Story behind “undruggable” KRAS in pancreatic cancer; full OS data needed at ASCO to validate early signal
This drug, daraxonrasib, is the topic of an ASCO’s plenary session at the end of the month, likely the one with the most fanfare. Pancreatic cancer has been a graveyard for oncology drug development for decades. That’s part of why the reported RASolute 302 data are getting so much attention.
The eventual drug traces back through decades of academic work, failed hypotheses, and persistence after most pharma/biotech companies abandoned the field.
Reported OS in metastatic PDAC was 13.2 months vs 6.7 months with chemotherapy (HR 0.4, P < 0.0001). Obviously need to see the full dataset from RASolute 302 at ASCO, but at face value that’s a striking signal in a space that hasn’t moved much.
This is in the ITT population, not limited to RAS-mutated disease. Really interested in the subgroup breakdown to understand how much of the effect is being driven by RAS-mutant patients vs broader activity. Will need to see the break down of the chemo used and if there any imbalance with what was used in more fit pts.
The OS number also stands out in what’s a 2nd line setting, but looks more comparable to 1st line OS numbers. Curious what second-line regimens patients actually received. Will want to see gr 3/4 ADEs and what discontinuation rates are, but FOLFIRINOX, usual 1st line treatment, is not an easy regimen to tolerate. This is me trying to cool expectations, but genuinely happy to see this incredible advancement in the pancreatic space.
We have FDA approved KRAS G12C inhibitors for those with that mutation in NSCLC and even in pancreatic cancer, but with more marginal results. Results that don’t have an overall survival benefit of significant magnitude and are only for the G12C mutant subset. In panc, it’s small subsets, not controlled, and an OS near ~7 mos. In NSCLC, no stat sig significant difference OS benefit as monotherapy in 2nd line treatment.
Back to this story, KRAS is described as a target with minimal places for a drug to attach to, which is how became known as the undruggable target. Approach to overcome this described in the story is: “developed a strategy to stick a drug onto another protein in the cell, cyclophilin, and then use the larger combined surface to wrap around KRAS and shut it down.”
NYT story of how the drug came to be: https://www.nytimes.com/2026/05/12/health/pancreatic-cancer-daraxonrasib-kras.html?smid=nytcore-ios-share
Limited available results:
https://www.onclive.com/view/daraxonrasib-yields-significant-survival-advantages-vs-chemotherapy-in-metastatic-pancreatic-cancer