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
Tomás Pascual, Mafalda Oliveira, Eva Ciruelos, Meritxell Bellet Ezquerra, Cristina Saura, Joaquín Gavilá, Sònia Pernas, Montserrat Muñoz-Mateu, María Vidal, Mireia Margelí Vila, Juan Miguel Cejalvo, Blanca González‐Farré, Martín Espinosa-Bravo, Josefina Cruz, Francisco Javier Salvador-Bofill, Juan Antonio Guerra, Ana María Luna Barrera, M. Arumi de Dios, Stephen Esker, Pang‐Dian Fan, Olga Martínez‐Sáez, Guillermo Villacampa, Laia Paré, J.M. Ferrero-Cafiero, Patricia Villagrasa, Aleix Prat
Abstract
Background: 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). Trial Design: 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. Trial Registration Number: EudraCT 2019-004964-23; NCT number: NCT04610528.