Multitude Therapeutics announced promising interim results from its ongoing Phase I/II study of AMT-116, a first-in-class CD44v9-directed antibody-drug conjugate, in patients with EGFR wild-type non-small cell lung cancer and other advanced solid tumors. The data, presented at the 2025 European Society for Medical Oncology Annual Meeting in Berlin, demonstrate significant antitumor activity across multiple cancer types without requiring CD44v9 pre-selection.
Clinical Trial Design and Patient Population
The multicenter, open-label dose escalation and expansion study is being conducted across Australia, the United States, and China. As of July 17, 2025, safety data were available for 164 patients who received AMT-116 administered once every two weeks at doses ranging from 1.5 to 5.0 mg/kg. The study population included patients with NSCLC, nasopharyngeal carcinoma, anal carcinoma, and salivary gland cancer.
The Phase Ia portion aims to determine the Maximum Tolerated Dose and Recommended Phase II Dose, while the Phase Ib/II portion focuses on characterizing safety and efficacy in select tumor types. The study evaluates safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of AMT-116 in patients with advanced solid tumors.
Efficacy Results in EGFR Wild-Type NSCLC
In heavily pretreated EGFR wild-type NSCLC patients with prior lines of therapy ranging from 1-5, AMT-116 demonstrated promising efficacy regardless of CD44v9 expression status. At dose levels greater than 3 mg/kg, the overall response rate was 40% (6/15) and the disease control rate was 93% (14/15) in EGFR wild-type NSCLC patients.
The most impressive results were observed at the highest dose level of 5.0 mg/kg, where five EGFR wild-type NSCLC patients achieved an 80% overall response rate (4/5) and 100% disease control rate (5/5). These results suggest dose-dependent efficacy with the potential for substantial clinical benefit at higher dose levels.
Activity Across Multiple Tumor Types
Preliminary antitumor activity was also observed in patients with other advanced solid tumors at doses greater than 3 mg/kg. Patients with nasopharyngeal carcinoma achieved a 50% overall response rate (3/6), while those with anal carcinoma demonstrated a 60% response rate (3/5). Salivary gland cancer patients showed a 33% response rate (2/6). Notably, antitumor activity was observed across patients with varying levels of CD44v9 expression, suggesting the ADC's effectiveness is not strictly dependent on high target expression.
Safety Profile and Tolerability
AMT-116 demonstrated a favorable safety profile consistent with other topoisomerase I inhibitor-based ADCs. Manageable hematologic toxicities were the most common treatment-related adverse events. Importantly, only low-grade and infrequent mucosal and skin toxicities were observed, representing a significant improvement over other ADCs in this class.
"The greatly reduced mucosal and skin toxicities reflect the desired outcome of a carefully selected linker-payload platform aimed at mitigating potential on-target toxicities from normal tissue expression," said Dr. Shu-Hui Liu, co-founder and Chief Scientific Officer of Multitude Therapeutics.
Drug Composition and Mechanism
AMT-116 is composed of a proprietary antibody with high CD44v9 binding affinity, a hydrolysable linker, and a belotecan derivative payload called KL610023, developed in collaboration with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. The ADC has a drug-to-antibody ratio of 7-8.
CD44v9 is involved in broad biological pathways and has an implicated role in cancer stem cells. The target is highly abundant and overexpressed broadly in solid tumors while having restrictive normal tissue expression, making it an attractive target for ADC development.
Future Development Plans
Based on these encouraging results, Multitude Therapeutics plans to expand the clinically efficacious dose levels of 4 mg/kg and 5 mg/kg administered every two weeks in select tumor types. The company aims to explore the full potential of this novel ADC for greater patient benefit in NSCLC and other solid tumors.
Dr. Liu expressed excitement about the results, stating, "We are excited by the impressive and durable efficacy shown in the early results of AMT-116, especially in unselected heavily pretreated EGFR Wild-type NSCLC and several other advanced solid tumors."
