Study of Pembrolizumab Given Prior to Surgery and in Combination With Radiotherapy Given Post-surgery for Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-689)

Phase 3

Active, not recruiting

• Conditions: Head and Neck Neoplasms
• Interventions: Biological: Pembrolizumab 200 mg; Radiation: Radiotherapy 60 Gray; Radiation: Radiotherapy 66 Gray; Radiation: Radiotherapy 70 Gray; Drug: Cisplatin 100 mg/m^2

• Registration Number: NCT03765918
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This is a randomized, active-controlled, open-label study of pembrolizumab (Pembro) given prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or without cisplatin), as post-surgical therapy in treatment naïve participants with newly diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell carcinoma (LA-HNSCC). Efficacy outcomes will be stratified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary hypothesis is that pembrolizumab given before surgery and after surgery in combination with radiotherapy (with or without cisplatin) improves event-free survival compared to radiotherapy (with or without cisplatin) given after surgery alone.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-11-06
• Study First Submitted QC: 2018-12-04
• Study First Posted: 2018-12-05
• Study Start: 2018-12-17
• Primary Completion: 2024-07-25
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-07
• Study Completion: 2026-09-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 714

Inclusion Criteria

• Has histologically confirmed new diagnosis of resectable, non-metastatic, squamous cell carcinoma that is either: Stage III Human Papillomavirus (HPV) positive oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no distant metastases (M0); Stage III or IVA oropharyngeal HPV negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries.
• Is eligible for primary surgery based on investigator decision and per local practice
• Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy.
• Male participants must refrain from donating sperm throughout the study period and for up to 180 days after the last dose of study therapy
• Female participant that is not pregnant or breastfeeding
• Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST version 1.1
• Has provided newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Has results from testing of HPV status for oropharyngeal cancer defined as p16
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of randomization

Exclusion Criteria

• Has Stage T4B and/or N3 LA HNSCC and/or distant metastases
• Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity. such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer (HNC)
• Female participant who has a positive urine pregnancy test within 72 hours prior to study start or within 24 hours prior to the start of radiotherapy with or without cisplatin.
• Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti-programmed cell death receptor ligand 1(PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor
• Has received prior radiotherapy treatment or systemic anti-cancer therapy including investigational agents for the HNC under study prior to study start
• Has received a live vaccine within 30 days prior to randomization
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy
• Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis
• Has Grade ≥2 audiometric hearing loss
• Has Grade ≥2 neuropathy
• Has Grade 3-4 bleeding due to the underlying malignancy
• Has received major surgery or has not recovered adequately from the toxicity and/or complications from the intervention prior to study start
• Has had previous allogeneic tissue/solid organ transplant
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, radiotherapy, cisplatin or their analogs
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of or is positive for Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C (defined as Hepatitis C virus [HCV] ribonucleic acid is detected).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the investigator
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembro Neoadjuvant+Pembro SOC Adjuvant	Pembrolizumab 200 mg	Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
Pembro Neoadjuvant+Pembro SOC Adjuvant	Radiotherapy 60 Gray	Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
Pembro Neoadjuvant+Pembro SOC Adjuvant	Radiotherapy 66 Gray	Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
Pembro Neoadjuvant+Pembro SOC Adjuvant	Radiotherapy 70 Gray	Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
Pembro Neoadjuvant+Pembro SOC Adjuvant	Cisplatin 100 mg/m^2	Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
No Neoadjuvant+SOC Adjuvant	Radiotherapy 60 Gray	Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.
No Neoadjuvant+SOC Adjuvant	Radiotherapy 66 Gray	Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.
No Neoadjuvant+SOC Adjuvant	Radiotherapy 70 Gray	Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.
No Neoadjuvant+SOC Adjuvant	Cisplatin 100 mg/m^2	Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m\^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.

Primary Outcome Measures

Name	Time	Method
Event-free Survival (EFS)	Up to ~80 months	EFS is the time from the date of randomization to the date of first record of any of the following events: radiographic disease progression; local or distant progression or recurrence as assessed with imaging or biopsy as indicated; or death due to any cause. Radiographic disease progression during neoadjuvant phase that precludes surgery will be considered an event; a secondary malignancy will not be considered an event.

Secondary Outcome Measures

Name	Time	Method
Major Pathological Response (mPR)	Up to ~64 months	The percentage of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.
Change From Baseline in Global Health Status/Physical Functioning Scales	Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)	Change from baseline in the combined score of physical functioning scale using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 1 through 5. Participant responses to questions regarding their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much) with a higher score indicating worse physical functioning.
Change from Baseline in Swallowing, Speech, and Pain Symptoms	Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)	Change from baseline in the combined score of swallowing, speech, and pain symptoms using the European Organization for Research and Treatment of Cancer Head and Neck Questionnaire (EORTC QLQ-H\&N35) items 31-38, 46, and 53-54. Participant responses to questions regarding problems with swallowing, speech and pain in the mouth will be scored on a 4-point scale (1=Not at all to 4=Very much) with a higher score indicating more problems.
Percentage of Participants Discontinuing Study Drug Due to AEs	From time of first dose of study treatment until the end of treatment (up to 12 months)	Percentage of participants discontinuing study drug due to an AE
Overall Survival (OS)	Up to ~92 months	OS is the time from randomization to death due to any cause.
Change From Baseline in Global Health Status/Quality of Life Scale (GHS/QoL)	Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)	Change from baseline in the combined score of global health status (GHS)/quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 29 and 30. Participant responses to questions regarding overall health/QoL will be scored on a 7-point scale (1=Very poor to 7=Excellent) with a higher score indicating better overall health status.
Pathological Complete Response (pCR)	Up to ~64 months	Pathological complete response (pCR) is measured as the percentage of participants with a pathological complete response as assessed by the central pathologist at the time of definitive surgery. pCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.
Percentage of Participants Experiencing An Adverse Event (AEs)	From time of first dose of study treatment until the end of follow-up (up to ~92 months)	Percentage of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy

Trial Locations

Locations (192)

University of Maryland ( Site 2031); 🇺🇸 Baltimore, Maryland, United States

Stony Brook University ( Site 2063); 🇺🇸 Stony Brook, New York, United States

Rutgers Cancer Institute of New Jersey ( Site 2071); 🇺🇸 New Brunswick, New Jersey, United States

University of Massachusetts Memorial Medical Center ( Site 1875); 🇺🇸 Worcester, Massachusetts, United States

Allegheny General Hospital ( Site 1833); 🇺🇸 Pittsburgh, Pennsylvania, United States

Dana Farber Cancer Center ( Site 1873); 🇺🇸 Boston, Massachusetts, United States

University of Miami, Sylvester Comprehensive Cancer Center ( Site 2008); 🇺🇸 Miami, Florida, United States

USA Clinical Trials ( Site 2068); 🇺🇸 San Antonio, Texas, United States

Universitätsklinikum Schleswig-Holstein ( Site 0411); 🇩🇪 Luebeck, Schleswig-Holstein, Germany

Henry Joyce Cancer Clinic ( Site 1827); 🇺🇸 Nashville, Tennessee, United States

University of Utah, Huntsman Cancer Institute ( Site 1855); 🇺🇸 Salt Lake City, Utah, United States

Centro de Investigacion Clinica del Country ( Site 0304); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Fundacion Estudios Clinicos-Oncology ( Site 0017); 🇦🇷 Rosario, Santa Fe, Argentina

PP PPC Acinus Medical and Diagnostic Centre ( Site 1704); 🇺🇦 Kropyvnytskyi, Kirovohradska Oblast, Ukraine

Medizinische Universität Wien ( Site 1903); 🇦🇹 Wien, Austria

Oncologos del Occidente S.A. ( Site 0310); 🇨🇴 Pereira, Risaralda, Colombia

Landeskrankenhaus - Universitatsklinikum Graz ( Site 1902); 🇦🇹 Graz, Steiermark, Austria

Clinica de la Costa S.A.S. ( Site 0307); 🇨🇴 Barranquilla, Atlantico, Colombia

Centre Antoine Lacassagne ( Site 0351); 🇫🇷 Nice, Alpes-Maritimes, France

Institut Gustave Roussy ( Site 0353); 🇫🇷 Villejuif, Val-de-Marne, France

Institut Claudius Regaud IUCT Oncopole ( Site 0355); 🇫🇷 Toulouse, Haute-Garonne, France

Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1705); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine

Institut Sainte Catherine ( Site 0352); 🇫🇷 Avignon, Vaucluse, France

University of Southern California Norris Comprehensive Cancer Center ( Site 1850); 🇺🇸 Los Angeles, California, United States

Moores Cancer Center ( Site 1885); 🇺🇸 La Jolla, California, United States

Hoag Memoriall Hospital Presbyterian ( Site 2056); 🇺🇸 Newport Beach, California, United States

St. Joseph Heritage Healthcare ( Site 1806); 🇺🇸 Santa Rosa, California, United States

MedStar Washington Hospital Center ( Site 2062); 🇺🇸 Washington, District of Columbia, United States

George Washington University Medical Faculty Associates ( Site 2035); 🇺🇸 Washington, District of Columbia, United States

Rush University Medical Center ( Site 1823); 🇺🇸 Chicago, Illinois, United States

NorthShore University HealthSystem ( Site 1812); 🇺🇸 Evanston, Illinois, United States

Loyola University Medical Center [Maywood, IL] ( Site 1817); 🇺🇸 Maywood, Illinois, United States

University of Kentucky Chandler Medical Center-Medical Oncology ( Site 2069); 🇺🇸 Lexington, Kentucky, United States

Levine Cancer Institute ( Site 2003); 🇺🇸 Charlotte, North Carolina, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 2014); 🇺🇸 New York, New York, United States

Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 2016); 🇺🇸 Edina, Minnesota, United States

University of Missouri Hospital-Otolaryngology - Head and Neck Surgery ( Site 2058); 🇺🇸 Columbia, Missouri, United States

St. Vincent Healthcare Frontier Cancer Center ( Site 1818); 🇺🇸 Billings, Montana, United States

Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 1897); 🇺🇸 Springfield, Missouri, United States

Memorial Sloan Kettering Cancer Center Basking Ridge ( Site 2036); 🇺🇸 Basking Ridge, New Jersey, United States

The University of New Mexico Comprehensive Cancer Center ( Site 1882); 🇺🇸 Albuquerque, New Mexico, United States

Memorial Sloan Kettering Cancer Center- Monmouth ( Site 2039); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 2041); 🇺🇸 Harrison, New York, United States

The Ohio State University ( Site 2012); 🇺🇸 Columbus, Ohio, United States

University Hospitals ( Site 2032); 🇺🇸 Cleveland, Ohio, United States

University of Vermont Medical Center ( Site 2009); 🇺🇸 Burlington, Vermont, United States

Sanford Cancer Center Oncology Clinic ( Site 1859); 🇺🇸 Sioux Falls, South Dakota, United States

UT Southwestern Medical Center ( Site 1841); 🇺🇸 Dallas, Texas, United States

Hospital Britanico de Buenos Aires ( Site 0012); 🇦🇷 Ciudad de Buenos Aires, Caba, Argentina

Avera Cancer Institute- Research ( Site 2070); 🇺🇸 Sioux Falls, South Dakota, United States

Inova Schar Cancer Institute ( Site 2026); 🇺🇸 Fairfax, Virginia, United States

Sanatorio Britanico ( Site 0013); 🇦🇷 Rosario, Santa Fe, Argentina

Hospital Universitario Austral ( Site 0009); 🇦🇷 Pilar, Buenos Aires, Argentina

Instituto de Oncologia de Rosario ( Site 0002); 🇦🇷 Rosario, Santa Fe, Argentina

Hospital Provincial del Centenario ( Site 0008); 🇦🇷 Rosario, Santa Fe, Argentina

Hopital de Jolimont ( Site 0103); 🇧🇪 Haine Saint Paul, Hainaut, Belgium

Sunnybrook Research Institute ( Site 0211); 🇨🇦 Toronto, Ontario, Canada

Hospital Marcio Cunha-Unidade de Pesquisa Clínica ( Site 0177); 🇧🇷 Ipatinga, Minas Gerais, Brazil

CHLN Hospital Santa Maria ( Site 0952); 🇵🇹 Lisboa, Portugal

National Hospital Organization Kyushu Cancer Center ( Site 0660); 🇯🇵 Fukuoka, Japan

Rambam Health Care Campus-Oncology Division ( Site 0550); 🇮🇱 Haifa, Israel

Instituto de Oncología Angel Roffo ( Site 0003); 🇦🇷 Buenos Aires, Argentina

Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 1901); 🇦🇹 Linz, Oberosterreich, Austria

UZ Gent ( Site 0101); 🇧🇪 Gent, Oost-Vlaanderen, Belgium

Royal Brisbane and Women s Hospital ( Site 0050); 🇦🇺 Herston, Queensland, Australia

Aichi Cancer Center Hospital ( Site 0658); 🇯🇵 Nagoya, Aichi, Japan

Hospital CUF Descobertas ( Site 0953); 🇵🇹 Lisboa, Portugal

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0950); 🇵🇹 Porto, Portugal

National Cancer Center Hospital ( Site 0650); 🇯🇵 Tokyo, Japan

Chonnam National University Hwasun Hospital ( Site 0705); 🇰🇷 Hwasun Gun, Jeonranamdo, Korea, Republic of

Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0169); 🇧🇷 Rio de Janeiro, Brazil

Hospital de Base de Sao Jose de Rio Preto ( Site 0153); 🇧🇷 Sao Jose do Rio Preto, Sao Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0167); 🇧🇷 Sao Paulo, Brazil

BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0175); 🇧🇷 Sao Paulo, Brazil

Universitaetsklinikum Koeln ( Site 0413); 🇩🇪 Köln, Nordrhein-Westfalen, Germany

Pecsi Tudomanyegyetem Onkoterapias Intezet ( Site 0452); 🇭🇺 Pecs, Baranya, Hungary

Kagawa University Hospital ( Site 0651); 🇯🇵 Kita-gun, Kagawa, Japan

Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0155); 🇧🇷 Salvador, Bahia, Brazil

Hadassah Medical Center. Ein Kerem ( Site 0554); 🇮🇱 Jerusalem, Israel

Seoul National University Bundang Hospital ( Site 0703); 🇰🇷 Seongnam-si, Kyonggi-do, Korea, Republic of

Hiroshima University Hospital ( Site 0655); 🇯🇵 Hiroshima, Japan

Hospital de Braga ( Site 0951); 🇵🇹 Braga, Portugal

Rabin Medical Center ( Site 0552); 🇮🇱 Petah Tikva, Israel

Chaim Sheba Medical Center. ( Site 0553); 🇮🇱 Ramat Gan, Israel

Liga Norte Riograndense Contra o Cancer ( Site 0171); 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0905); 🇵🇱 Krakow, Malopolskie, Poland

National Cancer Center ( Site 0702); 🇰🇷 Goyang-si, Kyonggi-do, Korea, Republic of

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (; 🇵🇱 Warszawa, Mazowieckie, Poland

Szpitale Pomorskie Sp. z o.o. ( Site 0935); 🇵🇱 Gdynia, Pomorskie, Poland

Hospital Vall D Hebron ( Site 1200); 🇪🇸 Barcelona, Spain

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1001); 🇷🇺 Yaroslavl, Yaroslavskaya Oblast, Russian Federation

Hopitaux Universitaires de Geneve HUG ( Site 1920); 🇨🇭 Geneve, Switzerland

Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1921); 🇨🇭 Bellinzona, Ticino, Switzerland

Taichung Veterans General Hospital ( Site 1301); 🇨🇳 Taichung, Taiwan

National Cheng Kung University Hospital ( Site 1302); 🇨🇳 Tainan, Taiwan

Hospital Clinico Universitario de Santiago ( Site 1207); 🇪🇸 Santiago de Compostela, La Coruna, Spain

Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1204); 🇪🇸 Badalona, Barcelona, Spain

Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov ( Site 1709); 🇺🇦 Dnipropetrovsk, Dnipropetrovska Oblast, Ukraine

National Cancer Institute of the MoH of Ukraine ( Site 1702); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

Ukrainian Center of Tomotherapy ( Site 1708); 🇺🇦 Kropyvnitskiy, Kirovohradska Oblast, Ukraine

Addenbrooke's Hospital ( Site 1610); 🇬🇧 Cambridge, Cambridgeshire, United Kingdom

Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1303); 🇨🇳 Kaohsiung, Taiwan

Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1703); 🇺🇦 Kapitanivka Village, Kyivska Oblast, Ukraine

LISOD. Hospital ( Site 1707); 🇺🇦 Pliuty, Kyiv, Ukraine

Hospital Universitario La Paz ( Site 1201); 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocio ( Site 1206); 🇪🇸 Sevilla, Spain

Kyiv City Clinical Oncology Centre ( Site 1701); 🇺🇦 Kyiv, Ukraine

Universitaetsspital Zurich ( Site 1923); 🇨🇭 Zuerich, Aargau, Switzerland

Guy s & St Thomas NHS Foundation Trust ( Site 1604); 🇬🇧 London, London, City Of, United Kingdom

Castle Hill Hospital ( Site 1601); 🇬🇧 Cottingham-Hull, Kingston Upon Hull, United Kingdom

Royal Marsden Hospital - Fulham Road London ( Site 1609); 🇬🇧 London, London, City Of, United Kingdom

Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1603); 🇬🇧 London, London, City Of, United Kingdom

Weston Park Hospital ( Site 1607); 🇬🇧 Sheffield, United Kingdom

Hopital Europeen Georges Pompidou ( Site 0358); 🇫🇷 Paris, France

National Cancer Center Hospital East ( Site 0661); 🇯🇵 Kashiwa, Chiba, Japan

Hyogo Cancer Center ( Site 0656); 🇯🇵 Akashi, Hyogo, Japan

Yokohama City University Hospital ( Site 0657); 🇯🇵 Yokohama, Kanagawa, Japan

Chiba Cancer Center ( Site 0652); 🇯🇵 Chiba, Japan

Tokyo Medical and Dental University Hospital ( Site 0654); 🇯🇵 Tokyo, Japan

Tokyo Medical University Hospital ( Site 0659); 🇯🇵 Tokyo, Japan

N.N. Blokhin NMRCO ( Site 1005); 🇷🇺 Moscow, Moskva, Russian Federation

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1000); 🇷🇺 Kazan, Tatarstan, Respublika, Russian Federation

Universitaetsklinikum Tuebingen - Medizinische Klinik ( Site 0401); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 0414); 🇩🇪 Berlin, Germany

Universitaetsklinikum Hamburg Eppendorf ( Site 0407); 🇩🇪 Hamburg, Germany

Sourasky Medical Center ( Site 0551); 🇮🇱 Tel Aviv, Israel

Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0019); 🇦🇷 Buenos Aires, Caba, Argentina

MSKCC-Bergen ( Site 2037); 🇺🇸 Montvale, New Jersey, United States

National Taiwan University Hospital ( Site 1300); 🇨🇳 Taipei, Taiwan

Saint Alphonsus Regional Medical Center ( Site 2021); 🇺🇸 Boise, Idaho, United States

Rutgers New Jersey Medical School-department of Hematology oncology ( Site 2053); 🇺🇸 Newark, New Jersey, United States

Sanford Health Roger Maris Cancer Center ( Site 2034); 🇺🇸 Fargo, North Dakota, United States

Beacon Cancer Care ( Site 2052); 🇺🇸 Post Falls, Idaho, United States

University of Kansas Cancer Center ( Site 2004); 🇺🇸 Westwood, Kansas, United States

Washington University School of Medicine ( Site 1800); 🇺🇸 Saint Louis, Missouri, United States

Erie County Medical Center ( Site 2047); 🇺🇸 Buffalo, New York, United States

Monter Cancer Center ( Site 2060); 🇺🇸 Lake Success, New York, United States

Memorial Sloan-Kettering Cancer Center at Commack ( Site 2038); 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Cancer Center ( Site 1857); 🇺🇸 New York, New York, United States

Weill Cornell Medical College ( Site 2050); 🇺🇸 New York, New York, United States

Northwell Health Cancer Institute ( Site 2030); 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center - Nassau ( Site 2040); 🇺🇸 Uniondale, New York, United States

St. Luke's University Health Network ( Site 1801); 🇺🇸 Bethlehem, Pennsylvania, United States

Sidney Kimmel Cancer Center - Jefferson Health ( Site 2059); 🇺🇸 Philadelphia, Pennsylvania, United States

UVA Health System - Emily Couric Cancer Center ( Site 1826); 🇺🇸 Charlottesville, Virginia, United States

Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 1865); 🇺🇸 Seattle, Washington, United States

IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0016); 🇦🇷 Buenos Aires, Argentina

Hospital Aleman Buenos Aires Argentina ( Site 0004); 🇦🇷 Buenos Aires, Argentina

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0010); 🇦🇷 San Juan, Argentina

The Crown Princess Mary Cancer Centre - Westmead Hospital ( Site 0051); 🇦🇺 Westmead, New South Wales, Australia

Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 1900); 🇦🇹 Salzburg, Austria

AZ Nikolaas ( Site 0104); 🇧🇪 Sint-Niklaas, Oost-Vlaanderen, Belgium

Centro Regional Integrado de Oncologia ( Site 0160); 🇧🇷 Fortaleza, Ceara, Brazil

Hospital Nossa Senhora da Conceicao ( Site 0165); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Cross Cancer Institute ( Site 0201); 🇨🇦 Edmonton, Alberta, Canada

Princess Margaret Cancer Centre ( Site 0202); 🇨🇦 Toronto, Ontario, Canada

McGill University Health Centre ( Site 0210); 🇨🇦 Montreal, Quebec, Canada

Fundacion Arturo Lopez Perez FALP ( Site 0251); 🇨🇱 Santiago, Region M. De Santiago, Chile

CIUSSS de l'Estrie-CHUS ( Site 0209); 🇨🇦 Sherbrooke, Quebec, Canada

Hopital de la Timone ( Site 0356); 🇫🇷 Marseille, Bouches-du-Rhone, France

Institut Curie ( Site 0350); 🇫🇷 Paris, France

Universitaetsklinikum Ulm ( Site 0402); 🇩🇪 Ulm, Baden-Wurttemberg, Germany

Universitaetsklinikum Erlangen-Strahlenklinik ( Site 0412); 🇩🇪 Erlangen, Bayern, Germany

Klinikum rechts der Isar der Technischen Universitaet ( Site 0409); 🇩🇪 Muenchen, Bayern, Germany

Klinikum rechts der Isar der Technischen Universität München-HNO Klinik ( Site 0405); 🇩🇪 München, Bayern, Germany

Klinikum Kassel GmbH ( Site 0404); 🇩🇪 Kassel, Hessen, Germany

Universitaetsklinikum Frankfurt ( Site 0403); 🇩🇪 Frankfurt, Hessen, Germany

SRH Wald-Klinikum Gera GmbH ( Site 0406); 🇩🇪 Gera, Thuringen, Germany

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0450); 🇭🇺 Szolnok, Jasz-Nagykun-Szolnok, Hungary

Eszak-Pesti Centrumkorhaz-Honvedkorhaz ( Site 0453); 🇭🇺 Budapest, Hungary

Orszagos Onkologiai Intezet ( Site 0454); 🇭🇺 Budapest, Hungary

St. James s Hospital ( Site 0500); 🇮🇪 Dublin, Ireland

The Catholic University of Korea St. Vincent s Hospital ( Site 0704); 🇰🇷 Gyeonggi-do, Kyonggi-do, Korea, Republic of

ICO L Hospitalet ( Site 1208); 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Severance Hospital, Yonsei University Health System ( Site 0701); 🇰🇷 Seoul, Korea, Republic of

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 2054); 🇺🇸 Orlando, Florida, United States

UC Davis Health System ( Site 1864); 🇺🇸 Sacramento, California, United States

University of Colorado Cancer Center ( Site 1838); 🇺🇸 Aurora, Colorado, United States

Providence Portland Medical Center ( Site 1843); 🇺🇸 Portland, Oregon, United States

Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 2022); 🇺🇸 Portland, Oregon, United States

Orlando Health Cancer Institute ( Site 2061); 🇺🇸 Orlando, Florida, United States

Karmanos Cancer Institute ( Site 1870); 🇺🇸 Detroit, Michigan, United States

Henry Ford Health System ( Site 1803); 🇺🇸 Detroit, Michigan, United States

Wake Forest Compenhensive Cancer Center ( Site 2029); 🇺🇸 Winston-Salem, North Carolina, United States

Oregon Health Science University ( Site 1871); 🇺🇸 Portland, Oregon, United States

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0901); 🇵🇱 Gliwice, Slaskie, Poland

Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi ( Site 0920); 🇵🇱 Lodz, Lodzkie, Poland

University of Florida ( Site 1832); 🇺🇸 Gainesville, Florida, United States

Ochsner Cancer Institute ( Site 2045); 🇺🇸 New Orleans, Louisiana, United States

Montefiore Einstein Center ( Site 2028); 🇺🇸 Bronx, New York, United States

Centro Medico Imbanaco de Cali S.A ( Site 0300); 🇨🇴 Cali, Valle Del Cauca, Colombia

Clinical oncology dispensary of Dnipro ( Site 1706); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine