Clinical trial NCT05170204: A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase I-III, Multicenter Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Patients Selected According to Biomarker Status, With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-12-27
Enrollment: 71
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 study will evaluate the efficacy and safety of multiple therapies in participants with locally advanced, unresectable, Stage III NSCLC with eligible biomarker status as determined by Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system.


Eligibility criteria: Inclusion Criteria (All Cohorts):

* Body weight \>/= 30 kg at screening
* Willingness and ability to use the electronic device(s) or application(s) for the electronic patient-reported outcome (PRO)
* Whole-body positron emission tomography/computed tomography scan (PET/CT) (from the base of skull to mid-thighs) for the purposes of staging, performed prior and within 42 days for Cohort A2 (ROS1 positive) and 50 days for Cohort A1 (ALK positive) of the first dose of cCRT or sCRT
* Histologically or cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology
* Prior receipt of at least two prior cycles of platinum-based chemotherapy given concurrently with radiotherapy (cCRT); or at least two prior cycles of platinum-based chemotherapy given prior to radiotherapy (sCRT)
* The RT component in the cCRT or sCRT must have been at a total dose of radiation of 60 (+/-10%) Gy (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or three dimension (3D)-conforming technique
* No disease progression during or following platinum-based cCRT or sCRT
* Life expectancy \>/= 12 weeks
* Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen
* Tumor PD-L1 status (TC score \< 1% vs. \>/= 1% vs. unknown) as determined using the VENTANA PD-L1 IHC SP263 assay (preferred) or the Dako PD-L1 IHC 22C3 pharmDx assay
* Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
* Adequate hematologic and end-organ function
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined by the protocol
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined by the protocol

Inclusion criteria specific to Cohort A1:

* Documented ALK fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or prior tissue-based testing performed in an accredited or certified laboratory

Inclusion criteria specific to Cohort A2:

* Documented ROS1 fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated ROS1 fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory
* Ability to swallow entrectinib intact, without chewing, crushing, or opening the capsules

Exclusion Criteria (All Cohorts):

* Any history of previous NSCLC and/or any history of prior treatment for NSCLC (patients must be newly diagnosed with unresectable Stage III disease)
* Any evidence of Stage IV disease, including, but not limited to, the following: pleural effusion, pericardial effusion, brain metastases, history of intracranial hemorrhage or spinal cord hemorrhage, bone metastases, distant metastases
* If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (T4 disease): when pleural fluid is visible on both the CT scan and chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative; participants with exudative pleural effusions are excluded regardless of cytology; participants with effusions that are minimal (i.e., not visible on chest X-ray) that are too small to safely tap are eligible
* NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing
* Liver disease, characterized by any of the following: impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices or active viral or active autoimmune, alcoholic, or other types of acute hepatitis
* Positive hepatitis B surface antigen (HBsAg) test at screening
* Participants known to be positive for hepatitis C virus (HCV) antibody (Ab) are excluded with the following exception: participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible
* HIV infection: participants are excluded if not well-controlled as defined by the protocol
* Known active tuberculosis
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest CT scan
* Grade \>/= 2 pneumonitis from prior cCRT or sCRT
* Any Grade \> 2 unresolved toxicity from prior cCRT or sCRT
* Any gastrointestinal (GI) disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post-major bowel resection
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study; participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
* Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer
* Major surgical procedure, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with exceptions defined by the protocol
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Prior allogeneic stem cell or solid organ transplantation
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
* Any condition that, in the opinion of the investigator, would interfere with the evaluation of the study drug or interpretation of patient safety or study results
* Any prior Grade \>/= 3 immune-mediated adverse event or any unresolved Grade \> 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents

Exclusion criteria specific to Cohort A1:

* Presence of clinically symptomatic interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention)
* NSCLC known to have one or more of the following ALK point mutations, as identified by site local testing or Sponsor central testing: I1171X (where X is any other amino acid), V1180L, G1202R
* Symptomatic bradycardia
* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina; participants with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
* Prior treatment with ALK inhibitors
* History of hypersensitivity to alectinib, durvalumab, or any of their excipients
* Inability to swallow oral study drug
* Known hereditary problems of galactose intolerance, a congenital lactase deficiency, or glucose-galactose malabsorption
* Pregnancy or breastfeeding, or intending to become pregnant during the study treatment or within 90 days after the final dose of alectinib or durvalumab

Exclusion criteria specific to Cohort A2:

* Symptomatic bradycardia
* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina; participants with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
* Left ventricular ejection fraction less than or equal to 50% observed during the screening for the study
* History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval \> 450 ms from ECGs performed at least 24 hours apart)
* History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome)
* Familial or personal history of congenital bone disorders or bone metabolism alterations
* Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of the treatment
* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
* Prior treatment with ROS1 inhibitors
* History of hypersensitivity to entrectinib, durvalumab, and their excipients
* Grade \>/= 3 toxicities due to any prior therapy (e.g., RT) (excluding alopecia) that have not shown improvement or are not stable and are considered to interfere with current study drug
* Known hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
* Grade \>/= 2 peripheral neuropathy
* Pregnancy or intention of becoming pregnant during study treatment, within 35 days after the final dose of entrectinib, or within 90 days after the final dose of durvalumab

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From randomization to the first documented disease progression as determined by blinded independent central review (BICR) per Response Evaluation Criterial in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurs first (up to 3 years)
Secondary outcomes:
measure: Time to central nervous system (CNS) progression
timeFrame: From randomization to the first occurrence of disease progression in the CNS as determined by BICR per RECIST v1.1 (up to 3 years)
measure: Distant metastasis-free survival (DMFS)
timeFrame: From randomization to the first occurrence of distant metastasis or death (whichever occurs first) as determined by BICR per RECIST v1.1 (up to 3 years)
measure: Objective response rate (ORR), defined as the percentage of participants with measurable disease who attain a complete response (CR) or partial response (PR) as determined by the investigator per RECIST v1.1
timeFrame: Up to 3 years
measure: PFS
timeFrame: From randomization to the first documented disease progression as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurs first (up to 3 years)
measure: Duration of response (DOR)
timeFrame: From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by the investigator per RECIST v1.1 (up to 3 years)
measure: ORR, defined as the percentage of participants with measurable disease who attain a CR or PR as determined by BICR per RECIST v1.1
timeFrame: Up to 3 years
measure: DOR
timeFrame: From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by BICR per RECIST v1.1 (up to 3 years)
measure: Overall survival (OS)
timeFrame: From randomization to death from any cause (up to 5 years)
measure: Time to CNS progression
timeFrame: From randomization to the first occurrence of disease progression in the CNS as determined by the investigator per RECIST v1.1 (up to 3 years)
measure: Time-to-confirmed deterioration (TTCD)
timeFrame: From randomization to the first deterioration of >/= 10 points that is either maintained for two consecutive assessments or followed by death from any cause within 3 weeks (up to 3 years)
measure: Proportion of participants who have maintained or improved baseline health as measured by the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 physical functioning and role functioning scales
timeFrame: 5, 11, and 17 months
measure: Proportion of participants who have maintained or improved from their baseline health in cough, chest pain, and dyspnea symptoms as measured using the EORTC QLQ-LC13
timeFrame: 5, 11, and 17 months
measure: Percentage of participants with adverse events (AEs)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Southern California Kaiser Permanente
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers - Lone Tree
state: Colorado
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Portland
country: United States
facility: Oregon Health Sciences Uni
state: Oregon
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center, UT Health San Antonio
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists (Fairfax) - USOR
state: Virginia
city: Camperdown
country: Australia
facility: Lifehouse
state: New South Wales
city: St Leonards
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research
state: Western Australia
city: Charleroi
country: Belgium
facility: GHdC Site Les Viviers
city: Gent
country: Belgium
facility: UZ Gent
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Tres Lagoas
country: Brazil
facility: Instituto do Cancer Brasil
state: Mato Grosso Do Sul
city: Belo Horizonte
country: Brazil
facility: Oncocentro Belo Horizonte
state: Minas Gerais
city: Uberlandia
country: Brazil
facility: COT - Centro Oncologico do Triangulo
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Clínica de Oncologia Reichow
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Oncoclinicas Rio de Janeiro S.A.
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Providencia
country: Chile
facility: K2 Oncology
city: Santiago
country: Chile
facility: Centro de Estudios Clínicos SAGA
city: Santiago
country: Chile
facility: OrlandiOncología
city: Santiago
country: Chile
facility: RedSalud Vitacura
city: Temuco
country: Chile
facility: James Lind Centro de Investigación Del Cáncer
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changsha City
country: China
facility: Hunan Cancer Hospital
city: Changsha City
country: China
facility: Hunan Cancer Hospital
city: Chongqing City
country: China
facility: Xinqiao Hospital of Third Military Medical University
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanjing City
country: China
facility: Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
city: Qingdao City
country: China
facility: The affiliated hospital of Qingdao university
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Tianjing
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xi'an
country: China
facility: Shanxi Cancer Hospital
city: Barranquilla
country: Colombia
facility: Clinica De La Costa
city: Bogota, D.C.
country: Colombia
facility: Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio
city: Medellin
country: Colombia
facility: Instituto Cancerología Medellin
city: San Jose
country: Costa Rica
facility: Clinica CIMCA
city: San José
country: Costa Rica
facility: ICIMED Instituto de Investigación en Ciencias Médicas
city: Angers
country: France
facility: CHU Angers,Service de Pneumologie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne Billancourt
country: France
facility: Hôpital Ambroise Paré - Boulogne-Billancourt
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille cedex 20
country: France
facility: Hopital Nord
city: St Mande
country: France
facility: Hôpitaux D'Instruction Des Armees Begin
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hopital Civil
city: Toulon
country: France
facility: Hia Sainte Anne
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Larrey
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring GmbH
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: München
country: Germany
facility: LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik V, Campus Innenstadt
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Inst.&Research Center
state: Delhi
city: Gurgaon
country: India
facility: Medanta-The Medicity
state: Haryana
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Kolkata
country: India
facility: Apollo Gleneagles Hospital
state: WEST Bengal
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
state: Emilia-Romagna
city: Roma
country: Italy
facility: IRCCS Istituto Regina Elena (IFO)
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: Genova
country: Italy
facility: IRCCS A.O.U San MArtino - IST
state: Liguria
city: Brescia
country: Italy
facility: Asst Degli Spedali Civili Di Brescia
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo di Oncologia (IEO)
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Orbassano
country: Italy
facility: A.O. Universitaria S. Luigi Gonzaga
state: Piemonte
city: Bari
country: Italy
facility: IRCCS Giovanni Paolo II Istituto Oncologico
state: Puglia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Peschiera Del Garda (VR)
country: Italy
facility: Ospedale P. Pederzoli Casa di cura Privata
state: Veneto
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Aomori
country: Japan
facility: Hirosaki University Hospital
city: Chiba
country: Japan
facility: National Cancer Center East
city: Ehime
country: Japan
facility: Shikoku Cancer Center
city: Fukuoka
country: Japan
facility: NHO Kyushu Cancer Center
city: Fukuoka
country: Japan
facility: Kurume University Hospital
city: Hyogo
country: Japan
facility: Kobe City Medical Center General Hospital
city: Hyogo
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital
city: Nara
country: Japan
facility: Nara Medical University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Okayama
country: Japan
facility: Kurashiki Central Hospital
city: Osaka-sayama
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: NHO Kinki Chuo Chest Medical Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Komagome Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tottori
country: Japan
facility: Tottori University Hospital
city: Yamaguchi
country: Japan
facility: National Hospital Organization Yamaguchi - Ube Medical Center
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
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: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
state: Jalisco
city: Mexico City
country: Mexico
facility: Clinstile S.A de C.V.
state: Mexico CITY (federal District)
city: Aguascalientes
country: Mexico
facility: Centro de Investigación Oncologica Galerias
city: Ciudad de México
country: Mexico
facility: ARKE Estudios Clínicos S.A. de C.V.
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Auckland
country: New Zealand
facility: Auckland City Hospital, Cancer and Blood Research
city: Oslo
country: Norway
facility: Oslo university hospital Radiumhospitalet
city: Lublin
country: Poland
facility: Instytut Genetyki i Immunologii GENIM
city: Olsztyn
country: Poland
facility: Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
city: Wroc?aw
country: Poland
facility: Dolno?l?skie Centrum Chorób P?uc we Wroc?awiu
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia
city: Belgrade
country: Serbia
facility: Hospital Medical Center Bezanijska kosa
city: Kragujevac
country: Serbia
facility: Univ Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
state: LA Coruna
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular?Materno Infantil
state: LAS Palmas
city: Alicante
country: Spain
facility: Hospital General Univ. de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Solna
city: New Taipei City
country: Taiwan
facility: Taipei Medical University ?Shuang Ho Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung Univ Hosp
city: Taipei City
country: Taiwan
facility: National Taiwan Uni Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Municipal Wan Fang Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Xitun Dist.
country: Taiwan
facility: Taichung Veterans General Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.
city: Dusit
country: Thailand
facility: Oncology Unit, Faculty of Medicine, Vajira Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Ankara
country: Turkey
facility: Ataturk Sanatoryum Egitim Ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Gazi Uni Medical Faculty Hospital
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Bakirkoy / Istanbul
country: Turkey
facility: Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
city: Diyarbakir
country: Turkey
facility: Dicle University Faculty of Medicine
city: Erzurum
country: Turkey
facility: Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty
city: Istanbul
country: Turkey
facility: Marmara Uni Faculty of Medicine
city: Samsun
country: Turkey
facility: Medikal Park Samsun
city: Seyhan
country: Turkey
facility: Medical Park Seyhan Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Harlow
country: United Kingdom
facility: North Middlesex Hospital
city: London
country: United Kingdom
facility: Barts & London School of Med
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: