ASCO 2024 – USP1 lives on, for now
Despite the dismal performance of Roche’s USP1 inhibitor RO7623066 in its first-in-human study the project’s development continues. The trial’s results, updated at ASCO yesterday to a 28 March cutoff, still showed just the one partial response stated in the abstract, and with 29 evaluable solid tumour patients the ORR stands at only 3%. The presenter, Dr Timothy Yap from MD Anderson, said the “limited single-agent activity” of RO7623066 had led to its development pivoting to a combination with Lynparza, where he presented preliminary data from 12 patients; however, here there were no responses to report at all, with three subjects who experienced tumour shrinkage all being graded as having stable or progressive disease. All three had BRCA1 or 2 mutations, so an effect being due largely to Lynparza can’t be ruled out. Roche licensed RO7623066, then known as KSQ-4279, from KSQ Therapeutics last June. The data will be of interest to Exelixis and Debiopharm, which both have USP1 inhibitor projects in early development, though Tango Therapeutics has discontinued its contender TNG348, citing liver toxicity.
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