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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: TCR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide Capsules; Drug: Albumin-bound paclitaxel; Drug: IL-2

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Meifang Li; Phone Number: 15985795022; Email: 362952772@qq.com
• Study Contact Backup: Name: Zhiyong He; Phone Number: 13805086391; Email: heyong1015@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have the willingness to communicate with investigator, be able to understand and follow the trail requirements, and voluntarily to participate in the trail;
2. 18 ~70 years old (gender is not limited;)
3. The expected survival period is at least 3 months;
4. ECOG score of 0-1;
5. Patients with recurrent or metastatic solid tumors confirmed by histopathology;
6. 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;
7. According to RECIST 1.1 standard, there is at least one measurable target lesion for efficacy evaluation;
8. NY-ESO-1 positive;
9. HLA type is HLA-A2 (except HLA-A*0203);

Exclusion Criteria:

1. Female subjects who are pregnant or breastfeeding, or have a positive blood pregnancy test at baseline;
2. Subjects who have had severe allergic reactions to any drug or its components in this trial in the past;
3. 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;
4. 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;
5. Patients who have received adoptive cell therapy in the past;
6. According to the judgment of the investigator, the condition of the subject is not suitable for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TCR-T cells; TCR-T cells will be infused to patients with advanced solid tumors after non-myeloablative lymphocyte-depleting preparative regimen.

Biological: TCR-T cells; patients will be administration of TCR-T cells; Drug: Fludarabine; Part of the non-myeloablative lymphocyte-depleting preparative regime; Drug: Cyclophosphamide Capsules; Part of the non-myeloablative lymphocyte-depleting preparative regime; Drug: Albumin-bound paclitaxel; Part of the non-myeloablative lymphocyte-depleting preparative regime; Drug: IL-2; Following cell infusion, the patient will be administration high-dose IL-2.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital
• Investigators: Principal Investigator: zhiyong He, Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Estimate): December 13, 2022

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Cyclophosphamide; Paclitaxel; Albumin-Bound Paclitaxel; Fludarabine
• Other Study ID Numbers: FJ002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No