Clinical trial NCT06455917: TIL Therapy in Non-small-cell Lung Cancer (NSCLC) Patients
Official title: A Phase II Trial of Adoptive Cell Therapy With Tumor-infiltrating Lymphocytes in Patients With Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: tumor-infiltrating lymphocytes
adoptive cell therapy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2024-06-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free rate at 6 months after Tumor-infiltrating lymphocytes transfer.
timeFrame: 5-7 months after TIL transfer
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: up to one year after TIL transfer
measure: Overall survival (OS)
timeFrame: up to one year after TIL transfer
measure: Severity of adverse events (CTCAE v5.0 criteria)
timeFrame: up to one year after TIL transfer
measure: Objective response rate (ORR)
timeFrame: up to one year after TIL transfer
measure: Duration of response (DOR)
timeFrame: up to one year after TIL transfer
measure: Frequency of adverse events (number)
timeFrame: up to one year after TIL transfer
measure: Incidence of adverse events (%)
timeFrame: up to one year after TIL transfer
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: David König, MD
role: PRINCIPAL_INVESTIGATOR
References: