Locally Advanced Gastric Adenocarcinoma with Microsatellite Instability-High/Deficient Mismatch Repair (MSI-H/dMMR)
Conditions
Interventions
Experimental Group:(1) Neoadjuvant Therapy: Iparomlimab/Tuvonralimab (Aituo combination antibody) at a dose of 5 mg/kg, administered on Day 1 (D1) of each 3-week cycle (q3w), for a total of 4 cycles o
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.The subject voluntarily participates in this study, is capable of signing the Informed Consent Form (ICF), and has good treatment compliance. 2.Aged 18 to 75 years old (at the time of ICF signing), both male and female subjects are eligible. 3.Histologically confirmed gastric adenocarcinoma, diagnosed as locally advanced disease (clinical stage II-III confirmed by endoscopic ultrasonography (EUS) or contrast-enhanced CT/MRI scan) in accordance with the 8th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual; the subject agrees to receive radical surgical resection, and the investigator assesses the lesion as resectable; no prior systemic therapy for the current disease, including anti-tumor radiotherapy, chemotherapy, or immunotherapy. 4.Tumor biopsy confirmed concurrent deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status. 5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 6.Expected overall survival time >= 6 months. 7.Adequate function of major organs, meeting the following criteria: a) Hematological tests (without blood transfusion or correction with hematopoietic growth factors within 14 days prior to the test): Hemoglobin (Hb) >=90g/L; Absolute Neutrophil Count (ANC) >=1.5×10^9/L; Platelet (PLT) >=100×10^9/L; b) Biochemical tests: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) =60mL/min; Coagulation function tests: Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR), Prothrombin Time (PT) =50%. 8.Subjects of childbearing potential must use appropriate contraceptive methods during the study and for 120 days after the end of the study; serum pregnancy test is negative within 7 days before study enrollment, and the subject must be non-lactating.
Exclusion criteria
Exclusion criteria: 1.Diagnosis of any malignancy other than gastric cancer within 5 years prior to the first dose, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, radically resected carcinoma in situ, and locally curable papillary thyroid carcinoma. 2.Current participation in an interventional clinical study, or receipt of any other investigational drug or investigational device therapy within 4 weeks prior to the first dose. 3.Systemic therapy with Chinese patent medicine indicated for anti-tumor treatment or immunomodulatory agents (including thymosin, interferon, interleukin, excluding local use for pleural effusion control) within 2 weeks prior to the first dose. 4.Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy. 5.Receipt of systemic corticosteroid therapy (excluding nasal, inhaled, or other topical corticosteroids) or any other immunosuppressive therapy within 7 days prior to the first dose. Note: Physiological doses of corticosteroids (=10 mg/day prednisone or equivalent) are permitted. 6.History of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation. 7.Known hypersensitivity to any study drug. 8.Peripheral neuropathy >= Grade 2. 9.Known human immunodeficiency virus (HIV) infection (positive HIV 1/2 antibody). 10.Administration of a live vaccine within 30 days prior to the first dose (Cycle 1, Day 1). Note: Inactivated seasonal influenza vaccine by injection within 30 days prior to the first dose is allowed; intranasal live attenuated influenza vaccine is not allowed. 11.Pregnant or lactating female subjects. 12.Presence of any severe or uncontrolled systemic disease, such as: a) Significant and clinically symptomatic uncontrolled abnormalities in rhythm, conduction, or morphology on resting electrocardiogram (ECG); b) Unstable angina pectoris, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) class >= 2; c) Any arterial thrombosis, embolism, or ischemia within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack; d) History of non-infectious pneumonia requiring corticosteroid therapy within 1 year prior to the first dose, or current clinically active interstitial lung disease; e) Active pulmonary tuberculosis; f) Active or uncontrolled infection requiring systemic therapy; g) Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction; h) Liver disease such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; i) Urinalysis showing urine protein >= ++ and confirmed 24-hour urinary protein quantification > 1.0 g; j) Mental disorder that precludes compliance with study procedures. 13.Any medical history, disease evidence, treatment, or abnormal laboratory values that may interfere with study results or prevent full study participation, or any other condition deemed inappropriate by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR) Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR);Overall Survival (OS);The 3-year Event-Free Survival (EFS) rate;3-year Disease-Free Survival (DFS) rate;Major Pathologic Response (MPR) Rate; | — |
Countries
China
Contacts
Public ContactBu Zhaode
Beijing Cancer Hospital
Outcome results
None listed