Phase 1/2 ifinatamab deruxtecan (B7-H3 topo-I ADC) in 2L/3L ESCC

This Phase 1/2 open-label KEYMAKER-U06 umbrella platform substudy evaluates ifinatamab deruxtecan (I-DXd; DS-7300a) in participants with unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) receiving second- or third-line therapy after progression. I-DXd is a B7-H3 (CD276)–directed antibody-drug conjugate that binds B7-H3 on tumor cells, is internalized, and releases a deruxtecan (DXd) topoisomerase I inhibitor payload to cause lethal DNA damage. The primary goal is objective response rate (tumor shrinkage) with dosing every 3 weeks until progression or discontinuation, typical for DXd ADC development. The program is sponsored by Merck Sharp & Dohme (MSD) and leverages Daiichi Sankyo’s DXd ADC technology platform; scientifically, it tests whether broadly expressed B7-H3 (seen across many solid tumors) can be an actionable target in ESCC beyond the current post–chemo/immunotherapy landscape. Today, patients progressing after first-line platinum/fluoropyrimidine-based therapy plus PD-1 therapy often move to taxane- or irinotecan-based regimens (and other region-dependent options), so this study explores a targeted ADC alternative in a setting with limited durable responses.