STAT+: RevMed’s pancreatic cancer drug nears European approval

The incidence of pancreatic ductal adenocarcinoma continues to rise, making it one of the most lethal human malignancies; although the field has gained considerable understanding of its biology, translating that knowledge into clinical benefit has been persistently difficult, and KRAS-targeted therapy is currently one of the most closely watched directions ^[1]. Genomic studies have repeatedly confirmed that KRAS is the core mutated driver gene in pancreatic cancer, and its mutations take far more than one form—some tumors even carry multiple KRAS mutations simultaneously ^[2,3]. However, existing direct targeted agents such as sotorasib are irreversible inhibitors designed specifically for the KRAS G12C mutation ^[4], and G12C accounts for only about 1-2% of pancreatic cancers ^[5] and just 3-4% of metastatic colorectal cancer, with limited efficacy as monotherapy ^[6]—leaving the vast majority of pancreatic cancer patients harboring other KRAS alterations effectively excluded from targeted therapy, which has long been the point where the field has been stuck.

According to a Nature Biotechnology brief, in August 2026 the US FDA approved Rasonque (daraxonrasib) from Revolution Medicines for the most common form of pancreatic cancer—metastatic pancreatic adenocarcinoma—a first-in-class RAS inhibitor. Just one month later, early clinical trial results reported in September showed the drug also holds promise in lung cancer. These results have heightened industry expectations that RAS inhibitors such as Rasonque could combat multiple refractory tumors, including pancreatic, lung, and colorectal cancers.

The significance of this advance lies first in target coverage: Rasonque blocks multiple forms of RAS proteins, including mutant KRAS as well as other RAS proteins present in more than 90% of pancreatic tumors, so it is no longer confined to the small subset of G12C patients. Its mechanism of action is also fundamentally different: unlike conventional KRAS G12C inhibitors such as sotorasib (Lumakras) and adagrasib (Krazati), which bind the protein's 'off' state, Rasonque binds the RAS GTPase in its GTP-bound, 'on' conformation that drives oncogenic signaling. Through a 'molecular glue' mechanism, the drug simultaneously binds cyclophilin A, which is highly abundant within cells, and RAS, preventing the latter from interacting with its signaling partners. This effectively moves the field beyond the old strategy of 'locking onto a single mutant subtype and waiting for the protein to switch off' to one of 'broad-spectrum blockade that directly strikes the active state.'

Of course, the problems are not thereby solved. The benefit in lung cancer so far comes only from early trials, and whether it holds up remains to be tested in larger studies; expectations for colorectal cancer and other tumor types remain more hope than confirmation for now; and the drug's long-term efficacy, resistance, and safety are questions that must be answered going forward.