Brief Summary
This randomized, open-label study evaluated the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 \[PD-L1\] antibody) in combination with carboplatin+paclitaxel with or without bevacizumab compared with treatment with carboplatin+paclitaxel+bevacizumab in chemotherapy-naïve participants with Stage IV non-squamous NSCLC. Participants were randomized in a 1:1:1 ratio to Arm A (Atezolizumab+Carboplatin+Paclitaxel), Arm B (Atezolizumab+Carboplatin+Paclitaxel+Bevacizumab), or Arm C (Carboplatin+Paclitaxel+Bevacizumab).
Brief Title
A Study of Atezolizumab in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Completion Date
Completion Date Type
Actual
Conditions
Carcinoma, Non-Small-Cell Lung
Eligibility Criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group performance status 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
* Participants with no prior treatment for Stage IV non-squamous NSCLC
* Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end organ function
Exclusion Criteria:
Cancer-Specific Exclusions:
* Active or untreated central nervous system metastases
* Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
General Medical Exclusions:
* Pregnant or lactating women
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Severe infection within 4 weeks prior to randomization
* Significant cardiovascular disease
* Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures
Exclusion Criteria Related to Medications:
* Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies
* Eastern Cooperative Oncology Group performance status 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
* Participants with no prior treatment for Stage IV non-squamous NSCLC
* Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end organ function
Exclusion Criteria:
Cancer-Specific Exclusions:
* Active or untreated central nervous system metastases
* Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
General Medical Exclusions:
* Pregnant or lactating women
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Severe infection within 4 weeks prior to randomization
* Significant cardiovascular disease
* Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures
Exclusion Criteria Related to Medications:
* Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies
Inclusion Criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group performance status 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
* Participants with no prior treatment for Stage IV non-squamous NSCLC
* Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end organ function
* Eastern Cooperative Oncology Group performance status 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
* Participants with no prior treatment for Stage IV non-squamous NSCLC
* Known PD-L1 status as determined by immunohistochemistry assay performed on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
* Measurable disease as defined by RECIST v1.1
* Adequate hematologic and end organ function
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02366143
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
GO29436
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Primary Outcomes
Outcome Description
Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
Outcome Measure
Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)
Outcome Description
Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Outcome Measure
Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
Outcome Time Frame
Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)
Outcome Description
Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Outcome Measure
Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
Outcome Time Frame
Baseline until death (up approximately 53 months)
Secondary Ids
Secondary Id
2014-003207-30
Secondary Outcomes
Outcome Description
PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population.
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
Outcome Measure
PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population
Outcome Description
PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population.
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
Outcome Measure
PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population
Outcome Description
PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population.
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
Outcome Measure
PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
Outcome Description
PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
Outcome Measure
PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup
Outcome Description
OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
Outcome Time Frame
Baseline until death (up to approximately 34 months)
Outcome Measure
OS in Arm B Versus Arm C by PD-L1 Subgroup
Outcome Description
OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population)
Outcome Time Frame
Baseline until death (up approximately 53 months)
Outcome Measure
OS in Arm A Versus Arm C by PD-L1 Subgroup
Outcome Time Frame
Baseline until death (up to approximately 34 months)
Outcome Measure
OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
Outcome Time Frame
Baseline until death (up approximately 53 months)
Outcome Measure
OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
Outcome Time Frame
Baseline until death (up approximately 53 months)
Outcome Measure
OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
Outcome Description
DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population.
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
Outcome Measure
Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C
Outcome Description
Percentage of Participants With an Objective Response (OR) (Complete Response \[CR\] or Partial Response \[PR\]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population.
Outcome Time Frame
Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)
Outcome Measure
Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population
Outcome Description
OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
Outcome Time Frame
Baseline to 2 years or death, whichever occurs first.
Outcome Measure
OS Rates at Years 1 and 2 in Arm B Versus Arm C
Outcome Description
OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population.
Outcome Time Frame
Baseline to 2 years or death, whichever occurs first.
Outcome Measure
OS Rates at Years 1 and 2 in Arm A Versus Arm C
Outcome Description
EORTC QLQ-C30 is a validated \& reliable self-report measure (Aaronson et al.1993;Fitzsimmons et al.1999) that consists of 30 questions that assess 5 aspects of patient functioning (physical,emotional,role, cognitive,and social), 3 symptom scales (fatigue,nausea \& vomiting, pain),global health/quality of life,and six single items (dyspnea,insomnia, appetite loss,constipation,diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life);however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998).
Outcome Time Frame
Baseline up to approximately 29 months
Outcome Measure
Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score
Outcome Description
QLQ-LC13 Quality-of-Life Questionnaire Lung Cancer Module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).
Outcome Time Frame
Baseline up to approximately 29 months
Outcome Measure
TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score
Outcome Description
The SILC (Symptoms in Lung Cancer) scale was used to assess patient-reported severity of lung cancer symptoms (chest pain, dyspnea, and cough). The SILC scale is a 9-item content validated self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a symptom severity score. The SILC questionnaire comprises three individual symptoms (dyspnea, cough, chest pain) and are scored at the individual symptom level, thus have a dyspnea score, chest pain score, and cough score. Each individual symptom score is calculated as the average of responses for the symptom items \[e.g. Chest Pain Score=mean (item 1; item 2)\]. An increase in score is suggestive of a worsening in symptomology (i.e. frequency or severity). A score change of ≥0.3 points for the dyspnea and cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for the chest pain score is considered to be clinically significant.
Outcome Time Frame
Baseline up to approximately 29 months
Outcome Measure
Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
Outcome Description
Percentage of participants with at least one adverse event.
Outcome Time Frame
Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months)
Outcome Measure
Percentage of Participants With Adverse Events
Outcome Time Frame
Baseline up to approximately 29 months
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Outcome Description
The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
Outcome Time Frame
Day 1 of Cycle 1 and 3 (Cycle length=21 days)
Outcome Measure
Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B
Outcome Time Frame
Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)
Outcome Measure
Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B
Outcome Time Frame
Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days)
Outcome Measure
Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C
Outcome Time Frame
Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)
Outcome Measure
Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C
Outcome Time Frame
Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)
Outcome Measure
Cmax of Bevacizumab in Arm B and Arm C
Outcome Time Frame
Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)
Outcome Measure
Cmin of Bevacizumab in Arm B and Arm C
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
ATEZOLIZUMAB
BEVACIZUMAB
CARBOPLATIN
PACLITAXEL
ANTIBODIES, MONOCLONAL, HUMANIZED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
COORDINATION COMPLEXES
ORGANIC CHEMICALS
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
DITERPENES
TERPENES