Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With Tyrosine Kinase Inhibitor- (TKI)-Resistant Epidermal Growth Factor Receptor- (EGFR)-Mutated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-789/KEYNOTE-789)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03515837
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib \[TAGRISSO®\] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status.
The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS.
Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 492
- Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC.
- Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R.
- Investigator-determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation; b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment; c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment.
- Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
- Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated.
- Life expectancy of at least 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization.
- Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents.
- Female participants must not be pregnant, not breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.
- Adequate organ function.
- Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible.
- Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
- Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40, CD137).
- Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. [Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.]
- Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- Received a live vaccine within 30 days prior to the first dose of study treatment.
- Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
- Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.)
- Known active untreated CNS metastases and/or carcinomatous meningitis.
- Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
- Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed.
- Active autoimmune disease that has required systemic treatment in past 2 years.
- History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Active infection requiring systemic therapy.
- Known history of human immunodeficiency virus (HIV) infection.
- Known history of Hepatitis B or known active Hepatitis C virus.
- Known history of active tuberculosis (TB; Bacillus tuberculosis)
- Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo+Pemetrexed+Chemo pemetrexed Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Placebo+Pemetrexed+Chemo saline solution Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Pembro+Pemetrexed+Chemo pembrolizumab Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve \[AUC\] 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Pembro+Pemetrexed+Chemo pemetrexed Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve \[AUC\] 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Pembro+Pemetrexed+Chemo carboplatin Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve \[AUC\] 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Pembro+Pemetrexed+Chemo cisplatin Participants receive pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve \[AUC\] 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Placebo+Pemetrexed+Chemo cisplatin Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Placebo+Pemetrexed+Chemo carboplatin Participants receive normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]).
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to ~40 months PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Overall Survival (OS) Up to ~51 months OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per RECIST 1.1 Up to ~51 months ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented.
Duration of Response (DOR) Per RECIST 1.1 Up to ~51 months DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score Baseline and Week 18 The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented.
Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea Baseline and up to ~51 months TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough \[EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?\], chest pain \[EORTC QLQ-LC13 Item 10; Have you had pain in your chest?\], or dyspnea \[EORTC QLQ-C30 Item 8; Were you short of breath?\]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-limit (Kaplan-Meier) method for censored data. The time to true deterioration in the composite endpoint of cough, chest pain or dyspnea is presented.
Percentage of Participants Who Experienced an Adverse Event (AE) Up to ~44 months An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented.
Percentage of Participants Who Discontinued Study Treatment Due to AEs Up to ~41 months An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented.
Trial Locations
- Locations (158)
Tangdu Hospital ( Site 0708)
🇨🇳XI An, Shanxi, China
Southwest Hospital, The Third Military Medical University ( Site 0725)
🇨🇳Chongqing, Chongqing, China
Henan Cancer Hospital ( Site 0711)
🇨🇳Zhengzhou, Henan, China
Xiangya Hospital of Central South University ( Site 0710)
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital ( Site 0722)
🇨🇳Changsha, Hunan, China
The First Hospital of Jilin University ( Site 0702)
🇨🇳Chang chun, Jilin, China
Jilin Cancer Hospital ( Site 0705)
🇨🇳Changchun, Jilin, China
Shanghai Chest Hospital ( Site 0700)
🇨🇳Shanghai, Shanghai, China
Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0701)
🇨🇳Urumqi, Xinjiang, China
Zhongshan Hospital Fudan University ( Site 0712)
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Xi an Jiaotong University ( Site 0709)
🇨🇳XI An, Shanxi, China
Sir Run Run Shaw Hospital School of Medicine, Zhejiang University ( Site 0715)
🇨🇳Hangzhou, Zhejiang, China
Clinique Victor Hugo ( Site 0802)
🇫🇷Le Mans, Sarthe, France
Fujita Health University Hospital ( Site 0619)
🇯🇵Toyoake, Aichi, Japan
Austin Health ( Site 0203)
🇦🇺Heidelberg, Victoria, Australia
Barzilai Medical Center ( Site 1706)
🇮🇱Ashkelon, HaDarom, Israel
Rabin Medical Center ( Site 1704)
🇮🇱Petah Tikva, HaMerkaz, Israel
National Hospital Organization Shikoku Cancer Center ( Site 0616)
🇯🇵Matsuyama, Ehime, Japan
Hyogo Cancer Center ( Site 0604)
🇯🇵Akashi, Hyogo, Japan
Shizuoka Cancer Center Hospital and Research Institute ( Site 0602)
🇯🇵Sunto-gun, Shizuoka, Japan
Taipei Tzu Chi Hospital ( Site 0512)
🇨🇳New Taipei City, New Taipei, Taiwan
Changhua Christian Hospital ( Site 0509)
🇨🇳Changhua, Taiwan
China Medical University Hospital ( Site 0505)
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital ( Site 0504)
🇨🇳Taichung, Taiwan
Leicester Royal Infirmary ( Site 1000)
🇬🇧Leicester, Leicestershire, United Kingdom
Sourasky Medical Center ( Site 1705)
🇮🇱Tel Aviv, Tell Abib, Israel
Niigata Cancer Center Hospital ( Site 0610)
🇯🇵Niigata, Japan
Osaka International Cancer Institute ( Site 0611)
🇯🇵Osaka, Japan
Oaxaca Site Management Organization SC ( Site 2001)
🇲🇽Oaxaca, Mexico
Instituto Jaliscience de Cancerologia ( Site 2000)
🇲🇽Guadalajara, Jalisco, Mexico
Soroka Medical Center ( Site 1702)
🇮🇱Beer-Sheva, HaDarom, Israel
National Hospital Organization Nagoya Medical Center ( Site 0608)
🇯🇵Nagoya, Aichi, Japan
Aichi Cancer Center Hospital ( Site 0612)
🇯🇵Nagoya, Aichi, Japan
Kanagawa Cancer Center ( Site 0609)
🇯🇵Yokohama, Kanagawa, Japan
National Taiwan University Hospital Hsin-Chu Branch ( Site 0511)
🇨🇳Hsinchu, Taiwan
Meir Medical Center ( Site 1701)
🇮🇱Kfar-Saba, HaMerkaz, Israel
Ha Emek Medical Center ( Site 1707)
🇮🇱Afula, HaTsafon, Israel
Rambam Medical Center ( Site 1703)
🇮🇱Haifa, Heifa, Israel
Kanazawa University Hospital ( Site 0617)
🇯🇵Kanazawa, Ishikawa, Japan
Kansai Medical University Hospital ( Site 0606)
🇯🇵Hirakata, Osaka, Japan
Okayama University Hospital ( Site 0614)
🇯🇵Okayama, Japan
Wakayama Medical University Hospital ( Site 0613)
🇯🇵Wakayama, Japan
Medica Sur S.A.B de C.V. ( Site 2003)
🇲🇽Mexico City, Mexico
Taipei Medical University Shuang Ho Hospital ( Site 0508)
🇨🇳New Taipei, Taiwan
National Cancer Center Hospital East ( Site 0601)
🇯🇵Kashiwa, Chiba, Japan
National Hospital Organization Kyushu Medical Center ( Site 0621)
🇯🇵Fukuoka, Japan
Instituto Nacional de Cancerologia. ( Site 2007)
🇲🇽Tlalpan, Mexico
Hualien Tzu Chi Medical Center-Hospital ( Site 0510)
🇨🇳Hualien, Taiwan
Kaohsiung Chang Gung Memorial Hospital ( Site 0507)
🇨🇳Kaohsiung, Taiwan
New York Oncology Hematology P.C ( Site 8000)
🇺🇸Albany, New York, United States
North Shore University Health System ( Site 0030)
🇺🇸Evanston, Illinois, United States
Siouxland Regioinal Cancer Center dba June E. Nylen Cancer Center ( Site 0065)
🇺🇸Sioux City, Iowa, United States
Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 0048)
🇺🇸Edina, Minnesota, United States
White Plains Hospital Center for Cancer Care ( Site 0014)
🇺🇸White Plains, New York, United States
Peking Union Medical College Hospital ( Site 0703)
🇨🇳Beijing, Beijing, China
Centre D Oncologie de Gentilly ( Site 0810)
🇫🇷Nancy, Meurthe-et-Moselle, France
Chris OBrien Lifehouse ( Site 0200)
🇦🇺Camperdown, New South Wales, Australia
Jewish General Hospital ( Site 0105)
🇨🇦Montreal, Quebec, Canada
Hopital Jean Minjoz Besancon ( Site 0805)
🇫🇷Besancon, Doubs, France
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 1903)
🇧🇷Sao Paulo, Brazil
Beijing Cancer Hospital ( Site 0718)
🇨🇳Beijing, Beijing, China
Emily Couric Clinical Cancer Center ( Site 0020)
🇺🇸Charlottesville, Virginia, United States
Westmead Hospital ( Site 0201)
🇦🇺Westmead, New South Wales, Australia
Memorial Sloan Kettering Cancer Center-Rockerfeller Patient Pavilion ( Site 0049)
🇺🇸New York, New York, United States
Hospital de Clinicas de Porto Alegre ( Site 1905)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Universitaetsklinikum Mannheim ( Site 0911)
🇩🇪Mannheim, Baden-Wurttemberg, Germany
Parkland Health & Hospital System ( Site 2102)
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center at Dallas ( Site 0035)
🇺🇸Dallas, Texas, United States
Sunnybrook Health Sciences, Odette Cancer Centre ( Site 0102)
🇨🇦Toronto, Ontario, Canada
The First Affiliated Hospital of Anhui Medical University ( Site 0721)
🇨🇳Hefei, Anhui, China
Liga Norte Riograndense Contra o Cancer ( Site 1909)
🇧🇷Natal, Rio Grande Do Norte, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1904)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Caridade de Ijui ( Site 1907)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
CHU Poitiers ( Site 0803)
🇫🇷Poitiers, Vienne, France
Princess Margaret Cancer Centre ( Site 0104)
🇨🇦Toronto, Ontario, Canada
Robert Bosch Krankenhaus Klinik Schillerhoehe ( Site 0904)
🇩🇪Gerlingen, Baden-Wurttemberg, Germany
Jiangsu Cancer Hospital ( Site 0719)
🇨🇳Nanjing, Jiangsu, China
Hospital Bruno Born ( Site 1913)
🇧🇷Lajeado, Rio Grande Do Sul, Brazil
Medizinische Fakultaet Carl Gustav Carus der TU Dresden ( Site 0907)
🇩🇪Dresden, Sachsen, Germany
Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1911)
🇧🇷Barretos, Sao Paulo, Brazil
William Osler Health System ( Site 0100)
🇨🇦Brampton, Ontario, Canada
Cancer Hospital Chinese Academy of Medical Sciences ( Site 0717)
🇨🇳Beijing, Beijing, China
The Affiliated Tumour Hospital of Harbin Medical University ( Site 0706)
🇨🇳Harbin, Heilongjiang, China
Florence Nightingale Krankenhaus ( Site 0912)
🇩🇪Duesseldorf, Nordrhein-Westfalen, Germany
Klinikum Wuerzburg Mitte gGmbH ( Site 0901)
🇩🇪Wuerzburg, Bayern, Germany
Asklepios Klinikum Hamburg ( Site 0908)
🇩🇪Hamburg, Germany
Hopital Prive d'Antony ( Site 0811)
🇫🇷Antony, Hauts-de-Seine, France
Azienda Ospedaliero Universitaria Careggi ( Site 1301)
🇮🇹Firenze, Italy
Centre Georges Francois Leclerc ( Site 0809)
🇫🇷Dijon, Cote-d'Or, France
Universitaetsklinikum Muenster ( Site 0906)
🇩🇪Muenster, Nordrhein-Westfalen, Germany
Kyushu University Hospital ( Site 0605)
🇯🇵Fukuoka, Japan
C.H.U. de Tours - Hopital Bretonneau ( Site 0806)
🇫🇷Tours, Indre-et-Loire, France
Samsung Medical Center ( Site 0403)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0406)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Hospitalo Univ. Germans Trias i Pujol ( Site 1100)
🇪🇸Badalona, Barcelona [Barcelona], Spain
Asan Medical Center ( Site 0407)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Hospital Universitario 12 de Octubre ( Site 1103)
🇪🇸Madrid, Spain
Seoul National University Hospital ( Site 0402)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Ulsan University Hospital ( Site 0401)
🇰🇷Ulsan, Ulsan-Kwangyokshi, Korea, Republic of
Hospital de la Santa Creu i Sant Pau ( Site 1102)
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital Ramon y Cajal ( Site 1101)
🇪🇸Madrid, Spain
Hospital Universitari Vall d Hebron ( Site 1106)
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Linkopings Universitetssjukhus ( Site 1504)
🇸🇪Linkoping, Ostergotlands Lan [se-05], Sweden
Complejo Hospitalario Carlos Haya de Malaga ( Site 1107)
🇪🇸Malaga, Spain
Hospital Universitario Virgen Macarena ( Site 1104)
🇪🇸Sevilla, Spain
Sussex University Hospitals ( Site 1003)
🇬🇧Brighton, Brighton And Hove, United Kingdom
National Cheng Kung University Hospital ( Site 0506)
🇨🇳Tainan, Taiwan
National Taiwan University Hospital ( Site 0500)
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation. Linkou ( Site 0502)
🇨🇳Taoyuan, Taiwan
Western General Hospital ( Site 1009)
🇬🇧Edinburgh, Edinburgh, City Of, United Kingdom
Barking Havering and Redbridge University Hospitals NHS Trust Queen s Hospital ( Site 1004)
🇬🇧Romford, United Kingdom
Istituto Europeo di Oncologia ( Site 1303)
🇮🇹Milano, Lombardia, Italy
AOU San Luigi Gonzaga di Orbassano ( Site 1300)
🇮🇹Orbassano, Torino, Italy
IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1305)
🇮🇹Bari, Italy
Universita Campus Bio-Medico di Roma ( Site 1304)
🇮🇹Roma, Italy
Azienda Ospedaliera dei Colli V. Monaldi ( Site 1306)
🇮🇹Napoli, Italy
Skanes Universitetssjukhus Lund ( Site 1503)
🇸🇪Lund, Skane Lan [se-12], Sweden
Karolinska Universitetssjukhuset Solna ( Site 1500)
🇸🇪Solna, Stockholms Lan [se-01], Sweden
Sahlgrenska Universitetssjukhuset ( Site 1502)
🇸🇪Goteborg, Vastra Gotalands Lan [se-14], Sweden
Pacific Cancer Care ( Site 0058)
🇺🇸Monterey, California, United States
Cedars-Sinai Medical Center ( Site 0070)
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0092)
🇺🇸Orange, California, United States
St. Joseph Heritage Healthcare ( Site 0003)
🇺🇸Santa Rosa, California, United States
Monter Cancer Center ( Site 0054)
🇺🇸Lake Success, New York, United States
Eastern Health ( Site 0202)
🇦🇺Box Hill, Victoria, Australia
Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1912)
🇧🇷Ribeirao Preto, Sao Paulo, Brazil
Fujian Cancer Hospital ( Site 0723)
🇨🇳Fuzhou, Fujian, China
Zhejiang Cancer Hospital ( Site 0716)
🇨🇳Hangzhou, Zhejiang, China
Centre Leon Berard ( Site 0801)
🇫🇷Lyon, Auvergne, France
CHU Caen Service de Pneumologie ( Site 0804)
🇫🇷Caen, Calvados, France
The First Affiliated Hospital.Zhejiang University ( Site 0713)
🇨🇳Hangzhou, Zhejiang, China
Pius Hospital Oldenburg ( Site 0905)
🇩🇪Oldenburg, Niedersachsen, Germany
Kliniken Essen-Mitte ( Site 0900)
🇩🇪Essen, Nordrhein-Westfalen, Germany
Chaim Sheba Medical Center. ( Site 1700)
🇮🇱Ramat Gan, Tell Abib, Israel
Ospedale San Vincenzo di Taormina ( Site 1302)
🇮🇹Taormina, Messina, Italy
Chungbuk National University Hospital ( Site 0404)
🇰🇷Cheongju si, Chungcheongbuk-do [Chungbuk], Korea, Republic of
National Cancer Center Hospital ( Site 0603)
🇯🇵Tokyo, Japan
Toranomon Hospital ( Site 0615)
🇯🇵Tokyo, Japan
Tokyo Metropolitan Komagome Hospital ( Site 0618)
🇯🇵Tokyo, Japan
National Cancer Center ( Site 0400)
🇰🇷Gyeonggi-do, Kyonggi-do, Korea, Republic of
Gachon University Gil Medical Center ( Site 0408)
🇰🇷Incheon, Incheon-gwangyeoksi [Incheon], Korea, Republic of
Seoul National University Bundang Hospital ( Site 0405)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Chelsea & Westminster Hospital ( Site 1001)
🇬🇧London, London, City Of, United Kingdom
University College London Hospitals NHS Foundation Trust ( Site 1006)
🇬🇧London, London, City Of, United Kingdom
Birmingham Heartlands Hospital ( Site 1002)
🇬🇧Birmingham, United Kingdom
St James s University Hospital ( Site 1008)
🇬🇧Leeds, United Kingdom
Providence Portland Medical Center ( Site 0097)
🇺🇸Portland, Oregon, United States
Saint Lukes Hospital of Kansas City ( Site 0060)
🇺🇸Kansas City, Missouri, United States
Utah Cancer Specialists ( Site 0001)
🇺🇸Salt Lake City, Utah, United States
Kaiser Permanente Northwest ( Site 0037)
🇺🇸Portland, Oregon, United States
Froedtert Hospital & the Medical College of Wisconsin ( Site 0041)
🇺🇸Milwaukee, Wisconsin, United States
Mackay Memorial Hospital ( Site 0503)
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital ( Site 0501)
🇨🇳Taipei, Taiwan
Hong Kong United Oncology Centre ( Site 0306)
🇭🇰Kowloon, Hong Kong
Queen Mary Hospital ( Site 0301)
🇭🇰Hong Kong, Hong Kong
Tuen Mun Hospital ( Site 0305)
🇭🇰Tuen Mun, Hong Kong
Queen Mary Hospital ( Site 0303)
🇭🇰Hong Kong, Hong Kong
Hong Kong Integrated Oncology Centre ( Site 0304)
🇭🇰Hong Kong, Hong Kong