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
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03191786
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 453
- 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
Cancer-Specific 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
General Medical Exclusion Criteria:
- 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
Exclusion Criteria Related to Atezolizumab:
- 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
Exclusion Criteria Related to Chemotherapy:
- Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody 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. Single Agent Chemotherapy (Vinorelbine or Gemcitabine) Vinorelbine Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice. Single Agent Chemotherapy (Vinorelbine or Gemcitabine) Gemcitabine Participants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From randomization up to death from any cause (up to approximately 55 months) 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.
- Secondary Outcome Measures
Name Time Method OS Rates at the 6, 12, 18, 24-Months Timepoints 6, 12, 18 and 24 months OS was defined as the time between the date of randomization and the date of death due to any cause. OS rate at 6, 12, 18 and 24 months were estimated for each treatment arm using Kaplan Meier methodology. Percentages were rounded off to the nearest decimal point.
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) Objective response rate (ORR)=best overall response (BOR) of either complete response (CR)/partial response (PR), as determined by investigator with use of RECIST v1.1. CR= disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 millimeters (mm). PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. A minimum interval of 6 weeks (42 days) was considered for stable disease (SD) to be assigned as BOR, i.e. in case the single response is SD, PR or CR, this single response must have been assessed no less than 6 weeks (at least 42 days) after start date of study treatment. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the diameters while in the study. Percentages were rounded off to the nearest decimal point.
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) PFS was defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurs first. Progressive disease (PD) was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. KM estimates were used to calculate median.
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) DOR was defined as the time from the first tumor assessment that supports the participants' objective response (CR or PR, whichever is first reported) to documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first, among participants who have a best overall response as CR or PR. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. KM estimates were used to calculate median.
Percentage of Participants With At Least One Adverse Event (AE) Baseline up to 90 days after last dose of atezolizumab (approximately 62 months) An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days) EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of patient functioning (physical, emotional, role, cognitive, and social), 3 symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). It was scored according to EORTC scoring manual (Fayers et al. 2001). All EORTC scales \& single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high/healthy level of functioning/HRQoL (Health-Related Quality of Life); however a high score for a symptom scale represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score was perceived by participants as clinically significant (Osoba et al. 1998). A positive change from baseline=improvement \& negative change from baseline indicated worsening.
Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days) The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 was scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A≥10-point change in the symptoms subscale score was perceived by participants as clinically significant (Osoba et al. 1998). A positive change from baseline indicates improvement and negative change from baseline indicated worsening.
Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score From baseline up to approximately 55 months TTD with use of the EORTC was defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms was defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC scale score was perceived by participants as clinically significant (Osoba et al. 1998).
TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score From baseline up to approximately 55 months TTD with use of the EORTC was defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms was defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC scale score was perceived by participants as clinically significant.
OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status From randomization up to death from any cause (up to approximately 55 months) OS was defined as the time between the date of randomization and the date of death due to any cause. OS was assessed in participants whose tumors express PD-L1 protein (i.e., tumor cell (TC) ≥1%) as measured by PD-L1 SP263 immunohistochemistry (IHC) assay. KM estimates were used to calculate the median.
PFS as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months) PFS was defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurs first. PD was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. Investigator-assessed PFS was assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay. KM estimates were used to calculate the median.
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (91)
LungenClinic Großhansdorf GmbH; Klinische Forschung
🇩🇪Großhansdorf, Germany
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
🇧🇪Brussel, Belgium
Grand Hôpital de Charleroi Notre Dame
🇧🇪Charleroi, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, 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 City, 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
🇨🇴Bogota, Colombia
Fundación Centro de Investigación Clínica CIC
🇨🇴Medellin, Colombia
Oncomedica S.A.
🇨🇴Monteria, 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
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
Max Super Speciality Hospital
🇮🇳New Delhi, Delhi, India
Indraprastha Apollo Hospitals
🇮🇳New Delhi, Delhi, India
Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
🇮🇳New Delhi, Delhi, India
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
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
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliera San Gerardo di Monza
🇮🇹Monza MI, Lombardia, Italy
HCG Manavata Cancer Centre
🇮🇳Nashik, Maharashtra, India
Grant Medical Foundation, Ruby Hall Clinic
🇮🇳Pune, Maharashtra, India
Indo-American Cancer Hospital & Research Center
🇮🇳Hyderabad, Telangana, India
Mater Misericordiae University Hospital - Institute for Cancer Research
🇮🇪Dublin, Ireland
University Hospital Limerick - Clinical Trials Department
🇮🇪Limerick, Ireland
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, Maharashtra, India
Tata Medical Center; Department of Medical Oncology
🇮🇳Kolkata, WEST Bengal, India
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
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
Oncologico Potosino
🇲🇽San Luis Potosí, SAN LUIS Potosi, Mexico
Centro Estatal de Cancerologia de Chihuahua; ONCOLOGY
🇲🇽Chihuahua, 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
🇵🇱Warszawa, 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
🇷🇴Floresti, 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
🇪🇸Malaga, Spain
Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, 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