Clinical trial NCT02031458: A Study of Atezolizumab in Participants With Programmed Death - Ligand 1 (PD-L1) Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase II, Multicenter, Single-Arm Study OF Atezolizumab In Patients With PD-L1-Positive Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-01-09
Enrollment: 667
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multicenter, single-arm study will evaluate the efficacy and safety of Atezolizumab in participants with PD-L1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Participants will receive Atezolizumab 1200 milligrams (mg) intravenously every 3 weeks as long as participants are experiencing clinical benefit as assessed by the investigator, that is , in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.


Eligibility criteria: Inclusion Criteria:

* Adult participants greater than or equal to 18 years of age
* Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) NSCLC
* Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens
* PD-L1-positive tumor status as determined by an immunohistochemistry (IHC) assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cells performed by a central laboratory
* Measurable disease, as defined by RECIST version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

* Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exception are allowed:

Hormone-replacement therapy or oral contraceptives tyrosine-kinase inhibitors (TKIs) approved for treatment of NSCLC discontinued \>7 days prior to Cycle 1, Day 1

* Central nervous system (CNS) disease, including treated brain metastases
* Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with negligible risk of metastases or death and treated with expected curative outcome
* History of autoimmune disease
* History of idiopathic pulmonary fibrosis (including pneumonia), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening CT scan. History of radiation pneumonitis in the radiation field (fibrosis) id permitted
* Active hepatitis B or hepatitis C
* Human Immunodeficiency virus (HIV) positive
* Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents

Primary outcomes:
measure: Percentage of Participants Achieving Objective Response (ORR) Per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 as Assessed by Independent Review Facility (IRF)
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
Secondary outcomes:
measure: Percentage of Participants Achieving Objective Response Per RECIST v1.1 as Assessed by the Investigator (INV)
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Percentage of Participants Achieving Objective Response Per Modified RECIST as Assessed by the INV
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Duration of Response (DOR) Assessed by IRF Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: DOR as Assessed by INV Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: DOR as Assessed by INV Per Modified RECIST
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Progression Free Survival (PFS) as Assessed by IRF Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: PFS as Assessed by INV Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: PFS as Assessed by INV Per Modified RECIST
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Overall Survival : Percentage of Participants Without Event (Death)
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Overall Survival : Median Time to Event (Death)
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Percentage of Participants Without an Event (Death) at 6 Months
timeFrame: Month 6
measure: Percentage of Participants Without an Event (Death) at 12 Months
timeFrame: Month 12
measure: PFS: Percentage of Participants Alive and Progression Free at 6 Months
timeFrame: Month 6
measure: PFS: Percentage of Participants Alive and Progression Free at 12 Months
timeFrame: Month 12
measure: Time in Response (TIR) as Assessed by INV Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: TIR as Assessed by INV Per Modified RECIST
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: TIR as Assessed by IRF Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Atezolizumab Serum Concentrations
timeFrame: Pre-dose (hour 0) and 0.5 hours post dose on Cycle 1 Day 1 (Cycle length = 21days), Cycle 1 Days 2, 4, 8, 15, and 21, Cycle 2 Day 21, Cycle 3 Day 21, Cycle 7 Day 21
measure: Percentage of Participants With Positive Anti-Therapeutic Antibody (Anti-Atezolizumab Antibody) Status
timeFrame: Baseline, post-baseline (up to 16 months)
measure: Percentage of Participants With Event (Disease Progression or Death) as Assessed by IRF Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
measure: Percentage of Participants With Event (Disease Progression or Death) as Assessed by INV Per Modified RECIST v1.1
timeFrame: Screening, Every 6 weeks (± 3 days) for 12 months following Cycle 1, Day 1 and every 9 weeks (± 1 week) thereafter until disease progression, intolerable toxicity or death until data cut-off on 28 May 2015 (Up to 16 months)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Bisgrove
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Angeles Clinic & Rsch Inst
state: California
city: South Pasadena
country: United States
facility: City of Hope National Medical Group
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Science Center; Biomedical Research Bldg. Room 511
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center; Medical Oncology
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists; SCRI
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Inst
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists.
state: Florida
city: Atlanta
country: United States
facility: Emory Uni - Winship Cancer Center; Hematology/Oncology
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Chicago
country: United States
facility: Northwestern University; Robert H. Lurie Comp Can Ctr
state: Illinois
city: Chicago
country: United States
facility: University Of Chicago Medical Center; Section Of Hematology/Oncology
state: Illinois
city: Baltimore
country: United States
facility: Uni of Maryland; Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr; Hem/Onc
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute, PLCC
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University; B406 Starling-Loving Hall
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center; Hematology/Oncology
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology PLLC - Nashville (20th Ave)
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute; University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia; Office of Sponsored Programs
state: Virginia
city: Seattle
country: United States
facility: University of Washington Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital; Oncology
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess AleXandra Hospital; Department of Medical Oncology
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute; Medical Oncology
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital; Medical Oncology
state: Western Australia
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Charleroi
country: Belgium
facility: GHdC Site Saint-Joseph
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska
city: Sarajevo
country: Bosnia and Herzegovina
facility: University Clinical Center Sarajevo;Clinic for Pulmonary disease
city: Sarajevo
country: Bosnia and Herzegovina
facility: University Clinical Center Sarajevo;Institute of oncology
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center (COC)-Plovidiv
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa; Oncology
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre; Oncology
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: Brest
country: France
facility: Hopital Augustin Morvan; Oncologie Thoracique
city: Caen
country: France
facility: Hopital Cote De Nacre; Pneumologie
city: Limoges
country: France
facility: CHU Limoges - Dupuytren; Oncologie Thoracique Cutanee
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Montpellier
country: France
facility: Hopital Arnaud De Villeneuve; Maladies Respiratoires
city: Nantes
country: France
facility: Centre René Gauducheau - cancer Nantes - Atlantique; Service Oncologie Médicale
city: Strasbourg
country: France
facility: Nouvel Hopital Civil; Pneumologie
city: Villejuif
country: France
facility: Institut Gustave Roussy; Departement Oncologie Medicale
city: Tbilisi
country: Georgia
facility: Research institute for Clinical Medicine
city: Tbilisi
country: Georgia
facility: Cancer Research Centre
city: Tbilisi
country: Georgia
facility: MediClab Georgia
city: Tbilisi
country: Georgia
facility: Chemotherapy and Immunotherapy Clinic Medulla
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
city: Großhansdorf
country: Germany
facility: LungenClinic Großhansdorf GmbH
city: Nürnberg
country: Germany
facility: Klinikum Nuernberg Nord; Medizinische Klinik 3, Schwerpunkt Pneumologie, Allergologie, Schlafmedizin
city: Oldenburg
country: Germany
facility: Pius-Hospital; Klinik fuer Haematologie und Onkologie
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum/VS GmbH; Onkologie/Hämatologie/Infektologie
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital; Clinical Oncology
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital; Dept. of Clinical Oncology
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp; Dept. Of Clinical Onc
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
state: Lombardia
city: Orbassano
country: Italy
facility: Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico
state: Piemonte
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center; Respiratory Internal Medicine
city: Kanagawa
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center; Respiratory Medicine
city: Kanagawa
country: Japan
facility: Yokohama Municipal Citizen'S Hospital; Respiratory Medicine
city: Kanagawa
country: Japan
facility: Kitasato University Hospital; Respiratory Medicine
city: Kyoto
country: Japan
facility: Kyoto University Hospital, Respiratory Medicine
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital; Pulmonary Medicine
city: Osaka
country: Japan
facility: Osaka International Cancer Institute; Thoracic Oncology
city: Osaka
country: Japan
facility: Kansai Medical university Hospital; Thoracic Oncology
city: Osaka
country: Japan
facility: Osaka Habikino Medical Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital; Thoracic Medical Oncology
city: Tokyo
country: Japan
facility: Toranomon Hospital; Respiratory Medicine
city: Amsterdam
country: Netherlands
facility: Antoni Van Leeuwenhoek Ziekenhuis; Thoracic Oncology
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis; Afdeling Longziekten
city: Groningen
country: Netherlands
facility: Academ Ziekenhuis Groningen; Medical Oncology
city: Singapore
country: Singapore
facility: National University Hospital; National University Cancer Institute, Singapore (NCIS)
city: Singapore
country: Singapore
facility: National Cancer Centre; Medical Oncology
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: ICO Badalona - Hospital Germans Trias i Pujol
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Oncologia
city: Basel
country: Switzerland
facility: Universitaetsspital Basel; Onkologie
city: Lausanne
country: Switzerland
facility: CHUV; Departement d'Oncologie
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen; Onkologie/Hämatologie
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Ankara
country: Turkey
facility: Ankara Ataturk Chest Diseases Training and Research Hospital
city: Izmir
country: Turkey
facility: Ege University School of Medicine; Chest Diseases Department
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
city: London
country: United Kingdom
facility: Barts & London School of Med; Medical Oncology
city: London
country: United Kingdom
facility: Royal Marsden Hospital - London
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Shemesh CS, Chan P, Legrand FA, Shames DS, Das Thakur M, Shi J, Bailey L, Vadhavkar S, He X, Zhang W, Bruno R. Pan-cancer population pharmacokinetics and exposure-safety and -efficacy analyses of atezolizumab in patients with high tumor mutational burden. Pharmacol Res Perspect. 2020 Dec;8(6):e00685. doi: 10.1002/prp2.685.