A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer

Inclusion Criteria:

• A female subject is eligible to participate if she is not pregnant or lactating andat 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 treatmentperiod and for at least 6 months after the final study drug administration.

• Female subject must agree not to breastfeed starting at screening and throughout thestudy period, and for 6 months after the final study drug administration.

• Female subject must not donate ova starting at screening and throughout the studyperiod, and for 6 months after the final study drug administration.

• A male subject with female partner(s) of child-bearing potential must agree to usecontraception during the treatment period and for at least 6 months after the finalstudy drug administration.

• A male subject must not donate sperm during the treatment period and for at least 6months after the final study drug administration.

• Male subject with a pregnant or breastfeeding partner(s) must agree to remainabstinent or use a condom for the duration of the pregnancy or time partner isbreastfeeding throughout the study period and for 6 months after the final studydrug administration.

• Subject agrees not to participate in other interventional studies while receivingstudy drug in present study.

• Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.

• Subjects must have metastatic pancreatic adenocarcinoma that has not been previouslytreated with chemotherapy.

• Prior treatment with fluorouracil (5-FU) or GEM administered as a radiationsensitizer during and up to 4 weeks after radiation therapy is allowed

• If a subject received adjuvant therapy, tumor recurrence or disease progressionmust have occurred at least 6 months after completing the last dose of theadjuvant therapy.

• Subjects whose disease progressed on prior treatment with Nab-P and GEM are noteligible.

• Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1within 28 days prior to randomization. For subjects with only 1 measurable lesionand prior radiotherapy, the lesion must be outside the field of prior radiotherapyor must have documented progression following radiation therapy.

• Subject's tumor sample has CLDN18.2 expression in ≥ 75% of tumor cells demonstratingmoderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing

• Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Subject has predicted life expectancy ≥ 12 weeks.

• Subject must meet all of the following criteria based on the laboratory tests thatwill be collected within 14 days prior to randomization. In case of multiplelaboratory data within this period, the most recent data should be used.

• Hemoglobin ≥ 9 g/dl (no transfusion within 14 days of start of study treatment)

• Absolute neutrophil count ≥ 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 ULNwithout liver metastases (≤ 5 x ULN if liver metastases are present)

• Estimated creatinine clearance ≥ 30 mL/min

• Prothrombin time/international normalized ratio (INR) and partialthromboplastin time ≤ 1.5 x ULN (except for subjects receiving anticoagulationtherapy)

Exclusion Criteria:

• Subject has received other investigational treatment within 28 days prior torandomization.

• Subject has received radiotherapy for metastatic pancreatic adenocarcinoma ≤ 14 daysprior to randomization and has not recovered from any related toxicity.

• Subject has received systemic immunosuppressive therapy, including systemiccorticosteroids within 14 days prior to randomization. Subject using a physiologicreplacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per dayof hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose ofsystemic corticosteroids or receiving systemic corticosteroids as premedication forradiologic imaging contrast use are allowed.

• Subject has prior severe allergic reaction or intolerance to known ingredients ofzolbetuximab or other monoclonal antibody, including humanized or chimericantibodies.

• Subject has known immediate or delayed hypersensitivity, intolerance orcontraindication to any component of study treatment.

• Subject has a known history of a positive test for human immunodeficiency virusinfection or known active hepatitis B (positive HBs antigen [Ag]) or hepatitis Cinfection. NOTE: Screening for these infections should be conducted per localrequirements.

1. For subjects who are negative for HBs Ag, but hepatitis B core antibodypositive, a hepatitis B virus DNA test will be performed and if positive, thesubject will be excluded.

2. Subjects with positive hepatitis C serology but negative hepatitis C virus RNAtest results are eligible.

3. Subjects treated for hepatitis C with undetectable viral load results areeligible.

• Subject has a history of interstitial pneumonia or pulmonary fibrosis.

• Subject has pleural effusion or ascites ≥ Grade 3.

• Subject has an active autoimmune disease that has required systemic treatment in thepast 3 months prior to randomization.

• Subject has active infection requiring systemic therapy that has not completelyresolved per investigator judgment within 7 days prior to randomization.

• Subject has significant cardiovascular disease, including:

• Congestive heart failure (defined as New York Heart Association Class III orIV), myocardial infarction, unstable angina, coronary angioplasty, coronarystenting, coronary artery bypass graft, cerebrovascular accident orhypertensive crisis within 6 months prior to randomization;

• History of clinically significant ventricular arrhythmias (i.e., sustainedventricular tachycardia, ventricular fibrillation or Torsades de Pointes);

• QTc interval > 450 msec for male subjects; QTc interval > 470 msec for femalesubjects;

• Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with ratecontrolled atrial fibrillation for > 1 month prior to randomization.)

• Subject has a history of central nervous system metastases and/or carcinomatousmeningitis from pancreatic adenocarcinoma.

• Subject has known peripheral sensory neuropathy ≥ Grade 2 unless the absence of deeptendon reflexes is the sole neurological abnormality.

• Subject has had a major surgical procedure ≤ 28 days prior to randomization.

• Subject without complete recovery from a major surgical procedure ≤ 14 days prior torandomization.

• 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 co-morbid condition that interfereswith the ability of the subject to participate in the study, which places thesubject at undue risk or complicates the interpretation of data.