December 17, 2025, according to the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China, Multitude Therapeutics’ key product AMT-253 (targeting MUC18 ADC) was included in the Breakthrough Therapy Program, with the proposed indication being – unresectable locally advanced, recurrent or metastatic melanoma that has not been previously treated with first-line therapy.
AMT-253 is the world’s first and only MUC18-targeted ADC to enter the clinical stage. It is the first ADC drug that can be used for melanoma and is expected to achieve a major breakthrough in treatment mechanism and paradigm in this indication.
In the Australian Phase I and Chinese Phase I/II trials of AMT-253, 36 patients with melanoma who had not received chemotherapy were treated with AMT-253. As of September 8, 2025, the objective response rate was 41.7%, the disease control rate was 80.6%, and the median progression-free survival was 8.5 months. Clinical research data suggest that AMT-253 has clinical advantages over existing standard treatments and potential treatments in terms of efficacy and safety. It can improve tumor response and quality of life in patients with unresectable locally advanced, recurrent, or metastatic melanoma who have previously received first-line treatment, providing patients with better and newer treatment options and showing more suitable therapeutic positioning in future treatment modalities.
The indication for AMT-253 to be included in the Breakthrough Therapy Program is “unresectable locally advanced, recurrent or metastatic melanoma that has not been previously treated with first-line therapy”. This is a life-threatening disease that seriously affects the quality of life of patients, and there is still a huge unmet clinical treatment need in this population.
Currently, treatment options for advanced melanoma are limited, primarily relying on targeted therapy, immunotherapy, and chemotherapy, but overall efficacy is limited, leaving significant unmet clinical needs. Given the reported objective response rates of approximately 8.8% to 42.9% and median progression-free survival of approximately 2.8 to 6.6 months for existing second-line melanoma therapies, these results support the potential of AMT-253 to become a best-in-class treatment for this indication, and the CDE has granted it Breakthrough Therapy designation.
About AMT-253
AMT-253, a MUC18 ADC, is composed of a proprietary antibody with high MUC18 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogenous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased “bystander effect” compared to the equivalent of competitor ADCs**. AMT-253 has a drug-to-antibody ratio of eight. AMT-253 is being evaluated in a Phase I/II study in patients with melanoma and other advanced solid tumors. Additional information on the AUS PhI(NCT05906862) and China PhI/II (NCT06209580) trials can be found at clinicaltrials.gov.
** Weng et al., (2023) Cancer Discovery 13:950–73