Spotlight: This phase III trial is comparing treatment with an intravenous drug (Zolbetuximab) and chemotherapy (mFOLFOX6), versus chemotherapy alone, in patients with CLDN, HER2- advanced or metastatic gastric or gastroesophageal junction cancerA Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Exclusion

• 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.