Abstract PO1-26-02: Enfortumab vedotin (EV): Correlation of estrogen receptor status and Nectin-4 expression with single agent efficacy in breast XPDX models

作者：Crystal Moreno, Johnnie Flores, Alyssa Simonson, Maci DeBoer, Natalia Baños, Armando Diaz, Morgan H. Lynch, J.C. Lund, Leonora Leykum, Tahmi Rouzbahan, Manuel Pedregal, Kyriakos P. Papadopoulos, Amy Lang, Arthur Rosenthal, Drew Rasco, Gladys Rodriguez, Luis Rodriguez, Nehal J. Lakhani, Muralidhar Beeram, Amita Patnaik, Maria De Miguel, Ronald Drengler, Steven Abbate, Bernard Doger de Spéville Uribe, Michael Wick · 发表于：Cancer Research · 年份：2024 · DOI：10.1158/1538-7445.sabcs23-po1-26-02 · 研究领域：Breast Lesions and Carcinomas

Abstract EV is a Nectin-4 targeting antibody-drug conjugate (ADC) with an MMAE payload, recently approved for treatment of bladder cancer patients. To better understand the potential for EV in treatment of breast cancer, we evaluated 175 breast XPDX models, including hormone receptor positive and negative cancer, some with actionable mutations, representing primary and metastatic disease from naïve or clinically treated patients. Each model was stained and scored for Nectin-4 protein and evaluated in vivo against single agent EV and activity correlated with ER status, Nectin-4 staining and known variants. 175 breast XPDX models were evaluated in this study, approximately 35% representing estrogen receptor positive and 20% clinically HER2+ cancers. Nectin-4 protein expression based on intensity and proportion was determined on a scale of 0+-3+, and models profiled using WES and RNAseq. For in vivo studies, models were evaluated against single agent EV administered by intravenous injection once weekly for three cycles at 3 mg/kg. Endpoints included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a T/C of ≤ 20% versus control was considered sensitive. Tumor regression (%T/C< 0%) versus Day 0 tumor volume was also reported. Overall, 40% of breast models stained positive for Nectin-4 including 50% of ER- and 20% of ER+ and 50% of HER2+ models. For ER- models, 50% were negative and 40% stained 1+ while 80% o...