A Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of TST001 in Patients With Locally Advanced or Metastatic Solid Tumors

Part A of the trial will consist of two cohorts, one dosed every 2 weeks and one dosed every 3 weeks in a standard 3+3 design. Part A is the dose finding portion of the trial.

27 to 54 participants will be enrolled.

Part B consists of 3 cohorts of approximately 20 participants each. For Part B, participants must have CLDN18.2 expressing tumors to qualify for participation. Cohort 1 is for participants with gastric and gastroesophageal junction cancers and dosed every 2 weeks. Cohort 2 is for participants with solid tumors except gastric and gastroesophageal cancers, dosed every 2 weeks. Cohort 3 is for all solid tumors dosed every 3 weeks. Up to 60 participants will be enrolled.

The trial will last approximately 2 years, with assessments including safety labs, ECGs, MUGA scans, PKs and PDs and CT/MRI tumor assessments, based on the Q2W and Q3W dosing schedules.

Inclusion Criteria:

1. Willing and able to provide signed and dated informed consent
2. Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors.
3. Patients must be: a) progressed after standard therapies, b) intolerant of standard therapies, or c) with a tumor type without standard therapy. d) Patients with HER2+ GC/GEJ cancer must have progressed after HER2-targeted therapy.
4. CLDN18.2 expression in tumor (Part B only): patients with locally advanced or metastatic unresectable GC, GEJ cancer, or other solid tumor including but not limited to pancreatic cancer, cholangiocarcinoma, ovarian cancer, and lung cancer.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS): Part A 0~1, Part B 0~2.
6. Life expectancy ≥ 3 months.
7. At least one measurable lesion per RECIST 1.1 (Part B only).
8. Provide archived tumor tissue samples
9. Adequate organ function
10. Recover to Grade 0-1 from adverse events related to prior anti-cancer therapy except alopecia

Exclusion Criteria:

1. Symptomatic central nervous system metastases.
2. Prior anticancer therapy:
   1. Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, or targeted therapy) within 4 weeks prior to Cycle 1 Day 1, or chemotherapy without delayed toxicity within the last 2 weeks preceding the first dose of study treatment with ≤ grade 1 treatment related AEs.
   2. Radiation therapy within 4 weeks prior to Cycle 1 Day 1;
   3. Prior treatment with an anti-CLDN18.2 antibody.
3. Major surgery within 8 weeks prior to study entry; Minor surgery within 2 weeks prior to study entry.
4. Gastrointestinal abnormalities including:
   1. Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥3 episodes within 24 hours
   2. Active peptic ulcer disease required treatment in the past 3 months
   3. Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
   4. Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis
   5. History of ulcerative colitis or Crohn's disease
5. Allergy or sensitivity to TST001 or known allergies to antibodies produced from Chinese hamster ovary cells, which in the opinion of the investigator suggests an increased potential for hypersensitivity to TST001.
6. History of a Grade 3-4 allergic reaction to treatment with another monoclonal antibody.
7. Severe cardiovascular disease.
8. QTc ≥470ms at baseline.
9. Concurrent malignancy within 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment (with or without resection), ductal carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma.
10. Prior stem cell, bone marrow or solid organ transplant.
11. Active infection requiring intravenous therapy within 2 weeks prior to entry.
12. Women of childbearing potential, unless they are using highly effective methods of contraception during the intervention period and for 90 days after the last dose of study intervention.
13. Men with a partner of childbearing potential who do not consent to use two highly effective methods of birth control during treatment and for an additional 90 days after the last administration of investigational drug.
14. Any condition that the investigator or primary physician believes may not be appropriate for participating the study.