SHANGHAI, China, July 2, 2026
Multitude Therapeutics Co., Ltd. announced encouraging interim Phase I clinical results for its CDH17-directed antibody-drug conjugate (ADC), AMT-676, during the 2026 ESMO Gastrointestinal Cancers Congress in Munich, Germany. The first-in-human, multicenter study is evaluating AMT-676 in patients with advanced colorectal cancer (CRC) and other gastrointestinal malignancies across Australia, the United States, and China. Interim findings demonstrated a favorable safety profile, promising antitumor activity, and durable disease control in heavily pretreated metastatic CRC patients, supporting the continued development of the investigational therapy as a potential first-in-class CDH17-targeted ADC designed with the company’s proprietary exatecan-based linker-payload platform.
Phase I Study Demonstrates Promising Antitumor Activity
As of May 22, 2026, a total of 246 patients had received AMT-676 without prior CDH17 biomarker selection, with patients enrolled across Australia (63.0%), China (27.6%), and the United States (9.3%). Patients received treatment every three weeks at doses ranging from 1.6 mg/kg to 12 mg/kg. Among 100 efficacy-evaluable colorectal cancer patients treated at doses between 7.2 mg/kg and 12 mg/kg, the investigational ADC achieved an overall response rate (ORR) of 20%, including 17 confirmed responses and three ongoing unconfirmed responses, while the disease control rate (DCR) reached an impressive 91%. At the 8 mg/kg dose, ORR increased to 26%, with 25 patients remaining on treatment. Patients with RAS wild-type tumors demonstrated particularly encouraging responses, achieving ORRs of 36% at 7.2 mg/kg and 38% at 8 mg/kg, suggesting meaningful clinical activity in this patient subgroup.
Safety Profile Supports Continued Clinical Development
The interim analysis showed that AMT-676 demonstrated a manageable safety profile comparable to other topoisomerase-1 (TOP1) inhibitor-based ADCs, while exhibiting reduced hematological toxicity, an important differentiating feature of the therapy. Most treatment-related adverse events consisted of grade 1 or grade 2 gastrointestinal and hematologic toxicities, which were considered clinically manageable. Investigators reported that the maximum tolerated dose (MTD) had not yet been reached, even after dose escalation to 12 mg/kg, while the relatively low incidence of grade 3 or higher treatment-related adverse events supports future dose optimization and potential combination strategies with chemotherapy. According to the company, the favorable safety profile is partially attributed to the ADC’s drug-to-antibody ratio (DAR) of four, designed to balance efficacy and tolerability.
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First-in-Class CDH17 ADC Advances in Global Development
AMT-676 combines a high-affinity CDH17-targeting antibody, a protease-cleavable linker, and a proprietary exatecan payload, creating a next-generation ADC intended to improve efficacy while minimizing toxicity. The therapy is designed to overcome common mechanisms of drug resistance by utilizing a payload that is a weak substrate for BCRP and P-glycoprotein drug efflux pumps, potentially enhancing activity against difficult-to-treat tumors. Multitude Therapeutics CEO Dr. Xun Meng stated that the encouraging early clinical findings demonstrate the potential for AMT-676 to improve outcomes in late-line metastatic colorectal cancer patients who have exhausted standard treatment options. The ongoing Phase I trial continues to evaluate the recommended Phase II dose (RP2D), pharmacokinetics, pharmacodynamics, immunogenicity, and long-term clinical activity as the company advances the development of this potential first-in-class CDH17-directed ADC.
Source: Multitude Therapeutics press release
