Interim Phase I data from China-based Multitude Therapeutics reported a 20% overall response rate and a 91% disease control rate for AMT-676, a CDH17-directed antibody-drug conjugate, in heavily pretreated metastatic colorectal cancer patients — results that, while early, suggest the target and linker-payload design may be viable in a population with few remaining options. Of note, objective responses are uncommon in refractory metastatic CRC, making a 20% ORR notable despite the early-stage nature of the data. The data were presented at the 2026 ESMO Gastrointestinal Cancers Congress in Munich.
CDH17, or cadherin-17, is expressed in more than 90% of colorectal cancers and is largely absent from normal adult tissue outside the gastrointestinal tract, making it an attractive ADC target. AMT-676 pairs a high-affinity anti-CDH17 antibody with a protease-cleavable linker and an exatecan payload — a topoisomerase I inhibitor. The molecule carries a drug-to-antibody ratio of 4, lower than some competing exatecan-based ADCs, a design choice the company says contributes to milder hematological toxicity. The exatecan payload is also a weak substrate for the BCRP and P-gp drug efflux pumps that drive resistance to many chemotherapy agents.
Key data
As of a May 22, 2026 data cutoff, 246 patients had been treated across dose levels from 1.6 to 12 mg/kg every three weeks in the NCT06400485 Phase I study, conducted without CDH17 biomarker preselection. The study is ongoing in Australia, China, and the US. Among 100 efficacy-evaluable CRC patients treated at doses of 7.2–12 mg/kg, the ORR was 20%, including 17 confirmed responses. The disease control rate reached 91%. At the 8 mg/kg dose, ORR rose to 26% among 47 patients, with 25 still on treatment. Patients with RAS wild-type tumors responded at higher rates — 38% at 8 mg/kg — compared with RAS-mutant patients, consistent with the biology of EGFR pathway dependency in this subgroup. The median number of prior treatment lines was 3, with a range of 1 to 9.
The maximum tolerated dose was not reached at 12 mg/kg. Gastrointestinal and hematological toxicities were the most common treatment-related adverse events, predominantly Grade 1 or 2. Specific Grade 3 or higher TRAE rates were not disclosed.
Competitive context
CDH17 is not a crowded target, but it is attracting attention. SOTIO Biotech presented preclinical data in 2025 for SOT109, a CDH17-directed ADC also using an exatecan payload at DAR 4, with an IND filing expected in 2026. Arbele's cabotamig (ARB202), a CDH17×CD3 bispecific T-cell engager, is in early Phase I in GI cancers, representing a mechanistically distinct approach to the same target. AMT-676 holds a meaningful first-mover advantage in the clinic.
The more immediate comparison is with other late-line CRC options. Bayer's Stivarga (regorafenib) and Taiho/Servier's Lonsurf (trifluridine/tipiracil) — the current salvage standards — produce ORRs typically below 5% in unselected patients, though they provide modest overall survival benefit. AbbVie's telisotuzumab adizutecan (Temab-A), a c-Met-directed ADC with a topoisomerase I payload, reported a 26.7% ORR in biomarker-unselected CRC patients at the 2025 ESMO meeting in combination with bevacizumab. Cross-trial comparisons are limited by differences in patient selection, prior therapies, and data maturity.