Overview

A Single-Arm, Open-Label, Interventional Study to Evaluate the Efficacy of HS-IT101 Autologous Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy After Lymphodepleting Preconditioning with Fludarabine and Cyclophosphamide and Subsequent Interleukin-2 Therapy in Patients with Advanced Renal Cancer.

Eligibility

Inclusion Criteria:

1. Aged 18 to 75 years old, regardless of gender;
2. Pathologically confirmed by histology and/or cytology as metastatic or unresectable clear cell renal cell carcinoma (defined as clear cell component accounting for more than 50%), and has experienced treatment failure after at least one previous first-line standard therapy;
3. Before screening, there is at least one biopsiable lesion that has not received radiation therapy or other local treatments (such as ablation therapy, oncolytic virus, etc.) within 28 days, and the lesion meets the sampling requirements;
4. After tumor tissue sampling, there is at least one measurable tumor lesion defined by the RECIST 1.1 criteria (Lesions located in areas that have received previous local treatment, including previous radiotherapy, are not considered measurable lesions, unless it is confirmed that the lesion in this area has developed disease progression as defined by RECIST 1.1 after local treatment); (5) ECOG performance status is 0 or 1;

(6) Expected survival time ≥ 3 months; (7) Evaluated via laboratory and other examinations during the screening period, the participant has good organ function; (8) Before tumor tissue collection, adverse reactions caused by previous treatment have recovered to ≤ Grade 1 in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) 6.0, except for toxicities that investigators judge have no safety risk, such as hyperthyroidism and hair loss; (9) Agree to take effective non-drug contraceptive measures from the date of signing the informed consent form to the end of the study; (10) Fully understand this trial, voluntarily sign the informed consent form, and are able to comply with the visit and relevant procedures specified in the study protocol.

Exclusion Criteria:

1. Use of any immunosuppressive medications, such as corticosteroids, within 4 weeks prior to tumor tissue collection, or presence of a concurrent disease requiring immunosuppressive medication during the study as judged by the investigator. Intranasal or topical corticosteroid use is allowed.
2. Major organ surgery or significant trauma within 4 weeks prior to screening, or requirement for elective surgery during the study, except cytoreductive surgery performed for tumor tissue collection.
3. Received systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to tumor tissue collection.
4. Received a live vaccine within 3 months prior to screening, or plans to receive a live vaccine during the study.
5. History of severe hypersensitivity reaction to any drug used in the study.
6. Prior treatment with similar cell therapy products.
7. Prior organ transplantation or hematopoietic stem cell transplantation.
8. Gastrointestinal bleeding requiring surgical treatment, intestinal ischemia, or perforation.
9. Any of the following events within 6 months prior to screening: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina pectoris; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, or cerebral embolism.
10. Diagnosis of another primary malignancy within 5 years prior to screening, except curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected carcinoma in situ.
11. Pleural effusion, pericardial effusion, or ascites that remains uncontrolled despite drainage or requires repeated drainage.
12. Surgical complications or delayed wound healing prior to screening that, in the investigator's judgment, would increase the risk of study treatment.

13Severe respiratory disease. 14.Known leptomeningeal metastasis; symptomatic central nervous system (CNS) metastases. Participants with previously treated brain metastases who are clinically stable (as confirmed by MRI) for at least 12 weeks may be enrolled.

15.Any uncontrolled clinical condition. 16.Active autoimmune disease requiring systemic treatment during the study. 17.Presence of acute or chronic infection. 18.Pregnant or breastfeeding women. 19.Known psychiatric illness, alcoholism, drug abuse, or substance abuse. 20.Any other condition that, in the investigator's opinion, makes the participant unsuitable for the study.