AUTHOR=Pascual Tomás , Oliveira Mafalda , Ciruelos Eva , Bellet Ezquerra Meritxell , Saura Cristina , Gavilá Joaquin , Pernas Sonia , Muñoz Montserrat , Vidal Maria J. , Margelí Vila Mireia , Cejalvo Juan M. , González-Farré Blanca , Espinosa-Bravo Martin , Cruz Josefina , Salvador-Bofill Francisco Javier , Guerra Juan Antonio , Luna Barrera Ana María , Arumi de Dios Miriam , Esker Stephen , Fan Pang-Dian , Martínez-Sáez Olga , Villacampa Guillermo , Paré Laia , Ferrero-Cafiero Juan M. , Villagrasa Patricia , Prat Aleix 

TITLE=SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.638482

DOI=10.3389/fonc.2021.638482

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Preclinical data support a key role for the human epidermal growth factor receptor 3 (HER3) pathway in hormone receptor (HR)–positive breast cancer. Recently, new HER3 directed antibody drug conjugates have shown activity in breast cancer. Given the need to better understand the molecular biology, tumor microenvironment, and mechanisms of drug resistance in breast cancer, we designed this window-of-opportunity study with the HER3 directed antibody drug conjugate patritumab deruxtecan (HER3-DXd; U3-1402).</p><p><bold>Trial Design:</bold> Based on these data, a prospective, multicenter, single-arm, window-of-opportunity study was designed to evaluate the biological effect of patritumab deruxtecan in the treatment of naïve patients with HR-positive/HER2-negative early breast cancer whose primary tumors are ≥1 cm by ultrasound evaluation. Patients will be enrolled in four cohorts according to the mRNA-based ERBB3 expression by central assessment. The primary endpoint is a CelTIL score after one single dose. A translational research plan is also included to provide biological information and to evaluate secondary and exploratory objectives of the study.</p><p><bold>Trial Registration Number:</bold> EudraCT 2019-004964-23; NCT number: NCT04610528.</p>