Weidong Han
Chinese PLA General Hospital China
Title: Chimeric antigen receptor modified T cell redirected to EGFR in patients with metastatic and advanced pancreatic adenocarcinoma and biliary tract cancers
Biography
Biography: Weidong Han
Abstract
Statement of the Problem: Limited effective treatment opinions and dismal prognosis in metastatic pancreatic adenocarcinoma (mPA) and biliary tract cancers (BTCs) require developing novel therapeutic approaches. Methodology & Theoretical Orientation: Epidermal growth factor receptor (EGFR) is a well-known candidate therapeutic target due to its frequent overexpression in epithelium-derived tumors. The purpose of this study is to further expand our clinical trial (NCT01869166) of EGFR-specific chimeric antigen receptor-engineered autologous T cell (CAR T-EGFR)-based therapeutic modality to mPA and mBTCs to evaluate its feasibility and efficacy. Patients were enrolled when >50% EGFR+ ratio was observed in tumor specimens by immunohistochemical staining. CAR copy number in peripheral blood was serially measured to determine the therapeutic cycles. Findings: A total 34 of patients including 12 mPA and 22 mBTCs received 1 to 3-cycle cell infusions (Range from 0.6 to 4.1×106/kg, median dose is 2.3×106/kg) within 6 months. The acute toxicities included infusion-associated febrile syndrome (Grade 1/2 in 34 cases) and pulmonary edema/pleural effusion (Grade 3 in 4 cases). The common toxicities occurred 1 week after cell infusions included febrile syndrome (Grade 1/2 in 11 cases) accompanied with the elevation of serum cytokine such as IL6 and/or TNFï¡, and CRP, and mucosal/cutaneous damages (Grade 1/2 in 19 cases). Of 31 patients who were treated by nab-paclitaxel/cyclophosphamide conditioned cell infusions, 5 obtained 8-16 weeks PR and 5 had 4-12 week SD in mPA patients, and 1 obtained a 22-month ongoing CR and 10 had 6-56 week SD in BTCs patients. 3 BTC patients were treated by cell infusion alone given their tolerance and relatively small disease burden, 1 obtained a 20-month ongoing CR, 1 had 8.5-month PR, and 1 had 9-month SD. Conclusion & Significance: This trial further indicated the controllable safety and efficacy of EGFR-targeted CAR T therapy, providing basis for further optimal combination strategy.