Abstract 4396: TROP2 expression in non-small cell lung cancer

Abstract

Abstract Introduction: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related deaths globally with high unmet need. A variety of novel therapeutic strategies are being explored to improve patient outcomes including the use of antibody drug conjugates (ADCs) to deliver highly potent, cytotoxic payloads to tumors. Trophoblast cell-surface antigen 2 (TROP2), also known as tumor-associated calcium signal transducer 2 (TACSTD2), has emerged as an attractive target for ADCs. Sacituzumab govitecan-hziy is a novel ADC composed of a TROP2 antibody coupled to SN-38 and is being evaluated in NSCLC. High TROP2 mRNA expression is observed in many tumor types, however, TROP2 protein expression in NSCLC is not well-established. Here we characterized TROP2 expression across three independent datasets to explore the TROP2 relationship to baseline characteristics, molecular features of interest, and its prognostic value in NSCLC. Methods: We analyzed three independent datasets: (1) The Cancer Genome Atlas (TCGA) NSCLC adenocarcinoma (LUAD, N=660) and squamous cell carcinoma (LUSC, N=484) mRNA expression data, (2) a NSCLC adenocarcinoma FFPE tumor sample set (“Translational data set”; N=107), (3) an independent clinical NSCLC adenocarcinoma (N=103) and squamous cell carcinoma (N=37) data set. TROP2 IHC was performed on tumor sample sets (2) and (3) using the SP295 antibody (Robust Prototype Assay, Ventana) with H-Score and assessment of the percentage of membrane-positive tumor cells as readouts. Wilcoxon rank-sum and Kruskal-Wallis tests (continuous variables), Kaplan-Meier method (survival probability curves) and log-rank test (time to event outcome) were used (GraphPad Prism 8.1.2 and R version 4.0.5). Results: TROP2 mRNA was highly expressed in NSCLC and expression was similar in adenocarcinoma and squamous cell carcinoma in the TCGA data set. TROP2 expression did not vary with patient’s age, gender, race or tumor stage. Furthermore, TROP2 expression was not associated with TP53, KRAS or driver mutation status (including EGFR, ALK, ROS, RET, MET). TROP2 expression in the Translational sample set was consistent with the findings from the TCGA data analysis: TROP2 mRNA and protein expression were high and independent of patient baseline demographics, tumor stage and TP53 and KRAS mutation status. Finally, in an independent clinical NSCLC dataset, TROP2 protein was highly expressed and there was no relationship between TROP2 and baseline demographics including gender and age. TROP2 membrane H-scores and percentage of membrane-positive tumor cells also highly correlated in the two independent datasets. Conclusions: Three large independent datasets confirmed high expression of TROP2 in NSCLC both, as mRNA and protein. TROP2 expression in tumors did not differ between histological subtypes, baseline characteristics or clinically relevant driver alterations. Based on the TCGA data set, TROP2 expression was not prognostic for survival. Citation Format: Peiwen Kuo, Emon Elboudwarej, Lauri Diehl, Jilpa Patel, Sabeen Mekan, Juliane M. Jürgensmeier. TROP2 expression in non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4396.