A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS

• Drug: SHR-A1904

Inclusion Criteria

1. Evidence of a personally signed and dated ICF indicating that the subject has been informed of all pertinent aspects of the study.
2. Age >18.
3. ECOG performance status of 0-1.
4. Life expectancy of ≥3 months.
5. Subjects with pathologically diagnosed advanced relapsed or refractory solid tumors, either gastric and gastroesophageal junction (GEJ) cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs, or pancreatic cancer, who are intolerable to SoC, have progressed through all available treatment options, or for whom there is no efficacious treatment available. Subjects must have pathological classification (e.g., adenocarcinomacancer arising from mucus-producing glands in organs etc.) documented.
6. Positive expression of Claudin 18.2 (>=50% of cellsthe basic structural and functional unit of all living things with 2+ or 3+ expression, either from fresh or archival tissuea group of cells that work together to perform a function) is required prior to enrollment and participation in this study. Positivity for Claudin 18.2 is defined as tumor cells showing partial or complete membrane staining. The percentage of tumor cells at four different staining intensities will be estimated: 0 (no staining), 1+ (weak), 2+ (moderate), and 3+ (strong). The sum of all 4 percentages should equal 100%. The H-score is determined according to the H-Score formula: [1 x Percentage of tumor cells stained at 1+] + [2 x Percentage of tumor cells stained at 2+] + [3 x Percentage of tumor cells stained at 3+] = H-Score (range 0 or 1-300). Actual figure of Claudin 18.2 expression tested by IHC should be documented. Subjects must have pathological classification (e.g., adenocarcinoma) documented.
7. Has at least one measurable lesion as defined by RECIST v1.1.
8. Has adequate organ and bone marrowsoft, spongy tissue found in bones that makes blood cells function within 7 days prior to administration of study treatment defined below: with no bloodthe red bodily fluid that transports oxygen and other nutrients around the body transfusion or hematopoietic growth factor support within 2 weeks prior to screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening): • Absolute neutrophil count (ANC) ≥1.5 × 109 /L • Platelet count (PLT) ≥100 × 109 /L • Hemoglobin (Hb) ≥90 g/L • TBIL ≤1.5 × ULN • ALT and AST ≤3 × ULN (≤5 × ULN for liver metastasiswhen the cancer has spread to other parts of the body, also known as mets) • Creatinine clearance ≥60 mL/min/1.73 m2 based on Cockcroft-Gault equation (Appendix 5) • Activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤1.5 × ULN. • Fridericia-corrected QT interval (QTcF) ≤450 msec. If ECG demonstrates QTc >450 msec at screening, an ECG re-examination is allowed, and subjects will be eligible if it demonstrates QTc ≤ 450 msec. • LVEF ≥50%.
9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days before the first dose. WOCBP and male subjects whose partners are WOCBP must agree to use effective contraception method during the study period and within 5 half-lives of SHR-A1904 + 6 months after the last dose of SHR-A1904. (see Appendix 2 for details).