A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC) (SKYSCRAPER-03)

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

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Atezolizumab; Drug: Tiragolumab; Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Actual): 829
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1431FWO
    • Cemic
  • Ciudad Autonoma Buenos Aires, Argentina, C1284AEB
    • Hospital Britanico de Buenos Aires
  • Córdoba, Argentina, X5004FHP
    • Clinica Universitaria Reina Fabiola
  • Rosario, Argentina, S2000QGB
    • Sanatorio Parque S.A.
• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Campbelltown, New South Wales, Australia, 2560
      • Macarthur Cancer Therapy Centre
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Victoria, Victoria, Australia, 3168
      • Monash Health Translational Precinct
  • Western Australia
    • Bull Creek, Western Australia, Australia, 6149
      • Fiona Stanley Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Tiroler Landeskrankenanstalten Ges.M.B.H.
  • Linz, Austria, 4020
    • Kepler Universitätskliniken GmbH - Med Campus III
  • Vienna, Austria, 1140
    • Klinik Penzing
• Belgium
  • Charleroi, Belgium, 6000
    • GHdC Site Les Viviers
  • Ghent, Belgium, 9000
    • AZ Maria Middelares
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
• Brazil
  • Ceará
    • Fortaleza, Ceará, Brazil, 60336-550
      • Crio - Centro Regional Integrado de Oncologia
  • Paraná
    • Curitiba, Paraná, Brazil, 80810-050
      • Centro Integrado de Oncologia de Curitiba
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Câncer do Estado de São Paulo - ICESP
• Canada
  • British Columbia
    • Abbotsford British Columbia, British Columbia, Canada, V2S 0C2
      • BC Cancer ? Abbotsford
    • Victoria, British Columbia, Canada, V8R 6V5
      • BC Cancer - Victoria
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System Brampton Civic Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
• China
  • Beijing, China, 101149
    • Beijing Chest Hospital
  • Beijing, China, 100142
    • Beijing Cancer Center
  • Changchun, China, 132013
    • Jilin Cancer Hospital
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Chengdu, China, 610041
    • Sichuan Provincial Cancer Hospital
  • Chongqing, China, 400030
    • Chongqing Cancer Hospital
  • Fujian, China, 350001
    • Fujian Medical University Union Hospital
  • Fuzhou, China, 350014
    • Fujian Provincial Cancer Hospital
  • Guangzhou, China, 510060
    • Cancer Center, Sun Yat-sen University of Medical Sciences
  • Hangzhou, China, 310002
    • Hangzhou Cancer Hospital
  • Jinan, China, 250117
    • Shandong Cancer Hospital
  • Nanjing, China, 210009
    • Zhongda Hospital Affiliated to Southeast University
  • Qingdao, China, 266042
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China, 200000
    • Shanghai Chest Hospital
  • Shantou, China, 515041
    • Cancer Hospital of Shantou University Medical College
  • Taiyuan, China, 030013
    • Shanxi Provincial Cancer Hospital
  • Tianjin, China, 300060
    • Tianjin Cancer Hospital
  • Wenzhou, China, 325000
    • The 2nd School of Medicine, WMU
  • Xiamen, China, 361003
    • The First Affiliated Hospital of Xiamen University
  • Xuzhou, China, 221000
    • The Affiliated Hospital of Xuzhou Medical College
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• France
  • Angers, France, 49933
    • CHU Angers
  • Caen, France, 14000
    • Centre Francois Baclesse
  • Marseille, France, 13015
    • Hopital Nord AP-HM
  • Montpellier, France, 34070
    • Clinique Clémentville
  • Vantoux, France, 57070
    • Hopital Robert Schuman
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Braunschweig, Germany, 38114
    • Klinikum Braunschweig
  • Cologne, Germany, 51109
    • Klinikum Koeln-Merheim
  • Göttingen, Germany, 37075
    • Universitaetsmedizin Goettingen
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • München, Germany, 81925
    • Klinikum Bogenhausen
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
• Greece
  • Asvestochóri, Greece, 570 10
    • General Hospital "G.Papanikolaou"
  • Athens, Greece, 11527
    • Sotiria Hospital
  • Kifissia, Greece, 145 64
    • Agioi Anargyroi Cancer Hospital
• Hong Kong
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital
  • Hong Kong, Hong Kong, DUMMY_VALUE
    • Queen Elizabeth Hospital
  • Hong Kong, Hong Kong, DUMMY_VALUE
    • Princess Margaret Hospital, Oncology
  • Pokfulam, Hong Kong, DUMMY_VALUE
    • Queen Mary Hospital
• Hungary
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem
  • Tatabánya, Hungary, 2800
    • Szent Borbala Korhaz
  • Törökbálint, Hungary, 2045
    • Tudogyogyintezet Torokbalint
• Israel
  • Beersheba, Israel, 8410100
    • Soroka Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
    • Parma, Emilia-Romagna, Italy, 43100
      • Azienda Ospedaliero Universitaria di Parma
  • Lazio
    • Rome, Lazio, Italy, 00128
      • Policlinico Universitario Campus Biomedico
    • Rome, Lazio, Italy, 00144
      • IRCCS Istituto Regina Elena (IFO)
  • Liguria
    • Genoa, Liguria, Italy, 16132
      • IRCCS AOU San Martino - IST
  • Lombardy
    • Brescia, Lombardy, Italy, 25123
      • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
    • Milan, Lombardy, Italy, DUMMY_VALUE
      • Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
    • Pavia, Lombardy, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo
  • Tuscany
    • Pisa, Tuscany, Italy, 56124
      • Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello
  • Veneto
    • Vicenza, Veneto, Italy, 36100
      • Azienda ULSS 8 Berica
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center
  • Chiba, Japan, 277-8577
    • National Cancer Center East
  • Hyōgo, Japan, 670-8520
    • National Hospital Organization Himeji Medical Center
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Miyagi, Japan, 981-0914
    • Sendai Kousei Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital
• Netherlands
  • Amersfoort, Netherlands, 3813 TZ
    • Meander Medisch Centrum
  • Breda, Netherlands, 4819 EV
    • Amphia Ziekenhuis
  • Leidschendam, Netherlands, 2262 BA
    • Medisch Centrum Haaglanden, locatie Antoniushove
  • Sittard-Geleen, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum - Sittard Geleen
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
• Poland
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Olsztyn, Poland, 10-228
    • Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii
  • Otwock, Poland, 05-400
    • Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
  • Warsaw, Poland, 02-781
    • Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
  • Wroc?aw, Poland, 53-413
    • Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii
• Portugal
  • Coimbra, Portugal, 3000-075
    • IPO de Coimbra
  • Lisbon, Portugal, 1500-650
    • Hospital da Luz
  • Porto, Portugal, 4100-180
    • Hospital CUF Porto
  • Porto, Portugal, 4200-072
    • IPO do Porto
• South Korea
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, South Korea, 16247
    • St. Vincent's Hospital
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Gyeonggi-do, South Korea, 16499
    • Ajou University Medical Center
  • Gyeongsangnam-do, South Korea, 50612
    • Pusan National University Yangsan Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Jeollanam-do, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 08308
    • Korea University Guro Hospital
  • Seoul, South Korea, 06591
    • Seoul St Mary's Hospital
  • Ulsan, South Korea, 44033
    • Ulsan University Hosiptal
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña (CHUAC)
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall D'Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Málaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41014
    • Hospital Univ. Nuestra Señora de Valme
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 07198
      • Hospital Son Llatzer
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • Castellon
    • Castellon, Castellon, Spain, 12002
      • Hospital Provincial de Castellon
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital
  • Bangkok, Thailand, 10300
    • Vajira Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital;Medicine/Oncology
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01220
    • Adana Baskent University Medical Faculty
  • Ankara, Turkey (Türkiye), 06500
    • Gazi University Medical Faculty, Oncology Hospital
  • Ankara, Turkey (Türkiye), 06100
    • Ankara University Medical Faculty
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe Universitesi Tip Fakultesi Hastanesi
  • Bornova, ?zm?r, Turkey (Türkiye), 35100
    • Ege University Medical Faculty
  • Diyarbakır, Turkey (Türkiye), 21280
    • Dicle University Faculty of Medicine
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul University Cerrahpaşa Faculty of Medicine
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol University Medical Faculty
  • Malatya, Turkey (Türkiye), 44280
    • Inonu University Faculty of Medicine Turgut Ozal Medical Center
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's NHS Trust
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Huddersfield, United Kingdom, HD3 3EA
    • Calderdale & Huddersfield Nhs Trust
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Maidstone, United Kingdom, ME16 9QQ
    • Maidstone & Tonbridge Wells Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Foundation Trust
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University
  • Colorado
    • Greeley, Colorado, United States, 80631
      • Banner MD Anderson Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901-8101
      • Florida Cancer Specialists
    • Palm Bay, Florida, United States, 32901
      • Cancer Care Centers of Brevard
    • Pensacola, Florida, United States, 32503
      • Woodlands Medical Specialists, P.A.
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist, North Region
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers PC - Marietta
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care
  • Maine
    • Brunswick, Maine, United States, 04011
      • New England Cancer Specialists
  • Massachusetts
    • Fairhaven, Massachusetts, United States, 02719
      • Southcoast Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Health
    • Springfield, Missouri, United States, 65807
      • Cox Health Systems
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89106
      • Optum Health Care
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Titan Health Partners LLC, d/b/a Astera Cancer Care
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology,P.C.-Albany
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health ? Upstate
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab + 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.	Drug: Atezolizumab; Atezolizumab 1680 mg every 4 weeks (Q4W) will be administered IV on Day 1 of each 28-day cycle.; Other Names: Tecentriq; RO5541267; Drug: Tiragolumab; Tiragolumab 840 mg Q4W will be administered IV on Day 1 of each 28-day cycle.; Other Names: MTIG7192A; RO7092284
Active Comparator: Durvalumab; Participants will receive durvalumab administered IV during each 28-day cycle for a maximum of 13 cycles.	Drug: Durvalumab; Durvalumab will be administered based on weight at 10 mg/kg IV every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle, or will be administered at a fixed dose of 1500 mg IV every 4 weeks (Q4W) (for participants whose weight >/= 30 kg) on Day 1 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS), as Assessed by an Independent Review Facility (IRF) in Programmed Death-ligand 1 (PD-L1) Positive Analysis Set (PPAS)	PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm) or unequivocal progression of existing non-target lesions. Kaplan-Meier (K-M) method was used to estimate median PFS.	From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
PFS, as Assessed by an IRF in FAS	PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.	From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in PPAS	OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS.	From randomization to death from any cause (up to approximately 57 months)
PFS, as Assessed by the Investigator in PPAS	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.	From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Confirmed Objective Response Rate (ORR), as Assessed by an IRF in PPAS	ORR was defined as the percentage of participants who achieved an objective response (OR), characterized by a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by an IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesion & normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.	Up to approximately 57 months
Confirmed ORR, as Assessed by the Investigator in PPAS	ORR was defined as the percentage of participants who achieved an OR, characterized by CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions & normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.	Up to approximately 57 months
Duration of Response (DOR), as Assessed by an IRF in PPAS	DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions & normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.	From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
DOR, as Assessed by the Investigator in PPAS	DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.	From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Time to Confirmed Deterioration (TTCD) in Cough, as Assessed Using European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) in PPAS	TTCD=time from randomization until first confirmed clinically meaningful deterioration (CCMD) on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Cough scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in Dyspnoea, as Assessed Using EORTC QLQ-LC13 in PPAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Dyspnoea was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in Chest Pain, as Assessed Using EORTC QLQ-LC13 in PPAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Chest pain was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in Global Health Status (GHS)/Quality-of-life (QoL), as Assessed Using European Organisation for Research and Treatment of Cancer Quality-of-life Core-30 (EORTC QLQ-C30) in PPAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, & social), 3 symptom scales (fatigue, nausea, vomiting, & pain), GHS/QoL, & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). GHS/QoL questions were scored on 7-point scale with scores ranging from 1=Very poor to 7=Excellent. Scores were linearly transformed to a score range of 0-100. High score for GHS/QoL scale=better health-related quality-of-life (HRQoL). CCMD=decrease from baseline (≥10 points) in GHS/QoL scale score, held for at least 2 consecutive assessments/initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in Physical Functioning (PF), as Assessed Using EORTC QLQ-C30 in PPAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, & social), 3 symptom scales (fatigue, nausea, vomiting, & pain), GHS/QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). PF was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a score range of 0-100. High score for PF=high/healthy level of functioning. CCMD=decrease from baseline (≥10 points) in PF score, held for at least 2 consecutive assessments or initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
OS in FAS	OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS.	From randomization to death from any cause (up to approximately 57 months)
PFS, as Assessed by the Investigator in FAS	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.	From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Confirmed ORR, as Assessed by an IRF in FAS	ORR was defined as the percentage of participants who achieved an OR, characterized by CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by an IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.	Up to approximately 57 months
Confirmed ORR, as Assessed by the Investigator in FAS	ORR was defined as the percentage of participants who achieved an OR, characterized by a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.	Up to approximately 57 months
DOR, as Assessed by an IRF in FAS	DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.	From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
DOR, as Assessed by the Investigator in FAS	DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.	From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
TTCD in Cough, as Assessed Using EORTC QLQ-LC13 in FAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Cough was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in Dyspnoea, as Assessed Using EORTC QLQ-LC13 in FAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Dyspnoea was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in Chest Pain, as Assessed Using EORTC QLQ-LC13 in FAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Chest pain was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in GHS/QoL, as Assessed Using EORTC QLQ-C30 in FAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, & social), 3 symptom scales (fatigue, nausea, vomiting, & pain), GHS/QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). GHS/QoL questions were scored on 7-point scale with scores ranging from 1=Very poor to 7=Excellent. Scores were linearly transformed to a score range of 0-100. High score for GHS/QoL scale=better HRQoL. CCMD=decrease from baseline (≥10 points) in GHS/QoL scale score, held for at least 2 consecutive assessments or initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
TTCD in PF, as Assessed Using EORTC QLQ-C30 in FAS	TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, & social), 3 symptom scales (fatigue, nausea, vomiting, & pain), GHS/QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). PF was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a score range of 0-100. High score for PF=high/healthy level of functioning. CCMD=decrease from baseline (≥10 points) in PF score, held for at least 2 consecutive assessments or initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.	Up to approximately 57 months
PFS Rate at 12, 18, and 24 Months, as Assessed by an IRF in PPAS	PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by an IRF, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS rate. Percentages have been rounded off.	At Months 12, 18, and 24
PFS Rate at 12, 18, and 24 Months, as Assessed by the Investigator in PPAS	PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS rate. Percentages have been rounded off.	At Months 12, 18, and 24
OS Rate at 12, 24, 36, and 48 Months in PPAS	OS rate at months 12, 24, 36 and 48 was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off.	At Months 12, 24, 36, and 48
Time-to-distant Metastasis (TTDM), as Assessed by the Investigator in PPAS	TTDM was defined as the time from the date of randomization until the date of first documented distant metastasis, as assessed by investigator according to RECIST v1.1, or death, whichever occurred first. Distant metastasis was defined as any new lesion that was outside of the radiation field. K-M method was used to estimate median TTDM.	Up to approximately 57 months
PFS Rate at 12, 18, and 24 Months, as Assessed by an IRF in FAS	PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by an IRF, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate PFS rate. Percentages have been rounded off.	At Months 12, 18, and 24
PFS Rate at 12, 18, and 24 Months, as Assessed by the Investigator in FAS	PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate PFS rate. Percentages have been rounded off.	At Months 12, 18, and 24
OS Rate at 12, 24, 36, and 48 Months in FAS	OS rate at months 12, 24, 36 and 48 was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off.	At Months 12, 24, 36, and 48
TTDM, as Assessed by the Investigator in FAS	TTDM was defined as the time from the date of randomization until the date of first documented distant metastasis, as assessed by investigator according to RECIST v1.1, or death, whichever occurred first. Distant metastasis was defined as any new lesion that was outside of the radiation field. K-M method was used to estimate median TTDM.	Up to approximately 57 months
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product.	Up to approximately 24.7 months
Number of Participants With Cytokine Release Syndrome (CRS)	CRS=supraphysiologic response following administration of any immune therapy that results in activation/engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms may be progressive, including fever at onset, and may also include hypotension, capillary leak (hypoxia), and end-organ dysfunction.	Up to approximately 24.7 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Actual): May 27, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; durvalumab; atezolizumab; Tiragolumab
• Other Study ID Numbers: GO41854; 2019-004773-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No