TCR-T Cells for the Treatment NY-ESO-1-positive Advanced Solid Tumors

Study Overview
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Brief Summary
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New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1) is a Cancer-Testis Antigen (CTA) which is expressed in various tumors. After selected the high affinity TCR gene to NY-ESO-1, the researchers insert genes into the cell that expressing a kind of protein that targeting NY-ESO-1. Then the engineered cells are re-infused in the patients with tumors for curing the tumor patient or prolonging life.

Detailed Description
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This is a single-center, open-label, Phase I clinical study of TCR-T cells for the treatment of the recurrent/metastatic solid tumors patients who had failed standard therapy. TCR-T cells are expanded from peripheral blood, and after ex vivo modification, 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 TCR-T cells in patients with recurrent/metastatic solid tumors. The second purpose of this study is to preliminarily explore the effectiveness of TCR-T cells in patients with recurrent/metastatic solid tumors. Eligibility: Adults aging 18-70 who were failed to standard treatment or have no standard treatment with recurrent/metastatic solid tumors.

Official Title
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A Single-arm, Open-label, Dose-finding Clinical Study of TCR-T Cells in Patients With HLA-A2-expressing and NY-ESO-1-positive Recurrent or Metastatic Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Biological: TCR-T cells
* Drug: Fludarabine
* Drug: Cyclophosphamide Capsules
* Drug: Albumin-bound paclitaxel
* 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  70 years old (gender is not limited;) The expected survival period is at least 3 months; ECOG score of 0-1; 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; According to RECIST 1.1 standard, there is at least one measurable target lesion for efficacy evaluation; NY-ESO-1 positive; HLA type is HLA-A2 (except HLA-A*0203); 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: 70 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCR-T cells<br>TCR-T cells will be infused to patients with advanced solid tumors after non-myeloablative lymphocyte-depleting preparative regimen. | Biological: TCR-T cells<br>* patients will be administration of TCR-T cells<br>Drug: Fludarabine<br>* Part of the non-myeloablative lymphocyte-depleting preparative regime<br>Drug: Cyclophosphamide Capsules<br>* Part of the non-myeloablative lymphocyte-depleting preparative regime<br>Drug: Albumin-bound paclitaxel<br>* Part of the non-myeloablative lymphocyte-depleting preparative regime<br>Drug: IL-2<br>* Following cell infusion, the patient will be administration high-dose IL-2.<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 TCR-T cells therapy | up to Day28 | 
| 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) | Objective response rate (ORR) is defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors [RECIST 1.1]) is observed as best overall response | up to 24 months | 
| Progression free survival (PFS) | PFS is defined as time from start of treatment to the first documentation of disease progression or death, whichever occurs first | up to 24 months | 
| Overall survival | OS defined as the time from start of treatment to the date of death due to any cause | up to 24 months |