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

Protein & Cell

Qingming Yang¹  Jingdan Qiu¹  Weidong Han¹  Kaichao Feng¹  Yang Liu²  Yao Wang³  Zhiqiang Wu³  Hanren Dai³  Yelei Guo³ 

[1] Department of Bio-therapeutic, Chinese PLA General Hospital;Department of Geriatric Hematology, Chinese PLA General Hospital;Department of Molecular & Immunology, Chinese PLA General Hospital;

关键词: HER2;    CART;    biliary tract cancers;    pancreatic cancers;    clinical trial;   

DOI  :  10.1007/s13238-017-0440-4

来源: DOAJ

【 摘 要 】

Abstract 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 nab-paclitaxel (100–200 mg/m2) and cyclophosphamide (15–35 mg/kg). CAR transgene copy number in the peripheral blood was serially 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+ T cell 2.1 × 106/kg). The conditioning treatment resulted in mild-to-moderate fatigue, 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 reversible 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 evaluable 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.

【 授权许可】

Unknown