Anti-EGFR chimeric antigen receptor-modified T cells in metastatic pancreatic carcinoma: A phase I clinical trial.

The current clinical outcome for patients with metastatic pancreatic carcinoma (PC) remains poor. Epidermal growth factor receptor (EGFR) is detectable in PC, suggesting that EGFR is a rational target in PC. We conducted a phase I clinical trial to evaluate the safety and efficacy of autologous anti-EGFR chimeric antigen receptor-modified T (CAR T-EGFR) cells in patients with metastatic PC. The expression levels of EGFR on tumor cells detected by immunohistochemistry were required to be more than 50%. Sixteen patients were enrolled and received one to three cycles of the CAR T-EGFR cell infusion within 6 months (median dose of CAR T cells: 3.48 × 10/kg; range, 1.31 to 8.9 × 10/kg) after the conditioning regimen with 100 to 200 mg/m nab-paclitaxel and 15 to 35 mg/kg cyclophosphamide. Grade ≥3 adverse events included fever/fatigue, nausea/vomiting, mucosal/cutaneous toxicities, pleural effusion and pulmonary interstitial exudation and were reversible. Of 14 evaluable patients, four achieved partial response for 2-4 months, and eight had stable disease for 2-4 months. The median progression-free survival was 3 months (range, 4-months) from the first cycle of CAR T-EGFR cell treatment, and the median overall survival of all 14 evaluable patients was 4.9 months (range, 2.9-30 months). Decreased EGFR expression on tumor cells was observed in patients who achieved stable disease with shrinkage of metastatic lesions in the liver, and enrichment of central memory T cells in infused cells improved the clinical response. In conclusion, the treatment with CAR T-EGFR cells is safe and effective in patients with metastatic PC. This trial was registered at www.clinicaltrials.gov (identifier no: NCT01869166).