Am J Cancer Res. 2021 Apr 15;11(4):1697-1708. eCollection 2021.
ABSTRACT
CAN017 (AV-203), a novel anti-HER3 antibody, exerts very promising anti-tumor activities in several human tumor models. The aim of this study was to further investigated the efficacy and possible responsive biomarkers of CAN017 in esophageal squamous cell carcinoma (ESCC) with Chinese characteristics. Two separate cohorts of ESCC patient-derived xenograft (PDX) models including 24 (cohort 1 as training models, from Crown Bioscience Inc.) and 22 (cohort 2 as validating models, from Peking University Cancer Hospital) models, respectively, were used to study the efficacy and safety of CAN017, as well as the correlation of NRG1 expression to the response of CAN017. In cohort 1, all PDX models showed good tolerance to CAN017 and 8 out of 24 (33.3%) PDX models responded to CAN017 with tumor growth inhibition (TGI) ≥70% compared to controls. Furthermore, the efficacy o f CAN017 was positively correlated with NRG1 expression and the response rates in cohort 1 were 73% (8/11) versus 0% (0/13) in NRG1 high and low expression models, respectively. These results were also validated in PDX models of cohort 2 indicated as the powerful anti-tumor activity of CAN017 in PDX models with NRG1 high expression. In our study, HER3-targeting therapy was first demonstrated to have potency in inhibiting ESCC tumor growth, and NRG1 served as a predictive biomarker to screen patients in future clinical trials.
PMID:33948383 | PMC:PMC8085865
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