A Phase I/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 - Claudin18.2 Monoclonal Antibody in the Treatment of Locally Advanced or Metastatic Solid Tumors

∙ The subjects who meet all inclusion criteria can be enrolled into the trial:

• Sign the Informed Consent Form (ICF) voluntarily, understand the study and be willing and able to comply with all study procedures;

• Male or female ≥ 18 years at signing the ICF;

• Suffer from histologically confirmed locally unresectable advanced or metastatic solid tumors and meet the criteria of corresponding cohort as follows:

• Part I - Mono-therapy dose escalation and expansion phase:

⁃ Mono-therapy dose escalation study: The subjects who have no option of or are intolerable to SOC.

⁃ Mono-therapy dose expansion study: The subjects with positive CDLN18.2 expression in tumor tissue (defined as CLDN18.2 membranous staining ≥1+ in ≥10% of tumor cells by immunohistochemistry (IHC) in the central laboratory) confirmed by the central laboratory at enrollment. The dose expansion study may include the following 3 cohorts:

• Cohort A: Subjects with G/GEJ adenocarcinoma who have no option of or are intolerable to SOC; Cohort B: Subjects with ductal adenocarcinoma of pancreas who have no option of or are intolerable to SOC; Cohort E: Subjects with other locally advanced or metastatic solid tumors excluding G/GEJ adenocarcinoma (limited to biliary tract neoplasms, lung adenocarcinoma or colorectal cancer) who have no option of or are intolerable to SOC; Part II - Dose escalation and expansion phase for combination medication

⁃ Dose escalation study of combination medication (dose escalation part):

‣ Cohort C/G: Subjects with HER2 negative or unknown G/GEJ adenocarcinoma who have not received prior systemic chemotherapy. The subjects who have completed neoadjuvant or adjuvant chemotherapy within at least 6 months prior to the initial dosing of the study can be enrolled.

‣ Cohort D: The subjects with G/GEJ adenocarcinoma who have received at least prior first-line systemic chemotherapy; Cohort F: The subjects with biliary neoplasm who have not received prior systematic chemotherapy. The subjects who have completed neoadjuvant or adjuvant chemotherapy within at least 6 months prior to the initial dosing of the study can be enrolled.

‣ Cohort H: The subjects with G/GEJ adenocarcinoma who have received at least prior second-line systemic chemotherapy;

⁃ Dose expansion study of combination medication (dose expansion part):

• The subjects with positive CDLN18.2 expression in tumor tissue confirmed by the central laboratory will be enrolled as follows:

• Cohort C/G: Subjects with HER2 negative or unknown G/GEJ adenocarcinoma who have not received prior systemic chemotherapy. The subjects who have completed neoadjuvant or adjuvant chemotherapy within at least 6 months prior to the initial dosing of the study can be enrolled.

• Cohort D: The subjects with G/GEJ adenocarcinoma who have received at least prior first-line systemic chemotherapy; Cohort F: The subjects with biliary neoplasm who have not received prior systematic chemotherapy. The subjects who have completed neoadjuvant or adjuvant chemotherapy within at least 6 months prior to the initial dosing of the study can be enrolled.

• Cohort H: The subjects with G/GEJ adenocarcinoma who have received at least prior second-line systemic chemotherapy;

• ECOG performance status of 0-1;

• Life expectancy ≥ 3 months;

• The results of laboratory examinations at screening must meet all the following criteria:

‣ Absolute neutrophil count (ANC) ≥ 1.5×109/L;

⁃ Absolute white blood cell (WBC) count ≥2.5×109/L;

⁃ Platelets ≥ 100×109/L;

⁃ Haemoglobin ≥ 9 g/dL;

⁃ International normalized ratio (INR) ≤ 1.5 times upper limit of normal (ULN) / or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN (for the test without anticoagulant);

⁃ INR ≤ 2.5 times ULN / or APTT ≤ 2.5 times ULN (for the test with anticoagulant);

⁃ Total bilirubin \<= 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \< 3.0 mg/dL).;

⁃ AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for subjects with hepatic cancer or liver metastases); ALT/AST ≤ 3xULN regardless of liver metastasis for cohort G and H only;

⁃ Albumin ≥ 30g/L;

‣ Serum creatinine ≤ 1.5 times ULN, or creatinine clearance rate ≥ 60 ml/min (creatinine clearance rate will be calculated using Cock-croft-Gault Equation);

• Male and female of childbearing age should agree to take effective contraception measures (refer to Appendix 3. Contraception) from signing the ICF till at least 120 days post the last dose of TST001 and other study drugs except nivolumab; female of childbearing age should agree to take effective contraception measures (refer to Appendix 3. Contraception) from signing the ICF till at least 5 months post the last dose of nivolumab; Serum β-HCG test for women of childbearing age within 72 hours prior to the initial dosing must be negative;

• (For dose expansion phase only) At least one measurable lesion conforming to per RECIST v1.1;