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A Phase 1/2 Study to Evaluate MEDI4736

Study Purpose

This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 99 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Age 18 or older.
  • - In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
  • - In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, participants must have failed, be intolerant to, be ineligible for, or have refused.
  • - Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
  • - Adequate organ and marrow function.
  • - Participants must have at least 1 measurable lesion.
  • - Available archived tumor tissue sample.
  • - Willingness to provide consent for biopsy sample (dose-expansion only)

    Exclusion Criteria:

    - Any prior Grade ≥ 3 immune-mediated adverse event (imAE) while receiving immunotherapy.
  • - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
  • - Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
  • - Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors.
  • - Active or prior documented autoimmune disease within the past 2 years.
  • - History of primary immunodeficiency.
  • - History of organ transplant that requires use of immunosuppressives.
  • - Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment.
  • - Other invasive malignancy within 2 years.
  • - Women who are pregnant or lactating.
  • - Uncontrolled intercurrent illness.
  • - Known history of tuberculosis.
  • - Known to be human immunodeficiency virus (HIV) positive.
- Known to be Hepatitis B or C positive (except HCC participants)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01693562
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

MedImmune LLC
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

MedImmune, LLC
Principal Investigator Affiliation MedImmune LLC
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Completed
Countries Belgium, Canada, France, Germany, Italy, Korea, Republic of, Taiwan, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Advanced Solid Tumors
Study Website: View Trial Website
Additional Details

A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death ligand-1 (PD-L1)) will evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (IM), and antitumor activity of MEDI4736 in adult participants with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.

Arms & Interventions

Arms

Experimental: Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)

Participants will receive intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

Participants will receive IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Escalation Cohort (MEDI4736 1 mg/kg Q2W)

Participants will receive IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Escalation Cohort (MEDI4736 3 mg/kg Q2W)

Participants will receive IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Escalation Cohort (MEDI4736 10 mg/kg Q2W)

Participants will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Escalation Cohort (MEDI4736 15 mg/kg Q3W)

Participants will receive IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Exploration Durvalumab 20 mg/kg (Q4W)

Participants will receive IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)

Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W)

Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with non-small-cell lung cancer (NSCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

Participants with hepatocellular carcinoma (HCC Total) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

Participants with advance cutaneous melanoma (ACM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)

Participants with uveal melanoma (UM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with gastroesophageal cancer (GEC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with triple-negative breast cancer (TNBC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with pancreatic adenocarcinoma (PAC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with urothelial carcinoma (UC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

Participants with glioblastoma multiforme (GBM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with ovarian cancer (OC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)

Participants with soft- tissue sarcoma (STS) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with small-cell lung cancer (SCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)

Participants with microsatellite instability (MSI)-high cancer will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Experimental: Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)

Participants with nasopharyngeal carcinoma (NPC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Interventions

Drug: - MEDI4736

Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Research Site, Scottsdale, Arizona

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Scottsdale, Arizona, 85258

Research Site, Burbank, California

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Burbank, California, 91505

Research Site, Gilroy, California

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Gilroy, California, 95020

Research Site, Los Angeles, California

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Los Angeles, California, 90025

Research Site, Los Angeles, California

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Los Angeles, California, 90095

Research Site, Orange, California

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Orange, California, 92868

Research Site, Palo Alto, California

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Palo Alto, California, 94304-5826

Research Site, San Francisco, California

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San Francisco, California, 94115

Research Site, Whittier, California

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Whittier, California, 90603

Research Site, New Haven, Connecticut

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New Haven, Connecticut, 06520

Research Site, Washington, District of Columbia

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Washington, District of Columbia, 20007

Research Site, Jacksonville, Florida

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Jacksonville, Florida, 32224

Research Site, Miami Beach, Florida

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Miami Beach, Florida, 33140

Research Site, Tampa, Florida

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Tampa, Florida, 33612

Research Site, Athens, Georgia

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Athens, Georgia, 30607

Research Site, Augusta, Georgia

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Augusta, Georgia, 30912

Research Site, Chicago, Illinois

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Chicago, Illinois, 60637

Research Site, Baltimore, Maryland

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Baltimore, Maryland, 21201

Research Site, Baltimore, Maryland

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Baltimore, Maryland, 21231

Research Site, Boston, Massachusetts

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Boston, Massachusetts, 02215

Research Site, Ann Arbor, Michigan

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Ann Arbor, Michigan, 48109

Research Site, Detroit, Michigan

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Detroit, Michigan, 48201

Research Site, Minneapolis, Minnesota

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Minneapolis, Minnesota, 55407

Research Site, Saint Louis Park, Minnesota

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Saint Louis Park, Minnesota, 55416

Research Site, Billings, Montana

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Billings, Montana, 59101

Research Site, Las Vegas, Nevada

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Las Vegas, Nevada, 89169

Research Site, Hackensack, New Jersey

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Hackensack, New Jersey, 07601

Research Site, Paterson, New Jersey

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Paterson, New Jersey, 07503

Research Site, Bronx, New York

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Bronx, New York, 10461

Research Site, New York, New York

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New York, New York, 10065

Research Site, Chapel Hill, North Carolina

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Chapel Hill, North Carolina, 27599

Research Site, Huntersville, North Carolina

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Huntersville, North Carolina, 28078

Research Site, Cleveland, Ohio

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Cleveland, Ohio, 44106

Research Site, Columbus, Ohio

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Columbus, Ohio, 43210

Research Site, Portland, Oregon

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Portland, Oregon, 97213

Research Site, Philadelphia, Pennsylvania

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Philadelphia, Pennsylvania, 19107-5097

Research Site, Pittsburgh, Pennsylvania

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Pittsburgh, Pennsylvania, 15212

Research Site, Greenville, South Carolina

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Greenville, South Carolina, 29605

Research Site, Nashville, Tennessee

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Nashville, Tennessee, 37203

Research Site, Dallas, Texas

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Dallas, Texas, 75201

Research Site, Houston, Texas

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Houston, Texas, 77030

Research Site, Houston, Texas

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Houston, Texas, 77090

Research Site, San Antonio, Texas

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San Antonio, Texas, 78229

Research Site, Salt Lake City, Utah

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Salt Lake City, Utah, 84403

Research Site, Blacksburg, Virginia

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Blacksburg, Virginia, 24060

Research Site, Fairfax, Virginia

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Fairfax, Virginia, 22031

Research Site, Seattle, Washington

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Seattle, Washington, 98104

International Sites

Research Site, Gent, Belgium

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Gent, , 9000

Research Site, Leuven, Belgium

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Leuven, , 3000

Research Site, Liege, Belgium

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Liege, , B-4000

Research Site, Namur, Belgium

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Namur, , 5000

Research Site, Ottawa, Ontario, Canada

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Ottawa, Ontario, K1H 8L6

Research Site, Toronto, Ontario, Canada

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Toronto, Ontario, M5G 2M9

Research Site, Montreal, Quebec, Canada

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Montreal, Quebec, H2X 3E4

Research Site, Paris Cedex 10, France

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Paris Cedex 10, , 75475

Research Site, Villejuif Cedex, France

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Villejuif Cedex, , 94800

Research Site, Berlin, Germany

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Berlin, , 12200

Research Site, Gauting, Germany

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Gauting, , 82131

Research Site, Heidelberg, Germany

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Heidelberg, , 69120

Research Site, Jena, Germany

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Jena, , 07747

Research Site, Minden, Germany

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Minden, , 32429

Research Site, Lecce, Italy

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Lecce, , 73100

Research Site, Milano, Italy

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Milano, , 20132

Research Site, Milan, Italy

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Milan, , 20141

Research Site, Napoli, Italy

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Napoli, , 80131

Research Site, Siena, Italy

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Siena, , 53100

Research Site, Gwangju, Korea, Republic of

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Gwangju, , 61469

Research Site, Seo-Gu, Korea, Republic of

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Seo-Gu, , 49241

Research Site, Seongnam-si, Korea, Republic of

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Seongnam-si, , 13620

Research Site, Seoul, Korea, Republic of

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Seoul, , 03080

Research Site, Seoul, Korea, Republic of

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Seoul, , 05505

Research Site, Seoul, Korea, Republic of

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Seoul, , 06351

Research Site, Tainan, Taiwan

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Tainan, , 70403

Research Site, Taipei, Taiwan

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Taipei, , 10002

Research Site, London, United Kingdom

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London, , EC1A 7BE

Research Site, London, United Kingdom

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London, , SW2 6JJ

Research Site, London, United Kingdom

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London, , W1G 6AD

Research Site, Oxford, United Kingdom

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Oxford, , OX3 7LE

Research Site, Sutton, United Kingdom

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Sutton, , SM2 5PT