The purpose of this study is to assess wether it is safe and feasible to treat patients with tumor infiltrating lymphocytes that have been silenced for PD-1, using CRISPR-Cas9.
Histologically confirmed inoperable or metastatic melanoma (stage IIIc or IV).
Progressive disease after standard treatment with anti-PD-1 check-point inhibition or combination of aforementioned with anti-CTLA-4 check-point inhibition.
Age: 18 - 75 years at the time of signed Informed consent.
ECOG performance status of ≤1 (Appendix 2).
Cytotoxic chemotherapy: Washout period 3 weeks before TR and LDC.
Small molecules/TKI: Washout period 1 week before TR and LDC.
Immune therapy (monoclonal AB therapy, CPI, and biologics): 2 weeks before TR and LDC
Prior T-cell therapy, including gene therapy using an integrating vector.
Single group
TIL therapy
Biological/VaccineCompared to traditional TIL-therapy, this study will include silencing of the PD-1 coding gene in the TILs using non-viral CRISPR-Cas9 prior to the rapid expansion protocol.
Feasibility
Assess feasibility measured by the number of subjects who undergo surgery and successfully undergo CRISPR-TIL infusion
Incidence rate of treatment-emergent adverse events
Determine the safety and tolerability measured by the incidence rate of grade 3 treatment-emergent adverse events and serious adverse events by severity and their relationship to the CRISPR-TIL infusion.
Objective response rate
Assess the clinical effect of the treatment by use of the objective response rate (using RECIST 1.1).
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Inge Marie Svane
Lead sponsor
Herlev Hospital
Sponsor institution
