biostudies-literatureUnknown31(8)Preusser MDaiichi Sankyo CompanyLeptomeningeal metastatic disease (LMD) is a severe complication of solid cancers with poor outcomes and limited treatment options. The antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated efficacy in breast and lung cancers, and HER3 is involved in central nervous system metastases, particularly in parenchymal colonization. In this study, we investigated HER3-DXd efficacy and safety in patients with LMD in cohort 3 of the TUXEDO-3 phase 2 trial. Key eligibility criteria included age ≥18 years, treatment-naive LMD or LMD progressing after radiotherapy from any solid tumor and Eastern Cooperative Oncology Group performance status of 0-2. Between January and July 2024, 20 evaluable patients (nine with type I and 11 with type II LMD) were accrued and received HER3-DXd 5.6 mg Nature medicine2797-2805https://www.ebi.ac.uk/biostudies/studies/S-EPMC12353872biostudies-literaturePatritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.PMC12353872Vaz-Batista MFurtner JGonzalez-Alonso POberndorfer FJimenez-Cortegana CGreil RArumi MLlombart-Cussac AGion MCampolier MRuiz-Borrego MGuerrero JAPreusser MBerghoff ASGarcia-Mosquera JJGarde-Noguera JRodriguez-Morato JCortes JBartsch RMarhold MFuereder TValero MfalsePatritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.Leptomeningeal metastatic disease (LMD) is a severe complication of solid cancers with poor outcomes and limited treatment options. The antibody-drug conjugate patritumab deruxtecan (HER3-DXd) demonstrated efficacy in breast and lung cancers, and HER3 is involved in central nervous system metastases, particularly in parenchymal colonization. In this study, we investigated HER3-DXd efficacy and safety in patients with LMD in cohort 3 of the TUXEDO-3 phase 2 trial. Key eligibility criteria included age ≥18 years, treatment-naive LMD or LMD progressing after radiotherapy from any solid tumor and Eastern Cooperative Oncology Group performance status of 0-2. Between January and July 2024, 20 evaluable patients (nine with type I and 11 with type II LMD) were accrued and received HER3-DXd 5.6 mg 2025-01-01T00:00:00Z2025 Aug2026-05-29T15:16:18.396Z2026-04-08T05:08:16.105ZS-EPMC123538724044785110.1038/s41591-025-03744-1