Metastatic Cutaneous Melanoma, Metastatic Uveal Melanoma
Conditions
Keywords
Adoptive Cell Therapy, Tumor Infiltrating Lymphocyte, Hepatic Arterial Infusion, Melphalan, Interleukin-2
Brief summary
The purpose of this study is to evaluate the feasibility, safety and tolerability of locoregional or systemic administration of autologous tumor infiltrating lymphocytes in patients with metastatic melanoma
Interventions
DRUGAutologous Tumor Infiltrating Lymphocytes (TIL)
Cohort 1: Administered via hepatic arterial infusion Cohort 2: Administered via intravenous infusion
DRUGMelphalan
1 mg/kg, IV
DRUGInterleukin-2
2 MIU, subcutaneous twice daily for up to 14 days.
Sponsors
Vastra Gotaland Region
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Cohort 1 Patients With Uveal Melanoma and Liver Metastases, locoregional admin using HAI Cohort 2 Patients With Cutaneous Melanoma and visceral metastases, IV admin
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must be at least 18 years of age. 2. Can provide a signed informed consent as described in the protocol, including compliance with the requirements and restrictions listed in the ICF and in this protocol. 3. World Health Organization (WHO) Performance Status 0 or 1. 4. Patient must have a histologically/cytologically confirmed diagnosis of: * stage IV uveal melanoma with confirmed progression following prior systemic therapy with tebentafusp (if HLA A2:01 positive) OR * stage IV cutaneous melanoma with confirmed progression following prior systemic therapy with a programmed cell death protein-1 (PD-1) inhibitor with or without a CTLA-4 inhibitor 5. At least one resectable lesion in the liver (or aggregate of lesions resected) of a minimum size of 0.5 cm in diameter to generate TILs. 6. Measurable disease by computed tomography (CT) per RECIST 1.1 criteria after resection of lesion for TILs production 7. No other malignancies, except if treated with curative intent and with a cancer-related life expectancy of more than 5 years. 8. Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Female patients of childbearing potential must be willing to use a highly efficient method of contraception (Pearl index \<1), for the course of the study through 120 days after the last dose of study medication. 10. Male patients with women of childbearing potential partners must agree to use a condom for contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion criteria
1. Any serious or uncontrolled medical conditions that, in the investigator's opinion, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy (including operation), or interfere with the interpretation of study results. 2. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 3. Women who are pregnant or breastfeeding. 4. Any condition that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before registration in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events | 5 years | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs). graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 2 years | RECIST 1.1 |
| Progression free-survival (PFS) | 2 years | Evaluation of Progression-free survival |
| hepatic Progression-free survival (hPFS) | 2 years | Evaluation of hepatic Progression-free survival |
| Duration of objective response (DOR) | 2 years | Evaluation of duration of a response by RECIST 1.1 |
| Overall Survival (OS) | 5 years | Evaluation of Overall Survival |
| Evaluation of feasibility of an automated production of TILs | 2 years | Defined as the proportion of patients included that receive treatment with the TIL product. |
Contacts
CONTACTLars Ny, PhD
CONTACTAxel Nelson, PhD
Outcome results
None listed