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

Non-Small Cell Lung Cancer Clinical Trial

— IPSOS  

Official title:

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03191786
• Other study ID #: MO29872
• Secondary ID: 2015-004105-16
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2017
• Est. completion date: October 25, 2023

Study information

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

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 453
• Est. completion date: October 25, 2023
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

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)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab will be administered via IV infusion once every three weeks (QW3).
• Vinorelbine
Vinorelbine will be administered per relevant local guidelines and Summary of Product Characteristics (SmPC) management.
• Gemcitabine
Gemcitabine will be administered per relevant local guidelines and SmPC management.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Hospital Privado de Comunidad	Mar del Plata
Argentina	Clinica Viedma S.A.	Viedma
Belgium	UZ Brussel	Brussel
Belgium	Grand Hôpital de Charleroi Notre Dame	Charleroi
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	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
Bulgaria	Umhat Dr Georgi Stranski; Clinic of Chemotherapy	Pleven
Bulgaria	Complex Oncology Center (COC)-Plovidiv	Plovdiv
Canada	Regional health authority A vitalite health network	Moncton	New Brunswick
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
China	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
Colombia	Fundacion Cardioinfantil	Bogota
Colombia	Fundación Centro de Investigación Clínica CIC	Medellin
Colombia	Oncomedica S.A.	Monteria
Colombia	Oncólogos de Occidente	Pereira
Czechia	Fakultni nemocnice Olomouc; Pneumologicka klinika	Olomouc
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Germany	Evang. Lungenklinik Berlin Klinik für Pneumologie	Berlin
Germany	Asklepios Klinik Gauting; Onkologisches Studienzentrum	Gauting
Germany	LungenClinic Großhansdorf GmbH	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
India	HealthCare Global Cancer Centre; Medical Oncology	Ahmedabad	Gujarat
India	Indo-American Cancer Hospital & Research Center	Hyderabad	Telangana
India	Tata Medical Center; Department of Medical Oncology	Kolkata	WEST Bengal
India	P.D. Hinduja Nat. Hospital & Med. Research Centre	Mahim(West)	Maharashtra
India	Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute; Department of Rheumatologz	Mumbai	Maharashtra
India	Tata Memorial Hospital; Dept of Medical Oncology	Mumbai	Maharashtra
India	HCG Manavata Cancer Centre	Nashik	Maharashtra
India	Indraprastha Apollo Hospitals	New Delhi	Delhi
India	Max Super Speciality Hospital	New Delhi	Delhi
India	Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology	New Delhi	Delhi
India	Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra
India	Grant Medical Foundation, Ruby Hall Clinic	Pune	Maharashtra
India	Kailash Cancer Hospital and Research Center	Vadodara	Gujarat
Ireland	Mater Misericordiae University Hospital - Institute for Cancer Research	Dublin
Ireland	University Hospital Limerick - Clinical Trials Department	Limerick
Italy	Azienda Ospedaliera San Gerardo di Monza	Monza MI	Lombardia
Italy	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
Kazakhstan	Almaty Oncology Center	Almaty
Kazakhstan	Kazakh Scientific Research Institution Of Oncology and Radiology	Almaty
Luxembourg	Centre Hospitalier de Luxembourg	Luxembourg
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Centro Estatal de Cancerologia de Chihuahua; ONCOLOGY	Chihuahua
Mexico	Oncologico Potosino	San Luis Potosí	SAN LUIS Potosi
Poland	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
Portugal	CHUC - Unidade de Pneumologia Oncológica; Hospital de Dia de Oncologia Edificio Sao Jeronimo	Coimbra
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca; Oncologie Medicala	Cluj Napoca
Romania	Centrul de Radioterapie AMETHYST	Floresti
Romania	Oncocenter Timisoara	Timi?oara
Slovakia	Specializovana nemocnica sv. Svorada Zobor, n.o.; Oddelenie klinickej onkologie	Nitra
Slovakia	Fakultna nemocnica Trnava	Trnava
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario de la Princesa; 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	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia
Switzerland	Ospedale Regionale di Bellinzona Medizin Onkologie	Bellinzona
Switzerland	Spital STS AG - Spital Thun Medizin Onkologie; MEDIZINISCHE KLINIK	Thun
Switzerland	Kantonsspital Winterthur; Medizinische Onkologie	Winterthur
United Kingdom	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
Vietnam	Bach Mai Hospital	Hanoi
Vietnam	Cho Ray Hospital	Hochiminh city

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival is defined as the time between the date of randomization and the date of death due to any cause.	From randomization up to death from any cause (up to approximately 55 months)
Secondary	OS Rates at the 6, 12, 18, 24-Months Timepoints	OS rate at 6, 12, 18 and 24 months were estimated for each treatment arm.	6, 12, 18 and 24 months
Secondary	Percentage of Participants With Objective Response Rate, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1)	Objective response rate (ORR) is defined as a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as determined by the investigator with use of RECIST v1.1. A minimum interval of 6 weeks (42 days) will be considered for Stable Disease (SD) to be assigned as best overall response, i.e. in the 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.	From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
Secondary	Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1	PFS is 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.	From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
Secondary	Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1	DOR is 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 patients who have a best overall response as CR or PR.	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)
Secondary	Percentage of Participants With At Lease One Adverse Event	Percentage of participants with at least one adverse event.	From randomization up to approximately 55 months
Secondary	Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score	EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three 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). EORTC QLQ-C30 is 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 is perceived by participants as clinically significant (Osoba et al. 1998).	Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)
Secondary	Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score	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 is 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 is perceived by participants as clinically significant (Osoba et al. 1998).	Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)
Secondary	Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score	TTD with use of the EORTC is 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 is 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 is perceived by participants as clinically significant (Osoba et al. 1998).	From baseline up to approximately 55 months
Secondary	Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score	TTD with use of the EORTC is 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 is 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 is perceived by participants as clinically significant.	From baseline up to approximately 55 months
Secondary	Overall Survival in Participants With PD-L1 Positive Status	Overall survival will be assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.	From randomization up to death from any cause (up to approximately 55 months)
Secondary	Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status	Investigator-assessed PFS according to RECIST v1.1 assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.	From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)