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NCT02367794

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]

Completed Phase 3 Results posted Last updated 21 March 2022
What this trial tests

Phase 3 trial testing Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody in Squamous Non-Small Cell Lung Cancer in 1,021 participants. Completed in 17 February 2021.

Timeline
11 June 2015
Primary endpoint
3 October 2018
17 February 2021

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1,021
Start date11 June 2015
Primary completion3 October 2018
Estimated completion17 February 2021
Sites242 locations across Italy, Japan, Taiwan, Netherlands, Russia, Belgium, Mexico, Lithuania

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Squamous Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin5.65.5 – 5.7
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin6.55.7 – 7.1
Arm A: Atezolizumab + Paclitaxel + Carboplatin5.65.5 – 6.9
Overall Survival (OS) in the ITT Population Primary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin13.512.2 – 15.1
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin14.212.3 – 16.8
Arm A: Atezolizumab + Paclitaxel + Carboplatin12.611.6 – 14.7
OS in the in the Teff Population Secondary · 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.

Teff >=-1.91
GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin16.412.2 – 19.7
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin17.412.3 – 23.8
Arm A: Atezolizumab + Paclitaxel + Carboplatin15.213.4 – 22.8
Teff<-1.91
GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin12.411.2 – 14.3
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin13.011.4 – 14.8
Arm A: Atezolizumab + Paclitaxel + Carboplatin10.59.1 – 12.6
PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population Secondary · 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.

Teff >=-1.91
GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin5.65.1 – 5.7
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin7.05.5 – 8.5
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.05.6 – 9.7
Teff<-1.91
GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin5.75.5 – 6.6
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin6.25.6 – 7.0
Arm A: Atezolizumab + Paclitaxel + Carboplatin5.54.5 – 5.6
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 Secondary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin5.65.1 – 5.7
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin8.46.8 – 10.4
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.05.6 – 8.3
PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population Secondary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin5.65.3 – 5.7
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin7.15.8 – 8.3
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.05.6 – 8.3
OS in the TC2/3 or IC2/3 Population Secondary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin14.512.1 – 17.2
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin20.413.8 – 24.1
Arm A: Atezolizumab + Paclitaxel + Carboplatin14.811.1 – 23.7
OS in the TC1/2/3 or IC1/2/3 Population Secondary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin15.012.4 – 17.2
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin14.812.1 – 19.6
Arm A: Atezolizumab + Paclitaxel + Carboplatin14.912.5 – 18.2
Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population Secondary · Up to approximately 30 months after first participant enrolled

Proportion of participants with an objective response (CR or PR) in the ITT population.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin41.0
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin49.7
Arm A: Atezolizumab + Paclitaxel + Carboplatin49.3
Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population Secondary · 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.

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin5.24.4 – 5.6
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin7.26.8 – 9.5
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.05.7 – 8.3
Event Free Rate at 1 and 2 Years in the ITT Population Secondary · 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.

1 Year
GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin56.28
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin56.34
Arm A: Atezolizumab + Paclitaxel + Carboplatin52.30
2 Year
GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin26.58
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin32.51
Arm A: Atezolizumab + Paclitaxel + Carboplatin27.79
Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population Secondary · 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 o

GroupValue95% CI
Arm C: Nab-Paclitaxel + Carboplatin3.22.6 – 4.1
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin4.23.2 – 5.6
Arm A: Atezolizumab + Paclitaxel + Carboplatin3.02.6 – 3.9

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first study drug administration to the data cutoff date: 17 February 2021 (up to approximately 68 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm C: Nab-Paclitaxel + Carboplatin
Serious: 96/334 (29%)
Deaths: 252/340
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
Serious: 168/334 (50%)
Deaths: 245/343
Arm A: Atezolizumab + Paclitaxel + Carboplatin
Serious: 151/332 (45%)
Deaths: 243/338

Serious adverse events (247 terms)

ReactionSystemArm C: Nab-Paclitaxel + Ca…Arm B: Atezolizumab + Nab-…Arm A: Atezolizumab + Pacl…
PNEUMONIAInfections and infestations
FEBRILE NEUTROPENIABlood and lymphatic system disorders
SEPSISInfections and infestations
CHRONIC OBSTRUCTIVE PULMONARY DISEASERespiratory, thoracic and mediastinal disorders
PNEUMONITISRespiratory, thoracic and mediastinal disorders
DEATHGeneral disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
ANAEMIABlood and lymphatic system disorders
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
ATRIAL FIBRILLATIONCardiac disorders
DIARRHOEAGastrointestinal disorders
PYREXIAGeneral disorders
BRONCHITISInfections and infestations
HAEMOPTYSISRespiratory, thoracic and mediastinal disorders
ATRIAL FLUTTERCardiac disorders
BACK PAINMusculoskeletal and connective tissue disorders
PERICARDIAL EFFUSIONCardiac disorders
DEHYDRATIONMetabolism and nutrition disorders
CEREBROVASCULAR ACCIDENTNervous system disorders
ACUTE KIDNEY INJURYRenal and urinary disorders
NEUTROPENIABlood and lymphatic system disorders
COLITISGastrointestinal disorders
VOMITINGGastrointestinal disorders
CHEST PAINGeneral disorders
FATIGUEGeneral disorders
Other adverse events (61 terms — click to expand)

ReactionSystemArm C: Nab-Paclitaxel + Ca…Arm B: Atezolizumab + Nab-…Arm A: Atezolizumab + Pacl…
ANAEMIABlood and lymphatic system disorders
NAUSEAGastrointestinal disorders
ALOPECIASkin and subcutaneous tissue disorders
NEUTROPENIABlood and lymphatic system disorders
FATIGUEGeneral disorders
CONSTIPATIONGastrointestinal disorders
DIARRHOEAGastrointestinal disorders
DECREASED APPETITEMetabolism and nutrition disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
ASTHENIAGeneral disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
VOMITINGGastrointestinal disorders
NEUROPATHY PERIPHERALNervous system disorders
NEUTROPHIL COUNT DECREASEDInvestigations
COUGHRespiratory, thoracic and mediastinal disorders
PLATELET COUNT DECREASEDInvestigations
PERIPHERAL SENSORY NEUROPATHYNervous system disorders
HYPOMAGNESAEMIAMetabolism and nutrition disorders
RASHSkin and subcutaneous tissue disorders
PYREXIAGeneral disorders
MYALGIAMusculoskeletal and connective tissue disorders
LEUKOPENIABlood and lymphatic system disorders
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
HEADACHENervous system disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
WHITE BLOOD CELL COUNT DECREASEDInvestigations
BACK PAINMusculoskeletal and connective tissue disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
HYPOTHYROIDISMEndocrine disorders
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
DIZZINESSNervous system disorders
WEIGHT DECREASEDInvestigations
PRURITUSSkin and subcutaneous tissue disorders
HYPOKALAEMIAMetabolism and nutrition disorders
INSOMNIAPsychiatric disorders
PNEUMONIAInfections and infestations
CHEST PAINGeneral disorders
PARAESTHESIANervous system disorders
URINARY TRACT INFECTIONInfections and infestations

Most-reported serious reactions: PNEUMONIA, FEBRILE NEUTROPENIA, SEPSIS, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, PNEUMONITIS, DEATH, DYSPNOEA, ANAEMIA.

Data from ClinicalTrials.gov NCT02367794 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
    Alsaab HO, Sau S, Alzhrani R, Tatiparti K, et al · · 2017 · cited 1206× · PMID 28878676 · DOI 10.3389/fphar.2017.00561
  3. Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial.
    Jotte R, Cappuzzo F, Vynnychenko I, Stroyakovskiy D, et al · · 2020 · cited 460× · PMID 32302702 · DOI 10.1016/j.jtho.2020.03.028
  4. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  5. Combining Immune Checkpoint Inhibitors With Conventional Cancer Therapy.
    Yan Y, Kumar AB, Finnes H, Markovic SN, et al · · 2018 · cited 163× · PMID 30100909 · DOI 10.3389/fimmu.2018.01739
  6. NRF2 Activation Promotes Aggressive Lung Cancer and Associates with Poor Clinical Outcomes.
    Singh A, Daemen A, Nickles D, Jeon SM, et al · · 2021 · cited 137× · PMID 33077574 · DOI 10.1158/1078-0432.ccr-20-1985
  7. Chemotherapy remains an essential element of personalized care for persons with lung cancers.
    Hellmann MD, Li BT, Chaft JE, Kris MG. · · 2016 · cited 92× · PMID 27456296 · DOI 10.1093/annonc/mdw271
  8. Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?
    Lazzari C, Karachaliou N, Bulotta A, Viganó M, et al · · 2018 · cited 91× · PMID 29662546 · DOI 10.1177/1758835918762094

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