A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer

NCT ID: NCT03800134

Last Updated: 2025-06-11

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

825 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-06

Study Completion Date

2028-09-11

Brief Summary

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This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study assessing the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of pathological complete response.

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

DOUBLE

Participants Caregivers

Study Groups

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Arm 1: Durvalumab with platinum-based chemotherapy

Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity

The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:

* cisplatin with pemetrexed
* carboplatin with pemetrexed
* carboplatin with paclitaxel
* cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

1500mg on Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and 1500mg on Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Carboplatin

Intervention Type DRUG

Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles

Cisplatin

Intervention Type DRUG

75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles

Pemetrexed

Intervention Type DRUG

500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Paclitaxel

Intervention Type DRUG

200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Gemcitabine

Intervention Type DRUG

1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.

Surgery

Intervention Type PROCEDURE

Expected within 40 days from the last dose of Investigational Product following the completion of neoadjuvant treatment.

Arm 2: Placebo with platinum-based chemotherapy

Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity

The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:

* cisplatin with pemetrexed
* carboplatin with pemetrexed
* carboplatin with paclitaxel
* cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Carboplatin

Intervention Type DRUG

Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles

Cisplatin

Intervention Type DRUG

75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles

Pemetrexed

Intervention Type DRUG

500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Paclitaxel

Intervention Type DRUG

200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Gemcitabine

Intervention Type DRUG

1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.

Surgery

Intervention Type PROCEDURE

Expected within 40 days from the last dose of Investigational Product following the completion of neoadjuvant treatment.

Interventions

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Durvalumab

1500mg on Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and 1500mg on Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Intervention Type DRUG

Placebo

Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Intervention Type OTHER

Carboplatin

Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles

Intervention Type DRUG

Cisplatin

75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles

Intervention Type DRUG

Pemetrexed

500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Intervention Type DRUG

Paclitaxel

200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Intervention Type DRUG

Gemcitabine

1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.

Intervention Type DRUG

Surgery

Expected within 40 days from the last dose of Investigational Product following the completion of neoadjuvant treatment.

Intervention Type PROCEDURE

Other Intervention Names

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MEDI4736

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years
* Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select \[ie, N2\] Stage IIIB) disease
* World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline
* No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines
* Adequate organ and marrow function
* Confirmation of a patient's tumour PD-L1 status
* Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status
* Planned surgery must comprise lobectomy, sleeve resection, or bilobectomy

Exclusion Criteria

* History of allogeneic organ transplantation
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome)
* History of another primary malignancy
* History of active primary immunodeficiency
* Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus
* Deemed unresectable NSCLC by multidisciplinary evaluation
* Patients who have pre-operative radiotherapy treatment as part of their care plan
* Patients who have brain metastases or spinal cord compression
* Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
* Known allergy or hypersensitivity to any of the study drugs or excipients
* Existence of more than one primary tumour such as mixed small cell and NSCLC histology
* Patients whose planned surgery at enrollment includes any of the following procedures: pneumonectomy, segmentectomies, or wedge resections
* Patients with a documented test result confirming the presence of EGFRm or ALK translocation
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 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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John Heymach, MD

Role: PRINCIPAL_INVESTIGATOR

UT MD Anderson Cancer Center

Locations

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Aurora, Colorado, United States

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Boca Raton, Florida, United States

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Phoenix, Arizona, United States

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Duarte, California, United States

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Orange, California, United States

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Jacksonville, Florida, United States

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Chicago, Illinois, United States

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Wichita, Kansas, United States

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Ashland, Kentucky, United States

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Lexington, Kentucky, United States

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Silver Spring, Maryland, United States

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Towson, Maryland, United States

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Duluth, Minnesota, United States

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Minneapolis, Minnesota, United States

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Morristown, New Jersey, United States

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New York, New York, United States

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New York, New York, United States

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Shirley, New York, United States

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Durham, North Carolina, United States

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Bend, Oregon, United States

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Medford, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Charleston, South Carolina, United States

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Austin, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Fairfax, Virginia, United States

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Kirkland, Washington, United States

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Seattle, Washington, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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La Plata, , Argentina

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Pergamino, , Argentina

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Rosario, , Argentina

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San Salvador de Jujuy, , Argentina

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Viedma, , Argentina

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Graz, , Austria

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Innsbruck, , Austria

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Rankweil, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Ghent, , Belgium

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Liège, , Belgium

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Mons, , Belgium

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Barretos, , Brazil

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Belo Horizonte, , Brazil

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Campinas, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Natal, , Brazil

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Porto Alegre, , Brazil

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Santa Maria, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Teresina, , Brazil

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Vitória, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Edmonton, Alberta, Canada

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Kitchener, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Santiago, , Chile

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Santiago, , Chile

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Temuco, , Chile

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Viña del Mar, , Chile

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Changsha, , China

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Changsha, , China

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Changzhou, , China

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Chengdu, , China

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Guangzhou, , China

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Guangzhou, , China

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Guiyang, , China

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Hangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hangzhou, , 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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Ningbo, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Shenyang, , China

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Shenzhen, , China

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Shenzhen, , China

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Tianjin, , China

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Ürümqi, , China

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Wuhan, , China

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Wuhan, , China

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Xiamen, , China

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Xintai, , China

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Yangzhou, , China

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Zhengzhou, , China

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San José, , Costa Rica

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San José, , Costa Rica

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Avignon, , France

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Lyon, , France

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Nice, , France

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Toulon, , France

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Vantoux, , France

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Bielefeld, , Germany

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Cologne, , Germany

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Frankfurt am Main, , Germany

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Immenstadt im Allgäu, , Germany

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Budapest, , Hungary

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Gyöngyös - Mátraháza, , Hungary

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Győr, , Hungary

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Székesfehérvár, , Hungary

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Törökbálint, , Hungary

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Ahmedabad, , India

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Gurgaon, , India

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Gurgaon, , India

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Kolkata, , India

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Manipal, , India

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Mumbai, , India

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Mumbai, , India

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Mysuru, , India

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Namakkal, , India

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Nashik, , India

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New Delhi, , India

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New Delhi, , India

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Thāne, , India

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Visakhapatnam, , India

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Ancona, , Italy

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Bari, , Italy

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Bergamo, , Italy

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Florence, , Italy

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Milan, , Italy

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Monza, , Italy

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Padua, , Italy

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Roma, , Italy

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Verona, , Italy

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Habikino-shi, , Japan

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Himeji-shi, , Japan

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Hiroshima, , Japan

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Hiroshima, , Japan

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Iwakuni-shi, , Japan

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Kitaadachi-gun, , Japan

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Kitakyushu-shi, , Japan

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Kurashiki Shi, , Japan

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Nagoya, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Osakasayama-shi, , Japan

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Toyoake-shi, , Japan

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Wakayama, , Japan

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Aguascalientes, , Mexico

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Chihuahua City, , Mexico

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Guadalajara, , Mexico

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México, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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Pachuca, , Mexico

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Arnhem, , Netherlands

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Nijmegen, , Netherlands

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Bellavista, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Davao City, , Philippines

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Iloilo City, , Philippines

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Makati, , Philippines

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Quezon City, , Philippines

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Bialystok, , Poland

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Olsztyn, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Suceava, , Romania

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Kazan', , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Obninsk, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Tomsk, , Russia

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Yaroslavl, , Russia

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Busan, , 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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Alicante, , Spain

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Barcelona, , Spain

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Donostia / San Sebastian, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Oviedo, , Spain

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Pamplona, , Spain

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Santiago de Compostela (A Coruña), , Spain

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Changhua, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Chiang Rai, , Thailand

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Khon Kaen, , Thailand

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Lampang, , Thailand

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Ho Chi Minh City, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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United States Argentina Austria Belgium Brazil Bulgaria Canada Chile China Costa Rica France Germany Hungary India Italy Japan Mexico Netherlands Peru Philippines Poland Romania Russia South Korea Spain Taiwan Thailand Vietnam

References

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Mitsudomi T, Heymach JV, Reck M, Taube JM, Gao S, Horio Y, You J, Li G, Van Luong D, Saeteng S, Tanaka F, Watzka SB, Urban L, Szalai Z, Akamatsu H, Kang JH, Orlandi FJ, Mukhametshina GZ, Pircher A, Teixeira CHA, Aperghis M, Doherty GJ, Doake R, Fouad TM, Harpole D. Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed by Adjuvant Durvalumab in Resectable NSCLC. J Thorac Oncol. 2025 Jun 20:S1556-0864(25)00780-4. doi: 10.1016/j.jtho.2025.06.015. Online ahead of print.

Reference Type DERIVED
PMID: 40545237 (View on PubMed)

Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. doi: 10.1056/NEJMoa2304875. Epub 2023 Oct 23.

Reference Type DERIVED
PMID: 37870974 (View on PubMed)

Other Identifiers

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2018-002997-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D9106C00001

Identifier Type: -

Identifier Source: org_study_id

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