HERTHENA-PanTumor01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated advanced solid tumors
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 <i>EGFR</i>-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.<b>Clinical trial registration:</b> NCT06172478 (ClinicalTrials.gov); 2023-507641-29-00 (EudraCT); jRCT2031230575 (Japan Registry of Clinical Trials).
Authors
- Meredith McKean (ORCID: https://orcid.org/0000-0003-0944-7418)
- Ragini R. Kudchadkar (ORCID: https://orcid.org/0000-0001-9070-5052)
- David Sternberg (ORCID: https://orcid.org/0000-0002-3925-1304)
- Barbara Ann Burtness (ORCID: https://orcid.org/0000-0003-4660-1859)
- Jérôme Fayette (ORCID: https://orcid.org/0000-0002-8126-7019)
- Dani Ran Castillo (ORCID: https://orcid.org/0000-0002-5762-6683)
- Christos Fountzilas (ORCID: https://orcid.org/0000-0003-3837-5644)
- Sunandana Chandra (ORCID: https://orcid.org/0000-0001-7936-5069)
- Hidetoshi Hayashi (ORCID: https://orcid.org/0000-0001-8787-5587)
- Izuma Nakayama (ORCID: https://orcid.org/0000-0003-4987-1934)
- Ariel Aguilo (ORCID: https://orcid.org/0000-0001-5002-1748)
- James William Smithy (ORCID: https://orcid.org/0000-0003-3126-1193)
- Takahiro Kogawa (ORCID: https://orcid.org/0000-0003-3730-6591)
- Funda Meric‐Bernstam (ORCID: https://orcid.org/0000-0001-6816-6072)
- Aarti Bhatia (ORCID: https://orcid.org/0000-0002-0491-4454)
- Fan Jin
- Tomohiro Nishina (ORCID: https://orcid.org/0000-0002-4073-3757)
- Thomas B. Powles (ORCID: https://orcid.org/0000-0001-7760-4724)
- Kendall Sullivan (ORCID: https://orcid.org/0000-0001-6873-8501)
- Graham Clinthorne (ORCID: https://orcid.org/0009-0001-0425-8717)
- Nicoletta Colombo (ORCID: https://orcid.org/0000-0003-2225-715X)
- Sue Yueh
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Roswell Park Comprehensive Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Queen Mary University of London (GB)
- Sarah Cannon Research Institute (GB)
- Daiichi Sankyo (Germany) (DE)
- Yale Cancer Center (US)
- Centre Léon Bérard (FR)
- City of Hope (US)
- Daiichi-Sankyo (South Korea) (KR)
- The Cancer Institute Hospital (JP)
- Shikoku Cancer Center (JP)
- National Cancer Center Hospital East (JP)
- European Institute of Oncology (IT)
- University of Milano-Bicocca (IT)
- Kindai University (JP)
Publication Details
- Journal
- Future Oncology
- Published
- 2025-10-14
- DOI
- https://doi.org/10.1080/14796694.2025.2561539
- Citations
- 4
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 4.18