On December 17, 2025, according to the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), the key product AMT-253 (a MUC18-targeting ADC) developed by PuZhong Discovery has been included in the Breakthrough Therapy Designation list. The intended indication is for previously treated, unresectable locally advanced, recurrent, or metastatic melanoma.

AMT-253 is the world's first and only MUC18-targeting ADC to have entered clinical development, representing a potential first-in-class ADC therapy for melanoma. It is expected to achieve significant breakthroughs in both treatment mechanisms and paradigms for this indication.

In the Australian Phase I and China Phase I/II trials of AMT-253, 36 chemotherapy-naïve melanoma patients were treated with AMT-253. As of September 8, 2025, the objective response rate (ORR) was 41.7%, the disease control rate (DCR) was 80.6%, and the median progression-free survival (mPFS) was 8.5 months. Clinical data suggest that AMT-253 demonstrates clinical advantages in both efficacy and safety compared to existing standard therapies and potential alternative treatments. It may improve tumor response and quality of life for patients with previously treated, unresectable locally advanced, recurrent, or metastatic melanoma, offering a superior and novel treatment option with a more suitable therapeutic positioning in future treatment paradigms.

The indication for which AMT-253 was included in the Breakthrough Therapy Designation is "previously treated, unresectable locally advanced, recurrent, or metastatic melanoma," a condition that severely threatens life and significantly impacts patients' quality of life. There remains a substantial and urgent unmet clinical need within this patient population.

Current treatment options for advanced melanoma are limited, primarily consisting of targeted therapy, immunotherapy, and chemotherapy, with overall efficacy remaining constrained and significant unmet clinical needs persisting. Given the reported ORR of approximately 8.8% to 42.9% and mPFS of about 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 therapy for this indication, justifying its designation as a Breakthrough Therapy by the CDE

Reference：https://bydrug.pharmcube.com/news/detail/f8f16a27c68ca0feed044164c32e8a0c