On May 19, 2025 Merck & Co. reported the first patient has been dosed in the IDeate-Esophageal01 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) versus investigator’s choice of chemotherapy in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) with disease progression following treatment with a platinum-containing systemic therapy and an immune checkpoint inhibitor (Press release, Merck & Co, MAY 19, 2025, View Source [SID1234653233]).
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Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed with Merck (NYSE: MRK), known as MSD outside of the United States and Canada.
ESCC accounts for nearly 90% of esophageal cancers globally with a five-year overall survival rate around 15% to 20% and has a worse prognosis for those diagnosed at an advanced stage of the disease. While the evolved landscape in the first-line metastatic setting of ESCC has helped to improve outcomes for patients, treatment options are limited for patients progressing after first-line therapy, reinforcing the need for new approaches.
"Patients with metastatic esophageal squamous cell carcinoma continue to experience poor outcomes despite currently available treatments," said Mark Rutstein, MD, head, therapeutic area oncology development, Daiichi Sankyo. "The encouraging clinical activity seen in our early-phase signal finding trial supports further evaluation of ifinatamab deruxtecan as a potential treatment strategy for these patients."
"Advanced esophageal squamous cell carcinoma is a difficult-to-treat disease, and unfortunately overall survival remains low," said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "The initiation of the pivotal Phase 3 IDeate-Esophageal01 clinical trial demonstrates our shared commitment with Daiichi Sankyo to further expand our clinical development program evaluating this potentially first-in-class ADC across multiple solid tumors where there are unmet needs for new treatment options."
The initiation of IDeate-Esophageal01 is based on results from the IDeate-PanTumor01 Phase 1/2 trial presented at both the 2022 and 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) where ifinatamab deruxtecan showed promising responses in heavily pretreated patients with ESCC.
About the IDeate-Esophageal01 trial
IDeate-Esophageal01 is a global, multicenter, open-label, randomized Phase 3 trial evaluating the safety and efficacy of ifinatamab deruxtecan (12 mg/kg) versus treatment of physician’s choice of chemotherapy (paclitaxel, docetaxel or irinotecan hydrochloride) in patients with advanced or metastatic ESCC with disease progression following treatment with platinum-based chemotherapy therapy and an immune checkpoint inhibitor. Eligible patients must have received no more than one prior line of systemic therapy in the advanced or metastatic setting.
The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival and objective response rate as assessed by blinded independent central review, and safety.
IDeate-Esophageal01 will enroll approximately 510 patients across Asia, Europe and North America. For more information, please visit ClinicalTrials.gov.
About esophageal squamous cell carcinoma
More than half a million esophageal cancer cases were diagnosed in 2022, with nearly half a million deaths globally.ESCC accounts for nearly 90% of esophageal cancers globally with a five-year overall survival rate around 15% to 20% and has a worse prognosis for those diagnosed at an advanced stage of the disease. ESCC is most prevalent in Eastern Asia where mortality rates are also the highest.
While the evolved landscape in the first-line metastatic setting of ESCC has helped to improve outcomes for patients, treatment options are limited for patients progressing after first-line therapy, reinforcing the need for new approaches.
About B7-H3
B7-H3 is a transmembrane protein that belongs to the B7 family of proteins which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including ESCC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer.
About ifinatamab deruxtecan
Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
In addition to IDeate-Esophageal01, ifinatamab deruxtecan is being evaluated in a global development program that includes IDeate-Lung01, a Phase 2 monotherapy trial in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC); IDeate-Lung02, a Phase 3 trial in patients with relapsed SCLC versus investigator’s choice of chemotherapy; IDeate-Lung03, a Phase 1b/2 trial in patients with ES-SCLC in combination with atezolizumab with or without carboplatin as first-line induction or maintenance therapy; IDeate-PanTumor02, a Phase 2 monotherapy trial in patients with recurrent or metastatic solid tumors; and,IDeate-PanTumor01, a Phase 1/2 first-in-human monotherapy trial in patients with advanced solid malignant tumors in collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN.
Ifinatamab deruxtecan has been granted orphan drug designation in the EU, Japan, Taiwan, and U.S. for the treatment of SCLC.