ZAP: This phase II trial is evaluating an immunotherapy (zolbetuximab) in combination with chemotherapy (gemcitabine and nab-paclitaxel) in patients who have pancreatic cancer that has spread to other parts of the bodyA Phase 2, Open-Label, Randomized Study to Assess the Antitumor Activity and Safety of Zolbetuximab (IMAB362) in Combination With Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects With Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma

Exclusion

• Subject has received other investigational treatment within 28 days prior to randomization.
• Subject has received radiotherapy for metastatic pancreatic 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. Subject 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 prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
• Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.

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

  1. For subjects who are negative for HBs Ag, but hepatitis B core antibody positive, a hepatitis B virus DNA test will be performed and if positive, the subject will be excluded.
  2. Subjects with positive hepatitis C serology but negative hepatitis C virus RNA test results are eligible.
  3. Subjects treated for hepatitis C with undetectable viral load results are eligible.
• 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 the past 3 months prior to randomization.
• Subject has active infection requiring systemic therapy that has not completely resolved 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 or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident 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;
  • Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization.)
• Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma.
• Subject has known peripheral sensory neuropathy ≥ Grade 2 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 without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
• 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 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.