An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03915951
- Lead Sponsor
- Pfizer
- Brief Summary
This is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with BRAFV600E-mutant metastatic non-small cell lung cancer (NSCLC). Patients who are either treatment-naïve, OR who have received 1) first-line treatment with standard platinum-based chemotherapy, OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 98
-
Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is currently Stage IV.
-
Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay or the presence of other BRAFV600 mutations other than V600E (i.e. K or D) will be considered
-
Patients who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), OR who have received 1) first-line platinum-based chemotherapy OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1(PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy.
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Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
-
Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1.
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Adequate bone marrow function characterized by the following at screening:
- absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
- Platelets ≥ 100 × 10⁹/L;
- Hemoglobin ≥ 8.5 g/dL (with or without blood transfusions).
-
Adequate hepatic and renal function characterized by the following at screening:
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases; Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m².
Key
-
Patients who have documentation of any of the following:
- epidermal growth factor receptor (EGFR) mutation
- anaplastic lymphoma kinase (ALK) fusion oncogene or
- ROS1 rearrangement
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Patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting.
-
Previous treatment with any BRAF inhibitor (e.g., dabrafenib, vemurafenib, XL281/BMS-908662, etc.), or any mitogen-activated protein kinase (MEK) inhibitor (e.g., trametinib, cobimetinib, selumetinib, RDEA119, etc.) prior to screening and enrollment.
-
Impaired cardiovascular function or clinically significant cardiovascular diseases
-
History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
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History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease.
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Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phospho)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
-
Patients with symptomatic brain metastasis, leptomeningeal disease or other active central nervous system (CNS) metastases are not eligible.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Period binimetinib Study treatment with encorafenib and binimetinib will be self-administered orally without regard to food. Patients will receive the following per 28-day (± 3 days) cycle: * Encorafenib: 450 mg (6 × 75 mg capsule) once daily (QD) * Binimetinib: 45 mg (3 × 15 mg tablet) twice daily (BID) Treatment Period encorafenib Study treatment with encorafenib and binimetinib will be self-administered orally without regard to food. Patients will receive the following per 28-day (± 3 days) cycle: * Encorafenib: 450 mg (6 × 75 mg capsule) once daily (QD) * Binimetinib: 45 mg (3 × 15 mg tablet) twice daily (BID)
- Primary Outcome Measures
Name Time Method Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR) From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months) Objective Response Rate (ORR) was defined as the percentage of participants who had achieved a confirmed best overall response (Complete Response \[CR\] or Partial Response \[PR\]) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes \[recorded as target lesion\] must have reduction in short axis to \<10 mm) and complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size \[\<10 mm in short axis\]). PR was defined by a 30% or more decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. ORR was calculated with the exact 2-sided Clopper-Pearson 95% CI.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months) ORR was defined as the percentage of participants who had achieved a confirmed best overall response (CR or PR) per RECIST version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes \[recorded as target lesion\] must have reduction in short axis to \<10 mm) and the complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size \[\<10 mm in short axis\]). PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. ORR according to derived investigator assessment was calculated with the exact 2-sided Clopper-Pearson 95% CI.
Time to Response (TTR) by IRR and Investigator Assessments From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months) TTR based on IRR and Investigator assessments was defined, for participants with an objective response, as the time, in months, from the date of first dose to the first documentation of objective response (CR or PR) which was subsequently confirmed (by IRR and by Investigator, respectively). TTR was calculated for the subgroup of participants with a confirmed objective tumor response.
Duration of Response (DoR) by IRR and Investigator Assessments From the date of the first confirmed documented response (CR or PR) to the earliest date of disease progression or death due to any cause (up to 36 months) DoR, based on IRR and Investigator assessments was defined as the time from the date of the first documented confirmed response (CR or PR) (by IRR and by Investigator, respectively) to the earliest date of disease progression, as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1, or death due to any cause. If a participant with a CR or PR had neither progressed nor died at the time of the analysis cutoff or at the start of any new anticancer therapy, the participant was censored at the date of last adequate tumor assessment. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. DoR was calculated for participants who had achieved a confirmed overall response (CR or PR). The estimate of the DoR survival function was constructed using the Kaplan-Meier method.
Disease Control Rate (DCR) by IRR and Investigator Assessments After 24 Weeks (≥168 days) from the date of first dose of study intervention DCR was defined as the percentage of participants who had achieved a confirmed overall response of CR, PR or stable disease (SD), as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1 after 24 weeks (≥168 days) from the date of first dose of study intervention. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. SD was assigned when neither sufficient shrinkage to qualify for CR or PR, nor sufficient increase to qualify for PD was observed, taking as reference the nadir. DCR was calculated along with the exact 2-sided Clopper-Pearson 95% CI.
Progression-free Survival (PFS) by IRR and Investigator Assessments From the date of first dose of study drug to the earliest date of disease progression, or death due to any cause (up to 36 months) PFS was defined as the time from the date of first dose of study intervention to the earliest date of disease progression, as determined by IRR and Investigator review of radiographic disease assessments per RECIST version 1.1, or death due to any cause, whichever occurred first. PD was defined by a 20% or more increase in the SOD of target lesions relative to nadir (smallest SOD considering baseline and all assessments prior to the time point under evaluation), with a minimum absolute increase of 5 mm relative to nadir; PD was assigned if any non-target lesion was marked "unequivocal progression". If a participant had not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. PFS (months) = \[(date of event or censoring - date of first dose) +1\]/30.4375. The survival distribution function for PFS was estimated using the Kaplan-Meier method.
Kaplan-Meier Estimates of Overall Survival (OS) The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months) OS was defined as the time from the date of first dose of study intervention to the date of death due to any cause. If a death had not been observed by the date of the analysis cutoff, OS was censored at the date of last contact. The survival distribution function for OS was estimated using the Kaplan-Meier method.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From the time the participant provided informed consent, through and including a minimum of 30 calendar days, after the last administration of the study intervention, and the safety follow-up visit (30 days [±7 days] after the EOT visit) (up to 36 months) TEAE was a treatment-emergent adverse event that occurred during the on-treatment period. The on-treatment period was defined as the time from the first dose date of study intervention to the last dose of study drug administration date (when both drugs were permanently discontinued) +30 days or the earliest date of subsequent anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study intervention was determined by the investigator. The investigator made an assessment of intensity for each AE reported during the study according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3 events = severe AEs; Grade 4 events = life-threatening consequences, urgent intervention indicated; Grade 5 events = death related to AEs.
Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Chemistry Laboratory Test Values Based on CTCAE Grade Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, EOT ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months) Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time.
Grade 4 was not applicable for the parameters of hyperglycemia and hypoalbuminemia as Grade 4 was not defined for these 2 parameters per CTCAE version 4.03.Number of Participants With Notable ECG (QTcF) Values Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months) The QTcF increase from baseline \>30/60 msec and new QTcF \>450/480/500 msec were defined as clinically notable ECG criteria. Triplicate ECG measurements were obtained. For new abnormal post-baseline values, the table below presents the number of participants with both non-missing baseline and post-baseline values, and baseline values not meeting the criteria. For abnormal changes from baseline, the table below presents the number of participants with both non-missing baseline and post-baseline evaluations. Baseline was defined as the average of the machine-read triplicate ECG measurements taken pre-dose on Day 1. Change from baseline was post-baseline - baseline values.
Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Hematology Laboratory Test Values Based on CTCAE Grade Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, End of Treatment (EOT) ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months) Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time.
Grade 4 was not applicable for the parameters of anemia, hemoglobin increased, leukocytosis and lymphocyte count increased as Grade 4 was not defined for these 4 parameters per CTCAE version 4.03.Number of Participants With Notable Abnormal Vital Signs Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days of Subsequent Cycles, EOT ±3 Days, and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months) Vital sign measurements were taken before blood collection for laboratory tests or at least 30 minutes after blood collection for laboratory tests, and were measured per institutional standards. Vital sign assessments included temperature, pulse rate, respiratory rate, and blood pressure (assessed in a recumbent, semi recumbent, or sitting position).
The criteria of notably abnormal vital signs are listed below:
Systolic blood pressure (mmHg): high: ≥160 mmHg with increase from baseline of ≥20 mmHg; low: ≤90 mmHg with decrease from baseline of ≥20 mmHg.
Diastolic blood pressure (mmHg): high: ≥100 mmHg with increase from baseline of ≥15 mmHg; low: ≤50 mmHg with decrease from baseline of ≥15 mmHg.
Pulse rate (bpm): high: ≥120 bpm with increase from baseline of ≥15 bpm; low: ≤50 bpm with decrease from baseline of ≥15 bpm.
Weight (kg): high: ≥10% increase from baseline; low: ≥20% decrease from baseline.
Temperature (°C): high: ≥37.5 °C; low: ≤36 °C.Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months) Cardiac ejection fraction was assessed by transthoracic echocardiogram (ECHO) or multigated acquisition (MUGA). Participants who developed signs/symptoms of congestive heart failure (CHF) at any point during the study were required to have an evaluation of LVEF measurements by ECHO or MUGA and were monitored per institutional guidelines.
Participants were considered as having a LVEF abnormality if the worst post-value was CTCAE Grade 2, 3 or 4 according to the following classification:
Grade 0: Non-missing value below Grade 2. Grade 2: LVEF between 40% and 50%, inclusive, or absolute change from baseline between -10% and \< -20%.
Grade 3: LVEF between 20% and 39%, inclusive, or absolute change from baseline ≤ -20%.
Grade 4: LVEF lower than 20%. Baseline was defined as the last available and valid assessment before or on the start date of study intervention.
Trial Locations
- Locations (117)
Ohio State CarePoint East
🇺🇸Columbus, Ohio, United States
The Ohio State University James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Ohio State Eye and Ear Institute
🇺🇸Columbus, Ohio, United States
Stefanie Spielman Comprehensive Breast Cancer
🇺🇸Columbus, Ohio, United States
Florida Cancer Specialists PAN - SCRI - PPDS
🇺🇸Tallahassee, Florida, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
MidAmerica Division, Inc. c/o Menorah Medical Center
🇺🇸Overland Park, Kansas, United States
UPMC Hillman Cancer Center - Passavant (OHA)
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Hillman Cancer Center - Upper St. Clair
🇺🇸Pittsburgh, Pennsylvania, United States
Ophthalmic Consultants of Boston Inc
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center/East
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Millennium Research & Clinical Development
🇺🇸Houston, Texas, United States
Eye associates Northwest
🇺🇸Seattle, Washington, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Providence Oncology and Hematology Care Clinic - Westside
🇺🇸Portland, Oregon, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute @ Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Houston Eye Associates - Gramercy Location
🇺🇸Houston, Texas, United States
Metropolitan Eye Care
🇺🇸Paramus, New Jersey, United States
UCLA Stein Eye Center Santa Monica (OPH)
🇺🇸Santa Monica, California, United States
Yuma Regional Medical Center Cancer Center
🇺🇸Yuma, Arizona, United States
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
UCLA Hematology/Oncology
🇺🇸Santa Monica, California, United States
Florida Cancer Specialists
🇺🇸Winter Park, Florida, United States
The Johns Hopkins Wilmer Eye Institute
🇺🇸Baltimore, Maryland, United States
Ophthalmic Consultants of Boston (OCB)
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center - 330 Brookline Ave
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute - Chestnut Hill
🇺🇸Newton, Massachusetts, United States
MidAmerica Division, Inc. c/o Centerpoint Medical Center
🇺🇸Independence, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care
🇺🇸New York, New York, United States
Weill Cornell Medical College - New York Presbyterian Hospital
🇺🇸New York, New York, United States
Weill Cornell Eye Associates
🇺🇸New York, New York, United States
The Ohio State University East Hospital
🇺🇸Columbus, Ohio, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
The Ohio State University Hospital
🇺🇸Columbus, Ohio, United States
The Ohio State University Medical Center - Thoracic Oncology Clinic
🇺🇸Columbus, Ohio, United States
Ohio State Outpatient Care Lewis Center
🇺🇸Lewis Center, Ohio, United States
Ohio State CarePoint Gahanna
🇺🇸Gahanna, Ohio, United States
Providence Cancer Institute Newberg Clinic
🇺🇸Newberg, Oregon, United States
Providence Cancer Institute, Franz Clinic
🇺🇸Portland, Oregon, United States
UPMC Hillman Cancer Center - Arnold Palmer - Mt View
🇺🇸Greensburg, Pennsylvania, United States
UPMC Hillman Cancer Center Erie
🇺🇸Erie, Pennsylvania, United States
UPMC Hillman Cancer Center Monroeville
🇺🇸Monroeville, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Eye Center, Eye and Ear Institute
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Hillman Cancer Center - Passavant (HOA)
🇺🇸Pittsburgh, Pennsylvania, United States
Weaver Eye Associates
🇺🇸York, Pennsylvania, United States
WellSpan Oncology Research
🇺🇸York, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Tennessee Oncology, PLLC
🇺🇸Smyrna, Tennessee, United States
Unita Operativa di Oculistica: UO Oncologia Oculare e Immunopatologia oculare
🇮🇹Milan, Lombardia, Italy
Departimento Oncologia Medica
🇮🇹Milan, Lombardia, Italy
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
UO Anatomia e lstologia Patologica
🇮🇹Milan, Lombardia, Italy
Unita Operativa Radiologia
🇮🇹Milan, Lombardia, Italy
SCDO Cardiologia
🇮🇹Orbassano, Torino, Italy
UO Medicina Nucleare
🇮🇹Milan, Lombardia, Italy
S.S.D. Oncologia Polmonare
🇮🇹Orbassano, Torino, Italy
SCDU Anatomia Patologica
🇮🇹Orbassano, Torino, Italy
SCDU Oftalmologia
🇮🇹Orbassano, Torino, Italy
SCDU Radiodiagnostica e S.S. Medicina Nucleare
🇮🇹Orbassano, Torino, Italy
Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
🇮🇹Torino, TO, Italy
UO Dermatologia Centro Tumori Cutanei (CTC)- Azienda Ospedaliero
🇮🇹Bologna, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milan, Italy
UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna
🇮🇹Bologna, Italy
Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
🇮🇹Napoli, Italy
UO Medicina Borghi- Azienda Ospedaliero Universitaria Di Bologna
🇮🇹Bologna, Italy
UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna
🇮🇹Bologna, Italy
Clinica Oculistica II, 2° Policlinico Federico II
🇮🇹Napli, Italy
S. C. Farmacia
🇮🇹Napoli, Italy
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
OLVG, locatie Oost; Ophthalmology department
🇳🇱Amsterdam, Netherlands
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Regional Universitario de Malaga - Hospital General
🇪🇸Malaga, Málaga, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
CETIR Centro Medico Teknon
🇪🇸Barcelona, Spain
Hospital Quiron Salud Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
lnstitut Catala d'Oncologia_L'Hospitalet
🇪🇸L'Hospitalet, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
CERCO
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Clinic de Barcelona
🇪🇸Badalona, Spain
Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Florida Cancer Specialist
🇺🇸Trinity, Florida, United States
Johns Hopkins Bayview Medical Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Martha Morehouse Medical Plaza
🇺🇸Columbus, Ohio, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
The Ohio State University East Hospital Ohio State Outpatient Care New Albany
🇺🇸Westerville, Ohio, United States
UO Dermatologia e Cosmetologia
🇮🇹Milan, Lombardia, Italy
UO Radiologia Golfieri- Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
🇮🇹Bologna, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Ophthalmology department
🇳🇱Groningen, Netherlands
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Grupo Cardiologico Corpal (Hospital de la Cruz Roja)
🇪🇸Cordoba, Spain
Centro Hospitalario Integral Privado (CHIP)
🇪🇸Malaga, Spain
Cetir
🇪🇸Esplugues de Llobregat, Spain
Winship Cancer Institute @ Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute @ Emory Johns Creek Hospital
🇺🇸Johns Creek, Georgia, United States
MidAmerica Division, Inc., c/o Research Medical Center
🇺🇸Kansas City, Missouri, United States
Yuma Regional Medical Center Ophthalmology
🇺🇸Yuma, Arizona, United States