AMT-253, a MUC18-targeted antibody-drug conjugate, has shown encouraging results in two phase 1 melanoma studies. Among 56 evaluable melanoma patients, the overall response rate was 28.6%, with 15 confirmed partial responses, and the disease control rate reached 73.2%. Responses varied by melanoma subtype, with acral and unknown primary melanoma showing particularly strong disease control. Patients without prior chemotherapy tended to respond better.
Early signs of benefit were also observed in several gynecologic cancers. Endometrial carcinoma showed a 38.5% response rate, cervical squamous cancer had a 30% response rate, and uterine leiomyosarcoma had a 30.8% response rate, with disease control rates reaching 90–100% across these groups.
The studies enrolled 170 patients with a median age of 57. About two-thirds were women. Melanoma accounted for 43.5% of cases, gynecologic cancers for 26.5%, and the rest were other solid tumors.
AMT-253 demonstrated a manageable safety profile, with the maximum tolerated dose determined to be 4.8 mg/kg. Treatment-related side effects occurred in most patients, and about half were grade 3 or higher, mainly due to low blood counts. No neuropathy or pneumonitis was reported. The most common side effects included nausea, anemia, fatigue, vomiting, diarrhea, neutropenia, and thrombocytopenia.
Overall, these results support further development of AMT-253 for melanoma and select gynecologic cancers.