more than 6 months before study enrollment is allowed
• •Previous exposure to VEGF inhibitor for anti-cancer treatment
• •Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms
• •Patients carries EGFR genotype T790M or exon20 insertion should be excluded.
• •Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of administration of atezolizumab.
• •Expected to require any other form of antineoplastic therapy while on study
• •Patients with untreated symptomatic brain metastases. Patients with treated brain metastases will be allowed if brain imaging obtained greater than 7 days from trial enrollment reveals stable disease. Patients with small (\< 3mm) asymptomatic brain metastasis are allowed to enroll. Patients on steroids doses higher than 10 mg of prednisone (or its equivalent) are excluded
• •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 study enrollment.
• •Leptomeningeal disease
• •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 study enrollment.
• •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.
• •Malignancies other than NSCLC within 5 years prior to study enrollment, 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)
• •On chronic systemic steroid therapy or on any other form of immunosuppressive medication
• •Has received a live-virus vaccination within 30 days of planned treatment start
• •Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
• •Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
• •Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed) (see Appendix V)
• •Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 3 weeks of the first dose of study medication
• •Active infection requiring therapy
• •History of Human Immunodeficiency Virus (HIV) unless recent serology test is negative.
• •Hepatitis B carrier: Patients with HBV infection were required to be receiving effective antiviral therapy and have a viral load less than 100 IU/mL at screening
• •Active Hepatitis C
• •Interstitial lung disease or pneumonitis requiring oral or IV glucocorticoids
• •Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
• •Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowable.
• •History of hemoptysis (≥ one-half teaspoon of bright red blood per episode) within 1 month prior to study enrollment
• •Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)