An anti-PMEL antibody-drug conjugate with a G(q/1)(1) inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial.

DYP688, an antibody-drug conjugate targeting PMEL with a Gq/11 inhibitor payload, shows promising activity in GNAQ/GNA11-mutant melanomas with a 19.7% response rate.

• Why it matters: Metastatic uveal melanoma has limited treatment options and high mortality, especially with prevalent GNAQ and GNA11 mutations, highlighting the need for targeted therapies.
• What they did: A phase 1 trial involving 66 patients tested DYP688, assessing safety, pharmacokinetics, and preliminary efficacy, with doses escalated to evaluate tolerability and antitumor activity.
• The result: DYP688 was well tolerated, with manageable adverse events, and demonstrated tumor responses and disease control, supporting further development of this targeted approach.