An anti-PMEL antibody-drug conjugate with a G(q/1)(1) inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial.
A custom-designed antibody drug targeting a specific mutation showed activity in uveal melanoma, a cancer with no approved treatments and extremely poor outcomes.
This phase 1 first-in-human trial of DYP688, a novel anti-PMEL ADC delivering a Gq/11 inhibitor payload specifically matched to GNAQ/GNA11-mutant tumor biology, enrolled 66 patients with metastatic uveal melanoma (a cancer with no FDA-approved systemic therapies and very poor prognosis). The 19.7% ORR, 71.2% tumor reduction rate, and 7.2-month median PFS with manageable safety profile support further clinical development of this biology-matched approach in a disease with extreme unmet need.
What the study was
- Study design
- Phase 1 dose-escalation first-in-human trial
- Population
- Patients with metastatic uveal melanoma and other GNAQ/GNA11-mutant melanomas (n=66)
- Sample size
- 66
- Category
- Treatment Innovation
- Maturity
- Exploratory
- Journal
- Nature medicine
Why it surfaced
Novel biology-matched ADC mechanism for metastatic uveal melanoma, a cancer lacking approved systemic options (85-90% GNAQ/GNA11-mutant); phase 1 data showing meaningful antitumor activity in a lethal rare cancer published in Nature Medicine warrants immediate pipeline attention.
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