A first-in-human trial generated early evidence for setidegrasib, a KRAS G12D-targeted therapy, in patients with advanced pancreatic ductal adenocarcinoma and non–small-cell lung cancer. The New England Journal of Medicine publication reported early activity across both tumor types, fueling interest in KRAS G12D strategies. However, other oncology programs faced major pivots. Erasca’s pan-RAS molecular glue ERAS-0015 also drew market attention after phase I results and a reported patient death, while AstraZeneca separately discontinued multiple late-stage and midstage trials due to disappointing efficacy. Separately, Janux Therapeutics halted clinical development of its masked EGFR/CD3 T-cell engager JANX008 after what it described as subpar and inconsistent activity in a metastatic solid tumor Phase 1 study. Together, the updates highlight the tight coupling between early clinical signals, safety outcomes, and portfolio rebalancing across multiple mechanism classes in oncology.