TIL Therapy in Non-small-cell Lung Cancer (NSCLC) Patients
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Drug: Combination of TIL Transfer and low dose IL-2
- Registration Number
- NCT06455917
- Lead Sponsor
- University Hospital, Basel, Switzerland
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (cf. Appendix).
- Histologically confirmed NSCLC.
- Disease progression after at least one standard therapy and without any approved curative-intended treatment option.
- Accessible tumor lesion/metastasis for tumor collection.
- Willingness of the patient to undergo a surgical intervention (eg, surgical resection and/or biopsy) to collect one or more tumor lesions/metastases.
- 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.
- Negative serum pregnancy test in women of childbearing potential, in peri-menopausal women and in women with less than 2 years of menopause.
- Active central nervous system (CNS) metastases. Patients with stable CNS metastases ≥ 1 month after definitive treatment (eg, surgery and/or radiotherapy) are eligible.
- Participants with an active second malignancy.
- 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.
- Prior immune-related adverse events that would preclude re-challenge with an immune checkpoint inhibitor or immunomodulatory agent per investigator's judgment.
- Immunosuppressive treatment that would preclude the patient from any of the study therapies per investigator's judgment.
- Severe active infections or uncontrolled infectious conditions requiring treatment.
- Any other conditions/diseases, allergies, dysfunctions, and/or findings, that would contraindicate the use of any of the study interventions or therapies.
- Contraindication for any of the planned measures, interventions and/or treatments.
- 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.
- Known hypersensitivity to any of study therapies or drugs used for TIL production.
- Known human immunodeficiency virus (HIV) infection (or tests positive for HIV 1 or 2 at Screening).
- Known hepatitis B or hepatitis C infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tumor-infiltrating lymphocyte product (TIL) transfer Combination of TIL Transfer and low dose IL-2 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.
- Primary Outcome Measures
Name Time Method Progression-free rate at 6 months after Tumor-infiltrating lymphocytes transfer. 5-7 months after TIL transfer Progression-free rate (PFR) (RECIST v1.1 / iRECIST) at 6 months after TIL transfer, defined by the Kaplan-Meier estimator for progression-free survival (RECIST v1.1 / iRECIST) at 6 months (+/- 4 weeks as we allow this interval in the tumor assessment at 6 months).
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) up to one year after TIL transfer DOR is defined as the time from the first documented response and the date of the first documented tumor progression, death, or the last tumor assessment that occurred before subsequent therapy. DOR time for responders who have not progressed or died will be censored at the time of last tumor assessment
Frequency of adverse events (number) up to one year after TIL transfer Frequency of adverse events (number) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2
Incidence of adverse events (%) up to one year after TIL transfer Incidence of adverse events (%) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2
Objective response rate (ORR) up to one year after TIL transfer ORR is defined as the proportion of patients with a best overall response of partial response or better (assessed by the local investigators
Severity of adverse events (CTCAE v5.0 criteria) up to one year after TIL transfer Severity of adverse events (CTCAE v5.0 criteria) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2
CTCAE (Common Terminology Criteria for Adverse Events): Grade 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal.Overall survival (OS) up to one year after TIL transfer OS is defined as the time from registration to the date of death due to any cause
Progression-free survival (PFS) up to one year after TIL transfer The progression-free survival (PFS) is defined as the time from registration to objective tumor progression (determined by local investigators), or death due to any cause, whichever occurred first. PFS time for patients who have not progressed or died will be censored at the time of the last tumor assessment
Trial Locations
- Locations (1)
University Hospital Basel
🇨🇭Basel, Basel-Stadt, Switzerland