This is a multicenter, randomized controlled, open-label Phase II clinical study designed to evaluate the efficacy and safety of HS-IT101 Injection versus the investigator's choice of chemotherapy in participants with advanced melanoma. A total of 90 participants are planned to be enrolled, and eligible participants will be randomly assigned to the experimental group or control group at a 1:1 ratio. The experimental group will receive a single administration of autologous tumor-infiltrating lymphocyte therapy, while the control group will receive chemotherapy regimens selected by the research physicians. Efficacy and safety evaluations will be conducted for all enrolled participants throughout the study.

Inclusion Criteria:

1. Participants aged 18 to 75 years, inclusive.
2. Patients with cytologically or histologically confirmed unresectable advanced, recurrent, or metastatic melanoma (excluding uveal melanoma), who have experienced disease progression after failure of systemic therapy recommended in the 2025 CSCO Guidelines.
3. Disease Progression Following Anti-PD-1 Therapy.
4. At least one tumor lesion not treated with radiotherapy or other local therapies within 28 days prior to resection, suitable for autologous tumor-infiltrating lymphocyte (TIL) preparation, with a minimum tissue weight of ≥0.050 g.
5. At least one measurable tumor lesion per RECIST 1.1 after tumor tissue sampling.
6. ECOG performance status ≤ 1.
7. Expected survival ≥ 3 months.
8. Adequate organ and bone marrow function as confirmed by screening assessments.
9. Documented by echocardiography showing left ventricular ejection fraction (LVEF) ≥50%；Absence of arrhythmia requiring therapeutic intervention；Electrocardiogram (ECG) criteria；QT interval corrected by Frederica's formula (QTcF) ≤470 ms；Baseline peripheral oxygen saturation (SpO₂) >91% in room air.
10. Adverse reactions from prior therapy have resolved to CTCAE v5.0 grade ≤1 before randomization, except for hypothyroidism and alopecia judged by the investigator as non-safety concerns.
11. Effective non-pharmacological contraceptive measures must be used from the signing of the informed consent form until 1 year after TIL cell infusion.
12. The subject fully understands the trial, voluntarily provides written informed consent, and is able to comply with scheduled visits and protocol-specified procedures.

Exclusion Criteria:

1. Patients with a history of severe hypersensitivity reactions (e.g., anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis) to any component of the following agents.

2. Presence of any uncontrolled clinical conditions, including but not limited to:

   • Poorly controlled hypertension (systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg at rest despite antihypertensive therapy);
   • Congestive heart failure (NYHA Class III/IV).

3. History of deep vein thrombosis (DVT) or pulmonary embolism (PE); myocardial infarction; severe or unstable arrhythmia or angina; percutaneous coronary intervention, acute coronary syndrome, or coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, or cerebral embolism within the past 6 months.

4. Active autoimmune diseases requiring systemic therapy during the study period（Subjects with the following conditions may be enrolled：Eczema, vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic therapy within the last 2 years and not expected to recur, or other autoimmune diseases under stable control;Hypothyroidism requiring only thyroid hormone replacement;Type 1 diabetes requiring only insulin replacement therapy.）

5. Organ transplant or history of hematopoietic stem cell transplantation.

6. Use of systemic immunosuppressive agents (e.g., corticosteroids) within 4 weeks prior to randomization, or presence of comorbid conditions requiring such medications during the trial period.Exception: Intranasal or topical corticosteroids are permitted.

7. Receipt of systemic anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization, or planned participation in another interventional clinical trial during the study period.

8. Acute or chronic infections, including:

   • HIV-positive status, Treponema pallidum antibody positivity, or clinically active hepatitis B or C(Note: For hepatitis B, HBsAg- or HBeAg-positive individuals with HBV DNA below the lower limit of normal at the study site may be enrolled; for hepatitis C, HCVAb-positive individuals with HCV RNA below the lower limit of normal at the study site may be enrolled);
   • Active infections requiring systemic therapy or active tuberculosis infection.

9. Subjects who received any live attenuated vaccine within 3 months prior to screening or planning to receive live vaccines during the trial period.

10. Subjects who have undergone major organ surgery or experienced clinically significant trauma within 4 weeks prior to screening, or require elective surgery during the trial period.

11. Patients presenting with pre-screening surgical complications or delayed wound healing, and deemed by the investigator to confer increased risks during lymphodepleting pretreatment, adoptive TIL therapy, and high-dose IL-2 adjuvant therapy.

12. Patients with a history of other primary malignancies diagnosed within 5 years prior to screening are excluded, except for radically treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or carcinoma in situ.

13. Patients with severe respiratory diseases (including but not limited to a documented history of or concurrent severe interstitial lung disease (ILD), severe chronic obstructive pulmonary disease (COPD), profound pulmonary insufficiency, or symptomatic bronchospasm).

14. Patients requiring surgical intervention for gastrointestinal hemorrhage, localized intestinal ischemia, or intestinal perforation.

15. Patients with symptomatic central nervous system (CNS) metastases

16. Patients with clinical symptoms of central nervous system (CNS) metastases who have received prior therapy for brain metastases and maintained radiographic stability (confirmed by MRI) for at least 12 weeks may be enrolled.

17. Pregnant or lactating women.

18. Individuals with a known history of psychiatric disorders, alcoholism, drug abuse, or substance abuse, as well as any other conditions deemed unsuitable for participation by the investigator .