SHR-A1811 for Subjects With Her2-positive Gastric Cancer and Gastroesophageal Junction Adenocarcinoma After Progression on or After First-line Anti-HER2 Therapy-containing Regimen

Inclusion Criteria:

1. Age 18-75 years old, male and female;
2. Histologically or cytologically confirmed gastric or gastroesophageal junctionadenocarcinoma, and unresectable locally advanced or metastatic disease
3. Prior anti-HER-2 containing treatment
4. Progression on or after first-line standard treatment (Prior neoadjuvant or adjuvanttherapy can be counted as a line of therapy if the subject progressed on or within 6months of completing neoadjuvant or adjuvant therapy);
5. Centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplificationby ISH) as classified by ASCO-CAP on a tumor biopsy
6. At least one measurable lesion according to the solid tumor response EvaluationCriteria (RECIST 1.1);
7. ECOG: 0-1;
8. Expected survival ≥12 weeks;
9. Good blood reserve and liver, kidney and coagulation function;
10. Willing to provide informed consent for study participation.

Exclusion Criteria:

1. Receive the last dose of anti-cancer therapy(including chemotherapy, radiotherapy,biological therapy, targeted therapy or immunotherapy) within 4 weeks, prior to thefirst dose;
2. Known allergies to monoclonal antibodies and inactive ingredients of this product, andallergies to paclitaxel, docetaxel, and irinotecan concurrently;
3. The toxicity of prior anti-tumor therapy did not recover to the level specified byCTCAE v5.0 grade evaluation ≤ Grade 1 or inclusion/exclusion criteria;
4. Clinically active central nervous system metastases;
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeateddrainage;
6. Clinically significant gastrointestinal disorder by the opinion of Investigator;
7. Has a history of immunodeficiency, including a positive HIV test;
8. During the screening visits and before the first dose, unexplained fever > 38.5℃,severe infection (CTC-AE > Grade 2), and active pulmonary inflammation were indicatedby screening imaging;
9. Subjects with interstitial pneumonia or with ≥ grade 3 interstitial pneumonia duringprior treatment with immune checkpoint inhibitors;
10. Active hepatitis B(HBV DNA ≥ 500 IU/mL), hepatitis C (positive for hepatitis Cantibody, and HCV-RNA above the lower limit of detection of the analytical method);
11. Clinically significant cardiovascular disease ,such as severe/unstable angina,symptomatic congestive heart failure (NYHA ≥ Class II.), clinically significantsupraventricular or ventricular arrhythmia requiring treatment or intervention,myocardial infarction within 6 months before the first dose, cerebrovascular accident (including transient ischemic attack); QTcF of 12-lead ECG was ≥470 ms; Leftventricular ejection fraction <50%; Clinically uncontrolled hypertension;
12. Had other malignancies with 5 years;
13. Pregnant or lactating women;
14. Other factors that might have led to drop out the study by the investigator opinion.