Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advance Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)

Phase 3

Completed

• Conditions: Malignant Melanoma
• Interventions: Biological: Pembrolizumab; Drug: Placebo for lenvatinib; Drug: Lenvatinib

• Registration Number: NCT03820986
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma.

The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Detailed Description

As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded.

Study Timeline

• Study First Submitted: 2019-01-22
• Study First Submitted QC: 2019-01-25
• Study First Posted: 2019-01-29
• Study Start: 2019-03-12
• Primary Completion: 2023-01-18
• Results First Submitted: 2023-12-21
• Results First Submitted QC: 2023-12-21
• Results First Posted: 2024-01-17
• Status Verified: 2024-11
• Study Completion: 2024-11-01
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 674

Inclusion Criteria

• Has histologically or cytologically confirmed melanoma.

• Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy.

• Has been untreated for advanced or metastatic disease except as follows:

  1. Proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. Participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after discussion with the medical monitor.
  2. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [anti-PD-1] therapy or interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation.

• Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the Screening period (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).

• Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

• Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.

• Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization.

• Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.

• Male participants must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period. Please note that 7 days after lenvatinib/placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed. Contraception use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

• Female participants must not be pregnant, not breastfeeding, and ≥1 of the following conditions applies:

  1. Not a woman of childbearing potential (WOCBP). OR
  2. A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment.

• The participant (or legally acceptable representative) has provided documented informed consent for the study.

• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.

• Has adequate organ function.

Exclusion Criteria

• Has a 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 before the first dose of study treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has ocular melanoma.
• Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has an active infection requiring systemic therapy.
• Has known history of human immunodeficiency virus (HIV) infection
• Has known history of or is positive for hepatitis B virus or hepatitis C virus infection.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has a history of active tuberculosis (Bacillus tuberculosis).
• Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
• Has had a major surgery within 3 weeks prior to first dose of study intervention. Note: Adequate wound healing after major surgery must be assessed clinically independent of time elapsed for eligibility.
• Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
• Has radiographic evidence of encasement or invasion of major blood vessel, or of intratumoral cavitation.
• Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study treatment.
• Has clinically significant cardiovascular disease from 12 months of the first dose of study treatment including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
• Has urine protein ≥1 g/24-hour. Note: Participants with ≥2+ (≥100 mg/dL) proteinuria on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
• Prolongation of QTcF interval to >480 ms. Note: If the QTcF is prolonged to >480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.
• Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram.
• Has received prior therapy in the adjuvant setting. Note: Targeted therapy, anti-CTLA-4, or anti-PD-1 may be allowed.
• Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy as noted in Inclusion Criteria above
• Has received prior therapy with a monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study treatment or not recovered (≤Grade 1 or at Baseline) from adverse events due to previously administered agents.

Exception to this rule would be use of denosumab, which is not excluded. Note: Participants with alopecia and ≤Grade 2 neuropathy are an exception and may enroll.

• Has received prior radiotherapy within 2 weeks of first dose of study treatment (Cycle 1 Day 1). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Has received live vaccine within 30 days before the first dose of study treatment.
• 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 the first dose of study treatment.
• 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 treating investigator.
• Has had an allogeneic tissue/solid organ transplant.
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab+Placebo	Placebo for lenvatinib	Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.
Pembrolizumab+Lenvatinib	Lenvatinib	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years.
Pembrolizumab+Lenvatinib	Pembrolizumab	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years.
Pembrolizumab+Placebo	Pembrolizumab	Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	Up to approximately 46 months	PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥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 ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Overall Survival (OS)	Up to approximately 46 months	OS is defined as the time from date of randomization to date of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1	Up to approximately 46 months	ORR is defined as the percentage of participants in the analysis population who have 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) per RECIST 1.1. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)	Up to approximately 46 months	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued any study treatment due to an AE is presented.
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS/QoL Score	Up to approximately 30 months	TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 GHS Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. TThe GHS/QoL Score consists of participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" GHS/QoL responses range in score from 0 to 100, with a higher score indicating a better outcome. A longer TTD indicates a better outcome
Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Global Health Status (GHS)/Quality of Life (QoL) Score	Baseline and Week 21	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS/QoL combined score consists of participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" GHS/QoL responses range in score from 0 to 100, with a higher score indicating a better outcome.
Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1	Up to approximately 46 months	For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the date of the first documented evidence of CR or PR until disease progression or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥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 ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Number of Participants With Adverse Events (AEs)	Up to approximately 46 months	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Physical Function (PF) Score	Baseline and Week 21	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities \[strenuous activities, long walks, short walks, bed/chair rest and needing help with eating, dressing, washing themselves or using the toilet\]). For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome.
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 in Physical Function (PF) Score	Up to approximately 30 months	TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 PF Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities \[strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves or using the toilet\]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome.

Trial Locations

Locations (119)

Princess Alexandra Hospital ( Site 0454); 🇦🇺 Wooloongabba, Queensland, Australia

University of North Carolina - Cancer Hospital ( Site 0751); 🇺🇸 Chapel Hill, North Carolina, United States

Yunnan Cancer Hospital ( Site 0604); 🇨🇳 Kunming, Yunnan, China

Mid-Florida Cancer Centers ( Site 0764); 🇺🇸 Orange City, Florida, United States

Valley Hospital ( Site 0749); 🇺🇸 Paramus, New Jersey, United States

Illinois Cancer Care, PC ( Site 0765); 🇺🇸 Peoria, Illinois, United States

Fudan University Shanghai Cancer Center ( Site 0607); 🇨🇳 Shanghai, Shanghai, China

Fujian Provincial Cancer Hospital ( Site 0612); 🇨🇳 Fuzhou, Fujian, China

Universitaetsklinikum Erlangen ( Site 0044); 🇩🇪 Erlangen, Bayern, Germany

Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394); 🇧🇷 Rio de Janeiro, Brazil

Eastern Health ( Site 0457); 🇦🇺 Box Hill, Victoria, Australia

St. Vincent Frontier Cancer Center ( Site 0724); 🇺🇸 Billings, Montana, United States

Tianjin Medical University Cancer Institute & Hospital ( Site 0606); 🇨🇳 Tianjin, Tianjin, China

Westmead Hospital ( Site 0451); 🇦🇺 Westmead, New South Wales, Australia

Hospital de Caridade de Ijui ( Site 0391); 🇧🇷 Ijui, Rio Grande Do Sul, Brazil

Henan Cancer Hospital ( Site 0610); 🇨🇳 Zhengzhou, Henan, China

Sun Yat-Sen University Cancer Center ( Site 0602); 🇨🇳 Guangzhou, Guangdong, China

Nanjing Drum Tower Hospital ( Site 0609); 🇨🇳 Nanjing, Jiangsu, China

Samsung Medical Center ( Site 0551); 🇰🇷 Seoul, Korea, Republic of

The Angeles Clinic and Research Institute ( Site 0707); 🇺🇸 Los Angeles, California, United States

John Wayne Cancer Institute ( Site 0706); 🇺🇸 Santa Monica, California, United States

Melanoma Institute Australia ( Site 0452); 🇦🇺 North Sydney, New South Wales, Australia

Inova Schar Cancer Institute ( Site 0739); 🇺🇸 Fairfax, Virginia, United States

Fiona Stanley Hospital ( Site 0456); 🇦🇺 Murdoch, Western Australia, Australia

Hospital Sao Vicente de Paulo ( Site 0396); 🇧🇷 Passo Fundo, Rio Grande Do Sul, Brazil

Sourasky Medical Center ( Site 0307); 🇮🇱 Tel Aviv, Israel

ASST Papa Giovanni XXIII ( Site 0062); 🇮🇹 Bergamo, Abruzzo, Italy

Baptist MD Anderson Cancer Center ( Site 0767); 🇺🇸 Jacksonville, Florida, United States

AMG Oncology ( Site 0714); 🇺🇸 Park Ridge, Illinois, United States

Minnesota Oncology Specialist, PA ( Site 0766); 🇺🇸 Fridley, Minnesota, United States

Medizinische Universitat Wien ( Site 0778); 🇦🇹 Wien, Austria

Sunnybrook Research Institute ( Site 0654); 🇨🇦 Toronto, Ontario, Canada

Pontificia Universidad Catolica de Chile ( Site 0422); 🇨🇱 Santiago, Region M. De Santiago, Chile

Sociedad Medica Aren y Bachero Limitada ( Site 0426); 🇨🇱 Santiago, Region M. De Santiago, Chile

Oncocentro ( Site 0424); 🇨🇱 Vina del Mar, Valparaiso, Chile

Hopital ARCHET 2 ( Site 0009); 🇫🇷 Nice, Alpes-Maritimes, France

Hopital La Timone ( Site 0002); 🇫🇷 Marseille, Bouches-du-Rhone, France

CHU Dijon Bourgogne ( Site 0010); 🇫🇷 Dijon, Cote-d Or, France

Institut Claudius Regaud IUCT Oncopole ( Site 0003); 🇫🇷 Toulouse, Haute-Garonne, France

CHU de Rouen ( Site 0013); 🇫🇷 Rouen, Seine-Maritime, France

Centre Hospitalier Victor Dupouy ( Site 0012); 🇫🇷 Argenteuil, Val-d Oise, France

Institut Gustave Roussy ( Site 0001); 🇫🇷 Villejuif, Val-de-Marne, France

CHU de la Miletrie Poitiers ( Site 0011); 🇫🇷 Poitiers, Vienne, France

Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035); 🇩🇪 Hannover, Baden-Wurttemberg, Germany

Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036); 🇩🇪 Wuerzburg, Bayern, Germany

Hautkrebszentrum Buxtehude ( Site 0037); 🇩🇪 Buxtehude, Niedersachsen, Germany

Universitaetsklinikum Carl Gustav Carus ( Site 0041); 🇩🇪 Dresden, Sachsen, Germany

Universitaetsklinikum Leipzig ( Site 0040); 🇩🇪 Leipzig, Sachsen, Germany

SRH Wald-Klinikum Gera GmbH ( Site 0042); 🇩🇪 Gera, Thuringen, Germany

HaEmek Medical Center ( Site 0306); 🇮🇱 Afula, Israel

Rabin Medical Center ( Site 0302); 🇮🇱 Petah Tikva, Israel

Shamir Medical Center-Assaf Harofeh ( Site 0308); 🇮🇱 Zerifin, Israel

Istituto Nazionale Tumori Fondazione Pascale ( Site 0061); 🇮🇹 Napoli, Italy

Kyungpook National University Chilgok Hospital ( Site 0553); 🇰🇷 Daegu, Taegu-Kwangyokshi, Korea, Republic of

Seoul National University Hospital ( Site 0554); 🇰🇷 Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System ( Site 0552); 🇰🇷 Seoul, Korea, Republic of

Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273); 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278); 🇵🇱 Gliwice, Slaskie, Poland

Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272); 🇵🇱 Poznan, Wielkopolskie, Poland

Pratia MCM Krakow ( Site 0280); 🇵🇱 Krakow, Malopolskie, Poland

Uniwersyteckie Centrum Kliniczne ( Site 0281); 🇵🇱 Gdansk, Pomorskie, Poland

Cancer Care Langenhoven Drive Oncology Centre ( Site 0805); 🇿🇦 Port Elizabeth, Eastern Cape, South Africa

Sandton Oncology Medical Group PTY LTD ( Site 0802); 🇿🇦 Johannesburg, Gauteng, South Africa

Hospital Duran i Reinals ICO de Hospitalet ( Site 0187); 🇪🇸 Hospitalet del Llobregat, Barcelona, Spain

Cape Town Oncology Trials Pty Ltd ( Site 0803); 🇿🇦 Kraaifontein, Western Cape, South Africa

Hospital Universitario Marques de Valdecilla ( Site 0181); 🇪🇸 Santander, Cantabria, Spain

Hospital Universitario La Paz ( Site 0184); 🇪🇸 Madrid, Spain

Hospital Universitario Insular de Gran Canaria ( Site 0189); 🇪🇸 Las Palmas de Gran Canaria, Las Palmas, Spain

Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182); 🇪🇸 A Coruna, La Coruna, Spain

Hospital Clinic i Provincial Barcelona ( Site 0190); 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Maranon ( Site 0191); 🇪🇸 Madrid, Spain

Hospital Universitario Ramon y Cajal ( Site 0183); 🇪🇸 Madrid, Spain

Hospital Universitario Carlos Haya ( Site 0186); 🇪🇸 Malaga, Spain

Laenssjukhuset Ryhov ( Site 0215); 🇸🇪 Jonkoping, Jonkopings Lan, Sweden

Centrallasarettet Vaxjo ( Site 0214); 🇸🇪 Vaxjo, Kronobergs Lan, Sweden

Skanes Universitetssjukhus ( Site 0213); 🇸🇪 Lund, Skane Lan, Sweden

Karolinska Universitetssjukhuset ( Site 0211); 🇸🇪 Solna, Stockholms Lan, Sweden

Akademiska Sjukhuset ( Site 0218); 🇸🇪 Uppsala, Uppsala Lan, Sweden

Sahlgrenska Universitetssjukhuset ( Site 0212); 🇸🇪 Goteborg, Vastra Gotalands Lan, Sweden

Kantonsspital Graubuenden ( Site 0091); 🇨🇭 Chur, Grisons, Switzerland

Universitaetsspital Zuerich ( Site 0092); 🇨🇭 Zuerich-Flughafen, Zurich, Switzerland

Kantonsspital Winterthur ( Site 0095); 🇨🇭 Winterthur, Zurich, Switzerland

Western General Hospital ( Site 0121); 🇬🇧 Edinburgh, Edinburgh, City Of, United Kingdom

Guys and St Thomas NHS Foundation Trust ( Site 0126); 🇬🇧 London, London, City Of, United Kingdom

Derriford Hospital ( Site 0129); 🇬🇧 Plymouth, United Kingdom

Singleton Hospital ( Site 0131); 🇬🇧 Swansea, United Kingdom

The First Hospital Of Jilin University ( Site 0603); 🇨🇳 Chang Chun, Jilin, China

Beijing Cancer Hospital ( Site 0601); 🇨🇳 Beijing, Beijing, China

Sir Run Run Shaw Hospital ( Site 0605); 🇨🇳 Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital ( Site 0608); 🇨🇳 Hangzhou, Zhejiang, China

Universitaetsspital Basel ( Site 0094); 🇨🇭 Basel, Basel-Stadt, Switzerland

PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399); 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033); 🇩🇪 Kiel, Schleswig-Holstein, Germany

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704); 🇺🇸 San Francisco, California, United States

California Pacific Medical Center Research Institute ( Site 0705); 🇺🇸 San Francisco, California, United States

Azienda Ospedaliera Universitaria Senese ( Site 0065); 🇮🇹 Siena, Toscana, Italy

Istituto Europeo di Oncologia ( Site 0067); 🇮🇹 Milano, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064); 🇮🇹 Milano, Italy

Istituto Oncologico Veneto ( Site 0063); 🇮🇹 Padova, Italy

Norrlands Universitetssjukhus ( Site 0216); 🇸🇪 Umea, Vasterbottens Lan, Sweden

University of Colorado Cancer Center ( Site 0708); 🇺🇸 Aurora, Colorado, United States

Yale Cancer Center ( Site 0709); 🇺🇸 New Haven, Connecticut, United States

OHSU Center for Health & Healing ( Site 0731); 🇺🇸 Portland, Oregon, United States

McGill University Health Centre ( Site 0651); 🇨🇦 Montreal, Quebec, Canada

Atlantic Health System ( Site 0768); 🇺🇸 Morristown, New Jersey, United States

Hopital Ambroise Pare Boulogne ( Site 0007); 🇫🇷 Boulogne-Billancourt, Hauts-de-Seine, France

BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661); 🇨🇦 Kelowna, British Columbia, Canada

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652); 🇨🇦 Montreal, Quebec, Canada

Centro Investigación del Cáncer James Lind ( Site 0425); 🇨🇱 Temuco, Araucania, Chile

Soroka Medical Center ( Site 0303); 🇮🇱 Beer Sheva, Israel

Lions Gate Hospital ( Site 0662); 🇨🇦 North Vancouver, British Columbia, Canada

Lismore Base Hospital ( Site 0453); 🇦🇺 Lismore, Australian Capital Territory, Australia

Fundacion Arturo Lopez Perez FALP ( Site 0421); 🇨🇱 Santiago, Region M. De Santiago, Chile

CHRU Lille - Hopital Claude Huriez ( Site 0004); 🇫🇷 Lille, Nord, France

Chaim Sheba Medical Center ( Site 0304); 🇮🇱 Ramat Gan, Israel

LKH Universitatsklinikum Graz ( Site 0776); 🇦🇹 Graz, Steiermark, Austria

Rambam Medical Center ( Site 0301); 🇮🇱 Haifa, Israel

Hadassah Ein Karem Hebrew University Medical Center ( Site 0305); 🇮🇱 Jerusalem, Israel