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Cancer Cells and Metastasis / Wnt/β Catenin Signaling in Development and Cancer / HER2/EGFR in Cancer Research · Journal article
Advanced Science · September 9, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a preclinical discovery and optimization report on AMT-676, a novel CDH17-targeting antibody-drug conjugate for gastrointestinal cancers. The compound showed sustained antitumor activity across multiple tumor xenograft models and favorable pharmacokinetics and toxicity in cynomolgus monkeys, but clinical efficacy and safety remain unknown; a Phase 1 trial is listed as ongoing with no results reported.
Preclinical discovery and optimization study with in vitro screening, cell line-derived and patient-derived xenograft models, and animal toxicology. GI tumor cell lines, patient-derived tumor xenografts with diverse CDH17 expression, and cynomolgus monkeys; no human subjects enrolled.. Intervention: AMT-676, a CDH17-targeting antibody-drug conjugate comprising a high-affinity CDH17-specific antibody, hydrophilic self-immolative T1000 linker, and exatecan (DAR = 4).
CDH17 identified as a promising ADC target in GI tumors with minimal expression in healthy organs via MabArray screening and immunohistochemistry AMT-676 demonstrated sustained antitumor responses across cell line-derived (CDX) and patient-derived tumor xenograft (PDX) GI models with diverse CDH17 expression AMT-676 notably inhibited metastatic growth in a colorectal cancer model
No human clinical data; Phase 1 trial is stated as 'underway' with no efficacy or safety results reported Cynomolgus monkey studies revealed favorable pharmacokinetics and manageable toxicity associated with AMT-676
This preclinical work identifies CDH17 as a potential therapeutic target and provides rationale for the ongoing Phase 1 trial. Clinicians should await Phase 1 results to assess tolerability and preliminary efficacy signals before considering clinical relevance.
Preclinical discovery and optimization study with in vitro, xenograft, and animal toxicology data, but no human clinical evidence; Phase 1 trial is only stated as 'underway' with no results reported.
As stated by the source record.
Quoted from the source exactly as published.
This preclinical work identifies CDH17 as a potential therapeutic target and provides rationale for the ongoing Phase 1 trial. Clinicians should await Phase 1 results to assess tolerability and preliminary efficacy signals before considering clinical relevance.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Advanced-stage gastrointestinal (GI) cancers present an unmet need for innovative therapies, and antibody-drug conjugates (ADCs) offer promising solutions. This study investigates the antitumor efficacy and toxicity of AMT-676, a novel ADC targeting Cadherin 17 (CDH17), in GI cancers. Utilizing MabArray screening and immunohistochemistry, CDH17 was identified as a promising ADC target in GI tumors with minimal expression in healthy organs. The ADC was optimized through comprehensive in vitro and in vivo evaluations of binding affinity, cytotoxicity, pharmacokinetics, and toxicity, with antitumor potential evaluated using cell line-derived (CDX) and patient-derived tumor xenograft (PDX) models. Leveraging the T moiety-exatecan platform, we synthesized AMT-676, comprising a high-affinity CDH17-specific antibody, a hydrophilic self-immolative T1000 linker, and exatecan with a Drug-to-Antibody Ratio (DAR) of 4. AMT-676 demonstrated sustained antitumor responses across CDX and PDX GI models with diverse CDH17 expression, notably inhibiting metastatic growth in a colorectal cancer model. Cynomolgus monkey studies revealed favorable pharmacokinetics and manageable toxicity associated with AMT-676. In conclusion, we developed a novel CDH17-targeting ADC characterized by a high therapeutic index and tolerable toxicity profile, highlighting its promise for GI cancer treatment. A first-in-human, phase I clinical trial of AMT-676 in patients with advanced solid tumors is currently underway (NCT06400485).
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