Phase 1 Study of T-cell Therapy Using CRISPR PD-1 Edited Tumor Infiltrating Lymphocytes for Adults with Advanced or Metastatic Melanoma

What this Trial Is About

Researchers are investigating a new treatment for patients with advanced or metastatic melanoma, a type of skin cancer. This study evaluates whether it is safe and feasible to use tumor infiltrating lymphocytes TILs that have been genetically edited to silence the PD-1 gene using CRISPR-Cas9 technology. The goal is to see if these modified immune cells can be safely infused back into patients and how well this approach works compared to traditional TIL therapy. Participants will receive TILs harvested from their tumors, which are then expanded in the lab over about six weeks. These TILs are modified using CRISPR-Cas9 to silence PD-1 before being infused after lymphodepleting chemotherapy with cyclophosphamide and fludarabine-phosphate. Following infusion, patients may receive up to six doses of high-dose interleukin-2. This treatment is given intravenously and follows a well-known TIL therapy regimen with the added CRISPR modification. During the study, participants will undergo tumor removal surgery, lab processing of TILs, chemotherapy, and TIL infusion. Researchers will monitor safety and feasibility from surgery through infusion over 5 to 10 weeks, and then track treatment-related side effects for three months. They will also assess tumor response up to 12 months after treatment using scans. Participants will have regular evaluations to measure heart, organ function, and overall health, and will be followed until the study ends in 2028.

T-cell Therapy with CRISPR PD1-edited Tumor Infiltrating Lymphocytes for Patients with Metastatic Melanoma