Phase Ⅰ study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers

摘要

This phase Ⅰ clinical trial (NCT01935843) is to evaluate the safety,feasibility,and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2)in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs).Eligible patients with HER2-positive (＞50％) BTCs and PCs were enrolled in the trial.Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nabpaclitaxel (100-200 mg/m2) and cyclophosphamide (15-35 mg/kg).CAR transgene copy number in the peripheral blood was ssrially measured to monitor the expansion and persistence of CART-HER2 cells in vivo.Eleven enrolled patients received 1 to 2-cycle CART-HER2 cell infusion (median CAR+ Tcell 2.1 x 106/kg).The conditioning treatment resulted in mild-to-moderate fatlgue,nausea/vomiting,myalgia/arthralgia,and lymphopenia.Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase (＞9 ULN),adverse events related to the infusion of CART-HER2 cells were mild-to-moderate.Post-infusion toxicities included one case of revereible severe upper gastrointestinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion,and 2 cases of grade 1-2 delayed fever,accompanied by the release of C-reactive protein and interleukin-6.All patients were evaluabie for assessment of clinical response,among which 1 obtained a 4.5-months partial response and 5 achieved stable disease.The median progression free survival was 4.8 months (range,1.5-8.3 months).Finally,data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy,and showed encouraging signals of clinical activity.