Thomas Powles, Aarti Bhatia, Barbara Burtness, Takahiro Kogawa, Tomohiro Nishina, Izuma Nakayama, Christos Fountzilas, Dani Ran Castillo, Meredith McKean, Funda Meric‐Bernstam, Nicoletta Colombo, James W. Smithy, Jérôme Fayette, Sunandana Chandra, David Sternberg, Fan Jin, Kendall Sullivan, Sue Yueh, Graham Clinthorne, Ariel Aguilo, Ragini R. Kudchadkar, Hidetoshi Hayashi
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.Clinical trial registration: NCT06172478 (ClinicalTrials.gov); 2023-507641-29-00 (EudraCT); jRCT2031230575 (Japan Registry of Clinical Trials).