A Study of Atezolizumab (MPDL3280A) Compared With a Platinum Agent (Cisplatin or Carboplatin) + (Pemetrexed or Gemcitabine) in Participants With Stage IV Non-Squamous or Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower110]

Non-Squamous Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase III, Open Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With a Platinum Agent (Cisplatin or Carboplatin) in Combination With Either Pemetrexed or Gemcitabine for PD-L1-Selected, Chemotherapy-Naive Patients With Stage IV Non-Squamous Or Squamous Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02409342
• Other study ID #: GO29431
• Secondary ID: 2014-003083-21
• Status: Completed
• Phase: Phase 3
• Start date: July 20, 2015
• Est. completion date: March 8, 2022

Study information

• Verified date: February 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, open-label study will evaluate the efficacy and safety of atezolizumab compared with chemotherapy consisting of a platinum agent (cisplatin or carboplatin per investigator discretion) combined with either pemetrexed (non-squamous disease) or gemcitabine (squamous disease) in programmed death-ligand 1 (PD-L1)-selected, chemotherapy-naive participants with Stage IV Non-Squamous or Squamous NSCLC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 572
• Est. completion date: March 8, 2022
• Est. primary completion date: February 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed, Stage IV non-squamous or squamous NSCLC
• No prior treatment for Stage IV non-squamous or squamous NSCLC. Participant known to have a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded from the study
• Tumor PD-L1 expression as determined by immunohistochemistry (IHC) assay of archival tumor tissue or tissue obtained at screening
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
• Adequate hematologic and end-organ function

Exclusion Criteria:

• Known sensitizing mutation in the EGFR gene or ALK fusion oncogene
• Active or untreated central nervous system (CNS) metastases as determined by Computed Tomography (CT) or magnetic resonance imaging (MRI) evaluation
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Pregnant or lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Positive test for Human Immunodeficiency Virus (HIV)
• Active hepatitis B or hepatitis C
• Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti PD1, and anti-PD-L1 therapeutic antibody
• Severe infection within 4 weeks prior to randomization
• Significant history of cardiovascular disease

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Squamous Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab (MPDL3280A) [TECENTRIQ], an engineered anti-PDL1 antibody
Atezolizumab 1200 milligram (mg) will be administered as intravenous infusion every 21 days until loss of clinical benefit (as assessed by the investigator), unacceptable toxicity, or death (maximum up to approximately 58 months).
• Carboplatin
Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) 6 when given in combination with pemetrexed or at a dose of AUC 5 when given in combination with gemcitabine, every 21 days for 4 or 6 cycles as per local standard of care.
• Cisplatin
Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (mg/m^2) every 21 days for 4 or 6 cycles as per local standard of care.
• Gemcitabine
Gemcitabine will be administered as intravenous infusion at a dose of 1250 mg/m^2 (in combination with cisplatin) or 1000 mg/m^2 (in combination with carboplatin), on Days 1 and 8 of each 21-day cycle for 4 or 6 cycles as per local standard of care.
• Pemetrexed
Pemetrexed will be administered as intravenous infusion at a dose of 500 mg/m^2 on Day 1 of each 21-day cycle as per local standard of care until disease progression (per RECIST v1.1), unacceptable toxicity, or death (maximum up to approximately 58 months).

Locations

Country	Name	City	State
Brazil	*X*Fundacao PIO XII	Barretos	SP
Brazil	Centro de Pesquisas Clinicas em Oncologia - CPCO	Cachoeiro de Itapemirim	ES
Brazil	Associacao Hospital de Caridade Ijui*X; Departamento De Oncologia	Ijui	RS
Brazil	Instituto Joinvilense de Hematologia E Oncologia	Joinville	SC
Brazil	Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia	Passo Fundo	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ
Brazil	Oncovida*X	Salvador	BA
Brazil	Hospital Santa Marcelina	Sao Paulo	SP
Brazil	Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira	São Paulo	SP
China	Harbin Medical University Tumor Hospital	Harbin City
France	CHU Angers	Angers
France	Hospital d Instructions des Armees Percy	Clamart
France	Hôpital Universitaire Dupuytren	Limoges
France	Clinique Clémentville	Montpellier
France	Centre D'oncologie de Gentilly	Nancy
France	Hopital Tenon	Paris
France	Centre Hospitalier Regional La Reunion Site Felix Guyon	Saint Denis Cedex
France	Hopital d'Instruction des Armees de Begin	Saint-Mande
France	Centre Hospitalier Regional Sud Reunion	Saint-pierre
France	Centre Paul Strauss	Strasbourg
Germany	Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie	Gauting
Germany	Pius-Hospital Oldenburg	Oldenburg
Greece	IASO General Hospital of Athens	Athens
Greece	Metropolitan Hospital	Athens
Greece	Sotiria Chest Hospital of Athens	Athens
Greece	Attikon University General Hospital	Chaidari
Greece	University General Hospital of Larissa	Larissa
Greece	University General Hospital of Patras	Patras
Greece	Thermi Clinic	Thermi, Thessaloniki
Greece	Bioclinic Thessaloniki	Thessaloniki
Greece	EUROMEDICA General Clinic of Thessaloniki; Gastroenterology Department	Thessaloniki
Greece	Georgios Papanikolaou General Hosp. of Thessaloniki	Thessaloniki
Greece	Papageorgiou General Hospital of Thessaloniki	Thessaloniki
Hungary	Uzsoki Utcai Korhaz	Budapest
Hungary	Szabolcs-Szatmar-Bereg Megyei; Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	Pecsi Tudomanyegyetem	Pecs
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet; Megyei Onkologiai Kozpont	Szolnok
Italy	Centro Di Riferimento Oncologico; Struttura Operativa Complessa Di Oncologia Medica B	Aviano	Friuli-Venezia Giulia
Italy	Asst Papa Giovanni XXIII	Bergamo	Lombardia
Italy	Azienda Ospedaliero-Universitaria ?PoliclinicoVittorio Emanuele?- P.O. G. Rodolico; Oncologia Medica	Catania	Sicilia
Italy	Azienda Ospedaliera Istituti Ospitalieri	Cremona	Lombardia
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Ospedale San Raffaele S.r.l.	Milano	Lombardia
Italy	Azienda Socio Sanitaria Territoriale ? ASST di Monza	Monza	Lombardia
Italy	Istituto Nazionale dei Tumori	Monza	Lombardia
Italy	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Italy	Azienda Ospedaliera Universitaria Integrata Verona; UOC Oncologia	Verona	Veneto
Japan	Aichi Cancer Center Hospital; Respiratory Medicine	Aichi
Japan	Nagoya University Hospital; Respiratory Medicine	Aichi
Japan	Kyushu University Hospital; Respiratory	Fukuoka
Japan	Hokkaido University Hospital	Hokkaido
Japan	Hyogo Cancer Center; Thoracic Oncology	Hyogo
Japan	Kobe City Medical Center General Hospital; Respiratory Medicine	Hyogo
Japan	Ibaraki Prefectural Central Hospital; Division of respiratory	Ibaraki
Japan	Sendai Kousei Hospital; Pulmonary Medicine	Miyagi
Japan	Okayama University Hospital; Respiratory and Allergy Medicine	Okayama
Japan	Kansai Medical university Hospital; Thoracic Oncology	Osaka
Japan	Osaka Habikino Medical Center	Osaka
Japan	Osaka International Cancer Institute; Thoracic Oncology	Osaka
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center	Sakai-shi
Japan	Saitama Cancer Center; Thoracic Oncology	Satima
Japan	National Cancer Center Hospital; Thoracic Medical Oncology	Tokyo
Japan	Tokyo Medical University Hospital; Dept of Surgery	Tokyo
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Poland	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy	Otwock
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan
Romania	Teo Health SA - Saint Constantin Hospital	Brasov
Romania	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca
Romania	Oncology Center Sf. Nectarie	Craiova
Romania	Institutul Regional de Oncologie Iasi; Clinica de Hematologie	Iasi
Romania	Sibiu Emergency Clinical County Hospital	Sibiu
Romania	Oncocenter Clinical Oncology	Timi?oara
Romania	Oncomed SRL	Timisoara
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk	Arhangelsk
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan	Tatarstan
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	Principal Military Clinical Hospital n.a. N.N. Burdenko	Moscow	Moskovskaja Oblast
Russian Federation	Federal State Institution Medical Radiology Research Center	Obninsk	Kaluga
Russian Federation	Regional Clinical Oncology Center	Ryazan
Russian Federation	Mordovia State University	Saransk
Russian Federation	Leningrad Regional Clinical Hospital	St Petersburg
Russian Federation	St. Petersburg Med Univ; n.a. I.P. Pavlov; Pulmonology Research	St Petersburg
Russian Federation	Saint Petersburg Clinical Hospital of the Russian Academy of Sciences	St. Petersburg	Sankt Petersburg
Russian Federation	Volgograd Regional Clinical Oncology Dispensary	Volgograd
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Institute for Oncology and Radiology of Serbia; Medical Oncology	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Institute of Lung Diseases Vojvodina	Sremska Kamenica
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Universitario Cruces	Barakaldo	Vizcaya
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Consorcio Hospitalario Provincial de Castellon	Castellon DE LA Plana/castello DE LA Plana	Castellon
Spain	Hospital Universitario A Coruña	Coruna	LA Coruña
Spain	Complejo Hospitalario de Jaen	Jaen
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Son Llatzer	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Spain	Hosp Clinico Univ Lozano Blesa; División De Oncología Médica	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza
Thailand	Prince of Songkla University; Department Of Internal Medicine, Faculty Of Medicine	Hat Yai
Thailand	Khon Kaen University	Khon Kaen
Thailand	Chiang Rai Prachanukroh Hospital	Muang
Thailand	Buddhachinnaraj Hospital	Phitsanulok
Turkey	Cukurova University Medical Faculty Balcali Hospital	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir
Turkey	Izmir Dr. Suat Seren Gogus Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi	Izmir
Turkey	Inonu University Faculty of Medicine Turgut Ozal Medical Center	Malatya
Ukraine	Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro City Council - PPDS; Chemotherapy	Dnipro	KIEV Governorate
Ukraine	Municipal Noncommercial Institution Regional Center of Oncology	Kharkiv	Kharkiv Governorate
Ukraine	Private Enterprise Private Manufacturing Company Acinus	Kirovograd
Ukraine	Kyiv Railway Clinical Hospital #3 of Branch Health Center of the PJSC Ukrainian Railway	Kyiv	KIEV Governorate
Ukraine	The Municipal Enterprise Volyn Regional Medical Oncology Centre of the Volyn Regional Council	Lutsk	Volhynian Governorate
Ukraine	Municipal Noncomercial Enterprise Odessa Regional Oncology Center ofthe Odessa StateAdministration	Odesa	Kherson Governorate
Ukraine	Municipal non profit enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Disp	Sumy	Kholm Governorate
Ukraine	Communal Nonprofit Enterprise Podilsky Regional Center Of Oncology OfTheVinnytsia Regional Council	Vinnytsia	KIEV Governorate
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Colchester General Hospital	Colchester, Essex
United Kingdom	Christie Hospital	Manchester
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Lynn Cancer Institute - West	Boca Raton	Florida
United States	Hematology Oncology Associates of Fredericksburg, Inc.	Fredericksburg	Virginia
United States	Sarah Cannon Cancer Center	Germantown	Tennessee
United States	University of California San Diego	La Jolla	California
United States	Vanderbilt University Medical Center; Multiple Sclerosis Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Oregon Health & Science Uni	Portland	Oregon
United States	VA Puget Sound Health Care Sys	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  China,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in the TC3 or IC3-WT Populations	OS is defined as the time from randomization to death from any cause.	From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
Primary	Overall Survival (OS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations	OS is defined as the time from randomization to death from any cause.	From randomization to death from any cause until data cut-off on 4 February 2020 (up to approximately 54.5 months)
Secondary	Progression-free Survival (PFS) in the TC3 or IC3-WT Populations	PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. PFS could not be formally tested.	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Progression-free Survival (PFS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations	PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. PFS could not be formally tested.	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months)
Secondary	Percentage of Participants With Objective Response (ORR) in the TC3 or IC3-WT Populations	Objective response (partial response plus complete response) as determined by the investigator according to RECIST v1.1.	Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 10 Sep 2018 (up to approximately 38 months)
Secondary	Percentage of Participants With Objective Response (ORR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations	Objective response (partial response plus complete response) as determined by the investigator according to RECIST v1.1.	Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 4 Feb 2020 (up to approximately 54.5 months)
Secondary	Duration of Response (DOR) in the TC3 or IC3-WT Populations	DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first.	From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Duration of Response (DOR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations	DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first.	From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months)
Secondary	Percentage of Participants Who Are Alive at 1 Year in the TC3 or IC3-WT Populations		Baseline to 1 year or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Percentage of Participants Who Are Alive at 2 Years in the TC3 or IC3-WT Populations		Baseline to 2 years or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Percentage of Participants Who Are Alive at 1 Year in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations		Baseline to 1 year or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)
Secondary	Percentage of Participants Who Are Alive at 2 Years in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations		Baseline to 2 years or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)
Secondary	Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Score as Assessed by the Symptoms in Lung Cancer (SILC) Scale Symptom Score in the TC3 or IC3-WT Populations	TTD in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant.	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations	Change from baseline in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant.	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	TTD as Assessed Using EORTC QLQ Supplementary Lung Cancer Module (EORTC QLQ-LC13) in the TC3 or IC3-WT Populations	TTD in patient-reported lung cancer symptoms, defined as time from randomization to deterioration (10-point change) in any of the following symptom subscales (cough, dyspnea [multi-item scale], and chest pain), whichever occurs first, as measured by the EORTC QLQ-LC13. EORTC QLQ-LC13 module incorporates one multi-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.	Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	OS in Participants With PD-L1 Expression	OS is defined as the time from randomization to death from any cause.	From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Investigator-Assessed PFS in Participants With PD-L1 Expression According to RECIST v1.1	Investigator-assessed PFS according to RECIST v1.1 in the PD-L1 (defined with SP263 IHC assay)	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	OS in Participants With Blood Tumor Mutational Burden (bTMB)	OS is defined as the time from randomization to death from any cause.	From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Investigator-Assessed PFS in Participants With bTMB According to RECIST v1.1	PFS according to RECIST v1.1 in the bTMB subpopulations.	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
Secondary	Minimum Observed Serum Concentration (Cmin) of Atezolizumab		Prior to infusion (0 hour) on Day 1 of Cycles 2, 3, 4, 8, 16, and every eighth cycle thereafter, and at treatment discontinuation until data cut-off on 10 September 2018 (up to approximately 38 months) (cycle duration = 21 days)
Secondary	Maximum Observed Serum Concentration (Cmax) of Atezolizumab		0 hour (predose) and 30 minutes after atezolizumab infusion on Day 1 (infusion duration = up to 1 hour)
Secondary	Percentage of Participants With at Least One Adverse Event	Percentage of participants with at least one adverse event.	Baseline up to until data cut-off on 8 March 2022 (up to approximately 79.5 months)
Secondary	Percentage of Participants With Anti-therapeutic Antibodies (ATAs)		Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)