Safety and Activity of Programmed Cell Death-1 Gene Knockout Engineered T Cells in Patients with Previously Treated Advanced Esophageal Squamous Cell Carcinoma: an Open-Label, Single-Arm Phase I Study.

3054 Background: We designed the clinical trial to investigate the safety and activity of Programmed death-1 (PD-1) knockout engineered T cell in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients (aged ≥18 years) with advanced ESCC whose disease had progressed after at least two systemic therapies were enrolled. Peripheral blood will be collected and PD-1 gene will be knocked out by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in the laboratory. T lymphocytes will be selected, expanded and reinfused back into patients after about 2-3 weeks. Response was assessed 4 weeks after each infusion. Patients continued receiving treatment until disease progression, intolerable toxicity, or consent withdrawal. The primary endpoint was to evaluate the safety of PD-1 knockout engineered T cells treatment. Results: Between Mar, 2017, and Jan, 2018, we enrolled 21 patients who received at least one cycle PD-1 knockout engineered T cells treatment. Among 21 treated patients, 7 accepted only 1 cycle of cell infusion, 12 accepted 2 cycles, and 2 accepted 3 cycles. Up to the study cutoff date of Jan 31, 2018, the most common adverse events were transient fever (7 patients, the highest was 39.1℃) and chills (3 patients) and moderate skin rash (1 patient). No grade 3 or 4 adverse events were observed in the study. Of the 17 evaluable patients, no complete or partial responses were observed. 6 patients had stable disease, and 11 patients had progressive disease. Disease control rate was 35% (6/17) and median overall survival was 127 days (95% CI 45–209). During the trial, 10 cancer progression related deaths occurred. Immunofluorescence analysis showed that the PD-1 knockout engineered T cells could infiltrate into and persist for a durable time in ESCC that responded to therapy. Conclusions: The results showed that PD-1 knockout engineered T cells infusion might be an effective treatment in patients with heavily pretreated advanced ESCC. The treatment was well tolerated with no unexpected safety concerns. The regimen warrant further clinical investigation. Clinical trial information: NCT03081715.