TILs Plus Third-Generation EGFR-TKI Therapy for TKI-Resistant NSCLC

Safety Study of Tumor-Infiltrating Lymphocytes (TILs) Combined With Third-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Therapy for TKI-Resistant Advanced Non-Small Cell Lung Cancer (NSCLC)

This is a single-arm study designed to evaluate the safety and efficacy of TILs combined with third-generation EGFR-TKIs therapy for patients with EGFR-mutant NSCLC resistant to TKI.

Study Overview

• Status: Not yet recruiting
• Conditions: EGFR-TKI-resistant Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: TILs infusion

Detailed Description

This study is an open-label, single-arm, prospective clinical trial. 50 subjects with advanced EGFR-TKI-resistant NSCLC, including those complicated with malignant pleural effusion, will be enrolled and receive TILs infusion combined with third-generation EGFR-TKIs. Adverse reactions, therapeutic efficacy and other relevant indicators will be closely observed and followed up to systematically evaluate the safety and efficacy of this combined regimen.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• (1) Age 18-75 years, male or female; (2) Patients with a history of surgical resection, pathologically diagnosed with NSCLC, genetically tested for EGFR mutation, who experienced disease progression (local recurrence or distant metastasis) after EGFR-TKI treatment and refused chemotherapy or other therapies; (3) Ability to obtain approximately 5 tumor samples via surgery, biopsy, or bronchoscopy for preparation of autologous tumor-infiltrating lymphocytes; (4) ECOG performance status score of 0-2; (5) HGB ≥70 g/L, transfusion-eligible; (6) No severe hepatic, renal, cardiac, or pulmonary dysfunction, with the following requirements met: Creatinine ≤ 1.5 × ULN; Oxygen saturation > 90%; Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN; (7) Expected survival > 3 months; complete clinical documentation.

Exclusion Criteria:

• (1) Patients with pathological diagnosis of small cell lung cancer components; (2) Patients who have previously undergone organ transplantation or cytoreductive therapy including lymph node clearance; (3) Patients currently receiving immunotherapy or steroid therapy; (4) Patients with concurrent severe or persistent infections that cannot be effectively controlled; (5) Patients with concurrent severe autoimmune diseases or congenital immunodeficiency; (6) History of severe allergic reactions to biological products (including antibiotics); (7) Active hepatitis (quantitative hepatitis B virus DNA [HBV-DNA] above the lower limit of detection for the assay method, or positive hepatitis C antibodies [HCV-Ab] with HCV-RNA above the lower limit of detection for the assay method); (8) HIV infection or syphilis infection; (9) Female patients who are pregnant, breastfeeding, or planning pregnancy within 12 months; (10) Conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: This is a single-arm study of TILs combination with third-generation EGFR-TKIs therapy for NSCLC; Experimental: Surgically collect fresh tumor tissue or malignant pleural effusion to isolate immune cells, and prepare TILs Infusion. Trial product: TILs Injection. Administration route: Intravenous Infusion	Drug: TILs infusion; Experimental: Surgically collect fresh tumor tissue or malignant pleural effusion to isolate immune cells, and prepare TILs Infusion. Trial product: TILs Injection. Administration route: Intravenous Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
According to the incidence of treatment-related adverse events (AEs) to evaluate the safety of Tumor-Infiltrating Lymphocytes (TILs) combined with third-Generation EGFR-TKI therapy for TKI-Resistant advanced Non-Small Cell Lung Cancer (NSCLC)	Incidence of treatment-related adverse events (AEs) Description: Number and severity of adverse events graded according to CTCAE v5.0.	up to three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
According to the subgroup analysis of TILs in patients with TKI-Resistant advanced NSCLC to analyze the correlation between TILs and disease prognosis.	TILs subgroup analysis Description: Composition, phenotype, and function of TILs	Up to three months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
According to the objective response rate (ORR) to evaluate the efficacy of TILs combined with third-Generation EGFR-TKI therapy for TKI-Resistant advanced NSCLC	Objective response rate (ORR) Description：The percentage of subjects with a Complete Response (CR) or Partial Response (PR) determined by RECIST 1.1 criteria.	Up to one year

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: March 16, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; TILs; EGFR-TKI-resistant
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: TILs TKI-SZ

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