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

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

Exclusion criteria

• Receive the last dose of anti-cancer therapy(including chemotherapy, radiotherapy, biological therapy, targeted therapy or immunotherapy) within 4 weeks, prior to the first dose;
• Known allergies to monoclonal antibodies and inactive ingredients of this product, and allergies to paclitaxel, docetaxel, and irinotecan concurrently;
• The toxicity of prior anti-tumor therapy did not recover to the level specified by CTCAE v5.0 grade evaluation ≤ Grade 1 or inclusion/exclusion criteria;
• Clinically active central nervous system metastases;
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Clinically significant gastrointestinal disorder by the opinion of Investigator;
• Has a history of immunodeficiency, including a positive HIV test;
• During the screening visits and before the first dose, unexplained fever > 38.5℃, severe infection (CTC-AE > Grade 2), and active pulmonary inflammation were indicated by screening imaging;
• Subjects with interstitial pneumonia or with ≥ grade 3 interstitial pneumonia during prior treatment with immune checkpoint inhibitors;
• Active hepatitis B(HBV DNA ≥ 500 IU/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA above the lower limit of detection of the analytical method);
• Clinically significant cardiovascular disease ,such as severe/unstable angina, symptomatic congestive heart failure (NYHA ≥ Class II.), clinically significant supraventricular 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; Left ventricular ejection fraction <50%; Clinically uncontrolled hypertension;
• Had other malignancies with 5 years;
• Pregnant or lactating women;
• Other factors that might have led to drop out the study by the investigator opinion.