A Study to Assess the Antitumor Activity, Safety, Pharmacokinetics and Biomarkers of Zolbetuximab (IMAB362) in Participants With Claudin (CLDN) 18.2 Positive, Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma

This is a study to assess the antitumor activity of zolbetuximab, an Immunoglobulin (IgG1)
chimeric monoclonal antibody directed against CLDN18.2, in subjects with recurrent locally
advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors have
high or intermediate CLDN18.2 expression. For each cohort, the study consists of the
following periods: pre-screening; screening; treatment; and follow-up for disease
progression. In addition, there will be a survival follow-up period for Cohort 1 subjects
only.

Inclusion Criteria:

- Female subject eligible to participate if she is not pregnant 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 6 months after the final study drug administration

- 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 agree not to donate ova starting at screening and throughout the
study period, and for 6 months after the final study drug administration.

- 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 gastric or GEJ adenocarcinoma.

- Subject has radiographically-confirmed, locally advanced, unresectable or metastatic
disease within 28 days prior to the first dose of study treatment

- Subject has measurable disease according to RECIST 1.1 within 28 days prior to the
first dose of study treatment. For subjects with only 1 measurable lesion and prior
radiotherapy, the lesion must be outside the field of prior radiotherapy or must have
documented progression following radiation therapy.

- Subject's tumor sample has CLDN18.2 expression (defined as moderate to strong
membranous staining by central IHC testing) as follows:

- Cohorts 1A and 2: CLDN18.2 high expression (≥ 75% of tumor cells)

- Cohort 1B: CLDN18.2 high or intermediate expression (≥ 50% of tumor cells)

- Cohorts 1A and 1B Only:

- Subject has disease progression on or after at least 2 prior regimens for their
advanced disease, including fluoropyrimidine and platinum-containing
chemotherapy, and if appropriate, HER2/neu-targeted therapy.

- Cohort 2 Only:

- Subject has not received prior systemic anti-cancer therapy for their advanced
disease (subject may have received neoadjuvant and/or fluorouracil-containing
adjuvant chemotherapy as long as it has been completed ≥ 6 months before the
first dose of study treatment).

- Subject has a gastric or GEJ tumor that is HER2-negative as determined by local
or central testing.

- Cohorts 1A and 2:

- Subject must have an additional available tumor specimen collected within 3
months prior to the first dose of study treatment.

- Subject is an appropriate candidate for a tumor biopsy and is amenable to undergo
a tumor biopsy during the screening period (if applicable) and treatment period.

- Subject agrees not to participate in another interventional study while on treatment.

- Subject has ECOG performance status 0 to 1.

- Subject has predicted life expectancy ≥ 12 weeks.

- Subject must meet all of the following criteria on the laboratory tests that will be
analyzed centrally within 14 days prior to the first dose of study treatment. In case
of multiple laboratory data within this period, the most recent data should be used.

- Hemoglobin (Hgb) ≥ 9 g/dL (no transfusion within 7 days of start of study
treatment)

- 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)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
without liver metastases (≤ 5 x ULN if liver metastases are present)

- Estimated creatinine clearance ≥ 30 mL

- Prothrombin time (PT)/international normalized ratio (INR) and partial
thromboplastin time (PTT) ≤ 1.5 x ULN (except for patients receiving
anticoagulation therapy)

Exclusion Criteria:

- Subject has had 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 or contraindication to any
component of study treatment.

- Subject has received other investigational agents or devices concurrently or within 28
days prior to first dose of study treatment.

- Subject has received systemic immunosuppressive therapy, including systemic
corticosteroids 14 days prior to first dose of study treatment. 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) or a single dose of
systemic corticosteroids are allowed.

- Subject has gastric outlet syndrome or persistent recurrent vomiting.

- Subject with recent gastric bleeding or symptomatic subjects with proven gastric
ulcers that would preclude the subject from participation.

- Subject has known active central nervous system metastases and/or carcinomatous
meningitis.

- 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 [HBsAg])
or hepatitis C infection. Subjects who are negative for HBsAg, but hepatitis B core
antibody positive, will have a hepatitis B DNA test performed and if positive will be
excluded. Subjects with positive serology, but negative hepatitis C virus RNA test
results, are eligible.

- Subject has had within 6 months prior to first dose of study treatment any of the
following: unstable angina, myocardial infarction, ventricular arrhythmia requiring
intervention or hospitalization for heart failure.

- Subject has active infection requiring systemic therapy.

- Subject has active autoimmune disease that has required systemic treatment in the past
2 years.

- Subject has a clinically significant disease or co-morbidity that may adversely affect
the safe delivery of treatment within this study or make the subject unsuitable for
study participation.

- Subject has psychiatric illness or social situations that would preclude study
compliance.

- Subject has had a major surgical procedure ≤ 28 days before start of study treatment.

- Subject without complete recovery from a major surgical procedure ≤ 14 days
before start of study treatment.

- Subject has had radiotherapy ≤ 14 days (Cohort 1) and ≤ 28 days (Cohort 2) prior to
start of study treatment. Subject who received palliative radiotherapy to peripheral
bone metastases ≤ 14 days prior to start of study treatment and has recovered from all
acute toxicities is allowed.

- Subject has another past or active malignancy, which is likely to require treatment.

- Cohort 2 Only, subject has any of the following:

- Prior severe allergic reaction or intolerance to any component of mFOLFOX6
chemotherapeutics in this study

- Known dihydropyrimidine dehydrogenase deficiency

- Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the
sole neurological abnormality does not render the subject ineligible).

- Sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if
present, should be stable or improving.

- History of clinically significant ventricular arrhymias (i.e. sustained
ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)

- QTc interval >450 msec for male subjects; QTc interval >470 for female subjects

- History or family history of congenital long QT syndrome

- Cardiac arrhymias requiring anti-arrhythmic medications (Subjects with rate
controlled atrial fibrillation for > 1 month prior to first dose of study
treatment are eligible)