DYP688 ADC Delivers Direct Gq/11 Inhibition with a 21.8% Response Rate in Metastatic Uveal Melanoma and other GNAQ/11 Mutant Melanomas

In the first-in-human Phase I dose-escalation study (NCT05415072, n = 66), DYP688 achieved a confirmed ORR of 21.8% (1 CR) in 55 evaluable patients with metastatic uveal or other GNAQ/11-mutant melanoma treated at ≥8 mg/kg; 63.6% had stable disease, median treatment lasted 7 months, grade 3 TRAEs were seen in 6% (hypercalcemia, hypotension, anemia, ↑GGT) with no toxicity-related discontinuations. Historically, tebentafusp and conventional chemotherapy offer ~9% and < 6% ORRs, respectively.