Zolbetuximab for Metastatic gastroesophageal adenocarcinoma (CLDN18.2-positive)

Inclusion criteria

• {"criterion_text":"- At least 18 years of age at the time of signing the Informed Consent Form (ICF)"}
• {"criterion_text":"- WHO performance status 0 - 1"}
• {"criterion_text":"- Histologically proven metastatic gastroesophageal adenocarcinoma"}
• {"criterion_text":"- Pretreatment with one 1st line therapy according to SOC (+/- immunotherapy)"}
• {"criterion_text":"- If relapse while adjuvant (immune/chemo) therapy or within 6 months ending adjuvant therapy the adjuvant therapy is considered a first line therapy"}
• {"criterion_text":"- CLDN18.2-positive (defined as ≥75% of tumour cells showing moderate-to-strong membranous CLDN18.2 staining, as determined by immunohistochemistry using the VENTANA CLDN18 [43-14A] RxDx Assay."}
• {"criterion_text":"- Any PDL1 score"}
• {"criterion_text":"- Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner."}
• {"criterion_text":"- Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures."}

Exclusion criteria

• {"criterion_text":"- Metastatic squamous cell cancer of the esophagus"}
• {"criterion_text":"- Absolute contra-indication for anti-VEGF inhibitors (tumour perforation, active proteinuria, recent stroke, myocardial infarction, acute arterial thrombosis, active wound problem)"}
• {"criterion_text":"- Other active malignancy"}
• {"criterion_text":"- Pretreatment with Zolbetuximab or other anti-CLDN18.2 direct therapy in first line setting once available"}
• {"criterion_text":"- Known hypersensitivity to the active substance Zolbetuximab or to any of the excipients [(Arginine, Phosphoric acid (E 338), Sucrose, Polysorbate 80 (E 433)]"}
• {"criterion_text":"- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive"}
• {"criterion_text":"- Participation in another interventional Trial with an investigational medicinal product (IMP) or device"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is OS (overall survival), which is defined as the time from the date of signature of informed consent until death from any cause. Patients starting a subsequent line of treatment after study discontinuation will not be censored for survival at the start of this subsequent treatment. Subjects who are still alive at the time of analysis will be censored at the last day known to be alive.","definition_or_measurement_approach":"Overall survival (OS): time from date of signature of informed consent until death from any cause. Patients starting subsequent anticancer treatment after study discontinuation will not be censored at start of that treatment. Alive subjects censored at last known alive date."}

Secondary endpoints

• {"endpoint_text":"- Secondary Endpoints PFS, which is defined as the time from the date of signature of informed consent until the date of radiological PD (per Response Evaluation Criteria in Solid Tumours [RECIST] 1.1) or death from any cause, whichever is earliest. Patients unprogressed at time of discontinuation for other causes, starting a subsequent line of treatment will be censored for progression at the start of this subsequent treatment.","definition_or_measurement_approach":"Progression-free survival (PFS): time from consent to radiological progressive disease per RECIST 1.1 or death; patients who start subsequent therapy without documented progression are censored at start of subsequent therapy."}
• {"endpoint_text":"- Safety will be assessed and reported continuously as per regulations.","definition_or_measurement_approach":"Safety: continuous assessment and reporting of adverse events as per regulatory requirements (no further measurement details provided)."}

Other endpoints

• {"endpoint_text":"- Efficacy of the triple combination compared to retrospective data (Progression free survival; Best overall response)","definition_or_measurement_approach":"Comparison to retrospective (historical) data using endpoints including PFS and Best Overall Response (BOR)."}
• {"endpoint_text":"- Safety will be assessed continuously","definition_or_measurement_approach":"Continuous safety monitoring (duplicative of secondary endpoint; no additional measurement details)."}
• {"endpoint_text":"- Exploratory quality of life during treatment","definition_or_measurement_approach":"Quality of life assessed during treatment (no specific instrument detailed here; QLQ-C30 documents present in file list)."}
• {"endpoint_text":"- Loss of CLDN18.2 positivity","definition_or_measurement_approach":"Assessment of change/loss of CLDN18.2 biomarker positivity (no specific assay timing detailed beyond baseline IHC definition)."}
• {"endpoint_text":"- Other exploratory biomarkers","definition_or_measurement_approach":"Assessment of additional exploratory biomarkers (no specific biomarkers or assays defined in the provided data)."}

Belgium

Earliest CTIS Part Ii Submission Date

04-09-2025

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

139

Number Of Sites

6

Number Of Participants

200

Primary sponsor

Full Name

UZ Leuven

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"Belgium","full_name":"Ziekenhuis Aan De Stroom","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Universitair Ziekenhuis Gent","duties_or_roles":"Relabeling and distribution IMP","organisation_type":"Hospital/Clinic/Other health care facility"}