A Study to Learn if a Combination of Fianlimab and Cemiplimab Versus Cemiplimab Alone is More Effective for Adult Participants With Advanced Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Advanced Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05785767
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an experimental drug called fianlimab (also called REGN3767), combined with a medication called cemiplimab (also called REGN2810), individually called a "study drug" or collectively called "study drugs". The study is focused on patients who have advanced non-small cell lung cancer (NSCLC).
The aim of the study is to see how effective the combination of fianlimab and cemiplimab is in treating advanced NSCLC, in comparison with cemiplimab by itself.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drugs
* How much study drug is in your blood at different times
* Whether the body makes antibodies against the study drugs (which could make the drug less effective or could lead to side effects)
* How administering the study drugs might improve your quality of life
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 850
- Patients with non-squamous or squamous histology NSCLC with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or stage IV (metastatic disease), who received no prior systemic treatment for recurrent or metastatic NSCLC.
- Availability of an archival or on-study formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample, without intervening therapy between biopsy collection and screening as described in the protocol
- For enrollment in phase 2, patients should have PD-L1 levels ≥ 50%, as determined by a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) (or equivalently licensed, according to local regulations) accredited laboratory, as described in the protocol. For enrollment in phase 3, patients should have expression of programmed cell death ligand-1 (PD-L1) in ≥50% of tumor cells stained using an assay performed by a central laboratory, as described in the protocol.
- At least 1 radiographically measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Adequate organ and bone marrow function, as described in the protocol.
Key
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Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime.
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Active or untreated brain metastases or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated, and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. Patients must be off (immunosuppressive doses of) corticosteroid therapy.
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Patients with tumors tested positive for actionable epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or c-ros oncogene 1 (ROS1) fusions, as described in the protocol.
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Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment.
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History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment.
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Known primary immunodeficiencies, either cellular (eg, DiGeorge syndrome, T-cell-negative severe combined immunodeficiency [SCID]) or combined T- and B-cell immunodeficiencies (eg, T- and B-cell negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency).
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Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-mediated treatment-emergent adverse events (imTEAEs). Patients with uncontrolled type 1 diabetes mellitus or with uncontrolled adrenal insufficiency are excluded. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
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Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization. Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Patients with clinically relevant systemic immune suppression within the last 3 months before trial enrollment are excluded. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
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Patients who have received prior systemic therapies are excluded with the exception of the following:
- Adjuvant or neoadjuvant platinum-based doublet chemotherapy (after surgery and/or radiation therapy) if recurrent or metastatic disease develops more than 6 months after completing therapy as long as toxicities have resolved to CTCAE grade ≤1 or baseline with the exception of alopecia and peripheral neuropathy.
- Anti-PD-(L) 1 with or without LAG-3 as an adjuvant or neoadjuvant therapy as long as the last dose is >12 months prior to enrollment.
- Prior exposure to other immunomodulatory or vaccine therapies as an adjuvant or neoadjuvant therapy, Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibodies as long as the last dose is >6 months prior to enrollment. Immune-mediated AEs must be resolved to CTCAE grade ≤1 or baseline by the time of enrollment. Endocrine immune-mediated AEs controlled with hormonal or other non-immunosuppressive therapies without resolution prior to enrollment are allowed.
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A: fianlimab+cemiplimab fianlimab Phase 2: fianlimab (HD) Phase 3: fianlimab (chosen dose) A: fianlimab+cemiplimab cemiplimab Phase 2: fianlimab (HD) Phase 3: fianlimab (chosen dose) B: fianlimab+cemiplimab fianlimab Phase 2: fianlimab (LD) Phase 3: fianlimab (chosen dose) B: fianlimab+cemiplimab cemiplimab Phase 2: fianlimab (LD) Phase 3: fianlimab (chosen dose) C: cemiplimab monotherapy+placebo cemiplimab Phase 2 and Phase 3 C: cemiplimab monotherapy+placebo Placebo Phase 2 and Phase 3
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) as assessed by blinded independent central review (BICR), using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) Up to 136 weeks Phase 2 Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR)
Overall survival (OS) Up to 5 years Phase 3 The time from randomization to the date of death due to any cause
- Secondary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (TEAEs) Up to 136 weeks Phase 2 and Phase 3 A TEAE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment
Incidence of treatment-related TEAEs Up to 136 weeks Phase 2 and Phase 3
ORR by investigator assessment, using RECIST 1.1 Up to 136 weeks Phase 2
Disease control rate (DCR) by BICR Up to 136 weeks Phase 2 and Phase 3 The proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD)
DCR by investigator assessment Up to 136 weeks Phase 2 and Phase 3
Time to tumor response (TTR) by BICR Up to 136 weeks Phase 2 and Phase 3 The time from randomization to the date of the first response of CR or PR (whichever is first recorded) for patients with confirmed CR or PR.
Duration of response (DOR) by BICR Up to 5 years Phase 2 and Phase 3 The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR.
DOR by investigator assessment Up to 5 years Phase 2 and Phase 3
Incidence of serious adverse events (SAEs) Up to 136 weeks Phase 2 and Phase 3
Any untoward medical occurrence that at any dose:
* Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger)
* Is life-threatening
* Requires in-patient hospitalization or prolongation of existing hospitalization • Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Is an important medical eventIncidence of adverse events of special interest (AESIs) Up to 136 weeks Phase 2 and Phase 3 Serious or non-serious; is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it.
Incidence of immune-mediated adverse events (imAEs) Up to 136 weeks Phase 2 and Phase 3 Immune-mediated AEs are thought to be caused by unrestrained cellular immune responses directed at normal host tissues. An imAE can occur shortly after the first dose or several months after the last dose of treatment. Early detection and management reduces the risk of severe drug induced toxicity
Occurrence of interruption of study drug(s) due to TEAEs Up to 136 weeks Phase 2 and Phase 3
Occurrence of discontinuation of study drug(s) due to TEAEs Up to 136 weeks Phase 2 and Phase 3
Occurrence of interruption of study drug(s) due to AESIs Up to 136 weeks Phase 2 and Phase 3
Occurrence of discontinuation of study drug(s) due to AESIs Up to 136 weeks Phase 2 and Phase 3
Occurrence of interruption of study drug(s) due to imAEs Up to 136 weeks Phase 2 and Phase 3
Occurrence of discontinuation of study drug(s) due to imAEs Up to 136 weeks Phase 2 and Phase 3 A unique set of toxicities thought to be caused by unrestrained cellular immune responses
Incidence of deaths due to TEAE Up to 136 weeks Phase 2 and Phase 3
Incidence of grade 3 to 4 laboratory abnormalities Up to 136 weeks Phase 2 and Phase 3
≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\]TTR by investigator assessment Up to 136 weeks Phase 2 and Phase 3
Progression free survival (PFS) by BICR Up to 5 years Phase 2 and Phase 3
PFS by investigator assessment Up to 5 years Phase 2 and Phase 3
Overall survival (OS) Up to 5 years Phase 2 The time from randomization to the date of death due to any cause
Change from baseline in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer (EORTC QLQ-LC13) Up to 5 years Phase 2 and Phase 3 EORTC QLQ-LC 13 is a lung cancer specific module developed to assess lung cancer-associated symptoms and treatment-related side effects among lung cancer patients
Change from baseline in patient-reported global health status/quality of life (GHS/QoL) per European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Up to 5 years Phase 2 and Phase 3 EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a GHS/QoL scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13 Up to 5 years Phase 2 and Phase 3
Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30 Up to 5 years Phase 2 and Phase 3
Change from baseline in patient-reported general health status per EuroQoL-5 Dimensions, 5-level Questionnaire-Visual Analogue Score (EQ-5D-5L VAS) Up to 5 years Phase 2 and Phase 3 The EQ-5D-5L VAS records the respondent's self-rated health on a 10 centimeter (cm) vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine".
Change from baseline in patient-reported severity with usual or daily activities due to fatigue per the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE). Up to 5 years Phase 2 and Phase 3 PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.
Concentrations of cemiplimab in serum Up to 136 weeks Phase 2 and Phase 3
Concentrations of fianlimab in serum Up to 136 weeks Phase 2 and Phase 3
Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab Up to 136 weeks Phase 2 and Phase 3
Immunogenicity, as measured by ADA to cemiplimab Up to 136 weeks Phase 2 and Phase 3
Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab Up to 136 weeks Phase 2 and Phase 3
Immunogenicity, as measured by NAb to cemiplimab Up to 136 weeks Phase 2 and Phase 3
Change from baseline in patient-reported physical functioning per EORTC QLQ-C30 Up to 5 years Phase 2 and Phase 3
Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 Up to 5 years Phase 2 and Phase 3
Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13 Up to 5 years Phase 2 and Phase 3
Change from baseline in patient-reported interference with usual or daily activities due to fatigue per the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE). Up to 5 years Phase 2 and Phase 3
Change from baseline in patient-reported cough per EORTC QLQ-LC13 Up to 5 years Phase 2 and Phase 3
Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13 Up to 5 years Phase 2 and Phase 3
Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13 Up to 5 years Phase 2 and Phase 3
Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13 Up to 5 years Phase 2 and Phase 3
Trial Locations
- Locations (110)
Arizona Clinical Research Center
🇺🇸Tucson, Arizona, United States
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
Desert Hematology Oncology Medical Group Incorporated
🇺🇸Rancho Mirage, California, United States
Emad Ibrahim, MD, Inc.
🇺🇸Redlands, California, United States
Eastern CT Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Clermont Oncology Center
🇺🇸Clermont, Florida, United States
Miami Veterans Administration HealthCare System
🇺🇸Miami, Florida, United States
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, Florida, United States
Pinellas Hematology and Oncology
🇺🇸Saint Petersburg, Florida, United States
Tallahassee Memorial Healthcare
🇺🇸Tallahassee, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Mercy South
🇺🇸Saint Louis, Missouri, United States
Capital Health Hopewell Medical Center
🇺🇸Pennington, New Jersey, United States
New Mexico Cancer Care Alliance
🇺🇸Albuquerque, New Mexico, United States
New York Cancer and Blood Specialists
🇺🇸Port Jefferson Station, New York, United States
Clinical Research Alliance Inc
🇺🇸Westbury, New York, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Thompson Cancer Survival Center (TCSC ) - Downtown
🇺🇸Knoxville, Tennessee, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Renovatio Clinical
🇺🇸El Paso, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
Bon Secours Cancer Institute Richmond
🇺🇸Midlothian, Virginia, United States
Macquarie University Health Science Center (MQ Health)
🇦🇺Macquarie Park, New South Wales, Australia
Riverina Cancer Care Centre (RCCC)
🇦🇺Wagga Wagga, New South Wales, Australia
Southern Medical Day Care Centre
🇦🇺Wollongong, New South Wales, Australia
Ballarat Regional Integrated Cancer Centre (BRICC)
🇦🇺Ballarat, Victoria, Australia
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
British Columbia Cancer Center-Kelowna
🇨🇦Kelowna, British Columbia, Canada
Cancer Center of Adjara
🇬🇪Batumi, Adjaria, Georgia
Israeli Georgian Medical Research Clinic Helsicore
🇬🇪Tbilisi, Georgia
NNLE New Vision University Hospital
🇬🇪Tbilisi, Georgia
The Institute of Clinical Oncology
🇬🇪Tbilisi, Georgia
TIM - Tbilisi Institute of Medicine
🇬🇪Tbilisi, Georgia
Research Institute of Clinical Medicine
🇬🇪Tbilisi, Georgia
Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
🇬🇪Tbilisi, Georgia
JSC Evex Hospitals - Caraps Medline
🇬🇪Tbilisi, Georgia
Soroka University Medical Center
🇮🇱Beer-Sheba, HaDarom, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Assuta Medical Centers
🇮🇱Tel Aviv, Israel
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungbuk, Korea, Republic of
St. Vincents Hospital - The Catholic University of Korea
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Jeonbuk National University Hospital
🇰🇷Jeonju, Jeollabuk-do, Korea, Republic of
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Hospital Sultan Ismail
🇲🇾Johor Bahru, Johor, Malaysia
Hospital Tengku Ampuan Afzan( HTTA)
🇲🇾Kuantan, Pahang, Malaysia
National Cancer Institute
🇲🇾Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Wilayah Persekutuan, Malaysia
Hospital Pulau Pinang
🇲🇾Pulau Pinang, Malaysia
Hospital Clinico Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruna, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Son Espases
🇪🇸Palma, Balearic Islands, Spain
Instituto Oncologico Dr Rosell Hospital Universitari Quiron Dexeus Location
🇪🇸Barcelona, Catalunya, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
🇪🇸Barcelona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital De Valme
🇪🇸Sevilla, Spain
Dalin Tzu Chi Hospital
🇨🇳Dalin, Chia-yi County, Taiwan
Buddhist Tzu Chi General Hospital
🇨🇳Hualien City, Hualien, Taiwan
Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taipei Medical University - Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Tri-Service General Hospital
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Navamindradhiraj University
🇹🇭Dusit, Bangkok, Thailand
Lampang Cancer Center
🇹🇭Lampang, Lampang Province, Thailand
Prince Of Songkla Hospital, Prince Of Songkhla University
🇹🇭Hat-Yai, Songkhla, Thailand
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Siriraj Hospital
🇹🇭Bangkok, Thailand
Chiang Mai University
🇹🇭Chiang Mai, Thailand
Hacettepe University Medical Faculty
🇹🇷Altindag, Ankara, Turkey
Medipol University Hospital
🇹🇷Istanbul, Bagcilar, Turkey
Bursa Uludag University Medical Faculty
🇹🇷Bursa, Gorukle Bursa Turkiye, Turkey
Istinye University VMMedical Park Pendik Hospital
🇹🇷Pendik, Istanbul, Turkey
Kocaeli University Hospital
🇹🇷Kocaeli, Marmara, Turkey
Necmettin Erbakan University Meram Faculty of Medicine
🇹🇷Konya, Turkey
Ondokuz Mayıs University
🇹🇷Kurupelit, Samsun, Turkey
Gaziantep Medicalpoint Hospital
🇹🇷Gaziantep, Sehitkamil, Turkey
Sakarya University
🇹🇷Sakarya, Serdivan, Turkey
Acibadem Adana Hastanesi
🇹🇷Adana, Seyhan, Turkey
Adana City Education and Research Hospital
🇹🇷Adana, Yuregir, Turkey
Baskent University
🇹🇷Adana, Turkey
Ankara Etlik Sehir Hastanesi Ankara Etlik City Hospital
🇹🇷Ankara, Turkey
Gulhane Research And Training Hospital
🇹🇷Ankara, Turkey
Ankara Yildirim Beyazit Universitesi - Tip Fakultesi
🇹🇷Ankara, Turkey
Gazi University
🇹🇷Ankara, Turkey
Liv Hospital Ankara
🇹🇷Ankara, Turkey
Sbu Doctor Abdurrahman Yurtaslan Ankara Onkoloji Suam
🇹🇷Ankara, Turkey
Memorial Ankara Hospital
🇹🇷Ankara, Turkey
Yuksek Ihtisas Unıversity Medicalpark Hospital
🇹🇷Ankara, Turkey
Trakya University
🇹🇷Edirne, Turkey
Koc University
🇹🇷Istanbul, Turkey
Bezmialem Vakif University
🇹🇷Istanbul, Turkey
Memorial Bahcelievler Hospital
🇹🇷Istanbul, Turkey
Istanbul University Cerrahpasa at Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Istanbul Medeniyet University Prof.Dr.Suleyman Yalcin Şehir Hospital
🇹🇷Istanbul, Turkey
Izmir Dr.Suat Seren Gogus Hastaliklari Ve Cerrahisi Egitim Ve Arastirma Hastanesi
🇹🇷Izmir, Turkey
Izmir Economy University Medical Point Hospital
🇹🇷Izmir, Turkey
Vm Medicalpark Hospital
🇹🇷Samsun, Turkey