Clinical trial NCT04513925: A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase III, Open-Label, Randomized Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Patients With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer Who Have Not Progressed After Concurrent Platinum-Based Chemoradiation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer (NSCLC)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-08-14
Enrollment: 829
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: The purpose of this study is to evaluate the efficacy and safety of atezolizumab in combination with tiragolumab compared with durvalumab in participants with locally advanced, unresectable Stage III non-small cell lung cancer (NSCLC) who have received at least two cycles of concurrent platinum-based chemoradiotherapy (CRT) and have not had radiographic disease progression.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Histologically or cytologically documented NSCLC with locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology
* Whole-body Positron Emission Tomography-Computed Tomography (PET-CT) scan, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (cCRT)
* At least two prior cycles of platinum-based chemotherapy administered concurrently with radiotherapy (RT), which must be completed within 1 to 42 days prior to randomization in the study (one cycle of cCRT is defined as 21 or 28 days)
* The radiotherapy (RT) component in the cCRT must have been at a total dose of radiation of 60 (±10 percent \[%\]) gray (Gy) (54 Gy to 66 Gy) administered by intensity modulated RT (preferred) or 3D-conforming technique
* No progression during or following concurrent platinum-based CRT
* A known PD-L1 result
* Life expectancy \>/= 12 weeks
* Adequate hematologic and end-organ function
* Female participants must be willing to avoid pregnancy for 90 days after the final dose of tiragolumab and 5 months after the final dose of atezolizumab, or for 3 months after the final dose of durvalumab
* Male participants must remain abstinent or use a condom during the treatment period and for 90 days after the final dose of tiragolumab
* Male participants must not donate sperm during the treatment period and for 90 days after the final dose of tiragolumab

Exclusion Criteria:

* Any history of prior NSCLC and/or any history of prior treatment for NSCLC (participants must be newly diagnosed with unresectable Stage III disease)
* NSCLC known to have a mutation in the epidermal growth factor receptor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene
* Any evidence of Stage IV disease
* Treatment with sequential CRT for locally advanced NSCLC
* Participants with locally advanced NSCLC who have progressed during or after the definitive cCRT prior to randomization
* Any Grade \>2 unresolved toxicity from previous CRT
* Grade \>= 2 pneumonitis from prior CRT
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis or evidence of active pneumonitis
* History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with a negligible risk of metastasis or death
* Prior allogeneic stem cell or solid organ transplantation
* Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-T-cell immunoreceptor with Ig and ITIM domains (anti-TIGIT), anti-PD-1 and anti-PD-L1
* Any prior Grade \>/= 3 immune-mediated adverse event or any unresolved Grade \> 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents
* Treatment with systemic immunosuppressive medication
* Women who are pregnant, or breastfeeding

Primary outcomes:
measure: Independent Review Facility (IRF)-assessed Progression Free Survival (PFS) in the PD-L1-positive Analysis Set (PPAS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
measure: IRF-assessed PFS in the Full Analysis Set (FAS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Secondary outcomes:
measure: Overall Survival (OS) in the PPAS
timeFrame: From randomization to death from any cause (up to approximately 114 months)
measure: Investigator-assessed PFS in the PPAS
timeFrame: Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months)
measure: IRF-assessed Confirmed Objective Response Rate (ORR) in the PPAS
timeFrame: From randomization up to approximately 114 months
measure: Investigator-assessed Confirmed ORR in the PPAS
timeFrame: From randomization up to approximately 114 months
measure: IRF-assessed Duration of Response (DOR) in the PPAS
timeFrame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
measure: Investigator-assessed DOR in the PPAS
timeFrame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
measure: Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score in the PPAS
timeFrame: Up to approximately 114 months
measure: OS in the FAS
timeFrame: From randomization to death from any cause (up to approximately 114 months)
measure: Investigator-assessed PFS in the FAS
timeFrame: Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months)
measure: IRF-assessed Confirmed ORR in the FAS
timeFrame: From randomization up to approximately 114 months
measure: Investigator-assessed Confirmed ORR in the FAS
timeFrame: From randomization up to approximately 114 months
measure: IRF-assessed DOR in the FAS
timeFrame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
measure: Investigator-assessed DOR in the FAS
timeFrame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
measure: TTCD Assessed Using EORTC QLQ-C30 Score in the FAS
timeFrame: Up to approximately 114 months
measure: IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS
timeFrame: 12, 18 and 24 months
measure: IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS
timeFrame: 12, 18 and 24 months
measure: Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS
timeFrame: 12, 18 and 24 months
measure: Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS
timeFrame: 12, 18 and 24 months
measure: OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the PPAS
timeFrame: 12, 24, 36 and 48 months
measure: OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the FAS
timeFrame: 12, 24, 36 and 48 months
measure: Investigator-assessed Time to Death or Distant Metastasis (TTDM) in the PPAS
timeFrame: From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months)
measure: Investigator-assessed TTDM in the FAS
timeFrame: From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months)
measure: Percentage of Participants With Adverse Events
timeFrame: Up to approximately 114 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Greeley
country: United States
facility: Banner MD Anderson Cancer Center
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Palm Bay
country: United States
facility: Cancer Care Centers of Brevard
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, P.A.
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist, North Region
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Brunswick
country: United States
facility: New England Cancer Specialists
state: Maine
city: Fairhaven
country: United States
facility: Southcoast Health System
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Kansas City
country: United States
facility: HCA Midwest Health
state: Missouri
city: Springfield
country: United States
facility: Cox Health Systems
state: Missouri
city: Las Vegas
country: United States
facility: Optum Health Care
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: East Brunswick
country: United States
facility: Titan Health Partners LLC, d/b/a Astera Cancer Care
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology,P.C.-Albany
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Greenville
country: United States
facility: Prisma Health ? Upstate
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Buenos Aires
country: Argentina
facility: CEMIC
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Cordoba
country: Argentina
facility: Clinica Universitaria Reina Fabiola
city: Rosario
country: Argentina
facility: Sanatorio Parque S.A.
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Campbelltown
country: Australia
facility: Macarthur Cancer Therapy Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Bull Creek
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Victoria
country: Australia
facility: Monash Health Translational Precinct
city: Innsbruck
country: Austria
facility: Tiroler Landeskrankenanstalten Ges.M.B.H.
city: Linz
country: Austria
facility: Kepler Universitätskliniken GmbH - Med Campus III
city: Wien
country: Austria
facility: Klinik Penzing
city: Charleroi
country: Belgium
facility: GHdC Site Les Viviers
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Curitiba
country: Brazil
facility: Centro Integrado de Oncologia de Curitiba
state: Paraná
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Abbotsford
country: Canada
facility: BC Cancer ? Abbotsford
state: British Columbia
city: Victoria
country: Canada
facility: BC Cancer - Victoria
state: British Columbia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Brampton
country: Canada
facility: William Osler Health System Brampton Civic Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Beijing City
country: China
facility: Beijing Cancer Center
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha City
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: Sichuan Provincial Cancer Hospital
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Fujian
country: China
facility: Fujian Medical University Union Hospital
city: Fuzhou City
country: China
facility: Fujian Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Cancer Center, Sun Yat-sen University of Medical Sciences
city: Hangzhou City
country: China
facility: Hangzhou Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Affiliated to Southeast University
city: Qingdao City
country: China
facility: The affiliated hospital of Qingdao university
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Angers
country: France
facility: CHU Angers
city: Caen
country: France
facility: Centre Francois Baclesse
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Montpellier
country: France
facility: Clinique Clémentville
city: Vantoux
country: France
facility: Hopital Robert Schuman
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Braunschweig
country: Germany
facility: Klinikum Braunschweig
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Köln
country: Germany
facility: Klinikum Koeln-Merheim
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Asvestochori
country: Greece
facility: General Hospital "G.Papanikolaou"
city: Athens
country: Greece
facility: Sotiria Hospital
city: Kifisia
country: Greece
facility: Agioi Anargyroi Cancer Hospital
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital, Oncology
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Tatabánya
country: Hungary
facility: Szent Borbala Korhaz
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
state: Campania
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
state: Emilia-Romagna
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
state: Lazio
city: Roma
country: Italy
facility: IRCCS Istituto Regina Elena (IFO)
state: Lazio
city: Genova
country: Italy
facility: IRCCS AOU San Martino - IST
state: Liguria
city: Brescia
country: Italy
facility: A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
state: Lombardia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
state: Lombardia
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
state: Toscana
city: Vicenza
country: Italy
facility: Azienda ULSS 8 Berica
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center
city: Chiba
country: Japan
facility: National Cancer Center East
city: Hyogo
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Kanagawa
country: Japan
facility: Kitasato University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: St. Vincent's Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Medical Center
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hosiptal
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Leidschendam
country: Netherlands
facility: Medisch Centrum Haaglanden, locatie Antoniushove
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum - Sittard Geleen
city: Auckland
country: New Zealand
facility: Auckland City Hospital, Cancer and Blood Research
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Olsztyn
country: Poland
facility: Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
city: Warszawa
country: Poland
facility: Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
city: Wroc?aw
country: Poland
facility: Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii
city: Coimbra
country: Portugal
facility: IPO de Coimbra
city: Lisboa
country: Portugal
facility: Hospital da Luz
city: Porto
country: Portugal
facility: Hospital CUF Porto
city: Porto
country: Portugal
facility: IPO do Porto
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Castellon de La Plana
country: Spain
facility: Hospital Provincial de Castellon
state: Castellon
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Bangkok
country: Thailand
facility: Vajira Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital;Medicine/Oncology
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Adana
country: Turkey
facility: Adana Baskent University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty, Oncology Hospital
city: Bornova, ?zm?r
country: Turkey
facility: Ege University Medical Faculty
city: Diyarbakir
country: Turkey
facility: Dicle University Faculty of Medicine
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Faculty of Medicine
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty
city: Malatya
country: Turkey
facility: Inonu University Faculty of Medicine Turgut Ozal Medical Center
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's NHS Trust
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Manchester
country: United Kingdom
facility: Christie Foundation Trust
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: