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Multitude Therapeutics Unveils Positive Interim Findings for AMT-253 at ESMO 2025

During the 2025 European Society for Medical Oncology (ESMO) Annual Meeting in Berlin, Multitude Therapeutics, a clinical-stage biopharmaceutical firm, announced exciting interim results from its ongoing Phase I/II study assessing AMT-253, a MUC18-directed antibody-drug conjugate (ADC). This study is pivotal as it evaluates the effectiveness and safety of AMT-253 in patients battling melanoma and other advanced solid tumors.

The ongoing trials are taking place in Australia and China, with the primary aim of determining the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) for AMT-253. The study includes an open-label, multicenter dose escalation approach designed to gather essential information regarding the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of the treatment. Importantly, the Phase I component will establish doses appropriate for subsequent expansion, while the Phase II part aims to further assess safety and eficacy in selected tumor types.

As of September 8, 2025, data from 170 patients have been compiled, focusing on those who've received AMT-253 every three weeks. The doses administered range between 1.6 to 5.6 mg/kg, targeting tumor types predominantly seen in melanoma, endometrial cancer, and cervical squamous cancer. Notably, patients who had undergone multiple prior therapies exhibited promising efficacy rates without initial selection based on MUC18 expression. The overall response rate (ORR) among melanoma patients was notably 28.6% across all dose levels, with higher efficacy seen in subsets without previous chemotherapy.

In particular, for melanoma patients who had yet to receive chemotherapy, the ORR spiked to 35% for those treated under specific conditions. The preliminary median progression-free survival (mPFS) durations ranged from 8.3 to 11.0 months across different melanoma subtypes. Encouraging antitumor activity was also reported among patients suffering from endometrial and cervical cancers, indicating AMT-253's potential broader therapeutic applications. Crucially, the efficacy of AMT-253 appeared consistent across various levels of MUC18 expression in the diverse tumor populations, reinforcing the investigational ADC's promise.

The safety profile of AMT-253 aligns with expectations based on prior studies of similar ADCs, exhibiting manageable hematologic toxicities as the prevalent adverse events. Notably, there have been no reports of treatment-related neuropathy or pneumonitis, emphasizing the drug's tolerability.

Dr. Shu-Hui Liu, the Co-founder and Chief Scientific Officer of Multitude Therapeutics, expressed enthusiasm for the early results, especially given the high unmet need in the late-stage melanoma patient cohort. He stated, “We are excited by the durable antitumor activity observed in the early clinical results of AMT-253. These initial data, along with our previous preclinical findings, underscore the potential of AMT-253 to significantly improve outcomes for patients who have exhausted all standard treatment options.”

Presentation Highlights

During the ESMO meeting, the findings are showcased under the poster titled “Ongoing Phase I trial results of AMT-253, a first-in-class MUC18-targeting antibody-drug conjugate in patients with melanoma and other advanced solid tumors.” The poster presentation is scheduled for October 19th from 09:00 to 17:00 in Hall 25, Level 2.

The AMT-253 Technology

AMT-253 is constructed from a specially designed antibody exhibiting high affinity for MUC18, combined with a protease-cleavable linker and an exatecan payload, which acts as a potent topoisomerase-1 inhibitor. This innovative combination allows for a high drug-to-antibody ratio while minimizing resistance, showcasing potential advantages over competitor ADCs. These features may provide a better therapeutic effect against advanced solid tumors.

In conclusion, Multitude Therapeutics is at the forefront of developing new treatments through its cutting-edge technology platforms and has already entered several ADCs into clinical trials, demonstrating its commitment to addressing significant cancer treatment gaps. For further details about AMT-253 and other developments, please visit Multitude Therapeutics.