TIL Cells for the Treatment of the Advanced Solid Tumors Patients

Study Overview
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Brief Summary
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This study is to investigate the safety and efficacy of tumor infiltrating lymphocyte (TILs) therapy in patients with Advanced malignant solid tumors. TILs are expanded from tumor resections or biopsies, and after ex vivo stimulation, activation and extensive expansion, are reinfused to patients after non-myeloablative lymphocyte-depleting preparative regimen.

Detailed Description
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This is a single-center, open-label, Phase I clinical study of TILs for the treatment of the recurrent/metastatic solid tumors patients who had failed standard therapy. TILs are expanded from tumor resections or biopsies, and after ex vivo stimulation, activation and extensive expansion, are reinfused to patients after non-myeloablative lymphocyte-depleting preparative regimen. The primary purpose of this study is to evaluate the safety and tolerability of TILs in patients with recurrent/metastatic solid tumors. The second purpose of this study is to preliminarily explore the effectiveness of TILs in patients with recurrent/metastatic solid tumors. Eligibility: Adults aging 18-75 who were failed to standard treatment or have no standard treatment with recurrent/metastatic solid tumors.

Official Title
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A Single-center, Open-label Clinical Study of TIL Cells for the Treatment of the Recurrent/Metastatic Solid Tumors Patients Who Had Failed Standard Therapy

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: Tumor Infiltrating Lymphocytes
* Drug: Fludarabine
* Drug: Cyclophosphamide Capsules
* Drug: IL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have the willingness to communicate with investigator, be able to understand and follow the trail requirements, and voluntarily to participate in the trail; 18   75 years; The expected survival period is at least 3 months; ECOG score of 0-1; There is at least one lesion that can be operated or biopsied for the preparation of TIL; According to RECIST 1.1 standard, there is at least one measurable target lesion for efficacy evaluation; Patients with recurrent or metastatic solid tumors confirmed by histopathology; Subjects who failed standard treatment in the past or have no standard treatment currently tor who are judged by the investigator to be unsuitable for current standard treatment for other reasons, and the objective imaging assessment is disease progression Exclusion Criteria: Female subjects who are pregnant or breastfeeding, or have a positive blood pregnancy test at baseline ; Subjects who have had severe allergic reactions to any drug or its components in this trial in the past; Subjects who have received any investigational drug within 28 days before the infusion of TIL cells, or participated in another clinical study at the same time; Subjects who have other known history of malignant tumors in the past 5 years, except for localized tumors that have been cured, including in situ cervical carcinoma, basal cell carcinoma of the skin, and in situ prostate carcinoma; Patients who have received adoptive cell therapy in the past; According to the judgment of the investigator, the condition of the subject is not suitable for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tumor Infiltrating Lymphocytes<br>TIL cells (2.5×10^9-5×10^10) will be infused i.v. to patients with advanced solid tumors after non-myeloablative lymphocyte-depleting preparative regimen. | Biological: Tumor Infiltrating Lymphocytes<br>* On day 0 patients will be intravenous infusion of TILs<br>Drug: Fludarabine<br>* Part of the non-myeloablative lymphocyte-depleting preparative regimen<br>Drug: Cyclophosphamide Capsules<br>* Part of the non-myeloablative lymphocyte-depleting preparative regimen.<br>Drug: IL-2<br>* Following cell infusion, the patient receives high-dose bolus IL-2, which is dosed to individual patient tolerance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity | Dose Limiting Toxicity (DLT) is defined as patients with the adverse event (AE) or laboratory abnormality recognized by Investigators, and should be possibly related to TILs therapy. | up to Day 28 | 
| Adverse Event | The severity and incidence of various adverse events and serious adverse events | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate(ORR) |  | up to 24 months | 
| Progression free survival (PFS) |  | up to 24 months | 
| Overall survival (OS) |  | up to 24 months |