A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

Inclusion Criteria

• Patient older than 18 years
• Subject affiliated to an appropriate social security system
• Signed informed consent before any trial related activities and according to local guidelines
• ECOG performance status of 0 or 1
• Histologically or cytologically confirmed, stage IIIB/IV non-squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 7th edition).
• Patient 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, osimertinib or another EGFR TKI appropriate for the treatment of EGFR-mutant NSCLC. Patients with stage IIIB had to be not operable (that means not eligible for radiochemotherapy followed by a maintenance treatment by Durvalumab)
• Patient with an ALK fusion oncogene (confirmed in local laboratory) must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib, alectinib, ceritinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene
• Patient with a ROS1 fusion oncogene (confirmed in local laboratory) must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ROS inhibitors (i.e., crizotinib,) appropriate for the treatment of NSCLC in patients having an ROS1 fusion oncogene
• No prior chemotherapy treatment for Stage IV non-squamous NSCLC except if less than 3 cycles, with treatment free-interval of at least 1 year from C1 since last chemotherapy
• Patient who has 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 C1since the last chemotherapy, radiotherapy, or chemoradiotherapy
• Patient with an history of asymptomatic CNS metastases is eligible, provided he meets 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 inclusion
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end-organ function, defined by the following laboratory
• Adequate method of contraception during the treatment period and at least 5 months after the last dose of atezolizumab or 6 months after the last dose of chemotherapy

Exclusion Criteria

Cancer-specific exclusions

• Active CNS metastases as determined by CT or magnetic resonance imaging (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 > or = 2 weeks prior to C1
• Leptomeningeal disease (Presence of cancer cells in cerebral CSF or MRI with leptomeningeal lesion strongly suspected of leptomeningeal disease )
• Uncontrolled tumour-related pain
• 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 calcium >12 mg/dL or corrected serum calcium > ULN)
• Malignancies other than NSCLC within 5 years prior to C1, with the exception of those with a negligible risk of metastasis or death 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