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

Inclusion Criteria:

1. Evidence of a personally signed and dated ICF indicating that the subject has beeninformed 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) cancer, or pancreatic cancer, whoare intolerable to SoC, have progressed through all available treatment options, orfor whom there is no efficacious treatment available. Subjects must havepathological classification (e.g., adenocarcinoma etc.) documented.

6. Positive expression of Claudin 18.2 (>=50% of cells with 2+ or 3+ expression, eitherfrom fresh or archival tissue) is required prior to enrollment and participation inthis study. Positivity for Claudin 18.2 is defined as tumor cells showing partial orcomplete membrane staining. The percentage of tumor cells at four different stainingintensities 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 determinedaccording to the H-Score formula: [1 x Percentage of tumor cells stained at 1+] + [2x Percentage of tumor cells stained at 2+] + [3 x Percentage of tumor cells stainedat 3+] = H-Score (range 0 or 1-300). Actual figure of Claudin 18.2 expression testedby 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 marrow function within 7 days prior to administration ofstudy treatment defined below: with no blood transfusion or hematopoietic growthfactor support within 2 weeks prior to 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 metastasis) • Creatinineclearance ≥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 msecat screening, an ECG re-examination is allowed, and subjects will be eligible if itdemonstrates QTc ≤ 450 msec. • LVEF ≥50%.

9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy testwithin 3 days before the first dose. WOCBP and male subjects whose partners areWOCBP must agree to use effective contraception method during the study period andwithin 5 half-lives of SHR-A1904 + 6 months after the last dose of SHR-A1904. (seeAppendix 2 for details).

Exclusion Criteria:

1. Plan to receive any other anti-tumor treatments during the treatment period of thisstudy.

2. Subjects participated in a prior investigational study or received anticancertreatment, and have not recovered from side effects of such therapy.

3. Underwent major surgical operation within 4 weeks before the first dose of this IP.

4. Received treatments with strong CYP3A4, CYP2D6, P-gp, or BCRP inhibitors or inducerswithin < 5 half-lives of the drug before the first dose of the study.

5. Previously received total gastrectomy (only for subjects of the dose-escalationpart.

6. Adverse events caused by previous anti-tumor treatments have not recovered to Grade ≤1 according to NCI-CTCAE 5.0 (except for alopecia; some tolerable chronic Grade 2toxicities may also be excluded as judged by the investigator after consultationwith the sponsor).

7. Known to be allergic to any component of SHR-A1904 product (antibody conjugatedtoxin, antibody), or allergic to humanized monoclonal antibody products.

8. Subjects with known brain metastases, unless the participant is > 1 month fromdefinitive therapy (surgery or radiotherapy), has no evidence of tumor growth on animaging study and is clinically stable with respect to the tumor at the start ofstudy intervention.

9. Subjects with a second primary cancer, except adequately treated non-melanoma skincancer, curatively treated in situ cancer of the cervix, and other solid tumorscuratively treated with no evidence of disease for ≥3 years prior to the first doseof the study.

10. Class III-IV cardiac insufficiency as per the New York Heart Association (NYHA)criteria; arrhythmia requiring long-term drug control; unstable angina or acutemyocardial infarction within 6 months before the first dose of the study.

11. Subjects with a history of clinically significant lung diseases (e.g., interstitialpneumonia, radiation pneumonia, and pulmonary fibrosis) or who are suspected to havethese diseases by chest imaging at screening period.

12. Serious infections that require use of intravenous antibiotics, antiviral drugs, orantifungal drugs during the study period.

13. Hepatitis B (HBV, chronic or acute; defined as having a known positive hepatitis Bsurface antigen [HbsAg] test at the time of screening) or hepatitis C (HCV)infection requiring treatment

14. Has a history of immunodeficiency (including positive results of HIV test inscreening, and other acquired and congenital immunodeficiencies) or organtransplant.

15. Presence of accompanying diseases (such as poorly controlled hypertension, seriousdiabetes mellitus, thyroid disorder, psychosis, etc.) that may pose serious risks tothe safety of the subject or may affect the subject's ability to complete the study,or any other situation as judged by the investigator.