HS-IT101 Injection in the Treatment of Advanced Solid Tumors

Inclusion Criteria:

• To be eligible for the study, patients must meet ALL of the following criteria priorto participation:

1. Age: 18 years to 75 years at the time of consent;
2. Histologically or cytological diagnosed as advanced soild tumor:
3. At least one resectable lesion that has not received radiotherapy or other localtherapy within 28 days, and the weight of the tissue must be ≥ 0.050g；orresectable lesions capable of producing sufficient TIL;
4. At least one measurable target lesion, as defined by RECIST v1.1，that has notreceived radiotherapy or other local therapy unless these therapies occurred 28days ago and target lesion shows significant progression;
5. ECOG score 0-1;
6. Expected life-span more than 3 months;
7. Adequate organ and bone marrow function: Absolute count of neutrophil ≥1.5×10^9/L; Platelet count ≥90×10^9/L; Hemoglobin ≥ 90g/L; AST, ALT≤2.5×ULN (subjects with liver metastasis ≤5×ULN); Totol bilirubin ≤1.5×ULN（Gilbert syndrome≤3×ULN）; Serum creatinine ≤1.5×ULN, or estimatedcreatinine clearance (CrCl)≥60 mL/min (Cockcroft-Gault formula); Activatedpartial thromboplastin time (APTT) ≤1.5×ULN, while international normalized ratio (INR) or prothrombin (PT) ≤1.5×ULN;
8. Left ventricular ejection fraction (LVEF) ≥ 50% detected by echocardiography;Arrhythmias that do not require treatment, the QT interval (QTcF) corrected bythe Fridericia method is ≤ 470 ms (QTcF is calculated using the Fridericiaformula, i.e. QTcF=QT/(RR ^ 0.33), RR is the standardized heart rate value,RR=60/heart rate); If there is an abnormality during the first inspection, it canbe retested twice with an interval of at least 5 minutes, and the overallresult/average value should be taken to determine the qualification; Basic bloodoxygen saturation in indoor natural air environment>91%;
9. Test subjects must have recovered from all prior therapy-related toxicities to ≤Grade 1 according to Common Terminology Criteria for Adverse Events (CTCAE)v5.0; except for alopecia (tumor resection);
10. Test subjects with child-bearing potential must be willing to practice approvedhighly effective methods of contraception at the time of informed consent, andcontinue within 1 year after the completion of treatment;
11. Be able to understand and sign the informed consent document.

Exclusion Criteria:

• Patients with any of the following criteria will not be allowed to participation:

1. Test subjects who have a history of hypersensitivity to any component orexcipient of HS-IT101 or other study drugs (cyclophosphamide, fludarabine andrecombinant human interleukin-2);
2. Test subjects have any uncontrollable clinical problems (including but notlimited): hypertension poorly controlled by medication (blood pressure ≥160/100mmHg at restafter taking medication); poorly controlled diabetes; cardiac disease (New YorkHeart Association class Ⅲ/Ⅳ congestive heart failure or heart block);
3. Test subjects who have active major medical illnesse(es) of the cardiovascular (within 6 months prior to enrollment), including deep vein thrombosis orpulmonary embolism; myocardial infarction; severe or unstable arrhythmia orangina pectoris; percutaneous coronary intervention, acute coronary syndrome,coronary artery bypass grafting; cerebrovascular accident, transient cerebralischemia Seizures, cerebral embolism;
4. Active autoimmune diseases that require systemic treatment during the studyperiod (eczema, vitiligo, psoriasis, alopecia or Grave's disease that do notrequire systematic treatment in the past two years, other autoimmune diseasesthat are not expected to recur, hypothyroidism that only requires thyroid hormonereplacement therapy, and type I diabetes subjects that only require insulinreplacement therapy can be included);
5. Organ transplantation and a history of hematopoietic stem cell transplantation;
6. Any immunosuppressive drugs, such as steroids, have been used within 4 weeksprior to tumor tissue sampling, or the researcher has determined the presence ofcomorbidities that require the use of immunosuppressive drugs during the trialperiod. However, physiological doses of glucocorticoids (i.e. ≤ 12 mg/m2/day ofhydrocortisone or other hormones within the equivalent dose range afterequivalent dose conversion) are allowed, and steroid drugs are allowed forintranasal or local use;
7. Individuals who have received systematic anti-tumor therapy within 4 weeks priorto pre-treatment (including those who have participated in other clinical trialdrug treatments; those who have metabolized 5 drugs with a half-life of less than 4 weeks, whichever is shorter) or those who plan to participate in otherintervention clinical trials during the study period;
8. Presence of acute or chronic infection: HIV positive, Treponema pallidum antibody positive, or clinically activehepatitis B and C, including virus carriers (excluding HBsAg and/or HBeAgpositive individuals for hepatitis B; excluding HCVAb positive individuals forhepatitis C);Active infections or active tuberculosis infections that requiresystemic treatment;
9. Vaccinated with the new coronavirus vaccine within 4 weeks propr to screening, orwho have received a live vaccine within 3 months, or who plan to receive livevaccine during the trial;
10. Major organs underwent surgery (excluding needle biopsy) or significant traumawithin 4 weeks before screening；required elective surgery during the study;
11. Patients who have surgical complications or delayed healing prior to screening,and have been determined by the researchers to increase the risk of gonorrheapretreatment, adoptive TIL therapy, and IL-2 adjuvant therapy;
12. Test subjects who have had another primary malignancy within the previous 5years, excluding basal cell carcinoma of the skin, squamous cell carcinoma of theskin and/or carcinoma in situ after radical resection;
13. Suffering from severe respiratory system diseases (with a history of or combinedwith severe interstitial lung disease, severe chronic obstructive pulmonarydisease, severe pulmonary insufficiency, and symptomatic bronchospasm);
14. Patients with gastrointestinal bleeding requiring surgical treatment, localintestinal ischemia or perforation;
15. Patients with known meninges metastasis; Patients with known uncontrolled oruntreated central nervous system metastases (excluding those who have receivedstable treatment symptoms and stopped glucocorticoid and anticonvulsant drugtreatment ≥ 4 weeks prior to pre-treatment);
16. Previously received similar cell therapy products;
17. Females in pregnancy or lactation;
18. Subject have mental illness, alcoholism, drug or substance abuse；or researchersconsidering the test subject as having other reasons inappropriate for theclinical study.