ASCO 2025 | Evaluating DYP688 and the future of GNAQ/11-targeted therapy in melanoma
Matteo Carlino, FRACP, PhD, The University of Sydney and Westmead Hospital, Sydney, Australia assesses antibody-drug conjugates (ADCs) in the treatment of melanoma. Although other ADCs other than DYP688 in patients with metastatic uveal melanoma (MUM) and other GNAQ/11 mutant melanomas, have been trialled, challenges including chemotherapy resistance and the delivery of cytotoxic payload remain. Irrespective of delivery method, cytotoxic toxicity profiles remain, signifying a shift in research to less toxic drugs like DYP688. However, it is uncertain whether ADCs similar to DYP688 will hold up in trial. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Like in many cancers, ADCs are being trialled in melanoma, but I think melanoma has some challenges but also benefits over other tumour streams. The first challenge is, as far as I’m aware, apart from DYP, every other ADC delivers a cytotoxic payload and melanoma is relatively chemoresistant. So we hope that by delivering this payload by an ADC we’ll get activity, but I still feel, unlike breast cancer or lung cancer, that chemoresistance will be a problem...
Like in many cancers, ADCs are being trialled in melanoma, but I think melanoma has some challenges but also benefits over other tumour streams. The first challenge is, as far as I’m aware, apart from DYP, every other ADC delivers a cytotoxic payload and melanoma is relatively chemoresistant. So we hope that by delivering this payload by an ADC we’ll get activity, but I still feel, unlike breast cancer or lung cancer, that chemoresistance will be a problem. The second issue we have, which is really the issue I think with ADCs across all cancers, is the toxicity profile. We see a cytotoxic toxicity profile irrespective of the ADC delivery. I would love to see more drugs like DYP with novel payloads in the future, both in melanoma and other cancers. But I think outside of DYP, I’m uncertain about whether we will get an antibody drug conjugate that is effective enough to lead to drug approval and really benefit melanoma patients.
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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
