A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW).
GLOW
A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
5 other identifiers
interventional
507
18 countries
165
Brief Summary
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called GEJ cancer. Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. 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. There is an unmet medical need to treat people with advanced stomach cancer or GEJ cancer. This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer. In this study, adults with advanced stomach cancer or GEJ cancer will either be given zolbetuximab with chemotherapy or a placebo with chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. Zolbetuximab with chemotherapy has already been approved to treat stomach cancer and GEJ cancer in some countries. This study is being done in countries where zolbetuximab has not yet been approved for use. If zolbetuximab becomes approved for use in those countries taking part in this study, the people taking part in those countries will leave this study and receive licensed zolbetuximab. The main aim(s) of the study is(are) to determine the efficacy of zolbetuximab combined with chemotherapy compared to a placebo combined with chemotherapy in treating adults with Claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. 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 of their cancer will also have the Claudin 18.2 protein. They may have been previously treated with certain standard therapies but have not been treated with chemotherapy for their cancer. 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 chemotherapy or placebo with chemotherapy. People who take part will receive just one of the treatments by chance. Study treatment will be double-blinded. That means that 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 cycles. The study treatment is given to people slowly through a tube into a vein. This is called an infusion. The chemotherapy is called CAPOX (capecitabine and oxaliplatin) and will be given as an infusion and also as tablets. People will have 1 infusion of either zolbetuximab or placebo together with oxaliplatin chemotherapy in 3-week (21-day) cycles. People will also take 1 tablet of capecitabine (chemotherapy) twice a day for the first 2 weeks (14 days) of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the treatment, or they need to start another cancer treatment. People will receive CAPOX for up to about 6 months (8 treatment cycles). After the 6 months, people may receive capecitabine chemotherapy only, until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will visit the clinic on certain days during their treatment. The study doctors will check if people had any medical problems from zolbetuximab or the other study treatments. Also, people in the study will have health checks. 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 after their study treatment has finished. People will visit the clinic within 7 days after they stop their study treatment. People will be asked about any medical problems and will have a health check. People who start treatment with licensed zolbetuximab will not need to attend the clinic for further visits and will receive standard of care health checks. People who continue study treatment will visit the clinic at 1 and 3 months after they stop their study treatment. They 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 treatment or not.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2018
Longer than P75 for phase_3
165 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 24, 2018
CompletedFirst Posted
Study publicly available on registry
August 31, 2018
CompletedStudy Start
First participant enrolled
November 28, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 25, 2022
CompletedResults Posted
Study results publicly available
January 27, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2026
ExpectedApril 17, 2026
April 1, 2026
3.9 years
August 24, 2018
November 13, 2024
April 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization until the date of radiological progressive disease (PD) (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 by independent review committee \[IRC\]) or death from any cause, whichever was earliest. PD was defined as development of new, or progression of existing metastases to the primary cancer under the study. Kaplan-Meier estimates was used.
From the date of randomization until 61 months and 12 days
Secondary Outcomes (14)
Overall Survival (OS)
From the date of randomization until 61 months and 12 days
Time to Confirmed Deterioration (TTCD) Using Physical Functioning as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30)
From the date of randomization until 61 months and 12 days
Time to Confirmed Deterioration (TTCD) Using Oesophago-gastric Questionnaire (OG25) on Abdominal Pain and Discomfort as Measured by EORTC QLQ-OG25 Plus STO22 Belching Subscale
From the date of randomization until 61 months and 12 days
Time to Confirmed Deterioration (TTCD) Using Global Health Status as Measured by EORTC QLQ-C30
From the date of randomization until 61 months and 12 days
Objective Response Rate (ORR)
From the date of randomization until 61 months and 12 days
- +9 more secondary outcomes
Study Arms (2)
Zolbetuximab plus CAPOX
EXPERIMENTALParticipants received an IV infusion (as a minimum of 2-hour infusion) of zolbetuximab at a loading dose of 800 mg/m\^2 on C1D1 followed by subsequent doses of 600 mg/m\^2 every 3 weeks starting from C1D22 until participant meets study treatment discontinuation criteria. Participants also received up to 8 treatments of CAPOX. Oxaliplatin was administered 130 mg/m\^2 IV on day 1 of each cycle over 2 hours for a maximum of 8 treatments; Capecitabine was administered orally at 1000 mg/m\^2 twice daily (bid) on days 1 through 14 of each cycle until the participant met study treatment discontinuation criteria. After a maximum of 8 treatments of oxaliplatin, participants may have continued to receive capecitabine taken twice daily on days 1 through 14 of each cycle at the investigator's discretion until the participant met study treatment discontinuation criteria. Each cycle was approximately 21 days.
Placebo plus CAPOX
PLACEBO COMPARATORParticipants received an IV infusion (as a minimum of 2-hour infusion) of placebo matched to zolbetuximab on C1D1 followed by subsequent doses every 3 weeks starting from C1D22 until participant meets study treatment discontinuation criteria. Participants also received up to 8 treatments of CAPOX. Oxaliplatin was administered 130 mg/m\^2 IV on day 1 of each cycle over 2 hours for a maximum of 8 treatments; Capecitabine was administered orally at 1000 mg/m\^2 bid on days 1 through 14 of each cycle until the participant met study treatment discontinuation criteria. After a maximum of 8 treatments of oxaliplatin, participants may have continued to receive capecitabine taken twice daily on days 1 through 14 of each cycle at the investigator's discretion until the participant met study treatment discontinuation criteria. Each cycle was approximately 21 days.
Interventions
Zolbetuximab were administered as a minimum 2-hour IV infusion.
Oxaliplatin were administered as a 2-hour IV infusion.
Capecitabine were administered orally twice daily (bid).
Eligibility Criteria
You may qualify if:
- A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
- Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
- Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
- A male subject with female partner(s) of childbearing potential:
- must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
- A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study treatment administration.
- Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
- Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
- Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects 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.
- Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
- Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
- Subject has ECOG performance status 0 or 1.
- +10 more criteria
You may not qualify if:
- Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject 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.
- Subject 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.
- Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to randomization.
- Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subjects 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.
- Subject has received other investigational agents or devices within 28 days prior to randomization.
- Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
- Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
- Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
- Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
- Subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation.
- Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
- For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
- Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
- Subjects treated for HCV with undetectable viral load results are eligible.
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (165)
Pacific Cancer Care
Monterey, California, 93940, United States
University of Kansas Cancer Center and Medical Pavilion
Fairway, Kansas, 66205, United States
Ochsner Clinic CCOP
New Orleans, Louisiana, 70121, United States
New Mexico Oncology Hematology
Albuquerque, New Mexico, 87109, United States
Weill Cornell Medical College (WCMC)
New York, New York, 10021, United States
Montefiore Medical Center (MMC)
The Bronx, New York, 10467, United States
Prisma Health Cancer Institute
Boiling Springs, South Carolina, 29316, United States
Parkland Hospital
Dallas, Texas, 75390, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Houston Methodist Cancer Center and Institute of Academic Medicine - Oncology
Houston, Texas, 77030, United States
Utah Cancer Specialist
Salt Lake City, Utah, 84106, United States
Site AR54009
Buenos Aires, Argentina
Site GB44005
Northwood, Argentina
Site AR54006
Pergamino, Argentina
Site AR54001
San Miguel de Tucumán, Argentina
Site AR54004
San Miguel de Tucumán, Argentina
Site AR54003
Viedma, Argentina
Site CA15003
Chicoutimi, Quebec, Canada
Site CA15002
Rimouski, Quebec, Canada
Site CA15004
Calgary, Canada
Site CN86034
Fuzhou, Fujian, China
Site CN86037
Fuzhou, Fujian, China
Site CN86032
Haikou, Hainan, China
Site CN86012
Zhengzhou, Henan, China
Site CN86029
Changsha, Hunan, China
Site CN86043
Hengyang, Hunan, China
Site CN86027
Suzhou, Jiangsu, China
Site CN86046
Wuxi, Jiangsu, China
Site CN86007
Hangzhou, Zhejiang, China
Site CN86044
Baoding, China
Site CN86035
Beijing, China
Site CN86050
Beijing, China
Site CN86025
Bengbu, China
Site CN86002
Changchun, China
Site CN86049
Changchun, China
Site CN86053
Changchun, China
Site CN86021
Changzhou, China
Site CN86039
Chengdu, China
Site CN86052
Dalian, China
Site CN86054
Dalian, China
Site CN86015
Fuzhou, China
Site CN86001
Guangzhou, China
Site CN86042
Guangzhou, China
Site CN86051
Haebrin, China
Site CN86036
Hangzhou, China
Site CN86038
Linyi, China
Site CN86016
Nanjing, China
Site CN86045
Nanning, China
Site CN86014
Shanghai, China
Site CN86026
Shantou, China
Site CN86047
Shenyang, China
Site CN86017
Shijiazhuang, China
Site CN86009
Tianjin, China
Site CN86040
Tianjin, China
Site CN86031
Ürümqi, China
Site CN86004
Wuhan, China
Site CN86005
Wuhan, China
Site CN86013
Xi'an, China
Site CN86030
Xiamen, China
Site CN86011
Xuzhou, China
Site CN86024
Zhengzhou, China
Site HR38501
Varaždin, Croatia
Site HR38502
Zagreb, Croatia
Site HR38503
Zagreb, Croatia
Site GR30001
Athens, Greece
Site GR30004
Heraklion, Greece
Site GR30003
Larissa, Greece
Site GR30005
Neo Faliro, Piraeus, Greece
Site GR30007
Rio Patras, Greece
Site GR30002
Thessaloniki, Greece
Site GR3006
Thessaloniki, Greece
Site IE35301
Dublin, Ireland
Site IE35302
Dublin, Ireland
Site JP81007
Fukuoka, Fukuoka, Japan
Site JP81008
Akashi, Hyōgo, Japan
Site JP81003
Kawasaki, Kanagawa, Japan
Site JP81001
Yokohama, Kanagawa, Japan
Site JP81010
Suita, Osaka, Japan
Site JP81005
Utsunomiya, Tochigi, Japan
Site JP81002
Chiba, Japan
Site JP81006
Kashiwa, Japan
Site JP81004
Kita-gun, Japan
Site JP81012
Kōtoku, Japan
Site JP81009
Matsuyama, Japan
Site JP81011
Tsukiji, Japan
Site MY60001
George Town, Malaysia
Site MY60004
Kota Kinabalu, Malaysia
Site MY60002
Kuala Lumpur, Malaysia
Site MY60003
Kuala Lumpur, Malaysia
Site MY60005
Kuala Lumpur, Malaysia
Site NL31004
Groningen, Netherlands
Site NL31003
Tilburg, Netherlands
Site PT35109
Braga, Portugal
Site PT35110
Coimbra, Portugal
Site PT35111
Guimarães, Portugal
Site PT35102
Lisbon, Portugal
Site PT35106
Lisbon, Portugal
Site PT35105
Porto, Portugal
Site PT35108
Porto, Portugal
Site PT35104
Santa Maria da Feira, Portugal
Site PT35101
Setúbal, Portugal
Site PT35107
Vila Real, Portugal
Site RO40002
Bucharest, Romania
Site RO40005
Cluj-Napoca, Romania
Site RO40007
Cluj-Napoca, Romania
Site RO40003
Craiova, Romania
Site RO40004
Floreşti, Romania
Site RO40001
Iași, Romania
Site RO40006
Iași, Romania
Site RO40008
Timișoara, Romania
Site KR82002
Daegu, South Korea
Site KR82006
Goyang-si, South Korea
Site KR82007
Gyeonggi-do, South Korea
Site KR82014
Incheon, South Korea
Site KR82008
Jeollanam-do, South Korea
Site KR82010
Jeonju, South Korea
Site KR82011
Seongnam-si, South Korea
Site KR82001
Seoul, South Korea
Site KR82003
Seoul, South Korea
Site KR82012
Seoul, South Korea
Site KR82013
Seoul, South Korea
Site KR82015
Seoul, South Korea
Site KR82009
Suwon, South Korea
Site ES34005
A Coruña, Spain
Site ES34006
Barcelona, Spain
Site ES34009
Barcelona, Spain
Site ES34010
Barcelona, Spain
Site ES34001
Elche, Spain
Site ES34002
Madrid, Spain
Site ES34003
Madrid, Spain
Site ES34008
Madrid, Spain
Site ES34013
Madrid, Spain
Site ES34011
Málaga, Spain
Site ES34004
Pamplona, Spain
Site ES34007
Valencia, Spain
Site ES34012
Valencia, Spain
Site TW88602
Kaohsiung City, Taiwan
Site TW88603
Taichung, Taiwan
Site TW88604
Taipei, Taiwan
Site TW88605
Tianan, Taiwan
Site TH66002
Bangkok, Thailand
Site TH66005
Bangkok, Thailand
Site TH66007
Bangkok, Thailand
Site TH66009
Bangkok, Thailand
Site TH66011
Laksi, Thailand
Site TH66001
Muang, Thailand
Site TH66003
Muang, Thailand
Site TH66006
Pathum Thani, Thailand
Site TH66010
Pathumwan, Thailand
Site TH66004
Songkhla, Thailand
Site TH66008
Vadhana, Thailand
Site TR90008
Pendik, Istanbul, Turkey (Türkiye)
Site TR90003
Atakum, Turkey (Türkiye)
Site TR90004
Balcalı, Turkey (Türkiye)
Site TR90012
Bornova, Turkey (Türkiye)
Site TR90001
Bursa, Turkey (Türkiye)
Site TR90002
Istanbul, Turkey (Türkiye)
Site TR90010
Istanbul, Turkey (Türkiye)
Site TR90015
Istanbul, Turkey (Türkiye)
Site TR90007
Konya, Turkey (Türkiye)
Site TR90013
Konyaalti, Turkey (Türkiye)
Site TR90011
Malatya, Turkey (Türkiye)
Site GB44002
Bristol, United Kingdom
Site GB44004
Cardiff, United Kingdom
Site GB44001
London, United Kingdom
Related Publications (2)
Shitara K, Shah MA, Lordick F, Bang YJ, Ilson D, Van Cutsem E, Enzinger P, Kim SS, Klempner SJ, Moran D, Park JW, Bhattacharya P, Ajani JA, Xu RH. Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary. Future Oncol. 2024;20(26):1861-1877. doi: 10.1080/14796694.2024.2342107. Epub 2024 May 24.
PMID: 38861294DERIVEDShah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, Lordick F, Van Cutsem E, Gallego Plazas J, Huang J, Shen L, Oh SC, Sunpaweravong P, Soo Hoo HF, Turk HM, Oh M, Park JW, Moran D, Bhattacharya P, Arozullah A, Xu RH. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023 Aug;29(8):2133-2141. doi: 10.1038/s41591-023-02465-7. Epub 2023 Jul 31.
PMID: 37524953DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Transparency
- Organization
- Astellas Pharma Global Development, Inc
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Global Development
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
August 24, 2018
First Posted
August 31, 2018
Study Start
November 28, 2018
Primary Completion
October 25, 2022
Study Completion (Estimated)
September 30, 2026
Last Updated
April 17, 2026
Results First Posted
January 27, 2025
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- 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.
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 products 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/.