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.

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]

Squamous Non-Small Cell Lung Cancer

Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (anti-PD-L1) antibody

Carboplatin

Nab-Paclitaxel

Paclitaxel

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

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.

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

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 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 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 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 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 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.

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

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 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.

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 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 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 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 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 at least one adverse event.

Percentage of participants with Anti-therapeutic Antibody (ATA) response to atezolizumab.

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). The predose samples will be collected on the same day of treatment administration.

Plasma concentrations for nab-paclitaxel.

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.

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.

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.

Ironwood Cancer & Research Centers

Highlands Oncology Group

Southern CA Permanente Med Grp

Kaiser Permanente Oakland Medical Center

Kaiser Permanente - Sacramento Medical Center and Medical Offices

Kaiser Permanente - San Leandro Medical Center

Kaiser Permanente - Santa Clara

Kaiser Permanente; Oncology Clinical Trials

Kaiser Permanente - Walnut Creek

Rocky Mountain Cancer Center

Danbury Hospital

Holy Cross Hospital Inc

SCRI Florida Cancer Specialists South

Florida Cancer Specialists

Hematology Oncology Associates of the Treasure Coast

Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)

University Cancer & Blood Center, LLC; Research

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital

Central Georgia Cancer Care PC

Southeastern Regional Medical Center, Inc.

University of Chicago

Joliet Oncology-Hematology; Associates, Ltd.

Quincy Medical Group

Fort Wayne Med Oncology & Hematology Inc

Hematology-Oncology; Associates of the Quad Cities

Siouxland Hematology/Oncology

Lahey Clinic Med Ctr

Norton Cancer Institute

Ochsner Clinic Foundation

New England Cancer Specialists

Southcoast Health System; Southcoast Centers For Cancer Care

St. Joseph Mercy Health System

Karmanos Cancer Institute

St. Luke's Regional Cancer Center

Hematology and Oncology Associates at Bridgepoint

Billings Clinic

Valley Hospital; Oncology Research

Regional Cancer Care Associates LLC

Clinical Research Alliance

W.G. Bill Hefner VA Medical Center

University of Cincinnati

Mark H. Zangmeister Center

Oncology Hematology Care, Inc.

Oregon Health & Science Uni

St. Luke's Cancer Care Associates

Maryland Oncology Hematology (Lanham) - USOR

Allegheny Cancer Center

Univ of Pittsburgh Medical Ctr

SCRI Tennessee Oncology Chattanooga

Tennessee Cancer Specialists

SCRI The Center For Cancer and Blood Disorders

Longview Cancer Center

Virginia Cancer Specialists, PC

Virginia Oncology Associates

Blue Ridge Cancer Care

Providence Regional Cancer Partnership

Medical Oncology Associates

Fundación CENIT para la Investigación en Neurociencias

Sanatorio Allende

Centro Oncologico Riojano Integral (CORI)

Clínica Pergamino

Fundacion Koriza

Centro de Investigacion; Clinica - Clinica Viedma S.A.

Chris O'Brien Lifehouse

Calvary Mater Newcastle; Medical Oncology

Prince Charles Hospital

Townsville Hospital

Princess Alexandra Hospital

Royal Adelaide Hospital

Austin Health

Cabrini Hospital Malvern

Sunshine Hospital

Sir Charles Gairdner Hospital

Paracelsus Medizinische Privatuniversität

Cliniques Universitaires St-Luc

CHU Sart-Tilman

Clinique Ste-Elisabeth

Werken Glorieux VZW

GasthuisZusters Antwerpen

Cenantron - Centro Avancado de Tratamento Oncologico

Instituto Do Cancer Delondrina_X; Unidade De Pesquisa Clinica

Liga Norte Riograndense Contra O Câncer

IPCEM; Instituto de Pesquisa de Estudos Multicêntricos

Hospital Bruno Born

Hospital das Clinicas - UFRGS

Hospital Mae de Deus

*X*Fundação Pio XII Hospital de Câncer de Barretos

Hospital de Base de Sao Jose do Rio Preto

Hospital Do Cancer A C Camargo

Multiprofile Hospital for Active Treatment Central Onco Hospital OOD

Multiprofile Hospital for Active Treatment Serdika EOOD

Royal Victoria Regional Health Centre

William Osler Health Centre

Lakeridge Health Center

Cite de La Sante de Laval; Hemato-Oncologie

Hôpital du Sacré-Coeur de Montreal

St. Jerome Medical Research

Health & Care SPA

Sociedad de Investigaciones Medicas Ltda (SIM)

CHU de Grenoble

All-cause mortality is reported for deaths that occurred during the study based on the ITT population, which included all randomized participants. Serious and other adverse events were reported based on the safety population, which included all randomized participants who received at least one dose of any study medication.

The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care.

Arm C: Nab-Paclitaxel + Carboplatin

The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.

Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.

Arm A: Atezolizumab + Paclitaxel + Carboplatin

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Medical Communications

Intent To Treat (ITT) was defined as all randomized participants, irrespective of whether the assigned treatment was actually received.

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

Overall Survival (OS) in the ITT Population

Teff >=-1.91

Teff<-1.91

The Teff (\>=-1.91) population and the Teff (\<-1.91) population, defined as patients in the ITT population with Teff signature expression \>=-1.91 and \<-1.91, respectively.

OS in the in the Teff Population

PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population

The PD-L1 TC2/3 or IC2/3 population is defined as particpants in the ITT population with PD-L1 TC2/3 or IC2/3 expression in baseline tumor tissue.

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

The PD-L1 TC1/2/3 or IC1/2/3 population is defined as participants in the ITT population with PD-L1 TC1/2/3 or IC1/2/3 expression in baseline tumor tissue.

PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population

OS in the TC2/3 or IC2/3 Population

OS 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

Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

1 Year

2 Year

Participants still alive at 1 or 2 years after randomization from the ITT population.

Event Free Rate at 1 and 2 Years in the ITT Population

Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population

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.

TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population

Chest Pain, Week 1

Chest Pain, Week 2

Chest Pain, Week 3

Chest Pain, Week 4

Chest Pain, Week 5

Chest Pain, Week 6

Chest Pain, Week 7

Chest Pain, Week 8

Chest Pain, Week 9

Chest Pain, Week 10

Chest Pain, Week 11

Chest Pain, Week 12

Chest Pain, Week 13

Chest Pain, Week 14

Chest Pain, Week 15

Chest Pain, Week 16

Chest Pain, Week 17

Chest Pain, Week 18

Chest Pain, Week 19

Chest Pain, Week 20

Chest Pain, Week 21

Chest Pain, Week 22

Chest Pain, Week 23

Chest Pain, Week 24

Chest Pain, Week 25

Chest Pain, Week 26

Chest Pain, Week 27

Chest Pain, Week 28

Chest Pain, Week 29

Chest Pain, Week 30

Chest Pain, Week 31

Chest Pain, Week 32

Chest Pain, Week 33

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)

Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population

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]

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?