In this study we aim to investigate safety and tolerability of tumor-infiltrating lymphocytes (TIL) adoptive cell therapy (ACT) incorporation in-vivo TIL expansion with ANV419 in patients with advanced melanoma
In brief, this trial consists of four study periods: screening, pre-treatment, treatment, and observational follow-up. In the screening period, patients are screened for trial eligibility. In the pre-treatment period, patients have excisional biopsy/surgical resection of tumor lesion(s) (tumor collection) and TILs are expanded from this lesion/these lesions (TIL expansion). Patients are permitted to receive bridging therapy outside of the study protocol. In the treatment period, patients have TIL-ACT. TIL-ACT includes a detailed procedure of preparative chemotherapy, followed by transfer of the TIL product, followed by in-vivo TIL expansion with ANV419 (2 doses). TIL transfer is defined as day 0 in the study protocol. Patients have an End of Treatment visit (14 days after the last study treatment), a safety follow-up (30 days after the last study treatment) and an efficacy follow up, which is the End of Study visit (day +90). Thereafter, patients will transfer to observational follow-up, which is conducted every 3 months until 1 year after TIL transfer. Patients who terminate the study prematurely during any of the treatment period due to e.g., disease progression, toxicity, patient wish, etc. will also transfer to observational follow-up. The regimen (TIL-ACT with ANV419) has not been tested. Review by the IDSMB (independent data safety monitoring board) will be performed after 3 patients (safety check).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
The study uses a personalized IMP (investigational medicinal product), i.e. TIL product in combination with ANV419. Day 0: Autologous TIL: (minimum 5 x 10\^9 and up to 2x 10\^11 lymphocytes) administered intravenously over 20 to 30 minutes. Day 0: Intravenous treatment with ANV419 at 243 μg/kg 2 hours after the TIL infusion. Actual body weight will be used to calculate the dose of ANV419. Day14: Intravenous treatment with ANV419 at 243 μg/kg. Actual body weight will be used to calculate the dose of ANV419.
University Hospital Basel
Basel, Basel, Switzerland
Incidence of adverse events (%)
Incidence of adverse events (%) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419
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 ANV419
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 ANV419. 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
Time frame: up to one year after TIL transfer
Progression-fee 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
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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