A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT04657991
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to learn about the effects of three study medicines (encorafenib, binimetinib, and pembrolizumab) given together for the treatment of melanoma that:
* is advanced or metastatic (spread to other parts of the body);
* has a certain type of abnormal gene called "BRAF"; and
* has not received prior treatment.
All participants in this study will receive pembrolizumab at the study clinic once every 3 weeks as an intravenous (IV) infusion (given directly into a vein). In addition, half of the participants will take encorafenib and binimetinib orally (by mouth) at home every day.
Participants may receive pembrolizumab for up to two years. Those participants taking encorafenib and binimetinib can continue until their melanoma is no longer responding. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
- Detailed Description
This study will compare the efficacy, safety, and tolerability of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus placebo plus pembrolizumab (Control Arm) in participants with metastatic or unresectable locally advanced BRAF V600E/K mutation-positive melanoma. The study will have an open-label safety lead-in (SLI) phase to determine the safety recommend Phase 3 dose (RP3D) and pharmacokinetics (PK) of encorafenib and binimetinib plus pembrolizumab combination therapy prior to initiation of the randomized Phase 3 part of the study. Two dose levels of encorafenib in combination with binimetinib plus pembrolizumab will be explored in parallel. A minimum of 12 evaluable participants will be enrolled per dose level. During the double-blind randomized Phase 3 part of the study, approximately 216 eligible participants will be randomized in a 1:1 ratio to the Triplet Arm (at RP3D determined in the SLI) or Control Arm (approximately 108 participants per arm). Randomization will be stratified by prior systemic adjuvant therapy and stage of disease by AJCC (ED8).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 256
- Male or female participants ≥ 18 years at the time of informed consent.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
- Presence of at least 1 measurable lesion as detected by radiological and/or photographic methods according to RECIST v1.1.
- ECOG performance status 0 or 1.
- Documented evidence of a BRAF V600E or V600K mutation in melanoma tumor tissue as previously determined by either PCR or NGS-based local laboratory assay (eg, US FDA-approved test, CE-marked [European conformity] in vitro diagnostic in EU countries, or equivalent), obtained during the course of normal clinical care, in a CLIA- or similarly certified laboratory.
- Submission of adequate tumor tissue (archival or newly obtained; block or slides to the sponsor central laboratory(ies) during the screening period and prior to enrollment (SLI)/randomization (Phase 3).
- Have not received prior first-line systemic therapy for metastatic or unresectable locally advanced melanoma.
- Adequate bone marrow function, hepatic and renal function.
- Capable of giving signed informed consent.
Exclusion Criteria
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study (including, but not limited to, a participant who is rapidly progressing or has clinically significant tumor related symptoms, in the judgment of the investigator).
- Mucosal or ocular melanoma.
- Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
- Unable to swallow, retain, and absorb oral medications.
- Impairment of GI function or disease which may significantly alter the absorption of oral study intervention (eg, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, including malabsorption syndrome secondary to prior GI surgery).
- Clinically significant cardiovascular diseases,
- History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to enrollment (SLI)/randomization (Phase 3). Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (ie, massive or sub-massive) deep vein thrombosis or pulmonary emboli.
- History or current evidence of RVO or current risk factors for RVO (eg, uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
- Concurrent neuromuscular disorder that is associated with the potential of elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- Current noninfectious pneumonitis or history of noninfectious pneumonitis requiring steroids, or history of radiation pnuemonitis
- Evidence of HBV or HCV infection.
- Known history of a positive test for HIV or known AIDS.
- Any active infection requiring systemic therapeutic treatment within 2 weeks prior to enrollment (SLI)/ randomization (Phase 3).
- Participants with prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
- Concurrent or previous other malignancy within 2 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease and Gleason ≤ 6 prostate cancer. Participants with a history of other curatively treated cancers must be reviewed with the sponsor or designee prior to entering the study.
- Participants who previously received and subsequently discontinued encorafenib and/or binimetinib and/or anti-PD-1/-L1 due to severe toxicity.
- For participants in the SLI only: Current use or anticipated need for food or drugs that are known moderate or strong CYP3A4 inhibitors during screening and through the DLT-evaluation period
- Participant has not recovered to Grade ≤ 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before enrollment (SLI)/ randomization (Phase 3).
- Receipt of protocol defined medications or treatments outside of required intervals before enrollment (SLI)/randomization (Phase 3):
- Previous administration with an investigational drug ≤ 6 months prior to enrollment (SLI)/randomization (Phase 3).
- Known sensitivity or contraindication to any component of study intervention (encorafenib, binimetinib and pembrolizumab), or their excipients.
- Pregnant, confirmed by a positive β-hCG laboratory test result, or is breastfeeding (lactating).
- Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Triplet Arm Encorafenib Encorafenib and Binimetinib in combination with Pembrolizumab Triplet Arm Binimetinib Encorafenib and Binimetinib in combination with Pembrolizumab Control Arm Pembrolizumab Pembrolizumab Triplet Arm Pembrolizumab Encorafenib and Binimetinib in combination with Pembrolizumab
- Primary Outcome Measures
Name Time Method Safety Lead In (SLI): Incidence of Dose Limiting Toxicities (DLTs) First 2 Cycles of Treatment (cycles are 21 days) A DLT is defined as any adverse event or laboratory value that is assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring within the first 2 cycles of treatment.
Phase 3: Objective Response (OR) by Blinded Independent Central Review (BICR) Time from the date of randomization until documented PD, start of subsequent anticancer therapy, or death due to any cause (approximately every 9 weeks). OR is defined as confirmed Best Overall response (BOR) of either CR or PR as determined by BICR assessment per RECIST 1.1
- Secondary Outcome Measures
Name Time Method Safety Lead in (SLI) and Phase 3: Disease Control (DC) Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks) DC is defined as confirmed BOR of CR, PR or SD, as determined by BICR and investigator assessment per RECIST v1.1.
Safety Lead In (SLI) and Phase 3: Progression Free Survival (PFS) by Investigator and BICR assessment The time from the date of randomization to the date of first documented disease progression, as determined by investigator and BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks) PFS by investigator is defined as the time from the date of randomization to the first date of documented disease progression as determined by investigator and BICR assessment per RECIST 1.1 or death due to any cause, whichever occurs first.
Phase 3: Change from baseline in Patient Global Impression of Severity (PGIS) score Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".
Safety Lead in (SLI) and Phase 3: Objective Response (OR) Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks). OR is defined as confirmed Best Overall Response (BOR) of either CR or PR as determined by investigator assessment per RECIST v1.1
Phase 3: Overall Survival (OS) Time from the date of randomization to the date of death due to any cause. OS is defined as the time from the date of randomization to the date of death due to any cause
Safety Lead in (SLI) and Phase 3: Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments. Time from first dose of study intervention through 28 days after the last dose of study intervention. AEs, laboratory parameters, vital signs and cardiac abnormalities will be graded according to the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 4.03).
Safety Lead in (SLI) and Phase 3: Time to Response (TTR) Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1 (approximately every 9 weeks) TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR), as determined by BICR and investigator or assessment per RECIST v1.1.
Safety Lead in (SLI): Plasma concentration-time profiles and Pharmacokinetic (PK) parameter estimates for encorafenib and binimetinib. Cycle 2, Day 1 To measure plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)
Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30): change from baseline in the global health status/QoL score. Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months EORTC QLQ-30 includes 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/Quality of Life scale
Phase 3: Change from baseline in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale score. Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, melanoma-specific items, and items related to melanoma surgery
Phase 3: Change from baseline in 5-level EuroQol-5D (EQ-5D-5L) index score and visual analog scale (VAS) Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months The EQ-5D-5L is a standardized measure of health utility that provides a single index value of health status and contains 1 item for each of 5 dimensions of HRQoL (ie, mobility, self-care, usual activities, pain or discomfort, and anxiety or depression).
Phase 3: Duration of Response (DOR) Time from date of first documented response (CR or PR) to the date of first documented disease progression, as determined by BICR and investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks) DOR is defined as the time from the date of first documented response to the date of first documented disease progression, as determined by BICR and investigator assessment or death due to any cause, whichever occurs first.
Phase 3: Plasma concentrations of encorafenib and binimetinib. Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 (Each Cycle is 21 days) To measure the plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)
Phase 3: Patient Global Impression of Change (PGIC) score Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"
Trial Locations
- Locations (213)
HELIOS Klinikum Erfurt
🇩🇪Erfurt, Germany
UCLA - Hematology/Oncology - Administrative Office
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center Drug Information Center , Dept. of Pharmaceutical Services (Drug
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center, Drug Information Center, Dept. of Pharmaceutical Services (Main O
🇺🇸Los Angeles, California, United States
UCLA Hematology/Oncology - Westwood (Building 100)
🇺🇸Los Angeles, California, United States
UCHealth Sue Anschutz-Rodgers Eye Center
🇺🇸Aurora, Colorado, United States
University of Colorado Denver CTO/CTRC
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
🇺🇸Aurora, Colorado, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
AdventHealth Orlando Infusion Center
🇺🇸Orlando, Florida, United States
AdventHealth Orlando, Investigational Drug Services
🇺🇸Orlando, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Advocate Medical Group-Park Ridge, Luther Lane-Oncology
🇺🇸Park Ridge, Illinois, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Ophthalmic Consultants of Boston Inc (OCB)
🇺🇸Boston, Massachusetts, United States
Revive Research Institute, Inc.
🇺🇸Farmington Hills, Michigan, United States
Michigan Health Professionals
🇺🇸Farmington Hills, Michigan, United States
St. Vincent Healthcare
🇺🇸Billings, Montana, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
University of Cincinnati Medical Center
🇺🇸West Chester, Ohio, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Texas Oncology - Carrollton
🇺🇸Carrollton, Texas, United States
North Dallas Eye Associates
🇺🇸Flower Mound, Texas, United States
Texas Oncology - Flower Mound
🇺🇸Flower Mound, Texas, United States
Baylor Clinic
🇺🇸Houston, Texas, United States
Baylor College of Medicine Medical Center
🇺🇸Houston, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
CHI St. Luke's Health Baylor College of Medicine Medical Center
🇺🇸Houston, Texas, United States
Harris Health System - Ben Taub Hospital
🇺🇸Houston, Texas, United States
Harris Health System - Smith Clinic
🇺🇸Houston, Texas, United States
Dan Brown O.D.
🇺🇸Paris, Texas, United States
Texas Oncology-Paris
🇺🇸Paris, Texas, United States
Baylor Scott & White Medical Center - Temple
🇺🇸Temple, Texas, United States
Utah Cancer Specialists
🇺🇸West Valley City, Utah, United States
Instituto Alexander Fleming
🇦🇷Caba, Buenos Aires, Argentina
Clinica Viedma S. A
🇦🇷Viedma, RÍO Negro, Argentina
Instituto de Oncologia de Rosario
🇦🇷Rosario, Santa FE, Argentina
Universitätsklinikum St. Pölten
🇦🇹St. Pölten, Niederösterreich, Austria
Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Oberösterreich, Austria
Medizinische Universität Wien
🇦🇹Vienna, Wien, Austria
Medizinische Universität Graz
🇦🇹Graz, Austria
UZ Brussel
🇧🇪Brussels, Bruxelles-capitale, Région DE, Belgium
UZ Gent
🇧🇪Gent, Oost-vlaanderen, Belgium
AZ Sint-Jan Brugge-Oostende AV
🇧🇪Brugge, West-vlaanderen, Belgium
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Belgium
Centre Hospitalier de Jolimont
🇧🇪Haine Saint Paul, Belgium
VITAZ
🇧🇪Sint-Niklaas, Belgium
Instituto de Oncologia do Paraná - IOP Matriz Mateus Leme
🇧🇷Curitiba, Paraná, Brazil
Instituto de Oncologia do Paraná - IOP Oncoville
🇧🇷Curitiba, Paraná, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA
🇧🇷Rio de Janeiro, RJ, Brazil
Hospital de Clínicas de Passo Fundo
🇧🇷Passo Fundo, RS, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
🇧🇷Barretos, SÃO Paulo, Brazil
Hospital Sírio-Libanês - Unidade Bela Vista
🇧🇷São Paulo, Brazil
Complex Oncology Center - Plovdiv EOOD
🇧🇬Plovdiv, Bulgaria
Complex Oncology Center-Ruse EOOD
🇧🇬Ruse, Bulgaria
Medical Center Nadezhda Clinical EOOD
🇧🇬Sofia, Bulgaria
Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda EAD
🇧🇬Sofia, Bulgaria
Umhato Ead
🇧🇬Sofia, Bulgaria
Kingston Health Sciences Centre-Kingston General Hospital Site
🇨🇦Kingston, Ontario, Canada
CIUSSS du Saguenay-Lac-Saint-Jean
🇨🇦Chicoutimi, Quebec, Canada
McGill University Health Centre - Glen Site
🇨🇦Montreal, Quebec, Canada
Saskatoon Cancer Center
🇨🇦Saskatoon, Saskatchewan, Canada
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Olomoucký KRAJ, Czechia
Olomouc University Hospital
🇨🇿Olomouc, Olomoucký KRAJ, Czechia
Masarykuv Onkologicky Ustav
🇨🇿Brno, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava-Poruba, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Všeobecná fakultní nemocnice
🇨🇿Praha 2, Czechia
Fakultni nemocnice Bulovka
🇨🇿Praha 8-Liben, Czechia
Tampereen yliopistollinen sairaala
🇫🇮Tampere, Pirkanmaa, Finland
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
🇫🇮Helsinki, Finland
CHG Le Mans
🇫🇷Le Mans, France
Chu Charles Nicolle
🇫🇷Rouen, Haute-normandie, France
CHU de Lille - Hôpital Claude Huriez Service
🇫🇷Lille, France
CHU d'Amiens - Hôpital Nord
🇫🇷Amiens, France
CHU d'Angers
🇫🇷Angers, France
Hôpital Saint André
🇫🇷Bordeaux, France
Hôpital Ambroise Paré
🇫🇷Boulogne-Billancourt, France
CHU de Dijon Bourgogne
🇫🇷Dijon Cedex, France
CHU Grenoble Alpes
🇫🇷La Tronche, France
Hôpital de la Timone
🇫🇷Marseille, France
Hôpital Lyon Sud
🇫🇷Pierre-Bénite, France
CHU de Poitiers
🇫🇷Poitiers, France
Hôpital Charles Nicolle - CHU de Rouen
🇫🇷Rouen, France
CHU de Saint-Etienne - Hôpital Nord
🇫🇷Saint-Etienne Cedex 2, France
Gustave Roussy
🇫🇷Villejuif, France
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Baden-württemberg, Germany
Universitaetsklinikum Erlangen
🇩🇪Erlangen, Bayern, Germany
Klinik und Poliklinik für Dermatologie und Allergologie
🇩🇪München, Bayern, Germany
Elbe Kliniken Stade-Buxtehude, Klinikum Buxtehude
🇩🇪Buxtehude, Niedersachsen, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Nordrhein-westfalen, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Nordrhein-westfalen, Germany
Universitätsmedizin Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Rheinland-pfalz, Germany
Universitaetsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Sachsen, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Universitaetsklinikum Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Schleswig-holstein, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Schleswig-holstein, Germany
SRH Wald-Klinikum Gera
🇩🇪Gera, Thüringen, Germany
Charité Universitaetsmedizin Berlin - Campus Mitte
🇩🇪Berlin, Germany
Vivantes Klinikum Neukölln
🇩🇪Berlin, Germany
Universitätsklinikum Essen (AöR)
🇩🇪Essen, Germany
Universitaetsklinikum Halle - Universitaetsklinik und Poliklinik fuer Dermatologie und Venerologie
🇩🇪Halle, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
University Hospital Muenster
🇩🇪Muenster, Germany
Fachklinik Hornheide
🇩🇪Münster, Germany
Klinikum Nürnberg Nord
🇩🇪Nürnberg, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
General Hospital of Athens "Laiko"
🇬🇷Athens, Attikí, Greece
Laiko Hospital
🇬🇷Athens, Attikí, Greece
Metropolitan Hospital
🇬🇷Piraeus, Attikí, Greece
University General Hospital of Heraklion
🇬🇷Heraklion, Irakleío, Greece
Bioclinic Thessalonikis Private Clinic Single Member S.A.
🇬🇷Thessaloniki, Kentrikí Makedonía, Greece
Pécsi Tudományegyetem Klinikai Központ
🇭🇺Pécs, Baranya, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház
🇭🇺Szolnok, Hungary
Ha'emek Medical Center.
🇮🇱Afula, Hatsafon, Israel
Soroka University Medical Center
🇮🇱Be'er-Sheva, Israel
Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem
🇮🇱Jerusalem, Israel
Rabin Medical Center, Beilinson Hospital
🇮🇱Petah Tikva, Israel
The Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Azienda Sanitaria Universitaria Friuli Centrale
🇮🇹Udine, Friuli Venezia Giulia, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, MI, Italy
Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
🇮🇹Roma, RM, Italy
A.O.U.S. Policlinico "Le Scotte"
🇮🇹Siena, SI, Italy
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
🇮🇹Candiolo, Torino, Italy
Istituto Tumori Giovanni Paolo II
🇮🇹Bari, Italy
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Italy
Istituto Europeo di Oncologia IRCCS
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
🇮🇹Napoli, Italy
Istituto Oncologico Veneto IOV - IRCCS
🇮🇹Padova, Italy
AO di Perugia - Ospedale S. Maria della Misericordia, S.C Oncologia Medica
🇮🇹Perugia, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
ONCARE Viaducto Nápoles
🇲🇽Benito Juárez, Ciudad DE México, Mexico
Preparaciones Oncológicas S.C.
🇲🇽León, Guanajuato, Mexico
I Can Oncology Center S.A. de C.V.
🇲🇽Monterrey, Nuevo LEÓN, Mexico
BRCR Global Mexico - CDMX
🇲🇽Ciudad de México, Mexico
El Cielo Medical Center RSB, S.C
🇲🇽Puebla, Mexico
El Cielo Medical Center
🇲🇽Puebla, Mexico
New Zealand Clinical Research (Christchurch)
🇳🇿Christchurch, Canterbury, New Zealand
Palmerston North Hospital
🇳🇿Palmerston North, Manawatu, New Zealand
Auckland City Hospital
🇳🇿Auckland, New Zealand
Akershus Universitetssykehus
🇳🇴Lørenskog, Akershus, Norway
Oslo universitetssykehus, Radiumhospitalet
🇳🇴Oslo, Norway
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Jagiellońskie Centrum Innowacji Sp. z o .o.
🇵🇱Krakow, Poland
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o .o.
🇵🇱Krakow, Poland
Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
🇵🇱Poznan, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Private Medical Institution "Euromedservice"
🇷🇺Pushkin, Saint-petersburg, Russian Federation
Ars Medika Center, LLC
🇷🇺Kaliningrad, Russian Federation
BIH of Omsk Region "Clinical Oncological Dispensary"
🇷🇺Omsk, Russian Federation
Eurocityclinic LLC
🇷🇺St.Petersburg, Russian Federation
Fakultná nemocnica s poliklinikou F.D. Roosevelta Banská Bystrica
🇸🇰Banska Bystrica, Slovakia
Onkologicky ustav sv. Alzbety, s.r.o.
🇸🇰Bratislava, Slovakia
Narodny onkologicky ustav
🇸🇰Bratislava, Slovakia
Vychodoslovensky onkologicky ustav, a.s.
🇸🇰Kosice, Slovakia
Nemocnica na okraji mesta, n.o.
🇸🇰Partizanske, Slovakia
POKO Poprad, s.r.o.
🇸🇰Poprad, Slovakia
Wits Clinical Research
🇿🇦Johannesburg, Gauteng, South Africa
Sandton Oncology Medical Group (Pty) Ltd
🇿🇦Johannesburg, Gauteng, South Africa
Drs Alberts, Bouwer and Jordaan Inc.
🇿🇦Pretoria, Gauteng, South Africa
Mary Potter Oncology Centre
🇿🇦Pretoria, South Africa
CHUS - Hospital Clinico Universitario
🇪🇸Santiago De Compostela, A Coruna, Spain
ICO-Badalona Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Murcia, Spain
Complejo Hospitalario De Navarra
🇪🇸Pamplona, Navarra, Spain
CHUAC-Hospital Teresa Herrera
🇪🇸A Coruña, Spain
Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica
🇪🇸Barcelona, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofía
🇪🇸Cordoba, Spain
Complejo Hospitalario de Jaen
🇪🇸Jaen, Spain
Hospital Universitario Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga - Hospital Civil
🇪🇸Málaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
UniversitätsSpital Zürich
🇨🇭Zürich Flughafen, Switzerland
Istanbul University Cerrahpasa Medical Faculty Hospital
🇹🇷Istanbul, İ̇stanbul, Turkey
Medipol Mega Universite Hastanesi
🇹🇷İstanbul, İ̇stanbul, Turkey
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
🇹🇷Istanbul, İ̇stanbul, Turkey
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Ankara Şehir Hastanesi
🇹🇷Ankara, Turkey
Medical and diagnostic center of MedX-Ray International Group Limited Liability Company Israeli
🇺🇦Pliuty Village, KYIV Region, Obukhiv District, Ukraine
Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
🇺🇦Dnipro, Ukraine
Municipal non-profit enterprise Khmelnytsky regional antitumor center of Khmelnytsky regional
🇺🇦Khmelnytskyi, Ukraine
Municipal non-profit enterprise "Kyiv City Clinical Hospital No. 2" of the executive body of the
🇺🇦Kyiv, Ukraine
National Cancer Institute
🇺🇦Kyiv, Ukraine
Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Oncological Regional Therapeutical
🇺🇦Lviv, Ukraine
Derzhavna ustanova Instytut zahalnoi ta nevidkladnoi khirurhii im.V.T.Zaitseva Natsionalnoi akademii
🇺🇦M. Kharkiv, Ukraine
Komunalne nekomertsiine pidpryiemstvo Kharkivskoi oblasnoi rady "Oblasnyi klinichnyi spetsializovany
🇺🇦M. Kharkiv, Ukraine
Municipal non-profit enterprise "Zaporizhzhia Regional Antitumor Center" Zaporizhzhya Regional Counc
🇺🇦Zaporizhzhia, Ukraine
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
St. Bartholomew's Hospital, Barts Health NHS Trust
🇬🇧London, United Kingdom
The South West Wales Cancer Institute, Swansea Bay University Health Board
🇬🇧Swansea, United Kingdom