Clinical Research Directory

Inclusion Criteria: * Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments. * Age ≥ 18 years on the day of signing the informed consent form. * Diagnosis of histologically confirmed gastroesophageal adenocarcinoma, either locally advanced unresectable or metastatic. * Locally assessed HER2-negative status and PD-L1 TAP score ≥5%. * No prior treatment for metastatic disease. Patients who received neoadjuvant, adjuvant or perioperative therapy and had disease recurrence beyond 6 months from the last dose are eligible. * Measurable and/or non-measurable evaluable disease according to RECIST v1.1. Note: The target lesion(s) selected have not been previously treated with local therapy OR The target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST v1.1. * ECOG Performance Status ≤ 1. * Life expectancy of at least 12 weeks in the opinion of the Investigator. * Adequate organ function as indicated by the following laboratory values during screening: a. Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection at screening for the following i. Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L ii. Platelets ≥ 100 x 10⁹/L iii. Hemoglobin ≥ 90 g/L b. Serum creatinine ≤ 1.5 x ULN (upper limit of normal) or estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73 sqm. c. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be \< 3 x ULN for patients with Gilberts syndrome). d. AST and/or ALT ≤ 2.5 x ULN, or ≤ 5 x ULN in case of liver metastases. e. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). * The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then 24-hour urine must be collected and must demonstrate \< 1000 mg of protein in 24 hours to allow participation in the study. * Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of amenorrhea, a single FSH measurement is insufficient. * Male subjects with female partners of childbearing potential and female subjects of childbearing potential must be willing to use adequate contraception as approved be the Investigator (barrier contraceptive measure or oral contraception), starting with the screening visit and ≥ 120 days after the last treatment dose of tislelizumab or ≥ 180 days after the last dose of chemotherapy or or ≥ 90 days after the last dose of ramucirumab. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. * Women must not be breastfeeding. * Archival tumor tissue (primary or metastatic) and blood samples are required for exploratory research at enrollment. Exclusion Criteria: * HER2-positive disease as determined by local standards. * Active leptomeningeal disease or uncontrolled brain metastases. Patients with treated, asymptomatic and radiologically stable brain metastases may be eligible according to protocol-defined criteria. * Active autoimmune disease or history of autoimmune disease that may relapse, except for protocol-specified conditions. * Any active malignancy within 3 years before enrollment, except for the cancer under investigation and protocol-specified malignancies treated with curative intent. * Any condition requiring systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days before the first study treatment, except as specified in the protocol. * Uncontrolled diabetes; Grade \>1 abnormalities in potassium, sodium, or corrected calcium despite standard medical management; or Grade ≥3 hypoalbuminemia within 14 days before enrollment. * Child-Pugh B or worse cirrhosis, or cirrhosis of any degree with a history of hepatic encephalopathy or clinically meaningful ascites. * History of interstitial lung disease, non-infectious pneumonitis or uncontrolled pulmonary disease, severe dyspnea at rest, or requirement for supplemental oxygen. * Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including protocol-defined recent severe infections or antibiotic treatment. * Known active HIV infection, unless protocol-defined criteria for controlled HIV infection are met. * Acute or chronic hepatitis B, except for patients meeting protocol-defined criteria. * Acute or chronic hepatitis C, except for patients meeting protocol-defined criteria. * Any major surgical procedure requiring general anesthesia within 28 days before the first study treatment. * Prior allogeneic stem cell transplantation or organ transplantation. * Evidence of bleeding diathesis or coagulopathy. * Significant bleeding episodes from the gastrointestinal tract, gastrointestinal perforation and/or fistulae within 3 months before the first study treatment. * Serious or non-healing wound, peptic ulcer, or bone fracture within 3 months before the first study treatment. * Ongoing chronic therapy with NSAIDs or other antiplatelet agents. Aspirin at doses up to 325 mg/day is permitted. * Protocol-defined cardiovascular risk factors, including recent cardiac chest pain, Grade ≥3 venous thromboembolism, significant vascular disease, myocardial infarction, NYHA Class III-IV heart failure, Grade ≥2 ventricular arrhythmia, QTc \>470 msec, cerebrovascular accident, or uncontrolled hypertension. * Known hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. * Complete DPYD deficiency. Additional restrictions based on uracilemia apply at German sites. * Known allergy or hypersensitivity to any components used in the ramucirumab or tislelizumab preparations, or contraindications to protocol chemotherapy according to local prescribing information. * Receipt of chemotherapy, immunotherapy, or investigational therapy within 14 days or 5 half-lives, whichever is shorter, before the first study drug administration. * Extended-field radiation within 4 weeks or limited-field radiation within 2 weeks before the first study treatment. * Receipt of any herbal medicine used to control cancer within 14 days before the first study drug administration. * Administration of a live vaccine within 4 weeks before the first dose of study treatment. * Underlying medical conditions, laboratory abnormalities, or alcohol or drug abuse or dependence that could interfere with study treatment administration, interpretation of toxicity or adverse events, or compliance with study procedures. * Concurrent participation in another therapeutic clinical study. PRE-RANDOMIZATION CHECKLIST * Patients must continue to meet all applicable Induction phase inclusion and exclusion criteria before randomization. * Completion of the 12-week Induction phase therapy. * No permanent discontinuation of any study treatment administered during the Induction phase. * CR, PR, or SD as best response to Induction therapy for patients with measurable disease, or non-PD for patients with non-measurable disease, according to RECIST v1.1. * No contraindications to receiving ramucirumab before randomization, including: * No arterial thromboembolism or Grade ≥3 venous thromboembolism within the previous 3 months. * No full-dose anticoagulant therapy with warfarin, LMWH, or NOACs within the previous 3 months. Low-dose prophylactic anticoagulants are permitted. * No significant gastrointestinal bleeding, gastrointestinal perforation, and/or fistulae within the previous 3 months. * No major surgical procedure requiring general anesthesia within 28 days before the first study treatment.