Astellas takes its G12D degrader pivotal

Last year, Astellas disclosed that it planned to evaluate its KRAS G12D degrader setidegrasib alongside chemo in its phase 3 trial, and now it’s official, with a new listing on clinicaltrials.gov. However, while the group previously appeared to be focusing on an mFolfirinox combo in study in the first-line G12D-mutated pancreatic cancer, it’s now become apparent that patients will also be able to receive Nalirifox chemo, as per physician’s choice. The combo will be compared against chemo alone, with a primary endpoint of overall survival; the 614-patient trial is set to start at the end of February, with primary completion in 2029. At January’s ASCO-GI meeting Astellas claimed a 58% response rate with setidegrasib 600mg plus chemo; excluding unconfirmed responses gave a 42% ORR. However, the combo was linked with a 59% rate of grade 3 or higher adverse events, and 23% rates of serious adverse events and drug-related discontinuations. Setidegrasib will become the third KRAS G12D-targeting project, and the first degrader, to enter phase 3; pivotal trials of Incyte’s INCB161734 and Revolution’s zoldonrasib are also set to start this year. Astellas recently discontinued a backup G12D degrader, ASP4396, to focus on setidegrasib.

KRAS G12D-targeting projects in late-stage development

Source: OncologyPipeline.