As daraxonrasib hits the clinic, Frank McCormick says RAS is bigger than pancreatic cancer

Last month, FDA approved the RAS inhibitor, daraxonrasib, sponsored by Revolution Medicines Inc. and also known as Rasonque, for patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy.In this week’s episode of In the Headlines, Jacquelyn Cobb, associate editor with The Cancer Letter, speaks with Frank McCormick, a leader in the KRAS space, about the history of RAS and where the field might be going next.McCormick is also the David A. Wood Chair of Tumor Biology and Cancer Research and a professor in the Helen Diller Family Comprehensive Cancer Center and the Department of Cellular and Molecular Pharmacology at the University of California, San Francisco.In the pancreatic cancer world, McCormick expects the field to improve upon what has worked.“We hope that the drugs that hit KRAS directly, or allele specifically, will hit the protein harder and have less side effects, and therefore will give better clinical outcomes than daraxonrasib. That's a hope or an aspiration. And potentially be more easy to combine with other drugs to help make it even more potent. So that's I think what we're all hoping from the wave of drugs coming down the pipe. So those results will emerge over the next year or two probably from multiple places, including Rev Med themselves have their own second generation drugs which are more specific and so on.“So, it'll be a lot more and hopefully a lot better drugs even than daraxonrasib. So that's again, aspirational. As we see in most fields, the first drug is great, the next one's even better, and so on.”But there are other paths ahead that have opened up after the success of daraxonrasib.“Another frontier is in colorectal cancer, which is still pretty much white space in terms of target therapy for KRAS mutant, which is about 50% of all colorectal cancers. So, there's nuances around that also, but colorectal cancer, a lot of the tumors are driven by KRAS and a lot of people are now moving towards colorectal cancer, probably in combination with cetuximab and other drugs. But if we can make an impact on there as well, that'll hopefully crack that open as well. That would be another standing ovation at ASCO if someone could really increase survival in a big way in colorectal cancer.”Stories mentioned in this podcast include:  KRAS pioneer and Stephenson Prize winner Frank McCormick aims to prevent all KRAS cancers with a pill Pancreatic cancer finally starts to budge as daraxonrasib doubles overall survivalThe story of daraxonrasib is the ultimate hero’s journey A narrative curve with twists, turns, intrigue, drama—and a blow to a mighty foe FDA permits expanded access for investigational pancreatic cancer drug daraxonrasibLong-awaited results from first phase III trial of a RAS inhibitor in pancreatic cancer shows that daraxonrasib doubles median OS PanCAN’s BerkenblitZoldonrasib + daraxonrasib show 81% ORR in patients with RAS G12D metastatic pancreatic cancer, phase I/II study finds A transcript of this podcast is available: https://cancerletter.com/podcastc/20260909-daraxonrasib/