A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors

This is an open-label, multi-center, Phase I trial of TST001. Subjects with locally advanced or metastatic solid tumors will be enrolled. The study will consist of two parts: Part A is dose escalation and dose expansion phase for mono-therapy, and Part B is dose escalation and dose expansion phase for combination therapy in gastric, gastroesophageal junction(G/GEJ) and biliary tract cancer, etc.

Inclusion Criteria: The subjects who meet all inclusion criteria can be enrolled into the trial: 1. Sign the Informed Consent Form (ICF) voluntarily, understand the study and be willing and able to comply with all study procedures; 2. Male or female ≥ 18 years at signing the ICF; 3. 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: 1. Mono-therapy dose escalation study: The subjects who have no option of or are intolerable to SOC. 2. 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 1. 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; 2. 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; 4. ECOG performance status of 0-1; 5. Life expectancy ≥ 3 months; 6. The results of laboratory examinations at screening must meet all the following criteria: 1. Absolute neutrophil count (ANC) ≥ 1.5×109/L; 2. Absolute white blood cell (WBC) count ≥2.5×109/L; 3. Platelets ≥ 100×109/L; 4. Haemoglobin ≥ 9 g/dL; 5. 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); 6. INR ≤ 2.5 times ULN / or APTT ≤ 2.5 times ULN (for the test with anticoagulant); 7. Total bilirubin \