A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy

NCT03191786 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MO298722015-004105-16
• Study Type: interventional
• Target: 453
• Locations: 24 countries
• Sites: 91

Brief Summary

This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group \[ECOG\] performance status of 2-3).

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time between the date of randomization and the date of death due to any cause. Kaplan-Meier (KM) estimates were used to calculate median.

  From randomization up to death from any cause (up to approximately 55 months)

Secondary Outcomes (11)

• OS Rates at the 6, 12, 18, 24-Months Timepoints

  6, 12, 18 and 24 months

• Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

  From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

• Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1

  From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

• Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1

  Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

• Percentage of Participants With At Least One Adverse Event (AE)

  Baseline up to 90 days after last dose of atezolizumab (approximately 62 months)

Study Arms (2)

Atezolizumab

EXPERIMENTAL

Participants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.

Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

ACTIVE COMPARATOR

Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.

Drug: Vinorelbine; Drug: Gemcitabine

Interventions

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody DRUG

Atezolizumab will be administered via IV infusion once every three weeks (QW3).

Also known as: MPDL3280A

Atezolizumab

Vinorelbine DRUG

Vinorelbine will be administered per relevant local guidelines and Summary of Product Characteristics (SmPC) management.

Also known as: Navelbine®

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

Gemcitabine DRUG

Gemcitabine will be administered per relevant local guidelines and SmPC management.

Also known as: Gemzar®

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the American Joint Committee on Cancer (AJCC) 7th edition
• No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
• No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition
• Life expectancy greater than or equal to (\>/=) 8 weeks
• Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to poor performance status (ECOG performance status of 2-3). However, participants \>= 70 years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy
• Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained during course of disease (archival tissue) or at screening
• Participants with treated, asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Measurable disease outside CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization; No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
• Adequate hematologic and end organ function
• Female participants of childbearing potential randomized to the atezolizumab treatment arm agree to use protocol defined methods of contraception

You may not qualify if:

• Participants younger than 70 years who have an ECOG performance status of 0 or 1
• Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation of the brain during screening and prior radiographic assessments
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled or symptomatic hyerpcalcemia (ionized calcium \> 1.5 mmol/L or calcium \>12 mg/dL or corrected serum calcium \>ULN)
• History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example \[e.g.\], radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
• Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy
• History of autoimmune disease except autoimmune-related hypothyroidism and controlled Type I diabetes mellitus
• History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
• Known positivity for human immunodeficiency virus (HIV)
• Known active hepatitis B or hepatitis C
• Active tuberculosis
• Severe infections within 4 weeks prior to randomization
• Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (91)

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, C1125ABD, Argentina

Location

Hospital Privado de Comunidad

Mar del Plata, B7602CBM, Argentina

Location

Clinica Viedma S.A.

Viedma, R8500ACE, Argentina

Location

UZ Brussel

Brussels, 1090, Belgium

Location

Grand Hôpital de Charleroi Notre Dame

Charleroi, 6000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, 90040-373, Brazil

Location

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Umhat Dr Georgi Stranski; Clinic of Chemotherapy

Pleven, 5800, Bulgaria

Location

Complex Oncology Center (COC)-Plovidiv

Plovdiv, 4000, Bulgaria

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Regional health authority A vitalite health network

Moncton, New Brunswick, E1C 8X3, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Hu Nan Provincial Cancer Hospital

Changsha, 410006, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, 310009, China

Location

Anhui Provincial Hospital

Hefei, 230001, China

Location

Shanghai Chest Hospital

Shanghai, 200000, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center

Wuhan, 430023, China

Location

Fundacion Cardioinfantil

Bogotá, Colombia

Location

Fundación Centro de Investigación Clínica CIC

Medellín, 050022, Colombia

Location

Oncomedica S.A.

Montería, 230002, Colombia

Location

Oncólogos de Occidente

Pereira, 600004, Colombia

Location

Fakultni nemocnice Olomouc; Pneumologicka klinika

Olomouc, 779 00, Czechia

Location

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, 5000, Denmark

Location

Evang. Lungenklinik Berlin Klinik für Pneumologie

Berlin, 13125, Germany

Location

Asklepios Klinik Gauting; Onkologisches Studienzentrum

Gauting, 82131, Germany

Location

LungenClinic Großhansdorf GmbH; Klinische Forschung

Großhansdorf, 22927, Germany

Location

Krankenhaus Martha-Maria Halle-Doelau gGmbH; Klinik fuer Innere Medizin II

Halle, 06120, Germany

Location

Fachklinik für Lungenerkrankungen

Immenhausen, 34376, Germany

Location

Klinikum der Philipps-Universität Marburg

Marburg, 35032, Germany

Location

Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie

Regensburg, 93053, Germany

Location

Universitätsklinikum Tübingen; Innere Medizin VIII, Medizinische Onkologie und Pneumologie

Tübingen, 72076, Germany

Location

HealthCare Global Cancer Centre; Medical Oncology

Ahmedabad, Gujarat, 380060, India

Location

Kailash Cancer Hospital and Research Center

Vadodara, Gujarat, 391760, India

Location

P.D. Hinduja Nat. Hospital & Med. Research Centre

Mahim(West), Maharashtra, 400016, India

Location

Tata Memorial Hospital; Dept of Medical Oncology

Mumbai, Maharashtra, 400012, India

Location

Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute; Department of Rheumatologz

Mumbai, Maharashtra, 400053, India

Location

HCG Manavata Cancer Centre

Nashik, Maharashtra, 422002, India

Location

Grant Medical Foundation, Ruby Hall Clinic

Pune, Maharashtra, 411001, India

Location

Deenanath Mangeshkar Hospital & Research Centre

Pune, Maharashtra, 411004, India

Location

Max Super Speciality Hospital

New Delhi, National Capital Territory of Delhi, 110017, India

Location

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, 110076, India

Location

Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology

New Delhi, National Capital Territory of Delhi, 110085, India

Location

Indo-American Cancer Hospital & Research Center

Hyderabad, Telangana, 500034, India

Location

Tata Medical Center; Department of Medical Oncology

Kolkata, West Bengal, 700160, India

Location

Mater Misericordiae University Hospital - Institute for Cancer Research

Dublin, 7, Ireland

Location

University Hospital Limerick - Clinical Trials Department

Limerick, Ireland

Location

Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica

Ravenna, Emilia-Romagna, 48100, Italy

Location

Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1

Rome, Lazio, 00152, Italy

Location

Azienda Ospedaliera San Gerardo di Monza

Monza MI, Lombardy, 20900, Italy

Location

Kazakh Scientific Research Institution Of Oncology and Radiology

Almaty, 050022, Kazakhstan

Location

Almaty Oncology Center

Almaty, 050054, Kazakhstan

Location

Centre Hospitalier de Luxembourg

Luxembourg, 1210, Luxembourg

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Oncologico Potosino

San Luis Potosí City, San Luis Potosí, 78209, Mexico

Location

Centro Estatal de Cancerologia de Chihuahua; ONCOLOGY

Chihuahua City, 31000, Mexico

Location

Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii

Otwock, 05-400, Poland

Location

Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers

Warsaw, 02-781, Poland

Location

CHUC - Unidade de Pneumologia Oncológica; Hospital de Dia de Oncologia Edificio Sao Jeronimo

Coimbra, 3000-075, Portugal

Location

IPO do Porto; Servico de Oncologia Medica

Porto, 4200-072, Portugal

Location

Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca; Oncologie Medicala

Cluj-Napoca, 400015, Romania

Location

Centrul de Radioterapie AMETHYST

Floreşti, 407280, Romania

Location

Oncocenter Timisoara

Timi?oara, 300166, Romania

Location

Specializovana nemocnica sv. Svorada Zobor, n.o.; Oddelenie klinickej onkologie

Nitra, 949 88, Slovakia

Location

Fakultna nemocnica Trnava

Trnava, 917 75, Slovakia

Location

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Hospital de Cruces; Servicio de Oncologia

Bilbao, Vizcaya, 48903, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Universitario de la Princesa; Servicio de Oncologia

Madrid, 28006, Spain

Location

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, 29010, Spain

Location

Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia

Murcia, 30008, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, 46015, Spain

Location

Ospedale Regionale di Bellinzona Medizin Onkologie

Bellinzona, 6500, Switzerland

Location

Spital STS AG - Spital Thun Medizin Onkologie; MEDIZINISCHE KLINIK

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur; Medizinische Onkologie

Winterthur, 8401, Switzerland

Location

Clatterbridge Cancer Centre

Bebington, CH63 4JY, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Royal Cornwall Hospital; Dept of Clinical Oncology

Cornwall, TR1 3LQ, United Kingdom

Location

New Victoria Hospital

Glasgow, G42 9LF, United Kingdom

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2PG, United Kingdom

Location

Christie Hospital Nhs Trust; Medical Oncology

Manchester, M2O 4BX, United Kingdom

Location

YORK DISTRICT HOSPITAL; Haematology/Oncology Department

York, YO31 8HE, United Kingdom

Location

Bach Mai Hospital

Hanoi, 100000, Vietnam

Location

Cho Ray Hospital

Hochiminh City, 700000, Vietnam

Location

Related Publications (4)

• Han B, Peters S, Le AT, Huang D, Wu G, Cao L, Pham CP, Zhao J, Wang K, Yang N, Zhong H, Hu Y, Morris S, Lam V, Graupner V, Gitlitz B, Hoglander E, Schulz C, Lee SM. First-line atezolizumab monotherapy vs. single-agent chemotherapy in patients with advanced or metastatic non-small cell lung cancer who are ineligible for platinum-based therapy: Analysis of the IPSOS Asian subpopulation. Chin Med J (Engl). 2025 Dec 17. doi: 10.1097/CM9.0000000000003796. Online ahead of print.

  PMID: 41424028 DERIVED

• Li B, Rong D, Lin H. Atezolizumab monotherapy as first-line treatment for non-small cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a cost-effectiveness analysis in the USA. BMJ Open. 2024 Nov 12;14(11):e083716. doi: 10.1136/bmjopen-2023-083716.

  PMID: 39532375 DERIVED

• Lee SM, Schulz C, Prabhash K, Kowalski D, Szczesna A, Han B, Rittmeyer A, Talbot T, Vicente D, Califano R, Cortinovis D, Le AT, Huang D, Liu G, Cappuzzo F, Reyes Contreras J, Reck M, Palmero R, Mak MP, Hu Y, Morris S, Hoglander E, Connors M, Biggane AM, Vollan HK, Peters S. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study. Lancet. 2023 Aug 5;402(10400):451-463. doi: 10.1016/S0140-6736(23)00774-2. Epub 2023 Jul 6.

  PMID: 37423228 DERIVED

• Gijtenbeek RG, de Jong K, Venmans BJ, van Vollenhoven FH, Ten Brinke A, Van der Wekken AJ, van Geffen WH. Best first-line therapy for people with advanced non-small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status. Cochrane Database Syst Rev. 2023 Jul 7;7(7):CD013382. doi: 10.1002/14651858.CD013382.pub2.

  PMID: 37419867 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Vinorelbine; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 19, 2017
• Study Start: September 11, 2017
• Primary Completion: April 30, 2022
• Study Completion: October 25, 2023
• Last Updated: October 23, 2024
• Results First Posted: May 17, 2023

Record last verified: 2024-09

Locations

AR (3); CZ (1); BU (2); DK (1); IN (13); PT (2); KA (2); VN (2); BR (3); IT (3); LU (1); ES (9); RO (3); ME (3); CN (7); BE (3); CO (4); SL (2); CH (3); DE (8); PL (2); GB (7); IE (2); CA (5)