How Significant is the Approval of Daraxonrasib in Pancreatic Cancer?

Since the first reporting of overall survival (OS) data from the phase 3 RASolute 302 trial (NCT06625320), a near doubling of OS with daraxonrasib (Rasonque) vs standard of care, patients and clinicians have been aware that daraxonrasib represented a real advancement in the treatment of not just pancreatic cancer, but oncology.¹ About 2 months later, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, when Brian M. Wolpin, MD, MPH, stood on the plenary stage and presented the OS curve from the trial, the room erupted in applause.²

From that first reporting on April 13, exactly 135 days passed before August 26, 2026, when the FDA approved daraxonrasib (Rasonque) for the treatment of patients with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or who are not candidates for multiagent systemic therapy.³ This approval symbolizes many things,but most of all it is the culmination of decades of tireless work from thousands of experts.

CancerNetwork® spoke with Nicholas Hornstein, MD, PhD, a gastrointestinal oncologist at Northwell Health and a 2024 ASCO Young Investigator Award winner, shortly after the approval to gather the significance of the moment, what the FDA’s indication means, and what’s next for daraxonrasib and the pancreatic cancer space.

CancerNetwork: What is the significance of the daraxonrasib approval?

Hornstein: The first thing to say is that we took what was called an “undruggable” target for many, many years, and now we have an effective drug against it. Now, we’ve had drugs against KRAS in the past against specific isoforms, so one mutation on one gene. What the difference is now is that daraxonrasib was created in an effort to move away from that and towards an effective therapy for patients with KRAS-mutated disease, regardless of the specific mutation. That moves us from being able to treat a few percentages of patients with [for example] G12C mutations, to treat patients in general with KRAS, NRAS, and just RAS in general mutations. That’s a huge step forward. We’ve also now seen the first ever effective systemic therapy for pancreas cancer that is not a chemotherapy. Overall, some major advances in the field, and this is something that is very exciting.

Specifically, for the last part of the FDA’s indication, “patients who are not candidates for a multi-agent systemic therapy”, does that read like something that may slip daraxonrasib into first-line settings?

It’s worth focusing on exactly what this approval was for. First off, pancreas cancer—this is what the study was in, and where we knew it was going to be coming. I know Revolution Medicine and some treating oncologists hoped that there would be an approval in a RAS-agnostic format. I just told you that this is a drug that targets RAS, and one might expect, ‘Oh well, the approval includes RAS.” Not true. You don’t need to have a RAS mutation, according to this approval, to get this drug. That is in line with the inclusion criteria of the original study that led to this approval, and it’s in part because at least 90% of pancreas cancers will have a RAS pathway mutation, and a lot of people think that in the remaining 10% potentially [RAS] is still there—we just haven’t found it. This approval is for all comers with pancreas cancer. In the second line, it’s clear cut. In the first line, if the treating oncologist, feel like a patient in front of you is not a candidate for systemic therapy, this is also on the table. Offhand, I can say there are a number of patients who come into clinic with pancreas cancer that may be malnourished, deconditioned, and just not up for systemic chemotherapy. Well, now we have an option for them, and that in and of itself is something amazing.

Is daraxonrasib the go-to option in a second-line patient?

We’re already having discussions about our clinical trial portfolio at Northwell Health, where we’re saying you know “We have these trials in the second line setting. Potentially, we need to change [them] because the second line has already changed.” Overnight, the standard of care is now to move to KRAS-targeted therapy. There are some trials in that space, potentially combining with chemotherapy and other things. All I can say is that the landscape is shifting very, very quickly, and that's a huge change for a disease where we have not seen major advances. We’ve seen chemotherapy repackaged in different forms, like changing the toxicity and slightly changing the efficacy, but we haven’t seen this kind of movement. I expect both in pancreatic cancer as well as other RAS-driven diseases like colon cancer, we’re going to see things shift very quickly.

What effect can the daraxonrasib approval have on other disease states?

This approval has been out for less than 12 hours, and I already have half a dozen emails in my inbox from patients with colorectal cancer who are asking, “Hey, I know I have a KRAS mutation. Can I get this drug? It’s approved now. Can we try to get it?” There is still a lot of data we’re waiting for to look at how effective this is. We know that RAS pathway mutations are not one size fits all. It depends on the cancer you have. Sometimes they’re a little bit more mercurial. Sometimes we need to add other drugs to ensure that we get the effect we want. For example, in KRAS G12C-mutated colon cancer, we have to add a second drug targeting EGFR. There are still things we don’t know. There are still things that we need to find out in other disease spaces, but this drug is coming to the market. I expect we’re going to see a number of treating oncologists and patients looking to this as an answer for the disease, especially if they’ve progressed on prior lines of therapy.

What’s next for daraxonrasib and the RAS-targeting space?

The next step is questioning how we can continue to target the RAS pathway. How can we take allele specific—G12C and G12D, and so on and so forth—and either combine it with chemotherapy or combine it with other agents. Revolution Medicine have an entire pipeline already built up to look at resistance mechanisms to try to cut things off at the pass, as it were. I expect that we’re going to continue to see major advances based on this technology. The space is going to continue to evolve, and the hope is that even though this drug promises less than a year, frankly, of additional time for patients with metastatic pancreas cancer, that we’re going to be able to take that advance and increase it. Because when you look back at the history of oncology, there are very few drugs or pathways where, when one of the first agents comes out, it truly is a game changer. Using the knowledge we gain, we can move forward as a field, and we can help patients move from staving off disease to curing it. That’s the goal here.

Is there anything else in this space that’s particularly exciting?

In terms of allele-specific agents, there are a lot of companies in addition to Revolution Medicine involved; Verastem and Incyte—we could go on and on and list many companies, but those 2 have very good allele-specific drugs. There are others in development. There are companies looking beyond just targeted agents and are developing cancer vaccines as a strategy. We all just saw some data come out from Merck and Moderna regarding their [phase 3 INTerpath-001 trial (NCT05933577)] that looks like it’s going to be positive for a cancer vaccine for patients with…melanoma.⁴ I expect we’re going to continue to see that. Elysio, for example, is another company that has a KRAS vaccine targeted strategy in pancreatic and colorectal cancer, but the list goes on. I'm excited for what the next few years of development are going to bring, both in the RAS space and the immune engineering space.

This approval came together very quickly under the Commissioner’s National Priority Voucher (CNPV) program. Going forward, is that a good thing or something clinicians and patients should be aware of?

In this scenario, this is relatively clear cut. Not all drugs and trials are as clear cut, and sometimes you do need the time to review, to ask questions, and to go into the details of how a clinical trial was conducted and the outcomes, because the devil is in the details, and trials have an exceptional number of details. Time will tell how the voucher program will expand. Clearly, the FDA wanted a win. This is an easy win for them, and they’ve done the right thing in this scenario. We’ll need to see how the voucher program is applied as more come forward, and we have more examples of this pathway.

What would you like someone to take away from this conversation?

It’s been a huge year, but it makes us think of the progress we’ve made and the progress we need to continue to make. I still see patients every day in clinic who are not doing well, who are dying from their disease, and advances like this approval are a strong motivator to acknowledge that we are doing better and we're continuing to move forward.

References

1. Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines Inc. April 13, 2026. Accessed August 27, 2026. https://tinyurl.com/44t5vh5d
2. Wolpin BM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5
3. FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma. News release. FDA. August 26, 2026. Accessed August 27, 2026. https://tinyurl.com/3rd5tt54
4. Merck and Moderna announce phase 3 INTerpath-001 trial of intismeran autogene plus KEYTRUDA® met endpoints of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with completely resected stage IIB-IV melanoma. News release. August 19, 2026. Accessed August 27, 2026. https://tinyurl.com/yxe3d24n