TriangleNCT03504397 · CITED IN SOURCE DOCUMENTS
A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-05-04
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. 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 gastric 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 study doctor will switch study treatment in those countries to the licensed zolbetuximab. If this happens, people taking part in those countries will leave this study and receive licensed zolbetuximab. The main aim of the study is to check if zolbetuximab and chemotherapy can prevent or delay the worsening of people's gastric cancer and GEJ cancer compared to placebo and chemotherapy. Adults with advanced 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 1 of the study 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. People will have 4 infusions in 6-week (42-day) cycles as follows: * Zolbetuximab or placebo - 2 infusions in a cycle. * Chemotherapy (called modified FOLFOX6 or mFOLFOX6) - 3 infusions in a cycle. The first infusion is combined with zolbetuximab or placebo on day 1 of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will receive mFOLFOX6 for up to 6 months (4 study treatment cycles). After the 6 months people may receive chemotherapy containing folinic acid and fluorouracil instead of mFOLFOX6. People may receive folinic acid and fluorouracil chemotherapy for more than 6 months, or 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 study treatment. The study doctors will check if people had any medical problems from taking 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 after they stop their study treatment. People who start treatment with licensed zolbetuximab or mFOLFOX6 outside of this study will not need to visit the clinic. People will be asked about any medical problems and will have a health check. People will visit the clinic at 1 month after they stop their study treatment. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. People 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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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression Free Survival (PFS)
Overall Survival (OS)
Time to Confirmed Deterioration (TTCD) Using Physical Functioning (PF) as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30)
Time to Confirmed Deterioration (TTCD) Using Oesophago-gastric Questionnaire (OG25) on Abdominal Pain and Discomfort as Measured by EORTC QLQ-OG25
Time to Confirmed Deterioration (TTCD) Using Global Health Status as Measured by EORTC QLQ-C30
Objective Response Rate (ORR)
Duration Of Response (DOR)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Change From Baseline in Health Related Quality of Life (HRQoL) Measured by the EORTC-QLQ-C30 Questionnaire
Change From Baseline in HRQoL Measured by the QLQ-OG25 Questionnaire
Change From Baseline in HRQoL Measured by Global Pain (GP)
Change From Baseline in HRQoL Measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) Questionnaire
Pharmacokinetics (PK) of Zolbetuximab in Serum: Trough Concentration (Ctrough)
Number of Participants With Anti-drug Antibodies (ADA)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are eligible) and at least one of the following conditions applies: * Not a woman of child-bearing potential (WOCBP) OR * WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 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 drug 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 sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration. * Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug 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 drug 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 immunohistochemistry (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 to 1. * Subject has predicted life expectancy ≥ 12 weeks. * Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility. * Hemoglobin (Hgb) ≥ 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL. * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Albumin ≥ 2.5 g/dL * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or \< 3.0 x ULN if liver metastases are present) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present) * Estimated creatinine clearance ≥ 30 mL/min * Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy) Exclusion Criteria: * 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 may have received treatment with herbal medications that have known antitumor activity \> 28 days 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 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 mFOLFOX6. * Subject has known dihydropyrimidine dehydrogenase 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 would 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. * Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization. * Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization. * Subject 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, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) 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 subjects; QTc interval \> 470 msec for female subjects * History or family history of congenital long QT syndrome * Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for \> 1 month prior to randomization are eligible). * Subject has a history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer. * Subject has known peripheral sensory neuropathy \> Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality. * Subject has had a major surgical procedure ≤ 28 days prior to randomization. * Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization. * Subject has psychiatric illness or social situations that would preclude study compliance. * Subject has another malignancy for which treatment is required. * Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m\^2) on cycle1 day1(C1D1) followed by 600 mg/m\^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85mg/m\^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days.
- intervention Names
- Drug: zolbetuximab
- Drug: oxaliplatin
- Drug: folinic acid
- Drug: fluorouracil
- label
- mFOLFOX6 + Zolbetuximab
- type
- EXPERIMENTAL
- description
- Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days.
- intervention Names
- Drug: placebo
- Drug: oxaliplatin
- Drug: folinic acid
- Drug: fluorouracil
- label
- Placebo plus mFOLFOX6
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- mFOLFOX6 + Zolbetuximab
- description
- Participants 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. Each cycle was approximately 42 days.
- name
- zolbetuximab
- other Names
- IMAB362
- type
- DRUG
- arm Group Labels
- Placebo plus mFOLFOX6
- description
- Participants 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 met study treatment discontinuation criteria. Each cycle was approximately 42 days.
- name
- placebo
- type
- DRUG
- arm Group Labels
- Placebo plus mFOLFOX6
- mFOLFOX6 + Zolbetuximab
- description
- Participants received up to 12 treatments of oxaliplatin administered 85 mg/m\^2 IV infusion over 2 hours) on Days 1, 15 and 29 of each cycle.. A maximum of 12 doses of oxaliplatin was permitted. Each cycle was approximately 42 days.
- name
- oxaliplatin
- type
- DRUG
- arm Group Labels
- Placebo plus mFOLFOX6
- mFOLFOX6 + Zolbetuximab
- description
- Participants received up to 12 treatments of folinic acid administered 400 mg/m\^2 IV infusion over 2 hours 4 or more cycles on Days 1, 15 and 29 of each cycle. participants could continue to receive folinic acid on Days 1, 15 and 29 of each cycle at the investigator's discretion or until the participant met the study treatment discontinuation criteria. Each cycle was approximately 42 days.
- name
- folinic acid
- type
- DRUG
- arm Group Labels
- Placebo plus mFOLFOX6
- mFOLFOX6 + Zolbetuximab
- description
- Participants received up to 12 treatments of 5-fluorouracil over 4 or more cycles administered by IV bolus 400 mg/m\^2 over 5 to 15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Participants could continue to receive 5-fluorouracil on Days 1, 15 and 29 of each cycle at the investigator's discretion or until the participant met the study treatment discontinuation criteria. Each cycle was approximately 42 days.
- name
- fluorouracil
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 565
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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 (KM) estimates was used.
- measure
- Progression Free Survival (PFS)
- time Frame
- From date of randomization until the date of first documented radiological progression or date of death from any cause, whichever occurred first (up to 62 months and 18 days)
- secondary Outcomes
- description
- OS was defined as the time from the date of randomization until the date of death from any cause. Kaplan-Meier estimates was used.
- measure
- Overall Survival (OS)
- time Frame
- From the date of randomization until 62 months and 18 days
- description
- TTCD: time from randomization to first clinically meaning full deterioration (CMD) that was confirmed at next scheduled visit. EORTC-QLQ-C30 was a 30-item cancer-specific instrument consisting of 5 functional scales (physical,role,emotional,social \& cognitive), 9 symptom scales (fatigue, nausea/vomiting,general pain,dyspnea,insomnia,appetite loss,constipation,diarrhea,financial difficulties) \& global health status scale. Most items were scored 1(not at all) to 4(very much) except for items contributing to global health status/QoL, which were scored 1(very poor) to 7(excellent). All raw domain scores were linearly transformed to 0-100scale with higher scores on symptoms indicate worse health state. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of -13. This was derived from an Exit Survey conducted using Patient Global Impression of Severity/Change(PGIS/PGIC) questionnaires as an anchor for estimating meaningful change. KM estimates was used.
- measure
- Time to Confirmed Deterioration (TTCD) Using Physical Functioning (PF) as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30)
- time Frame
- From the date of randomization until 62 months and 18 days
- description
- TTCD: time from randomization to first CMD that was confirmed at next scheduled visit. EORTC QLQ-OG25 evaluated gastric and GEJ cancer specific symptoms. A 25 item instrument with 6 scales: dysphagia (3 items), eating restrictions (4 ), reflux (2), odynophagia (2), pain and discomfort (2), anxiety (2), as well as 10 single items: eating in front of others, dry mouth, trouble with taste, body image, trouble swallowing saliva, choked when swallowing, trouble with coughing, trouble talking, weight and hair loss. Items were scored:1: not at all; 2: a little, 3: quite a bit, 4: very much, and were transformed linearly into scores (0 to 100) with higher scores indicating worse symptoms. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of 16.67. This was derived from an Exit Survey conducted to use PGIS/PGIC questionnaires as an anchor for estimating the meaningful change. KM estimates was used.
- measure
- Time to Confirmed Deterioration (TTCD) Using Oesophago-gastric Questionnaire (OG25) on Abdominal Pain and Discomfort as Measured by EORTC QLQ-OG25
- time Frame
- From the date of randomization until 62 months and 18 days
- description
- TTCD: time from randomization to first CMD that was confirmed at the next scheduled visit. The EORTC-QLQ-C30 was a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items were scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which were scored 1 ("very poor") to 7 ("excellent"). All raw domain scores were linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of -10. This was derived from an Exit Survey conducted to use PGIS/PGIC questionnaires as an anchor for estimating the meaningful change. KM estimates was used.
- measure
- Time to Confirmed Deterioration (TTCD) Using Global Health Status as Measured by EORTC QLQ-C30
- time Frame
- From the date of randomization until 62 months and 18 days
- description
- ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as was assessed by IRC per RECIST 1.1. CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.
- measure
- Objective Response Rate (ORR)
- time Frame
- From the date of randomization until 62 months and 18 days
- description
- DOR was defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.PD was defined as development of new, or progression of existing metastases to the primary cancer under the sudy.
- measure
- Duration Of Response (DOR)
- time Frame
- From date of first response (CR/PR) until 62 months and 18 day
- description
- An Adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not have to have a causal relationship with this treatment. 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 a medicinal product, whether or notconsidered related to the medicinal product. TEAE defined as an AE observed after starting administration of the study drug through 30 days after the last dose.
- measure
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)
- time Frame
- From first dose until 62 months and 18 days
- description
- ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.
- measure
- Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
- time Frame
- Baseline, cycle (C) 1 day (D) 22, D1 and D22 of C2 through C39
- description
- The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state.
- measure
- Change From Baseline in Health Related Quality of Life (HRQoL) Measured by the EORTC-QLQ-C30 Questionnaire
- time Frame
- Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
- description
- The EORTC-QLQ-OG25 consists of a 25-item instrument that evaluates gastric and GEJ cancer-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion. This module consists of 6 scales: dysphagia (3 items), eating restrictions (4 items), reflux (2 items), odynophagia (2 items), pain and discomfort (2 items) and anxiety (2 items), as well as 10 single items: eating in front of others, dry mouth, trouble with taste, body image, trouble swallowing saliva, choked when swallowing, trouble with coughing, trouble talking, weight loss and hair loss. All questions have four response alternatives (1:not at all; 2:a little, 3:quite a bit, 4:very much). Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 For symptom scales/items, higher scores indicate worse symptoms.
- measure
- Change From Baseline in HRQoL Measured by the QLQ-OG25 Questionnaire
- time Frame
- Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
- description
- The GP instrument is a single assessment of overall pain. Participants were assessed in global pain according to the following response categories: 1= no pain (anymore), 2 = less pain, 3 = no change and 4 = more pain.
- measure
- Change From Baseline in HRQoL Measured by Global Pain (GP)
- time Frame
- Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
- description
- EQ-5D-5L is a standardized instrument for use as a measure of health outcomes consisting of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale for health status.It was developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
- measure
- Change From Baseline in HRQoL Measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) Questionnaire
- time Frame
- Baseline, C1D22, D1 and D22 of C2 through C25, C26D1, C27D1,C28D1 30 day follow up, 90 day follow up
Full study description
- 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 gastroesophageal junction (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 gastric 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 study doctor will switch study treatment in those countries to the licensed zolbetuximab. If this happens, people taking part in those countries will leave this study and receive licensed zolbetuximab. The main aim of the study is to check if zolbetuximab and chemotherapy can prevent or delay the worsening of people's gastric cancer and GEJ cancer compared to placebo and chemotherapy. Adults with advanced 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 1 of the study 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. People will have 4 infusions in 6-week (42-day) cycles as follows: * Zolbetuximab or placebo - 2 infusions in a cycle. * Chemotherapy (called modified FOLFOX6 or mFOLFOX6) - 3 infusions in a cycle. The first infusion is combined with zolbetuximab or placebo on day 1 of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will receive mFOLFOX6 for up to 6 months (4 study treatment cycles). After the 6 months people may receive chemotherapy containing folinic acid and fluorouracil instead of mFOLFOX6. People may receive folinic acid and fluorouracil chemotherapy for more than 6 months, or 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 study treatment. The study doctors will check if people had any medical problems from taking 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 after they stop their study treatment. People who start treatment with licensed zolbetuximab or mFOLFOX6 outside of this study will not need to visit the clinic. People will be asked about any medical problems and will have a health check. People will visit the clinic at 1 month after they stop their study treatment. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. People 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
- After the marketing approval in Japan on 26 Mar 2024, this study continued as "post marketing clinical study" in Japan. In the rest of the countries which participated in this study, this study continued as clinical study.
Source references
- references
- citation
- Yamaguchi K, Shoji H, Yasui H, Oki E, Sakai D, Hamaguchi T, Tsuji A, Oshima T, Tsuda M, Minashi K, Yang J, Guerrero A, Ueno Y, Matsangou M, Gourgioti G, Nakanishi Y, Furuki S, Kuwamoto K, Yamada S, Shitara K. Zolbetuximab plus chemotherapy in Japanese patients with claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma: a combined subgroup analysis of the phase 3 SPOTLIGHT and GLOW trials. Gastric Cancer. 2026 Jul;29(4):777-787. doi: 10.1007/s10120-026-01738-7. Epub 2026 May 7.
- pmid
- 42095986
- type
- DERIVED
- citation
- Stratton SP, Pang L, Pugh J, Kouzova M, Baldwin D, McDonald J, Lawrence-Glaze R, Moran S, Guerrero A, Moran D. Analytical and Clinical Performance of the VENTANA CLDN18 (43-14A) RxDx Assay in Gastric and Gastroesophageal Junction Adenocarcinoma Tissue Samples in SPOTLIGHT and GLOW. Mod Pathol. 2025 Dec;38(12):100844. doi: 10.1016/j.modpat.2025.100844. Epub 2025 Jul 16.
- pmid
- 40680855
- type
- DERIVED
- citation
- 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
- 38861294
- type
- DERIVED
- citation
- Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023 May 20;401(10389):1655-1668. doi: 10.1016/S0140-6736(23)00620-7. Epub 2023 Apr 15.
- pmid
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- type
- DERIVED
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- Updated: February 21, 2025
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Preserved source evidence · Not medical advice