Who is this trial for?
This study was for adults with advanced pancreatic cancer carrying a RAS mutation, whose cancer had already worsened despite standard chemotherapy.
People in the trial had:
- Pancreatic ductal adenocarcinoma (PDAC) — the most common and most aggressive form of pancreatic cancer.
- A RAS mutation in the tumor — most often KRAS G12D, G12V, or G12R. About 9 in 10 patients had a mutation at a spot called “G12,” but you did not need that specific version: the remaining roughly 1 in 10 had a RAS mutation elsewhere (such as at a spot called “Q61”), and these patients appeared to benefit too.
- Advanced or metastatic disease (the cancer had spread, most often to the liver or lungs) that had already been treated with at least one round of chemotherapy. On average, people had received two prior treatments.
What kind of trial is this?
This was an early-phase (phase 1–2) study — the kind of trial done early in a drug’s development to find the right dose, check safety, and look for the first signs that it works. There was no comparison group: everyone received daraxonrasib.
Background: why researchers asked this question
Pancreatic cancer is one of the most lethal cancers. Most people are diagnosed once it has already spread, and for metastatic disease the average survival is less than a year — only about 3% of patients are alive five years later. Once the first chemotherapy stops working, the options are limited: second-line chemotherapy shrinks the tumor in fewer than 1 in 10 people, and typically holds the cancer back for only 2 to 3 months.
For decades, scientists knew the root cause but couldn’t do anything about it. Mutations in the RAS family of genes are found in more than 90% of pancreatic cancers, and most are at a single hotspot (KRAS codon 12). RAS was considered impossible to target with a drug. The first breakthrough — drugs against a variant called KRAS G12C — helped very little here, because G12C is found in only 1–2% of pancreatic cancers, and those drugs only catch RAS when the switch is already OFF.
Daraxonrasib was designed differently. It is “multiselective,” meaning it works against many different RAS mutations at once, and it targets RAS in its active, switched-ON state — the form that actually drives the cancer. Researchers asked: in people whose RAS-mutated pancreatic cancer had already progressed on chemotherapy, is daraxonrasib safe, and does it show signs of working?
The trial: what was tested and how
The study (formally called RMC-6236-001) enrolled 168 people with RAS-mutated pancreatic cancer that had already been treated, across 16 centers in the United States. Everyone received daraxonrasib as a daily pill. Earlier in the study, different doses (from 10 mg up to 400 mg) were tested to find the best one; 300 mg once daily was selected for further study.
Because this was an early-phase study, the main goal was safety — understanding the side effects and finding the right dose. How well the drug worked (tumor shrinkage, time before the cancer grew, and survival) was measured as a secondary goal. Crucially, there was no comparison group: every participant got the drug, so the results are best understood against what is already known about standard second-line chemotherapy, rather than as a head-to-head test.
Results: what they found
Among people treated with the 300 mg dose as their second-line treatment (one prior therapy), daraxonrasib shrank tumors in a meaningful share of patients and was linked to longer tumor control and survival than is typically seen with chemotherapy at this stage. The numbers below are from the second-line group; the figures in gray are not a head-to-head comparison — they are the typical results historically reported with second-line chemotherapy, shown only for context.
Daraxonrasib 300 mg, second-line — vs historical chemotherapy (for context only)
Tumors shrank significantly in about 1 in 3 people (29% across all RAS mutations; 35% in the “G12” subgroup). Counting everyone whose cancer shrank or stopped growing, the disease was controlled in about 95%.
The cancer was held back for a median of about 8 months — substantially longer than the 2 to 3 months usually seen with second-line chemotherapy.
Median survival was about 15.6 months (13.1 months in the G12 subgroup) from the start of this treatment — notably longer than is historically reported. Because there was no comparison group, this needs confirmation in a randomized trial.
Most side effects were mild to moderate. About one third of patients had a more serious side effect — most commonly rash and diarrhea — but these were usually manageable, and almost no one had to stop the drug because of side effects. There were no treatment-related deaths.
Responses tended to be deeper and last longer when daraxonrasib was given earlier (second-line rather than later), and tumors shrank across many different RAS mutations — including the common KRAS G12D, G12V, and G12R forms that currently have no approved targeted treatment, as well as in some patients whose mutation lay elsewhere on the RAS gene (such as Q61) rather than at G12.
Why do these results need to be confirmed?
This was a phase 1–2 study with a single group of patients — everyone received daraxonrasib, and there was no comparison (control) group. That design is excellent for spotting early signs that a drug works and for understanding its side effects, but it cannot prove that the drug is better than existing treatment. The patients who enroll in early trials may also differ from the average patient. The historical chemotherapy figures shown above come from other studies, so the comparison is only a rough guide. To know for sure, the drug is now being tested against chemotherapy in a large randomized phase 3 trial (called RASolute 302), where neither the patients nor their cancers are cherry-picked.
Why does a RAS drug cause a rash and diarrhea?
Healthy skin and gut cells rely on normal (non-mutated) RAS to do their everyday work. Because daraxonrasib acts broadly on RAS — not only the mutated version in the tumor — it can also affect these fast-renewing normal tissues, which shows up as rash, mouth sores, and diarrhea. Doctors call these “on-target” effects: they are a sign the drug is doing what it was designed to do. In the study they were mostly mild to moderate and were managed with familiar measures such as skin creams, antibiotics for the rash, anti-diarrhea medicine, and, when needed, brief dose adjustments.
The bottom line
For decades, the RAS mutation that drives more than 90% of pancreatic cancers was considered impossible to target. Daraxonrasib, an oral RAS(ON) inhibitor, changes that. In this early-phase study of previously treated, RAS-mutated pancreatic cancer, it shrank tumors in about a third of patients and was linked to tumor control of roughly 8 months and survival of over a year — well beyond what is historically seen with second-line chemotherapy, and with side effects that were mostly manageable. Because there was no comparison group, these results are promising but not yet proven. A large randomized phase 3 trial (RASolute 302) is now testing daraxonrasib against chemotherapy to confirm the benefit.
What this could mean for you
- RAS testing matters. The drug targets RAS-mutated cancers. Most pancreatic cancers carry a RAS mutation, but ask your team whether your tumor’s genetics have been tested.
- This is early evidence. These results come from an early-phase study without a comparison group. They are encouraging, but the definitive trial is still underway.
- It is a pill, not chemotherapy. Daraxonrasib is taken by mouth once a day. Its main side effects — rash, mouth sores, and diarrhea — differ from those of standard chemotherapy and were usually manageable.
- Access may be through a trial. Until the phase 3 results are in and the drug is approved, the way to receive daraxonrasib is generally by joining a clinical trial. Ask your oncologist whether one is open near you.
An oncologist’s perspective
As oncologists, we have always felt discouraged when we meet a patient with advanced pancreatic cancer. There have been very few options for treatment, and rarely do patients truly feel better during that time. When this trial was presented at our annual oncology conference in June 2026, the data were just so strikingly good that the presenter received a five-minute standing ovation. Finally, a drug that gives real hope for pancreas cancer patients. We eagerly await the results of further trials, and cannot wait to access this drug as soon as we can.
Questions & comments
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