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A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC

NCT05211895 · AstraZeneca
In plain English

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Official title
A Phase III, Randomised, Double-blind, Placebo-controlled, Multicentre, International Study of Durvalumab Plus Domvanalimab(AB154) in Participants With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer Whose Disease Has Not Progressed Following Definitive Platinum-based Concurrent Chemoradiation Therapy
About this study
This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive platinum-based cCRT.
Eligibility criteria
INCLUSION CRITERIA: 1. Participant must be ≥ 18 years at the time of screening. 2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease 3. Provision of a tumour tissue sample obtained prior to CRT 4. Documented tumour PD-L1 status ≥ 1% by central lab 5. Documented EGFR and ALK wild-type status (local or central). 6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy 7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy 8. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique. 9. WHO performance status of 0 or 1 at randomization 10. Adequate organ and marrow function EXCLUSION CRITERIA: 1. History of another primary malignancy, except for: * Malignancies treated with curative intent and adequate follow-up with no known active disease and have not required active treatment within the past 3 years before the first dose of study intervention and of low potential risk of recurrence. * Adequately resected non melanoma skin cancer or lentigo maligna without evidence of disease . * Adequately treated carcinoma in situ, including Ta tumors without evidence of disease. 2. Mixed small cell and non-small cell lung cancer histology. 3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC. 4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT. 5. Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia). 6. Participants with ≥ grade 2 pneumonitis from prior chemoradiation therapy. 7. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis 8. Active or prior documented autoimmune or inflammatory disorders (with exceptions) 9. Active EBV infection, or known or suspected chronic active EBV infection at screening 10. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
Study design
Enrollment target: 860 participants
Allocation: randomized
Masking: quadruple
Age groups: adult, older_adult
Timeline
Starts: 2022-02-18
Estimated completion: 2030-10-01
Last updated: 2026-06-10
Interventions
Drug: DurvalumabDrug: DomvanalimabOther: Placebo
Primary outcomes
  • Progression Free Survival (PFS) (Up to 8 years after randomization)
Sponsor
AstraZeneca · industry
With: Arcus Biosciences, Inc.
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
ContactAstraZeneca Lung Cancer Study Locator Service · contact · az-lcsl@careboxhealth.com · 1-884-432-3892
InvestigatorHidehito Horinouchi, MD, PhD · principal_investigator, National Cancer Center Hospital
InvestigatorAlexander Spira, MD, PhD · principal_investigator, Virginia Cancer Specialists Research Institute
InvestigatorJinming Yu, MD, PhD · principal_investigator, Shandong Cancer Hospital and Institute
All locations (264)
Research SiteRecruiting
Chandler, Arizona, United States
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Phoenix, Arizona, United States
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Fountain Valley, California, United States
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Santa Rosa, California, United States
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Washington D.C., District of Columbia, United States
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Jacksonville, Florida, United States
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Orlando, Florida, United States
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Saint Augustine, Florida, United States
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Macon, Georgia, United States
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Elmhurst, Illinois, United States
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Maywood, Illinois, United States
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Naperville, Illinois, United States
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Louisville, Kentucky, United States
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Baltimore, Maryland, United States
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Silver Spring, Maryland, United States
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Ann Arbor, Michigan, United States
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Detroit, Michigan, United States
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Minneapolis, Minnesota, United States
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Rochester, Minnesota, United States
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Reno, Nevada, United States
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East Brunswick, New Jersey, United States
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Florham Park, New Jersey, United States
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Buffalo, New York, United States
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Johnson City, New York, United States
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Asheville, North Carolina, United States
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Asheville, North Carolina, United States
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Charlotte, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Columbus, Ohio, United States
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Columbus, Ohio, United States
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Maumee, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Pittsburgh, Pennsylvania, United States
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Charleston, South Carolina, United States
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Chattanooga, Tennessee, United States
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Nashville, Tennessee, United States
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Nashville, Tennessee, United States
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Fort Sam Houston, Texas, United States
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Kingwood, Texas, United States
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Arlington, Virginia, United States
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Fort Belvoir, Virginia, United States
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Spokane Valley, Washington, United States
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Appleton, Wisconsin, United States
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Brussels, Belgium
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Edegem, Belgium
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Haine-Saint-Paul, Belgium
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Leuven, Belgium
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Liège, Belgium
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Sint-Niklaas, Belgium
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Barretos, Brazil
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Londrina, Brazil
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Porto Alegre, Brazil
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Porto Velho, Brazil
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Rio de Janeiro, Brazil
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Santo André, Brazil
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São Paulo, Brazil
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São Paulo, Brazil
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São Paulo, Brazil
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São Paulo, Brazil
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Taubaté, Brazil
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Calgary, Alberta, Canada
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Kelowna, British Columbia, Canada
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Laval, Quebec, Canada
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Montreal, Quebec, Canada
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Las Condes, Chile
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Port Montt, Chile
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Santiago, Chile
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Santiago, Chile
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Santiago, Chile
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Santiago, Chile
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Temuco, Chile
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Aix-en-Provence, France
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Angers, France
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Bobigny, France
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Clermont-Ferrand, France
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Lille, France
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Paris, France
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Pau, France
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Quimper, France
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Saint-Grégoire, France
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Saint-Quentin, France
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Vantoux, France
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Villeurbanne, France
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Berlin, Germany
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Berlin-Zehlendorf, Germany
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Braunschweig, Germany
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Chemnitz, Germany
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Cologne, Germany
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Erlangen, Germany
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Essen, Germany
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Georgsmarienhütte, Germany
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Giessen, Germany
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Halle, Germany
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Hamburg, Germany
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Homburg, Germany
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Koblenz, Germany
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Krefeld, Germany
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Löwenstein, Germany
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Moers, Germany
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München, Germany
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Regensburg, Germany
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Regensburg, Germany
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Tübingen, Germany
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Athens, Greece
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Athens, Greece
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Athens, Greece
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Athens, Greece
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Holargos, Athens, Greece
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Thessaloniki, Greece
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Thessaloniki, Greece
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Thessaloniki, Greece
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Hong Kong, Hong Kong
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Budapest, Hungary
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Budapest, Hungary
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Deszk, Hungary
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Győr, Hungary
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Salgótarján, Hungary
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Székesfehérvár, Hungary
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Törökbálint, Hungary
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Ahmedabad, India
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Bangalore, India
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Bangalore, India
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Delhi, India
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Gurgaon, India
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Howrah, India
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Hyderabad, India
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Jaipur, India
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Jaipur, India
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Kolkata, India
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Marg Jaipur, India
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Mohali, India
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Namakkal, India
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New Delhi, India
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New Delhi, India
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Varanasi, India
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Bergamo, Italy
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Roma, Italy
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Rozzano, Italy
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Udine, Italy
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Bunkyō City, Japan
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Bunkyō City, Japan
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Chiba, Japan
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Fukuoka, Japan
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Hidaka-shi, Japan
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Hirosaki-shi, Japan
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Itabashi-ku, Japan
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Kashihara-shi, Japan
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Kōtoku, Japan
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Kumamoto, Japan
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Matsuyama, Japan
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Nagoya, Japan
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Osaka, Japan
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Osakasayama-shi, Japan
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Sapporo, Japan
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Tokyo, Japan
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Yokohama, Japan
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Yokohama, Japan
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Johor Bahru, Malaysia
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Kuala Lumpur, Malaysia
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Kuala Selangor, Malaysia
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Kuching, Malaysia
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Aguascalientes, Mexico
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Chihuahua City, Mexico
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Guadalajara, Mexico
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Guadalajara, Mexico
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Mexico City, Mexico
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Monterrey, Mexico
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Oaxaca City, Mexico
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San Pedro Garza García, Mexico
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Sonora, Mexico
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Veracruz, Mexico
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Bodø, Norway
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Gjøvik, Norway
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Oslo, Norway
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Trondheim, Norway
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Bacolod, Philippines
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City of Muntinlupa, Philippines
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Iloilo City, Philippines
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Manila, Philippines
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Pasig, Philippines
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Quezon City, Philippines
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Quezon City, Philippines
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Bialystok, Poland
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Gliwice, Poland
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Gliwice, Poland
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Katowice, Poland
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Lodz, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Zielona Góra, Poland
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Bucharest, Romania
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Bucharest, Romania
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Craiova, Romania
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Floreşti, Romania
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Iași, Romania
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Oradea, Romania
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Sibiu, Romania
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Suceava, Romania
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Timișoara, Romania
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Cape Town, South Africa
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eManzimtoti, South Africa
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eManzimtoti, South Africa
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Johannesburg, South Africa
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Parktown, South Africa
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Pretoria, South Africa
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Daegu, South Korea
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Goyang-si, South Korea
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Incheon, South Korea
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Incheon, South Korea
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Jinju, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Suwon, South Korea
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Bilbao (Vizcaya), Spain
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Castellon, Spain
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Córdoba, Spain
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El Palmar, Spain
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Palma de Mallorca, Spain
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Sabadell (Barcelona), Spain
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Basel, Switzerland
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Bern, Switzerland
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Lausanne, Switzerland
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Hsinchu, Taiwan
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New Taipei City, Taiwan
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Taichung, Taiwan
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Taichung, Taiwan
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Tainan, Taiwan
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Taipei, Taiwan
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Taipei, Taiwan
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Taipei, Taiwan
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Taoyuan, Taiwan
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Bangkok, Thailand
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Bangkok, Thailand
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Bangkok, Thailand
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Hat Yai, Thailand
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Adapazarı, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Antalya, Turkey (Türkiye)
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Çankaya, Turkey (Türkiye)
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Edirne, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Konya, Turkey (Türkiye)
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Birmingham, United Kingdom
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Brighton, United Kingdom
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Cambridge, United Kingdom
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Cardiff, United Kingdom
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Cheltenham, United Kingdom
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Edinburgh, United Kingdom
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High Heaton/Newcastle Upon Tyn, United Kingdom
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Leeds, United Kingdom
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London, United Kingdom
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Nottingham, United Kingdom
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Truro, United Kingdom
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Hanoi, Vietnam
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Hanoi, Vietnam
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Ho Chi Minh City, Vietnam
A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC · TrialPath