Study of TST005 in Patients With Locally Advanced or Metastatic Solid Tumors

Exclusion Criteria

• •1. Concurrent malignancy within 3 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.
• •2. Untreated or symptomatic central nervous system (CNS) metastases.
• •3. Any unresolved Grade 2 or greater toxicity from previous anticancer therapy except alopecia.
• •4. Active leptomeningeal disease.
• •5. Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:
• •* Controlled type 1 diabetes
• •* Hypothyroidism (provided it is managed with hormone-replacement therapy only)
• •* Controlled celiac disease
• •* Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
• •* Any other disease that is not expected to recur in the absence of external triggering factors
• •6. Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of investigational product, with the following exceptions:
• •* Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
• •* Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
• •* Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)
• •7. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, active pneumonitis.
• •8. Severe cardiovascular disease, including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina, New York Heart Association class III or IV heart failure or uncontrolled arrhythmia within 6 months of first dose.
• •9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening.
• •10. Clinically significant bleeding within three months of the first dose.
• •11. Uncontrolled hypertension, defined as systolic ≥150 mm Hg or diastolic ≥90 mm Hg maintained over time and despite antihypertensive treatment.
• •12. Patients with QTcF \> 480 ms on screening ECG or with a history of additional risk factors for TdP (e.g., heart failure, hypokalemia，family history of Long QT Syndrome)
• •13. Pregnant or nursing.
• •14. Known human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• •15. A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
• •16. Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study.
• •17. Active autoimmune disease requiring systemic therapy in the last 2 years prior to the first dose (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug).
• •• Subjects with Type 1 diabetes mellitus (TD1M), hypothyroidism requiring only hormone replacement, or skin disorders not requiring systemic treatment are permitted to enroll.
• •18. A history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• •19. \< 4 weeks after any major procedures/surgery; clinically significant unhealed wound; any unhealed ulceration in GI prior to first dose of TST005.
• •20. History of severe immune-related adverse effects from checkpoint inhibitor (CPI) therapy (NCI CTCAE Grade 3 or 4) with the exception of endocrinopathy managed with replacement therapy or subjects who discontinued CPI therapy for CPI-associated toxicity or intolerability.