Aim of the study is to investigate the efficacy and safety of adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) in patients with advanced pre-treated non-small cell lung cancer (NSCLC).
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. TIL-ACT involves the infusion of autologous CD4+ and CD8+ T lymphocytes collected from tumor material and expanded ex-vivo with IL-2. These polyclonal immune cells can recognize and target multiple individualized tumor-specific antigens. Clinical trials have demonstrated significant response rates in advanced melanoma patients. However, few trials have investigated TIL-ACT in other solid tumors, including NSCLC. For NSCLC patients experiencing disease progression after standard therapies (immune checkpoint inhibitors, targeted therapies), effective options are limited, often restricted to traditional chemotherapy with modest response rates, short durability, and significant toxicity. TIL-ACT represents an attractive individualized treatment approach for NSCLC patients. The BaseTIL-02L study is a single-arm phase II trial investigating TIL-ACT efficacy in pretreated NSCLC patients. The study protocol includes preconditioning non-myeloablative chemotherapy (cyclophosphamide and fludarabine) and in-vivo TIL activation with high-dose interleukin 2 (for up to 15 doses, every 8 hours) following TIL transfer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
The study procedures are: * Tumor collection: Study-specific intervention (eg, surgical resection and/or biopsy) to collect tumor material from one or more tumor lesions/metastases for the generation of the TIL product (tumor-infiltrating lymphocytes, TILs). * TIL expansion: Production of the TIL product in the Good-Manufacturing-Practice (GMP) Facility for Advanced Therapies of the University Hospital of Basel. * Lymphodepleting chemotherapy (lymphodepletion): Chemotherapy with cyclophosphamide and fludarabine (day -7 until day -3). * TIL transfer: Infusion of the TIL product back to the patient. TIL transfer is scheduled on day 0. * Interleukin-2 (IL-2) therapy: Therapy with high-dose IL-2 (Aldesleukin) every 8 hours for up to 15 doses. IL-2 therapy starts on day 0.
Department of Medical Oncology, University Hospital Basel
Basel, Canton of Basel-City, Switzerland
RECRUITINGProgression-free rate at 6 months after Tumor-infiltrating lymphocytes 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).
Time frame: 5-7 months after TIL transfer
Progression-free survival (PFS)
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
Time frame: up to one year after TIL transfer
Overall survival (OS)
OS is defined as the time from registration to the date of death due to any cause
Time frame: up to one year after TIL transfer
Severity of adverse events (CTCAE v5.0 criteria)
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.
Time frame: up to one year after TIL transfer
Objective response rate (ORR)
ORR is defined as the proportion of patients with a best overall response of partial response or better (assessed by the local investigators
Time frame: up to one year after TIL transfer
Duration of response (DOR)
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
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Time frame: up to one year after TIL transfer
Frequency of adverse events (number)
Frequency of adverse events (number) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2
Time frame: up to one year after TIL transfer
Incidence of adverse events (%)
Incidence of adverse events (%) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2
Time frame: up to one year after TIL transfer