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

NCT ID: NCT03191786

Last Updated: 2024-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 453 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-11
• Study Completion Date: 2023-10-25

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

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

Group Type: ACTIVE_COMPARATOR

Vinorelbine

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

Vinorelbine

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

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Other Intervention Names

MPDL3280A; Navelbine®; Gemzar®

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
• Prior allogeneic bone marrow transplantation or solid organ transplant
• Participants with an illness or condition that may interfere with capacity or compliance with the study protocol, as per investigator's judgment
• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• Oral or IV antibiotic treatment
• Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study
• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to randomization
• Treatment with systemic corticosteroids or other immunosuppressive medications
• Participants not willing to stop treatment with traditional herbal medicines

• Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, , Argentina

Hospital Privado de Comunidad

Mar del Plata, , Argentina

Clinica Viedma S.A.

Viedma, , Argentina

UZ Brussel

Brussels, , Belgium

Grand Hôpital de Charleroi Notre Dame

Charleroi, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Umhat Dr Georgi Stranski; Clinic of Chemotherapy

Pleven, , Bulgaria

Complex Oncology Center (COC)-Plovidiv

Plovdiv, , Bulgaria

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Regional health authority A vitalite health network

Moncton, New Brunswick, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Beijing Cancer Hospital

Beijing, , China

Hu Nan Provincial Cancer Hospital

Changsha, , China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, , China

Anhui Provincial Hospital

Hefei, , China

Shanghai Chest Hospital

Shanghai, , China

Tianjin Cancer Hospital

Tianjin, , China

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

Wuhan, , China

Fundacion Cardioinfantil

Bogotá, , Colombia

Fundación Centro de Investigación Clínica CIC

Medellín, , Colombia

Oncomedica S.A.

Montería, , Colombia

Oncólogos de Occidente

Pereira, , Colombia

Fakultni nemocnice Olomouc; Pneumologicka klinika

Olomouc, , Czechia

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, , Denmark

Evang. Lungenklinik Berlin Klinik für Pneumologie

Berlin, , Germany

Asklepios Klinik Gauting; Onkologisches Studienzentrum

Gauting, , Germany

LungenClinic Großhansdorf GmbH; Klinische Forschung

Großhansdorf, , Germany

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

Halle, , Germany

Fachklinik für Lungenerkrankungen

Immenhausen, , Germany

Klinikum der Philipps-Universität Marburg

Marburg, , Germany

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

Regensburg, , Germany

Universitätsklinikum Tübingen; Innere Medizin VIII, Medizinische Onkologie und Pneumologie

Tübingen, , Germany

HealthCare Global Cancer Centre; Medical Oncology

Ahmedabad, Gujarat, India

Kailash Cancer Hospital and Research Center

Vadodara, Gujarat, India

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

Mahim(West), Maharashtra, India

Tata Memorial Hospital; Dept of Medical Oncology

Mumbai, Maharashtra, India

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

Mumbai, Maharashtra, India

HCG Manavata Cancer Centre

Nashik, Maharashtra, India

Grant Medical Foundation, Ruby Hall Clinic

Pune, Maharashtra, India

Deenanath Mangeshkar Hospital & Research Centre

Pune, Maharashtra, India

Max Super Speciality Hospital

New Delhi, National Capital Territory of Delhi, India

Indraprastha Apollo Hospitals

New Delhi, National Capital Territory of Delhi, India

Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology

New Delhi, National Capital Territory of Delhi, India

Indo-American Cancer Hospital & Research Center

Hyderabad, Telangana, India

Tata Medical Center; Department of Medical Oncology

Kolkata, West Bengal, India

Mater Misericordiae University Hospital - Institute for Cancer Research

Dublin, , Ireland

University Hospital Limerick - Clinical Trials Department

Limerick, , Ireland

Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica

Ravenna, Emilia-Romagna, Italy

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

Rome, Lazio, Italy

Azienda Ospedaliera San Gerardo di Monza

Monza MI, Lombardy, Italy

Kazakh Scientific Research Institution Of Oncology and Radiology

Almaty, , Kazakhstan

Almaty Oncology Center

Almaty, , Kazakhstan

Centre Hospitalier de Luxembourg

Luxembourg, , Luxembourg

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), Mexico

Oncologico Potosino

San Luis Potosí City, San Luis Potosí, Mexico

Centro Estatal de Cancerologia de Chihuahua; ONCOLOGY

Chihuahua City, , Mexico

Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii

Otwock, , Poland

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

Warsaw, , Poland

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

Coimbra, , Portugal

IPO do Porto; Servico de Oncologia Medica

Porto, , Portugal

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

Cluj-Napoca, , Romania

Centrul de Radioterapie AMETHYST

Floreşti, , Romania

Oncocenter Timisoara

Timi?oara, , Romania

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

Nitra, , Slovakia

Fakultna nemocnica Trnava

Trnava, , Slovakia

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

Santiago de Compostela, LA Coruña, Spain

Hospital de Cruces; Servicio de Oncologia

Bilbao, Vizcaya, Spain

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Hospital Universitario de la Princesa; Servicio de Oncologia

Madrid, , Spain

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, , Spain

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

Murcia, , Spain

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, , Spain

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, , Spain

Ospedale Regionale di Bellinzona Medizin Onkologie

Bellinzona, , Switzerland

Spital STS AG - Spital Thun Medizin Onkologie; MEDIZINISCHE KLINIK

Thun, , Switzerland

Kantonsspital Winterthur; Medizinische Onkologie

Winterthur, , Switzerland

Clatterbridge Cancer Centre

Bebington, , United Kingdom

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Royal Cornwall Hospital; Dept of Clinical Oncology

Cornwall, , United Kingdom

New Victoria Hospital

Glasgow, , United Kingdom

University College London Hospitals NHS Foundation Trust - University College Hospital

London, , United Kingdom

Christie Hospital Nhs Trust; Medical Oncology

Manchester, , United Kingdom

YORK DISTRICT HOSPITAL; Haematology/Oncology Department

York, , United Kingdom

Bach Mai Hospital

Hanoi, , Vietnam

Cho Ray Hospital

Hochiminh City, , Vietnam

Countries

Argentina; Belgium; Brazil; Bulgaria; Canada; China; Colombia; Czechia; Denmark; Germany; India; Ireland; Italy; Kazakhstan; Luxembourg; Mexico; Poland; Portugal; Romania; Slovakia; Spain; Switzerland; United Kingdom; Vietnam

References

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.

Reference Type: DERIVED

PMID: 39532375 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37423228 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37419867 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004105-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO29872

Identifier Type: -

Identifier Source: org_study_id