Frontiers in Oncology (Apr 2021)

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

DOI
https://doi.org/10.3389/fonc.2021.638482
Journal volume & issue
Vol. 11

Abstract

Read online

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.

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