Triple meeting 2025 – Astellas touts a degrader turnaround

At ESMO 2024, Astellas’s KRAS G12D degrader ASP3082 looked lacklustre, but data presented at the Triple meeting in relapsed NSCLC put the project in line with Revolution Medicines’ selective G12D inhibitor, zoldonrasib. On the face of it, a 38% ORR with ASP3082 at the go-forward dose of 600mg weekly looks below the 61% that Revolution claimed with zoldonrasib in NSCLC at AACR. But if only confirmed responses are taken into account, ASP3082 comes out on top, with an ORR of 33%, versus zoldonrasib’s 28%. Both trials are early, and patient numbers are small, but perhaps it’s too soon to write off ASP3082. Toxicity has been a question with the Astellas project, with three dose-limiting toxicities, including liver enzyme elevations, previously seen. However, there were no DLTs in second-line NSCLC, and only two grade 3 treatment-related adverse events, of anaemia and neutropenia. Astellas plans to start a phase 3 trial of ASP3082 in pancreatic cancer by March 2026, is prepping for a registrational NSCLC study, and expects to make a decision soon on whether to press on in colorectal cancer. The Japanese company is also developing another KRAS G12D degrader, ASP4396, which uses a different enzyme for degradation.

Cross-trial comparison of ASP3082 and zoldonrasib in relapsed NSCLC

Note: ASP3082 at 600mg weekly dose; zoldonrasib data at 1,200mg daily dose. Source: EORTC-NCI-AACR & AACR 2025.