ZOLBETUXIMAB for Gastric adenocarcinoma | Gastroesophageal junction adenocarcinoma

Inclusion criteria

• {"criterion_text":"-1.Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures.\n-10. Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.\n-11. Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.\n-12. Subject has radiologically evaluable disease (measurable and/or non-measurable) 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.\n-13. Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.\n-14. Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.\n-15. Subject has ECOG performance status 0 or 1.\n-16. Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.\n-\"17. 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 (ANC) ≥ 1.5x109/L c. Platelets ≥ 100x109/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 (AST) and alanine aminotransferase (ALT) ≤ 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 (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)\"\n-2. 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\n-3. A 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 (βhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies: - Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3 Contraception Requirements] OR - 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.\n-4. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.\n-5. Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs\n-6. A male subject with female partner(s) of childbearing potential: - must agree to use contraception as detailed in [Appendix 12.3 Contraception Requirements] during the treatment period and for 6 months after the final study treatment administration.\n-7. A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.\n-8. Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study treatment administration.\n-9. Subject agrees not to participate in another interventional study while receiving study drug in present study."}

Exclusion criteria

• {"criterion_text":"-1. 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.\n-10. Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.\n-11. Per investigator judgment, subject has significant gastric bleeding and/or untreated gastric ulcers that exclude the subject from participation.\n-\"12. 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 virus (HCV) serology but negative HCV RNA test are eligible. c. Subjects treated for HCV with undetectable viral load results are eligible.\"\n-13. Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.\n-14. Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.\n-15. Subject has significant cardiovascular disease, including any of the following: a. Congestive heart failure (defined as New York Heart Association [NYHA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), 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 Pointes); c. QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects; d. History or family history of congenital long QT syndrome e. Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible.)\n-16. Subject has history of central nervous system (CNS) metastases and/or carcinomatous meningitis from gastric/GEJ cancer.\n-\"17. Subject has known peripheral sensory neuropathy > grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality\"\n-18. Subject has had a major surgical procedure ≤ 28 days prior to randomization. a. Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.\n-19. Subject has psychiatric illness or social situations that would preclude study compliance, per investigator judgment\n-2. 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\n-20. Subject has another malignancy for which treatment is required per investigator's clinical judgment.\n-21. 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 in the opinion of the investigator.\n-3. Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to randomization.\n-4. 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 is eligible.\n-5. Subject has received other investigational agents or devices within 28 days prior to randomization.\n-6. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.\n-7. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment. 8. Subject has prior severe allergic reaction or intolerance to any component of CAPOX.\n-8. Subject has prior severe allergic reaction or intolerance to any component of CAPOX.\n-9. Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)"}

Primary endpoints

• {"endpoint_text":"-The primary endpoint is progression free survival (PFS), defined as the time from the date of randomization until the date of radiological progressive disease (PD) per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) by independent review committee (IRC) or death from any cause, whichever is earliest.","definition_or_measurement_approach":"Time from randomization to radiological PD per RECIST 1.1 assessed by independent review committee (IRC), or death from any cause, whichever occurs first."}

Secondary endpoints

• {"endpoint_text":"-OS, defined as the time from the date of randomization until the date of death from any cause","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"-\"Time to confirmed deterioration (TTCD) using the PF, OG25-Pain and GHS/QoL scores as measured by EORTC QLQ-C30 and QLQ-OG25 plus STO22 Belching subscale. TTCD is defined as time to first confirmed deterioration, i.e., time from randomization to first clinically meaningful deterioration that is confirmed at the next scheduled visit.\"","definition_or_measurement_approach":"Time from randomization to first clinically meaningful deterioration in PF, OG25-Pain or GHS/QoL scores as measured by specified EORTC questionnaires, confirmed at the next scheduled visit."}
• {"endpoint_text":"-ORR, defined as the proportion of subjects who have a best overall response of complete response (CR) or partial response (PR) as assessed by IRC per RECIST 1.1","definition_or_measurement_approach":"Proportion of subjects with best overall response of CR or PR assessed by IRC per RECIST 1.1."}
• {"endpoint_text":"-DOR, defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest","definition_or_measurement_approach":"Time from first documented CR/PR to radiological PD per RECIST 1.1 by IRC or death from any cause."}
• {"endpoint_text":"-Safety and tolerability, as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status","definition_or_measurement_approach":"Assessment of adverse events, labs, vital signs, ECGs and ECOG as safety/tolerability measures."}
• {"endpoint_text":"-HRQoL using the additional parameters as measured by EORTC QLQC30, QLQ-OG25 plus STO22 Belching subscale, GP and EQ5D-5L questionnaires","definition_or_measurement_approach":"Health-related quality of life measured by EORTC QLQ-C30, QLQ-OG25 (+ STO22 Belching), Global Pain and EQ-5D-5L instruments."}
• {"endpoint_text":"-Pharmacokinetics of zolbetuximab, Ctrough","definition_or_measurement_approach":"Pharmacokinetic sampling to determine trough concentrations (Ctrough) of zolbetuximab."}
• {"endpoint_text":"-Immunogenicity of zolbetuximab as measured by the frequency of antidrug-antibody (ADA) positive subject","definition_or_measurement_approach":"Frequency of subjects positive for anti-drug antibodies (ADA) measured per immunogenicity assays."}

Spain

Latest Decision Or Authorization Date

11-03-2025

Number Of Sites

6

Number Of Participants

57

Romania

Latest Decision Or Authorization Date

07-08-2024

Number Of Sites

2

Number Of Participants

25

Portugal

Latest Decision Or Authorization Date

14-08-2024

Number Of Sites

6

Number Of Participants

26

Primary sponsor

Full Name

Astellas Pharma Global Development Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

IVRS treatment randomisation

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties code: 5

Name

Almac Clinical Services Limited

Responsibilities

Clinical Supply Chain Support IP management

Name

Fortrea Inc.

Responsibilities

Statistical programming and Data management

Name

Labcorp Early Development Laboratories Inc.

Responsibilities

Biorepository

Name

Medidata Solutions Inc.

Responsibilities

sponsorDuties code: 7 (data platform/services)

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"IVRS treatment randomisation (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: 4,5","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Shin Nippon Biomedical Laboratories Ltd.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"biorepository (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Clinical Supply Chain Support IP management (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties code: 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"Clinical Supply Chain Support IP management (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Other - provision of CLND 18.2 assay test kits (sponsorDuties code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC (duplicate entry)","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Statistical programming Data management (sponsorDuties codes 10,15)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}