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NCT02367781: IMpower130

A Study of Atezolizumab in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin+Nab-Paclitaxel in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Completed Phase 3 Results posted Last updated 9 August 2021
What this trial tests

Phase 3 trial testing Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody in Carcinoma, Non-Squamous Non-Small Cell Lung in 723 participants. Completed in 18 January 2021.

Timeline
16 April 2015
Primary endpoint
15 March 2018
18 January 2021

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment723
Start date16 April 2015
Primary completion15 March 2018
Estimated completion18 January 2021
Sites132 locations across France, Italy, Belgium, Germany, Israel, Canada, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Squamous Non-Small Cell Lung. 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 ITT-WT Population Primary · Up to approximately 35 months after first patient enrolled

PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first in the ITT-WT population.

GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.06.3 – 7.3
Arm B (Nab-Paclitaxel+Carboplatin)5.54.4 – 5.9
Overall Survival (OS) in the ITT-WT Population Primary · Up to approximately 35 months after first patient enrolled

OS is defined as the time between the date of randomization and date of death from any cause in the ITT-WT population.

GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)18.615.8 – 21.2
Arm B (Nab-Paclitaxel+Carboplatin)13.912.0 – 18.7
PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population Secondary · Up to approximately 35 months after first subject enrolled

PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. The ITT population was defined as all randomized participants, regardless of receipt of the assigned treatment. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT partic

ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.06.3 – 7.3
Arm B (Nab-Paclitaxel+Carboplatin)5.64.5 – 5.9
TC1/2/3 or IC1/2/3 ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.57.0 – 9.1
Arm B (Nab-Paclitaxel+Carboplatin)5.74.5 – 6.6
TC1/2/3 or IC1/2/3-WT ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.57.0 – 9.0
Arm B (Nab-Paclitaxel+Carboplatin)5.94.5 – 6.6
OS as Determined by the Investigator Using Recist v1.1 in the ITT Population Secondary · Up to approximately 41 months after first subject 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 A (Atezolizumab+Nab-Paclitaxel+Carboplatin)17.014.9 – 19.7
Arm B (Nab-Paclitaxel+Carboplatin)13.511.9 – 17.7
OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population Secondary · Up to approximately 35 months after first patient enrolled

OS is defined as the time between the date of randomization and date of death from any cause in the PD-L1 Expression Population and PD-L1 Expression WT Population. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expressio

TC1/2/3 or IC1/2/3 ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)21.217.3 – 28.2
Arm B (Nab-Paclitaxel+Carboplatin)16.912.5 – 22.0
TC1/2/3 or IC1/2/3 WT ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)21.218.1 – 28.2
Arm B (Nab-Paclitaxel+Carboplatin)16.912.5 – 22.0
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 ITT-WT Population Secondary · Up to approximately 41 months after first subject enrolled

ORR (confirmation not required) is defined as the proportion of participants with an objective response, either CR or PR, with the use of RECIST v1.1, as determined by the investigator in the ITT-WT population.

GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)60.2
Arm B (Nab-Paclitaxel+Carboplatin)41.0
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 ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population Secondary · Up to approximately 35 months after first subject enrolled

ORR (confirmation not required) is defined as proportion of participants with an objective response, either CR or PR, with the use of RECIST v1.1, as determined by investigator in ITT population, PD-L1 Expression population, and PD-L1 Expression WT population. ITT population was defined as all randomized participants, regardless of receipt of the assigned treatment. PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 po

ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)59.1
Arm B (Nab-Paclitaxel+Carboplatin)42.2
TC1/2/3 or IC1/2/3 ITT WT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)65.6
Arm B (Nab-Paclitaxel+Carboplatin)46.2
TC1/2/3 or IC1/2/3 ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)64.6
Arm B (Nab-Paclitaxel+Carboplatin)45.0
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 in ITT-WT Population, ITT Population, and PD-L1 Expression Population and PD-L1 Expression WT Population Secondary · Up to approximately 35 months after first subject enrolled

DOR,defined for participants with objective response (OR) as time from 1st documented OR to documented disease progression as determined by investigator using RECIST v1.1,or death from any cause,whichever occurs 1st.ITT defined as all randomized participants,regardless of receipt of assigned treatment.ITT-WT defined as ITT population excluding participants with activating EGFR mutation or ALK translocation.PD-L1 expression population is defined as one of following:PD-L1 IHC TC1/2/3 or IC1/2/3 population,defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor

ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)6.25.6 – 7.9
Arm B (Nab-Paclitaxel+Carboplatin)5.44.1 – 5.8
ITT-WT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)6.75.6 – 8.0
Arm B (Nab-Paclitaxel+Carboplatin)5.43.9 – 5.8
TC1/2/3 or IC1/2/3 ITT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.25.7 – 9.0
Arm B (Nab-Paclitaxel+Carboplatin)5.03.2 – 6.1
TC1/2/3 or IC1/2/3 ITT WT Population
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.25.7 – 9.0
Arm B (Nab-Paclitaxel+Carboplatin)5.03.2 – 6.1
Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population Secondary · Up to 41 months after first patient enrolled, years 1 and 2 reported

The OS rate at the 1- and 2-year landmark time points after randomization.

Event Free Rate (%) at Year 1 ITT WT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)62.0257.53 – 66.51
Arm B (Nab-Paclitaxel+Carboplatin)54.5648.04 – 61.08
Event Free Rate (%) at Year 2 ITT WT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)40.4335.64 – 45.22
Arm B (Nab-Paclitaxel+Carboplatin)32.3625.80 – 38.92
Event Free Rate (%) at Year 1 ITT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)61.6557.29 – 66.02
Arm B (Nab-Paclitaxel+Carboplatin)54.4748.09 – 60.84
Event Free Rate (%) at Year 2 ITT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)39.7335.10 – 44.37
Arm B (Nab-Paclitaxel+Carboplatin)32.2125.79 – 38.63
Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population Secondary · Up to 35 months after first patient enrolled, years 1 and 2 reported

The OS rate at the 1- and 2-year landmark time points after randomization in the PD-L1 Expression Population and PD-L1 Expression WT Population. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor

Event Free Rate (%) at Year 1 TC1/2/3 or IC1/2/3 ITT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)68.5662.46 – 74.66
Arm B (Nab-Paclitaxel+Carboplatin)61.8652.55 – 71.17
Event Free Rate (%) at Year 2 TC1/2/3 or IC1/2/3 ITT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)44.6335.99 – 53.27
Arm B (Nab-Paclitaxel+Carboplatin)35.9823.25 – 48.72
Event Free Rate (%) at Year 1 TC1/2/3 or IC1/2/3 ITT WT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)68.8462.56 – 75.13
Arm B (Nab-Paclitaxel+Carboplatin)62.5153.07 – 71.94
Event Free Rate (%) at Year 2 TC1/2/3 or IC1/2/3 ITT WT
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)44.0234.86 – 53.18
Arm B (Nab-Paclitaxel+Carboplatin)35.3322.06 – 48.60
Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population Secondary · Up to approximately 35 months after first subject enrolled

Defined as time from randomization to confirmed deterioration (10-point change) on the combined European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core (EORTC QLQ-C30) and supplemental lung cancer module (EORTC QLQ-LC13) symptom subscales.

GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)2.21.8 – 3.1
Arm B (Nab-Paclitaxel+Carboplatin)1.91.5 – 2.4
Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale Secondary · Up to approximately 35 months after first subject 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 questi

Chest Pain, Week 1
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)0.19± 0.86
Arm B (Nab-Paclitaxel+Carboplatin)0.14± 0.90
Chest Pain, Week 2
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.02± 0.89
Arm B (Nab-Paclitaxel+Carboplatin)0.03± 0.91
Chest Pain, Week 3
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.05± 0.95
Arm B (Nab-Paclitaxel+Carboplatin)0.01± 0.92
Chest Pain, Week 4
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.11± 0.95
Arm B (Nab-Paclitaxel+Carboplatin)0.01± 1.02
Chest Pain, Week 5
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.12± 0.99
Arm B (Nab-Paclitaxel+Carboplatin)0.00± 1.03
Chest Pain, Week 6
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.24± 1.07
Arm B (Nab-Paclitaxel+Carboplatin)0.03± 1.03
Chest Pain, Week 7
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.23± 1.11
Arm B (Nab-Paclitaxel+Carboplatin)0.03± 1.08
Chest Pain, Week 8
GroupValue95% CI
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)-0.21± 0.99
Arm B (Nab-Paclitaxel+Carboplatin)-0.14± 1.00

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first study drug to the data cutoff date: 18 January 2021 (approximately 69 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)
Serious: 252/473 (53%)
Deaths: 338/473
Arm B Without Crossover Participants (Nab-Paclitaxel+Carboplatin)
Serious: 63/131 (48%)
Deaths: 108/131
Arm B With Crossover Participants (Nab-Paclitaxel+Carboplatin, After Crossover Atezo Monotherapy)
Serious: 24/101 (24%)
Deaths: 70/101

Serious adverse events (220 terms)

ReactionSystemArm A (Atezolizumab+Nab-Pa…Arm B Without Crossover Pa…Arm B With Crossover Parti…
PNEUMONIAInfections and infestations
PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders
ANAEMIABlood and lymphatic system disorders
NEUTROPENIABlood and lymphatic system disorders
DIARRHOEAGastrointestinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASERespiratory, thoracic and mediastinal disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
FEBRILE NEUTROPENIABlood and lymphatic system disorders
PNEUMONITISRespiratory, thoracic and mediastinal disorders
PYREXIAGeneral disorders
PLEURAL EFFUSIONRespiratory, thoracic and mediastinal disorders
SEPSISInfections and infestations
THROMBOCYTOPENIABlood and lymphatic system disorders
PERICARDIAL EFFUSIONCardiac disorders
VOMITINGGastrointestinal disorders
BRONCHITISInfections and infestations
NEUTROPHIL COUNT DECREASEDInvestigations
HAEMOPTYSISRespiratory, thoracic and mediastinal disorders
NAUSEAGastrointestinal disorders
CHEST PAINGeneral disorders
INFLUENZAInfections and infestations
SEPTIC SHOCKInfections and infestations
RENAL FAILURERenal and urinary disorders
ATRIAL FIBRILLATIONCardiac disorders
GENERAL PHYSICAL HEALTH DETERIORATIONGeneral disorders
Other adverse events (71 terms — click to expand)

ReactionSystemArm A (Atezolizumab+Nab-Pa…Arm B Without Crossover Pa…Arm B With Crossover Parti…
ANAEMIABlood and lymphatic system disorders
NAUSEAGastrointestinal disorders
FATIGUEGeneral disorders
NEUTROPENIABlood and lymphatic system disorders
DIARRHOEAGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
ALOPECIASkin and subcutaneous tissue disorders
DECREASED APPETITEMetabolism and nutrition disorders
COUGHRespiratory, thoracic and mediastinal disorders
DYSPNOEARespiratory, thoracic and mediastinal disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
VOMITINGGastrointestinal disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
PLATELET COUNT DECREASEDInvestigations
HYPOMAGNESAEMIAMetabolism and nutrition disorders
NEUTROPHIL COUNT DECREASEDInvestigations
ASTHENIAGeneral disorders
BACK PAINMusculoskeletal and connective tissue disorders
HEADACHENervous system disorders
PYREXIAGeneral disorders
DIZZINESSNervous system disorders
HYPOKALAEMIAMetabolism and nutrition disorders
RASHSkin and subcutaneous tissue disorders
OEDEMA PERIPHERALGeneral disorders
INSOMNIAPsychiatric disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
URINARY TRACT INFECTIONInfections and infestations
WEIGHT DECREASEDInvestigations
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
PRURITUSSkin and subcutaneous tissue disorders
PERIPHERAL SENSORY NEUROPATHYNervous system disorders
NEUROPATHY PERIPHERALNervous system disorders
ABDOMINAL PAINGastrointestinal disorders
DEHYDRATIONMetabolism and nutrition disorders
LEUKOPENIABlood and lymphatic system disorders
HYPOTHYROIDISMEndocrine disorders
MYALGIAMusculoskeletal and connective tissue disorders
WHITE BLOOD CELL COUNT DECREASEDInvestigations
DYSGEUSIANervous system disorders
PARAESTHESIANervous system disorders

Most-reported serious reactions: PNEUMONIA, PULMONARY EMBOLISM, ANAEMIA, NEUTROPENIA, DIARRHOEA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, DYSPNOEA, FEBRILE NEUTROPENIA.

Data from ClinicalTrials.gov NCT02367781 adverse events section.

Sponsor's own description

This randomized Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 \[PD-L1\] antibody) in combination with carboplatin+nab-paclitaxel compared with treatment with carboplatin+nab-paclitaxel in chemotherapy-naive participants with Stage IV non-squamous NSCLC. Participants were randomized in a 2:1 ratio to Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin) or Arm B (Nab-Paclitaxel+Carboplatin).

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. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial.
    West H, McCleod M, Hussein M, Morabito A, et al · · 2019 · cited 1254× · PMID 31122901 · DOI 10.1016/s1470-2045(19)30167-6
  3. 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
  4. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
    Morad G, Helmink BA, Sharma P, Wargo JA. · · 2021 · cited 1197× · PMID 34624224 · DOI 10.1016/j.cell.2021.09.020
  5. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.
    Yi M, Zheng X, Niu M, Zhu S, et al · · 2022 · cited 1018× · PMID 35062949 · DOI 10.1186/s12943-021-01489-2
  6. Ferroptosis, necroptosis, and pyroptosis in anticancer immunity.
    Tang R, Xu J, Zhang B, Liu J, et al · · 2020 · cited 939× · PMID 32778143 · DOI 10.1186/s13045-020-00946-7
  7. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study.
    Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, et al · · 2017 · cited 760× · PMID 27932067 · DOI 10.1016/s1470-2045(16)30624-6
  8. Lung cancer immunotherapy: progress, pitfalls, and promises.
    Lahiri A, Maji A, Potdar PD, Singh N, et al · · 2023 · cited 737× · PMID 36810079 · DOI 10.1186/s12943-023-01740-y

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