A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

NCT ID: NCT05221840

Last Updated: 2025-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1027 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-07

Study Completion Date

2030-07-02

Brief Summary

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This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Detailed Description

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Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-Blind

Study Groups

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Arm A: Durvalumab and Oleclumab

Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab IV (intravenous infusion)

Oleclumab

Intervention Type DRUG

Oleclumab IV (intravenous infusion)

Arm B: Durvalumab and Monalizumab

Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab IV (intravenous infusion)

Monalizumab

Intervention Type DRUG

Monalizumab IV (intravenous infusion)

Placebo

Intervention Type OTHER

Placebo IV (intravenous infusion)

Arm C: Durvalumab and Placebo

Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months

Group Type ACTIVE_COMPARATOR

Durvalumab

Intervention Type DRUG

Durvalumab IV (intravenous infusion)

Placebo

Intervention Type OTHER

Placebo IV (intravenous infusion)

Interventions

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Durvalumab

Durvalumab IV (intravenous infusion)

Intervention Type DRUG

Oleclumab

Oleclumab IV (intravenous infusion)

Intervention Type DRUG

Monalizumab

Monalizumab IV (intravenous infusion)

Intervention Type DRUG

Placebo

Placebo IV (intravenous infusion)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Participant must be ≥ 18 years at the time of screening.
* Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
* Provision of a tumour tissue sample obtained prior to CRT
* Documented tumour PD-L1 status by central lab
* Documented EGFR and ALK wild-type status (local or central).
* Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
* Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
* 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.
* WHO performance status of 0 or 1 at randomization
* Adequate organ and marrow function

Exclusion Criteria

* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
* Mixed small cell and non-small cell lung cancer histology.
* Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
* Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
* Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia).
* Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
* 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 - diagnosed in the past 6 months prior to randomization.
* Active or prior documented autoimmune or inflammatory disorders (with exceptions)
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fabrice Barlesi, MD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

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San Diego, California, United States

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New Haven, Connecticut, United States

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Stuart, Florida, United States

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Urbana, Illinois, United States

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New Albany, Indiana, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Annapolis, Maryland, United States

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Baltimore, Maryland, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Grand Rapids, Michigan, United States

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Duluth, Minnesota, United States

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Billings, Montana, United States

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Ridgewood, New Jersey, United States

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Ithaca, New York, United States

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Greensboro, North Carolina, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Maumee, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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York, Pennsylvania, United States

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Sioux Falls, South Dakota, United States

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Houston, Texas, United States

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Charlottesville, Virginia, United States

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Fairfax, Virginia, United States

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Fredericksburg, Virginia, United States

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Richmond, Virginia, United States

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Richland, Washington, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Milwaukee, Wisconsin, United States

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Box Hill, , Australia

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East Melbourne, , Australia

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Elizabeth Vale, , Australia

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Gosford, , Australia

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Heidelberg, , Australia

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Kogarah, , Australia

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South Brisbane, , Australia

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St Albans, , Australia

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Westmead, , Australia

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Barretos, , Brazil

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Belo Horizonte, , Brazil

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Florianópolis, , Brazil

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Fortaleza, , Brazil

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Jaú, , Brazil

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Natal, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Recife, , Brazil

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São Paulo, , Brazil

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Uberlândia, , Brazil

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Vitória, , Brazil

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Edmonton, Alberta, Canada

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Barrie, Ontario, Canada

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Hamilton, Ontario, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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Mississauga, Ontario, Canada

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Toronto, Ontario, Canada

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Rimouski, Quebec, Canada

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Anyang, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hefei, , China

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Hefei, , China

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Kunming, , China

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Linhai, , China

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Nanchang, , China

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Nanning, , China

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Nantong, , China

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Neijiang, , China

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Ningbo, , China

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Shaoguan, , China

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Tianjin, , China

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Wuhan, , China

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Wuhan, , China

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Wuhan, , China

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Zhanjiang, , China

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Zhengzhou, , China

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Zhongshan, , China

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Barranquilla, , Colombia

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Bogota D.C., , Colombia

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Medellín, , Colombia

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Valledupar, , Colombia

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Avignon, , France

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Besançon, , France

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Bordeaux, , France

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Clermont-Ferrand, , France

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Créteil, , France

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Lorient, , France

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Marseille, , France

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Montpellier, , France

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Rennes, , France

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Rouen, , France

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Toulouse, , France

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Villejuif, , France

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Erfurt, , Germany

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Erlangen, , Germany

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Essen, , Germany

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Esslingen am Neckar, , Germany

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Georgsmarienhütte, , Germany

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Gütersloh, , Germany

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Hanover, , Germany

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Oldenburg, , Germany

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Würzburg, , Germany

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Brescia, , Italy

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Florence, , Italy

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Lucca, , Italy

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Meldola, , Italy

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Orbassano, , Italy

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Parma, , Italy

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Pavia, , Italy

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Roma, , Italy

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Himeji-shi, , Japan

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Hiroshima, , Japan

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Kashiwa, , Japan

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Kurume-shi, , Japan

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Natori-shi, , Japan

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Niigata, , Japan

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Osaka, , Japan

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Sendai, , Japan

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Tokushima, , Japan

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Toon-shi, , Japan

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Wakayama, , Japan

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Koszalin, , Poland

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Poznan, , Poland

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Siedlce, , Poland

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Tomaszów Mazowiecki, , Poland

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Warsaw, , Poland

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Lisbon, , Portugal

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Lisbon, , Portugal

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Loures, , Portugal

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Porto, , Portugal

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Changwon-si, , South Korea

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Cheongju-si, , South Korea

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Seongnam-si, , 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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Suwon, , South Korea

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Barcelona, , Spain

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Granada, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Santiago de Compostela, , Spain

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Valencia, , Spain

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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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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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Hat Yai, , Thailand

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Khon Kaen, , Thailand

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Khon Kaen, , Thailand

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Lampang, , Thailand

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Muang, , Thailand

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Muang, , Thailand

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Mueang, , Thailand

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Naimuang, , Thailand

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Diyarbakır, , Turkey (Türkiye)

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Goztepe Istanbul, , Turkey (Türkiye)

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Karşıyaka, , Turkey (Türkiye)

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Belfast, , United Kingdom

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Bristol, , United Kingdom

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Dundee, , United Kingdom

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Edinburgh, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Middlesbrough, , United Kingdom

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Poole, , United Kingdom

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Torquay, , United Kingdom

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Truro, , United Kingdom

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Wolverhampton, , United Kingdom

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Haiphong, , Vietnam

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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United States Australia Brazil Canada China Colombia France Germany Italy Japan Peru Poland Portugal South Korea Spain Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

References

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Barlesi F, Cho BC, Goldberg SB, Yoh K, Zimmer Gelatti AC, Mann H, Gopinathan A, Bielecka ZF, Newton M, Aggarwal C. PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer. Future Oncol. 2024;20(29):2137-2147. doi: 10.1080/14796694.2024.2354160. Epub 2024 Jul 18.

Reference Type DERIVED
PMID: 39023287 (View on PubMed)

Related Links

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Other Identifiers

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2023-503999-24-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-004346-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D9078C00001

Identifier Type: -

Identifier Source: org_study_id

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