Patritumab Deruxtecan Enters Phase 3 for Metastatic HR+ Breast Cancer

The landscape of advanced breast cancer therapy continues to evolve with the initiation and first patient dosing of the HERTHENA-Breast04 trial (NCT07060807), a pivotal phase 3 study evaluating the HER3-directed antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. This landmark trial seeks to establish patritumab deruxtecan as a new treatment option for a patient population that has progressed following standard endocrine and CDK4/6 inhibitor therapy.¹

“Despite significant development in the treatment landscape, HR-positive, HER2-negative metastatic breast cancer is a highly complex and challenging disease with an overall poor prognosis,” said Mark Rutstein, MD, head, Therapeutic Area Oncology Development, Daiichi Sankyo, in a press release. “The promising clinical activity observed in our early phase studies including ICARUS-Breast01 [NCT04965766] suggest that patritumab deruxtecan has the potential to become a meaningful new treatment option for this specific type of breast cancer.”

The HERTHENA-Breast04 study is currently enrolling patients across 4 sites in the US, Israel, and Taiwan, with an anticipated enrollment of 1000 patients.² They will be randomized to receive patritumab deruxtecan every 3 weeks for approximately 13 months or treatment of physician’s choice, which may be paclitaxel, nab-paclitaxel, capecitabine, liposomal doxorubicin, or trastuzumab deruxtecan (T-DXd; Enhertu).

The study’s primary end points are progression-free survival and overall survival, and secondary end points include objective response rate (ORR), duration of response, change from baseline in quality of life, incidence of adverse events (AEs), and treatment discontinuation due to AEs.

To be eligible for study participation, patients must have must have experienced disease progression following CDK4/6 and endocrine therapy, measurable disease per RECIST v1.1, and an ECOG performance status of 0 or 1. Those with breast cancer amenable to curative intent, who are eligible to receive endocrine-based therapy in the advanced setting, with a known germline BRCA mutation, who have a known additional malignancy within the past 3 years, with a diagnosis of immunodeficiency, or with a history of noninfectious interstitial lung disease or pneumonitis are not eligible for enrollment.

Data from a phase 2 study (NCT04699630) presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting showed that, in patients with heavily pretreated estrogen receptor (ER)-positive and triple-negative metastatic breast cancers,the ORR with patritumab deruxtecan was 35.0% and the clinical benefit rate (CBR) was 43.3%. In patients with HR-positive disease, the ORR was 41.4%.³

FAQs

What is the HERTHENA-Breast04 trial?

The HERTHENA-Breast04 trial is a Phase 3 clinical study that Merck & Co Inc, in collaboration with Daiichi Sankyo, has initiated. Its primary purpose is to evaluate the safety and efficacy of an investigational drug called patritumab deruxtecan (HER3-DXd) as a treatment for a specific type of advanced breast cancer.

Who is eligible to participate in the HERTHENA-Breast04 trial?

Patients eligible for the HERTHENA-Breast04 trial are those with unresectable locally advanced or metastatic hormone receptor (HR) positive, HER2 negative breast cancer. Crucially, these patients must have experienced disease progression after undergoing prior treatments with endocrine therapy and CDK4/6 inhibitors.

Who are the key collaborators in the development and testing of patritumab deruxtecan?

The development and testing of patritumab deruxtecan for the HERTHENA-Breast04 trial is a collaborative effort between Merck & Co Inc and Daiichi Sankyo. This partnership allows them to combine their expertise in oncology research and development.

This article was generated with assistance from Google Gemini and NotebookLM. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. HERTHENA-Breast04 Phase 3 Trial of Patritumab Deruxtecan Initiated in Patients with Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer Previously Treated with Endocrine Therapy. News release. Merck & Co. August 27, 2025. Accessed August 27, 2025. https://tinyurl.com/2skahvtn

2. A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016). ClinicalTrials.gov. Updated August 22, 2025. Accessed August 27, 2025. https://clinicaltrials.gov/study/NCT07060807

3. Hamilton EP, Dosunmu O, Shastry M, et al. A phase 2 study of HER3-DXd in patients (pts) with metastatic breast cancer (MBC). J Clin Oncol. 2023;41(suppl_16):1004. doi:10.1200/JCO.2023.41.16_suppl.1004