Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer

A Randomized, Double-blind, Placebo-controlled, Phase III Study of Neoadjuvant-Adjuvant Durvalumab and FLOT Chemotherapy Followed by Adjuvant Durvalumab in Patients With Resectable Gastric and Gastroesophageal Junction Cancer (GC/GEJC)

This is a Global Study of Neoadjuvant-Adjuvant Durvalumab or Placebo and FLOT Chemotherapy Followed by Adjuvant Durvalumab or Placebo in Patients with Resectable Gastric and Gastroesophageal Cancer (GC/GEJC) (MATTERHORN).

Study Overview

• Status: Active, not recruiting
• Conditions: Gastrointestinal Neoplasms; Esophagogastric Junction
• Intervention / Treatment: Drug: FLOT chemotherapy; Drug: Durvalumab

Detailed Description

This study investigates treatment of durvalumab or placebo therapy combined with FLOT chemotherapy (flurouroacil + leucovorin + oxaliplatin + docetaxel) given before surgery (neoadjuvant) and durvalumab or placebo therapy combined with FLOT chemotherapy after surgery (adjuvant), will work and be safe for the treatment of resectable (removable by surgery) gastric or gastroesophageal cancer, and also to better understand the studied disease and associated health problems.

• Study Type: Interventional
• Enrollment (Actual): 957
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1431FWO
    • Research Site
  • Ciudad Autonoma Buenos Aires, Argentina, 1093
    • Research Site
  • Ciudad de Buenos Aires, Argentina, 1280
    • Research Site
  • Ciudad de Buenos Aires, Argentina, C1426ANZ
    • Research Site
  • Rosario, Argentina, 3101
    • Research Site
  • Rosario, Argentina, S2000DEJ
    • Research Site
• Belgium
  • Charleroi, Belgium, 6060
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Natal, Brazil, 59075-740
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90035-903
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
• Canada
  • Montreal, Canada, H3T 1E2
    • Research Site
  • Alberta
    • Edmonton, Alberta, Canada, t6G1Z2
      • Research Site
  • Ontario
    • North York, Ontario, Canada, M2K 1E1
      • Research Site
    • Oshawa, Ontario, Canada, L1G 2B9,
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Research Site
• Chile
  • La Serena, Chile, 1720430
    • Research Site
  • Santiago, Chile, 7500921
    • Research Site
  • Santiago, Chile, 7500653
    • Research Site
  • Talca, Chile, 3461341
    • Research Site
  • Temuco, Chile, 4810218
    • Research Site
  • Temuco, Chile, 4800827
    • Research Site
• Denmark
  • Aalborg, Denmark, 9000
    • Research Site
  • København Ø, Denmark, 2100
    • Research Site
  • Odense, Denmark, 5000
    • Research Site
• France
  • Avignon, France, 84918
    • Research Site
  • Besançon, France, 25030
    • Research Site
  • Brest, France, 29609
    • Research Site
  • Dijon, France, 21000
    • Research Site
  • Lyon, France, 69373
    • Research Site
  • Montpellier, France, 34298
    • Research Site
  • Nantes, France, 44093
    • Research Site
  • Nice, France, 06100
    • Research Site
  • Paris, France, 75012
    • Research Site
  • Paris, France, 75475
    • Research Site
  • Paris, France, 75900
    • Research Site
  • Rennes, France, 35033
    • Research Site
• Germany
  • Berlin, Germany, 13353
    • Research Site
  • Dresden, Germany, 01307
    • Research Site
  • Frankfurt, Germany, 60488
    • Research Site
  • Hamburg, Germany, 20246
    • Research Site
  • Hamburg, Germany, 20249
    • Research Site
  • Heidelberg, Germany, 69120
    • Research Site
  • Heilbronn, Germany, 74078
    • Research Site
  • Jena, Germany, 7743
    • Research Site
  • Mainz Am Rhein, Germany, 55131
    • Research Site
  • München, Germany, 81675
    • Research Site
  • Schweinfurt, Germany, 97421
    • Research Site
  • Tübingen, Germany, 72016
    • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Győr, Hungary, 9024
    • Research Site
  • Kecskemét, Hungary, 6000
    • Research Site
  • Szekszárd, Hungary, 7100
    • Research Site
  • Szolnok, Hungary, 5004
    • Research Site
• Japan
  • 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
  • Kochi, Japan, 781-8555
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Nagoya, Japan, 464-8681
    • Research Site
  • Niigata, Japan, 951-8566
    • Research Site
  • Ogaki-shi, Japan, 503-8502
    • Research Site
  • Osaka, Japan, 541-8567
    • Research Site
  • Osaka, Japan, 534-0021
    • Research Site
  • Suita-shi, Japan, 565-0871
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Tokyo, Japan, 135-8550
    • Research Site
  • Toyoake-shi, Japan, 470-1192
    • Research Site
  • Wakayama, Japan, 641-8510
    • Research Site
  • Yokohama, Japan, 241-8515
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Eindhoven, Netherlands, 5623EJ
    • Research Site
  • Rotterdam, Netherlands, 3015GD
    • Research Site
• Peru
  • Bellavista, Peru, CALLAO 2
    • Research Site
  • Lima, Peru, LIMA 34
    • Research Site
  • Lima, Peru, LIMA 29
    • Research Site
  • Lima, Peru, Lima 32
    • Research Site
  • San Isidro, Peru, 27
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Gdansk, Poland, 80-952
    • Research Site
  • Krakow, Poland, 30-688
    • Research Site
  • Lodz, Poland, 93-513
    • Research Site
  • Poznan, Poland, 60-569
    • Research Site
  • Poznan, Poland, 61-866
    • Research Site
  • Warsaw, Poland, 02-034
    • Research Site
  • Warsaw, Poland, 04-141
    • Research Site
• Russia
  • Kaluga, Russia, 248007
    • Research Site
  • Moscow, Russia, 115478
    • Research Site
  • Moscow, Russia, 111123
    • Research Site
  • Moscow, Russia, 125284
    • Research Site
  • Novosibirsk, Russia, 630108
    • Research Site
  • Obninsk, Russia, 249036
    • Research Site
  • Saint Petersburg, Russia, 197089
    • Research Site
• South Korea
  • Hwasun-gun, South Korea, 58128
    • Research Site
  • Seongnam-si, South Korea, 13620
    • Research Site
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
  • Seoul, South Korea, 06591
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08025
    • Research Site
  • Barcelona, Spain, 08908
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Málaga, Spain, 29009
    • Research Site
  • Ourense, Spain, 32005
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Seville, Spain, 41013
    • Research Site
  • Valencia, Spain, 46010
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Research Site
  • Taichung, Taiwan, 40443
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taipei, Taiwan, 10048
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Research Site
  • Ankara, Turkey (Türkiye), 06340
    • Research Site
  • Erzurum, Turkey (Türkiye), 25240
    • Research Site
  • Istanbul, Turkey (Türkiye), 34098
    • Research Site
  • Istanbul, Turkey (Türkiye), 34457
    • Research Site
  • Samsun, Turkey (Türkiye), 55139
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
  • Glasgow, United Kingdom, G12 0YN
    • Research Site
  • Leicester, United Kingdom, LE2 7LZ
    • Research Site
  • London, United Kingdom, EC1A 7BE
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Research Site
  • Surrey, United Kingdom, SM2 5PT
    • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • Los Angeles, California, United States, 90027
      • Research Site
    • Los Angeles, California, United States, 90095
      • Research Site
    • Sylmar, California, United States, 91342
      • Research Site
  • Florida
    • St. Petersburg, Florida, United States, 33705
      • Research Site
    • Tallahassee, Florida, United States, 32308
      • Research Site
    • West Palm Beach, Florida, United States, 33401
      • Research Site
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site
    • Lancaster, Texas, United States, 75216
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 200 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Patients with histologically documented gastric or gastroesophageal junction adenocarcinoma with resectable disease (Stage II or higher per AJCC 8th edition).
• Patients must undergo radical surgery.
• No prior anti-cancer therapy for the current malignancy.
• World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment.
• Adequate organ and marrow function.
• Availability of tumor sample prior to study entry.
• Must have a life expectancy of at least 24 weeks.

Key Exclusion Criteria:

• Patients with peritoneal dissemination or distant metastasis.
• Patients with adenosquamous cell carcinoma, squamous cell carcinoma, or GI stromal tumor.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
• Contra-indication to any of the study drugs.
• History of allogeneic organ transplantation.

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
Placebo Comparator: Arm B; placebo product and FLOT chemotherapy	Drug: FLOT chemotherapy; A combination treatment made up of flurouroacil + leucovorin + oxaliplatin + docetaxel
Experimental: Arm A; Durvalumab and FLOT chemotherapy	Drug: FLOT chemotherapy; A combination treatment made up of flurouroacil + leucovorin + oxaliplatin + docetaxel; Drug: Durvalumab; Human monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	EFS is the time from date of randomization until the date of disease progression or death.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare Arm A relative to Arm B on overall survival (OS)	Overall survival is length of time from randomization until the date of death due to any cause.	Up to 5 years
To compare Arm A relative to Arm B on pathological complete response (pCR) rate	pCR rate is the proportion of patients who have no residual viable tumor in the resected specimens.	Up to 5 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Janjigian YY, Van Cutsem E, Muro K, Wainberg Z, Al-Batran SE, Hyung WJ, Molena D, Marcovitz M, Ruscica D, Robbins SH, Negro A, Tabernero J. MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. Future Oncol. 2022 Jun;18(20):2465-2473. doi: 10.2217/fon-2022-0093. Epub 2022 May 10.
• Cowzer D, Janjigian YY. Top advances in esophageal/gastroesophageal junction cancers in 2021. Cancer. 2022 May 15;128(10):1894-1899. doi: 10.1002/cncr.34140. Epub 2022 Feb 18. No abstract available.
• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.
• Janjigian YY, Al-Batran SE, Wainberg ZA, Muro K, Molena D, Van Cutsem E, Hyung WJ, Wyrwicz L, Oh DY, Omori T, Moehler M, Garrido M, Oliveira SCS, Liberman M, Oliden VC, Smyth EC, Stein A, Bilici M, Alvarenga ML, Kozlov V, Rivera F, Kawazoe A, Serrano O, Heilbron E, Negro A, Kurland JF, Tabernero J; MATTERHORN Investigators. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. N Engl J Med. 2025 Jul 17;393(3):217-230. doi: 10.1056/NEJMoa2503701. Epub 2025 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): December 20, 2024
• Study Completion (Estimated): September 27, 2027

Study Registration Dates

• First Submitted: August 26, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; durvalumab
• Other Study ID Numbers: D910GC00001; 2019-001555-40 (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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• 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 deidentified 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
• product manufactured in and exported from the U.S.: Yes