Clinical trial NCT02409342: 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]
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Squamous Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-04-06
Enrollment: 572
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS) in the TC3 or IC3-WT Populations
timeFrame: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: Overall Survival (OS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
timeFrame: From randomization to death from any cause until data cut-off on 4 February 2020 (up to approximately 54.5 months)
Secondary outcomes:
measure: Progression-free Survival (PFS) in the TC3 or IC3-WT Populations
timeFrame: 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)
measure: Progression-free Survival (PFS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
timeFrame: 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)
measure: Percentage of Participants With Objective Response (ORR) in the TC3 or IC3-WT Populations
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Duration of Response (DOR) in the TC3 or IC3-WT Populations
timeFrame: 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)
measure: Duration of Response (DOR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
timeFrame: 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)
measure: Percentage of Participants Who Are Alive at 1 Year in the TC3 or IC3-WT Populations
timeFrame: Baseline to 1 year or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: Percentage of Participants Who Are Alive at 2 Years in the TC3 or IC3-WT Populations
timeFrame: Baseline to 2 years or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: 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
timeFrame: Baseline to 1 year or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)
measure: 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
timeFrame: Baseline to 2 years or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)
measure: 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
timeFrame: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: 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
timeFrame: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: TTD as Assessed Using EORTC QLQ Supplementary Lung Cancer Module (EORTC QLQ-LC13) in the TC3 or IC3-WT Populations
timeFrame: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: OS in Participants With PD-L1 Expression
timeFrame: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: Investigator-Assessed PFS in Participants With PD-L1 Expression According to RECIST v1.1
timeFrame: 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)
measure: OS in Participants With Blood Tumor Mutational Burden (bTMB)
timeFrame: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)
measure: Investigator-Assessed PFS in Participants With bTMB According to RECIST v1.1
timeFrame: 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)
measure: Minimum Observed Serum Concentration (Cmin) of Atezolizumab
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of Atezolizumab
timeFrame: 0 hour (predose) and 30 minutes after atezolizumab infusion on Day 1 (infusion duration = up to 1 hour)
measure: Percentage of Participants With at Least One Adverse Event
timeFrame: Baseline up to until data cut-off on 8 March 2022 (up to approximately 79.5 months)
measure: Percentage of Participants With Anti-therapeutic Antibodies (ATAs)
timeFrame: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Boca Raton
country: United States
facility: Lynn Cancer Institute - West
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Portland
country: United States
facility: Oregon Health & Science Uni
state: Oregon
city: Germantown
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center; Multiple Sclerosis Center
state: Tennessee
city: Fredericksburg
country: United States
facility: Hematology Oncology Associates of Fredericksburg, Inc.
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care Sys
state: Washington
city: Salvador
country: Brazil
facility: Oncovida*X
state: BA
city: Cachoeiro de Itapemirim
country: Brazil
facility: Centro de Pesquisas Clinicas em Oncologia - CPCO
state: ES
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCa; Oncologia
state: RJ
city: Ijui
country: Brazil
facility: Associacao Hospital de Caridade Ijui*X; Departamento De Oncologia
state: RS
city: Passo Fundo
country: Brazil
facility: Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
state: RS
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Joinville
country: Brazil
facility: Instituto Joinvilense de Hematologia E Oncologia
state: SC
city: Barretos
country: Brazil
facility: *X*Fundacao PIO XII
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: SP
city: São Paulo
country: Brazil
facility: Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira
state: SP
city: Harbin City
country: China
facility: Harbin Medical University Tumor Hospital
city: Angers
country: France
facility: CHU Angers
city: Clamart
country: France
facility: Hospital d Instructions des Armees Percy
city: Limoges
country: France
facility: Hôpital Universitaire Dupuytren
city: Montpellier
country: France
facility: Clinique Clémentville
city: Nancy
country: France
facility: Centre D'oncologie de Gentilly
city: Paris
country: France
facility: Hopital Tenon
city: Saint Denis Cedex
country: France
facility: Centre Hospitalier Regional La Reunion Site Felix Guyon
city: Saint-Mande
country: France
facility: Hopital d'Instruction des Armees de Begin
city: Saint-pierre
country: France
facility: Centre Hospitalier Regional Sud Reunion
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Gauting
country: Germany
facility: Asklepios-Fachklinik Muenchen-Gauting; Klinik Für Pneumologie
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg
city: Athens
country: Greece
facility: Sotiria Chest Hospital of Athens
city: Athens
country: Greece
facility: IASO General Hospital of Athens
city: Athens
country: Greece
facility: Metropolitan Hospital
city: Chaidari
country: Greece
facility: Attikon University General Hospital
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Thermi, Thessaloniki
country: Greece
facility: Thermi Clinic
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki
city: Thessaloniki
country: Greece
facility: EUROMEDICA General Clinic of Thessaloniki; Gastroenterology Department
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: Georgios Papanikolaou General Hosp. of Thessaloniki
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei; Korhazak es Egyetemi Oktatokorhaz
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet; Megyei Onkologiai Kozpont
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico; Struttura Operativa Complessa Di Oncologia Medica B
state: Friuli-Venezia Giulia
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII
state: Lombardia
city: Cremona
country: Italy
facility: Azienda Ospedaliera Istituti Ospitalieri
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l.
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale ? ASST di Monza
state: Lombardia
city: Monza
country: Italy
facility: Istituto Nazionale dei Tumori
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
state: Piemonte
city: Catania
country: Italy
facility: Azienda Ospedaliero-Universitaria ?PoliclinicoVittorio Emanuele?- P.O. G. Rodolico; Oncologia Medica
state: Sicilia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona; UOC Oncologia
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital; Respiratory Medicine
city: Aichi
country: Japan
facility: Nagoya University Hospital; Respiratory Medicine
city: Fukuoka
country: Japan
facility: Kyushu University Hospital; Respiratory
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogo
country: Japan
facility: Kobe City Medical Center General Hospital; Respiratory Medicine
city: Hyogo
country: Japan
facility: Hyogo Cancer Center; Thoracic Oncology
city: Ibaraki
country: Japan
facility: Ibaraki Prefectural Central Hospital; Division of respiratory
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital; Pulmonary Medicine
city: Okayama
country: Japan
facility: Okayama University Hospital; Respiratory and Allergy Medicine
city: Osaka
country: Japan
facility: Osaka International Cancer Institute; Thoracic Oncology
city: Osaka
country: Japan
facility: Kansai Medical university Hospital; Thoracic Oncology
city: Osaka
country: Japan
facility: Osaka Habikino Medical Center
city: Sakai-shi
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Satima
country: Japan
facility: Saitama Cancer Center; Thoracic Oncology
city: Tokyo
country: Japan
facility: National Cancer Center Hospital; Thoracic Medical Oncology
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital; Dept of Surgery
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Olsztyn
country: Poland
facility: Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
city: Poznan
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Brasov
country: Romania
facility: Teo Health SA - Saint Constantin Hospital
city: Cluj Napoca
country: Romania
facility: Prof. Dr. I. Chiricuta Institute of Oncology
city: Craiova
country: Romania
facility: Oncology Center Sf. Nectarie
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi; Clinica de Hematologie
city: Sibiu
country: Romania
facility: Sibiu Emergency Clinical County Hospital
city: Timi?oara
country: Romania
facility: Oncocenter Clinical Oncology
city: Timisoara
country: Romania
facility: Oncomed SRL
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Dispensary
state: Arhangelsk
city: Obninsk
country: Russian Federation
facility: Federal State Institution Medical Radiology Research Center
state: Kaluga
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Principal Military Clinical Hospital n.a. N.N. Burdenko
state: Moskovskaja Oblast
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg Clinical Hospital of the Russian Academy of Sciences
state: Sankt Petersburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
state: Tatarstan
city: Ryazan
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Saransk
country: Russian Federation
facility: Mordovia State University
city: St Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
city: St Petersburg
country: Russian Federation
facility: St. Petersburg Med Univ; n.a. I.P. Pavlov; Pulmonology Research
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Clinical Oncology Dispensary
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia; Medical Oncology
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Institute of Lung Diseases Vojvodina
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Castellon DE LA Plana/castello DE LA Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
state: Castellon
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: Coruna
country: Spain
facility: Hospital Universitario A Coruña
state: LA Coruña
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Zaragoza
country: Spain
facility: Hosp Clinico Univ Lozano Blesa; División De Oncología Médica
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Hat Yai
country: Thailand
facility: Prince of Songkla University; Department Of Internal Medicine, Faculty Of Medicine
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Muang
country: Thailand
facility: Chiang Rai Prachanukroh Hospital
city: Phitsanulok
country: Thailand
facility: Buddhachinnaraj Hospital
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty Balcali Hospital
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi
city: Izmir
country: Turkey
facility: Izmir Dr. Suat Seren Gogus Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
city: Malatya
country: Turkey
facility: Inonu University Faculty of Medicine Turgut Ozal Medical Center
city: Kharkiv
country: Ukraine
facility: Municipal Noncommercial Institution Regional Center of Oncology
state: Kharkiv Governorate
city: Odesa
country: Ukraine
facility: Municipal Noncomercial Enterprise Odessa Regional Oncology Center ofthe Odessa StateAdministration
state: Kherson Governorate
city: Sumy
country: Ukraine
facility: Municipal non profit enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Disp
state: Kholm Governorate
city: Dnipro
country: Ukraine
facility: Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro City Council - PPDS; Chemotherapy
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Kyiv Railway Clinical Hospital #3 of Branch Health Center of the PJSC Ukrainian Railway
state: KIEV Governorate
city: Vinnytsia
country: Ukraine
facility: Communal Nonprofit Enterprise Podilsky Regional Center Of Oncology OfTheVinnytsia Regional Council
state: KIEV Governorate
city: Lutsk
country: Ukraine
facility: The Municipal Enterprise Volyn Regional Medical Oncology Centre of the Volyn Regional Council
state: Volhynian Governorate
city: Kirovograd
country: Ukraine
facility: Private Enterprise Private Manufacturing Company Acinus
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Colchester, Essex
country: United Kingdom
facility: Colchester General Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Ozguroglu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. doi: 10.1056/NEJMoa1917346.