TCR-T Cell Immunotherapy of Lung Cancer and Other Solid Tumors

Phase 1

Recruiting

• Conditions: Nonsmall Cell Lung Cancer; Solid Tumor, Adult
• Interventions: Biological: TCR-T cells

• Registration Number: NCT03778814
• Lead Sponsor: Second Affiliated Hospital of Guangzhou Medical University

Brief Summary

Tumor organoids and TILs (and/or peripheral T cells) cultures will be established from fresh tissure of lung cancer and other solid tumors. Coculture will be utilized to screen tumor-responsive T cells which are further selected for monoclonal expansion and TCR cloning for engineered reconstitution of TCR-T cells. After verification by multiple in vitro and in vivo studies, a large number of TCR-T cells will be introduced back into the patients via vein, artery or fine needle punctured to the tumor, or combinations. In this phase I study, the safety, tolerance and preliminary efficacy of the TCR-T cell immunotherapy on human will firstly be assessed.

Detailed Description

1. Choose appropriate patients with KK-LC-1 expression in advanced lung cancer or other solid tumors and matched MHC-A11 typing, with written consent for this study; For cancer without expression of KK-LC-1, fresh tumor tissue should be obtained for RNA/DNA sequencing to computationally identify neoantigen peptides that can be captured by specifically personizedly synthesized poly-MHCI which can be further used to fish appropriate T cells from the patient.

2. Perform biopsy to obtain tissue from tumor/lymph node for organoids, TILs, DC and T cells culture, coculture to screening anti-tumor T cells, establish and select monoclonal T cells for TCR cloning;

3. Clone TCR sequence that targets KK-LC-1 or neoantigens; collect PBMCs from the blood of the patients, isolate and activate the T cells and generate the TCR-T cells;

4. Test the quality and killing activity of the TCR-T cells in vitro and then transplant back the patients via systemic (vein and/or artery) or local injections, and follow up closely to collect related clinical data as needed;

5. Evaluate the clinical results as needed.

Study Timeline

• Study Start: 2018-12-01
• Study First Submitted: 2018-12-16
• Study First Submitted QC: 2018-12-16
• Study First Posted: 2018-12-19
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-22
• Last Update Posted: 2024-06-25
• Primary Completion: 2029-12-30
• Study Completion: 2036-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. patients with advanced lung tumor or other solid tumor where biopsy is obtainable
2. Life expectancy >12 weeks
3. Child-Pugh-Turcotte score <7
4. Adequate heart,lung,liver,kidney function
5. Available autologous transduced T cells with greater than or equal to 20% expression of targeted TCR sequences determined by flow-cytometry and killing of tumor cells greater than or equal to 20% in cytotoxicity assay
6. Informed consent explained to, understood by and signed by patient/ guardian. Patient/guardian given copy of informed consent. -

Exclusion Criteria

1. Had accepted gene therapy before;
2. Tumor size more than 25cm;
3. Severe virus infection such as HBV, HCV, HIV, et al
4. Known HIV positivity
5. History of lung transplantation
6. Active infectious disease related to bacteria, virus,fungi,et al
7. Other severe diseases that the investigators consider not appropriate;
8. Pregnant or lactating women
9. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
10. Other conditions that the investigators consider not appropriate.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TCR-T cell therapy group	TCR-T cells	Appropriate lung cancer or other solid tumor patients who could benefit from immunotherapy will be treated with targeting TCR-T cells.

Primary Outcome Measures

Name	Time	Method
Number of Patients with Dose Limiting Toxicity	three months	A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the TCR-T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.

Secondary Outcome Measures

Name	Time	Method
Percent of Patients with best response as either complete remission or partial remission	three months	Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.

Trial Locations

Locations (1)

The Second Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guanzhou, Guangdong, China