Pashtoon Kasi, M.D., on daraxonrasib's impact on patients: 'You have to see it to believe it' | ASCO 2026

When RASolute 302 data were presented at the American Society of Clinical Oncology (ASCO) annual meeting, the room responded with not one but two standing ovations. The randomized phase 3 trial, conducted in patients with previously treated metastatic pancreatic cancer, showed that daraxonrasib, a first-in-class multi-RAS inhibitor, roughly doubled median overall survival compared with standard second-line chemotherapy: 13.2 months versus 6.7.

But the significance of the findings stretches beyond pancreatic cancer. Because RAS mutations drive malignancies across tumor types, a mutation-agnostic inhibitor capable of targeting multiple KRAS alleles represents a potential inflection point for oncology broadly.

In part 1 of this Q&A with Managed Healthcare Executive^® (MHE^®), City of Hope’s Pashtoon Kasi, M.D., M.S., an investigator on RASolute 302, walks through the trial design, explains how daraxonrasib differs mechanistically from earlier allele-specific inhibitors, and reflects on what the numbers don't fully capture about its impact on patients.

Read part 2 of this interview here.

This interview has been edited for length and clarity.

MHE: Can you give us a brief overview of the RASolute 302 findings and why they’re exciting, and what stood out to you most?

Kasi: RASolute, at a high level, was a randomized trial done in second-line pancreatic cancer. Patients had already had one treatment that failed, or they had progression, or the treatment couldn’t be tolerated anymore. Then they would get another type of chemotherapy in the second line, and either they got the new drug, the multi-RAS inhibitor daraxonrasib, or standard-of-care dealer’s choice chemotherapy.

I think what stood out that everybody is aware of — even prior to the presentation [at ASCO], which got a standing ovation twice, which kind of speaks for itself — is that overall survival was doubled from 6-odd months to 13-plus months. That part is groundbreaking, and I think what's important and relevant for patients and caregivers and oncologists in the field is it's not just about second-line pancreatic cancer. The story is bigger than that. It's about having a multi-RAS inhibitor, and for the so-called “undruggable” KRAS. Over a decade ago, one of my teachers said that we'd probably never see a drug that is a multi-RAS inhibitor in our lifetime — but that myth or dogma is broken in a good way. That is huge, because patients who have RAS-driven malignancies tend to have a bad prognosis. While the study was done in metastatic pancreatic cancer, it's important to realize that that's because over 90% of pancreatic cancers are KRAS or RAS driven. But it's not uncommon. Colorectal cancer is at least 55% to 60% RAS-driven, and ovarian cancer, lung cancer, breast cancer, and beyond. This drug is going to pave the way for those patients as well — currently through trials, but then later on, this efficacy and minimal toxicity can be replicated across disease types.

MHE: The pan-RAS mechanism is what makes this different from allele-specific inhibitors. Can you explain why that broad activity is key?

Kasi: Compared to the first generation of drugs, like sotorasib or adagrasib, several key differences at a higher level are: first, it's mutation agnostic, as opposed to the previous drugs that were looking at one aberration: G12C. Daraxonrasib is mutation agnostic in the sense that it's targeting multiple alleles. Also, the way they bind to the protein is what's different about this drug. It has better tumor penetration as well, which is important for a disease like pancreas cancer, with gut penetration being an issue. These are several reasons why this works where other drugs didn't.

MHE: You were an investigator on RASolute 302. Is there anything you observed in your patients on daraxonrasib that the data alone can't fully capture?

Kasi: The overall response rate and the reported side effects don’t necessarily encompass the tangible impact that we're having in the actual lives of the human beings that we're treating. Pancreas cancer is an unforgiving disease, to say the least. Patients decline very quickly. They have this global decline, some of which is directly related to the cancer and some of which is related to the cumulative toxicity of chemotherapy. And this study was second-line, but the harsh reality is there's so much treatment nihilism against pancreatic cancer, and many patients never even see an oncologist.

Daraxonrasib is not a cure, but when you have a non-chemotherapy option, you can pivot back and forth and use chemotherapy when the targeted therapy stops working, or vice versa.

I had patients who were on disability who had robust improvement in their pain and quick improvement in tumor markers that were in the 1000s but then essentially normalized within weeks. That's not necessarily captured by the slides in the presentation.

With some of these quality-of-life tools or time to deterioration, which was significantly different than patients on chemotherapy, the trial results do not capture that. I had patients who went from disability to working full-time and enjoying what they're doing, whether it's work or family or otherwise. There are a lot of symptoms that the cancer itself brings that could range from pain to ascites or just overall producing chemicals or cytokines that cause lack of appetite and global decline. When you have something that reverses all of that, you have to see it to believe it, to say the least. Sometimes buzzwords like “unprecedented” or “milestone” or “dramatic” are used loosely, but this drug and what we saw in trials and patients were all of the above.

MHE: Is there anything else you’d like to highlight about the study or the findings?

Kasi: Another thing to add is that even right now, I get questions about activity in other KRAS aberrations. While the primary analysis was powered for the G12-specific mutation, the drug has activity in the other KRAS aberrations too, including the not-so-common Q61 mutations and even in the wild type. It's intriguing. We often tell patients and caregivers that targeted therapies are more like a lock and key — you have to have the lock for the key to work. But it's intriguing that it's not just the KRAS G12D or G12V or the traditional G12 aberrations where this drug was studied. If you look at the subset analysis in the table, they had an 8% subgroup in the actual study that was the wild type and these other not-so-common KRAS aberrations. In the real world, if you look at different data, at least 10% are probably wild type and don't have the KRAS mutation, and I would say another 5% to 8% are these other not-so-common KRAS aberrations. If you're looking at the traditional KRAS G12 type of pancreas cancer, it’s probably in the 80% to 85% range if you look at all the numbers. But with these other subsets too, it will be intriguing how the label comes out and how FDA approves it, but in preclinical and clinical trials, they had such analyses that suggested, while not every single aberration was studied, it was something that had activity for second-line pancreas cancer, not necessarily second-line pancreas cancer with a mutation from the alphabet soup.

Read part 2 of the interview here.