TQB2102 for injection is a novel antibody-coupled drug (ADC) that enhances binding to tumor cell surface HER2 proteins by simultaneously targeting the two non-overlapping epitopes of the HER2 protein, Endothelial Cell Dysfunction 2 (ECD2) and Endothelial Cell Dysfunction 4 (ECD4), increasing HER2 internalization, and then down-regulating the tumor cell surface HER2 proteins more effectively, and doubly blocking the HER2 signaling, to achieve the effects of trastuzumab and Pertuzumab alone and in combination. This is a Phase II study to evaluate the efficacy and safety of TQB2102 for injection in combination with Benmelstobart Injection /Penpulimab Injection ± chemotherapy in patients with unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma

Inclusion Criteria:

• 18 to 75 years of age, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and life expectancy≥3 months;
• Histopathologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma;
• HER2 expression levels of Immunohistochemistry(IHC) 3+ or IHC 2+ and In Situ Hybridization (ISH) positivity were confirmed in tumor tissue;
• Subject is able to provide previous compliant PD-L1 expression level test results or is able to provide sufficient and competent tumor tissue for PD-L1 expression level testing;
• Patients who have not received prior systemic therapy for locally advanced or metastatic gastric cancer and who have experienced tumor recurrence or metastasis at least 6 months after the completion of prior adjuvant or neoadjuvant therapy may be enrolled;
• Confirmation of at least one measurable lesion according to RECIST 1.1 criteria;
• The main organs function well;
• Male or female patient had no plans to become pregnant and voluntarily take effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug.

Exclusion Criteria:

• Concurrent secondary malignancy. or other malignancy with no evidence of disease for more than 5 years;
• Uncontrollable toxic reactions above CTC AE grade 1 due to any prior therapy, excluding alopecia;
• Major surgical treatment, incisional biopsy or significant traumatic injury or prolonged unhealed wound or fracture within 28 days prior to first dose;
• Prior history of interstitial lung disease/pneumonia (non-infectious) requiring steroidal drug intervention or current concomitant (or suspected) interstitial lung disease/pneumonia;
• Arterial/venous thrombotic events, such as cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism, have occurred within 6 months prior to the first dose;
• Individuals with a history of psychiatric drug abuse who are unable to quit or have mental disorders;
• Subjects with the presence of any severe and/or uncontrolled disease；
• Subjects who have received other antitumor drugs such as chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to the first dose, or who are still within the 5 half-life of the drug (whichever occurs shortest); have received a proprietary Chinese medicine with an antitumor indication as specified in the National Medical Products Administration(NMPA) -approved drug insert within 2 weeks prior to the first dose; and have experienced any hemorrhagic or bleeding event in the month prior to the initiation of study treatment ≥CTC Patients with AE grade 3;
• Subjects with known Central nervous system (CNS) metastases and/or carcinomatous meningitis
• Presence of severe bone damage and spinal cord compression due to tumor bone metastases;
• History of live attenuated vaccination within 28 days prior to the first dose or planned live attenuated vaccination during the study;
• History of severe hypersensitivity reactions to large molecule drugs or hypersensitivity to known components of TQB2102, benmelstobart or pembrolizumab for injection;
• Active autoimmune disease requiring systemic therapy (e.g., use of disease-mitigating drugs, corticosteroids, or immunosuppressive agents) within 2 years prior to the first dose of medication
• Diagnosis of immunodeficiency or undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy that was continued within 2 weeks prior to initiation of study treatment.
• Participants who have participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first medication use
• Unstable or serious concurrent medical conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.