A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Interventions
- Registration Number
- NCT04513925
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 829
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Tiragolumab Tiragolumab Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles. Atezolizumab + Tiragolumab Atezolizumab Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles. Durvalumab Durvalumab Participants will receive durvalumab administered IV during each 28-day cycle for a maximum of 13 cycles.
- Primary Outcome Measures
Name Time Method Independent Review Facility (IRF)-assessed Progression Free Survival (PFS) in the PD-L1-positive Analysis Set (PPAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months) IRF-assessed PFS in the Full Analysis Set (FAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
- Secondary Outcome Measures
Name Time Method Investigator-assessed PFS in the PPAS Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months) IRF-assessed Confirmed Objective Response Rate (ORR) in the PPAS From randomization up to approximately 114 months IRF-assessed Duration of Response (DOR) in the PPAS From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months) Overall Survival (OS) in the PPAS From randomization to death from any cause (up to approximately 114 months) 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 Up to approximately 114 months TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS) and physical functioning from baseline that must be held for all subsequent assessment timepoints or followed by death attributable to cancer progression. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and quality of life (QoL), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
TTCD Assessed Using EORTC QLQ-C30 Score in the FAS Up to approximately 114 months TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS) and physical functioning from baseline that must be held for all subsequent assessment timepoints or followed by death attributable to cancer progression. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and quality of life (QoL), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the FAS 12, 24, 36 and 48 months Investigator-assessed Confirmed ORR in the PPAS From randomization up to approximately 114 months OS in the FAS From randomization to death from any cause (up to approximately 114 months) Investigator-assessed DOR in the PPAS From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months) Investigator-assessed PFS in the FAS Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months) IRF-assessed DOR in the FAS From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months) IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS 12, 18 and 24 months IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS 12, 18 and 24 months OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the PPAS 12, 24, 36 and 48 months Investigator-assessed Time to Death or Distant Metastasis (TTDM) in the PPAS From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months) Percentage of Participants With Adverse Events Up to approximately 114 months IRF-assessed Confirmed ORR in the FAS From randomization up to approximately 114 months Investigator-assessed Confirmed ORR in the FAS From randomization up to approximately 114 months Investigator-assessed DOR in the FAS From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months) Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS 12, 18 and 24 months Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS 12, 18 and 24 months Investigator-assessed TTDM in the FAS From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months)
Trial Locations
- Locations (178)
Clinique Clémentville
🇫🇷Montpellier, France
Hopital Robert Schuman
🇫🇷Vantoux, France
Ulsan University Hosiptal
🇰🇷Ulsan, Korea, Republic of
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
Amphia Ziekenhuis
🇳🇱Breda, Netherlands
Medisch Centrum Haaglanden, locatie Antoniushove
🇳🇱Leidschendam, Netherlands
Zuyderland Medisch Centrum - Sittard Geleen
🇳🇱Sittard-Geleen, Netherlands
Auckland City Hospital, Cancer and Blood Research
🇳🇿Auckland, New Zealand
Uniwersyteckie Centrum Kliniczne
🇵🇱Gda?sk, Poland
Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii
🇵🇱Olsztyn, Poland
Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
🇵🇱Otwock, Poland
Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
🇵🇱Warszawa, Poland
Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii
🇵🇱Wroc?aw, Poland
IPO de Coimbra
🇵🇹Coimbra, Portugal
Hospital da Luz
🇵🇹Lisboa, Portugal
Hospital CUF Porto
🇵🇹Porto, Portugal
IPO do Porto
🇵🇹Porto, Portugal
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Shandong Cancer Hospital
🇨🇳Jinan, China
Zhongda Hospital Affiliated to Southeast University
🇨🇳Nanjing, China
The affiliated hospital of Qingdao university
🇨🇳Qingdao City, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, China
Shanxi Provincial Cancer Hospital
🇨🇳Taiyuan, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
The 2nd School of Medicine, WMU
🇨🇳Wenzhou City, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
The Affiliated Hospital of Xuzhou Medical College
🇨🇳Xuzhou, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
CHU Angers
🇫🇷Angers, France
Centre Francois Baclesse
🇫🇷Caen, France
Hopital Nord AP-HM
🇫🇷Marseille, France
Hangzhou Cancer Hospital
🇨🇳Hangzhou City, China
Stanford University
🇺🇸Palo Alto, California, United States
Banner MD Anderson Cancer Center
🇺🇸Greeley, Colorado, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
Cancer Care Centers of Brevard
🇺🇸Palm Bay, Florida, United States
Woodlands Medical Specialists, P.A.
🇺🇸Pensacola, Florida, United States
Florida Cancer Specialist, North Region
🇺🇸Saint Petersburg, Florida, United States
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
New England Cancer Specialists
🇺🇸Brunswick, Maine, United States
Southcoast Health System
🇺🇸Fairhaven, Massachusetts, United States
Minnesota Oncology Hematology
🇺🇸Minneapolis, Minnesota, United States
HCA Midwest Health
🇺🇸Kansas City, Missouri, United States
Cox Health Systems
🇺🇸Springfield, Missouri, United States
Optum Health Care
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Titan Health Partners LLC, d/b/a Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
New York Oncology Hematology,P.C.-Albany
🇺🇸Albany, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Prisma Health ? Upstate
🇺🇸Greenville, South Carolina, United States
Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Sarah Cannon Research Institute / Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
CEMIC
🇦🇷Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Clinica Universitaria Reina Fabiola
🇦🇷Cordoba, Argentina
Sanatorio Parque S.A.
🇦🇷Rosario, Argentina
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Macarthur Cancer Therapy Centre
🇦🇺Campbelltown, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Fiona Stanley Hospital
🇦🇺Bull Creek, Western Australia, Australia
Monash Health Translational Precinct
🇦🇺Victoria, Australia
Tiroler Landeskrankenanstalten Ges.M.B.H.
🇦🇹Innsbruck, Austria
Kepler Universitätskliniken GmbH - Med Campus III
🇦🇹Linz, Austria
Klinik Penzing
🇦🇹Wien, Austria
GHdC Site Les Viviers
🇧🇪Charleroi, Belgium
AZ Maria Middelares
🇧🇪Gent, Belgium
Jessa Zkh (Campus Virga Jesse)
🇧🇪Hasselt, Belgium
Crio - Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Ceará, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Hospital de Base de Sao Jose do Rio Preto
🇧🇷Sao Jose do Rio Preto, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
BC Cancer ? Abbotsford
🇨🇦Abbotsford, British Columbia, Canada
BC Cancer - Victoria
🇨🇦Victoria, British Columbia, Canada
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
William Osler Health System Brampton Civic Hospital
🇨🇦Brampton, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Beijing Cancer Center
🇨🇳Beijing City, China
Beijing Chest Hospital
🇨🇳Beijing, China
Jilin Cancer Hospital
🇨🇳Changchun, China
Xiangya Hospital Central South University
🇨🇳Changsha City, China
Sichuan Provincial Cancer Hospital
🇨🇳Chengdu, China
Chongqing Cancer Hospital
🇨🇳Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fujian, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou City, China
Cancer Center, Sun Yat-sen University of Medical Sciences
🇨🇳Guangzhou, China
Institut Gustave Roussy
🇫🇷Villejuif cedex, France
Klinikum Braunschweig
🇩🇪Braunschweig, Germany
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Klinikum Koeln-Merheim
🇩🇪Köln, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
General Hospital "G.Papanikolaou"
🇬🇷Asvestochori, Greece
Sotiria Hospital
🇬🇷Athens, Greece
Agioi Anargyroi Cancer Hospital
🇬🇷Kifisia, Greece
Pamela Youde Nethersole Eastern Hospital
🇭🇰Hong Kong, Hong Kong
Princess Margaret Hospital, Oncology
🇭🇰Hong Kong, Hong Kong
Queen Elizabeth Hospital
🇭🇰Hong Kong, Hong Kong
Tuen Mun Hospital
🇭🇰Hong Kong, Hong Kong
Pécsi Tudományegyetem
🇭🇺Pécs, Hungary
Szent Borbala Korhaz
🇭🇺Tatabánya, Hungary
Tudogyogyintezet Torokbalint
🇭🇺Torokbalint, Hungary
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
🇮🇹Meldola, Emilia-Romagna, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Emilia-Romagna, Italy
Policlinico Universitario Campus Biomedico
🇮🇹Roma, Lazio, Italy
IRCCS Istituto Regina Elena (IFO)
🇮🇹Roma, Lazio, Italy
IRCCS AOU San Martino - IST
🇮🇹Genova, Liguria, Italy
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
🇮🇹Brescia, Lombardia, Italy
Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
🇮🇹Milano, Lombardia, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Lombardia, Italy
Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
🇮🇹Pisa, Toscana, Italy
Azienda ULSS 8 Berica
🇮🇹Vicenza, Veneto, Italy
Aichi Cancer Center
🇯🇵Aichi, Japan
National Cancer Center East
🇯🇵Chiba, Japan
National Hospital Organization Himeji Medical Center
🇯🇵Hyogo, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Sendai Kousei Hospital
🇯🇵Miyagi, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Saitama Cancer Center
🇯🇵Saitama, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
St. Vincent's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Pusan National University Yangsan Hospital
🇰🇷Gyeongsangnam-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Provincial de Castellon
🇪🇸Castellon de La Plana, Castellon, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸La Coruna, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Regional Universitario Carlos Haya
🇪🇸Malaga, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Vajira Hospital
🇹🇭Bangkok, Thailand
Rajavithi Hospital
🇹🇭Bangkok, Thailand
Ramathibodi Hospital;Medicine/Oncology
🇹🇭Bangkok, Thailand
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
Adana Baskent University Medical Faculty
🇹🇷Adana, Turkey
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷Ankara, Turkey
Gazi University Medical Faculty, Oncology Hospital
🇹🇷Ankara, Turkey
Ege University Medical Faculty
🇹🇷Bornova, ?zm?r, Turkey
Dicle University Faculty of Medicine
🇹🇷Diyarbakir, Turkey
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
🇹🇷Edirne, Turkey
Istanbul University Cerrahpasa Faculty of Medicine
🇹🇷Istanbul, Turkey
Medipol University Medical Faculty
🇹🇷Istanbul, Turkey
Inonu University Faculty of Medicine Turgut Ozal Medical Center
🇹🇷Malatya, Turkey
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Addenbrooke's NHS Trust
🇬🇧Cambridge, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Christie Foundation Trust
🇬🇧Manchester, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom