Patritumab Deruxtecan from Merck and DS enters Phase 3 for metastatic HR+ /HER2- Breast Cancer following standard endocrine and CDK4/6 inhibitor therapy

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.

The HERTHENA-Breast04 study is currently enrolling patients across 4 sites in the US, Israel, and Taiwan, with an anticipated enrollment of 1000 patients. 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%.

The development and testing of patritumab deruxtecan for the HERTHENA-Breast04 trial is a collaborative effort between Merck & Co Inc and Daiichi Sankyo.