Brief Summary
This is a randomized, Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab in combination with cisplatin or carboplatin + pemetrexed compared with treatment with cisplatin or carboplatin + pemetrexed in participants who are chemotherapy-naive and have Stage IV non-squamous NSCLC. Eligible participants will be randomized by a 1:1 ratio into 2 groups: Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) and Arm B (Carboplatin or Cisplatin + Pemetrexed). The study will be conducted in two phases: Induction Phase and Maintenance Phase.
Brief Title
A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower 132)
Completion Date
Completion Date Type
Actual
Conditions
Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC. Participants with tumors of mixed non-small cell histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous
* No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded. Participants with unknown EGFR and ALK status require test results at screening from a local or central laboratory
* Participants who have received prior neo-adjuvant, radiotherapy, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy
* Participants should submit a pre-treatment tumor tissue sample if available before or within 4 weeks after enrollment. If tumor tissue is not available, participants are still eligible
* For participants enrolled in the extended China enrollment phase: current resident of mainland China, Hong Kong, or Taiwan and of Chinese ancestry
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end organ function
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of cisplatin
* For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
Exclusion Criteria:
Cancer-Specific Exclusions
* Participants with a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
* Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
* Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than or equal to (\>= 2) weeks prior to randomization
* Leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled or symptomatic hypercalcemia (greater than \[\>\] 1.5 millimole/Liter ionized calcium or calcium \>12 milligrams/deciliter or corrected serum calcium \>upper limit of normal)
* Malignancies other than NSCLC within 5 years prior to randomization
* Known tumor programmed death-ligand 1 (PD-L1) expression status from other clinical studies (e.g., participants whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD L1 antibodies but were not eligible are excluded)
General Medical Exclusions:
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* History of certain autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
* All participants will be tested for human immunodeficiency virus (HIV) prior to the inclusion into the study and HIV-positive participants will be excluded from the clinical study
* Severe infections within 4 weeks prior to randomization
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Illness or condition that may interfere with a participant's capacity to understand, follow, and/or comply with study procedures
Exclusion Criteria Related to Medications and Chemotherapy:
* Prior treatment with EGFR inhibitors or ALK inhibitors
* Any approved anti-cancer therapy, including hormonal therapy within 21 days prior to initiation of study treatment
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks prior to randomization
* Treatment with systemic immunosuppressive medications
Exclusion Criteria Related to Chemotherapy:
* History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds
* Participants with hearing impairment (cisplatin)
* Grade \>=2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria (cisplatin)
* Creatinine clearance (CRCL) \<60 milliliters/minute (mL/min) for cisplatin or \<45 mL/min for carboplatin
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC. Participants with tumors of mixed non-small cell histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous
* No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded. Participants with unknown EGFR and ALK status require test results at screening from a local or central laboratory
* Participants who have received prior neo-adjuvant, radiotherapy, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy
* Participants should submit a pre-treatment tumor tissue sample if available before or within 4 weeks after enrollment. If tumor tissue is not available, participants are still eligible
* For participants enrolled in the extended China enrollment phase: current resident of mainland China, Hong Kong, or Taiwan and of Chinese ancestry
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end organ function
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of cisplatin
* For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
Exclusion Criteria:
Cancer-Specific Exclusions
* Participants with a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
* Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
* Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than or equal to (\>= 2) weeks prior to randomization
* Leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled or symptomatic hypercalcemia (greater than \[\>\] 1.5 millimole/Liter ionized calcium or calcium \>12 milligrams/deciliter or corrected serum calcium \>upper limit of normal)
* Malignancies other than NSCLC within 5 years prior to randomization
* Known tumor programmed death-ligand 1 (PD-L1) expression status from other clinical studies (e.g., participants whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD L1 antibodies but were not eligible are excluded)
General Medical Exclusions:
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* History of certain autoimmune disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
* All participants will be tested for human immunodeficiency virus (HIV) prior to the inclusion into the study and HIV-positive participants will be excluded from the clinical study
* Severe infections within 4 weeks prior to randomization
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Illness or condition that may interfere with a participant's capacity to understand, follow, and/or comply with study procedures
Exclusion Criteria Related to Medications and Chemotherapy:
* Prior treatment with EGFR inhibitors or ALK inhibitors
* Any approved anti-cancer therapy, including hormonal therapy within 21 days prior to initiation of study treatment
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks prior to randomization
* Treatment with systemic immunosuppressive medications
Exclusion Criteria Related to Chemotherapy:
* History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds
* Participants with hearing impairment (cisplatin)
* Grade \>=2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria (cisplatin)
* Creatinine clearance (CRCL) \<60 milliliters/minute (mL/min) for cisplatin or \<45 mL/min for carboplatin
Inclusion Criteria
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC. Participants with tumors of mixed non-small cell histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous
* No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded. Participants with unknown EGFR and ALK status require test results at screening from a local or central laboratory
* Participants who have received prior neo-adjuvant, radiotherapy, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy
* Participants should submit a pre-treatment tumor tissue sample if available before or within 4 weeks after enrollment. If tumor tissue is not available, participants are still eligible
* For participants enrolled in the extended China enrollment phase: current resident of mainland China, Hong Kong, or Taiwan and of Chinese ancestry
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end organ function
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of cisplatin
* For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
inclusion into the study and HIV-positive participants will be excluded from the clinical study
* Severe infections within 4 weeks prior to randomization
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Illness or condition that may interfere with a participant's capacity to understand, follow, and/or comply with study procedures
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC. Participants with tumors of mixed non-small cell histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous
* No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded. Participants with unknown EGFR and ALK status require test results at screening from a local or central laboratory
* Participants who have received prior neo-adjuvant, radiotherapy, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy
* Participants should submit a pre-treatment tumor tissue sample if available before or within 4 weeks after enrollment. If tumor tissue is not available, participants are still eligible
* For participants enrolled in the extended China enrollment phase: current resident of mainland China, Hong Kong, or Taiwan and of Chinese ancestry
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end organ function
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of cisplatin
* For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
inclusion into the study and HIV-positive participants will be excluded from the clinical study
* Severe infections within 4 weeks prior to randomization
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Illness or condition that may interfere with a participant's capacity to understand, follow, and/or comply with study procedures
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
NCT02657434
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
GO29438
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 or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer
Primary Outcomes
Outcome Description
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurred first.
Outcome Measure
Progression Free Survival (PFS) as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Outcome Time Frame
Randomization up to approximately 39 months
Outcome Description
OS is defined as time from randomization to death from any cause.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Randomization up to approximately 39 months
Secondary Ids
Secondary Id
2015-003605-42
Secondary Outcomes
Outcome Description
The Overall Survival Rate at the 1-year landmark time point is defined as the probabilities that participants are alive 1-year after randomization.
Outcome Time Frame
Year 1
Outcome Measure
Overall Survival Rate at Year 1
Outcome Description
The Overall Survival Rate at the 2-year landmark time point is defined as the probabilities that participants are alive 2-years after randomization.
Outcome Time Frame
Year 2
Outcome Measure
Overall Survival Rate Year 2
Outcome Description
An objective response is defined as either an unconfirmed CR or a PR, as determined by the investigator using RECIST v1.1. Objective Response Rate is defined as the proportion of patients who had an objective response.
Outcome Time Frame
Randomization up to approximately 25 months
Outcome Measure
Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1
Outcome Description
DOR is defined as the time interval from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented, whichever occurs first.
Outcome Time Frame
Randomization up to approximately 25 months
Outcome Measure
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1
Outcome Description
EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and 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 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)
Outcome Measure
Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score
Outcome Description
The EORTC QLQ-LC13 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 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)
Outcome Measure
Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score
Outcome Description
Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms \& are scored at individual symptom level, thus have a dyspnea score, chest pain score, \& cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 \& maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 \& 2, 'Cough' score is mean of question 3 \& 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea \& cough symptom scores is considered to be clinically significant; whereas a score change of≥0.5 points for chest pain score is considered to be clinically significant.
Outcome Time Frame
Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)
Outcome Measure
Change From Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score
Outcome Description
Minimum observed serum atezolizumab concentration (Cmin) prior to infusion at selected cycles (Arm A)
Outcome Time Frame
Predose (Prd; 0 hour [h]) on D1 of Cy 2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle (up to approximately 25 months)
Outcome Measure
Minimum Observed Serum Atezolizumab Concentration (Cmin)
Outcome Description
Maximum observed serum atezolizumab concentration (Cmax) after infusion (Arm A)
Outcome Time Frame
Day 1 of Cycle 1 (Cycle length=21 days)
Outcome Measure
Maximum Observed Serum Atezolizumab Concentration (Cmax)
Outcome Time Frame
Prd (0 h), 5-10 minutes (mins) before end of carboplatin infusion (infusion duration=1-2 h), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)
Outcome Measure
Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
Outcome Time Frame
Prd (0 h), 5-10 mins before end of cisplatin infusion (infusion duration=30-60 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)
Outcome Measure
Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
Outcome Time Frame
Prd (0 h), 5-10 mins before end of pemetrexed infusion (infusion duration=10 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)
Outcome Measure
Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
Outcome Description
Baseline prevalence and post-baseline incidence of anti-drug antibodies (ADA) to Atezolizumab in the Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
Outcome Time Frame
Prd (0 h) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle, at treatment discontinuation & then every 30 days (up to 120 days) after last dose of atezolizumab (up to app 25 months)
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab
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
CARBOPLATIN
CISPLATIN
PEMETREXED
COORDINATION COMPLEXES
ORGANIC CHEMICALS
CHLORINE COMPOUNDS
INORGANIC CHEMICALS
NITROGEN COMPOUNDS
PLATINUM COMPOUNDS
GUANINE
HYPOXANTHINES
PURINONES
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
GLUTAMATES
AMINO ACIDS, ACIDIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
AMINO ACIDS, DICARBOXYLIC