A Multicenter, Randomized, Controlled,Open Label, Phase II Trial of Autologous Tumor Infiltrating Lymphocytes (GC101 TIL) in Subjects With Advanced Melanoma

Inclusion Criteria:

• Signed the informed consent form (ICF) and able to comply with the visits andrelated procedures specified in the protocol;

• Aged ≥18 years and ≤75 years, regardless of gender;

• Patients with unresectable advanced, recurrent or metastatic melanoma (excludinguveal melanoma) ;

• Patients who have failed or resisted to PD-1 antibodies；

• Patients must have failed or resisted to at least two frontlines systemic tehrapy(ifknowed with BRAF V600 mutate, then need to failed to BRAF/MEK inhibitor; if knowedwith NRAS mutate, then need to failed to Tunlametinib) ；

• TILs can be isolated from a surgically resectable tumor region: the tissue volumemust be >150mm3, and the lesion has not received local treatment (such asradiotherapy, radiofrequency ablation, oncolytic virus, etc.) or progressed afterlocal treatment;There are still at least 1 measurable lesion (according to RECIST1.1criteria ) even after TIL sampling and resection of surgically resectable tissue;

• ECOG performance status 0-1;

• Expected survival time >3 months;

• With sufficient hematology and end-organ function;

• Good compliance and able to adhere to the study visit plan and other agreementrequirements.

Exclusion Criteria:

• Patients receive any drug under study within 28 days prior to screening;

• Combination of 2 or more malignant tumors, except: Eradicated malignant tumors thathave been inactive for ≥5 years prior to study entry and are at minimal risk ofrecurrence; adequately treated non-melanoma skin cancer or malignant nevus offreckle-like nevus without evidence of disease recurrence; adequately treatedcarcinoma in situ without evidence of disease recurrence;

• Has received live attenuated vaccination after signing informed consent or isscheduled to receive it during the study;

• Has not recovered from a prior procedure or treatment-related adverse reaction to ≤grade 1 nci ctcae 5.0 (except for toxicities such as alopecia, hypothyroidism etc.,which in the judgment of the investigator pose no safety risk);

• Known history of allergy to streptomycin, ciprofloxacin, or micafungin or allergy toany component of the infused product formulation;

• Uncontrolled co-morbidities including, but not limited to, uncontrolled arterialhypertension (systolic blood pressure ≥160 mmhg and/or diastolic blood pressure ≥100mmhg) even with standardized treatment or any unstable cardiovascular diseaseincluding transient ischemic attack, cerebrovascular accident, myocardialinfarction, unstable angina pectoris within 6 months prior to enrollment; new yorkheart association ( nyha class iii or iv congestive heart failure with an ejectionfraction <50%; or severe cardiac rhythm or conduction abnormalities, such asventricular arrhythmias, degree ii-iii atrioventricular block, etc., requiringclinical intervention; ecg results showing clinically significant abnormalities or aqtcf ≥450ms (if the first test is abnormal, it may be retested at least 5 minutesapart twice and the combined result/mean value to determine eligibility) ;

• Patients with esophageal or gastric varices that require immediate intervention (e.g., taping or sclerotherapy) or are considered to be at high risk for bleedingbased on the opinion of the investigator or consultation with a gastroenterologistor hepatologist, have evidence of portal hypertension (including splenomegalydetected on imaging), or have a prior history of variceal bleeding must haveundergone endoscopic evaluation within 3 months prior to enrollment;

• Uncontrolled metabolic disorders, such as diabetes mellitus known to beuncontrolled, or other non-malignant organ or systemic diseases or secondaryreactions to cancer, and which can lead to higher medical risk and/or uncertainty insurvival evaluation;

• Hepatic encephalopathy, hepatorenal syndrome or child-pugh class b or more severecirrhosis, liver failure;

• With other serious organic diseases or mental disorders;

• Suffering from systemic active infection requiring treatment, with positive bloodculture or imaging evidence of infection, including but not limited to activetuberculosis;

• Suffering from infectious diseases such as hepatitis B, hepatitis C, syphilis, AIDS,etc;

• Individuals with active autoimmune diseases (such as eczema, vitiligo, psoriasis,alopecia or Graves' disease that do not require systemic treatment within the pasttwo years, other autoimmune diseases that are not expected to recur, hypothyroidismthat only requires thyroid hormone replacement therapy, and type 1 diabetes thatonly requires insulin replacement therapy can be enrolled);

• Any NCI CTCAE 5.0 immune-related adverse reaction (iRAE) grade ≥3 occurred duringany previous immunotherapy(except for cases where it recovered to ≤1 after treatmentor reached stability as assessed by the investigator);

• Those who had undergone organ allotransplantation, allogeneic stem celltransplantation and renal replacement therapy;

• Pulmonary fibrosis, interstitial lung disease (including past history and currentcondition), acute lung disease;

• Those with leptomeningeal metastasis;

• Patients with clinical symptoms of central nervous system metastases (such ascerebral edema, requiring hormone intervention, or progression of brain metastases),Patients who have previously received treatment for brain metastases, such as thosewho have maintained clinical stability (MRI) for at least 2 months and have stoppedsystemic hormone therapy (dose > 10mg/ day prednisone or other equivalent hormones)for more than 4 weeks, can be included;

• Women who are pregnant or breastfeeding;

• There is a history of TIL cell therapy, allogeneic T cell therapy, or NK celltherapy within 6 months;

• Situations that are not suitable for enrollment assesed by investigators;