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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

— SKYSCRAPER-03  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04513925
• Other study ID #: GO41854
• Secondary ID: 2019-004773-29
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 24, 2020
• Est. completion date: December 30, 2027

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 829
• Est. completion date: December 30, 2027
• Est. primary completion date: October 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Atezolizumab
Atezolizumab 1680 mg every 4 weeks (Q4W) will be administered IV on Day 1 of each 28-day cycle.
• Tiragolumab
Tiragolumab 840 mg Q4W will be administered IV on Day 1 of each 28-day cycle.
• 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.

Locations

Country	Name	City	State
Argentina	Cemic; Oncologia Clinica	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires
Argentina	Clinica Universitaria Reina Fabiola	Cordoba
Argentina	Sanatorio Parque S.A.	Rosario
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit	Bull Creek	Western Australia
Australia	Macarthur Cancer Therapy Centre	Campbelltown	New South Wales
Australia	St George Hospital; Cancer Care Centre	Kogarah	New South Wales
Australia	Monash Health Translational Precinct; Clinical Trials Centre, Level 3	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie	Innsbruck
Austria	Kepler Universitätskliniken GmbH - Med Campus III; Abt. für Lungenkrankheiten	Linz
Austria	Klinik Penzing; Abteilung für Atemwegs- und Lungenkrankheiten	Wien
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	AZ Maria Middelares	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Centro Integrado de Oncologia de Curitiba	Curitiba	PR
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	BC Cancer ? Abbotsford	Abbotsford	British Columbia
Canada	Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials	Barrie	Ontario
Canada	William Osler Health System Brampton Civic Hospital	Brampton	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	BC Cancer - Victoria	Victoria	British Columbia
China	Beijing Chest Hospital; Oncology Department	Beijing
China	Beijing Cancer Center; Renal Cancer And Melanoma Department.	Beijing City
China	Jilin Cancer Hospital	Changchun
China	Xiangya Hospital Central South University	Changsha City
China	Changzhou Cancer hospital	Changzhou
China	Sichuan Provincial Cancer Hospital	Chengdu
China	Chongqing Cancer Hospital	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou City
China	Fujian Provincial Cancer Hospital	Fuzhou City
China	Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology	Guangzhou City
China	Hangzhou Cancer Hospital	Hangzhou City
China	Sir Run Run Shaw Hospital Zhejiang University	Hangzhou City
China	Shandong Cancer Hospital	Jinan
China	Zhongda Hospital Affiliated to Southeast University	Nanjing
China	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City
China	The affiliated hospital of Qingdao university	Qingdao City
China	Shanghai Chest Hospital	Shanghai
China	Shanghai Pulmonary 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	Hubei Cancer Hospital	Wuhan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou
China	Henan Cancer Hospital	Zhengzhou
France	CHU Angers	Angers
France	CENTRE FRANCOIS BACLESSE; Oncologie- Pneumologie	Caen
France	Hopital Nord AP-HM	Marseille
France	Clinique Clémentville	Montpellier
France	Hopital Robert Schuman; Pneumologie	Vantoux
France	Institut Gustave Roussy; Pathologie Thoracique	Villejuif cedex
Germany	Klinikum Braunschweig; Medizinische Klinik III; Klinik für Hämatologie und Onkologie	Braunschweig
Germany	Universitaetsmedizin Goettingen; Abteilung Haematologie und Onkologie	Göttingen
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Klinikum Koeln-Merheim; Lungenklinik	Köln
Germany	Klinikum Bogenhausen; Klinik für Pneumologie und Pneumologische Onkologie	München
Germany	Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie	Regensburg
Greece	General Hospital "G.Papanikolaou"; Pulmonogy Clinic	Asvestochori
Greece	Sotiria Hospital	Athens
Greece	Univ General Hosp Heraklion; Medical Oncology	Heraklion
Greece	Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.	Kifisia
Hong Kong	Pamela Youde Nethersole Eastern Hospital; Clinical Oncology	Hong Kong
Hong Kong	Princess Margaret Hospital, Oncology; Department of Oncology	Hong Kong
Hong Kong	Queen Elizabeth Hospital; Clinical Oncology	Hong Kong
Hong Kong	Tuen Mun Hospital; Clinical Onc	Hong Kong
Hong Kong	Queen Mary Hospital	Pokfulam
Hungary	Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet	Pécs
Hungary	Szent Borbala Korhaz	Tatabánya
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Israel	Soroka Medical Center; Oncology Dept	Beer Sheva
Israel	Rambam Medical Center; Oncology	Haifa
Israel	Shaare Zedek Medical Center; Oncology Dept	Jerusalem
Israel	Rabin Medical Center; Oncology Dept	Petah Tikva
Italy	A.O. Spedali Civili Di Brescia-P.O. Spedali Civili; U.O. Radioterapia	Brescia	Lombardia
Italy	IRCCS AOU San Martino - IST	Genova	Liguria
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)	Milano	Lombardia
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Azienda Ospedaliero Universitaria di Parma	Parma	Emilia-Romagna
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia	Lombardia
Italy	Azienda Ospedaliera Universitaria Pisana - Ospedale Cisanello; Dipartimento Cardio Toraco Vascolare	Pisa	Toscana
Italy	IRCCS Istituto Regina Elena (IFO); Oncologia Medica B	Roma	Lazio
Italy	Policlinico Universitario Campus Biomedico; U.O.C. di Radioterapia Oncologica	Roma	Lazio
Italy	Azienda ULSS 8 Berica; Oncologia Medica - Ospedlae di Vicenza	Vicenza	Veneto
Japan	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
Korea, Republic of	Chungbuk National University Hospital	Cheongju si
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Ajou University Medical Center	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 Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Ulsan University Hosiptal	Ulsan
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Medisch Centrum Haaglanden, locatie Antoniushove	Leidschendam
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
New Zealand	Auckland City Hospital, Cancer and Blood Research	Auckland
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdansk
Poland	Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii; ZAK?.I O.KLINICZNY RADIOTERAPII	Olsztyn
Poland	Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii	Otwock
Poland	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa
Poland	Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii; Oddz. Onkologii Klin. i Chemioterapii	Wroc?aw
Portugal	IPO de Coimbra; Servico de Oncologia Medica	Coimbra
Portugal	Hospital da Luz; Departamento de Oncologia Medica	Lisboa
Portugal	Hospital CUF Porto; Servico Pneumologia	Porto
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Taiwan	China Medical University Hospital; Pulmonary and Critical Care Medicine	Taichung
Taiwan	Taipei Veterans General Hospital; Chest Dept , Section of Thoracic Oncology	Taipei
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Ramathibodi Hospital; Medicine/Oncology; Clinical Research Center	Bangkok
Thailand	Vajira Hospital	Bangkok
Thailand	Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory	Songkhla
Turkey	Adana Baskent University Medical Faculty; Oncology	Adana
Turkey	Ankara University Medical Faculty; Medikal Onkoloji	Ankara
Turkey	Gazi University Medical Faculty, Oncology Hospital	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Ege University Medical Faculty; Medical Oncology Department	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; Oncology Department	Istanbul
Turkey	Inonu University Faculty of Medicine Turgut Ozal Medical Center; Onkoloji, Elazig Yolu,	Malatya
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Addenbrooke's NHS Trust	Cambridge
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Calderdale & Huddersfield Nhs Trust; Oncology	Huddersfield
United Kingdom	Leicester Royal Infirmary; Oncology Department	Leicester
United Kingdom	Maidstone & Tonbridge Wells Hospital; Kent Oncology Center	Maidstone
United Kingdom	Christie Foundation Trust	Manchester
United Kingdom	Weston Park Hospital	Sheffield
United States	New York Oncology Hematology,P.C.-Albany	Albany	New York
United States	Montefiore Medical Center	Bronx	New York
United States	New England Cancer Specialists	Brunswick	Maine
United States	Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Titan Health Partners LLC, d/b/a Astera Cancer Care	East Brunswick	New Jersey
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Southcoast Health System	Fairhaven	Massachusetts
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Florida Cancer Specialists; Department of Oncology	Fort Myers	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Prisma Health ? Upstate	Greenville	South Carolina
United States	Genesis Cancer and Blood Institute	Hot Springs	Arkansas
United States	HCA Midwest Health	Kansas City	Missouri
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Optum Health Care	Las Vegas	Nevada
United States	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Stanford University	Palo Alto	California
United States	Woodlands Medical Specialists, P.A.	Pensacola	Florida
United States	Illinois Cancer Care	Peoria	Illinois
United States	Cancer Care Centers of Brevard	Rockledge	Florida
United States	Minnesota Oncology Hematology	Saint Paul	Minnesota
United States	Florida Cancer Specialist, North Region	Saint Petersburg	Florida
United States	Cox Health Systems	Springfield	Missouri
United States	Arizona Clinical Research Center, Inc	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Portugal,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Overall Survival (OS) in the PPAS		From randomization to death from any cause (up to approximately 114 months)
Secondary	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)
Secondary	IRF-assessed Confirmed Objective Response Rate (ORR) in the PPAS		From randomization up to approximately 114 months
Secondary	Investigator-assessed Confirmed ORR in the PPAS		From randomization up to approximately 114 months
Secondary	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)
Secondary	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)
Secondary	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	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.	Up to approximately 114 months
Secondary	OS in the FAS		From randomization to death from any cause (up to approximately 114 months)
Secondary	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)
Secondary	IRF-assessed Confirmed ORR in the FAS		From randomization up to approximately 114 months
Secondary	Investigator-assessed Confirmed ORR in the FAS		From randomization up to approximately 114 months
Secondary	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)
Secondary	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)
Secondary	TTCD Assessed Using EORTC QLQ-C30 Score in the FAS	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.	Up to approximately 114 months
Secondary	IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS		12, 18 and 24 months
Secondary	IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS		12, 18 and 24 months
Secondary	Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS		12, 18 and 24 months
Secondary	Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS		12, 18 and 24 months
Secondary	OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the PPAS		12, 24, 36 and 48 months
Secondary	OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the FAS		12, 24, 36 and 48 months
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants With Adverse Events		Up to approximately 114 months