LUCERNA: A treatment that combines a targeted antibody therapy, another type of immunotherapy, and chemotherapy for people with advanced stomach or gastro-oesophageal junction cancer that cannot be removed by surgery or has spread, and has certain markers: CLDN18.2-positive, PD-L1-positive and HER2-negative.A Phase 3, Double-blind, Randomized Study of Zolbetuximab in Combination With Pembrolizumab and Chemotherapy (CAPOX or mFOLFOX6) in First-line Treatment of Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma in Participants Whose Tumors Are HER2-negative, Claudin (CLDN) 18.2-positive and Programmed Death-ligand 1 (PD-L1)-Positive

Exclusion

• Participant has prior severe allergic reaction or intolerance to zolbetuximab or other monoclonal antibodies, pembrolizumab, mFOLFOX6 or CAPOX.
• 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 would preclude the participant from participation.
• Participant has unresolved pneumonitis or history of non-infectious pneumonitis such as immune-related pneumonitis, radiation induced pneumonitis.
• Participant has history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.

• Participant has a known history of a positive test for Human Immunodeficiency Virus (HIV) infection or known active Hepatitis B Surface Antigen (positive HBsAg) or hepatitis 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 (HBcAb) positive, a hepatitis B 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 results are eligible.
  • Participants treated for HCV with undetectable viral load results are eligible.
• Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
• Participant has active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
• Participant has a clinically significant disease or comorbidity that may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
• Participant has another malignancy for which treatment is required.
• Participant has known Dihydropyrimidine Dehydrogenase (DPD) deficiency (screening for DPD deficiency should be conducted per local requirements).
• Participant has known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the participant ineligible).
• Participant has sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving.

• 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 randomization.
  • History of clinically significant ventricular arrhythmias (i.e., sustained; ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).
  • 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 atrial fibrillation for > 1 month prior to randomization are eligible).
• Participant has ongoing or previous interstitial lung disease, active diverticulitis or peptic ulcerative disease, or solid organ or stem cell transplant or other uncontrolled or clinically significant medical disorders.
• Participant has type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed.
• Participant has received prior systemic chemotherapy and/or immunotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, except for a maximum of 1 treatment course of mFOLFOX6 (day 1 to 14) or CAPOX (day 1 to 21) with or without pembrolizumab. However, participants 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. Participant may have received treatment with herbal medications that have known antitumor activity > 28 days prior to randomization.
• Participant has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to randomization. Participants 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.
• Participant has had major surgical procedure ≤ 28 days before randomization and has not completely recovered from the surgical procedure ≤ 14 days before randomization.
• Participant 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. Palliative radiotherapy is allowed and must be completed > 14 days prior to randomization.
• Participant has received prior CLDN18.2 agents.
• Participant received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Participant has received other investigational agents or devices concurrently or within 28 days prior to randomization or within 5 half-lives of the investigational medicinal product (IMP), whichever is longer.
• Participant has any condition which makes the participant unsuitable for study participation.
• 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.
• Treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to randomization or within 5 half-lives of the IMP, whichever is shorter, is strictly prohibited.
• Pernicious anemia or other anemias due to vitamin B12 deficiency.
• Participant has a known history of a positive test for tuberculosis or known active tuberculosis infection. NOTE: Screening for these infections should be conducted per local requirements.