'A decade in the making': Pashtoon Kasi, M.D., on what comes after RASolute 302 | ASCO 2026

A drug that doubles overall survival compared with the current standard of care is a headline result. But for investigators who watched patients respond week over week — stopping pain medications, even returning to work — the RASolute 302 data presented at the American Society of Clinical Oncology (ASCO) annual meeting represent something larger: a turning point in how pancreatic cancer is treated.

In this second part of Managed Healthcare Executive^®’s conversation with RASolute 302 investigator Pashtoon Kasi, M.D., M.S., of City of Hope, Kasi moves beyond the phase 3 findings to discuss what happens next. The RASolute program already extends into first-line treatment and a post-surgical ctDNA-positive population, and investigator-initiated trials are exploring combinations with chemotherapy. With daraxonrasib already added to the FDA Expanded Access Program, the path toward approval is moving faster than many expected, and the decade-long effort to drug the "undruggable" KRAS is now a race to get there.

Read part 1 of this interview here.

This interview was edited for length and clarity.

MHE: The findings presented at ASCO are second-line results. What's the thinking around moving daraxonrasib into earlier lines of treatment, and what does that pathway look like?

That pathway is already in place. This study was RASolute 302, but there's also RASolute 303, which is first-line; there's RASolute 304 for patients with ctDNA positivity who have had curative-intent surgery, chemotherapy, and radiation and unfortunately are still not cured. We see this new paradigm shift of using non-invasive biomarkers like ctDNA. We've been part of trials where they're using that as an integral biomarker to enroll, because for patients who are ctDNA positive, unfortunately, it’s just a matter of time before the scan shows disease. So why wait?

I think, unfortunately, some of that is the traditional regulatory pathway that a lot of these drugs have to take, but I think it's time to kind of reinvent some of that process. Back to your question, it's not a future path; it's already happening, including studies or investigator-initiated trials about doing it in combinations and in the neoadjuvant setting, because it does not have overlapping toxicity with chemotherapy. And we're not reinventing the wheel here — we have seen in so many other cancer types that if you have a targeted therapy and you also have chemotherapy that could be efficacious, there can be synergy between the two.

Coming up with rational combinations that are tolerable is also important, because at the end of the day, we have to remind ourselves we are giving this treatment to human beings and not doing an experiment in a petri dish. Not everything that is going to be more efficacious is going to be more tolerable, so keeping in mind the skin toxicity and the other side effects is key, and there's a lot of work that's already ongoing.

MHE: How does the oral once-daily administration of the drug factor into access and value conversations?

A pill is always more appealing to a patient than an intravenous infusion. The fact that they're taking a pill doesn't mean that they don't need to see the doctor or do labs, but it's a lot more convenient and patient-friendly and caregiver-friendly. There is a lot of time toxicity, as we call it — the amount of time that a patient spends in cancer centers, whether it's community or academic — for infusions. Infusion times or suites are also overbooked, and there are a lot of delays there in terms of getting patients scheduled for infusion. [With a pill,] so you don't need to worry about infusion times or getting them scheduled, so it's a lot more appealing.

This does not mean supportive care is not necessary. Specifically, regarding the skin toxicity, I know there are a lot of extreme cases being discussed on social media. I would like to point out to the average patient or caregiver and oncologists who may have not had experience with this drug that it's not entirely new or anything that we oncologists haven't been used to. There's a lot of TKIs or pills or infusions that have skin-related toxicities. In the study protocol, we had preemptive skincare guidelines, and we often partnered with our colleagues in dermatology.

In the grand scheme of things, an unforgiving pancreas cancer could kill a person in a few months, and managing some skin-related issues with treatment was doable. It does take two-way communication and often entails partnering with the patient and caregiver, as well as the supportive care, including dermatology colleagues, for unique side effects.

Overall, this new addition to the treatment algorithm is a monumental moment and a big hope for a disease like pancreatic cancer. While not FDA approved yet, daraxonrasib was added to the FDA’s Expanded Access Program within two days of the results, which has not happened before, so that also shows the positive reception from regulatory agencies. When the drug hopefully gets approved in the next few months, if not sooner, for metastatic second-line pancreas cancer, I also suspect it will be used a little earlier, as well, or maybe providers will pivot earlier as the effects of first-line chemotherapy accumulate. As one of my colleagues put it, if tomorrow this drug were approved, I’d see virtually no reason why somebody would not be using it in the second-line setting as it was studied, or even a pivot earlier, if feasible and possible.

MHE: Any closing thoughts?

There are the numbers that you see on the Kaplan-Meier curves, and then there is the tangible impact in patients with pancreas cancer. We saw these patients week by week, and we saw improvement within a week. A patient told me that she stopped taking her pain medicine, or she felt better to the point that she wanted to start working. Those are not the kinds of things that you ever hear routinely, so that speaks to the efficacy of the drug and speaks to the fact that while there are side effects, they're manageable.

There is a reason why there was a standing ovation during and after the presentation [at ASCO], and all I can say is we're glad and thankful to be part of this moment. At City of Hope, we were one of the few sites that had both trials running; we've been part of the story all along, and with the expanded access, we are hoping to open that. We're getting requests from all over the world, and the drug cannot be approved soon enough.

Our institution just had the portal activated and expanded access going through the regulatory channels to help patients benefit from the drug until it is approved, and hopefully we're talking about some number of weeks, if not more than a few months, here before we can get it to our patients. I'm getting requests several every day, even before the results were announced, because patients and caregivers and advocacy groups and doctors and physicians could already see what we were seeing on the trial. Before phase 3 even started, in phase 2, people saw what it did. [ASCO] was the big moment, but it's been almost a decade in the making.

Also, it paves the way for the plethora of companies that have some sort of KRAS inhibitor, whether it's multi-RAS or mutation-specific. It kind of opened the floodgates for not just this one company, which also has a pipeline of other drugs, but for other companies, too. It has just accelerated the progress there. Another thing that is very heartening and important to note is that they're also looking at drugs to work on resistance mechanisms as we speak.