HS-IT101 Injection in the Treatment of Advanced Melanoma

Inclusion Criteria

• •1. Age between 18 and 75 years (inclusive).
• •2. Histologically or cytologically confirmed advanced, recurrent, or metastatic melanoma (excluding uveal melanoma) that has failed at least one prior line of standard systemic therapy. Subjects with BRAF V600 mutations must have failed BRAF-targeted therapy or been intolerant to such therapy due to toxicity. The necessity and appropriateness of targeted therapy shall be determined by the investigator based on the subject's clinical status.
• •3. At least one tumor lesion (not subjected to radiotherapy or local therapy within 28 days prior to sampling) must be available for autologous tumor-infiltrating lymphocyte (TIL) preparation, with a minimum tissue weight of ≥0.050 g.
• •4. At least one measurable lesion (per RECIST 1.1 criteria) must remain after sampling. This lesion must not have received prior radiotherapy or local therapy unless performed \>28 days before tumor sampling and demonstrating clear progression.
• •5. ECOG performance status ≤1.
• •6. Life expectancy ≥3 months.
• •7. Adequate organ and bone marrow function at screening, defined as:
• •Hematology:
• •Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet count (PLT) ≥90×10⁹/L; Hemoglobin (HGB) ≥90 g/L (no transfusion or erythropoietin within 14 days).
• •Liver function:
• •ALT/AST ≤2.5×ULN (≤5×ULN for liver metastases); Total bilirubin (TBil) ≤1.5×ULN (≤3×ULN if Gilbert's syndrome is confirmed).
• •Renal function:
• •Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Ccr) ≥60 mL/min (Cockcroft-Gault formula).
• •Coagulation:
• •Activated partial thromboplastin time (APTT) ≤1.5×ULN; International normalized ratio (INR) and prothrombin time (PT) ≤1.5×ULN.
• •8. Cardiac function criteria:
• •Left ventricular ejection fraction (LVEF) ≥50% by echocardiography; No clinically significant arrhythmias requiring treatment; QTcF interval ≤470 ms (calculated using Fridericia's formula: QTcF = QT/(RR⁰.³³), where RR = 60/heart rate. If initial result is abnormal, repeat twice at 5-minute intervals; use mean value for eligibility); Baseline oxygen saturation \>91% in room air.
• •9. Prior treatment-related toxicities resolved to CTCAE v5.0 Grade ≤1 (excluding alopecia or other toxicities deemed non-risk by the investigator) before tumor sampling.
• •10. Agreement to use effective non-pharmacologic contraception from informed consent signing until 1 year post-TIL infusion.
• •11. Willing and able to comply with study visits/procedures, with full understanding of the trial and provision of written informed consent.
• •* Active infections requiring systemic therapy or active tuberculosis.
• •9. Major organ surgery, significant trauma within 4 weeks prior to screening, or planned elective surgery during the trial.
• •10. Surgical complications or delayed wound healing (investigator-assessed to increase risks of preconditioning, TIL therapy, or IL-2 administration).
• •11. Other primary malignancies diagnosed within 5 years prior to screening (exceptions: radically treated basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ).
• •12. Severe respiratory diseases (e.g., interstitial lung disease, severe COPD, pulmonary insufficiency, symptomatic bronchospasm).
• •13. Gastrointestinal bleeding requiring surgery, intestinal ischemia, or perforation.
• •14. Leptomeningeal metastasis or uncontrolled/untreated CNS metastases (excludes asymptomatic CNS metastases stable for ≥4 weeks post-treatment without corticosteroids/anticonvulsants).
• •15. Prior treatment with cell therapy products of the same class.
• •16. Pregnancy, lactation, or refusal to use contraception.
• •17. Psychiatric disorders, substance abuse, or other investigator-determined contraindications.