Study of Durvalumab Versus Placebo in Combination With Definitive Chemoradiation Therapy in Patient With ESCC (KUNLUN)

A Phase III, Randomized, Double-Blind, Placebo Controlled, Multi-Center, International Study of Durvalumab Given Concurrently With Definitive Chemoradiation Therapy in Patients With Locally Advanced, Unresectable Esophageal Squamous Cell Carcinoma (KUNLUN)

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study to assess the efficacy and safety of durvalumab administered concurrently with dCRT in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC).

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Durvalumab; Drug: cisplatin + fluorouracil; Drug: cisplatin + capecitabine; Radiation: Radiation; Drug: Placebo

Detailed Description

Approximately 600 patients with locally advanced, unresectable ESCC (AJCC 8th cStage II-IVA) will be randomized in a 2:1 ratio to receive either durvalumab + dCRT or placebo + dCRT. The primary objectives of this study are to assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of progression free survival (PFS, per RECIST 1.1 as assessed by BICR) in PD-L1 High population.

• Study Type: Interventional
• Enrollment (Actual): 640
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Research Site
  • Charleroi, Belgium, 6060
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Namur, Belgium, 5000
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Fortaleza, Brazil, 60430-230
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90050-170
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • Vitória, Brazil, 29043-260
    • Research Site
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Research Site
    • Greater Sudbury, Ontario, Canada, P3E 5J1
      • Research Site
• China
  • Anyang, China, 455000
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Beijing, China, 100036
    • Research Site
  • Bengbu, China, 233004
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changzhi, China, 46000
    • Research Site
  • Chengdu, China, 610042
    • Research Site
  • Chongqing, China, 400030
    • Research Site
  • Fuzhou, China, 350014
    • Research Site
  • Fuzhou, China, 350001
    • Research Site
  • Guangzhou, China, 510000
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Hangzhou, China
    • Research Site
  • Hefei, China, 230031
    • Research Site
  • Huai'an, China, 223300
    • Research Site
  • Jieyang, China, 522000
    • Research Site
  • Jinan, China, 250117
    • Research Site
  • Kunming, China, 650118
    • Research Site
  • Liangyugang, China, 222002
    • Research Site
  • Nantong, China, 226361
    • Research Site
  • Qingdao, China, 266042
    • Research Site
  • Quanzhou, China, 362000
    • Research Site
  • Shenzhen, China, 518116
    • Research Site
  • Tianjin, China, 300060
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Xuzhou, China, 221000
    • Research Site
  • Yangzhou, China, 225001
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
  • Zhenjiang, China, 212002
    • Research Site
• France
  • Besançon, France, 25030
    • Research Site
  • Lille, France, 59000
    • Research Site
  • Lyon, France, 69008
    • Research Site
  • Montpellier, France, 34070
    • Research Site
  • Reims, France, 51100
    • Research Site
  • Rouen, France, 76031
    • Research Site
  • Strasbourg, France, 67033
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8431
    • Research Site
  • Chūōku, Japan, 104-0045
    • Research Site
  • Hidaka-shi, Japan, 350-1298
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Research Site
  • Hiroshima, Japan, 730-8518
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Kitaadachi-gun, Japan, 362-0806
    • Research Site
  • Kumamoto, Japan, 860-8556
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Research Site
  • Maebashi, Japan, 371-8511
    • Research Site
  • Matsuyama, Japan, 791-0280
    • Research Site
  • Niigata, Japan, 951-8566
    • Research Site
  • Okayama, Japan, 700-8558
    • Research Site
  • Osaka, Japan, 545-8586
    • Research Site
  • Osaka, Japan, 541-8567
    • Research Site
  • Ota-shi, Japan, 373-8550
    • Research Site
  • Sendai, Japan, 980-8574
    • Research Site
  • Shinagawa-ku, Japan, 142-8666
    • Research Site
  • Yokohama, Japan, 241-8515
    • Research Site
  • Yokohama, Japan, 232-0024
    • Research Site
• Mexico
  • Chihuahua City, Mexico, 31210
    • Research Site
  • Cuernavaca, Mexico, 62290
    • Research Site
  • Monterrey, Mexico, 66220
    • Research Site
  • Mérida, Mexico, 97134
    • Research Site
  • Veracruz, Mexico, 91851
    • Research Site
• Poland
  • Katowice, Poland, 40-074
    • Research Site
  • Krakow, Poland, 31-115
    • Research Site
  • Lodz, Poland, 90-513
    • Research Site
  • Siedlce, Poland, 08-110
    • Research Site
  • Warsaw, Poland, 02-034
    • Research Site
• Russia
  • Chelyabinsk, Russia, 454087
    • Research Site
  • Krasnodar, Russia, 350040
    • Research Site
  • Moscow, Russia, 115478
    • Research Site
  • Obninsk, Russia, 249031
    • Research Site
  • Saint Petersburg, Russia, 197758
    • Research Site
  • Tyumen, Russia, 6250041
    • Research Site
  • Ufa, Russia, 450054
    • Research Site
  • Yekaterinburg, Russia, 620905
    • Research Site
• South Korea
  • Daegu, South Korea, 41404
    • Research Site
  • Seoul, South Korea, 06273
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
  • Seoul, South Korea, 138-736
    • Research Site
  • Suwon, South Korea, 16247
    • Research Site
• Spain
  • Barcelona, Spain, 8035
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Taiwan
  • Changhua, Taiwan, 50006
    • Research Site
  • Kaohsiung City, Taiwan, 82445
    • Research Site
  • Kaohsiung City, Taiwan, 83301
    • Research Site
  • Kaohsiung City, Taiwan, 80756
    • Research Site
  • Taichung, Taiwan, 40443
    • Research Site
  • Taichung, Taiwan, 407
    • Research Site
  • Tainan, Taiwan, 710
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10210
    • Research Site
  • Bangkok, Thailand, 10300
    • Research Site
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10400
    • Research Site
  • Chanthaburi, Thailand, 22000
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • Research Site
  • Diyarbakır, Turkey (Türkiye), 21280
    • Research Site
  • Erzurum, Turkey (Türkiye), 25240
    • Research Site
  • Goztepe Istanbul, Turkey (Türkiye)
    • Research Site
  • Izmir, Turkey (Türkiye), 35575
    • Research Site
  • Van, Turkey (Türkiye), 65080
    • Research Site
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Ho Chi Minh City, Vietnam
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older at the time of signing the ICF.
• Histologically or cytologically confirmed esophageal squamous cell carcinoma, and present with locally advanced disease (Stage II-IVA).
• Unresectable or refusing surgery, and has been deemed suitable for definitive chemoradiation therapy.
• Patients with at least an evaluable lesion per RECIST 1.1.
• Mandatory provision of available tumor tissue for PD-L1 expression analysis.
• ECOG PS 0 or 1.
• Adequate organ and marrow function.
• Life expectancy of more than 3 months.

Exclusion Criteria:

• Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma.
• Prior anti-cancer treatment for ESCC.
• Patient with a great risk of perforation and massive bleeding.
• History of allogeneic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders.
• Uncontrolled intercurrent illness.
• History of another primary malignancy.
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Durvalumab + definitive CRT; Durvalumab + concurrent chemoradiation	Drug: Durvalumab; Durvalumab intravenous infusion; Other Names: MEDI4736; Drug: cisplatin + fluorouracil; cisplatin + fluorouracil, as per Standard of Care; Drug: cisplatin + capecitabine; cisplatin + capecitabine, as per Standard of Care; Radiation: Radiation; 50-64Gy in total
Placebo Comparator: Arm 2: Placebo + definitive CRT; Placebo + concurrent chemoradiation	Drug: cisplatin + fluorouracil; cisplatin + fluorouracil, as per Standard of Care; Drug: cisplatin + capecitabine; cisplatin + capecitabine, as per Standard of Care; Radiation: Radiation; 50-64Gy in total; Drug: Placebo; Durvalumab matching placebo for intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) per RECIST 1.1 as assessed by BICR	To assess the efficacy in terms of PFS in PD-L1 High population	up to approximately 56 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To assess the efficacy in terms of OS in all randomized patients and in PD-L1 High population until the date of death	up to approximately 72 months
Progression free survival (PFS) per RECIST 1.1 as assessed by BICR	To assess the efficacy in terms of PFS in all randomized patients.	up to approximately 56 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	To assess the safety and tolerability profile of durvalumab + dCRT compared to placebo + dCRT in patients with ESCC	up to approximately 72 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Luhua Wang, MD, Cancer Hospital of Chinese Academy of Medical Science; Principal Investigator: Nabil Saba, MD, Department of Hematology and Medical Oncology, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2020
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PD-L1; Durvalumab; Locally Advanced unresectable ESCC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Physical Phenomena; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Platinum Compounds; Deoxyribonucleosides; Fluorouracil; Capecitabine; Cisplatin; Radiation; durvalumab; CF regimen
• Other Study ID Numbers: D910SC00001; 2020-001001-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No