ASCO 2025 | DYP688 as a treatment option in patients with HLA-A*02:01-negative MUM
Matteo Carlino, FRACP, PhD, The University of Sydney and Westmead Hospital, Sydney, Australia, comments on a first-in-human study (NCT05415072) of DYP688, an antibody drug conjugate delivering a direct Gq/11 inhibitor, in patients with metastatic uveal melanoma (MUM) and other GNAQ/11 mutant melanomas. Until recently, there have been no therapies for HLA-A*02:01-negative patients. Tebentafusp, although an active agent with survival advantage, is restricted to HLA-A*02:01-positive patients. DYP688 can be used as treatment for those negative or tebentafusp treatment-resistant positive patients. Although addressing these current unmet needs, future trials will compare DYP688 against other therapies such as darovasertib and crizotinib in Phase III trials. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
I think we really have two challenges. Up until the development and approval of tebentafusp, we had no effective agents. Tebentafusp is an active agent with a survival advantage, but only an option for that 30% or so of patients who are HLA-A02-01 positive. For the rest of our patients, we don’t really have an effective treatment. So Dabrafenib is useful in two settings, I think...
I think we really have two challenges. Up until the development and approval of tebentafusp, we had no effective agents. Tebentafusp is an active agent with a survival advantage, but only an option for that 30% or so of patients who are HLA-A02-01 positive. For the rest of our patients, we don’t really have an effective treatment. So Dabrafenib is useful in two settings, I think. Patients who are A02, A01 negative, and A02, A01 positive having failed tebentafusp, but I think that’ll be its main role. Of course, as the drug develops, we’ll answer the question how this compares to other therapies that are currently in development, the most relevant one being the combination of darovasertib in crizotinib, which is currently in Phase III trials.
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Disclosures
Honoraria – Bristol-Myers Squibb; MSD; Novartis
Consulting or Advisory Role – Amgen; Bristol-Myers Squibb; Eisai; IDEAYA Biosciences; Innovent Biologics; Medison; Medison; Merck Serono; Moderna Therapeutics; MSD; Nektar; Novartis; OncoSec; Pierre Fabre; QBiotics; Regeneron; Roche; Sanofi
