Background: Standard therapy for advanced NSCLC consists of platinum (plat)-based doublet chemotherapy (chemo), bevacizumab (bev), pemetrexed (pem), targeted agents and PD-L1/PD-1–targeted immunotherapy. Atezolizumab (MPDL3280A; atezo) inhibits binding of PD-L1 to PD-1 and B7.1. A Phase Ib study of 1L atezo + chemo demonstrated promising efficacy regardless of PD-L1 expression, with acceptable safety. Bev may further enhance atezo efficacy by inhibiting VEGF-related immunosuppression. Four Phase III randomized, multicenter, open-label studies are evaluating 1L therapy with atezo + plat-based chemo ± bev, or atezo + pem, in chemo-naive pts with advanced NSCLC (Table). Methods: Eligible pts must have previously untreated stage IV NSCLC, measurable disease per RECIST v1.1 and ECOG PS 0-1; pts with untreated CNS metastases, autoimmune disease or prior immunotherapy will be excluded. Archival tumor or biopsy sample will be obtained at screening. Stratification factors include sex, presence of liver metastases and PD-L1 expression. In IMpower130, 131 and 150, pts will be randomized to receive atezo 1200 mg with standard plat-based chemo ± bev (bev in IMpower150 only) for 4 or 6 21-day cycles, then maintenance with atezo. In IMpower132, pts will receive atezo + plat-based chemo + pem, then maintenance with atezo + pem. Endpoints include OS, PFS, ORR, DOR, safety, PK and QOL. Tumor biopsies at RECIST progression will be evaluated to distinguish pseudoprogression/tumor-immune infiltration from actual progression and to evaluate biomarkers associated with response and immune escape. Clinical trial information: NCT02367781, NCT02367794, NCT02657434, NCT02366143