A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Advanced Gastric Cancer.

A Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in EGFR-Positive, HER2-Negative Advanced Gastric Cancer.

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in patients with EGFR-positive, HER2-negative, inoperable locally advanced or metastatic gastric cancer.

Approximately 6054 patients will be enrolled to evaluate the safety and preliminarily efficacy of MRG003. Patients will receive 2.0 mg/kg dose of MRG003 intravenously every 3 weeks (Q3W) and may receive up to 24 months of MRG003 if there is evidence of clinical benefit to the patients.

Inclusion Criteria:

• - Willing to sign the ICF and follow the requirements specified in the protocol.
• Age: 18-75 years (including 18 and 75), both genders.
• Expected survival time≥3 months.
• Patients with histologically confirmed inoperable locally advanced or metastatic gastric adenocarcinoma.
• Tumor tissue must be EGFR positive and HER2 negative.
• Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
• ECOG performance score 0 or 1.
• Organ functions and coagulation function must meet the basic requirements.
• No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) ≥ 50%.
• Serum or urine pregnancy test negative within 7 days before the first dose of investigational drug.
• Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.

Exclusion Criteria:

• - Squamous cell carcinoma, carcinoid, neuroendocrine carcinoma, undifferentiated carcinoma, or other gastric cancers,or adenocarcinoma with other pathological components that cannot be classified, or adenocarcin oma accompanied by other pathological components.
• History of hypersensitivity to any component of the study drug or to other EGFR-targeting agents.
• Antitumor biological therapy or immunotherapy, targeted small molecule therapy and have history of systemic chemotherapy within 4 weeks before the first administration of the investigational drug, or major surgery. Traditional Chinese medicine, Chinese patent medicine or traditional Chinese medicine formula with anti-tumor effect should not be used within 2 weeks before the first administration.
• Potent CYP3A4 inhibitors or inducers are in use and cannot be discontinued.
• Known active CNS metastasis.
• Uncontrolled pleural effusion, pericardial effusion or recurrent ascites.
• Patients with intestinal obstruction requiring treatment were excluded.
• Residual toxicity reactions caused by previous anti-tumor treatment or abnormal values of laboratory tests higher than grade 1 (CTCAE v5.0).

Peripheral neuropathy ≥ Grade 2 (NCICTCAE version 5.0).

• Uncontrolled or poorly controlled hypertension.
• Uncontrolled or poorly controlled heart disease.
• Known active hepatitis B or C.
• Active bacterial, viral, fungal, rickettsia, or parasitic infections that require systemic anti-infective treatment.
• Known history of malignancy.
• History of ophthalmologic abnormalities
• History of severe skin disease
• Moderate to severe dyspnea at rest caused by advanced cancer or its complications, or severe primary lung disease, oxygen saturation < 93% in non-oxygen state, or history of any interstitial lung disease or interstitial lung disease (ILD) requiring oral or intravenous glucocorticoids or non-infectious pneumonia.
• Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy.
• History of pulmonary embolism or deep vein thrombosis within 6 months before the first administration of the investigational drug.
• Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy.

Decompensated cirrhosis of Child-Pugh class B, C

• Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation.
• Vaccination of live virus vaccine within 30 days before the first administration of the study drug. Inactivated seasonal influenza vaccine or approved COVID-19 vaccine is allowed.
• Uncontrolled intercurrent illness
• Patients requiring parenteral nutrition within 4 weeks
• Women who are lactating or pregnant.
• Other conditions that in the clinical judgement of the investigator make the patient not suitable for participation in this study.