A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer (LUCERNA)

A Phase 3, Double-blind, Randomized Study of Zolbetuximab in Combination With Pembrolizumab and Chemotherapy (CAPOX or mFOLFOX6) in First-line Treatment of Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma in Participants Whose Tumors Are HER2-negative, Claudin (CLDN) 18.2-positive and Programmed Death-ligand 1 (PD-L1)-Positive

Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Zolbetuximab with chemotherapy may be used to treat stomach and GEJ cancer when the cancer cells do not have a protein called HER2 (human epidermal growth factor receptor 2) on their surface (HER2-negative) but do have a protein called Claudin 18.2 (Claudin 18.2-positive). Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. Certain stomach and GEJ cancers may be treated with immunotherapy, which helps the body's immune system fight cancer. This study will give more information about how well zolbetuximab works when given with an immunotherapy medicine called pembrolizumab and chemotherapy. In this study, adults with stomach cancer or GEJ cancer will either be given zolbetuximab with pembrolizumab and chemotherapy or a placebo with pembrolizumab and chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it.

The main aim of the study is to check how long people with stomach cancer and GEJ cancer live after treatment with zolbetuximab with pembrolizumab and chemotherapy compared to placebo with pembrolizumab and chemotherapy.

Adults with locally advanced unresectable or metastatic stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample (biopsy) of their cancer will have the Claudin 18.2 protein, PD-L1 protein, and be HER2-negative. They may have been previously treated with certain standard therapies. People can also take part if they need to take medicines like steroids to suppress their immune system. They cannot take part if they have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.

The study treatments are either zolbetuximab with pembrolizumab and chemotherapy, or placebo with pembrolizumab and chemotherapy. People who take part will receive just 1 of the study treatments by chance. The people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in 6-week (42-day) cycles. The study treatment is mainly given to people slowly through a tube into a vein. This is called an infusion. People will receive study treatment as follows: Zolbetuximab or placebo: 1 infusion every 2 or 3 weeks (2 or 3 infusions in a cycle) together with: Chemotherapy (1 of the following types of chemotherapy): 1. CAPOX (capecitabine and oxaliplatin): 1 infusion of oxaliplatin every 3 weeks (2 infusions in a cycle). People will also take 1 tablet of capecitabine twice a day for 2 weeks (14 days) at the start of each cycle (Day 1) and again in the middle of each cycle (Day 22). After 8 study treatments people will receive capecitabine only. 2. Modified FOLFOX6 or mFOLFOX6 (5-fluorouracil, folinic acid and oxaliplatin): 1 infusion every 2 weeks (3 infusions in a cycle). After 12 study treatments people will receive folinic acid and fluorouracil only, instead of mFOLFOX6. Pembrolizumab: 1 infusion every 3 or 6 weeks (1 or 2 infusions in a cycle). People can be in the study and will receive study treatment until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People may receive pembrolizumab for up to 2 years. People will visit the clinic on certain days to receive their study treatment and have health checks. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample if they stop treatment because their cancer has worsened. People will visit the clinic after they stop their study treatment. People will be asked about any medical problems and will have a health check. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their study treatment or not.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer; Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer; Metastatic Gastric Adenocarcinoma or Cancer; Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
• Intervention / Treatment: Drug: zolbetuximab; Drug: Pembrolizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Folinic acid (leucovorin or local equivalent); Drug: 5-fluorouracil (5-FU); Drug: Placebo

Detailed Description

Zolbetuximab (Vyloy), has received marketing approval in Japan. The study is considered a post marketing study in Japan.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development Inc.; Phone Number: 800-888-7704; Email: astellas.registration@astellas.com

Study Locations

• Australia
  • Fitzroy, Australia
    • Recruiting
    • Site AU61001
  • New South Wales
    • Kogarah, New South Wales, Australia
      • Recruiting
      • Site AU61002
  • Queensland
    • Brisbane, Queensland, Australia
      • Recruiting
      • Site AU61004
  • Victoria
    • Clayton, Victoria, Australia
      • Recruiting
      • Site AU61003
• Belgium
  • Bonheiden, Belgium
    • Recruiting
    • Site BE32002
  • Brussels, Belgium
    • Recruiting
    • Site BE32001
  • Edegem, Belgium
    • Recruiting
    • Site BE32006
  • Ghent, Belgium
    • Recruiting
    • Site BE32003
  • Leuven, Belgium
    • Recruiting
    • Site BE32005
  • Liège, Belgium
    • Recruiting
    • Site BE32004
• Brazil
  • Belo Horizonte, Brazil
    • Recruiting
    • Site BR55014
  • Blumenau, Brazil
    • Recruiting
    • Site BR55002
  • Fortaleza, Brazil
    • Recruiting
    • Site BR55012
  • Jaú, Brazil
    • Recruiting
    • Site BR55008
  • Lages, Brazil
    • Recruiting
    • Site BR55004
  • Porto Alegre, Brazil
    • Recruiting
    • Site BR55003
  • São Caetano do Sul, Brazil
    • Recruiting
    • Site BR55006
  • São José do Rio Preto, Brazil
    • Recruiting
    • Site BR55001
  • São Paulo, Brazil
    • Recruiting
    • Site BR55007
• China
  • Baoding, China, 71000
    • Active, not recruiting
    • Affiliated Hospital of Hebei University
  • Beijing, China
    • Active, not recruiting
    • Peking Union Medical College Hospital - Dongdan Campus
  • Anhui
    • Hefei, Anhui, China, 230031
      • Active, not recruiting
      • Anhui Provincial Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • Active, not recruiting
      • Fujian Provincial Hospital - Department of Medical Oncology
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Active, not recruiting
      • Sun Yat-sen University - Cancer Center
    • Guangzhou, Guangdong, China, 510555
      • Active, not recruiting
      • Sun Yat-sen University - Cancer Center
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Active, not recruiting
      • Harbin Medical University Cancer Hospital - Oncology
  • Henan
    • Zhenngzhou, Henan, China
      • Active, not recruiting
      • Henan Cancer Hospital - Oncology
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Active, not recruiting
      • Hubei Cancer Hospital - Oncology
  • Qinghai
    • Xining, Qinghai, China
      • Active, not recruiting
      • Qinghai University Affiliated Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200127
      • Active, not recruiting
      • Renji Hospital Shanghai Jiaotong Univ School of Medicine
    • Shanghai, Shanghai Municipality, China
      • Active, not recruiting
      • Ruijin Hospital of Shanghai Jiaotong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610200
      • Active, not recruiting
      • Sichuan Cancer Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Active, not recruiting
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Active, not recruiting
      • The First Affiliated Hospital of Zhejiang University
• Czechia
  • Brno, Czechia
    • Recruiting
    • Site CZ42006
  • Olomouc, Czechia
    • Recruiting
    • Site CZ42005
  • Prague, Czechia
    • Recruiting
    • Site CZ42002
  • Prague, Czechia
    • Recruiting
    • Site CZ42003
  • Prague, Czechia
    • Recruiting
    • Site CZ42004
• France
  • Bordeaux, France
    • Recruiting
    • Site FR33016
  • Brest, France
    • Recruiting
    • Site FR33008
  • Caen, France
    • Recruiting
    • Site FR33012
  • Carassonne, France
    • Recruiting
    • Site FR33009
  • Dijon, France
    • Recruiting
    • Site FR33005
  • Lille, France
    • Recruiting
    • Site FR33007
  • Lille, France
    • Recruiting
    • Site FR33002
  • Lyon, France
    • Recruiting
    • Site FR33014
  • Lyon, France
    • Recruiting
    • Site FR33017
  • Montpellier, France
    • Recruiting
    • Site FR33020
  • Nice, France
    • Recruiting
    • Site FR33018
  • Paris, France
    • Recruiting
    • Site FR33003
  • Paris, France
    • Recruiting
    • Site FR33010
  • Paris, France
    • Recruiting
    • Site FR33013
  • Plérin, France
    • Recruiting
    • Site FR33015
  • Poitiers, France
    • Recruiting
    • Site FR33004
  • Rouen, France
    • Recruiting
    • Site FR33006
  • Saint Herbian Cedex, France
    • Recruiting
    • Site FR33019
  • Strasbourg, France
    • Recruiting
    • Site FR33011
• Germany
  • Berlin, Germany
    • Recruiting
    • Site DE49013
  • Essen, Germany
    • Recruiting
    • Site DE49010
  • Frankfurt am Main, Germany
    • Recruiting
    • Site DE49017
  • Hanover, Germany
    • Recruiting
    • Site DE49007
  • Leipzig, Germany
    • Recruiting
    • Site DE49004
  • Mainz, Germany
    • Recruiting
    • Site DE49001
  • Munich, Germany
    • Recruiting
    • Site DE49014
  • Nuremberg, Germany
    • Recruiting
    • Site DE49006
  • Saarbrücken, Germany
    • Recruiting
    • Site DE49002
  • Schweinfurt, Germany
    • Recruiting
    • Site DE49011
  • Wolfsburg, Germany
    • Recruiting
    • Site DE49016
• Italy
  • Bergamo, Italy
    • Recruiting
    • Site IT39019
  • Bologna, Italy
    • Recruiting
    • Site IT39017
  • Brescia, Italy
    • Recruiting
    • Site IT39009
  • Candiolo, Italy
    • Recruiting
    • Site IT39014
  • Cremona, Italy
    • Recruiting
    • Site IT39006
  • Florence, Italy
    • Recruiting
    • Site IT39011
  • Meldola, Italy
    • Recruiting
    • Site IT39007
  • Milan, Italy
    • Recruiting
    • Site IT39012
  • Milan, Italy
    • Recruiting
    • Site IT39018
  • Milan, Italy
    • Recruiting
    • Site IT39020
  • Naples, Italy
    • Recruiting
    • Site IT39021
  • Pisa, Italy
    • Recruiting
    • Site IT39015
  • Reggio Emilia, Italy
    • Recruiting
    • Site IT39004
  • Roma, Italy
    • Recruiting
    • Site IT39016
  • Rome, Italy
    • Recruiting
    • Site IT39001
  • Torrette Di Ancona, Italy
    • Recruiting
    • Site IT39003
  • Udine, Italy
    • Recruiting
    • Site IT39022
  • Verona, Italy
    • Recruiting
    • Site IT39002
• Japan
  • Chiba
    • Chiba, Chiba, Japan
      • Active, not recruiting
      • Chiba Cancer Center
    • Kashiwa, Chiba, Japan
      • Active, not recruiting
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama, Ehime, Japan
      • Active, not recruiting
      • National Hospital Organization Shikoku Cancer Center
  • Fukuoka
    • Fukuoka, Fukuoka, Japan
      • Active, not recruiting
      • Kyushu University Hospital (Hematology, Oncology & Cardiovascular medicine)
    • Fukuoka, Fukuoka, Japan
      • Active, not recruiting
      • Kyushu University Hospital(Gastrointestinal Surgery)
    • Fukuoka, Fukuoka, Japan
      • Active, not recruiting
      • National Hospital Organization Kyushu Cancer Center
  • Gunma
    • Maebashi, Gunma, Japan
      • Active, not recruiting
      • Gunma University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Active, not recruiting
      • Hokkaido University Hospital
  • Hyōgo
    • Akashi-shi, Hyōgo, Japan
      • Active, not recruiting
      • Hyogo Cancer Center
    • Kobe, Hyōgo, Japan
      • Active, not recruiting
      • Kobe City Medical Center General Hospital
  • Kagawa-ken
    • Kida-gun, Kagawa-ken, Japan
      • Active, not recruiting
      • Kagawa University Hospital
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan
      • Active, not recruiting
      • St. Marianna University Hospital
    • Yokohama, Kanagawa, Japan
      • Active, not recruiting
      • Kanagawa Cancer Ctr Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • Active, not recruiting
      • Tohoku University Hospital
  • Osaka
    • Osaka, Osaka, Japan
      • Active, not recruiting
      • Osaka General Medical Center
    • Osaka, Osaka, Japan
      • Active, not recruiting
      • Osaka International Cancer Institute
    • Suita-shi, Osaka, Japan
      • Active, not recruiting
      • Osaka University Hospital
  • Saitama
    • Hidaka-shi, Saitama, Japan
      • Active, not recruiting
      • Saitama Medical University International Medical Center
    • Kitaadachi-gun Ina-machi, Saitama, Japan
      • Active, not recruiting
      • Saitama Cancer Center
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan
      • Active, not recruiting
      • Shizuoka Cancer Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan
      • Active, not recruiting
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan
      • Active, not recruiting
      • The Cancer Institute Hospital of JFCR
• Lithuania
  • Kaunas, Lithuania
    • Recruiting
    • Site LT37001
  • Vilnius, Lithuania
    • Recruiting
    • Site LT37002
• Mexico
  • Mexico City, Mexico
    • Recruiting
    • Site MX52003
  • Oaxaca City, Mexico
    • Recruiting
    • Site MX52001
• Netherlands
  • Leeuwarden, Netherlands
    • Recruiting
    • Site NL31002
  • Nijmegen, Netherlands
    • Recruiting
    • Site NL31001
• Poland
  • Gliwice, Poland
    • Recruiting
    • Site PL48006
  • Olsztyn, Poland
    • Recruiting
    • Site PL48008
  • Przemyśl, Poland
    • Recruiting
    • Site PL48002
  • Swidnica, Poland
    • Recruiting
    • Site PL48009
  • Warsaw, Poland
    • Recruiting
    • Site PL48007
  • Lubusz Voivodeship
    • Lubin, Lubusz Voivodeship, Poland
      • Recruiting
      • Site PL48005
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland
      • Recruiting
      • Site PL48004
  • Woj Podkarpackie
    • Brzozów, Woj Podkarpackie, Poland
      • Recruiting
      • Site PL48001
• Portugal
  • Almada, Portugal
    • Recruiting
    • Site PT35106
  • Braga, Portugal
    • Recruiting
    • Site PT35103
  • Guimarães, Portugal
    • Recruiting
    • Site PT35104
  • Lisbon, Portugal
    • Recruiting
    • Site PT35102
  • Lisbon, Portugal
    • Recruiting
    • Site PT35107
  • Porto, Portugal
    • Recruiting
    • Site PT35105
  • Porto, Portugal
    • Recruiting
    • Site PT35108
  • Porto, Portugal
    • Recruiting
    • Site PT35109
• Romania
  • Bucharest, Romania
    • Recruiting
    • Site RO40008
  • Cluj-Napoca, Romania
    • Recruiting
    • Site RO40001
  • Cluj-Napoca, Romania
    • Recruiting
    • Site RO40005
  • Cluj-Napoca, Romania
    • Recruiting
    • Site RO40006
  • Craiova, Romania
    • Recruiting
    • Site RO40003
  • Floreşti, Romania
    • Recruiting
    • Site RO40002
  • Iași, Romania
    • Recruiting
    • Site RO40007
  • Timișoara, Romania
    • Recruiting
    • Site RO40004
• South Korea
  • Daegu, South Korea
    • Active, not recruiting
    • Site KR82004
  • Incheon, South Korea
    • Active, not recruiting
    • Site KR82005
  • Seoul, South Korea
    • Active, not recruiting
    • Site KR82001
  • Seoul, South Korea
    • Active, not recruiting
    • Site KR82002
  • Seoul, South Korea
    • Active, not recruiting
    • Site KR82006
  • Seoul, South Korea
    • Active, not recruiting
    • Site KR82008
  • Seoul, South Korea
    • Active, not recruiting
    • Site KR82010
  • Seoul, South Korea
    • Active, not recruiting
    • Site KR82012
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea
      • Active, not recruiting
      • Site KR82011
    • Seongnam-si, Gyeonggi-do, South Korea
      • Active, not recruiting
      • Site KR82007
    • Suwon, Gyeonggi-do, South Korea
      • Active, not recruiting
      • Site KR82013
    • Suwon, Gyeonggi-do, South Korea
      • Active, not recruiting
      • Site KR82015
  • Joellanamdo
    • Hwasungun, Joellanamdo, South Korea
      • Active, not recruiting
      • Site KR82014
  • North Chungcheong
    • Cheongju-si, North Chungcheong, South Korea
      • Active, not recruiting
      • Site KR82009
  • Seoul
    • Seocho-gu, Seoul, South Korea
      • Active, not recruiting
      • Site KR82003
• Spain
  • A Coruña, Spain
    • Recruiting
    • Site ES34005
  • Barcelona, Spain
    • Recruiting
    • Site ES34011
  • Barcelona, Spain
    • Recruiting
    • Site ES34006
  • Barcelona, Spain
    • Recruiting
    • Site ES34009
  • Barcelona, Spain
    • Recruiting
    • Site ES34010
  • Barcelona, Spain
    • Recruiting
    • Site ES34024
  • Barcelona, Spain
    • Recruiting
    • Site ES34026
  • Barcelona, Spain
    • Recruiting
    • Site ES34028
  • El Palmar, Spain
    • Recruiting
    • Site ES34021
  • Lleida, Spain
    • Recruiting
    • Site ES34014
  • Madrid, Spain
    • Recruiting
    • Site ES34008
  • Madrid, Spain
    • Recruiting
    • Site ES34003
  • Madrid, Spain
    • Recruiting
    • Site ES34031
  • Madrid, Spain
    • Recruiting
    • Site ES34016
  • Madrid, Spain
    • Recruiting
    • Site ES34017
  • Murcia, Spain
    • Recruiting
    • Site ES34030
  • Pozuelo de Alarcón, Spain
    • Recruiting
    • Site ES34013
  • Santiago de Compostela, Spain
    • Recruiting
    • Site ES34029
  • Seville, Spain
    • Recruiting
    • Site ES34012
  • Seville, Spain
    • Recruiting
    • Site ES34025
  • Valencia, Spain
    • Recruiting
    • Site ES34004
  • Valencia, Spain
    • Recruiting
    • Site ES34007
  • Zaragoza, Spain
    • Recruiting
    • Site ES34018
  • Zaragoza, Spain
    • Recruiting
    • Site ES34015
  • Alicante
    • Elche, Alicante, Spain
      • Recruiting
      • Site ES34022
  • Cataluyna
    • San Cugat Del Valles Barcelona, Cataluyna, Spain
      • Recruiting
      • Site ES34023
  • Madrid
    • Madrid, Madrid, Spain
      • Recruiting
      • Site ES34019
    • Madrid, Madrid, Spain
      • Recruiting
      • Site ES34027
  • Pamplona
    • Navarra, Pamplona, Spain
      • Recruiting
      • Site ES34002
• Taiwan
  • Kaohsiung City, Taiwan
    • Active, not recruiting
    • Site TW88604
  • Taichung, Taiwan
    • Active, not recruiting
    • Site TW88601
  • Tainan, Taiwan
    • Active, not recruiting
    • Site TW88606
  • Taipei, Taiwan
    • Active, not recruiting
    • Site TW88605
  • Taiwan
    • Dawan, Taiwan, Taiwan
      • Active, not recruiting
      • Site TW88603
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye)
    • Recruiting
    • Site TR90011
  • Ankara, Turkey (Türkiye)
    • Recruiting
    • Site TR90001
  • Ankara, Turkey (Türkiye)
    • Recruiting
    • Site TR90006
  • Ankara, Turkey (Türkiye)
    • Recruiting
    • Site TR90004
  • Bursa, Turkey (Türkiye)
    • Recruiting
    • Site TR90014
  • Istanbul, Turkey (Türkiye)
    • Recruiting
    • Site TR90005
  • Konya, Turkey (Türkiye)
    • Recruiting
    • Site TR90013
  • Samsun, Turkey (Türkiye)
    • Recruiting
    • Site TR90009
  • Van, Turkey (Türkiye)
    • Recruiting
    • Site TR90015
• United Kingdom
  • Bristol, United Kingdom
    • Recruiting
    • Site UK44001
  • Cardiff, United Kingdom
    • Recruiting
    • Site GB44003
  • Coventry, United Kingdom
    • Recruiting
    • Site GB44002
  • Dundee, United Kingdom
    • Recruiting
    • Site UK44006
  • Glasgow, United Kingdom
    • Recruiting
    • Site GB44004
  • London, United Kingdom
    • Recruiting
    • Site GB44005
  • London, United Kingdom
    • Recruiting
    • Site UK44011
  • London, United Kingdom
    • Recruiting
    • Site UK44014
  • London, United Kingdom
    • Recruiting
    • Site UK44015
  • London, United Kingdom
    • Recruiting
    • Site UK44016
  • Manchester, United Kingdom
    • Recruiting
    • Site UK44009
  • Sheffield, United Kingdom
    • Recruiting
    • Site GB44008
  • East Riding Of Yorkshire
    • Cottingham, East Riding Of Yorkshire, United Kingdom
      • Recruiting
      • Site GB44010
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • UAB Medicine - UAB Hospital
  • California
    • Bakersfield, California, United States, 93309
      • Recruiting
      • CBCC Global Research - Comprehensive Blood & Cancer Center
    • Cerritos, California, United States, 90703
      • Recruiting
      • TOI Clinical Research
    • La Jolla, California, United States, 92037-0845
      • Recruiting
      • University of California, San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90025
      • Recruiting
      • The Angeles Clinic and Research Institute, West Los Angeles Office
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Recruiting
      • Hartford HealthCare - Hartford Hospital
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University School Of Medicine
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital / Lombardi Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Piedmont Physician Medical Oncology Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Recruiting
      • Franciscan Health Oncology and Hematology Specialists
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Holden Comprehensive Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Cancer Center
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Recruiting
      • Saint Elizabeth Medical Center Edgewood
  • Maryland
    • Baltimore, Maryland, United States, 21021
      • Recruiting
      • University of Maryland Medical System - University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber/Harvard Cancer Center
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts - UMass Chan Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Health System
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Center
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Henry Ford Cancer Institute-Henry Ford Hospital
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Recruiting
      • Metro Minnesota Community Oncology Research Consortium (MMCORC)
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Oncology Hematology West PC dba Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68105
      • Recruiting
      • University of Nebraska Medical Center
  • New Jersey
    • Pennington, New Jersey, United States, 08534
      • Recruiting
      • Capital Health - Hematology Oncology Specialists
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center - Duke Cancer Centre
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Allegheny General Hospital (AGH)-Allegheny Singer Research Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • The University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology-Baylor Charles A Sammons Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • The Center For Cancer And Blood Disorders (Texas Cancer Care)
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Recruiting
      • Utah Cancer Specialists Cancer Center - Medical Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has histologically confirmed gastric or Gastroesophageal Junction (GEJ) adenocarcinoma.
• Participant has radiographically confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to randomization.
• Participant has radiologically evaluable disease (measurable and/or nonmeasurable) according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1, ≤ 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
• Participant has Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0 to 1.
• Participant has predicted life expectancy ≥ 12 weeks.
• Participant must be a candidate to receive mFOLFOX6 or CAPOX and pembrolizumab.

• Female participant is not pregnant and at least 1 of the following conditions apply:

  • Not a woman of child bearing potential (WOCBP)
  • WOCBP who has a negative urine or serum pregnancy test at screening (Specific to Japan: with a medical interview), and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study interventions.
  • Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study interventions).
  • Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for 9 months after the final administration of oxaliplatin and for 6 months after final administration of all other study interventions.
• Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period, and for 6 months after final investigational study intervention administration.
• Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after the final investigational study intervention administration.
• Male participant must not donate sperm during the treatment period and for 6 months after the final investigational study intervention administration
• Participant has a Human Epidermal Growth Factor Receptor 2 (HER2) -negative tumor.
• Participant's tumor expresses Claudin18.2 (CLDN18.2) in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
• Participant's tumor expresses Programmed death ligand (PD-L1) combined positive score (CPS) ≥ 1 as determined by central IHC testing.
• Participants with known microsatellite instability-high or mismatch repair deficient status may enroll as long as they meet the PD-L1 positivity criteria.
• Participant must meet all of the criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In case of multiple central laboratory data within this period, the most recent data should be used.
• Participant agrees not to participate in another interventional study while receiving study intervention in the present study.

Exclusion Criteria:

• Participant has prior severe allergic reaction or intolerance to zolbetuximab or other monoclonal antibodies, pembrolizumab, mFOLFOX6 or CAPOX.
• Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.
• Participant has significant gastric bleeding and/or untreated gastric ulcers that would preclude the participant from participation.
• Participant has unresolved pneumonitis or history of non-infectious pneumonitis such as immune-related pneumonitis, radiation induced pneumonitis.
• Participant has history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.

• Participant has a known history of a positive test for Human Immunodeficiency Virus (HIV) infection or known active Hepatitis B Surface Antigen (positive HBsAg) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements.

  • For participants who are negative for HBsAg, but hepatitis B core antibody (HBcAb) positive, a hepatitis B DNA test will be performed and if positive the participant will be excluded.
  • Participants with positive Hepatitis C virus (HCV) serology, but negative HCV RNA test results are eligible.
  • Participants treated for HCV with undetectable viral load results are eligible.
• Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
• Participant has active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization. Participants with stable autoimmune disease who are receiving physiologic replacement doses of hydrocortisone or its equivalent are allowed.
• Participant has a clinically significant disease or comorbidity that may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
• Participant has another malignancy for which treatment is required.
• Participant has known complete Dihydropyrimidine Dehydrogenase (DPD) deficiency (screening for DPD deficiency should be conducted per local requirements).
• Participant has known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the participant ineligible).
• Participant has sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving.

• Participant has significant cardiovascular disease, including any of the following:

  • Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization.
  • History of clinically significant ventricular arrhythmias (i.e., sustained; ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
  • QTc interval > 450 msec for male participants; QTc interval > 470 msec for female participants.
  • History or family history of congenital long QT syndrome.
  • Cardiac arrhythmias requiring anti-arrhythmic medications (participants with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
• Participant has ongoing or previous interstitial lung disease, active diverticulitis or peptic ulcerative disease, or solid organ or stem cell transplant or other uncontrolled or clinically significant medical disorders.
• Participant has type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed.
• Participant has received prior systemic chemotherapy and/or immunotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, except for a maximum of 1 treatment course of mFOLFOX6 (day 1 to 14) or CAPOX (day 1 to 21) with or without pembrolizumab. However, participants may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies as long as their disease progression occurred at least 6 months after the last dose. Participant who has received treatment with herbal medications that have known antitumor activity > 28 days prior to randomization is allowed.
• Participant has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to randomization. Participant using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single-dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use is allowed.
• Participant has had major surgical procedure ≤ 28 days before randomization and has not completely recovered from the surgical procedure ≤ 14 days before randomization.
• Participant has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to randomization and has NOT recovered from any related toxicity. Palliative radiotherapy is allowed and must be completed > 14 days prior to randomization.
• Participant has received prior CLDN18.2 agents.
• Participant received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Participant has received other investigational agents or devices concurrently or within 28 days prior to randomization or within 5 half-lives of the drug, whichever is longer.
• Participant has any condition which makes the participant unsuitable for study participation.
• Participant has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the participant to participate in the study, which places the participant at undue risk or complicates the interpretation of data.
• Treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to randomization or within 5 half-lives of the drug, whichever is shorter, is strictly prohibited.
• Pernicious anemia or other anemias due to vitamin B12 deficiency.
• Participant has a known history of a positive test for tuberculosis or known active tuberculosis infection. NOTE: Screening for these infections should be conducted per local requirements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: zolbetuximab in combination with pembrolizumab and chemotherapy; Participants will receive zolbetuximab as an intravenous (via a vein) infusion at 800 mg/m2 loading dose at C1D1 followed by subsequent doses of 400 mg/m2 every 2 weeks; or 800 mg/m2 loading dose at C1D1 followed by subsequent doses of 600 mg/m2 every 3 weeks, followed by an intravenous infusion of pembrolizumab at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks. Participants will then receive chemotherapy over 4 or more cycles of either up to 8 CAPOX treatments (oxaliplatin: 130 mg/m2 once every 3 weeks, capecitabine: 1000 mg/m2 twice daily on days 1 through 14 and days 22 through 35 of each cycle), or, up to 12 mFOLFOX6 treatments (oxaliplatin: 85 mg/m2, Folinic acid (leucovorin/local equivalent): 400 mg/m2, 5-FU bolus: 400 mg/m2, 5-FU infusion: 2400 mg/m2) once every 2 weeks (or components of mFOLFOX6 if some components are discontinued due to toxicity). The choice of chemotherapy for each participant is based on investigator's judgment. Each cycle is approximately 42 days.	Drug: zolbetuximab; Participants will receive an IV infusion of zolbetuximab on Cycle 1 Day 1 (C1D1) followed by subsequent IV infusion every 2 weeks or every 3 weeks.; Other Names: IMAB362; VYLOY; Drug: Pembrolizumab; Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.; Drug: Capecitabine; Participants receiving CAPOX regimen of chemotherapy will receive capecitabine Tablet twice daily orally on days 1 through 14 and days 22 through 35 of each cycle.; Drug: Oxaliplatin; Participants receiving CAPOX or mFOLFOX6 regimen of chemotherapy will receive an IV infusion of oxaliplatin once every 2 or 3 weeks.; Drug: Folinic acid (leucovorin or local equivalent); Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion of Folinic acid (leucovorin or local equivalent) once every 2 weeks.; Drug: 5-fluorouracil (5-FU); Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.
Active Comparator: Arm B: Placebo in combination with pembrolizumab and chemotherapy; Participants will receive matching placebo as an intravenous (via a vein) infusion followed by an intravenous infusion of pembrolizumab at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks. Participants will then receive chemotherapy over 4 or more cycles of either up to 8 CAPOX treatments (oxaliplatin: 130 mg/m2 once every 3 weeks, capecitabine: 1000 mg/m2 twice daily on days 1 through 14 and days 22 through 35 of each cycle), or, up to 12 mFOLFOX6 treatments (oxaliplatin: 85 mg/m2, Folinic acid (leucovorin/local equivalent): 400 mg/m2, 5-FU bolus: 400 mg/m2, 5-FU infusion: 2400 mg/m2) once every 2 weeks (or components of mFOLFOX6 if some components are discontinued due to toxicity). The choice of chemotherapy for each participant is based on investigator's judgment. Each cycle is approximately 42 days.	Drug: Pembrolizumab; Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.; Drug: Capecitabine; Participants receiving CAPOX regimen of chemotherapy will receive capecitabine Tablet twice daily orally on days 1 through 14 and days 22 through 35 of each cycle.; Drug: Oxaliplatin; Participants receiving CAPOX or mFOLFOX6 regimen of chemotherapy will receive an IV infusion of oxaliplatin once every 2 or 3 weeks.; Drug: Folinic acid (leucovorin or local equivalent); Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion of Folinic acid (leucovorin or local equivalent) once every 2 weeks.; Drug: 5-fluorouracil (5-FU); Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.; Drug: Placebo; Participants will receive an IV infusion of placebo (0.9% of sodium chloride) on C1D1 followed by subsequent IV infusion every 2 weeks or every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death from any cause.	Up to 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Defined as the proportion of participants who have a Best Overall Response (BOR) or Complete Response (CR) or Partial Response (PR) as investigator assessed per RECIST V1.1.	Up to 57 Months
Number of participants with adverse Events (AEs)	Adverse events (AEs) will coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.	Up to 57 Months
Number of participants with electrocardiograms (ECG) abnormalities and/or AEs	Number of participants with potentially clinically significant ECG values.	Up to 57 Months
Number of Participants with Vital Sign abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to 57 Months
Number of participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status score	The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.	Up to 57 Months
Number of participants with laboratory assessments abnormalities and/ or AEs	Number of participants with potentially clinically significant laboratory values.	Up to 57 Months
Pharmacokinetics (PK) of zolbetuximab in serum: End of Infusion Concentration	Concentration will be derived from the PK serum samples collected at time of end of infusion.	Up to 57 Months
Pharmacokinetics (PK) of zolbetuximab in serum: Concentration Immediately Prior to Dosing at multiple dosing (Ctrough)	Ctrough will be derived from the PK serum samples collected.	Up to 57 Months
Number of participants with positive antidrug antibodies (ADA) to zolbetuximab		Up to 57 Months
Progression Free Survival (PFS)	Defined as the time from the date of randomization until the date of radiologic disease progression [investigator-assessed per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1] or death from any cause, whichever is earlier.	Up to 72 Months
Duration of Response (DOR)	Defined as the time from the date of the first response (CR/PR) until the date of disease progression as investigator-assessed per RECIST V1.1 or date of death from any cause, whichever is earlier.	Up to 72 Months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Monitor, Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: PD-L1; zolbetuximab; Human epidermal growth factor receptor 2 (HER2) Negative; Claudin 18.2; Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma Cancer; Locally Advanced Unresectable Gastric Adenocarcinoma Cancer; Metastatic Gastric Adenocarcinoma Cancer; Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms; Adenocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Capecitabine; Oxaliplatin; Fluorouracil; Leucovorin; pembrolizumab; zolbetuximab
• Other Study ID Numbers: 8951-CL-0305; 2024-519773-19 (Registry Identifier: CTIS (EU)); jRCT2031250021 (Registry Identifier: Japan Registry of Clinical Trials (jRCT)); CTR20253090 (Registry Identifier: ChinaDrugTrials.org.cn)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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