Inclusion Criteria:
* Participant has histologically confirmed gastric or GEJ adenocarcinoma.
* Participant has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to enrollment.
* Participant has radiologically evaluable disease (measurable and/or non measurable) according to RECIST 1.1, per investigator assessment, ≤ 28 days prior to enrollment. For participants with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
* Participant has ECOG performance status 0 or 1.
* Participant has predicted life expectancy ≥ 12 weeks.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a woman of childbearing potential (WOCBP).
* WOCBP who has a negative urine or serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent through 9 months after the final administration of oxaliplatin 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 9 months after the final administration of oxaliplatin and for 6 months after 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 final investigational study intervention administration.
* Male participant must not donate sperm during the treatment period and for 6 months after final investigational study intervention administration.
* The participant or legally authorized representative has provided informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.
* Participant's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by local immunohistochemistry testing.
* Participant has a human epidermal growth factor receptor 2 (HER2)-negative tumor as determined by local testing on a gastric or GEJ tumor specimen.
* Participant must meet all of the criteria based on the locally analyzed laboratory tests collected within 14 days prior to enrollment. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study.
Exclusion Criteria:
* Participant has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, mFOLFOX6 or CAPOX.
* Participant has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
* 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 exclude the participant from participation.
* Participant has a known history of a positive test for human immunodeficiency virus infection or known active hepatitis B (positive hepatitis B surface antigen \[HBsAg\]) or 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 positive, an hepatitis B virus 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 are eligible.
* Participants treated for HCV with undetectable viral load results are eligible.
* Participant has an active autoimmune disease that has required systemic treatment within the past 3 months prior to enrollment.
* Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to enrollment.
* 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 enrollment;
* History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes);
* QT corrected (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 arterial fibrillation for \> 1 month prior to enrollment are eligible.)
* Participant has history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
* Participant has known peripheral sensory neuropathy \> grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
* Participant has had a major surgical procedure ≤ 28 days before enrollment and has not completely recovered from the surgical procedure ≤ 14 days before enrollment.
* Participant has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, participant 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 enrollment.
* Participant has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to enrollment and has not recovered from any related toxicity. Palliative radiotherapy is allowed and must be completed \> 14 days prior to enrollment.
* Participant has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to enrollment.
* Participant has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to enrollment. 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 eligible.
* Participant has received any investigational therapy within 28 days prior to enrollment.
* Participant has any condition, which makes the participant unsuitable for study participation.
* Participant has another malignancy for which treatment is required.
* 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.
