Inclusion Criteria:
- - Signed the informed consent form (ICF) and able to comply with the visits and
related procedures specified in the protocol;
- Aged ≥18 years and ≤75 years, regardless of gender;
- Patients with unresectable advanced, recurrent or metastatic melanoma (excluding
uveal melanoma) ;
- Patients who have failed or resisted to PD-1 antibodies；
- Patients must have failed or resisted to at least two frontlines systemic tehrapy(if
knowed with BRAF V600 mutate, then need to failed to BRAF/MEK inhibitor; if knowed
with NRAS mutate, then need to failed to Tunlametinib) ；
- TILs can be isolated from a surgically resectable tumor region: the tissue volume
must be >150mm3, and the lesion has not received local treatment (such as
radiotherapy, radiofrequency ablation, oncolytic virus, etc.) or progressed after
local treatment;There are still at least 1 measurable lesion (according to RECIST1.1
criteria ) 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 agreement
requirements.
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 that
have been inactive for ≥5 years prior to study entry and are at minimal risk of
recurrence; adequately treated non-melanoma skin cancer or malignant nevus of
freckle-like nevus without evidence of disease recurrence; adequately treated
carcinoma in situ without evidence of disease recurrence;
- Has received live attenuated vaccination after signing informed consent or is
scheduled 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 to
any component of the infused product formulation;
- Uncontrolled co-morbidities including, but not limited to, uncontrolled arterial
hypertension (systolic blood pressure ≥160 mmhg and/or diastolic blood pressure ≥100
mmhg) even with standardized treatment or any unstable cardiovascular disease
including transient ischemic attack, cerebrovascular accident, myocardial
infarction, unstable angina pectoris within 6 months prior to enrollment; new york
heart association ( nyha class iii or iv congestive heart failure with an ejection
fraction <50%; or severe cardiac rhythm or conduction abnormalities, such as
ventricular arrhythmias, degree ii-iii atrioventricular block, etc., requiring
clinical intervention; ecg results showing clinically significant abnormalities or a
qtcf ≥450ms (if the first test is abnormal, it may be retested at least 5 minutes
apart 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 bleeding
based on the opinion of the investigator or consultation with a gastroenterologist
or hepatologist, have evidence of portal hypertension (including splenomegaly
detected on imaging), or have a prior history of variceal bleeding must have
undergone endoscopic evaluation within 3 months prior to enrollment;
- Uncontrolled metabolic disorders, such as diabetes mellitus known to be
uncontrolled, or other non-malignant organ or systemic diseases or secondary
reactions to cancer, and which can lead to higher medical risk and/or uncertainty in
survival evaluation;
- Hepatic encephalopathy, hepatorenal syndrome or child-pugh class b or more severe
cirrhosis, liver failure;
- With other serious organic diseases or mental disorders;
- Suffering from systemic active infection requiring treatment, with positive blood
culture or imaging evidence of infection, including but not limited to active
tuberculosis;
- 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 past
two years, other autoimmune diseases that are not expected to recur, hypothyroidism
that only requires thyroid hormone replacement therapy, and type 1 diabetes that
only requires insulin replacement therapy can be enrolled);
- Any NCI CTCAE 5.0 immune-related adverse reaction (iRAE) grade ≥3 occurred during
any previous immunotherapy(except for cases where it recovered to ≤1 after treatment
or reached stability as assessed by the investigator);
- Those who had undergone organ allotransplantation, allogeneic stem cell
transplantation and renal replacement therapy;
- Pulmonary fibrosis, interstitial lung disease (including past history and current
condition), acute lung disease;
- Those with leptomeningeal metastasis;
- Patients with clinical symptoms of central nervous system metastases (such as
cerebral edema, requiring hormone intervention, or progression of brain metastases),
Patients who have previously received treatment for brain metastases, such as those
who have maintained clinical stability (MRI) for at least 2 months and have stopped
systemic 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 cell
therapy within 6 months;
- Situations that are not suitable for enrollment assesed by investigators;
