Merck Announces First Patient Dosage in HERTHENA-Breast04 Phase 3 Trial

Merck & Co. (MRK) has announced the first patient dosage in the HERTHENA-Breast04 phase 3 trial, evaluating the efficacy and safety of investigational patritumab deruxtecan (HER3-DXd) in patients with unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The drug is a specifically engineered HER3-directed DXd antibody drug conjugate under joint development by Merck & Co., Inc. and Daiichi Sankyo.

Title: Merck & Co. Initiates Phase 3 Trial for Patritumab Deruxtecan in Metastatic Breast Cancer

July 2, 2025 — Merck & Co. (MRK) has announced the first patient dosage in the HERTHENA-Breast04 phase 3 trial, evaluating the efficacy and safety of investigational patritumab deruxtecan (HER3-DXd) in patients with unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The drug is a specifically engineered HER3-directed DXd antibody drug conjugate under joint development by Merck & Co., Inc. and Daiichi Sankyo.

The HERTHENA-Breast04 trial is an open-label, randomized study that will enroll approximately 1,000 patients across Asia, Europe, North America, and South America. Participants will be randomized 1:1 to receive patritumab deruxtecan or physician’s choice of treatment, consisting of either chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, liposomal doxorubicin) or HER2 directed ADC (trastuzumab deruxtecan). The primary endpoints of the trial are progression-free survival and overall survival, with secondary endpoints including objective response rate, duration of response, and safety.

Patritumab deruxtecan is a novel HER3-directed ADC designed using Daiichi Sankyo’s proprietary DXd ADC Technology. It consists of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The drug is being developed jointly by Merck & Co., Inc. and Daiichi Sankyo, with the collaboration expanding to include gocatamig (MK-6070/DS3280) in August 2024.

The trial is based on promising clinical activity observed in earlier phase studies, including ICARUS-Breast01, which showed promise in patients with metastatic breast cancer. The need for additional treatment options for HR positive, HER2 negative metastatic breast cancer is highlighted by the poor prognosis and outcomes for patients who progress following initial treatment.

The collaboration between Merck & Co., Inc. and Daiichi Sankyo is part of a broader effort to develop innovative treatments for breast cancer. Merck’s commitment to advancing breakthrough science and reducing disparities in cancer care aligns with the global health mission of both companies.

References:
[1] https://www.merck.com/news/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/