HER3-DXd in Breast Cancer and NSCLC Brain Metastases and Solid Tumor Leptomeningeal Disease

Summary

The goal of this phase II clinical trial\] is to analyze the efficacy of patritumab deruxtecan (HER3-DXd) in patients with metastatic breast cancer (MBC) or advanced non-small cell lung cancer (aNSCLC) with active brain metastases (BM) who have received at least one line of systemic therapy in the advanced setting, or patients with active leptomeningeal carcinomatosis/disease (LMD) after radiotherapy from an advanced solid tumor who do not need immediate local treatment, and have not received prior treatment with an anti-HER3 targeted drug\]. The main questions it aims to answer are: * The intracranial objective response rate (ORR-IC) per local investigator as judged by best central nervous system (CNS) response according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria of HER3-DXd in patients with active BM from MBC (Cohort 1) and aNSCLC (Cohort 2). * The overall survival (OS) rate at 3 months of HER3-DXd in patients with advanced solid tumors with untreated LMD (Cohort 3). Participants will receive HER3-DXd on day (D1) of each 21-day cycle until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Researchers will compare historical groups to see if HER3-DXd positively impacts patient outcomes.

Timeline

Start

2023-11-24

Primary completion

2024-11-29

Completion

2026-04-03

Publications

• Bartsch R, Marhold M, Garde-Noguera J, Gion M, Ruiz-Borrego M, Greil R, Valero M, Llombart-Cussac A, Garcia-Mosquera JJ, Arumi M, Cortes J, Campolier M, Guerrero JA, Slebe F, Martinez-Garcia E, Jimenez-Cortegana C, Vaz-Batista M, Oberndorfer F, Furtner J, Fuereder T, Berghoff AS, Preusser M. Patritumab deruxtecan (HER3-DXd) in patients with active brain metastases of breast cancer (TUXEDO-3): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2025 Nov;26(11):1467-1478. doi: 10.1016/S1470-2045(25)00470-X.
• Fuereder T, Garde-Noguera J, Garcia-Mosquera JJ, Ruiz-Borrego M, Valero M, Llombart-Cussac A, Gion M, Greil R, Arumi M, Campolier M, Guerrero JA, Raimondi G, Mancino M, Jimenez-Cortegana C, Vaz-Batista M, Oberndorfer F, Marhold M, Berghoff AS, Furtner J, Bartsch R, Preusser M. Patritumab deruxtecan (HER3-DXd) in patients with active brain metastases of non-small-cell lung cancer (TUXEDO-3): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2025 Nov;26(11):1454-1466. doi: 10.1016/S1470-2045(25)00465-6.
• Preusser M, Garde-Noguera J, Garcia-Mosquera JJ, Gion M, Greil R, Arumi M, Ruiz-Borrego M, Llombart-Cussac A, Valero M, Cortes J, Campolier M, Guerrero JA, Gonzalez-Alonso P, Jimenez-Cortegana C, Rodriguez-Morato J, Vaz-Batista M, Oberndorfer F, Marhold M, Berghoff AS, Furtner J, Fuereder T, Bartsch R. Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial. Nat Med. 2025 Aug;31(8):2797-2805. doi: 10.1038/s41591-025-03744-1. Epub 2025 May 30.

Drugs

Indications