To Evaluate IAH0968 in Combination With CAPEOX in HER2-positive Gastric Cancer

Exclusion Criteria

• •1\) Phase II Cohort 2 only: received antitumor therapy such as chemotherapy, radiotherapy, biologic therapy, endocrine therapy, immunotherapy, etc. within 4 weeks prior to the first use of study drug, except for the following:
• •* Nitrosourea or mitomycin C within 6 weeks prior to first use of study drug;
• •② Oral fluorouracil analogs and small molecule targeted drugs for 2 weeks prior to the first use of the study drug or within 5 half-lives of the drug (whichever is longer);
• •③ Within 2 weeks prior to first use of the study drug for proprietary Chinese medicines with antitumor indications.
• •2\) Received other unlisted clinical investigational drug or therapy within 4 weeks prior to first use of the study drug.
• •3\) Adverse effects of prior antineoplastic therapy have not returned to NCI CTCAE 5.0 grade rating of ≤ grade 1 or relevant provisions of the enrollment criteria (except for toxicities judged by the investigator to pose no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacement therapy).
• •4\) Known hypersensitivity to any antibody-based drug (NCI CTCAE 5.0 grade rating ≥ 3) or hypersensitivity to the study drug and the active ingredient or inactive excipients of the CAPEOX regimen.
• •5\) Diagnosed defective mismatch repair (dMMR) or high microsatellite instability (MSI-H) solid tumor (except unknown MSI/MMR status).
• •6\) Major surgical procedure (excluding puncture biopsy), major trauma within 4 weeks prior to first use of study drug, or need for elective surgery during the trial.
• •7\) Received systemic glucocorticosteroids (prednisone \> 10 mg/day or equivalent) within 14 days prior to the first dose of study drug, except for the following: treatment with topical, ocular, intra-articular, intranasal, and inhaled glucocorticosteroids; and short-term prophylactic glucocorticosteroids (e.g., for prevention of allergy to contrast media).
• •8\) Other immunosuppressive therapy within 28 days or 5 half-lives (whichever is longer) prior to first use of study drug.
• •9\) Use of immunomodulatory drugs within 14 days prior to first use of study drug.
• •10\) Use of any live vaccine within 4 weeks prior to the first dose of study drug.
• •11\) Previous allogeneic hematopoietic stem cell transplantation or organ transplantation.
• •12\) Parenchymal brain metastases or meningeal metastases with clinical symptoms.
• •13\) Have an active infection that currently requires intravenous anti-infective therapy.
• •14\) Have a history of immunodeficiency, including a positive antibody test for human immunodeficiency virus (HIV).
• •15\) Have active hepatitis B (HBsAg positive and HBV-DNA positive or greater than the upper limit of normal) and active hepatitis C (hepatitis C virus antibody positive and HCV RNA positive or greater than the upper limit of normal).
• •16\) Have severe and uncontrollable lung disease (severe infectious pneumonia, interstitial lung disease, etc.).
• •17\) Have a history of severe cardiovascular disease, including but not limited to:
• •* Having severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block;
• •* Mean QT interval (QTcF) corrected by the Fridericia method \> 470 ms;
• •③ Acute coronary syndrome, congestive heart failure, aortic coarctation, stroke, or other grade 3 or higher cardiovascular event within 6 months prior to the first dose;
• •④ Presence of New York Heart Association (NYHA) Cardiac Function Class ≥ Grade II heart failure or left ventricular ejection fraction (LVEF) \< 50%, or other structural heart disease judged by the investigator to be of high risk;
• •⑤ Clinically uncontrolled hypertension. 18) Active, or previous autoimmune disease with potential for relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroid disease, type I diabetes mellitus, vitiligo, cured atopic dermatitis in children, and psoriasis that does not require systemic therapy (within the past 2 years).
• •19\) Presence of other malignancies within 5 years prior to the start of study dosing, except: malignancies for which cure can be expected with treatment (including, but not limited to, adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated by radical surgery).
• •20\) Presence of clinically uncontrollable third interstitial fluid that, in the judgment of the Investigator, makes enrollment inappropriate.
• •21\) Known alcohol or drug dependence. 22) Have a mental disorder or poor compliance. 23) Pregnant or lactating females. 24) In the opinion of the investigator, the subject has a history of other serious systemic disease or is otherwise unsuitable for enrollment in this clinical study.