Clinical trial NCT02367781: 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)
Official title: A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Squamous Non-Small Cell Lung
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-02-20
Enrollment: 723
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group performance status of 0 or 1
* Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
* Participants with no prior treatment for Stage IV non-squamous NSCLC
* Previously obtained archival tumor tissue or tissue obtained from fresh biopsy at screening
* Measurable disease, as defined by RECIST v1.1
* Adequate hematologic and end organ function

Exclusion Criteria:

Cancer-Specific Exclusions:

* Active or untreated central nervous system metastases
* 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

General Medical Exclusions:

* 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 scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Positive test for human immunodeficiency virus
* Active hepatitis B or hepatitis C
* Severe infection within 4 weeks prior to randomization
* Significant cardiovascular disease
* Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures

Exclusion Criteria Related to Medications:

* Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies

Primary outcomes:
measure: 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
timeFrame: Up to approximately 35 months after first patient enrolled
measure: Overall Survival (OS) in the ITT-WT Population
timeFrame: Up to approximately 35 months after first patient enrolled
Secondary outcomes:
measure: PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population
timeFrame: Up to approximately 35 months after first subject enrolled
measure: OS as Determined by the Investigator Using Recist v1.1 in the ITT Population
timeFrame: Up to approximately 41 months after first subject enrolled
measure: OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population
timeFrame: Up to approximately 35 months after first patient enrolled
measure: 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
timeFrame: Up to approximately 41 months after first subject enrolled
measure: 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
timeFrame: Up to approximately 35 months after first subject enrolled
measure: 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
timeFrame: Up to approximately 35 months after first subject enrolled
measure: Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population
timeFrame: Up to 41 months after first patient enrolled, years 1 and 2 reported
measure: Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population
timeFrame: Up to 35 months after first patient enrolled, years 1 and 2 reported
measure: Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population
timeFrame: Up to approximately 35 months after first subject enrolled
measure: Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
timeFrame: Up to approximately 35 months after first subject enrolled
measure: Percentage of Participants With Adverse Events
timeFrame: Up to approximately 69 months after first patient enrolled
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: Up to approximately 35 months after first subject enrolled
measure: Maximum Observed Serum Concentration (Cmax) of Atezolizumab for Patients in Atezolizumab+Carboplatin+Nab-Paclitaxel Arm
timeFrame: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days)
measure: Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Atezolizumab+Carboplain+Nab-Paclitaxel
timeFrame: Cycle 1 Day 21, Cycle 2 Day 21, Cycle 3 Day 21, and Cycle 7 Day 21 (Cycle length = 21 days)
measure: Plasma Concentrations of Carboplatin
timeFrame: Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 hour after carboplatin infusion (infusion duration=15 to 30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months)
measure: Plasma Concentrations of Nab-Paclitaxel Reported as Total Paclitaxel
timeFrame: Predose (same day of treatment administration), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after nab-paclitaxel infusion (infusion duration=30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Oakland
country: United States
facility: Kaiser Permanente Oakland Medical Center
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Medical Center - Roseville
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento Medical Center and Medical Offices
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente - San Francisco Medical Center
state: California
city: San Jose
country: United States
facility: Kaiser Permanente - San Jose Medical Center
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente - San Leandro Medical Center
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente - Santa Clara
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente - South San Francisco
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente; Oncology Clinical Trials
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente - Walnut Creek
state: California
city: Greeley
country: United States
facility: Banner MD Anderson Cancer Center
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates; (ECHO)
state: Connecticut
city: Deerfield Beach
country: United States
facility: University of Miami School of Medicine - Sylvester at Deerfield
state: Florida
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)
state: Florida
city: West Palm Beach
country: United States
facility: SCRI Florida Cancer Specialists East
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC; Research
state: Georgia
city: Carrollton
country: United States
facility: Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
state: Georgia
city: Lawrenceville
country: United States
facility: Suburban Hematology / Oncology Associates
state: Georgia
city: Newnan
country: United States
facility: Southeastern Regional Medical Center, Inc.
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology; Associates, Ltd.
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University, Simmons Cancer Institute
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Med Oncology & Hematology Inc
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: Lahey Clinic Med Ctr
state: Kentucky
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Center For Cancer and Blood Disorders
state: Maryland
city: Fairhaven
country: United States
facility: Southcoast Health System
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Tupelo
country: United States
facility: Hematology and Oncology Associates at Bridgepoint
state: Mississippi
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Ctr
state: Nebraska
city: Reno
country: United States
facility: Va Sierra Nevada Health Care System
state: Nevada
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Inst. of New Jersey
state: New Jersey
city: New York
country: United States
facility: Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center; Department of Medicine
state: North Carolina
city: Salisbury
country: United States
facility: W.G. Bill Hefner VA Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Mark H. Zangmeister Center
state: Ohio
city: Hamilton
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Harrisburg
country: United States
facility: Pinnacle Health
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Health System; Cancer Center
state: South Carolina
city: Chattanooga
country: United States
facility: University Oncology Associates
state: Tennessee
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Denton
country: United States
facility: SCRI The Center For Cancer and Blood Disorders
state: Texas
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Network of South Texas - SAT & BC
state: Texas
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Ronse
country: Belgium
facility: Werken Glorieux VZW
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen
city: Surrey
country: Canada
facility: BC Cancer - Surrey
state: British Columbia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Etobicoke
country: Canada
facility: William Osler Health Centre
state: Ontario
city: Laval
country: Canada
facility: Cite de La Sante de Laval; Hemato-Oncologie
state: Quebec
city: Montreal
country: Canada
facility: Hôpital Maisonneuve - Rosemont
state: Quebec
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Levallois-Perret
country: France
facility: Institut Hospitalier Franco-Britannique; Cancerologie
city: Marseille
country: France
facility: Fondation Hopital Saint Joseph;Cardiologie Clinique
city: Montpellier
country: France
facility: Clinique Clementville; Hopital De Jour
city: Nancy
country: France
facility: Centre D'oncologie de Gentilly; Service Oncologie Medicale
city: Nantes
country: France
facility: Clinique Catherine de Sienne
city: Neuilly sur Seine
country: France
facility: Hopital American de Paris (American Hospital of Paris)
city: Orleans
country: France
facility: HOPITAL DE LA SOURCE; Service de Cardiologie, Point Jaune
city: Rennes
country: France
facility: Hopital Pontchaillou
city: Saint Pierre
country: France
facility: Centre Hospitalier Regional Sud Reunion; Service de Pneumologie
city: Saint-Mande
country: France
facility: Hopital d'Instruction des Armees de Begin
city: Vandoeuvre-lès-nancy
country: France
facility: CHRU Nancy; Pneumologie
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin; Klinik fur Infektiologie und Pneumologie
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Ebensfeld
country: Germany
facility: Bezirksklinikum Obermain
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Esslingen Am Neckar
country: Germany
facility: Klinikum Esslingen GmbH; Frauenklinik
city: Flensburg
country: Germany
facility: Malteser Krankenhaus St. Franziskus-Hospital
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest
city: Gauting
country: Germany
facility: Asklepios Fachkliniken GmbH
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
city: Gerlingen
country: Germany
facility: Robert Bosch Krankenhaus; Pneumologie und pneumologische Onkologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken Karlsruhe
city: Kassel
country: Germany
facility: Klinikum Kassel; Hautklinik
city: Koblenz Am Rhein
country: Germany
facility: Katholisches Klinikum Marienhof
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I
city: Mannheim
country: Germany
facility: Klinikum Mannheim GmbH Universitätsklinikum
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Munchen
country: Germany
facility: LMU Klinikum der Universitat Munchen
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Velbert
country: Germany
facility: Praxis fur Haematologie und Internistische Onkologie
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum/VS GmbH; Onkologie/Hämatologie/Infektologie
city: Wuppertal
country: Germany
facility: Helios Klinik Wuppertal
city: Beer Sheva
country: Israel
facility: Soroka University Medical Centre
city: Beer Yaakov
country: Israel
facility: Assaf Harofeh Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Oncology Dept
city: Kfar-Saba
country: Israel
facility: Meir Medical Center; Oncology
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petach Tiqwa
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rambam
country: Israel
facility: Rambam Health Corporation; Oncology Institute
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Ctr; Oncology
city: Chieti
country: Italy
facility: Ospedale Clinicizzato SS Annunziata
state: Abruzzo
city: Avellino
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
state: Campania
city: Napoli
country: Italy
facility: Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
state: Campania
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
state: Campania
city: Macerata
country: Italy
facility: Ospedale Di Macerata; Oncologia
state: Marche
city: Perugia
country: Italy
facility: Ospedale Santa Maria Della; Misericordia Di Perugia; Farmacia Ospedaliera
state: Umbria
city: Castellon DE LA Plana/castello DE LA Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
state: Castellon
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: LA Coruña
city: Torrejon de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: S. Cristobal De La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Caceres
country: Spain
facility: Hospital de San Pedro de Alcantara
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Guadalajara
country: Spain
facility: Hospital General Universitario de Guadalajara
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital NisA 9 de Octubre
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ton TGN, Pal N, Trinh H, Mahrus S, Bretscher MT, Machado RJM, Sadetsky N, Chaudhary N, Lu MW, Riely GJ. Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non-Small Cell Lung Cancer Trials Using Real-World Data. Clin Cancer Res. 2022 Jul 1;28(13):2844-2853. doi: 10.1158/1078-0432.CCR-22-0471.
citation: West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ, Kopp HG, Daniel D, McCune S, Mekhail T, Zer A, Reinmuth N, Sadiq A, Sandler A, Lin W, Ochi Lohmann T, Archer V, Wang L, Kowanetz M, Cappuzzo F. 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. Lancet Oncol. 2019 Jul;20(7):924-937. doi: 10.1016/S1470-2045(19)30167-6. Epub 2019 May 20.