Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC). Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).
Interventions
DRUGTocilizumab
Tocilizumab is administered for the management of cytokine-release syndrome in the RO6958688-containing arms.
DRUGIpatasertib
Ipatasertib will be administered orally once a day on Days 1-21 of each 28-day cycle.
DRUGBevacizumab
Bevacizumab is administered by IV on Day 1 of each 21-day cycle.
DRUGAtezolizumab
Atezolizumab is administered by IV on Day 1 of each 21 day cycle or on Days 1 and 15 of each 28 day cycle.
DRUGCobimetinib
Cobimetinib is administered orally on Days 1-21 of a 28 day cycle.
DRUGRO6958688
Cycle 1: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle at increasing dosage. Subsequent cycles: RO6958688 is administered by IV infusion on Days 1, 8, and 15 of a 21 day cycle.
DRUGDocetaxel
Docetaxel is administered by IV on Day 1 of each 21 day cycle.
DRUGCPI-444
CPI-444 is administered orally twice daily on Days 1- 21, of a 21 day cycle.
DRUGPemetrexed
Pemetrexed is administered by IV on Day 1 of a 21 day cycle.
DRUGCarboplatin
Carboplatin is administered by IV on day 1 of the first 4 or 6 cycles out of a 21 day cycle.
DRUGGemcitabine
Gemcitabine is administered by IV on Days 1 and 8 of the first 4 or 6 cycles out of a 21 day cycle.
DRUGLinagliptin
Linagliptin is administered orally once daily on Days 1 to 21 out of a 21 day cycle.
DRUGSacituzumab Govitecan
Sacituzumab Govitecan is administered by IV on Day 1 and 8 of each 21-day cycle.
OTHERRadiation
Radiotherapy up to 21 days
DRUGEvolocumab
Evolocumab is administered subcutaneously at a dose of 140 mg on Days 1 and 15 of each 28-day cycle.
DRUGTiragolumab
Tiragolumab is administered on Day 1 of each 21 day cycle.
DRUGXL092
XL092 is administered orally once a day on Day 1 to Day 21 of a 21 day cycle.
DRUGCamonsertib
Camonsertib is administered orally on Days 1-3, Days 8-10 of a 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
General Inclusion Criteria * Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1 * Life expectancy greater than or equal to 3 months * Histologically or cytologically confirmed metastatic, non-squamous or squamous Non-Small Cell Lung Cancer (NSCLC) * Measurable disease (at least one target lesion) * Adequate hematologic and end-organ function * Tumor accessible for biopsy * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Inclusion Criteria for Cohort 1 * No prior systemic therapy for metastatic NSCLC * High tumor PD-L1 expression, defined as Tumor Proportion Score (TPS) or TCs \>= 50% or TC3 Inclusion Criteria for Cohort 2 \- Disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC
Exclusion criteria
* Prior allogeneic stem cell or solid organ transplantation * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan * History of malignancy other than NSCLC within 2 years prior to screening * Active tuberculosis * Severe infection within 4 weeks prior to initiation of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Objective Response | Every 6 weeks (starting on Day 1, Cycle 1) for the first 48 weeks and then every 6 or 12 weeks thereafter |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival After Randomization | Randomization to death from any cause (up to approximately 8 years) |
| Percentage of Participants Who Are Alive at Month 6 and at Month 12 | Month 6, Month 12 |
| Progression Free Survival (PFS) | Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years) |
| Disease Control | Randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years) |
| Percentage of Participants with Adverse Events | Baseline through the end of the study (approximately 8 years) |
| Duration of Response | First occurrence of a documented objective response to disease progression or death (up to approximately 8 years) |
Countries
Australia, France, Israel, South Korea, Spain, United Kingdom, United States
Outcome results
None listed