An anti-PMEL antibody-drug conjugate with a G q/1 1 inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial
Published report from the trial registered as NCT05415072, in Nature Medicine (2026), chosen as the most cited paper whose own text cites the registry id.
Overview
Metastatic uveal melanoma (mUM) is an aggressive cancer with limited treatment options; 85-90% of tumors harbor activating GNAQ and GNA11 mutations. Uveal melanoma cells also express PMEL (also known as PMEL17 or gp100), a melanocyte lineage antigen. DYP688, a novel biology-matched antibody-drug conjugate, binds surface PMEL and delivers the potent Gα q /Gα 11 (G q/11) inhibitor SDZ475 as payload by internalization. This dose-escalating first-in-human phase 1 study of DYP688 in patients with metastatic uveal melanoma and other GNAQ/GNA11-mutant melanomas assessed safety as the primary endpoint and pharmacokinetics and preliminary antitumor activity as secondary endpoints. Sixty-six patients received varying DYP688 doses and schedules. Grade 3 treatment-related adverse events occurred in five patients (7.6%), including one dose-limiting toxicity of grade 3 hypotension. Objective responses were seen in 13 out of 66 patients (19.7%) and tumor reduction in 47 out of 66 patients (71.2%). Median progression-free survival was 7.2 (95% CI: 5.3-7.8) months. In summary, DYP688 was well tolerated and showed preliminary efficacy, supporting this novel therapeutic approach. ClinicalTrials.gov identifier: NCT05415072.
Indexed on Europe PMC as PubMed record 42443515 (DOI 10.1038/s41591-026-04518-z). Its abstract cites the registry id NCT05415072, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT05415072 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.