Abstract 344: Correlative biomarker analyses: Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in an open-label, single arm phase 2 trial in locally advanced esophageal squamous carcinoma

Background: NCT04177797 was an open-label, single arm phase 2 trial in locally advanced esophageal squamous carcinoma (ESCC), which adopted toripalimab, plus paclitaxel and carboplatin as neoadjuvant immunotherapy regimen. Here we report correlative biomarker analyses for all 18 included patients. Methods: After two cycles of neoadjuvant immunotherapy, sixteen patients underwent surgery and seven of them achieved major pathological response (MPR). Two patients did not receive surgery but their imaging evaluation were both clinical complete response (cCR). We defined MPR or cCR as responders, and others as non-responders.  Peripheral blood, gastroscopic tumor and adjacent normal tissues were collected before the first dose of drug and so did surgery samples. Whole exome sequencing (WES) and RNA-seq were conducted for the pretreatment tissues, and surgery samples were performed for multiplex immunohistochemistry (mIHC) with 5 markers. Results: In pretreatment tumor tissues, there was no significant difference either in the CD8+ (p=0.19) or CD68+HLA-DR- (p=0.57) density between responders and non-responders. However, CD8+ density increased (p=0.0078) and CD68+HLA-DR- density decreased (p=0.039) significantly in responders after neoadjuvant combined immunotherapy, whereas these two markers did not in non-responders (p=0.13 and p=0.36, respectively). Meanwhile, responders were associated with higher baseline gene expression levels of CXCL 5 (p=0.03) and lower baseline CCL 19 (p=0.017) and UMODL1 (p=0.03). Conclusions: The mechanism of tumor response may be associated reduction of M2 macrophages and CD8 cells recruitment after combined immunotherapy in locally advanced resectable ESCC. Citation Format: Wenwu He, Lin Peng, Yu Bao, Wenguang Xiao, Qiang Fang, Xuefeng Leng, Jiaxin Yan, Tianqin Mao, Xudong Shen, Depei Huang, Hushan Zhang, Xueke She, Yongtao Han. Correlative biomarker analyses: Toripalimab plus paclitaxel and carboplatin as neoadjuvant therapy in an open-label, single arm phase 2 trial in locally advanced esophageal squamous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 344.