A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
- Conditions
- Advanced BRAFV600 Wild-type Melanoma
- Interventions
- Registration Number
- NCT03273153
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a Phase III, multicenter, open-label, randomized study designed to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 446
Disease-Specific Inclusion Criteria
- Histologically confirmed locally advanced and unresectable or metastatic melanoma
- Naive to prior systemic anti-cancer therapy for melanoma
- Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a clinical mutation test approved by the local health authority
- A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study entry. If 20 slides are not available or the tissue block is not of sufficient size, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Age >=18 years at time of signing Informed Consent Form
- Ability to comply with the study protocol, in the investigator's judgment
- Histologically or cytologically confirmed BRAFV600 wild-type melanoma
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy >=3 months
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent or use at least two forms of effective contraceptive with a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib and at least 5 months after the last dose of atezolizumab or pembrolizumab
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures (e.g. condom), and agreement to refrain from donating sperm, for at least 3 months after the last dose of cobimetinib
- Willingness and ability of patients to report selected study outcomes (e.g., GHS and HRQoL) using an electronic device or paper backup questionnaires.
General Exclusion Criteria
- Inability to swallow medications
- Malabsorption condition that would alter the absorption of orally administered medications
- Pregnancy, breastfeeding, or intention of becoming pregnant during the study
- History of severe hypersensitivity reactions to components of the cobimetinib, atezolizumab, or pembrolizumab formulations
- Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or systemic immunostimulatory/immunosuppresive medication
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study Cancer-Related Exclusion Criteria
- Ocular melanoma
- Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation of needing such procedure while receiving study treatment
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
- Active or untreated central nervous system (CNS) metastases Exclusions Related to Cardiovascular Disease
- Unstable angina, new-onset angina within last 3 months, myocardial infarction within the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure classified as New York Heart Association Class II or higher
- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or <50%, whichever is lower
- Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic baseline hypertension consistently above 159/99 mmHg despite optimal medical management
- History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction Exclusions Related to Infections
- HIV infection
- Active tuberculosis infection
- Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of Cycle 1
- Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
- Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular Disease
- Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and Immunomodulatory Drugs
- Active or history of autoimmune disease or immune deficiency
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1, Cycle 1 Exclusions Related to Other Medical Conditions or Medications
- Active malignancy (other than melanoma) or a prior malignancy within the past 3 years
- Any Grade >=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
- History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1
- Proteinuria >3.5 gm/24 hr
- Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cobimetinib and Atezolizumab Cobimetinib Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle. Cobimetinib and Atezolizumab Atezolizumab Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle. Pembrolizumab Pembrolizumab Participants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC) Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
- Secondary Outcome Measures
Name Time Method Serum Concentration of Atezolizumab Day 1 of Cycles 1, 2, and 3 Objective Response as Determined by IRC Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1
Objective Response as Determined by the Investigator Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis).
PFS as Determined by the Investigator Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
Overall Survival (OS) From randomization up to approximately 3 years OS is defined as the time from randomization to death from any cause.
Duration of Objective Response Determined by the Investigator Up to 3 years Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.
Number of Participants With Adverse Events (AEs) Up to approximately 16 months An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Plasma Concentration of Cobimetinib Days 1 and 15 of Cycle 1 Duration of Objective Response Determined by the IRC Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.
Two-year Landmark Survival At 2 years Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'
Change From Baseline in Health-related Quality of Life (HRQoL) Scores Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months. HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher ("better") level of functioning.
Disease Control Rate (DCR) Week 16 DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
Number of Participants With Abnormal Vital Signs From baseline up to approximately 3 years Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Number of Participants With Laboratory Abnormalities Up to approximately 16 months Participants with laboratory abnormalities (values outside of a defined range) will be reported.
Percentage of Participants With Anti-drug Antibodies (ADAs) Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.
Trial Locations
- Locations (121)
USC Norris Cancer Center; USC Oncology Hematology Newport Beach
🇺🇸Newport Beach, California, United States
Florida Cancer Specialists
🇺🇸West Palm Beach, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
SCRI Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
West Virginia University Hospitals Inc
🇺🇸Morgantown, West Virginia, United States
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
🇮🇹Napoli, Campania, Italy
Townsville General Hospital
🇦🇺Douglas, Queensland, Australia
Cairns Base Hospital
🇦🇺Cairns, Queensland, Australia
AZ Groeninge
🇧🇪Kortrijk, Belgium
Hopital Claude Huriez; Sce Dermatologie
🇫🇷Lille, France
Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen
🇩🇪Tübingen, Germany
Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
🇵🇱Poznań, Poland
Hospital Clínic i Provincial; Servicio de Oncología
🇪🇸Barcelona, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
University of California at Irvine Medical Center; Department of Oncology
🇺🇸Orange, California, United States
TriHealth Hatton Institute; Surgical Education
🇺🇸Cincinnati, Ohio, United States
M.D Anderson Cancer Center; Uni of Texas At Houston
🇺🇸Houston, Texas, United States
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)
🇺🇸Ann Arbor, Michigan, United States
Forsythe Memorial Hospital Inc., dba Novant Health Oncology Specialists
🇺🇸Winston-Salem, North Carolina, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Stanford Comprehensive Cancer Center
🇺🇸Stanford, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Florida Cancer Specialist, North Region
🇺🇸Saint Petersburg, Florida, United States
Massachusetts General Hospital;Hematology/ Oncology
🇺🇸Boston, Massachusetts, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
St. Luke's University Health network
🇺🇸Bethlehem, Pennsylvania, United States
Thomas Jefferson University Hospital;Medical Oncology
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Instituto Nacional de Cancer - INCa; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, RS, Brazil
Hopital Avicenne; Dermatologie
🇫🇷Bobigny, France
Hopital Saint Andre CHU De Bordeaux; Dermatologie
🇫🇷Bordeaux, France
Centre Hospitalier Le Mans; Dermatologie
🇫🇷Le Mans, France
CHU de Grenoble - Hôpital Nord
🇫🇷Grenoble, France
Chu Site Du Bocage;Dermatologie
🇫🇷Dijon, France
Hopital Timone Adultes; Dermatologie
🇫🇷Marseille, France
CHU de Nantes; Cancéro-dermatologie
🇫🇷Nantes, France
Groupe Hospitalier Bichat Claude Bernard
🇫🇷Paris, France
Hopital Saint Louis; Dermatologie 1
🇫🇷Paris, France
Hopital Robert Debre; DERMATOLOGIE
🇫🇷Reims, France
Institut Gustave Roussy; Dermatologie
🇫🇷Villejuif, France
Centre Eugene Marquis; Service d'oncologie
🇫🇷Rennes, France
Hopital Charles Nicolle; Dermatologie Serv.
🇫🇷Rouen, France
Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
🇫🇷Toulouse, France
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Dermatologie
🇩🇪Dresden, Germany
HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie
🇩🇪Erfurt, Germany
Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
🇩🇪Frankfurt, Germany
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
🇩🇪Gera, Germany
Universitatsklinikum Essen; Klinik für Dermatologie
🇩🇪Essen, Germany
Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie
🇩🇪Hannover, Germany
UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
🇩🇪Kiel, Germany
Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie
🇩🇪Mannheim, Germany
Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie
🇩🇪München, Germany
Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie
🇩🇪Mainz, Germany
Johannes Wesling Klinikum Minden; Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin
🇩🇪Minden, Germany
Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly
🇭🇺Budapest, Hungary
Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine
🇬🇷Athens, Greece
Fachklinik Hornheide; Dermatologie
🇩🇪Münster, Germany
Laiko General Hospital Athen
🇬🇷Athens, Greece
Metropolitan Hospital; Dept. of Oncology
🇬🇷Pireaus, Greece
University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology
🇭🇺Szeged, Hungary
Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika
🇭🇺Pecs, Hungary
IFO - Istituto Regina Elena; Oncologia Medica
🇮🇹Roma, Lazio, Italy
A.O. Universitaria Policlinico Di Modena; Ematologia
🇮🇹Modena, Emilia-Romagna, Italy
Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
🇮🇹Napoli, Campania, Italy
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
🇮🇹Milano, Lombardia, Italy
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
🇮🇹Genova, Liguria, Italy
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Veneto, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
🇮🇹Candiolo, Piemonte, Italy
A.O.U. Cons. Policlinico Bari - Consorzlale Policlinico; Scienze Biomediche e Oncologia Umana
🇮🇹Bari, Puglia, Italy
Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde
🇳🇱Amsterdam, Netherlands
Amphia Ziekenhuis, locatie Langendijk;Oncology
🇳🇱Breda, Netherlands
Zuyderland ziekenhuis locatie Geleen
🇳🇱Sittard-Geleen, Netherlands
Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie
🇳🇱Rotterdam, Netherlands
Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
🇵🇱Gdansk, Poland
COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
🇵🇱Lublin, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
🇵🇱Szczecin, Poland
Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii
🇵🇱Wrocław, Poland
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
🇷🇺Saint-Petersburg, Russian Federation
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
🇷🇺Moscow, Russian Federation
Hospital Universitario Son Espases; Servicio de Oncologia
🇪🇸Palma De Mallorca, Islas Baleares, Spain
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸Badalona, Barcelona, Spain
St. Petersburg Oncology Hospital
🇷🇺St Petersburg, Russian Federation
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
🇪🇸Santiago de Compostela, LA Coruña, Spain
Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Clinica Universitaria de Navarra; Servicio de oncología
🇪🇸Pamplona, Navarra, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
Instituto Valenciano Oncologia; Oncologia Medica
🇪🇸Valencia, Spain
Hospital General Universitario de Valencia; Servicio de oncologia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department
🇬🇧Bristol, United Kingdom
Western General Hospital; Edinburgh Cancer Center
🇬🇧Edinburgh, United Kingdom
Leicester Royal Infirmary; Dept. of Medical Oncology
🇬🇧Leicester, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
Guys & St Thomas Hospital; Department of Oncology
🇬🇧London, United Kingdom
Singleton Hospital; Pharmacy
🇬🇧Swansea, United Kingdom
University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
🇬🇧Stoke-On-Trent, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Dartmouth-Hitchcock Medical Center; Hematology/Oncology
🇺🇸Lebanon, New Hampshire, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
🇮🇹Milano, Lombardia, Italy
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hopital l Archet 2; Ginestriere, Service de; Dermatologie
🇫🇷Nice cedex 3, France
Bioclinic Thessaloniki
🇬🇷Thessaloniki, Greece
Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico
🇮🇹Pisa, Toscana, Italy