A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer

Triple Negative Breast Neoplasms Clinical Trial

— IMpassion132  

Official title:

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03371017
• Other study ID #: MO39193
• Secondary ID: 2016-005119-42
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 11, 2018
• Est. completion date: June 30, 2024

Study information

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

Clinical Trial Summary

This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 572
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic

• Documented disease progression occurring within 12 months from the last treatment with curative intent

• Prior treatment (of early breast cancer) with an anthracycline and taxane

• Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted

• Measurable or non-measurable disease, as defined by RECIST 1.1

• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.

• Eastern Cooperative Oncology Group performance status 0-1

• Life expectancy = 12 weeks

• Adequate haematologic and end-organ function

• Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening

• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening

• The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.

• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.

• Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of =1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.

• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

Exclusion Criteria:

• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomisation

• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.

• Symptomatic or rapid visceral progression

• No prior treatment with an anthracycline and taxane

• History of leptomeningeal disease

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)

• Uncontrolled tumour-related pain

• Uncontrolled or symptomatic hypercalcemia

• Malignancies other than TNBC within 5 years prior to randomisation)

• Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina

• Presence of an abnormal ECG

• Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.

• Current treatment with anti-viral therapy for HBV.

• Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis

• Treatment with investigational therapy within 28 days prior to randomisation

• Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.

Exclusion Criteria Related to Atezolizumab:

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins

• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation

• History of autoimmune disease

• Prior allogeneic stem cell or solid organ transplantation

• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

• Active tuberculosis

• Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo

• Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents

• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation

• Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

Exclusion Criteria Related to Capecitabine:

• Inability to swallow pills

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis

• Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine

Exclusion Criteria Related to Carboplatin/Gemcitabine:

-Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered, 1200 mg by IV infusion with : gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle
• Placebo
Placebo will be administered, 1200 mg by IV infusion with : gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle
• Gemcitabine
Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle
• Capecitabine
Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle
• Carboplatin
Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Hospital Provincial del Centenario	Rosario
Argentina	Instituto de Oncología de Rosario	Rosario
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Clinical center University of Sarajevo	Sarajevo
Brazil	Centro de Oncologia de Santa Catarina LTDA	Chapeco	SC
Brazil	Oncocentro Serviços Medicos E Hospitalares Ltda	Fortaleza	CE
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Hospital Sao Vicente de Paulo	Passo Fundo	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital do Cancer de Pernambuco - HCP	Recife	PE
Brazil	Hospital Perola Byington	Sao Paulo	SP
Brazil	Instituto de Pesquisa Grupo NotreDame Intermedica	Sao Paulo	SP
Brazil	Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA	Sao Paulo	SP
Chile	Patagonia Research	Puerto Montt
Chile	Bradford Hill Centro de Investigaciones Clinicas	Recoleta
Chile	Clinica Vespucio	Santiago
Chile	Fundacion Arturo Lopez Perez	Santiago
Chile	James Lind Centro de Investigación Del Cáncer	Temuco
Chile	ONCOCENTRO APYS; Oncología	Vina Del Mar
China	Beijing Cancer Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	Cancer Hospital , Chinese Academy of Medical	Beijing City
China	the First Affiliated Hospital of Bengbu Medical College	Bengbu City
China	Jilin Cancer Hospital	Changchun
China	Hunan Cancer Hospital	Changsha CITY
China	The First Affiliated Hospital, Chongqing Medical University	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou City
China	Sun Yat-sen Memorial Hospital	Guangzhou
China	Sir Run Run Shaw Hospital Zhejiang University	Hangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Shandong Cancer Hospital	Jinan
China	The First Affiliated Hospital Of Jinzhou Medical University	Jinzhou City
China	Jiangsu Province Hospital	Nanjing
China	The Affiliated Hospital of Medical College Qingdao University	Qingdao
China	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City
China	Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)	Shijiazhuang
China	Shanxi Province Cancer Hospital	Taiyuan City
China	Tianjin Cancer Hospital	Tianjin
China	The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)	Xi'an
China	Zhejiang Cancer Hospital	Zhejiang
Cuba	Hospital Hermanos Ameijeiras	La Habana
Cuba	Instituto Nacional de Oncología y Radiología (INOR)	La Habana
Finland	Helsinki University Central Hospital; Dept of Oncology	Helsinki
Finland	Tampere University Hospital; Dept of Oncology	Tampere
France	Centre Georges-François Lecler; Ctr de Lutte Contre le Canc	Dijon
France	Centre Leon Berard; Oncologie Genetique	Lyon
France	Institut Paoli-Calmettes; Oncologie Medicale 1	Marseille Cedex 09
France	Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque	Montpellier
France	Centre Eugene Marquis; Service d'oncologie	Rennes
France	INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.	St Cloud
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy
France	IGR	Villejuif
Germany	Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe	Dresden
Germany	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen
Germany	Varisano Klinikum Frankfurt Höchst GmbH	Frankfurt
Germany	Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie	Halle
Germany	Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe	Hannover
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	Medizinisches Zentrum für Hämatologie und Onkologie	München
Hungary	Budapesti Uzsoki Utcai Kórház	Budapest
Hungary	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest
Hungary	Szent Margit Hospital	Budapest
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez	Miskolc
Hungary	Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet	Pécs
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico	Candiolo	Piemonte
Italy	Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia	Firenze	Toscana
Italy	Azienda Ospedaliero Universitaria San Martino	Genova	Liguria
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica	Milano	Lombardia
Italy	Ospedale San Raffaele S.r.l.	Milano	Lombardia
Italy	Ospedale San Gerardo	Monza	Lombardia
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Kazakhstan	Kazakh Scientific Research Institution Of Oncology and Radiology	Almaty
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Centro Medico Dalinde	Cdmx	Mexico CITY (federal District)
Mexico	CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO	Mexico City
Mexico	Instituto Nacional de Cancerologia; Oncology	Mexico City
Montenegro	Clinical Center of Montenegro; Clinic for Oncology and Radiotherapy	Podgorica
Morocco	Centre Hospitalier Universitaire Hassan II	FES
Morocco	Centre Hospitalier Universitaire Mohamed VI; Oncologie-Hématologie	Marrakech
Morocco	Clinique specialise Menara; Oncology Medical	Marrakech
Morocco	Institut National D'oncologie Sidi Med Benabdellah	Rabat
Panama	The Panama Clinic	Panama
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Poland	?wi?tokrzyskie Centrum Onkologii; Dzia? Chemioterapii	Kielce
Poland	Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr	Warszawa
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia	Porto
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	FSBI "National Medical Research Center of Oncology N.N. Blokhin?	Moscow	Moskovskaja Oblast
Russian Federation	Moscow Clinical Scientific Center	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Oncology Dispensary, SPb SBIH CCOD	Saint-Petersburg	Sankt Petersburg
Russian Federation	FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"	Saint-Petersburg	Sankt Petersburg
Russian Federation	Private Healthcare Institution Clinical Hospital RZhD Medicine	St. Petersburg	Sankt Petersburg
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Serbia	University Hospital Medical Center Bezanijska kosa	Belgrade
Serbia	Clinical Centre Nis, Clinic for Oncology	Nis
Serbia	Oncology Institute of Vojvodina	Sremska Kamenica
Singapore	National Cancer Centre; Medical Oncology	Singapore
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
South Africa	Wits Clinical Research; Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg
South Africa	Private Oncology Centre	Pretoria
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
Turkey	Ankara Oncology Hospital; Medical Oncology Department	Ankara
Turkey	Hacettepe University Medical Faculty; Department of Internal Medicine	Ankara
Turkey	Ege University Medical Faculty; Medical Oncology Department	Bornova, ?zm?r
Turkey	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne
Turkey	Marmara University Pendik Training and Research Hospital; Medikal Onkoloji	Istanbul
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases	Konya
United Kingdom	Velindre Cancer Centre; Oncology Dept	Cardiff
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Western General Hospital; Edinburgh Cancer Center	Edinburgh
United Kingdom	Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust	Lancaster
United Kingdom	Barts	London
United Kingdom	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London
United Kingdom	Christie Hospital NHS Trust	Manchester
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent
United States	Inova Schar Cancer Institute	Falls Church	Virginia
United States	Florida Cancer Specialists - Fort Myers (Broadway)	Fort Myers	Florida
United States	Magee-Woman's Hospital; UPMC Pinnacle Cancer Center	Harrisburg	Pennsylvania
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	The Valley Hospital	Paramus	New Jersey
United States	Magee-Woman's Hospital	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists & Research Institute	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Bosnia and Herzegovina,  Brazil,  Chile,  China,  Cuba,  Finland,  France,  Germany,  Hungary,  Italy,  Kazakhstan,  Korea, Republic of,  Mexico,  Montenegro,  Morocco,  Panama,  Peru,  Poland,  Portugal,  Russian Federation,  Serbia,  Singapore,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Primary	Overall Survival (OS) in Modified Intent-To-Treat (mITT) Popluation	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Secondary	Proportion of Participants Alive 12 Months		Randomization to 12 months post randomization
Secondary	Proportion of Participants Alive 18 Months		Randomization to 18 months post randomization
Secondary	Progression-Free Survival (PFS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Secondary	Progression-Free Survival (PFS) in mITT population	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Secondary	Objective Response Rate (ORR) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Secondary	Objective Response Rate (ORR) in Modified Intent-To-Treat (mITT) Popluation	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Secondary	Duration of Objective Response (DoR)	DoR as determined by the investigator according to RECIST 1.1.	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.	8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)
Secondary	Confirmed Objective Response Rate (C-ORR)		Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Secondary	Duration of Response for Confirmed Responders (C-DoR)		Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Secondary	Time to Confirmed Deterioration (TTD) of GHS/QoL	TTD of GHS/QoL, defined by a minimally important decrease of =10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.	Baseline to end of study (approximately 58 months)
Secondary	Percentage of Participants With Adverse Events		Baseline to end of study (approximately 58 months)
Secondary	Maximum Serum Concentration (Cmax) of Atezolizumab		At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
Secondary	Minimum Serum Concentration (Cmin) of Atezolizumab		At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
Secondary	Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab		Baseline to end of study (approximately 58 months)
Secondary	Relationship Between PD-L1 Protein Expression in Screening Tumour Tissue and Clinical Outcomes		Baseline to end of study (approximately 58 months)
Secondary	Overall Survival (OS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Secondary	Overall Survival (OS) in mITT China Popluation	OS will be tested hierarchically in the following fixed order: In the population with programmed deathligand 1 (PD-L1)-positive tumour status; In the modified intent-to-treat (mITT) population	Baseline to end of study (approximately 58 months)
Secondary	Proportion of Participants Alive 12 Months in China Population		Randomization to 12 months post randomization
Secondary	Proportion of Participants Alive 18 Months in China Population		Randomization to 18 months post randomization
Secondary	Progression Free Survival (PFS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Secondary	Progression Free Survival (PFS) in mITT China Population	PFS defined as the time from randomisation to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death from any cause, whichever occurs first.; PFS will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
Secondary	Objective Response Rate (ORR) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Secondary	ORR in Modified Intent-To-Treat (mITT) China Popluation	ORR defined as the proportion of patients with an objective response, defined as a complete response (CR) or a partial response (PR), as determined by the investigator according to RECIST 1.1. ORR will be tested hierarchically in the following fixed order: In the PD-L1-positive population; In the mITT population	Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Secondary	Duration of Objective Response (DoR) in China Population	DoR as determined by the investigator according to RECIST 1.1.	Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Secondary	Clinical Benefit Rate (CBR) in China Population	CBR is defined as the proportion of participants with a CR or a PR or stable disease as determined by the investigator according to RECIST 1.1.	8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)
Secondary	Confirmed Objective Response Rate (C-ORR) in China Population		Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
Secondary	Duration of Response for Confirmed Responders (C-DoR) in China Population		Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
Secondary	Time to Confirmed Deterioration (TTD) of GHS/QoL in China Population	TTD of GHS/QoL, defined by a minimally important decrease of =10 points at two consecutive assessment time-points on the GHS/QoL scale (Items 29, 30) of the EORTC QLQ-C30.	Baseline to end of study (approximately 58 months)