Daraxonrasib in RAS-Mutant Lung Cancer: What the Phase 1/2 Trial Found

A drug that arrived by way of the pancreas

On September 2, 2026, The New England Journal of Medicine published the first large set of lung cancer results for daraxonrasib. It is an oral drug. A week earlier it had become the first RAS inhibitor of its kind approved in the United States — for pancreatic cancer, not lung cancer.

The Food and Drug Administration approved it on August 26, 2026, under the brand name Rasonque. The approval is for adults with metastatic pancreatic adenocarcinoma who have had at least one prior systemic therapy or who are not candidates for multiagent chemotherapy. Television coverage called the new lung cancer data "promising results for a drug". What it was describing is this sequence. An approved pancreatic cancer drug, tested in a different disease, at an early stage.

The lung cancer use is investigational. Nothing published on September 2 changes what is approved.

What RAS is, and why this drug is different

RAS is a family of proteins. They sit just inside the cell membrane and act as switches. In their "on" state they tell a cell to grow and divide. Normally they switch off quickly. A mutation can jam the switch on.

RAS mutations, taken as a group, are the most common oncogenic drivers in non-small cell lung cancer. The published report puts them in roughly 30 percent of patients. For decades they were called undruggable. The first approved drugs to hit RAS directly were sotorasib and adagrasib. They target only one version, KRAS G12C. That version accounts for a minority of RAS-mutant lung cancers.

Daraxonrasib works differently. It is described as a RAS(ON) multiselective tri-complex inhibitor. It does not lock the switch in its off state. Instead it forms a complex that binds the active, GTP-bound form of multiple mutant RAS proteins, as well as normal RAS. That broader reach is the reason for the interest. It is also a likely reason for the side effects. Normal cells use RAS too.

Our page on how targeted therapy works explains the general idea. Biomarker testing explains how a person would learn whether their tumor carries one of these mutations.

Trial at a glance

Field	Detail
Trial	RMC-6236-001
Registry number	NCT05379985
Phase	1–2, multicenter, dose escalation and dose expansion
Design	Single-arm — no comparison group
Participants analyzed	136 with NSCLC treated at 300 mg or less
Population	Previously treated advanced RAS-mutant NSCLC
Doses tested	10 to 400 mg orally once daily, 21-day cycles
Primary end point	Safety
Data cutoff	July 21, 2025
Funder	Revolution Medicines

Every amount above is a trial dose, fixed by the study protocol and given under trial monitoring. Daraxonrasib is not a drug anyone takes at home on their own judgement, and none of these figures is a prescription.

The primary end point was safety, not benefit. That is normal for a phase 1–2 study. It matters when reading the response numbers. They are secondary and investigator-assessed. They were not the question the trial was built to answer. See clinical trial phases for why.

The numbers, in two versions

There are two ways these results have been reported, and the difference is worth understanding.

The full analysis population. All 136 patients were treated at 300 mg or less. The share whose tumors shrank enough to count as an objective response was 31 percent at doses of 120 mg or less, 34 percent at 160 to 220 mg, and 37 percent at 300 mg. The published conclusion states that antitumor activity was reported in more than 30 percent of patients.

The dose-selected subgroup. MD Anderson led the study. It and the sponsor both highlighted a smaller group. That group was 38 patients treated at 160 to 220 mg, the range chosen for the phase 3 trial. They had already received platinum-based chemotherapy and immunotherapy, but had not yet received docetaxel. In that subgroup the response rate was 42 percent (95% CI 26–59). Median duration of response was 11.5 months. Median progression-free survival was 8.3 months (95% CI 4.0–12.5). Median overall survival was 16.0 months (95% CI 9.5–not estimable). Disease control was 89 percent.

The 42 percent figure is the one that traveled. It comes from 38 people. Its confidence interval runs from 26 to 59 percent. So the real rate could be near the historical rate for existing chemotherapy, or roughly four times it. Our page on what trial results mean covers why small subgroups picked after the fact carry less weight than the headline number suggests.

For context, the group leading the trial cites historical results for docetaxel in this setting. Response rates of 9 to 14 percent. Median progression-free survival of 3 to 4.5 months. Median overall survival of about 9 to 12 months. Those are historical comparisons, not a randomized head-to-head.

What it costs the patient

Adverse events of any grade, regardless of cause, occurred in 99 percent of the 136 patients. Rash, diarrhea, nausea, vomiting, and mucositis or stomatitis each occurred in at least 30 percent. Stomatitis is painful swelling of the mouth lining.

Grade 3 or higher adverse events occurred in 54 percent. These were reported in at least 5 percent of patients: pneumonia (10 percent), diarrhea (9 percent), rash (8 percent), and anemia (5 percent). Four grade 5 events — deaths — occurred.

MD Anderson also reported on the dose range chosen for phase 3. There, 51 percent had a grade 3 or higher adverse effect. 71 percent needed a dose modification. 10 percent stopped treatment because of side effects. Rash occurred in 90 percent of that group. It was grade 3 or above in 8 percent.

David Hong, M.D., is deputy chair of investigational cancer therapeutics at MD Anderson and the senior author. He put it this way: "Most patients experienced some adverse effects with daraxonrasib, which highlights the importance of dose optimization to minimize these effects." He added that "the toxicities are largely manageable compared to the alternatives available."

The FDA label for the pancreatic cancer indication covers a separate and higher approved dose of 300 mg daily. That is the labelled figure for a different cancer, set by the prescriber who writes it — not a number to weigh against your own prescription. Its warnings include dermatologic toxicity, stomatitis, diarrhea, gastrointestinal perforation, interstitial lung disease, and embryo-fetal toxicity.

What comes next

A randomized trial is already running. RASolve 301 (NCT06881784) is a global, open-label phase 3 study. It compares daraxonrasib against docetaxel in people with previously treated locally advanced or metastatic RAS-mutant NSCLC. It began enrolling on May 6, 2025, and is recruiting. Estimated enrollment is 590 patients randomized 1:1.

It has two primary end points. One is progression-free survival by blinded independent central review. The other is overall survival. Both are in the RAS G12X population excluding G12C. That is, in patients whose mutations the currently approved G12C drugs do not cover. Primary completion is estimated for December 2027. At MD Anderson the phase 3 trial is led by Ferdinandos Skoulidis, M.D., Ph.D.

Until that trial reports, the honest description of the lung cancer evidence is short. Single-arm, early-phase, encouraging, unproven. People who want to take part can start with finding a clinical trial.

Symptoms that mean a call, not a wait

For anyone living with lung cancer, or newly concerned about it:

• A cough that changes, worsens, or lasts more than three weeks.
• Coughing up blood, even a small amount, at any time.
• Chest pain that worsens with a deep breath or a cough.
• Breathlessness that is new or worse than usual.
• Unexplained weight loss, or a hoarse voice lasting more than three weeks.
• On any oral targeted therapy: a spreading or blistering rash. Mouth sores that stop eating or drinking. Diarrhea that does not settle. New shortness of breath with a dry cough. These need the treating team, not a wait-and-see.

What this trial cannot tell you

• There was no control group. Everyone received the drug. So the comparison is to historical figures, and historical comparisons flatter new drugs.
• The primary end point was safety. Response rates were secondary. The treating investigators assessed them, not a blinded central review.
• The widely quoted 42 percent came from 38 patients in one dose range who had not yet had docetaxel. The all-patient figures were 31 to 37 percent.
• Response rate and progression-free survival are not the same as living longer. The overall survival figure of 16 months comes from the same small subgroup. It is not a randomized result.
• Fifty-four percent of patients had a grade 3 or higher adverse event and four died of one. This is a real cost, not a footnote.
• Nothing here applies to lung cancers without a RAS mutation. Who qualifies depends on biomarker testing.
• SEER is the federal cancer surveillance program. It reports that 53 percent of lung and bronchus cancers are already distant-stage at diagnosis. Five-year relative survival is 8.9 percent in that group, against 63.7 percent when caught while still localized. Those are population averages from people diagnosed years ago. They describe groups, not individuals. And they are the strongest argument for lung cancer screening in people who qualify.

Sources

• N Engl J Med 2026: Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer, 395(9):882-893, PMID 42685317 — record retrieved via NCBI eutils
• ClinicalTrials.gov API v2 record for NCT05379985 (RMC-6236-001)
• ClinicalTrials.gov API v2 record for NCT06881784 (RASolve 301)
• FDA: FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma, August 26, 2026
• FDA press announcement: FDA Approves First in Class Targeted Therapy for Metastatic Pancreatic Cancer, August 26, 2026
• NCI SEER Cancer Stat Facts: Lung and Bronchus Cancer
• NCI: Non-Small Cell Lung Cancer Treatment (PDQ) — Patient Version
• MD Anderson news release, September 2, 2026: Daraxonrasib shows promise in RAS-mutant lung cancer

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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