TIL Therapy in Non-small-cell Lung Cancer (NSCLC) Patients

NCT ID: NCT06455917

Last Updated: 2024-12-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2029-12-31

Brief Summary

Aim of the study is to investigate the efficacy and safety of Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in NSCLC patients in a phase II clinical trial.

Detailed Description

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a personalized immunotherapy. In patients with advanced Non-Small Cell Lung Cancer (NSCLC), a phase I clinical trial has investigated TIL-ACT in patients who progressed during ICI-treatment.

For TIL-ACT, tumor-specific T cells are expanded from excised tumor samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous TILs are then re-infused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Activation of TILs in the patient is then supported by IL-2 administration.

Conditions

Non-Small Cell Lung Cancer

Keywords

tumor-infiltrating lymphocytes; adoptive cell therapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tumor-infiltrating lymphocyte product (TIL) transfer

Tumor-specific T cells are expanded from excised tumor samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous TILs are then re-infused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Activation of TILs in the patient is then supported by IL-2 administration. The transplant product will be produced in the Good Manufacturing Practice (GMP) facility of the University Hospital in Basel.

Group Type: EXPERIMENTAL

Combination of TIL Transfer and low dose IL-2

Intervention Type: DRUG

The study uses a personalized IMP, i.e. TIL product and in combination with IL-2 treatment.

• TIL transfer: transfer of the TIL product (i.v., 1 infusion of 5 x109 - 2 x1011 lymphocytes, day 0).
• Interleukin-2 (IL-2) therapy: administration of Aldesleukin (600'000 IU/kg body weight, i.v., every 8 hours for up to 15 doses).

Interventions

Combination of TIL Transfer and low dose IL-2

The study uses a personalized IMP, i.e. TIL product and in combination with IL-2 treatment.

• TIL transfer: transfer of the TIL product (i.v., 1 infusion of 5 x109 - 2 x1011 lymphocytes, day 0).
• Interleukin-2 (IL-2) therapy: administration of Aldesleukin (600'000 IU/kg body weight, i.v., every 8 hours for up to 15 doses).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Ability of the patient to understand the purpose of the study, provide signed and dated informed consent prior to performing any protocol-related procedures (including screening evaluations), and be able and willing to comply with the study procedures.

2. Age ≥ 18 years.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (cf. Appendix).

4. Histologically confirmed NSCLC.

5. Disease progression after at least one standard therapy and without any approved curative-intended treatment option.

6. Accessible tumor lesion/metastasis for tumor collection.

7. Willingness of the patient to undergo a surgical intervention (eg, surgical resection and/or biopsy) to collect one or more tumor lesions/metastases.

8. Adequate organ function (pulmonary, cardiovascular, hematological, hepatic, and renal function) per investigator's judgment. Cardiac stress testing is required for all patients with underlying cardiac conditions and patients with age ≥ 50 years.

9. Negative serum pregnancy test in women of childbearing potential, in peri-menopausal women and in women with less than 2 years of menopause.

Exclusion Criteria

1. Active central nervous system (CNS) metastases. Patients with stable CNS metastases ≥ 1 month after definitive treatment (eg, surgery and/or radiotherapy) are eligible.

2. Participants with an active second malignancy.

3. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol, including autoimmune or immunodeficient conditions, significant pulmonary disease, significant cardiac and/or vascular disease per investigator's judgment.

4. Prior immune-related adverse events that would preclude re-challenge with an immune checkpoint inhibitor or immunomodulatory agent per investigator's judgment.

5. Immunosuppressive treatment that would preclude the patient from any of the study therapies per investigator's judgment.

6. Severe active infections or uncontrolled infectious conditions requiring treatment.

7. Any other conditions/diseases, allergies, dysfunctions, and/or findings, that would contraindicate the use of any of the study interventions or therapies.

8. Contraindication for any of the planned measures, interventions and/or treatments.

9. Pregnant or breastfeeding women, or female subject who are not willing to use an acceptable, highly effective method of contraception until the End-of-Study visit.

10. Known hypersensitivity to any of study therapies or drugs used for TIL production.

11. Known human immunodeficiency virus (HIV) infection (or tests positive for HIV 1 or 2 at Screening).

12. Known hepatitis B or hepatitis C infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David König, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

Countries

Switzerland

Central Contacts

David König, MD

Role: CONTACT

Phone: +41 61 265 5074

Email: david.koenig@usb.ch

Heinz Läubli, Prof.

Role: CONTACT

Phone: +41 61 265 5074

Email: heinz.laeubli@usb.ch

Facility Contacts

David König, MD

Role: primary

Heinz Läubli, Prof.

Role: backup

Other Identifiers

2024-00254; th22Laeubli

Identifier Type: -

Identifier Source: org_study_id