A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer
NCT ID: NCT06901531
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
500 participants
INTERVENTIONAL
2025-05-22
2029-12-31
Brief Summary
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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 cannot take part if they need to take medicines to suppress their immune system, 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.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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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.
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.
Pembrolizumab
Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.
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.
Oxaliplatin
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)
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)
Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.
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.
Pembrolizumab
Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.
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.
Oxaliplatin
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)
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)
Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.
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.
Interventions
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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.
Pembrolizumab
Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.
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.
Oxaliplatin
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)
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)
Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 intervention.
* 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 final study intervention administration).
* 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 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.
* 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 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 it was completed at least 6 months prior to randomization. Participant may have received treatment with herbal medications that have known antitumor activity \> 28 days prior to randomization.
* Participant has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to randomization. Participants 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 are 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 investigational medicinal product (IMP), 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 IMP, 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.
18 Years
ALL
No
Sponsors
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Astellas Pharma Global Development, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Monitor
Role: STUDY_DIRECTOR
Astellas Pharma Global Development, Inc.
Locations
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Yale University School of Medicine
New Haven, Connecticut, United States
Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
Dana Farber/Harvard Cancer Center
Boston, Massachusetts, United States
Metro Minnesota Community Oncology Research Consortium (MMCORC)
Saint Louis Park, Minnesota, United States
Oncology Hematology West PC dba Nebraska Cancer Specialists
Omaha, Nebraska, United States
NYU Langone Medical Center
New York, New York, United States
The University of Tennessee Medical Center
Knoxville, Tennessee, United States
The Center For Cancer And Blood Disorders (Texas Cancer Care)
Fort Worth, Texas, United States
BE32002
Bonheiden, , Belgium
BE32001
Brussels, , Belgium
BE32003
Ghent, , Belgium
BE32004
Liège, , Belgium
Sun Yat-sen University - Cancer Center
Guangzhou, Guangdong, China
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, China
Affiliated Hospital of Hebei University
Baoding, , China
FR33016
Bordeaux, , France
FR33012
Caen, , France
FR33002
Lille, , France
FR33007
Lille, , France
FR33014
Lyon, , France
FR33017
Lyon, , France
FR33003
Paris, , France
FR33010
Paris, , France
FR33013
Paris, , France
FR33006
Rouen, , France
FR33011
Strasbourg, , France
DE49002
Saarbrücken, , Germany
DE49011
Schweinfurt, , Germany
IT39017
Bologna, , Italy
IT39009
Brescia, , Italy
IT39006
Cermona, , Italy
IT39011
Florence, , Italy
IT39007
Meldola, , Italy
IT39003
Torrette Di Ancona, , Italy
IT39002
Verona, , Italy
Chiba Cancer Center
Chiba, Chiba, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, Japan
Kyushu University Hospital (Hematology, Oncology & Cardiovascular medicine)
Fukuoka, Fukuoka, Japan
Kyushu University Hospital(Gastrointestinal Surgery)
Fukuoka, Fukuoka, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, Japan
Gunma University Hospital
Maebashi, Gunma, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, Japan
Hyogo Cancer Center
Akashi-shi, Hyōgo, Japan
Kobe City Medical Center General Hospital
Kobe, Hyōgo, Japan
Kagawa University Hospital
Kida-gun, Kagawa-ken, Japan
St. Marianna University Hospital
Kawasaki-shi, Kanagawa, Japan
Kanagawa Cancer Ctr Hospital
Yokohama, Kanagawa, Japan
Tohoku University Hospital
Sendai, Miyagi, Japan
Osaka General Medical Center
Osaka, Osaka, Japan
Osaka University Hospital
Suita-shi, Osaka, Japan
Saitama Medical University International Medical Center
Hidaka-shi, Saitama, Japan
Saitama Cancer Center
Kitaadachi-gun Ina-machi, Saitama, Japan
Shizuoka Cancer Center
Sunto-gun, Shizuoka, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
The Cancer Institute Hospital of JFCR
Koto-ku, Tokyo, Japan
LT37001
Kaunas, , Lithuania
LT37002
Vilnius, , Lithuania
NL31001
Nijmegen, , Netherlands
PL48005
Lubin, Lubusz Voivodeship, Poland
PL48004
Warsaw, Masovian Voivodeship, Poland
PL48001
Brzozów, Woj Podkarpackie, Poland
PL48008
Olsztyn, , Poland
PL48002
Przemyśl, , Poland
PL48007
Warsaw, , Poland
PT35106
Almada, , Portugal
PT35104
Guimarães, , Portugal
RO40008
Bucharest, , Romania
RO40001
Cluj-Napoca, , Romania
RO40006
Cluj-Napoca, , Romania
RO40002
Floreşti, , Romania
RO40007
Iași, , Romania
RO40004
Timișoara, , Romania
KR82011
Goyang-si, Gyeonggi-do, South Korea
KR82007
Seongnam-si, Gyeonggi-do, South Korea
KR82013
Suwon, Gyeonggi-do, South Korea
KR82015
Suwon, Gyeonggi-do, South Korea
KR82014
Hwasungun, Joellanamdo, South Korea
KR82009
Cheongju-si, North Chungcheong, South Korea
KR82004
Daegu, , South Korea
KR82005
Incheon, , South Korea
KR82001
Seoul, , South Korea
KR82002
Seoul, , South Korea
KR82006
Seoul, , South Korea
KR82008
Seoul, , South Korea
KR82010
Seoul, , South Korea
KR82012
Seoul, , South Korea
ES34022
Elche, Alicante, Spain
ES34023
San Cugat Del Valles Barcelona, Cataluyna, Spain
ES34019
Madrid, Madrid, Spain
ES34027
Madrid, Madrid, Spain
ES34002
Navarra, Pamplona, Spain
ES34006
Barcelona, , Spain
ES34009
Barcelona, , Spain
ES34010
Barcelona, , Spain
ES34024
Barcelona, , Spain
ES34026
Barcelona, , Spain
ES34014
Lleida, , Spain
ES34003
Madrid, , Spain
ES34008
Madrid, , Spain
ES34016
Madrid, , Spain
ES34017
Madrid, , Spain
ES34013
Pozuelo de Alarcón, , Spain
ES34012
Seville, , Spain
ES34025
Seville, , Spain
ES34004
Valencia, , Spain
ES34007
Valencia, , Spain
TW88604
Kaohsiung City, , Taiwan
GB44010
Cottingham, East Riding Of Yorkshire, United Kingdom
UK44001
Bristol, , United Kingdom
UK44006
Dundee, , United Kingdom
GB44004
Glasgow, , United Kingdom
UK44011
London, , United Kingdom
UK44014
London, , United Kingdom
UK44015
London, , United Kingdom
UK44016
London, , United Kingdom
UK44009
Manchester, , United Kingdom
Countries
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Central Contacts
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Other Identifiers
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2024-519773-19
Identifier Type: REGISTRY
Identifier Source: secondary_id
jRCT2031250021
Identifier Type: REGISTRY
Identifier Source: secondary_id
CTR20253090
Identifier Type: REGISTRY
Identifier Source: secondary_id
8951-CL-0305
Identifier Type: -
Identifier Source: org_study_id