Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)

Inclusion Criteria

• Signed written informed consent before any trial related procedure
• Male or female participants aged greater than or equal to (>=) 18 years
• Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment
• Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory
• Participants with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression
• Participants must have progressed after an acceptable therapy defined as follows:
• Participants must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR
• Participants must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease
• Participants with non-squamous cell NSCLC of unknown epidermal growth factor receptor (EGFR) mutation status will require testing (local laboratory, or central laboratory if local testing is not available). Participants with a tumor that harbors an activating EGFR mutation will not be eligible
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
• Estimated life expectancy of more than 12 weeks
• Adequate hematological function defined by White Blood Cell (WBC) count >= 2.5 × 10^9/L with absolute neutrophil count (ANC) >= 1.5 × 10^9/L, lymphocyte count >=0.5 × 10^9/L, platelet count >= 100 × 10^9/L, and hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)
• Adequate hepatic function defined by a total bilirubin level less than or equal to ( 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method).

Other protocol defined inclusion criteria could apply

Exclusion criteria

• In the United States only, participants with a squamous cell histology will be excluded
• Systemic anticancer therapy administered after disease progression during or following a platinum based combination
• Participants with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Participants of unknown ALK and/or EGFR mutation status will require testing at screening (local laboratory, or central laboratory if local testing is not available)
• Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4).
• Concurrent anticancer treatment
• Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the participant has not fully recovered from the surgery within 4 weeks of randomization
• Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment.
• All participants with brain metastases, except those meeting the following criteria:
• Brain metastases have been treated locally, and
• No ongoing neurological symptoms that are related to the brain localization of the disease
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
• Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Participants requiring hormone replacement with cor