Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (MK-7902-012/E7080-G000-318/LEAP-012)

Phase 3

Active, not recruiting

• Conditions: Carcinoma, Hepatocellular
• Interventions: Drug: Oral Placebo; Drug: Lenvatinib; Drug: IV Placebo; Biological: Pembrolizumab; Procedure: TACE

• Registration Number: NCT04246177
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of lenvatinib and pembrolizumab in combination with TACE versus TACE plus oral and intravenous (IV) placebos in participants with incurable, non-metastatic hepatocellular carcinoma (HCC). The primary hypotheses are that pembrolizumab plus lenvatinib in combination with TACE is superior to placebo plus TACE with respect to progression-free survival (PFS) and overall survival (OS).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-01-27
• Study First Posted: 2020-01-29
• Study Start: 2020-05-22
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Primary Completion: 2028-06-30
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• Has a diagnosis of HCC confirmed by radiology, histology, or cytology
• Has HCC localized to the liver and not amenable to curative treatment
• Participants with Hepatitis C virus (HCV) are eligible if treatment was completed at least 1 month prior to starting study intervention
• Participants with Hepatitis B virus (HBV) are eligible
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function

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Exclusion Criteria

• Is currently a candidate for liver transplantation
• Has had gastric bleeding within the last 6 months
• Has ascites that is not controlled with medication
• Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as congestive heart failure
• Has a serious nonhealing wound, ulcer, or bone fracture
• Has received locoregional therapy to existing liver lesions

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Placebo plus IV Placebo plus TACE	Oral Placebo	Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (\~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).
Oral Placebo plus IV Placebo plus TACE	IV Placebo	Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (\~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).
Lenvatinib plus Pembrolizumab plus TACE	Pembrolizumab	Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years \[\~35 cycles\] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).
Lenvatinib plus Pembrolizumab plus TACE	TACE	Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years \[\~35 cycles\] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).
Oral Placebo plus IV Placebo plus TACE	TACE	Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (\~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).
Lenvatinib plus Pembrolizumab plus TACE	Lenvatinib	Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years \[\~35 cycles\] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).

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 ~43 months	PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR).
Overall Survival (OS)	Up to ~95 months	OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Time to Progression (TTP) per mRECIST	Up to ~95 months	TTP is defined as the time from randomization to the first documented disease progression. Responses are according to mRECIST as assessed by BICR.
ORR per RESCIST 1.1	Up to ~95 months	ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by BICR.
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)	Up to ~95 months	An SAE is an AE that results in death, is life threatening, requires or prolongs a hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants who experience at least one SAE will be reported.
DCR per RECIST 1.1	Up to ~95 months	DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), or SD. Responses are according to RECIST 1.1 as assessed by BICR.
DOR per RECIST 1.1	Up to ~95 months	DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR.
TTP per RECIST 1.1	Up to ~95 months	TTP is defined as the time from randomization to the first documented disease progression. Responses are according to RECIST 1.1 as assessed by BICR.
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	Up to ~43 months	PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.
Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI)	Up to ~95 months	Percentage of participants with Hepatic ECIs not due to disease progression or TACE as assessed by the investigator will be reported.
Disease Control Rate (DCR) per mRECIST	Up to ~95 months	DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of any intratumoral arterial enhancement in all target lesions), PR (at least a 30% decrease in the sum of diameters of viable \[enhancement in the arterial phase\] target lesions, taking as reference the baseline sum of the diameters of target lesions), or stable disease (SD). Responses are according to mRECIST as assessed by BICR.
Duration of Response (DOR) per mRECIST	Up to ~95 months	DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of any intratumoral arterial enhancement in all target lesions) or PR (at least a 30% decrease in the sum of diameters of viable \[enhancement in the arterial phase\] target lesions, taking as reference the baseline sum of the diameters of target lesions) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.
Percentage of Participants Who Experience At Least One Adverse Event (AE)	Up to ~95 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
Percentage of Participants Who Discontinue Study Drug Due to an AE	Up to ~95 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug due to an AE will be reported.
Objective Response Rate (ORR) per mRECIST	Up to ~95 months	ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable \[enhancement in the arterial phase\] target lesions, taking as reference the baseline sum of the diameters of target lesions). Responses are according to mRECIST as assessed by BICR.

Trial Locations

Locations (207)

University of Cincinnati Medical Center ( Site 0791); 🇺🇸 Cincinnati, Ohio, United States

The Ohio State University Wexner Medical Center ( Site 0759); 🇺🇸 Columbus, Ohio, United States

Anhui Provincial Hospital ( Site 0092); 🇨🇳 Heifei, Anhui, China

Guangdong Provincial People s Hospital ( Site 0100); 🇨🇳 Guangzhou, Guangdong, China

Hainan General Hospital ( Site 0112); 🇨🇳 Haikou, Hainan, China

Harbin Medical University Cancer Hospital ( Site 0090); 🇨🇳 Harbin, Heilongjiang, China

Emek Medical Center ( Site 0307); 🇮🇱 Afula, Israel

Hadassah Ein Karem Jerusalem ( Site 0303); 🇮🇱 Jerusaelm, Israel

C.H.U. de Nancy. Hopital de Brabois Adultes ( Site 0180); 🇫🇷 Vandoeuvre les Nancy, Meurthe-et-Moselle, France

Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0056); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

University of Kansas Cancer Center ( Site 0731); 🇺🇸 Westwood, Kansas, United States

Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0057); 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0215); 🇩🇪 Luebeck, Schleswig-Holstein, Germany

Royal Perth Hospital ( Site 0002); 🇦🇺 Perth, Western Australia, Australia

Alfred Health ( Site 0004); 🇦🇺 Melbourne, Victoria, Australia

Yale Cancer Center ( Site 0724); 🇺🇸 New Haven, Connecticut, United States

Zala Megyei Szent Rafael Korhaz ( Site 0265); 🇭🇺 Zalaegerszeg, Zala, Hungary

Kurume University Hospital ( Site 0362); 🇯🇵 Kurume, Fukuoka, Japan

Kanagawa Cancer Center ( Site 0352); 🇯🇵 Yokohama, Kanagawa, Japan

Shizuoka Cancer Center Hospital and Research Institute ( Site 0365); 🇯🇵 Sunto-gun, Shizuoka, Japan

The University of Tokyo Hospital ( Site 0348); 🇯🇵 Tokyo, Japan

Centro de Cancer Nuestra Senora de la Esperanza ( Site 0065); 🇨🇱 Santiago, Region M. De Santiago, Chile

A.P.H. Paris, Hopital Henri Mondor ( Site 0179); 🇫🇷 Creteil, Val-de-Marne, France

St Vincents University Hospital ( Site 0690); 🇮🇪 Dublin, Ireland

Centro de Oncología de Precisión-Oncology ( Site 0068); 🇨🇱 Santiago, Region M. De Santiago, Chile

Rambam Health Care Campus-Oncology Division ( Site 0305); 🇮🇱 Haifa, Israel

Ehime University Hospital ( Site 0368); 🇯🇵 Toon, Ehime, Japan

Kagawa Prefectural Central Hospital ( Site 0364); 🇯🇵 Takamatsu, Kagawa, Japan

Kindai University Hospital ( Site 0358); 🇯🇵 Osakasayama, Osaka, Japan

Saitama Medical University Hospital ( Site 0370); 🇯🇵 Iruma-gun, Saitama, Japan

Japanese Red Cross Osaka Hospital ( Site 0356); 🇯🇵 Osaka, Japan

Centro Hospitalar de Lisboa Central, EPE - Hosp St. Ant dos Capuchos ( Site 0505); 🇵🇹 Lisboa, Portugal

Puerto Rico Medical Research Center LLC ( Site 0523); 🇵🇷 San Juan, Puerto Rico

China Medical University Hospital-Surgical Department ( Site 0610); 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital ( Site 0613); 🇨🇳 Taichung, Taiwan

Shalimov s NI of Surgery and Transplantation ( Site 0671); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

Maastricht University Medical Centre ( Site 0440); 🇳🇱 Maastricht, Limburg, Netherlands

Nara Medical University Hospital ( Site 0359); 🇯🇵 Kashihara, Nara, Japan

Jichi Medical University Hospital ( Site 0353); 🇯🇵 Shimotsuke, Tochigi, Japan

Osaka International Cancer Institute ( Site 0357); 🇯🇵 Osaka, Japan

AMC ( Site 0438); 🇳🇱 Amsterdam, Noord-Holland, Netherlands

Leids Universitair Medisch Centrum-Medical Oncology ( Site 0442); 🇳🇱 Leiden, Zuid-Holland, Netherlands

Erasmus University Medical Center ( Site 0439); 🇳🇱 Rotterdam, Zuid-Holland, Netherlands

VA Caribbean Healthcare System ( Site 0524); 🇵🇷 San Juan, Puerto Rico

FDI Clinical Research ( Site 0522); 🇵🇷 San Juan, Puerto Rico

Chulalongkorn University ( Site 0627); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

National Hospital Organization Kyushu Medical Center ( Site 0361); 🇯🇵 Fukuoka, Japan

Kumamoto University ( Site 0372); 🇯🇵 Kumamoto, Japan

University Hospital, Kyoto Prefectural University of Medicine ( Site 0367); 🇯🇵 Kyoto, Japan

National Cheng Kung University Hospital ( Site 0608); 🇨🇳 Tainan, Taiwan

Chang Gung Medical Foundation. Linkou ( Site 0607); 🇨🇳 Taoyuan, Taiwan

Hiroshima University Hospital ( Site 0360); 🇯🇵 Hiroshima, Japan

Juntendo University Hospital ( Site 0371); 🇯🇵 Tokyo, Japan

Centro Hospitalar e Universitario de Coimbra ( Site 0502); 🇵🇹 Coimbra, Portugal

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0503); 🇵🇹 Porto, Portugal

Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0441); 🇳🇱 Utrecht, Netherlands

Ad-Vance Medical Research LLC ( Site 0527); 🇵🇷 Ponce, Puerto Rico

Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0609); 🇨🇳 Kaohsiung City, Kaohsiung, Taiwan

Faculty of Medicine Siriraj Hospital ( Site 0629); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Asan Medical Center ( Site 0565); 🇰🇷 Seoul, Korea, Republic of

Arizona Oncology Associates PC- HOPE ( Site 0770); 🇺🇸 Tucson, Arizona, United States

Scripps Clinic Torrey Pines ( Site 0714); 🇺🇸 La Jolla, California, United States

USC Norris Comprehensive Cancer Center ( Site 0717); 🇺🇸 Los Angeles, California, United States

UCLA Hematology/Oncology - Santa Monica ( Site 0720); 🇺🇸 Los Angeles, California, United States

UC Irvine Health ( Site 0718); 🇺🇸 Orange, California, United States

Tampa General Hospital ( Site 0764); 🇺🇸 Tampa, Florida, United States

Mountain States Tumor Institute ( Site 0773); 🇺🇸 Boise, Idaho, United States

University of Iowa Hospital and Clinics ( Site 0729); 🇺🇸 Iowa City, Iowa, United States

University Medical Center New Orleans ( Site 0733); 🇺🇸 New Orleans, Louisiana, United States

Tulane Medical Center ( Site 0787); 🇺🇸 New Orleans, Louisiana, United States

Henry Ford Hospital-GI/Hepatology Research ( Site 0735); 🇺🇸 Detroit, Michigan, United States

University of Louisville ( Site 0757); 🇺🇸 Louisville, Kentucky, United States

Saint Louis University ( Site 0769); 🇺🇸 Saint Louis, Missouri, United States

University of New Mexico Comprehensive Cancer Center ( Site 0805); 🇺🇸 Albuquerque, New Mexico, United States

Wake Forest Baptist Health ( Site 0741); 🇺🇸 Winston-Salem, North Carolina, United States

Monter Cancer Center ( Site 0780); 🇺🇸 Lake Success, New York, United States

Icahn School of Medicine at Mount Sinai ( Site 0744); 🇺🇸 New York, New York, United States

Penn State Hershey Medical Center ( Site 0766); 🇺🇸 Hershey, Pennsylvania, United States

OHSU Center for Health & Healing ( Site 0746); 🇺🇸 Portland, Oregon, United States

ProMedica Flower Hospital ( Site 0796); 🇺🇸 Sylvania, Ohio, United States

Stephenson Cancer Center ( Site 0745); 🇺🇸 Oklahoma City, Oklahoma, United States

Edwards Comprehensive Cancer Center ( Site 0786); 🇺🇸 Huntington, West Virginia, United States

Houston Methodist Research Institute ( Site 0784); 🇺🇸 Houston, Texas, United States

St George Hospital ( Site 0005); 🇦🇺 Kogarah, New South Wales, Australia

Princess Alexandra Hospital ( Site 0006); 🇦🇺 Brisbane, Queensland, Australia

Westmead Hospital-Gastroenterology & Hepatology ( Site 0009); 🇦🇺 Westmead, New South Wales, Australia

Austin Health ( Site 0008); 🇦🇺 Heidelberg, Victoria, Australia

Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 0058); 🇧🇷 Barretos, Sao Paulo, Brazil

Clinica de Oncologia Reichow ( Site 0052); 🇧🇷 Blumenau, Santa Catarina, Brazil

Fundacao Dr Amaral Carvalho ( Site 0050); 🇧🇷 JAU, Sao Paulo, Brazil

Hospital de Base de Sao Jose de Rio Preto ( Site 0043); 🇧🇷 Sao Jose do Rio Preto, Sao Paulo, Brazil

A.C. Camargo Cancer Center ( Site 0054); 🇧🇷 Sao Paulo, Brazil

BP - A Beneficencia Portuguesa de São Paulo ( Site 0046); 🇧🇷 São Paulo, Sao Paulo, Brazil

Centro Investigación del Cáncer James Lind ( Site 0064); 🇨🇱 Temuco, Araucania, Chile

Beijing Cancer Hospital ( Site 0099); 🇨🇳 Beijing, Beijing, China

Bradfordhill ( Site 0066); 🇨🇱 Santiago, Region M. De Santiago, Chile

Peking Union Medical College Hospital ( Site 0087); 🇨🇳 Beijing, Beijing, China

Beijing Cancer Hospital ( Site 0105); 🇨🇳 Beijing, Beijing, China

Chinese People s Liberation Army Army Characteristic Medical Center ( Site 0117); 🇨🇳 Chongqing, Chongqing, China

Chongqing Three Gorges Central Hospital ( Site 0859); 🇨🇳 Wanzhou, Chongqing, China

Mengchao Hepatobiliary Hospital of Fujian Medical University ( Site 0121); 🇨🇳 Fuzhou, Fujian, China

Fujian Provincial Cancer Hospital ( Site 0085); 🇨🇳 Fuzhou, Fujian, China

The First Affiliated Hospital of Fujian Medical University ( Site 0089); 🇨🇳 Fuzhou, Fujian, China

Zhongshan Hospital Fudan University (Xiamen Branch) ( Site 0133); 🇨🇳 Xiamen, Fujian, China

Zhujiang Hospital of Southern Medical University ( Site 0115); 🇨🇳 Guangzhou, Guangdong, China

Nanfang Hospital of Southern Medical University ( Site 0088); 🇨🇳 Guangzhou, Guangdong, China

SUN YAT-SEN UNIVERSITY CANCER CENTRE-Department of Medical Imaging and Interventional Radiology ( Si; 🇨🇳 Guangzhou, Guangdong, China

Jinan University - Zhuhai People's Hospital-Intervention Department ( Site 0856); 🇨🇳 Zhuhai, Guangdong, China

Guangxi Medical University Affiliated Tumor Hospital-Hepatological surgery ( Site 0862); 🇨🇳 Nanning, Guangxi, China

Henan Cancer Hospital ( Site 0114); 🇨🇳 Zhengzhou, Henan, China

Hubei Cancer Hospital ( Site 0101); 🇨🇳 Wuhan, Hubei, China

Tongji Hospital Tongji Medical,Science & Technology ( Site 0126); 🇨🇳 Wuhan, Hubei, China

Hunan Provincial People's Hospital ( Site 0113); 🇨🇳 Changsha, Hunan, China

Hunan Cancer Hospital ( Site 0096); 🇨🇳 Changsha, Hunan, China

Jiangxi Provincial Cancer Hospital-Cancer Hospital ( Site 0134); 🇨🇳 Nanchang, Jiangxi, China

Xi'an International Medical Center Hospital ( Site 0860); 🇨🇳 Xi'an, Shaanxi, China

The First Affiliated Hospital of Soochow University ( Site 0120); 🇨🇳 Suzhou, Jiangsu, China

The Third Affiliated Hospital of Naval Medical University ( Site 0123); 🇨🇳 Shanghai, Shanghai, China

Fudan University Shanghai Cancer Center ( Site 0106); 🇨🇳 Shanghai, Shanghai, China

The First Affiliated Hospital of Xi an Jiaotong University ( Site 0108); 🇨🇳 XI An, Shanxi, China

Zhongshan Hospital Fudan University ( Site 0084); 🇨🇳 Shanghai, Shanghai, China

Tianjin Third Central Hospital ( Site 0861); 🇨🇳 Tianjin, Tianjin, China

West China Hospital of Sichuan University ( Site 0119); 🇨🇳 Chengdu, Sichuan, China

Suining Central Hospital ( Site 0857); 🇨🇳 Suining, Sichuan, China

Tianjin Medical University Cancer Institute & Hospital ( Site 0098); 🇨🇳 Tianjin, Tianjin, China

The First Hospital of Kunming ( Site 0124); 🇨🇳 Kunming, Yunnan, China

2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0110); 🇨🇳 Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital ( Site 0094); 🇨🇳 Hangzhou, Zhejiang, China

Fundacion Cardiovascular de Colombia ( Site 0136); 🇨🇴 Piedecuesta, Santander, Colombia

Hospital Pablo Tobon Uribe ( Site 0145); 🇨🇴 Medellin, Antioquia, Colombia

Ningbo Medical Center ( Site 0132); 🇨🇳 Ningbo, Zhejiang, China

Zhejiang Cancer Hospital ( Site 0103); 🇨🇳 Hangzhou, Zhejiang, China

Administradora Country S.A. ( Site 0137); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Herlev Hospital ( Site 0170); 🇩🇰 Herlev, Hovedstaden, Denmark

Aarhus Universitets hospital ( Site 0175); 🇩🇰 Aarhus N, Midtjylland, Denmark

Fundacion Valle del Lili ( Site 0140); 🇨🇴 Cali, Valle Del Cauca, Colombia

Odense Universitetshospital ( Site 0160); 🇩🇰 Odense, Syddanmark, Denmark

Hopital de la Croix-Rousse ( Site 0193); 🇫🇷 Lyon, Auvergne, France

Hopital Paul Brousse ( Site 0182); 🇫🇷 Villejuif, Val-de-Marne, France

Hopital de la Timone ( Site 0188); 🇫🇷 Marseille, Bouches-du-Rhone, France

CHU Bordeaux Haut-Leveque ( Site 0185); 🇫🇷 Pessac Cedex, Gironde, France

Krankenhaus Nord-West GmbH ( Site 0208); 🇩🇪 Frankfurt am Main, Hessen, Germany

Universitaetsklinikum Freiburg ( Site 0199); 🇩🇪 Freiburg, Baden-Wurttemberg, Germany

Universitaetsklinikum Halle ( Site 0213); 🇩🇪 Halle (Saale), Sachsen-Anhalt, Germany

Universitaetsklinikum Bonn ( Site 0203); 🇩🇪 Bonn, Nordrhein-Westfalen, Germany

Medizinische Hochschule Hannover ( Site 0200); 🇩🇪 Hannover, Niedersachsen, Germany

Universitaetsklinikum Leipzig ( Site 0202); 🇩🇪 Leipzig, Sachsen, Germany

Charite - Universitaetsmedizin ( Site 0204); 🇩🇪 Berlin, Germany

Universitaetsklinikum Hamburg-Eppendorf ( Site 0207); 🇩🇪 Hamburg, Germany

Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0267); 🇭🇺 Kaposvár, Somogy, Hungary

Prince of Wales Hospital ( Site 0242); 🇭🇰 Shatin, Hong Kong

Semmelweis University ( Site 0264); 🇭🇺 Budapest, Hungary

Rabin Medical Center ( Site 0304); 🇮🇱 Petah Tikva, Israel

Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0333); 🇮🇹 Torino, Piemonte, Italy

ASST Grande Ospedale Metropolitano Niguarda-Oncologia Falck ( Site 0331); 🇮🇹 Milan, Milano, Italy

Sourasky Medical Center ( Site 0306); 🇮🇱 Tel Aviv, Israel

AOU Policlinico G. Martino ( Site 0324); 🇮🇹 Messina, Sicilia, Italy

Ospedale del Mare ( Site 0327); 🇮🇹 Napoli, Campania, Italy

Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0334); 🇮🇹 Brescia, Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico ( Site 0325); 🇮🇹 Milano, Italy

Az Osp di Rilievo Nazionale A. Cardarelli ( Site 0329); 🇮🇹 Napoli, Italy

Policlinico Universitario -Agostino Gemelli ( Site 0328); 🇮🇹 Roma, Italy

Azienda USL della Romagna-Dipartimento di Oncologia ed Ematologia ( Site 0332); 🇮🇹 Ravenna, Italy

National Cancer Center Hospital East ( Site 0347); 🇯🇵 Kashiwa, Chiba, Japan

Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0345); 🇯🇵 Sapporo, Hokkaido, Japan

Yokohama City University Medical Center ( Site 0351); 🇯🇵 Yokohama, Kanagawa, Japan

Kanazawa University Hospital ( Site 0354); 🇯🇵 Kanazawa, Ishikawa, Japan

Toranomon Hospital Kajigaya ( Site 0369); 🇯🇵 Kawasaki, Kanagawa, Japan

Chiba University Hospital ( Site 0346); 🇯🇵 Chiba, Japan

Saga-Ken Medical Centre Koseikan ( Site 0363); 🇯🇵 Saga, Japan

Toranomon Hospital ( Site 0349); 🇯🇵 Tokyo, Japan

Chonnam National University Hwasun Hospital ( Site 0572); 🇰🇷 Hwasun, Jeonranamdo, Korea, Republic of

Pusan National University Hospital ( Site 0568); 🇰🇷 Busan, Pusan-Kwangyokshi, Korea, Republic of

Kyungpook National University Hospital ( Site 0569); 🇰🇷 Daegu, Taegu-Kwangyokshi, Korea, Republic of

Seoul National University Hospital ( Site 0567); 🇰🇷 Seoul, Korea, Republic of

Seoul National University Bundang Hospital ( Site 0570); 🇰🇷 Seongnam-si, Kyonggi-do, Korea, Republic of

Korea University Guro Hospital ( Site 0573); 🇰🇷 Seoul, Korea, Republic of

Auckland City Hospital ( Site 0459); 🇳🇿 Auckland, New Zealand

Oslo Universitetssykehus Ullevål ( Site 0500); 🇳🇴 Oslo, Norway

Centro Hospitalar do Porto, E.P.E. - Hospital Geral de Sto. Antonio ( Site 0504); 🇵🇹 Porto, Portugal

Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 0501); 🇵🇹 Porto, Portugal

Hospital Universitario Puerta de Hierro ( Site 0596); 🇪🇸 Majadahonda, Madrid, Spain

Hospital Ramon y Cajal ( Site 0593); 🇪🇸 Madrid, Spain

Hospital General Universitario de Valencia ( Site 0595); 🇪🇸 Valencia, Valenciana, Comunitat, Spain

Kaohsiung Medical University Hospital ( Site 0611); 🇨🇳 Kaohsiung, Taiwan

Hospital Virgen del Rocio ( Site 0591); 🇪🇸 Sevilla, Spain

National Taiwan University Hospital ( Site 0606); 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital-Division of Gastroenterology & Hepatology, Department of Medicine (; 🇨🇳 Taipei, Taiwan

Ramathibodi Hospital, Mahidol University ( Site 0628); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Trakya University Medical Faculty Balkan Oncology Hospital ( Site 0648); 🇹🇷 Edirne, Turkey

Hacettepe University Medical Faculty ( Site 0653); 🇹🇷 Ankara, Turkey

Ankara City Hospital-Medical Oncology ( Site 0661); 🇹🇷 Ankara, Turkey

Bezmialem Vakf Üniversitesi-Oncology ( Site 0660); 🇹🇷 Istanbul, Turkey

Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 0654); 🇹🇷 Izmir, Turkey

I.E.U. Medical Point Hastanesi ( Site 0649); 🇹🇷 Izmir, Turkey

Konya Necmettin Erbakan University Medical Faculty ( Site 0652); 🇹🇷 Konya, Turkey

Inonu Universitesi Medical Fakultesi ( Site 0650); 🇹🇷 Malatya, Turkey

Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0673); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Communal non profit enterprise Regional Clinical Oncology Center ( Site 0669); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Royal Marsden NHS Trust ( Site 0693); 🇬🇧 Sutton, London, City Of, United Kingdom

Barts Health NHS Trust ( Site 0692); 🇬🇧 London, London, City Of, United Kingdom

Royal Marsden NHS Foundation Trust ( Site 0694); 🇬🇧 London, London, City Of, United Kingdom

Severance Hospital Yonsei University Health System ( Site 0564); 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center ( Site 0566); 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea St. Mary s Hospital ( Site 0571); 🇰🇷 Seoul, Korea, Republic of

Hospital General Universitario Gregorio Maranon ( Site 0598); 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos ( Site 0597); 🇪🇸 Madrid, Spain