Clinical Trials

Inclusion Criteria

• Signed written informed consent before any trial related procedure 
• Male or female subjects aged ≥ 18 years 
• Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for Programmed death-ligand 1 (PD-L1) expression assessment 
• Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory 
• Subjects with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression 
• Subjects must have progressed after an acceptable therapy defined as follows
  • 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 
  • Within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease 
• Subjects 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)
  • For subjects with a tumor that harbors an activating EGFR mutation, acceptable prior therapy is also defined as a treatment with an EGFR-targeting tyrosine kinase inhibitor (TKI) given before or after treatment with a platinum-based combination chemotherapy as defined above
  • Subjects with a tumor that harbors an activating EGFR mutation must have failed both the platinum-based doublet and the EGFR-targeting TKI
  • Treatment with more than 1 EGFR targeting TKI is acceptable
• 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 (may have been transfused) defined by
  • White blood cells (WBC) count ≥ 2.5 × 10^9 per liter (/L)
  • 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)
• Adequate hepatic function defined by
  • A total bilirubin level ≤ 1.0 × the upper limit of normal (ULN) range
  • And aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects 
• Adequate renal function defined by
  • An estimated creatinine clearance > 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method)
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
• Administration of steroids through a route known to result in a minimal systemic exposure are acceptable
• Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone
• Other protocol defined criteria could apply

Exclusion Criteria

• In the United States only, subjects with a squamous cell histology will be excluded
• Systemic anticancer therapy administered after disease progression during or following a platinum based combination, with the following exception
  • Subjects whose disease harbors an activating EGFR mutation who received an EGFR inhibitor after a minimum of 2 cycles of first-line platinum-based therapy
  • Subjects who tested undetermined or wild-type for EGFR but were previously treated with a TKI are not eligible unless retested and confirmed to be activating EGFR mutation positive
• Subjects with non-squamous cell NSCLC whose disease harbors an anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial
  • Subjects of unknown ALK status will require testing for ALK rearrangement (local laboratory, or central laboratory if local testing is not available)
  • must be determined to be ALK wild-type to be eligible for this trial
• 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)
  • Prior therapy with a cancer vaccine is acceptable
• Concurrent anticancer treatment 
• Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the subject has not fully recovered from the surgery within 4 weeks of randomization 
• Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment
• All subjects with brain metastases, except those meeting the following criteria
  • Brain metastases have been treated locally
  • Has 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
  • diabetes type I
  • vitiligo
  • psoriasis
  • hypo- or hyperthyroid disease not requiring immunosuppressive treatment is eligible 
• Other protocol defined criteria could apply