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 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).
Effective and tolerable treatment options are needed for patients with advanced cancer that stops responding to standard therapy. Human epidermal growth factor receptor 3, or HER3, is a protein that is found on the surface of tumor cells in many types of cancer. However, there is currently no approved treatment that targets only HER3. Patritumab deruxtecan (also called HER3‑DXd) is a type of targeted cancer drug called an antibody-drug conjugate, or ADC. It consists of a specially designed antibody (patritumab) linked to a chemotherapy drug (deruxtecan). The antibody in HER3-DXd attaches to HER3 on the surface of a tumor cell and then moves inside the cancer cell, where the chemotherapy is released, killing the cell. This article describes a clinical study called HERTHENA-PanTumor01 that is evaluating HER3-DXd in patients with cancer that stopped responding to standard therapy. All participants will have cancer that cannot be removed by surgery (unresectable), and in some cases has spread (metastatic). The study will enroll patients with different types of cancer, including skin, head and neck, stomach, ovarian, cervical, endometrial, bladder, esophageal, pancreatic, and prostate cancer. HERTHENA-PanTumor01 is an open-label study, meaning the doctor and the participant will know what treatment is being given. All study participants will receive HER3-DXd every 3 weeks through an IV infusion. HERTHENA-PanTumor01 will help doctors know more about how well HER3-DXd can shrink a patient’s tumor, and the side effects patients have while being treated. Currently, HER3-DXd is an investigational treatment, and doctors are not able to prescribe it.
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