Evaluate the Safety and Efficacy of Autologous Tumor-infiltrating Lymphocyte in Patients With Refractory Melanoma Who Failed to Immune Checkpoint Inhibitors

Inclusion criteria

• Age ≥19 and ≤80 years at the time of informed consent.
• Histologically or cytologically confirmed melanoma, classified as refractory/unresponsive Stage IIIc or IV after failure of prior immune checkpoint inhibitor therapy.
• At least one measurable and evaluable lesion as defined by RECIST version 1.1.
• ECOG performance status of 0 or 1.
• Estimated life expectancy ≥12 weeks.
• Ability to undergo tumor tissue biopsy for the purpose of producing a sufficient quantity of autologous tumor-infiltrating lymphocytes (CT-SP).

• Willingness to undergo tissue collection procedures after enrollment in the study.
• For surgical specimens: at least one lesion with a minimum diameter of 1 cm. For biopsy samples: a minimum of 20-25 tissue fragments must be obtainable.
• Adequate organ function as defined by the following laboratory values (up to two retests permitted; transfusions or medical correction allowed):

• Hemoglobin ≥ 9.0 g/dL
• Absolute Neutrophil Count (ANC) ≥ 1,500/μL
• Absolute Lymphocyte Count (ALC) ≥ 500/μL
• Platelet count ≥ 100,000/μL
• Serum creatinine clearance (estimated by Cockcroft-Gault) ≥ 50 mL/min
• Total bilirubin ≤ 2.0 mg/dL
• AST and/or ALT ≤ 3 × ULN (≤ 5 × ULN if liver metastasis is present)
• Subjects of childbearing potential must agree to use acceptable contraceptive methods during the study, including but not limited to:

Complete abstinence, Sterilization (patient or partner), Intrauterine device, Hormonal contraception, Barrier methods (e.g., condom + spermicide, diaphragm)

• Written informed consent voluntarily provided before any study-specific procedures are conducted.

Exclusion criteria

• History of solid organ transplantation.
• Diagnosis of another malignancy within the past 5 years, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or non-invasive cervical cancer.
• History of active or latent tuberculosis infection within 1 year prior to screening (except for those declared cured after treatment).
• Pregnant or breastfeeding women.
• Positive test for anti-HIV antibodies.
• Active HBV or HCV infection considered clinically inappropriate for study participation by the investigator.
• Uncontrolled central nervous system (CNS) metastases (note: patients with treated and stable brain metastases for ≥30 days prior to screening are eligible).
• Any surgery, radiotherapy, or systemic anticancer therapy within 3 weeks prior to CT-SP administration.
• Participation in another interventional clinical trial and receipt of any investigational drug within 3 weeks prior to CT-SP administration.
• Known hypersensitivity or contraindication to: Cyclophosphamide, Fludarabine, Interleukin-2 (IL-2), CT-SP excipients: 5% human serum albumin, sterile saline, 5% DMSO
• Unresolved toxicity from prior therapy not recovered to Grade ≤1 (per NCI CTCAE v5.0), except for clinically non-significant events such as alopecia.
• Receipt of systemic immunosuppressive therapy (including corticosteroids) within 10 days prior to tumor tissue collection for CT-SP manufacturing (exceptions: local/inhaled steroids; systemic corticosteroids ≤ prednisolone 20 mg/day equivalent may be permitted at investigator discretion).
• Clinically significant cardiovascular disease, including but not limited to:

Uncontrolled hypertension (systolic BP > 180 mmHg and/or diastolic BP > 100 mmHg), Unstable angina, Pulmonary embolism, Cerebrovascular accident, Valvular heart disease, Congestive heart failure (NYHA Class III or IV), Myocardial infarction or significant arrhythmia within 24 weeks prior to screening

• Known contraindications to dopamine or other pressor agents.
• Other serious comorbid medical conditions that may interfere with study participation, as determined by the investigator.
• Active or severe infection requiring hospitalization or intravenous antibiotics, deemed unsuitable for participation by the investigator.
• Significant psychiatric illness that, in the investigator's opinion, may affect subject compliance or study conduct.
• Subjects with autoimmune or inflammatory disorders, where the investigator deems abnormal autoantibody test results to be clinically relevant.
• Any other condition not listed above that the investigator considers to make the subject ineligible for participation.
• Subjects determined to be unsuitable for participation based on the anticipated manufacturing timeline and logistics of CT-SP.