A Phase I Trial Of Pd-1 Deficient Engineered T Cells With Crispr/Cas9 In Patients With Advanced Non-Small Cell Lung Cancer.

3050Background: We performed the first phase I clinical trial (NCT02793856) to assess safety of CRISPR/Cas9-mediated knockout of PD-1 gene in autologous T lymphocytes (PD-1-/- T) therapy in patients with metastatic non-small cell lung cancer (NSCLC). Methods: We assigned patients with advanced NSCLC with positive PD-L1 expression who had progressed after 3rd line standard therapeutic regimens. Two patients were enrolled in Pre-A cohort who received PD-1-/- T therapy with 2 x 107 cells/kg for one cycle and were observed for another cycle. Then 3 cohorts (A, B, C) enrolled 3 patients in each group receiving PD-1-/- T cells therapy with 1×107/kg, 2×107/kg, 4×107/kg in each cycle, respectively. Patients received PD-1-/- T therapy until disease progression or study withdrawal. Primary outcome was safety. Secondary end points were 8 weeks disease control rate (DCR) and progression-free survival (PFS). In exploratory analyses, next-generation sequencing was performed on PD-1 editing region of T cells and CDR3 re...