Phase II RAINSPOT: Zolbetuximab-Paclitaxel-Ramucirumab for CLDN18.2 Positive Gastro-esophageal Cancer

Inclusion Criteria: 1. At least 18 years of age at the time of ICF 2. WHO performance status 0 - 1 3. Histologically proven metastatic gastroesophageal adenocarcinoma 4. Pretreatment with one 1st line therapy according to SOC (+/- immunotherapy) 5. If relapse while adjuvant (immune/chemo) therapy or within 6 months ending adjuvant therapy the adjuvant therapy is considered a first line therapy 6. 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. 7. Any PDL1 score 8. Use of highly effective methods of birth control 9. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures. Exclusion Criteria: \- 1. Metastatic squamous cell cancer of the esophagus 2. Absolute contra-indication for anti-VEGF inhibitors (tumor perforation, active proteinuria, recent stroke, myocardial infarction, acute arterial thrombosis, active wound problem) 3. Other active malignancy 4. Pretreatment with Zolbetuximab or other anti-CLDN18.2 direct therapy in first line setting once available. 5\. Known hypersensitivity to the active substance Zolbetuximab or to any of the excipients \[(Arginine, Phosphoric acid (E 338), Sucrose, Polysorbate 80 (E 433)\] 6. 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 7. Participation in another interventional Trial with an investigational medicinal product (IMP) or device