Tumor-infiltrating lymphocyte (TIL) therapy for advanced NSCLC

A Phase II Trial of Adoptive Cell Therapy With Tumor-infiltrating Lymphocytes in Patients With Non-Small Cell Lung Cancer

This trial will try using a patient's own tumor-infiltrating lymphocytes, given after short chemotherapy and IL-2, to shrink tumors in adults with advanced NSCLC who have progressed after standard treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Basel, Switzerland (other)
• Drugs / interventions: chemotherapy, immunotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Basel, Canton of Basel-City)
• Trial ID: NCT06455917 on ClinicalTrials.gov

What this trial studies

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL-ACT) is a personalized immunotherapy in which a patient's own CD4+ and CD8+ T cells are expanded outside the body and returned to target tumor-specific antigens. This single-arm Phase II trial enrolls pretreated NSCLC patients who undergo surgical tumor collection, receive non-myeloablative cyclophosphamide and fludarabine, then an infusion of autologous TILs followed by in vivo activation with high-dose interleukin-2 (up to 15 doses every 8 hours). The protocol monitors tumor response, durability of response, and treatment-related toxicity. While TIL-ACT has shown notable activity in melanoma, evidence in NSCLC is limited, so this study examines feasibility and clinical activity in that population.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed NSCLC, ECOG performance status 0–1, disease progression after at least one standard therapy, an accessible tumor lesion for collection, and adequate organ function who can tolerate surgery and intensive immunotherapy.

Not a fit: Patients unlikely to benefit include those with poor performance status (ECOG >1), inadequate organ function, rapidly progressive disease that prevents tumor harvest, or inability to tolerate the required preconditioning chemotherapy and high‑dose IL‑2.

Why it matters

Potential benefit: If successful, this approach could produce durable tumor responses and extend progression-free and overall survival for some patients with pretreated NSCLC.

How similar studies have performed: TIL-ACT has produced significant responses and durable remissions in advanced melanoma, but its application to NSCLC is novel and only a few early trials have explored it.

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.

Where this trial is running

Basel, Canton of Basel-City

• Department of Medical Oncology, University Hospital Basel — Basel, Canton of Basel-City, Switzerland (RECRUITING)

Study contacts

• Principal investigator: David König, Dr. med. — University Hospital, Basel, Switzerland
• Study coordinator: David König, Dr. med.

Conditions: Non-Small Cell Lung Cancer, Lung Cancer, tumor-infiltrating lymphocytes, adoptive cell therapy