A Dose Escalation and Dose Expansion Clinical Study of STI-7349 in Subjects With Advanced Solid Tumors

Inclusion Criteria:

• To be enrolled in this study, subjects must meet all of the following inclusion criteria:

1. Subjects should have fully understood the study and voluntarily signed an informedconsent form.

2. Age 18 to 80 years (inclusive).

3. ECOG(Eastern U.S. Oncology Collaborative Group) score of 0 to 1.

4. Expected survival ≥ 12 weeks.

5. According to Response Evaluation Criteria in Solid Tumors (RECIST1.1), the subjecthas at least one measurable lesion, that is, the subject has at least one lymph nodelesion (minimum diameter ≥ 1.5 cm) or non-lymph node lesion (maximum diameter ≥ 1cm) diagnosed by computed tomography (CT)/magnetic resonance imaging (MRI)examination; if the lesion that previously received local therapy (radiotherapy,ablation, vascular intervention, etc.) is the only lesion, there must be a clearimaging basis for disease progression of this lesion after local therapy.

6. Subjects with malignant advanced solid tumors confirmed by histopathology orcytology who have failed standard treatment, or cannot tolerate standard treatment,or cannot obtain standard treatment for various reasons, or have no standardtreatment.

7. The subject has major organ function meeting the following criteria within 7 daysprior to first dose [The subject had not received blood component transfusion within 14 days prior to testing. Subjects had not received supportive treatment with humangranulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), thrombopoietinreceptor agonist, interleukin-11, and erythropoietin (EPO) within 7 days prior totesting.]:

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

9. Platelet (PLT) ≥ 100 × 109/L;

10. Hemoglobin (HGB) ≥ 90 g/L;

11. Alanine aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN(Upper limit of normalvalue) if liver involvement is known);

12. Aspartate aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if liver involvement isknown);

13. Total bilirubin (TBIL) ≤ 1.5 × ULN (≤ 3.0 × ULN if Gilbert's syndrome isdiagnosed);

14. Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR,calculated according to the Cockcroft-Gault formula, or by measuring 24-hoururine) ≥ 40 mL/min;

15. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastintime (APTT) ≤ 1.5 × ULN.

16. The toxic reaction of previous anti-tumor therapy returned to ≤ grade 1 (except forthe following cases: Grade 2 neurotoxicity and grade 2 hypothyroidism caused byanti-tumor therapy, hair loss and pigmentation of any grade, grade 2 AE that cannotbe returned to ≤ grade 1 and will remain stable for a long time as determined by theinvestigator based on the actual clinical situation, laboratory detection indicatorsare shown in inclusion Criterion 7) .

17. Subject is willing and able to comply with the study schedule and all other studyprotocol requirements.

18. Women of childbearing potential (women of non-childbearing potential are defined assexually mature women who have undergone hysterectomy or bilateral oophorectomy orbilateral salpingectomy or bilateral tubal ligation/occlusion, or who are unable tohave children because of congenital or acquired disease, or have natural menopausefor ≥ 12 months) must have a negative blood pregnancy test during screening. Femalesubjects of childbearing potential and male subjects must use a highly effectivemethod of contraception at screening through 6 months after the last treatment.

Exclusion Criteria:

• To be enrolled in this study, subjects must not meet any of the following exclusion criteria:

1. The subject has a known hypersensitivity to any component of the investigationalproduct or IL-2.

2. Subjects have participated in any therapeutic clinical study within 28 days prior tofirst dose, were enrolled and treated. In addition, subjects are in the survivalfollow-up phase of observational or interventional studies.

3. Subjects have used immunomodulatory drugs within 14 days or 5 half-lives (whicheveris longer) prior to the first dose, including but not limited to thymosin, IL-2,IL-15, interferon, etc.

4. The subject has received chimeric antigen receptor T-cell immunotherapy (CAR-T)within 3 months prior to the first dose; the subject has received chemotherapy (atleast 6 weeks for chemotherapeutic agents nitrosoureas and mitomycin C, and at least 14 days for oral fluoropyrimidines), endocrine therapy, targeted therapy (washoutperiod of 14 days or 5 half-lives for small-molecule targeted therapy, whichever islonger), immunotherapy (for immunomodulatory agents see exclusion criterion 3),tumor embolization, etc. within 28 days prior to the first dose; the subject hasreceived radiotherapy within 14 days prior to the first dose, palliativeradiotherapy for symptom control is allowed to be completed at least 7 days prior tothe first dose; the subject has received traditional Chinese medicine for anapproved indication of anti-tumor within 7 days prior to the first dose.Except whensubjects assessed by the investigator could be enrolled.

5. The subject has undergone major surgery within 28 days or minor surgery within 7days prior to the first dose, or had an unhealed wound, ulcer, or bone fracture orrequired elective surgery during the study (except for diagnostic biopsy, insertionof vascular access device).

6. Subjects have received a live attenuated vaccine within 28 days prior to the firstdose or plan to receive it during the study.

7. Subjects have received systemic immunosuppressants within 28 days prior to firstdose excluding:

8. Intranasal inhaled topical steroid therapy or topical steroid injection (eg,intra-articular injection);

9. Systemic corticosteroid therapy not exceeding 10 mg/day prednisone or itsphysiologic equivalent doses;

10. Corticosteroids as prophylaxis for allergic reactions (eg, premedication forCT);

11. As prophylaxis for infusion reactions.

12. See exclusion criteria 8 for systemic use of sex hormones in patients withbrain metastases.

13. Active central nervous system (CNS) metastases or cancerous meningitis with known orsymptomatic symptoms at the screening stage (Note: ① Patients with CNS metastaseswith symptoms prior to initial administration who have been treated and stable for ≥4 weeks and have been off systemic sex hormone therapy (at any dose) for >3 daysmay be included. ②Asymptomatic brain metastases (i.e. no neurological symptoms, noneed for corticosteroids, and no lesions >1.5cm) can be enrolled, but regular brainimaging examinations are required as a disease site).

14. Subjects had uncontrolled third space effusions requiring repeated drainage, such aspleural effusion, ascites, pericardial effusion, etc. (subjects who do not requiredrainage of effusion or have no significant increase in effusion after stoppingdrainage for 3 days may be enrolled), or third space effusions that are bloody bydiagnostic puncture.

15. The subject had another malignancy within 5 years prior to the first dose, exceptfor radically treated early malignancies (carcinoma in situ or Stage I tumor), suchas adequately treated basal or squamous cell carcinoma of the skin, carcinoma insitu of the cervix or breast after radical resection, early papillary thyroidcarcinoma, or prostate cancer with local Gleason score ≤ 6.

16. The subject had active autoimmune or inflammatory diseases, including inflammatorybowel disease (eg, ulcerative colitis or Crohn's disease), diverticulitis (otherthan diverticular disease), celiac disease, systemic lupus erythematosus,Sarcoidosis syndrome or Wegener' s syndrome (granuloma with polyangiitis), Graves'disease, rheumatoid arthritis, hypophysitis, uveitis, etc.), or a history of thedisease within the previous 2 years (subject with vitiligo, psoriasis, alopecia, orGraves' disease not requiring systemic therapy within the last 2 years,hypothyroidism requiring thyroid hormone replacement therapy only, and Type 1diabetes mellitus requiring insulin replacement therapy only may be enrolled).

17. The subject has active or uncontrolled HBV（Hepatitis B Virus） (HBsAg positive and/orHBcAb positive and HBV DNA titer positive), HCV (HCV-Ab positive and HCV RNA titerpositive), HIV(Human Immunodeficiency Virus) positive.

18. The subject had an active bacterial, viral, or fungal infection (defined as asubject demonstrating persistent signs/symptoms related to infection that do notimprove despite appropriate antibiotic or other therapy) or required intravenous (IV) antibiotics within 72 hours prior to the first dose.

19. Severe or uncontrolled cardiovascular or cerebrovascular disease requiringtreatment, including but not limited to:

20. New York Heart Association (NYHA) cardiac functional classification > 2;

21. Unstable angina not controlled by medication;

22. Subject has had a myocardial infarction within 6 months prior to first dose;

23. History of myocarditis;

24. Cardiac tamponade;

25. Poorly controlled arrhythmias (eg, subjects who develop ventricular tachycardiaduring antiarrhythmic drug therapy will be excluded; subjects with first degreeatrioventricular block or asymptomatic left anterior bundle branch block/rightbundle branch block will not be excluded);

26. 12-lead electrocardiogram QTcF（The QT interval values were corrected for heartrate using Fridericia's formula） > 470 msec;

27. Left ventricular ejection fraction (LVEF) < 50%;

28. Poorly controlled hypertension (On the basis of lifestyle modification, thesubject has been taking adequate doses of 2 or more antihypertensive agentsreasonably tolerated for more than 1 month, but blood pressure remainssubstandard. Or subjects have been taking 4 or more antihypertensive drugs foreffective blood pressure control) or hypotension;

29. Epilepsy not controlled by medication;

30. The subject had a stroke, cerebrovascular accident, or transient ischemicattack within 6 months prior to first dose.

31. The subject has known chronic obstructive pulmonary disease (COPD) and forcedexpiratory volume in one second (FEV1) < 50% of predicted normal. It should be notedthat subjects suspected of having COPD must have FEV1 testing and must be excludedif FEV1 is < 50% of predicted normal.

32. The subject has known moderate or severe persistent asthma, or had a history ofasthma within the past 2 years, or has uncontrolled asthma of any classificationcurrently (note that subjects with current controllable intermittent asthma orcontrollable mild persistent asthma are allowed).

33. The subject has previous and current pulmonary disease such as interstitialpneumonia (including drug-induced), pneumoconiosis, pulmonary fibrosis, or severelyimpaired pulmonary function; the subject has active pulmonary tuberculosis and isreceiving anti-tuberculosis treatment or has received anti-tuberculosis treatmentwithin 1 year prior to the first dose.

34. The subject has experienced clinically significant bleeding symptoms within 3 monthsprior to first dose. The subject had evident symptoms of coughing up blood within 28days prior to the first dose with hemoptysis of half a teaspoon (2.5 mL) or more persession.

35. The subject had a history of abdominal fistula, gastrointestinal perforation,intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior tothe first dose.

36. The subject had a history of deep vein thrombosis, pulmonary embolism, or any otherserious thromboembolism (except thrombosis caused by a vascular access device, orsuperficial venous thrombosis) within 3 months prior to the first dose.

37. The subject has hepatic encephalopathy, or hepatorenal syndrome, or Child-Pugh classB (> 7 points) or more severe cirrhosis.

38. The subject had a known history of primary immunodeficiency.

39. The subject had a known history of allogeneic organ transplantation and allogeneichematopoietic stem cell transplantation (except corneal transplantation).

40. Pregnant or lactating women.

41. Subject has any active serious psychiatric disorder, medical condition, or othersymptoms/conditions that could affect treatment, compliance, or ability to giveinformed consent at the discretion of the investigator. The following exclusion criteria apply only to combined dosing subjects:

42. Previous allergy to pabolizumab or other approved PD-1/PD-L1 inhibitors (e.g.,Tislelizumab, etc.).

43. Permanent discontinuation of drug related AE due to pabolizumab or other approvedPD-1/PD-L1 inhibitors (e.g., Tislelizumab, etc.) or similar drugs.

44. Permanent discontinuation of the drug due to previous allergy to standard treatmentor occurrence of drug-related AE.