TIL Therapy Combined With Pembrolizumab for Advanced or Metastatic Refractory Lung Cancer

NCT06538012 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202472
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) immunotherapy in patients with advanced or metastatic refractory lung cancer. Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has demonstrated significant success in treating unresectable or metastatic melanoma by utilizing the patient's own immune cells to combat cancer. This study aims to apply a similar approach to lung cancer. TILs will be harvested from patients' tumors, expanded in vitro, and infused back into the patients following a non-myeloablative lymphodepletion regimen. Pembrolizumab, a monoclonal antibody targeting the PD-1 receptor on T cells, will be administered to enhance the immune response. The primary endpoint is to determine the objective response rate (ORR) of this combined therapy. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and quality of life (QoL). This trial aims to offer a novel, personalized treatment option for patients with limited therapeutic alternatives.

Conditions

Lung Cancer; Lung Cancer Metastatic; Lung Cancer, Non-small Cell; Lung Cancer Recurrent

Keywords

Tumor Infiltrating Lymphocytes; CAR-T CELL; Biological Therapy; Advanced or Metastatic Refractory; Immunotherapy; TIL

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  To characterize the safety profile of (TIL) and natural autologous TIL in patients with advanced solid tumors who were failed to standard treatment as assessed by incidence of adverse events.

  6 months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to 36 months

• Disease Control Rate (DCR）

  Up to 36 months

• Duration of Response (DOR)

  Up to 36 months

• Progression-Free Survival (PFS)

  Up to 36 months

Study Arms (1)

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

EXPERIMENTAL

Patients receive pembrolizumab IV on day -14, cyclophosphamide IV QD on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and TILs IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80. MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Biological: Tumor Infiltrating Lymphocytes (TIL); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: Pembrolizumab

Interventions

Tumor Infiltrating Lymphocytes (TIL) BIOLOGICAL

Tumor Infiltrating Lymphocytes (TIL) IV

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Cyclophosphamide DRUG

Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Fludarabine DRUG

Fludarabine will be administered as an intravenous (IV) infusion for five days.

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Interleukin-2 DRUG

After TIL infusion, IL-2 will be started as a bolus administration every eight hours, for a maximum of eight doses.

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Pembrolizumab DRUG

Intravenous (IV) infusion

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Eligibility Criteria

• Age: 16 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 16 years to 90 years
• Histologically diagnosed as primary/relapsed/metastasized Lung cancer
• Expected life span more than 3 months
• Karnofsky≥60% or ECOG score 0-2
• Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
• Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated
• At least 1 evaluable tumor lesion
• Hematology and Chemistry（within 7 days prior to enrollment）:
• Absolute count of white blood cells≥2.5×10\^9/L
• Absolute count of neutropils≥1.5×10\^9/L
• Absolute count of lymphocytes ≥0.7×109/L
• Platelet count≥100×10\^9
• hemoglobin≥90 g/L
• Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
• International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)

You may not qualify if:

• Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment
• Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%
• Significant cardiovascular anomalies according to any of the following definitions:
• New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant
• Low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular conductive block, etc.
• Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive.
• Severe physical or mental diseases;
• Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection).
• Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy.
• History of allergy to chemical compounds consisting of chemical and biological substances resembling cell therapy.
• Having received immunotherapy and developed an irAE level greater than Level 3.
• Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded).
• Females in pregnancy or lactation. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy.
• Researchers consider the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Cyclophosphamide; fludarabine; Interleukin-2; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: August 5, 2024
• Study Start: August 20, 2024
• Primary Completion (Estimated): September 10, 2026
• Study Completion (Estimated): December 28, 2026
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)