Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or CancerPhase 3LUCERNANCT06901531
A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer
A Phase 3 study testing zolbetuximab, Pembrolizumab and Capecitabine in people with Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer and Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer, run by Astellas Pharma Global Development, Inc. at 252 sites in 22 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer, Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer, Metastatic Gastric Adenocarcinoma or Cancer
- What is being tested?
- zolbetuximab, Pembrolizumab and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 252 sitesin 22 countries
- Study dates
- 22 May 2025to 30 Sep 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
252 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
252 sites in 22 countries
United States37 sites, 35 recruiting
- Recruiting
University of Michigan Health System
Ann Arbor, Michigan, 48109
- Recruiting
Piedmont Physician Medical Oncology Atlanta
Atlanta, Georgia, 30318
- Recruiting
CBCC Global Research - Comprehensive Blood & Cancer Center
Bakersfield, California, 93309
- Recruiting
University of Maryland Medical System - University of Maryland Medical Center
Baltimore, Maryland, 21021
- Withdrawn
UAB Medicine - UAB Hospital
Birmingham, Alabama, 35294
- Recruiting
Dana Farber/Harvard Cancer Center
Boston, Massachusetts, 02215
- Recruiting
TOI Clinical Research
Cerritos, California, 90703
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
- Recruiting
Northwestern Memorial Hospital
Chicago, Illinois, 60611
- Recruiting
Texas Oncology-Baylor Charles A Sammons Cancer Center
Dallas, Texas, 75246
- Recruiting
Barbara Ann Karmanos Cancer Center
Detroit, Michigan, 48201
- Recruiting
Henry Ford Cancer Institute-Henry Ford Hospital
Detroit, Michigan, 48201
- Recruiting
Duke University Medical Center - Duke Cancer Centre
Durham, North Carolina, 27710
- Recruiting
Saint Elizabeth Medical Center Edgewood
Edgewood, Kentucky, 41017
- Recruiting
Inova Schar Cancer Institute Clinical Trials
Fairfax, Virginia, 22031
- Recruiting
The Center For Cancer And Blood Disorders (Texas Cancer Care)
Fort Worth, Texas, 76104
- Recruiting
Hartford HealthCare - Hartford Hospital
Hartford, Connecticut, 06102
- Recruiting
Houston Methodist Cancer Center
Houston, Texas, 77030
- Recruiting
Franciscan Health Oncology and Hematology Specialists
Indianapolis, Indiana, 46237
- Recruiting
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
- Recruiting
The University of Tennessee Medical Center
Knoxville, Tennessee, 37920
- Recruiting
University of California, San Diego Moores Cancer Center
La Jolla, California, 92037-0845
- Recruiting
The Angeles Clinic and Research Institute, West Los Angeles Office
Los Angeles, California, 90025
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
Yale University School of Medicine
New Haven, Connecticut, 06510
- Recruiting
NYU Langone Medical Center
New York, New York, 10016
- Recruiting
Oncology Hematology West PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130
- Withdrawn
University of Nebraska Medical Center
Omaha, Nebraska, 68198
- Recruiting
Capital Health - Hematology Oncology Specialists
Pennington, New Jersey, 08534
- Recruiting
Allegheny General Hospital (AGH)-Allegheny Singer Research Institute
Pittsburgh, Pennsylvania, 15212
- Recruiting
Rhode Island Hospital
Providence, Rhode Island, 02903
- Recruiting
Metro Minnesota Community Oncology Research Consortium (MMCORC)
Saint Louis Park, Minnesota, 55426
- Recruiting
Utah Cancer Specialists Cancer Center - Medical Oncology
Salt Lake City, Utah, 84106
- Recruiting
Montefiore Medical Center
The Bronx, New York, 10461
- Recruiting
MedStar Georgetown University Hospital / Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
- Recruiting
University of Kansas Cancer Center
Westwood, Kansas, 66205
- Recruiting
University of Massachusetts - UMass Chan Medical School
Worcester, Massachusetts, 01655
Spain29 sites, 29 recruiting
- Recruiting
Site ES34005
A Coruña
- Recruiting
Site ES34006
Barcelona
- Recruiting
Site ES34009
Barcelona
- Recruiting
Site ES34010
Barcelona
- Recruiting
Site ES34011
Barcelona
- Recruiting
Site ES34024
Barcelona
- Recruiting
Site ES34026
Barcelona
- Recruiting
Site ES34028
Barcelona
- Recruiting
Site ES34021
El Palmar
- Recruiting
Site ES34022
Elche, Alicante
- Recruiting
Site ES34014
Lleida
- Recruiting
Site ES34019
Madrid, Madrid
- Recruiting
Site ES34027
Madrid, Madrid
- Recruiting
Site ES34003
Madrid
- Recruiting
Site ES34008
Madrid
- Recruiting
Site ES34016
Madrid
- Recruiting
Site ES34017
Madrid
- Recruiting
Site ES34031
Madrid
- Recruiting
Site ES34030
Murcia
- Recruiting
Site ES34002
Navarra, Pamplona
- Recruiting
Site ES34013
Pozuelo de Alarcón
- Recruiting
Site ES34023
San Cugat Del Valles Barcelona, Cataluyna
- Recruiting
Site ES34029
Santiago de Compostela
- Recruiting
Site ES34012
Seville
- Recruiting
Site ES34025
Seville
- Recruiting
Site ES34004
Valencia
- Recruiting
Site ES34007
Valencia
- Recruiting
Site ES34015
Zaragoza
- Recruiting
Site ES34018
Zaragoza
Japan22 sites
- Active, not recruiting
Hyogo Cancer Center
Akashi-shi, Hyōgo
- Active, not recruiting
Chiba Cancer Center
Chiba, Chiba
- Active, not recruiting
National Cancer Center Hospital
Chuo-ku, Tokyo
- Active, not recruiting
Kyushu University Hospital (Hematology, Oncology & Cardiovascular medicine)
Fukuoka, Fukuoka
- Active, not recruiting
Kyushu University Hospital(Gastrointestinal Surgery)
Fukuoka, Fukuoka
- Active, not recruiting
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka
- Active, not recruiting
Saitama Medical University International Medical Center
Hidaka-shi, Saitama
- Active, not recruiting
National Cancer Center Hospital East
Kashiwa, Chiba
- Active, not recruiting
St. Marianna University Hospital
Kawasaki-shi, Kanagawa
- Active, not recruiting
Kagawa University Hospital
Kida-gun, Kagawa-ken
- Active, not recruiting
Saitama Cancer Center
Kitaadachi-gun Ina-machi, Saitama
- Active, not recruiting
Kobe City Medical Center General Hospital
Kobe, Hyōgo
- Active, not recruiting
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo
- Active, not recruiting
Gunma University Hospital
Maebashi, Gunma
- Active, not recruiting
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime
- Active, not recruiting
Osaka General Medical Center
Osaka, Osaka
- Active, not recruiting
Osaka International Cancer Institute
Osaka, Osaka
- Active, not recruiting
Hokkaido University Hospital
Sapporo, Hokkaido
- Active, not recruiting
Tohoku University Hospital
Sendai, Miyagi
- Active, not recruiting
Osaka University Hospital
Suita-shi, Osaka
- Active, not recruiting
Shizuoka Cancer Center
Sunto-gun, Shizuoka
- Active, not recruiting
Kanagawa Cancer Ctr Hospital
Yokohama, Kanagawa
France19 sites, 19 recruiting
- Recruiting
Site FR33016
Bordeaux
- Recruiting
Site FR33008
Brest
- Recruiting
Site FR33012
Caen
- Recruiting
Site FR33009
Carassonne
- Recruiting
Site FR33005
Dijon
- Recruiting
Site FR33002
Lille
- Recruiting
Site FR33007
Lille
- Recruiting
Site FR33014
Lyon
- Recruiting
Site FR33017
Lyon
- Recruiting
Site FR33020
Montpellier
- Recruiting
Site FR33018
Nice
- Recruiting
Site FR33003
Paris
- Recruiting
Site FR33010
Paris
- Recruiting
Site FR33013
Paris
- Recruiting
Site FR33015
Plérin
- Recruiting
Site FR33004
Poitiers
- Recruiting
Site FR33006
Rouen
- Recruiting
Site FR33019
Saint Herbian Cedex
- Recruiting
Site FR33011
Strasbourg
Italy18 sites, 17 recruiting
- Withdrawn
Site IT39003
Ancona
- Recruiting
Site IT39019
Bergamo
- Recruiting
Site IT39017
Bologna
- Recruiting
Site IT39009
Brescia
- Recruiting
Site IT39014
Candiolo
- Recruiting
Site IT39006
Cremona
- Recruiting
Site IT39011
Florence
- Recruiting
Site IT39007
Meldola
- Recruiting
Site IT39012
Milan
- Recruiting
Site IT39018
Milan
- Recruiting
Site IT39020
Milan
- Recruiting
Site IT39021
Naples
- Recruiting
Site IT39015
Pisa
- Recruiting
Site IT39004
Reggio Emilia
- Recruiting
Site IT39016
Roma
- Recruiting
Site IT39001
Rome
- Recruiting
Site IT39022
Udine
- Recruiting
Site IT39002
Verona
China15 sites
- Active, not recruiting
Affiliated Hospital of Hebei University
Baoding, 71000
- Active, not recruiting
Peking Union Medical College Hospital - Dongdan Campus
Beijing
- Active, not recruiting
Sichuan Cancer Hospital
Chengdu, Sichuan, 610200
- Active, not recruiting
Fujian Provincial Hospital - Department of Medical Oncology
Fuzhou, Fujian
- Active, not recruiting
Sun Yat-sen University - Cancer Center
Guangzhou, Guangdong, 510060
- Active, not recruiting
Sun Yat-sen University - Cancer Center
Guangzhou, Guangdong, 510555
- Active, not recruiting
The First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang
- Active, not recruiting
Harbin Medical University Cancer Hospital - Oncology
Harbin, Heilongjiang
- Active, not recruiting
Anhui Provincial Cancer Hospital
Hefei, Anhui, 230031
- Active, not recruiting
Renji Hospital Shanghai Jiaotong Univ School of Medicine
Shanghai, Shanghai Municipality, 200127
- Active, not recruiting
Ruijin Hospital of Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality
- Active, not recruiting
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality
- Active, not recruiting
Hubei Cancer Hospital - Oncology
Wuhan, Hubei, 430079
- Active, not recruiting
Qinghai University Affiliated Hospital
Xining, Qinghai
- Active, not recruiting
Henan Cancer Hospital - Oncology
Zhenngzhou, Henan
South Korea15 sites
- Active, not recruiting
Site KR82009
Cheongju-si, North Chungcheong
- Active, not recruiting
Site KR82004
Daegu
- Active, not recruiting
Site KR82011
Goyang-si, Gyeonggi-do
- Active, not recruiting
Site KR82014
Hwasungun, Joellanamdo
- Active, not recruiting
Site KR82005
Incheon
- Active, not recruiting
Site KR82003
Seocho-gu, Seoul
- Active, not recruiting
Site KR82007
Seongnam-si, Gyeonggi-do
- Active, not recruiting
Site KR82001
Seoul
- Active, not recruiting
Site KR82002
Seoul
- Active, not recruiting
Site KR82006
Seoul
- Withdrawn
Site KR82008
Seoul
- Active, not recruiting
Site KR82010
Seoul
- Active, not recruiting
Site KR82012
Seoul
- Active, not recruiting
Site KR82013
Suwon, Gyeonggi-do
- Active, not recruiting
Site KR82015
Suwon, Gyeonggi-do
United Kingdom13 sites, 13 recruiting
- Recruiting
Site UK44001
Bristol
- Recruiting
Site GB44003
Cardiff
- Recruiting
Site GB44010
Cottingham, East Riding Of Yorkshire
- Recruiting
Site GB44002
Coventry
- Recruiting
Site UK44006
Dundee
- Recruiting
Site GB44004
Glasgow
- Recruiting
Site GB44005
London
- Recruiting
Site UK44011
London
- Recruiting
Site UK44014
London
- Recruiting
Site UK44015
London
- Recruiting
Site UK44016
London
- Recruiting
Site UK44009
Manchester
- Recruiting
Site GB44008
Sheffield
Brazil12 sites, 12 recruiting
- Recruiting
Site BR55014
Belo Horizonte
- Recruiting
Site BR55002
Blumenau
- Recruiting
Site BR55012
Fortaleza
- Recruiting
Site BR55008
Jaú
- Recruiting
Site BR55004
Lages
- Recruiting
Site BR55003
Porto Alegre
- Recruiting
Site BR55006
São Caetano do Sul
- Recruiting
Site BR55001
São José do Rio Preto
- Recruiting
BR55009
São Paulo
- Recruiting
BR55010
São Paulo
- Recruiting
Site BR55007
São Paulo
- Recruiting
Site BR55011
São Paulo
Germany11 sites, 10 recruiting
- Recruiting
Site DE49013
Berlin
- Recruiting
Site DE49010
Essen
- Recruiting
Site DE49017
Frankfurt am Main
- Recruiting
Site DE49007
Hanover
- Recruiting
Site DE49004
Leipzig
- Recruiting
Site DE49001
Mainz
- Recruiting
Site DE49014
Munich
- Recruiting
Site DE49006
Nuremberg
- Recruiting
Site DE49002
Saarbrücken
- Recruiting
Site DE49011
Schweinfurt
- Withdrawn
Site DE49016
Wolfsburg
Turkey (Türkiye)9 sites, 9 recruiting
- Recruiting
Site TR90011
Adana
- Recruiting
Site TR90001
Ankara
- Recruiting
Site TR90004
Ankara
- Recruiting
Site TR90006
Ankara
- Recruiting
Site TR90014
Bursa
- Recruiting
Site TR90005
Istanbul
- Recruiting
Site TR90013
Konya
- Recruiting
Site TR90009
Samsun
- Recruiting
Site TR90015
Van
Poland8 sites, 8 recruiting
- Recruiting
Site PL48001
Brzozów, Woj Podkarpackie
- Recruiting
Site PL48006
Gliwice
- Recruiting
Site PL48005
Lubin, Lubusz Voivodeship
- Recruiting
Site PL48008
Olsztyn
- Recruiting
Site PL48002
Przemyśl
- Recruiting
Site PL48009
Swidnica
- Recruiting
Site PL48004
Warsaw, Masovian Voivodeship
- Recruiting
Site PL48007
Warsaw
Portugal8 sites, 8 recruiting
- Recruiting
Site PT35106
Almada
- Recruiting
Site PT35103
Braga
- Recruiting
Site PT35104
Guimarães
- Recruiting
Site PT35102
Lisbon
- Recruiting
Site PT35107
Lisbon
- Recruiting
Site PT35105
Porto
- Recruiting
Site PT35108
Porto
- Recruiting
Site PT35109
Porto
Romania8 sites, 8 recruiting
- Recruiting
Site RO40008
Bucharest
- Recruiting
Site RO40001
Cluj-Napoca
- Recruiting
Site RO40005
Cluj-Napoca
- Recruiting
Site RO40006
Cluj-Napoca
- Recruiting
Site RO40003
Craiova
- Recruiting
Site RO40002
Floreşti
- Recruiting
Site RO40007
Iași
- Recruiting
Site RO40004
Timișoara
Belgium6 sites, 5 recruiting
- Recruiting
Site BE32002
Bonheiden
- Recruiting
Site BE32001
Brussels
- Withdrawn
Site BE32006
Edegem
- Recruiting
Site BE32003
Ghent
- Recruiting
Site BE32005
Leuven
- Recruiting
Site BE32004
Liège
Czechia5 sites, 5 recruiting
- Recruiting
Site CZ42006
Brno
- Recruiting
Site CZ42005
Olomouc
- Recruiting
Site CZ42002
Prague
- Recruiting
Site CZ42003
Prague
- Recruiting
Site CZ42004
Prague
Taiwan5 sites
- Active, not recruiting
Site TW88603
Dawan, Taiwan
- Active, not recruiting
Site TW88604
Kaohsiung City
- Active, not recruiting
Site TW88601
Taichung
- Active, not recruiting
Site TW88606
Tainan
- Active, not recruiting
Site TW88605
Taipei
Australia4 sites, 4 recruiting
- Recruiting
Site AU61004
Brisbane, Queensland
- Recruiting
Site AU61003
Clayton, Victoria
- Recruiting
Site AU61001
Fitzroy
- Recruiting
Site AU61002
Kogarah, New South Wales
Chile2 sites, 1 recruiting
- Recruiting
Site CL56004
Las Condes
- Withdrawn
Site CL56001
Santiago
Lithuania2 sites, 2 recruiting
- Recruiting
Site LT37001
Kaunas
- Recruiting
Site LT37002
Vilnius
Mexico2 sites, 2 recruiting
- Recruiting
Site MX52003
Mexico City
- Recruiting
Site MX52001
Oaxaca City
Netherlands2 sites, 2 recruiting
- Recruiting
Site NL31002
Leeuwarden
- Recruiting
Site NL31001
Nijmegen
About this study
Official title: 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.
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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.
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Zolbetuximab (Vyloy), has received marketing approval in Japan. The study is considered a post marketing study in Japan.
- 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
- Being tested
- zolbetuximab, Pembrolizumab, Capecitabine, Oxaliplatin, Folinic acid (leucovorin or local equivalent)
- Keywords
- Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma Cancer, Locally Advanced Unresectable Gastric Adenocarcinoma Cancer, Metastatic Gastric Adenocarcinoma Cancer, Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma, Claudin 18.2, PD-L1, Human epidermal growth factor receptor 2 (HER2) Negative, zolbetuximab
- Medical subject headings
- Adenocarcinoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zolbetuximabDrug
Also called IMAB362, VYLOY
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.
PembrolizumabDrug
Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.
CapecitabineDrug
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.
OxaliplatinDrug
Participants receiving CAPOX or mFOLFOX6 regimen of chemotherapy will receive an IV infusion of oxaliplatin once every 2 or 3 weeks.
Folinic acid (leucovorin or local equivalent)Drug
Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion of Folinic acid (leucovorin or local equivalent) once every 2 weeks.
5-fluorouracil (5-FU)Drug
Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: zolbetuximab in combination with pembrolizumab and chemotherapy | Experimental | 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. Receives: Drug: zolbetuximab; Drug: Pembrolizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Folinic acid (leucovorin or local equivalent); Drug: 5-fluorouracil (5-FU) |
| Arm B: Placebo in combination with pembrolizumab and chemotherapy | Active comparator | 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. Receives: Drug: Pembrolizumab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Folinic acid (leucovorin or local equivalent); Drug: 5-fluorouracil (5-FU); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is defined as the time from the date of randomization until the date of death from any cause.
Measured: Up to 72 months
Secondary outcomes (11)
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.
Measured: Up to 72 Months
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.
Measured: Up to 57 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.
Measured: Up to 72 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.
Measured: Up to 57 Months
Number of participants with electrocardiograms (ECG) abnormalities and/or AEs
Number of participants with potentially clinically significant ECG values.
Measured: Up to 57 Months
Number of Participants with Vital Sign abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Measured: 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.
Measured: Up to 57 Months
Number of participants with laboratory assessments abnormalities and/ or AEs
Number of participants with potentially clinically significant laboratory values.
Measured: 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.
Measured: 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.
Measured: Up to 57 Months
Number of participants with positive antidrug antibodies (ADA) to zolbetuximab
Measured: Up to 57 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2025
- Study start22 May 2025
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or CancerStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06901531
- Sponsor's protocol ID
- 8951-CL-0305
- Other IDs
- 2024-519773-19, jRCT2031250021, CTR20253090
- Acronym
- LUCERNA
- Status last verified
- Oct 2026
- First submitted
- 27 Mar 2025
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.
- Expanded access
- Available