A 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

Phase 1

Conditions: Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
MedDRA version: 20.0Level: PTClassification code: 10001150Term: Adenocarcinoma gastric Class: 100000004864
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2024-511365-11-00

Lead Sponsor: Astellas Pharma Global Development Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 537

Inclusion Criteria

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] Authorization for US sites) must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures, Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma, Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization, Subject has radiologically evaluable disease (measurable and/or nonmeasurable disease according to RECIST 1.1), per local assessment, = 28 days prior to randomization. For subjects with only 1 evaluable lesion and prior radiotherapy =3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy, Subject's tumor expresses CLDN18.2 in = 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing, Subject has a known HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor), Subject has ECOG performance status 0 to 1, Subject has predicted life expectancy ~12 weeks in the opinion of the investigator, Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility. a.Hemoglobin (Hgb) = 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb = 9 g/dL. b.Absolute neutrophil count = 1.5 x 109/L c.Platelets = 100 x 109/L d.Albumin = 2.5 g/dL e.Total bilirubin = 1.5 x upper limit of normal (ULN) without liver metastases (or < 3.0 x ULN if liver metastases are present) f.Aspartate aminotransferase and alanine aminotransferase = 2.5 x ULN without liver metastases (or = 5 x ULN if liver metastases are present) g.Estimated creatinine clearance = 30 mL/min h.Prothrombin time/international normalized ratio and partial thromboplastin time = 1.5 x ULN (except for subjects receiving anticoagulation therapy), Subject is considered an adult (e.g., = 18 years of age in the US) according to local regulation at the time of signing the informed consent, Subject agrees not to participate in another interventional study while on study treatment, Female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at Screening; female subjects with elevated serum beta human chorionic gonadotropin (ßhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies: a.Not a woman of childbearing potential (WOCBP) as defined in Appendix 12.3 Contraception Requirements OR b. WOCBP who agrees to follow the contraceptive guidance as defined in Appendix 12.3 Contraception Requirements throughout the treatment period and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs, Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after th

Exclusion Criteria

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 randomization, 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 (DPD). (NOTE: Screening for DPD deficiency should be conducted per local requirements), Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting, 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. a.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, per investigator judgment, Subject has another malignancy for which treatment is required per investigator's clinical judgment, Per investigator judgment, subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation, 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 in the opinion of the investigator, Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive HBs Ag) or C infection. NOTE: Screening for these infections should be conducted per local requirements. a.For subjects who are negative for HBs Ag, but HBc Ab positive, an HB DNA test will be performed and if positive, the subject will be excluded. b.Subjects with positive hepatitis C (HCV) serology, but negative HCV RNA test are eligible. c.Subjects treated with 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: a.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 or hypertensive crisis within 6 months prior to randomization. b.History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointesc. QTc interval > 450 msec for