A Study of Atezolizumab in Combination With Carboplatin + Paclitaxel or Carboplatin + Nab-Paclitaxel Compared With Carboplatin + Nab-Paclitaxel in Participants With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower131]
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| ClinicalTrials.gov Identifier: NCT02367794 |
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Recruitment Status :
Completed
First Posted : February 20, 2015
Results First Posted : November 12, 2019
Last Update Posted : March 21, 2022
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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Brief Summary:
This randomized, open-label study will evaluate the safety and efficacy of atezolizumab (MPDL3280A) in combination with carboplatin + paclitaxel or carboplatin + nab-paclitaxel compared with treatment with carboplatin + nab-paclitaxel in chemotherapy-naive participants with Stage IV squamous NSCLC.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Squamous Non-Small Cell Lung Cancer | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody Drug: Carboplatin Drug: Nab-Paclitaxel Drug: Paclitaxel | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1021 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer |
| Actual Study Start Date : | June 11, 2015 |
| Actual Primary Completion Date : | October 3, 2018 |
| Actual Study Completion Date : | February 17, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A: Atezolizumab + Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab, paclitaxel, and carboplatin will be administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
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Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody
Atezolizumab 1200 milligrams (mg) intravenous infusion (IV) on day 1 of each 21-day cycle.
Other Name: Tecentriq Drug: Carboplatin Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles. Drug: Paclitaxel Paclitaxel 200 mg/m^2 IV on Day 1 of each 21-day cycle for 4 or 6 cycles. Participants of Asian race/ethnicity will be administered paclitaxel 175 mg/m^2 IV. |
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Experimental: Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; atezolizumab and carboplatin will be administered on Day 1 of each 21-day cycle. Nab-Paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experience no further clinical benefit at any time during the induction phase will discontinue all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants will begin maintenance therapy with atezolizumab. Atezolizumab will be continued as long as there is a clinical benefit to the participant.
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Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody
Atezolizumab 1200 milligrams (mg) intravenous infusion (IV) on day 1 of each 21-day cycle.
Other Name: Tecentriq Drug: Carboplatin Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles. Drug: Nab-Paclitaxel Nab-paclitaxel 100 milligrams per meter squared (mg/m^2) IV on Day 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles. |
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Active Comparator: Arm C: Nab-Paclitaxel + Carboplatin
The induction phase of the study will consist of four or six cycles; carboplatin will be administered on Day 1 of each 21-day cycle, nab-paclitaxel will be administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration is as follows: nab-paclitaxel, then carboplatin. Participants who experience disease progression at any time during the induction phase will discontinue all study treatment. In the maintenance phase, participants will receive best supportive care.
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Drug: Carboplatin
Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles. Drug: Nab-Paclitaxel Nab-paclitaxel 100 milligrams per meter squared (mg/m^2) IV on Day 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles. |
Primary Outcome Measures :
- Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT population.
- Overall Survival (OS) in the ITT Population [ Time Frame: Up to approximately 39 months after first participant enrolled ]OS is defined as the time between the date of randomization and date of death from any cause in the ITT population.
Secondary Outcome Measures :
- OS in the in the Teff Population [ Time Frame: Up to approximately 39 months after first participant enrolled ]OS is defined as the time between the date of randomization and date of death from any cause in the in the Teff Population.
- PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the Teff Population.
- PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population.
- PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the TC1/2/3 or IC1/2/3 Population.
- OS in the TC2/3 or IC2/3 Population [ Time Frame: Up to approximately 39 months after first participant enrolled ]OS is defined as the time between the date of randomization and date of death from any cause, in the TC2/3 or IC2/3 Population.
- OS in the TC1/2/3 or IC1/2/3 Population [ Time Frame: Up to approximately 39 months after first participant enrolled ]OS is defined as the time between the date of randomization and date of death from any cause in the TC1/2/3 or IC1/2/3 Population.
- Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]Proportion of participants with an objective response (CR or PR) in the ITT population.
- Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]Duration of response is defined as the time from the first documented objective response to documented PD or death from any cause, whichever occurred first, in the ITT Population.
- Event Free Rate at 1 and 2 Years in the ITT Population [ Time Frame: 1 and 2 years ]Event free rate at 1 and 2 years is defined as the proportion of participants alive at 1 and 2 years after randomization estimated using Kaplan-Meier (KM) methodology for the ITT population.
- Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population [ Time Frame: Up to approximately 30 months after first participant enrolled ]TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population. The 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 scales and single-item measures will be linearly transformed so that each score has a range of 0-100. A high score for a functional scale represents a high or healthy level of functioning, and a high score for the global health status and HRQoL represents a high HRQoL; however, a high score for a symptom scale or item represents a high level of symptomatology or problems.
- TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population [ Time Frame: Up to approximately 30 months after the first participant enrolled ]TTD was documented for a 3-symptom composite endpoint using the following EORTC QLQ-LC13 symptom scores: cough, chest pain, and dyspnea multi--item scale. In this instance, symptom deterioration will be determined as a >= 10-point increase above baseline in any of the listed symptom scores, whichever occurs first (cough, chest pain, and dyspnea multi-item scale). Confirmed clinically meaningful symptom deterioration will need to be held for the original symptom; a >= 10-point increase above baseline in a symptom score must be held for at least two consecutive assessments or an initial>=10-point increase above baseline followed by death within 3 weeks from the last assessment. A >= 10-point change in the EORTC scale score is perceived by patients as clinically significant.
- Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population [ Time Frame: Baseline up to approximately 30 months after first participant enrolled ]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. (Note: PD=progression of disease)
- PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B) [ Time Frame: Up to approximately 30 months after first participant enrolled ]PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT Population Arm A and Arm B.
- OS in the ITT Population (Arm A and Arm B) [ Time Frame: Up to approximately 39 months after first participant enrolled ]OS is defined as the time between the date of randomization and date of death from any cause in the ITT Population, Arm A and Arm B.
- Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 68 months after first participant enrolled ]Percentage of participants with at least one adverse event.
- Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab [ Time Frame: Up to approximately 30 months after first participant enrolled ]Percentage of participants with Anti-therapeutic Antibody (ATA) response to atezolizumab.
- Maximum Observed Serum Atezolizumab Concentration (Cmax) [ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days) ]Maximum observed serum atezolizumab concentration (Cmax). The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
- Minimum Observed Serum Atezolizumab Concentration (Cmin) [ Time Frame: Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 30 months), at treatment discontinuation (up to 30 months), and at 120 days after the last dose of atezolizumab (up to approximately 30 months, each cycle is 21 days) ]Minimum observed serum atezolizumab concentration (Cmin). The predose samples will be collected on the same day of treatment administration.
- Plasma Concentrations for Paclitaxel [ Time Frame: Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 180 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days) ]Plasma concentrations for paclitaxel.
- Plasma Concentrations for Nab-Paclitaxel [ Time Frame: Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days) ]Plasma concentrations for nab-paclitaxel.
- Plasma Concentrations for Carboplatin [ Time Frame: Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 15 to 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days) ]Plasma concentrations for carboplatin.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Histologically or cytologically confirmed, treatment-naïve Stage IV squamous NSCLC
- Previously obtained archival tumor tissue or tissue obtained from biopsy at screening
- Measurable disease as defined by RECIST v1.1
- Adequate hematologic and end organ function
Exclusion Criteria:
- Active or untreated central nervous system (CNS) metastasis
- 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
- 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 (CT) scan, History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Positive test for Human Immunodeficiency Virus (HIV)
- Active hepatitis B or hepatitis C
- Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
- Severe infection within 4 weeks prior to randomization
- Significant history of cardiovascular disease
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02367794
Locations
Show 242 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
Study Documents (Full-Text)
Documents provided by Hoffmann-La Roche:
Documents provided by Hoffmann-La Roche:
Study Protocol [PDF] October 24, 2018
Statistical Analysis Plan [PDF] January 11, 2018
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT02367794 |
| Other Study ID Numbers: |
GO29437 2014-003208-59 ( EudraCT Number ) |
| First Posted: | February 20, 2015 Key Record Dates |
| Results First Posted: | November 12, 2019 |
| Last Update Posted: | March 21, 2022 |
| Last Verified: | March 2022 |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Paclitaxel Albumin-Bound Paclitaxel Carboplatin |
Atezolizumab Antibodies Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs Immune Checkpoint Inhibitors Antineoplastic Agents, Immunological |