MRK, Daiichi Begin Pivotal Esophageal Cancer Study With ADC Drug

Merck MRK and Japan’s Daiichi Sankyo announced the dosing of the first patient in the phase III IDeate-Esophageal01 study evaluating their B7-H3 directed DXd antibody-drug conjugate (ADC), ifinatamab deruxtecan (I-DXd), in certain patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC).

The IDeate-Esophageal01 study will evaluate the safety and efficacy of I-DXd versus an investigator’s choice of chemotherapy in ESCC patients whose disease progressed following treatment with a platinum-containing systemic therapy and an immune checkpoint inhibitor.

The initiation of the IDeate-Esophageal01 study is based on data from the phase I/II IDeate-PanTumor01 study in which I-DXd demonstrated promising responses in heavily pretreated patients with ESCC.

The primary endpoint of the IDeate-Esophageal01 study will be overall survival, while secondary endpoints include progression-free survival and objective response rate as assessed by blinded independent central review and safety.

MRK Stock Performance

Year to date, shares of Merck have plunged 22.3% compared with the industry’s decline of 5.2%.

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

Besides esophageal cancer, I-DXd is being evaluated in a phase III study for treating small cell lung cancer (SCLC). The ADC drug candidate is also being evaluated both as monotherapy and in combination with other therapies in several early-to-mid-stage studies for treating extensive-stage small cell lung cancer (ES-SCLC) and other solid tumors.

Merck acquired global co-development and co-commercialization rights to I-DXd and two other ADCs, patritumab 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.

Last June, the FDA issued a complete response letter (“CRL”) to the biologics license application seeking accelerated approval for patritumab deruxtecan for previously-treated EGFR-mutated non-small cell lung cancer. The CRL was based on observations made after the inspection of a third-party manufacturing facility.

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

Stiff 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.

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

Post this acquisition, PFE added three ADCs to its portfolio — Adcetris, Padcev and Tivdak — all approved across solid tumors and hematologic malignancies. These products contributed meaningfully to Pfizer’s revenues in 2024.

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.

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

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