locally advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.
Conditions
Interventions
Trial group:Iparomlimab and Tuvonralimab in Combination with Regorafenib and Chemotherapy:
1. Iparomlimab and Tuvonralimab: On Day 1 of each 21-day cycle, 5mg/kg via intravenous infusion until diseas
Capecitabine 1000mg/m^2 orally twice daily (morning and evening) from Day 1 to Day 14. Cycle length: 21 days.
SOX Regimen: Oxaliplatin 130mg/m^2 intravenous infusion on Day 1
S-1 40mg/m^2 orally twice daily from Day 1 to Day 14. Cycle length: 21 days.
Sponsors
Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntary participation in the study and signed informed consent form; 2. Age >18 years, any gender; 3. Histologically confirmed unresectable locally advanced or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma; 4. No prior systemic therapy for unresectable locally advanced or metastatic G/GEJ adenocarcinoma. Prior neoadjuvant and/or adjuvant therapy is permitted, provided all systemic treatments were completed at least 6 months before diagnosis of unresectable or metastatic disease; 5. PD-L1 Combined Positive Score (CPS) 3 months; 9. Adequate organ and bone marrow function: (1) Hematology: 1) Hemoglobin (HGB) >=90g/L 2) Absolute neutrophil count (ANC) >=1.5×10^9/L 3) Platelet count (PLT) >=80×10^9/L (2) Biochemistry: 1) AST and ALT =45mL/min (Cockcroft-Gault formula) 4) APTT <=1.5×ULN and INR or PT <=1.5×ULN (if not on anticoagulant therapy); 10. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days before enrollment and agree to use effective contraception during the study and for 8 weeks after the last dose of study drug; men must be surgically sterilized or agree to use effective contraception during the study and for 8 weeks after the last dose; 11. Willing and able to comply with follow-up until death, study completion, or study termination.
Exclusion criteria
Exclusion criteria: 1. Known HER2-positive patients (immunohistochemistry (IHC) 3+ or 2+ and fluorescence in situ hybridization HER2:CEP17 ratio >=2); 2. Concurrent other malignancies within 5 years before treatment, except adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, locally treated prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery (hormonal therapy for non-metastatic prostate cancer or breast cancer is allowed); 3. Known central nervous system metastases and/or carcinomatous meningitis; 4. Patients with severe cardiac, pulmonary, hepatic or renal dysfunction; 5. Patients with hypertension that cannot be controlled by antihypertensive medications alone (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg); 6. History of bleeding within 4 weeks before screening, any bleeding event graded as grade 3 or higher per CTCAE 5.0; 7. Arterial or venous thrombotic events within 6 months before screening, such as cerebrovascular accident, deep vein thrombosis (except venous thrombosis judged by investigator as recovered from prior venous thrombosis), and pulmonary embolism; 8. History of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation; 9. Patients who have previously received anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies at any time; 10. Patients requiring systemic glucocorticoid therapy (daily dose >=10mg prednisolone [or equivalent]) or other immunosuppressive therapy within 14 days before first dose of Ipalolimab Tovorelimab. Note: For patients without obvious autoimmune diseases, inhaled or topical glucocorticoids, or adrenaline replacement therapy (daily dose >=10mg prednisolone [or equivalent]) are acceptable; 11. Multiple factors affecting oral medication administration (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.); 12. Patients with active hepatitis B or hepatitis C; 13. Concurrent severe infection within 4 weeks before treatment (e.g., requiring intravenous antibiotics, antifungal or antiviral drugs), or unexplained fever >38.5°C during screening period/before first dose; 14. Patients with known hypersensitivity or allergic reactions to any component of the study treatment; 15. Pregnant or breastfeeding women; 16. Patients with known psychotropic drug abuse that cannot be discontinued or psychiatric disorders; 17. Patients deemed unsuitable for participation in this study by the investigator;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS);Disease Control Rate (DCR);Duration of Response (DoR);Overall Survival (OS);Tumor Biomarker Analysis (including but not limited to circulating tumor DNA (ctDNA), peripheral blood immune cell subsets, and gut microbiota analysis); | — |
Countries
China
Contacts
Public ContactWu Hao
Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
Outcome results
None listed