Faculty, Staff and Student Publications

Language

English

Publication Date

10-1-2025

Journal

Future Oncology

DOI

10.1080/14796694.2025.2561539

PMID

41088723

PMCID

PMC12536771

PubMedCentral® Posted Date

10-14-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is expressed in numerous solid tumors. Higher levels of HER3 expression in multiple tumor types are associated with adverse clinical outcomes, such as reduced survival. However, there is currently no HER3-directed antibody-drug conjugate approved for the treatment of any cancer. Improved treatment options are needed, in particular for patients who progress on standard therapies. HER3-DXd is an investigational HER3-directed antibody-drug conjugate composed of an anti-HER3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. In previous clinical trials, HER3-DXd demonstrated a manageable safety profile and durable efficacy in previously treated, advanced EGFR-mutated NSCLC and advanced breast cancer across a range of baseline tumor HER3 expression levels. HER3-DXd has also shown preclinical antitumor efficacy in HER3-expressing cancers including cutaneous melanoma, gastric cancer, and prostate cancer, among others. The aim of this global phase II HERTHENA-PanTumor01 multicohort study is to assess the efficacy and safety of HER3-DXd in patients with relapsed or refractory locally advanced or metastatic solid tumors including melanoma, head and neck squamous cell, gastric/gastroesophageal junction, ovarian, cervical, endometrial, bladder, esophageal squamous cell, pancreatic, and prostate cancers.

Keywords

Humans, Receptor, ErbB-3, Immunoconjugates, Antibodies, Monoclonal, Humanized, Neoplasms, Clinical Trials, Phase II as Topic, Female, Camptothecin, Male, Broadly Neutralizing Antibodies, Gastric cancer, melanoma, head and neck carcinoma, pancreatic cancer, prostate cancer, bladder cancer, esophageal cancer, gynecologic cancers, HER3, HER3-DXd, ADC

Comments

Clinical trial registration: NCT06172478 (ClinicalTrials.gov); 2023-507641-29-00 (EudraCT); jRCT2031230575 (Japan Registry of Clinical Trials).

Published Open-Access

yes

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