A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03178552
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a phase 2/3, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic NSCLC determined to harbor oncogenic somatic mutations or positive by tumor mutational burden (TMB) assay as identified by a blood-based next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assay.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1000
- Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Measurable disease
- Adequate recovery from most recent systemic or local treatment for cancer
- Adequate organ function
- Life expectancy greater than or equal to (>/=) 12 weeks
- For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception
- Inability to swallow oral medication
- Women who are pregnant or lactating
- Symptomatic, untreated CNS metastases
- History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with negligible risk of metastasis or death
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
- Known active or uncontrolled human immunodeficiency virus (HIV) infection
- Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
- Inability to comply with other requirements of the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Alectinib 600 Milligrams (mg) Alectinib This cohort includes participants with anaplastic lymphoma kinase (ALK) positive NSCLC. Participants will receive alectinib 600 mg orally twice in a day (BID) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort A is complete. Cohort C: Gemcitabine, Cisplatin or Carboplatin Gemcitabine This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m\^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m\^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete. Cohort D: Entrectinib 600 Milligrams (mg) Entrectinib This cohort includes participants with c-ros oncogene 1 positive (ROS1+) NSCLC. Participants will receive entrectinib 600 mg orally once a day (QD) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort D is complete. Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib Atezolizumab This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete. Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed Pemetrexed This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete. Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed Bevacizumab This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete. Cohort G: Divarasib or Docetaxel Divarasib Experimental: Cohort G: GDC-6036 or Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD or IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity New participants will no longer receive docetaxel. Cohort G: Divarasib or Docetaxel Docetaxel Experimental: Cohort G: GDC-6036 or Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD or IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity New participants will no longer receive docetaxel. Cohort B: Dose Finding Phase (DFP) Alectinib Alectinib This cohort includes participants with rearranged during transfection (RET) positive NSCLC. Participants may receive alectinib 900 or 1200 mg orally BID until disease progression, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study. Participants may receive 750 mg or 600 mg, if it is unsafe to pursue the higher starting dose. Enrollment to Cohort B is complete. Cohort B: Dose Expansion Phase (DEP) Alectinib Alectinib This cohort includes participants with RET positive NSCLC. Participants will receive alectinib at the RP2D established in the DFP of Cohort B or a separate clinical study. Participants will continue receiving study treatment until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort B is complete. Cohort C: Atezolizumab 1200 mg Atezolizumab This cohort includes participants with bTMB positive NSCLC. Participants will receive atezolizumab at a dose of 1200 mg administered by IV infusion every 21 days (Q21D) until disease progression, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort C is complete. Cohort C: Pemetrexed, Cisplatin or Carboplatin Pemetrexed This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m\^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete. Cohort C: Pemetrexed, Cisplatin or Carboplatin Carboplatin This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m\^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete. Cohort C: Gemcitabine, Cisplatin or Carboplatin Cisplatin This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m\^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m\^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete. Cohort C: Pemetrexed, Cisplatin or Carboplatin Cisplatin This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m\^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete. Cohort C: Gemcitabine, Cisplatin or Carboplatin Carboplatin This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m\^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m\^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete. Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib Vemurafenib This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete. Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib Cobimetinib This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete. Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed Atezolizumab This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete. Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed Carboplatin This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete.
- Primary Outcome Measures
Name Time Method Cohort A: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on RECIST v1.1 in bTMB PP1 Baseline up to disease progression or death (up to approximately 6 years) Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohort E: Time in Response (TIR) as Assessed by the Investigator Based on RECIST v1.1 Month 12 Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohort G: Incidence of Adverse Events (AEs) Baseline to last dose of study treatment + 30 days or until initiation of new anticancer therapy, whichever occurs first (up to approximately 6 years)
- Secondary Outcome Measures
Name Time Method Cohort E: TIR as Assessed by IRF Month 12 Cohorts A-F: Overall Survival (OS) Baseline up to approximately 6 years Cohorts C, E, F: Change from Baseline in Patient-Reported Lung Cancer Symptom (Cough, Dyspnea, Chest pain) Score as Measured by the SILC Scale Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohorts A, B, D, E, F: Change from Baseline in HRQoL Scores as Measured by the SILC Scale Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohorts A, B, D, E, F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the SILC Scale Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohorts A-F: Duration of Response (DOR) as Assessed by the Investigator Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by the Investigator Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A, B, D, F: PFS as Assessed by the Investigator Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A-F: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by IRF Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A-F: PFS as Assessed by IRF Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A-F: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohorts A-F: Percentage of Participants with Adverse Events (AEs) Baseline up to approximately 6 years Cohorts A, B, D, E, F: Percentage of Participants with Improvement Compared with Baseline in Total Severity Symptom Score as Measured by Symptoms in Lung Cancer (SILC) Scale in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohorts A-F: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by the SILC Scale Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohorts A-F: Change from Baseline in Health Related Quality of Life (HRQoL) Scores as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohorts A-F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the EORTC QLQ-C30 Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) Cohort B: Metabolite to Parent Exposure Ratio for Cmax DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) Cohort D: Time to CNS progression as Assessed by the Investigator Based on RECIST v1.1 Baseline up to CNS progression (up to approximately 6 years) Cohort D: Time to CNS progression as Assessed by the IRF Based on RECIST v1.1 Baseline up to CNS progression (up to approximately 6 years) Cohorts A-F: Health Status Assessed as an Index Score Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs) Day 1 to Day 28 of Cycle 1 (cycle length = 28 days) Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib DFP: pre-dose (0 hours [hr]) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) DFP: Dose-Finding Phase; DEP: Dose-Expanding Phase.
Cohort B: Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of Alectinib DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) Cohort B: Time to Reach Cmax (Tmax) of Alectinib DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) Cohort B: Half-Life (t1/2) of Alectinib DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) Cohort C: Percentage of Participants with Objective Response as Assessed by the Investigator Based on RECIST v1.1 Baseline up to disease progression or death (up to approximately 6 years) Cohort C: Percentage of Participants Free from Disease Progression as Assessed by the Investigator Based on RECIST v1.1 at Months 6 and 12 Months 6, 12 Cohort C: PFS as Assessed by the Investigator based on RECIST v1.1 in bTMB PP2 Baseline up to disease progression or death (up to approximately 6 years) Cohort C: OS in bTMB PP2 Baseline up to approximately 6 years Cohort D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-C30 Baseline, every 4 weeks until disease progression, up to approximately 6 years Cohort D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-BN20 Baseline, every 4 weeks until disease progression, up to approximately 6 years Cohort D: Mean Plasma Concentration of Entrectinib Metabolite M5 Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days). Cohorts E, F: Proportion of Participants who Improve Compared with Baseline in Participant-Reported Lung Cancer Symptoms of Cough, Dyspnea, and Chest Pain, as Measured by the SILC Baseline up to approximately 6 years Cohorts E, F: Change from Baseline in Anti-Drug Antibodies (ADAs) Baseline up to approximately 6 years Cohort D: Mean Plasma Concentration of Entrectinib Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days). Cohort E: TIR as Assessed by the Investigator Based on RECIST v1.1 Month 9 Cohorts E, F: Serum Concentration of Atezolizumab Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days) Cohorts E, F: Time to Confirmed Deterioration (TTCD) in Participant-Reported Lung Cancer Symptoms of Cough, Dyspnea, and Chest Pain, as Measured by the Symptoms in Lung Cancer (SILC) Baseline up to approximately 6 years Cohort G: Plasma Concentration of Divarasib Baseline up to approximately 6 years
Trial Locations
- Locations (159)
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
Instituto Peruano de Oncología y Radioterapia
🇵🇪Lima, Peru
Clinica Ricardo Palma
🇵🇪San Isidro, Peru
Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
🇵🇱Gda?sk, Poland
Krakowski Szpital Specjalistyczny im sw.Jana Pawla II
🇵🇱Krakow, Poland
Chang Gung Medical Foundation - Linkou
🇨🇳Taoyuan, Taiwan
Jilin Cancer Hospital
🇨🇳Changchun, China
Hunan Cancer Hospital
🇨🇳Changsha City, China
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
University Hospital Medical Center Bezanijska kosa
🇷🇸Belgrade, Serbia
Clinical Center Nis
🇷🇸NIS, Serbia
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
UC Davis
🇺🇸Sacramento, California, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
SCRI Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialist, North Region
🇺🇸Saint Petersburg, Florida, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Weill Cornell Medical College-New York Presbyterian Hospital
🇺🇸New York, New York, United States
Oregon HSU
🇺🇸Portland, Oregon, United States
St. Luke's University Health network
🇺🇸Bethlehem, Pennsylvania, United States
Sarah Cannon Research Institute / Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
Hospital Italiano
🇦🇷Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Ashford Cancer Center Research
🇦🇺Kurralta Park, South Australia, Australia
UZ Brussel
🇧🇪Brussel, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
🇧🇷Ijui, 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
🇧🇷Sao Paulo, São Paulo, Brazil
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
William Osler Health System Brampton Civic Hospital
🇨🇦Brampton, Ontario, Canada
London Health Sciences Centre · Victoria Hospital
🇨🇦London, Ontario, Canada
Lakeridge Health Center
🇨🇦Oshawa, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
IUCPQ (Hôpital Laval)
🇨🇦Quebec City, Quebec, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Bradford Hill Centro de Investigaciones Clinicas
🇨🇱Recoleta, Chile
The second Xiangya hospital of central south university
🇨🇳Changsha City, China
Sichuan Cancer Hospital
🇨🇳Chengdu City, China
West China Hospital - Sichuan University
🇨🇳Chengdu City, China
The First Affiliated Hospital of Guangzhou Medical University Pharmacy
🇨🇳Guangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou City, China
Shandong Cancer Hospital
🇨🇳Jinan, China
The Second Affiliated Hospital to Nanchang University
🇨🇳Nanchang, China
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing City, China
Fudan Unviversity Shanghai Cancer Center
🇨🇳Shanghai, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Centre Oscar Lambret
🇫🇷Lille, France
Centre Léon Bérard
🇫🇷Lyon, France
Hopital Caremeau
🇫🇷Nimes, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Hopital Tenon
🇫🇷Paris, France
CHU Poitiers
🇫🇷Poitiers, France
Hopital Pontchaillou
🇫🇷Rennes, France
CHU de Toulouse - Hôpital Larrey
🇫🇷Toulouse Cedex 9, France
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Asklepios-Fachklinik Muenchen-Gauting
🇩🇪Gauting, Germany
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
HSK Dr.-Horst-Schmidt-Kliniken Klinik für Innere Medizin III Onkologie Hämatologie und Palliativmed
🇩🇪Wiesbaden, Germany
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hosp
🇭🇰Shatin, Hong Kong
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar-Saba, Israel
Rabin MC
🇮🇱Petach Tikva, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Sourasky / Ichilov Hospital; Dept. of Oncology
🇮🇱Tel Aviv, Israel
Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
🇮🇹Meldola, Emilia-Romagna, Italy
Irccs Centro Di Riferimento Oncologico (CRO)
🇮🇹Aviano, Friuli-Venezia Giulia, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Lazio, Italy
Asst Papa Giovanni XXIII
🇮🇹Bergamo, Lombardia, Italy
ASST di Cremona - Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹Cremona, Lombardia, Italy
Irccs Istituto Europeo di Oncologia (IEO)
🇮🇹Milano, Lombardia, Italy
Asst Di Monza
🇮🇹Monza, Lombardia, Italy
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
🇮🇹Orbassano (TO), Piemonte, Italy
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
🇯🇵Bunkyo-ku, Japan
National Hospital Organization Kyushu Medical Center
🇯🇵Fukuoka, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Kanazawa University Hospital
🇯🇵Ishikawa, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Sendai Kousei Hospital
🇯🇵Miyagi, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Saga University Hospital
🇯🇵Saga, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Kyorin University Hospital
🇯🇵Tokyo, Japan
Fujita Health University Hospital
🇯🇵Toyoake-shi, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
National Hospital Organization Yamaguchi - Ube Medical Center
🇯🇵Yamaguchi, Japan
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System/Severance Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Angeles Tijuana
🇲🇽Tijuana, BAJA California, Mexico
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
AVIX Investigación Clínica S.C
🇲🇽Monterrey, Nuevo LEON, Mexico
Oncologico Potosino
🇲🇽San Luis Potosí, SAN LUIS Potosi, Mexico
Auckland City Hospital
🇳🇿Auckland, New Zealand
Hemato Oncología de Panamá Especializada
🇵🇦Panama City, Panama
Hospital Nacional Edgardo Rebagliati Martins
🇵🇪Lima, Peru
Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
🇵🇱Olsztyn, Poland
Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
🇵🇱Otwock, Poland
Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
🇵🇱Poznan, Poland
Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
🇵🇱Warszawa, Poland
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
Principal Military Clinical Hospital n.a. N.N. Burdenko
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
🇷🇺Saint-Petersburg, Sankt Petersburg, Russian Federation
Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
National University Hospital
🇸🇬Singapore, Singapore
National Cancer Centre
🇸🇬Singapore, Singapore
Insititut Catala D'Oncologia
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
🇪🇸Santiago de Compostela, LA Coruna, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital General Univ. de Alicante
🇪🇸Alicante, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clínic i Provincial
🇪🇸Barcelona, Spain
ICO Badalona - Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Quiron de Madrid
🇪🇸Madrid, Spain
Hospital Regional Universitario Carlos Haya
🇪🇸Malaga, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan Uni Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chulalongkorn Hospital
🇹🇭Bangkok, Thailand
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Faculty of Med. Siriraj Hosp.
🇹🇭Bangkok, Thailand
Prince of Songkla University
🇹🇭Hat Yai, Thailand
Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
🇹🇷Adana, Turkey
Akdeniz University Medical Faculty; Medical Oncology Department
🇹🇷Antalya, Turkey
Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
🇹🇷Edirne, Turkey
Medipol University Medical Faculty; Oncology Department
🇹🇷Istanbul, Turkey
Marmara University Pendik Training and Research Hospital; Medikal Onkoloji
🇹🇷Istanbul, Turkey
Medikal Park Izmir Hospital
🇹🇷Kar??yaka, Turkey
Hacettepe Uni Medical Faculty Hospital; Oncology Dept
🇹🇷Sihhiye/Ankara, Turkey