Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
This Phase III, multicenter, open-label, randomized, controlled study is designed to evaluate the efficacy and safety of the anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab compared with docetaxel in participants with locally advanced or metastatic NSCLC who have progressed during or following a platinum-containing regimen. Treatment may continue until disease progression, loss of clinical benefit, or unacceptable toxicity.
Interventions
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle.
DRUGDocetaxel
Docetaxel will be administered as 75 milligrams per square meter (mg/m\^2) via IV infusion on Day 1 of each 21-day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented, locally advanced or metastatic NSCLC * Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens available or at least 12 unstained, freshly cut serial sections with associated pathology report that are evaluable for PD-L1 expression and epidermal growth factor receptor (EGFR) mutation status prior to enrollment, except for known sensitizing EGFR mutations in which case 10 unstained slides are required and there is no need for central testing of EGFR mutation status * Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable, inoperable, or metastatic NSCLC, or disease recurrence within 6 months of treatment with a platinum-based adjuvant and/or neoadjuvant regimen or combined modality with curative intent * Measurable disease per RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy greater than or equal to (\>/=) 12 weeks * Adequate hematologic and end organ function * Agreement to remain abstinent or use contraceptive methods among women of childbearing potential or male partners of women of childbearing potential * Recovery from all acute toxicities from previous therapy
Exclusion criteria
* Active or untreated central nervous system (CNS) metastases * Spinal cord compression not definitively treated or not clinically stable * Leptomeningeal disease * Uncontrolled pleural or pericardial effusions or ascites requiring recurrent drainage * Uncontrolled tumor-related pain * Uncontrolled hypercalcemia * Malignancies other than NSCLC within 5 years prior to randomization, except for those curatively treated with negligible risk of metastasis or death * Pregnant or lactating women * Significant cardiovascular, pulmonary, or autoimmune disease * Severe infection or major surgery within 4 weeks, or antibiotic treatment within 2 weeks prior to randomization * Prior treatment with or hypersensitivity to study drug(s) or related compounds * Inability to discontinue strong cytochrome P450 (CYP) 3A4 inhibitors * Prior allogeneic bone marrow or solid organ transplant * Known PD-L1-negative expression status * Positive human immunodeficiency virus (HIV) or active hepatitis B or C * Receipt of a live attenuated vaccine within 4 weeks prior to randomization * Treatment with systemic immunomodulators within 4 weeks or five half-lives (whichever is shorter) prior to randomization * Treatment with systemic corticosteroids within 2 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | Baseline until death from any cause (up to approximately 3 years) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Objective Response According to RECIST v1.1 | Baseline until disease progression or death from any cause (up to approximately 3 years) |
| Duration of Objective Response According to RECIST v1.1 | From first objective response until disease progression or death from any cause (up to approximately 3 years) |
| Percentage of Participants with Adverse Events | From start of treatment until 90 days after treatment discontinuation or initiation of other anti-cancer therapy (up to approximately 3 years) |
| Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, and every eight cycles thereafter (cycle length of 21 days) until/at treatment discontinuation (up to approximately 3 years) and 120 days after last dose (up to approximately 3 years overall) |
| Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | Baseline until disease progression or death from any cause (up to approximately 3 years) |
| Time to Deterioration (TTD) in Lung Cancer Symptoms According to European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 C30) | From start of treatment until treatment discontinuation (up to approximately 3 years) |
| TTD in Lung Cancer Symptoms According to EORTC QLQ Lung Cancer Module (LC13) | From start of treatment until treatment discontinuation (up to approximately 3 years) |
| Health-Related Quality of Life According to EORTC QLQ-C30 Score | Day 1 of every cycle (cycle length of 21 days) until/at treatment discontinuation (up to approximately 3 years) |
| Health-Related Quality of Life According to EORTC QLQ-LC13 Score | Day 1 of every cycle (cycle length of 21 days) until/at treatment discontinuation (up to approximately 3 years) |
| Minimum Observed Serum Concentration (Cmin) of Atezolizumab | Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, and every eight cycles thereafter (cycle length of 21 days) until/at treatment discontinuation (up to approximately 3 years) and 120 days after last dose (up to approximately 3 years overall) |
Countries
China, Malaysia, Singapore, South Korea, Thailand
Outcome results
None listed