Non-small Cell Lung Cancer
Conditions
Sponsors
Merck Biopharma Co., Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed written informed consent before any trial related procedure Male or female participants aged greater than or equal to (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: 1.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 2.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 greater than or equal to 2.5 x 10^9/L with absolute neutrophil count (ANC) >= 1.5 x 10^9/L, lymphocyte count greater than or equal to 0.5 x 10^9/L, platelet count greater than or equal to 100 x 10^9/L, and hemoglobin greater than or equal to 9 gram per deciliter (g/dL) (may have been transfused) Adequate hepatic function defined by a total bilirubin level less than or equal to (less than or equal to) 1.5 x the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels less than or equal to 2.5 x ULN for all participants Adequate renal function defined by an estimated creatinine clearance greater than 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
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: 1.Brain metastases have been treated locally, and 2.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: 1.Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible 2.Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to (less than or equal to) 10 milligram (mg) or equivalent prednisone per day 3.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 less than or equal to 10 mg per day of equivalent prednisone Other protocol defined exclusion criteria could apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy 1. Overall Survival (OS) Time in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 2. Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 3. Progression-Free Survival (PFS) Time in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 4. Number of Participants With Confirmed Best Overall Response (BOR) in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 5. Number of Participants With Confirmed Best Overall Response (BOR) in PD-L1+ Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 6. Percentage of Participants With Objective Response in Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 7. Percentage of Participants With Objective Response in PD-L1+ Full Analysis Set Population [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 907 days) ] 8. Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ] 9. Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ] 10. Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) [ Time Frame: Baseline, End of treatment visit (up to Week 124) ] 11. Change From Baseline in European Organi | — |
Countries
Africa, Asia except Japan, Europe, Japan, North America, Oceania, South America
Outcome results
None listed