A Clinical Study of TK216 in Patients With Relapsed or Refractory Ewing's Sarcoma

Inclusion Criteria:

Participants must meet all of the following inclusion criteria to be eligible for this study:

1. Willing to sign the informed consent form.

2. Participants with relapsed or refractory ES (including ESFT, except Ewing-likesarcoma) confirmed by cytohistology or molecular biology.

3. Life expectancy of at least 3 months.

4. Participants age ≥ 14 years, regardless of gender.

5. At least one measurable lesion according to RECIST version 1.1.

6. Agree to have a central venous catheter in place prior to initiating infusion ofstudy drug.

7. Prior radiotherapy is allowed if ≥ 2 weeks must have elapsed for local palliativeexternal beam radiotherapy; ≥ 6 months must have elapsed if systemic radiotherapy,external craniospinal irradiation or > 50% pelvic radiotherapy; and ≥ 6 weeks musthave elapsed for other substantial bone marrow radiotherapy before the first dose.Participants who have received brain radiotherapy must have completed whole brainradiotherapy and/or gamma knife surgery at least 4 weeks prior to enrollment.

8. Stem Cell Transplant or Rescue without TBI：no evidence of active graft-versus-hostdisease and ≥ 3 months must have elapsed since transplant.

9. Symptomatic CNS metastases must have been treated and remain stable for at least 4weeks prior to the first dose of the study drug, or patients with asymptomatic brainmetastases.

10. Adequate hematological and organ functions fulfilling the following laboratoryrequirements, and these results should be obtained within 7 days prior to the firstdose:

11. ECOG performance score 0-2.

12. Cardiac ejection fraction ≥ 50% or shortening fraction ≥ 28%.

13. Eligible male and female participants of childbearing potential must consent to usereliable methods of contraception with their partners for at least 4 weeks beforethe start of protocol therapy, for the duration of study participation, and for atleast 6 months after the last dose. Women of childbearing potential must have anegative blood pregnancy test within 7 days prior to the first dose.

14. Without any contraindication to vincristine.

Exclusion Criteria:

Participants will not be enrolled if they meet any of the following exclusion criteria:

1. Current participation in another therapeutic clinical trial.

2. Having received anti-tumor chemotherapy, targeted therapy or immunotherapy within 4weeks prior to the first dose; having received Chinese herbal medicine or Chinesepatent medicine-based therapies with definite anti-tumor indications within 3 weeksbefore study drug usage.

3. Having received systemic corticosteroids or other systemic immunosuppressive agentswithin 14 days prior to study, with the following exceptions:

4. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroids withminimal systemic absorption;

5. Short-term (≤ 7 days), prophylactic use of corticosteroids or for the treatmentof non-autoimmune diseases

6. Unresolved, > Grade 1 toxicity related to prior anti-tumor therapy prior to thestudy, according to the CTCAE version 5.0.

7. History of previous cancer, except squamous cell or basal -cell carcinoma of theskin or any in situ carcinoma that has been completely resected, which requiredtherapy within the previous 3 years.

8. Any of the following within 6 months: uncontrolled congestive heart failure (NYHAIII-IV); uncontrolled angina; onset of cerebrovascular event or transient ischemicattack; pulmonary embolism; deep vein thrombosis and symptomatic bradycardia thatrequire the use of antiarrhythmic drugs.

9. History of QTc prolongation

10. History of additional risk factors for torsades de pointes

11. Use of concomitant medications that may increase or possibly increase the risk toprolong the QTc interval and/or induce torsades de pointes ventricular arrhythmia.

12. Having received surgical therapies (except diagnostic surgery, such as tumor biopsy,diagnostic puncture, etc.), including surgical and interventional therapies, within 4 weeks prior to treatment.

13. Systemic use of antibiotics for ≥ 7 days within 4 weeks before TK216 treatment, orhave fever of unknown origin (> 38.5 °C）

14. Positive test results for hepatitis B surface antigen, hepatitis C antibody and HIVantibody during screening.

15. Females who are pregnant or lactating.

16. Have taken potent inducers or inhibitors of CYP3A4, potent inhibitors of CYP2C19within 2 weeks prior to the first dose of study drug, or substrates ofCYP3A4/CPY2C19 with a narrow therapeutic window.

17. Other severe acute or chronic medical or psychiatric conditions or laboratoryabnormalities that may increase the risk associated with study participation orstudy drug management, or may interfere with the interpretation of the studyresults.

18. Participants who are not suitable for participating in this study due to any reasonas judged by the investigator.