Phase I data for DYP688, a first-in-class antibody-drug conjugate targeting metastatic uveal melanoma, demonstrated disease control in more than 80% of patients and tumor shrinkage in approximately 20%, according to results published in Nature Medicine and announced by Northwell Health's Feinstein Institutes for Medical Research.
The Nature Medicine publication reports data from the completed Phase I portion of the study. Although the trial remains listed as active but not recruiting on ClinicalTrials.gov, investigators note that Novartis has made a business decision not to advance the program further. Novartis has not publicly disclosed the rationale for halting further development, leaving the positive Phase I findings at odds with the company's portfolio decision.
The clinical signal matters because metastatic uveal melanoma remains one of oncology's most intractable problems. Median survival after metastasis is under two years, and approved systemic options are narrow. Immunocore's Kimmtrak (tebentafusp-tebn), the only therapy with a demonstrated overall survival benefit in a randomized trial, is restricted to patients carrying the HLA-A*02:01 genotype — roughly half the eligible population. Delcath Systems' Hepzato Kit (melphalan delivered via hepatic perfusion) addresses liver-dominant disease only. No approved second-line systemic therapy exists.
DYP688 is designed to work differently from either approved option. The drug is an ADC in which an antibody targeting PMEL17, a protein expressed on GNAQ/GNA11-mutant melanoma cells, delivers a Gq/11 signaling inhibitor payload directly to tumor cells. Rather than carrying a broadly cytotoxic warhead, the conjugate exploits the near-universal GNAQ/GNA11 mutation that drives uveal melanoma to selectively block the cancer's growth pathway, potentially sparing normal tissue and avoiding the severe systemic toxicities associated with conventional chemotherapy-linked ADCs.
The Phase I/II multicenter open-label trial enrolled patients with metastatic uveal melanoma and other GNAQ/11-mutant melanomas. The drug was described as well-tolerated, with severe systemic toxicities mitigated. Detailed safety data are available in the Nature Medicine publication. Early clinical data from the same first-in-human study had been presented at ASCO in May 2025.