MRK, Daiichi Begin Phase III Breast Cancer Study With ADC Candidate

Merck MRK and Japan’s Daiichi Sankyo announced the dosing of the first patient in the phase III HERTHENA-Breast04 study evaluating their investigational HER3-directed DXd antibody-drug conjugate (ADC), patritumab deruxtecan (HER3-DXd), for treating certain patients with breast cancer.

The open-label, randomized HERTHENA-Breast04 study will evaluate HER3-DXd versus an investigator’s choice of treatment in patients with unresectable locally advanced or metastatic hormone receptor (HR) positive, HER2 negative breast cancer whose disease progressed following endocrine and CDK4/6 inhibitor therapy in either adjuvant or first-line metastatic settings.

The initiation of the HERTHENA-Breast04 study is based on data from ICARUS-Breast01 and a phase I/II breast cancer study in which HER3-DXd demonstrated promising responses in patients with metastatic breast cancer.

The primary endpoint of the HERTHENA-Breast04 study will be progression-free survival by blinded independent central review and overall survival. The secondary endpoints of the study include objective response rate, duration of response and safety.

MRK's Price Performance

Year to date, shares of Merck have plunged 15.4% compared with the industry’s decline of 0.6%.

MRK & Daiichi's Deal for HER3-DXd & Other ADC Candidates

Merck and Daiichi’s global clinical program is advancing HER3-DXd as a potential treatment across various cancer indications, including combination studies with other anticancer medicines.

Besides HER3-DXd, Merck acquired global co-development and co-commercialization rights to two other ADCs, ifinatamab deruxtecan and raludotatug deruxtecan, from Daiichi Sankyo in October 2023 for a total potential consideration of up to $22 billion. However, Daiichi Sankyo has retained exclusive rights for the development of the candidates in Japan.

In August last year, Merck expanded the collaboration to co-develop and co-commercialize MK-6070, an investigational T-cell engager targeting delta-like ligand 3 (DLL3), which it obtained from its recent acquisition of Harpoon Therapeutics.

Ifinatamab deruxtecan is being developed in separate phase III studies for treating small cell lung cancer, esophageal cancer and prostate cancer. The ADC candidate is also being evaluated both as monotherapy and in combination with other therapies in several early-to-mid-stage studies for treating various other solid tumors, including extensive-stage small cell lung cancer.

Raludotatug deruxtecan is being developed in various mid-stage studies for ovarian cancer as well as other cancer indications.

MRK’s Competition in the ADC Space

ADCs are being considered a disruptive innovation in the pharmaceutical industry, as these will enable better treatment of cancer by harnessing the targeting power of antibodies to deliver cytotoxic molecule drugs to tumors.

Daiichi Sankyo has several ADCs in clinical development across multiple types of cancer. It markets Enhertu, a HER2-directed ADC, in partnership with AstraZeneca AZN, which is presently approved across multiple indications, including HER2-mutated breast, lung and gastric cancers.

In January 2025, the FDA approved AZN and Daiichi’s second ADC drug, Datroway, for treating unresectable or metastatic HR-positive, HER2-negative breast cancer in adult patients who have received prior endocrine-based therapy and chemotherapy. The FDA approved Datroway for its second indication, non-small-cell lung cancer, in June.

Pfizer PFE also forayed into the lucrative ADC space with the acquisition of Seagen for $43 billion in late 2023.

Following this acquisition, PFE added three ADCs to its portfolio — Adcetris, Padcev, Tukysa and Tivdak — all approved across various types of solid tumors and hematologic malignancies. These products contributed meaningfully to Pfizer’s revenues in 2024 and in the first half of 2025.

MRK's Zacks Rank

Merck currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report

This article originally published on Zacks Investment Research (zacks.com).

Zacks Investment Research