MedPath

SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients

Phase 3
Active, not recruiting
Conditions
Non-small Cell Lung Cancer Metastatic
Interventions
Registration Number
NCT04154956
Lead Sponsor
Sanofi
Brief Summary

Primary Objectives:

* Study was designed with multiple primary endpoints analyzed on randomized participants at the time of the cut-off date for each given analysis (progression free survival \[PFS\] and overall survival \[OS\])

* Study success was defined either on PFS or OS

* The primary objective was to determine whether tusamitamab ravtansine improves the progression free survival (PFS) when compared to docetaxel in participants with metastatic non-squamous non-small-cell lung cancer (NSCLC) expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor (ICI)

* The primary objective was to determine whether tusamitamab ravtansine improves the overall survival (OS) when compared with docetaxel in participants with metastatic non-squamous NSCLC expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor.

Secondary Objectives:

* Compared the objective response rate (ORR) of tusamitamab ravtansine with docetaxel

* Compared the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel

* Evaluated the safety of tusamitamab ravtansine compared to docetaxel

* Assessed the duration of response (DOR) of tusamitamab ravtansine as compared with docetaxel

Detailed Description

The median expected duration of study per participant was estimated as median 9 months in docetaxel arm (1 month for screening, 4 months for treatment, and 4 months for the EOT and follow-up visits) and 12.5 months in SAR408701 arm (1 month for screening, 6.5 months for treatment, and 5 months for end of treatment follow-up).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
389
Inclusion Criteria
  • At least 18 years of age or above (or country's legal age of maturity if above 18 years) and signed the informed consent.
  • Histologically or cytologically proven diagnosis of non-squamous NSCLC with metastatic disease at study entry; progression after platinum-based chemotherapy and immune checkpoint inhibitor.
  • Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5 expression of greater than or equal to 2+ in archival tumor sample (or if not available, fresh biopsy sample) involving at least 50% of the tumor cell population as demonstrated prospectively by central laboratory via immune histochemistry (IHC).
  • At least one measurable lesion by RECIST v1.1 as determined by local site investigator /radiologist assessment.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • A female participant who agreed to use highly effective contraceptive methods during and for at least 7 months after the last dose of study intervention.
  • A male participant who agreed to use highly effective contraception methods during and for at least 6 months after the last dose of study intervention.
Exclusion Criteria
  • Participants with untreated brain metastases and history of leptomeningeal disease. if previously treated brain metastases no documentation of non-progressive disease in brain by imaging performed at least 4 weeks after CNS directed treatment and at least 2 weeks prior to the first dose of study intervention.
  • Significant concomitant illnesses, including all severe medical conditions that would impair the participation in the study or interpretation of the results.
  • History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
  • Non-resolution of any prior treatment related toxicity to less than grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (V) 5.0, except for alopecia, vitiligo and active thyroiditis controlled with hormonal replacement therapy
  • History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis
  • Previous history of and/or unresolved corneal disorders. The use of contact lenses was not permitted.
  • Concurrent treatment with any other anticancer therapy.
  • Prior treatment with docetaxel or maytansinoid derivatives (DM1 or DM4 antibody drug conjugate) or any drug targeting CEACAM5.
  • Contraindicated the use of corticosteroid premedication.
  • Previous enrollment in this study and current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
  • Poor bone marrow, liver or kidney functions
  • Hypersensitivity to any of the study interventions, or components thereof (EDTA), or drug (paclitaxel, polysorbate 80) or other allergy that, in the opinion of the Investigator, contraindicated participation in the study.

The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAR408701 (tusamitamab ravtansine)SAR408701Participants received tusamitamab ravtansine 100 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion, once every 2 weeks (Q2W) until objective progressive disease (PD), unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).
DocetaxelDocetaxelParticipants received docetaxel 75 mg/m\^2 by IV infusion, once every 3 weeks (Q3W) until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Primary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS)Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

PFS was defined as the time from the date of randomization to the date of the first documentation of objective PD as assessed by radiological review committee (IRC) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) definitions or death due to any cause before the study cut-off date, whichever occurred first. PD was defined as unequivocal progression of existing non-target lesions; appearance of 1 or more new lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm).

Overall Survival (OS)From date of first study treatment administration (Day 1) until the date of death due to any cause, up to 189 weeks

Overall survival was defined as the time from date of randomization to date of death due to any cause.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With PCSA in Clinical ChemistryFrom date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks

Blood samples were collected to determine the clinical chemistry laboratory abnormalities.

Objective Response Rate (ORR)Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

ORR was defined as the percentage of participants who had a complete response (CR) or partial response (PR), as best overall response derived from overall response (OR) determined by the IRC per RECIST 1.1. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time to Deterioration (TTD) in Disease-related Symptoms as Determined by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire and Lung Cancer-specific Module With 13 Items (EORTC QLQ LC-13)Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks

The TTD was defined as the time from baseline (Cycle 1, Day 1) until the first ≥10-point change from baseline up to the end of treatment assessment before the initiation of further anticancer therapy and the analysis cut-off date. For the TTD in disease-related symptoms (cough, dyspnea, pain) from EORTC QLQ LC-13, a deterioration was defined as an increase from baseline score of at least 10 points in any 1 of these 3 symptoms. The EORTC QLQ-LC13 (LC13) is the lung cancer module of the EORTC QLQ-C30 that assesses lung-cancer-associated symptoms (cough, dyspnea, pain, hemoptysis) and side-effects from conventional chemotherapy and radiotherapy (sore mouth, hair loss, dysphagia and neuropathy). The EORTC QLQ-LC13 contains 13 items. Items on the LC13 were scored using the LC13 scoring algorithms which standardize the raw scores to a 0-100 range. Lower scores indicate lower symptomology/symptom burden (lower scores better).

TTD in Physical Function as Determined by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Cancer-specific Module With 30 Items (EORTC QLQ C30)Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks

TTD was defined as time from baseline(Cycle 1,Day 1) until first ≥10-point change from baseline up to end of treatment assessment before initiation of further anticancer therapy and analysis cut-off date.For TTD in physical function from EORTC QLQ-C30, deterioration=decrease of at least 10 points from baseline score.EORTC QLQ-C30(C30) is 30-item, cancer specific that includes global health status/health-related quality of life(GHS/QoL), functional scales(physical,role,emotional,cognitive,social), symptom scales(fatigue,nausea\&vomiting,pain), 5 symptom items(dyspnea,insomnia,appetite loss,constipation,diarrhea,perceived financial difficulties). Most questions from QLQ-C30 were rated on 4-point scale(1/Not at All to 4/Very Much), except Items 29-30,which comprise GHS scale and were rated on 7-point scale(1/Very Poor to 7/Excellent). All scales were transformed from raw scores to linear scales ranging 0-100. High score represented favorable outcome with best quality of life.

TTD in Role Function Measured by EORTC QLQ C30Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks

TTD was defined as time from baseline (Cycle 1, Day 1) until first ≥10-point change from baseline up to end of treatment assessment before initiation of further anticancer therapy and analysis cut-off date. For TTD in role function from EORTC QLQ-C30, deterioration = decrease of at least 10 points from baseline score. EORTC QLQ-C30 (C30) is a 30-item, cancer specific that includes GHS/QoL, functional scales (physical, role, emotional, cognitive, social), symptom scales (fatigue, nausea \& vomiting, pain), 5 symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, perceived financial difficulties item). Most questions from QLQ-C30 were rated on a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were rated on a 7-point scale (1/Very Poor to 7/Excellent). All scales were transformed from raw scores to linear scales ranging 0 to 100. A high score represented a favorable outcome with a best quality of life for participant.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment period.

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology ParametersFrom date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks

Blood samples were collected to determine the abnormalities in hematology parameters.

Duration of Response (DOR)Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

DOR was defined as the time from the date of first initial occurrence of a CR or PR to the date of first documentation of objective PD according to RECIST 1.1 before the initiation of any posttreatment anticancer therapy or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as unequivocal progression of existing non-target lesions; appearance of 1 or more new lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Trial Locations

Locations (204)

Investigational Site Number : 3560011

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Trivandrum, India

National Jewish Health Site Number : 8400033

🇺🇸

Denver, Colorado, United States

Florida Cancer Specialists South Division Site Number : 8400020

🇺🇸

Fort Myers, Florida, United States

Florida Cancer Specialists North Division Site Number : 8400019

🇺🇸

Saint Petersburg, Florida, United States

Ca & Hem Center Of W Michigan Site Number : 8400016

🇺🇸

Grand Rapids, Michigan, United States

Roswell Park Cancer Institute Site Number : 8400011

🇺🇸

Buffalo, New York, United States

Lankenau Hospital Cancer Center Site Number : 8400017

🇺🇸

Wynnewood, Pennsylvania, United States

Renovatio Clinical Site Number : 8400032

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El Paso, Texas, United States

Renovatio Clinical Site Number : 8400013

🇺🇸

The Woodlands, Texas, United States

Medical College of Wisconsin Site Number : 8400006

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Milwaukee, Wisconsin, United States

Investigational Site Number : 0320009

🇦🇷

Caba, Buenos Aires, Argentina

Investigational Site Number : 0320012

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Capital Federal, Buenos Aires, Argentina

Investigational Site Number : 0320008

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Pergamino, Buenos Aires, Argentina

Investigational Site Number : 0320003

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Viedma, Río Negro, Argentina

Investigational Site Number : 0320005

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Rosario, Santa Fe, Argentina

Investigational Site Number : 0320001

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Buenos Aires, Argentina

Investigational Site Number : 0320004

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Buenos Aires, Argentina

Investigational Site Number : 0320014

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Ciudad De Cordoba, Argentina

Investigational Site Number : 0320002

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Salta, Argentina

Investigational Site Number : 0360002

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Blacktown, New South Wales, Australia

Investigational Site Number : 0360003

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Waratah, New South Wales, Australia

Investigational Site Number : 0360001

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Woolloongabba, Queensland, Australia

Investigational Site Number : 0560006

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Anderlecht, Belgium

Investigational Site Number : 0560007

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Charleroi, Belgium

Investigational Site Number : 0560004

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Edegem, Belgium

Investigational Site Number : 0560005

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Gent, Belgium

Investigational Site Number : 0560001

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Leuven, Belgium

Investigational Site Number : 0560003

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Liège, Belgium

Investigational Site Number : 0560002

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Sint-Lambrechts-Woluwe, Belgium

Centro Regional Integrado De Oncologia - CRIO Site Number : 0760002

🇧🇷

Fortaleza, Ceará, Brazil

Instituto De Oncologia Parana Site Number : 0760008

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Curitiba, Paraná, Brazil

Centro Avancado de Oncologia CECAN - Liga Contra o Cancer Site Number : 0760026

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Natal, Rio Grande Do Norte, Brazil

Clínica de Oncologia Reichow Site Number : 0760023

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Blumenau, Santa Catarina, Brazil

Hospital de Base Sao Jose do Rio Preto Site Number : 0760001

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Sao Jose do Rio Preto, São Paulo, Brazil

IEP - Instituto de Ensino e Pesquisa Sao Lucas Site Number : 0760010

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Sao Paulo, São Paulo, Brazil

Hospital Sirio Libanes Site Number : 0760018

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Sao Paulo, São Paulo, Brazil

Hospital Alemao Oswaldo Cruz Site Number : 0760022

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Sao Paulo, São Paulo, Brazil

Investigational Site Number : 1000008

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Burgas, Bulgaria

Investigational Site Number : 1000010

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Pleven, Bulgaria

Investigational Site Number : 1000007

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Plovdiv, Bulgaria

Investigational Site Number : 1000004

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Sofia, Bulgaria

Investigational Site Number : 1000002

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Sofia, Bulgaria

Investigational Site Number : 1000003

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Sofia, Bulgaria

Investigational Site Number : 1000005

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Sofia, Bulgaria

Investigational Site Number : 1000001

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Sofia, Bulgaria

Investigational Site Number : 1240008

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Halifax, Nova Scotia, Canada

Investigational Site Number : 1240003

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Greenfield Park, Quebec, Canada

Investigational Site Number : 1240010

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Montreal, Quebec, Canada

Investigational Site Number : 1240009

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Montreal, Quebec, Canada

Investigational Site Number : 1520007

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Santiago, Reg Metropolitana De Santiago, Chile

Investigational Site Number : 1520006

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Santiago, Reg Metropolitana De Santiago, Chile

Investigational Site Number : 1520009

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Santiago, Reg Metropolitana De Santiago, Chile

Investigational Site Number : 1520002

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Santiago, Reg Metropolitana De Santiago, Chile

Investigational Site Number : 1520001

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Viña del Mar, Valparaíso, Chile

Investigational Site Number : 1560026

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Beijing, China

Investigational Site Number : 1560042

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Beijing, China

Investigational Site Number : 1560009

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Changchun, China

Investigational Site Number : 1560010

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Changchun, China

Investigational Site Number : 1560015

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Changsha, China

Investigational Site Number : 1560039

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Changsha, China

Investigational Site Number : 1560032

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Chengdu, China

Investigational Site Number : 1560038

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Chengdu, China

Investigational Site Number : 1560044

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Chongqing, China

Investigational Site Number : 1560043

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Chongqing, China

Investigational Site Number : 1560024

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Fuzhou, China

Investigational Site Number : 1560051

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Ganzhou, China

Investigational Site Number : 1560001

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Guangzhou, China

Investigational Site Number : 1560036

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Guangzhou, China

Investigational Site Number : 1560037

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Guangzhou, China

Investigational Site Number : 1560017

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Guangzhou, China

Investigational Site Number : 1560034

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Guangzhou, China

Investigational Site Number : 1560025

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Hangzhou, China

Investigational Site Number : 1560033

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Hangzhou, China

Investigational Site Number : 1560021

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Hangzhou, China

Investigational Site Number : 1560018

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Hangzhou, China

Investigational Site Number : 1560011

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Hangzhou, China

Investigational Site Number : 1560005

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Harbin, China

Investigational Site Number : 1560014

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Hefei, China

Investigational Site Number : 1560004

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Hefei, China

Investigational Site Number : 1560050

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Huizhou, China

Investigational Site Number : 1560047

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Jinan, China

Investigational Site Number : 1560035

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Nanchang, China

Investigational Site Number : 1560023

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Nanjing, China

Investigational Site Number : 1560019

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Nanjing, China

Investigational Site Number : 1560012

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Nanning, China

Investigational Site Number : 1560045

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Tianjin, China

Investigational Site Number : 1560006

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Wuhan, China

Investigational Site Number : 1560016

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Zhanjiang, China

Investigational Site Number : 1560041

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Zhengzhou, China

Investigational Site Number : 1560040

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Zhengzhou, China

Investigational Site Number : 1560048

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Zhongshan, China

Investigational Site Number : 2500010

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Bordeaux Cedex, France

Investigational Site Number : 2500008

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CAEN Cedex 05, France

Investigational Site Number : 2500006

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Creteil, France

Investigational Site Number : 2500005

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Dijon, France

Investigational Site Number : 2500007

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GRENOBLE Cedex 9, France

Investigational Site Number : 2500001

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Marseille, France

Investigational Site Number : 2500013

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Montpellier, France

Investigational Site Number : 2500011

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Paris, France

Investigational Site Number : 2500014

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Paris, France

Investigational Site Number : 2500009

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Pierre Benite, France

Investigational Site Number : 2500003

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RENNES Cedex 09, France

Investigational Site Number : 2500012

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Saint Herblain, France

Investigational Site Number : 2500002

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Saint-mande, France

Investigational Site Number : 2500004

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Villejuif, France

Investigational Site Number : 2760002

🇩🇪

Essen, Germany

Investigational Site Number : 2760001

🇩🇪

Heidelberg, Germany

Investigational Site Number : 3000005

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Athens, Greece

Investigational Site Number : 3000001

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Athens, Greece

Investigational Site Number : 3000003

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Heraklion, Greece

Investigational Site Number : 3000004

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Ioannina, Greece

Investigational Site Number : 3000002

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Larisa, Greece

Investigational Site Number : 3000006

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Thessaloniki, Greece

Investigational Site Number : 3480003

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Budapest, Hungary

Investigational Site Number : 3480004

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Budapest, Hungary

Investigational Site Number : 3480007

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Budapest, Hungary

Investigational Site Number : 3480005

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Kaposvár, Hungary

Investigational Site Number : 3560010

🇮🇳

Bhubaneswar, India

Investigational Site Number : 3560008

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Jaipur, India

Investigational Site Number : 3560007

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New Delhi, India

Investigational Site Number : 3560001

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Pune, India

Investigational Site Number : 3560006

🇮🇳

Pune, India

Investigational Site Number : 3760001

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Haifa, Israel

Investigational Site Number : 3760002

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Kfar-Saba, Israel

Investigational Site Number : 3760003

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Petach Tikva, Israel

Investigational Site Number : 3800004

🇮🇹

Ravenna, Emilia-Romagna, Italy

Investigational Site Number : 3800005

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Rozzano, Milano, Italy

Investigational Site Number : 3800003

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Orbassano, Torino, Italy

Investigational Site Number : 3800006

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Catania, Italy

Investigational Site Number : 3800001

🇮🇹

Milano, Italy

Investigational Site Number : 3920002

🇯🇵

Nagoya-shi, Aichi, Japan

Investigational Site Number : 3920015

🇯🇵

Nagoya-shi, Aichi, Japan

Investigational Site Number : 3920012

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Fukuoka-shi, Fukuoka, Japan

Investigational Site Number : 3920008

🇯🇵

Kurume-shi, Fukuoka, Japan

Investigational Site Number : 3920016

🇯🇵

Sapporo-shi, Hokkaido, Japan

Investigational Site Number : 3920017

🇯🇵

Himeji-shi, Hyogo, Japan

Investigational Site Number : 3920006

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Kanazawa-shi, Ishikawa, Japan

Investigational Site Number : 3920005

🇯🇵

Yokohama-shi, Kanagawa, Japan

Investigational Site Number : 3920009

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Natori-shi, Miyagi, Japan

Investigational Site Number : 3920001

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Hirakata-shi, Osaka, Japan

Investigational Site Number : 3920013

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Osaka Sayama-shi, Osaka, Japan

Investigational Site Number : 3920003

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Osaka-shi, Osaka, Japan

Investigational Site Number : 3920014

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Sakai-shi, Osaka, Japan

Investigational Site Number : 3920004

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Sunto-gun, Shizuoka, Japan

Investigational Site Number : 3920011

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Bunkyo-ku, Tokyo, Japan

Investigational Site Number : 3920018

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Mitaka-shi, Tokyo, Japan

Investigational Site Number : 3920007

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Wakayama-shi, Wakayama, Japan

Investigational Site Number : 3920010

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Ube-shi, Yamaguchi, Japan

Investigational Site Number : 4100008

🇰🇷

Busan, Busan-gwangyeoksi, Korea, Republic of

Investigational Site Number : 4100005

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Cheongju-si, Chungcheongbuk-do, Korea, Republic of

Investigational Site Number : 4100006

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Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 4100007

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Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 4100003

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 4100004

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 4100001

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Seoul, Korea, Republic of

Investigational Site Number : 4400003

🇱🇹

Kaunas, Lithuania

Investigational Site Number : 4400001

🇱🇹

Vilnius, Lithuania

Investigational Site Number : 4840003

🇲🇽

Cuauhtémoc, Ciudad De Mexico, Mexico

Investigational Site Number : 4840009

🇲🇽

Ciudad de Mexico, Mexico

Investigational Site Number : 5280003

🇳🇱

's Hertogenbosch, Netherlands

Investigational Site Number : 5280004

🇳🇱

Breda, Netherlands

Investigational Site Number : 5280005

🇳🇱

Utrecht, Netherlands

Investigational Site Number : 6160004

🇵🇱

Olsztyn, Warminsko-mazurskie, Poland

Investigational Site Number : 6160001

🇵🇱

Warsaw, Poland

Investigational Site Number : 6200002

🇵🇹

Almada, Portugal

Investigational Site Number : 6200001

🇵🇹

Lisboa, Portugal

Investigational Site Number : 6200004

🇵🇹

Lisboa, Portugal

Investigational Site Number : 6200005

🇵🇹

Porto, Portugal

Investigational Site Number : 6200006

🇵🇹

Porto, Portugal

Investigational Site Number : 6420008

🇷🇴

Alba Iulia, Romania

Investigational Site Number : 6420009

🇷🇴

Brasov, Romania

Investigational Site Number : 6420003

🇷🇴

Bucaresti, Romania

Investigational Site Number : 6420010

🇷🇴

Cluj-Napoca, Romania

Investigational Site Number : 6420011

🇷🇴

Cluj, Romania

Investigational Site Number : 6420006

🇷🇴

Craiova, Romania

Investigational Site Number : 6420012

🇷🇴

Otopeni, Romania

Investigational Site Number : 6420005

🇷🇴

Timisoara, Romania

Investigational Site Number : 6420004

🇷🇴

Timisoara, Romania

Investigational Site Number : 6430001

🇷🇺

Moscow, Russian Federation

Investigational Site Number : 6430003

🇷🇺

Saint -Petersburg, Russian Federation

Investigational Site Number : 7020001

🇸🇬

Singapore, Singapore

Investigational Site Number : 7020002

🇸🇬

Singapore, Singapore

Investigational Site Number : 7240007

🇪🇸

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7240005

🇪🇸

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7240001

🇪🇸

Hospitalet de Llobregat, Barcelona [Barcelona], Spain

Investigational Site Number : 7240009

🇪🇸

Madrid / Madrid, Madrid, Comunidad De, Spain

Investigational Site Number : 7240006

🇪🇸

Pamplona, Navarra, Spain

Investigational Site Number : 7240002

🇪🇸

Madrid, Spain

Investigational Site Number : 7240004

🇪🇸

Málaga, Spain

Investigational Site Number : 7240011

🇪🇸

Sevilla, Spain

Investigational Site Number : 7240008

🇪🇸

Valencia, Spain

Investigational Site Number : 7920008

🇹🇷

Adana, Turkey

Investigational Site Number : 7920012

🇹🇷

Adana, Turkey

Investigational Site Number : 7920002

🇹🇷

Adana, Turkey

Investigational Site Number : 7920011

🇹🇷

Ankara, Turkey

Investigational Site Number : 7920005

🇹🇷

Istanbul, Turkey

Investigational Site Number : 7920001

🇹🇷

Istanbul, Turkey

Investigational Site Number : 7920006

🇹🇷

Istanbul, Turkey

Investigational Site Number : 7920007

🇹🇷

Izmir, Turkey

Investigational Site Number : 7920010

🇹🇷

Izmir, Turkey

Investigational Site Number : 7920014

🇹🇷

Kocaeli, Turkey

Investigational Site Number : 7920009

🇹🇷

Malatya, Turkey

Investigational Site Number : 8260004

🇬🇧

Truro, Cornwall, United Kingdom

Investigational Site Number : 8260002

🇬🇧

London, United Kingdom

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