Lung Cancer Patients Want to Know About Daraxonrasib: What Does RAS Mutant Mean?

By Terri Conneran, Founder, KRAS Kickers

Reviewed for clinical accuracy by Salman R. Punekar, MD, MSc, Perlmutter Cancer Center at NYU Langone Health

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For this daraxonrasib lung cancer study, eligible RAS mutations were found at G12, G13, or Q61. The exact gene and exact mutation still matter because different RAS mutations can behave differently and may affect treatment or clinical trial options.

For example, KRAS G12D, KRAS G12V, and KRAS G12C are all RAS mutations, but they are not the same mutation.

Daraxonrasib in RAS Mutant Lung Cancer

Help Patients Understand a little Better

What Patients Want to Know

New research published September 3, 2026, in the New England Journal of Medicine reports results for daraxonrasib, also known as RMC 6236, in people with previously treated advanced RAS mutant non small cell lung cancer.

At KRAS Kickers, the first questions are always:

Which exact RAS mutation? Which cancer? Which treatment situation? What is RAS mutation?

What was studied?

Cancer: Previously treated advanced non small cell lung cancer

Eligible RAS genes: KRAS, NRAS, and HRAS

RAS mutations studied: G12, G13, and Q61

Important: KRAS G12C was excluded from this lung cancer analysis. These efficacy results therefore do not tell us how daraxonrasib performs in people with KRAS G12C lung cancer.

Among the 136 people included in the analysis, the most common RAS mutations were:

• G12V: 50 people, 37%

• G12D: 41 people, 30%

• Other G12 mutations: 26 people, 19%

• G13, Q61, and other eligible RAS mutations made up the remainder

Other variants represented in the study included KRAS G12A, G12R, G12S, G12F, G13C, G13D, G13R, Q61H, and Q61L. NRAS Q61K was also represented.

Representation in the study does not establish effectiveness for an individual mutation. Some mutation groups included only a small number of people, so knowing the exact KRAS or RAS variant still matters.

What if I have KRAS G12C?

KRAS G12C was excluded from this Phase 1 to 2 lung cancer analysis.

That exclusion reflects the study design. It should not be interpreted to mean that researchers expect daraxonrasib to lack activity in G12C. Because people with G12C were not included in this analysis, these results cannot answer how daraxonrasib performs in G12C lung cancer.

G12C also has its own rapidly developing treatment landscape, including approved G12C targeted therapies and investigational drugs. Revolution Medicines is separately developing elironrasib, formerly RMC 6291, a RAS ON G12C selective inhibitor being studied in KRAS G12C cancers.

RASolve 301 also permits eligible patients with G12C, G13, and Q61 mutations. Its primary progression free survival and overall survival analyses focus on RAS G12 mutations excluding G12C.

Previous direct RAS targeted therapy is an exclusion for RASolve 301, so eligibility for someone with G12C depends importantly on prior treatment history.

The key point: G12C was outside this published daraxonrasib lung cancer analysis. The exclusion itself does not tell us whether daraxonrasib can or cannot have activity in G12C.

What does RAS mutant mean?

RAS is a family of genes that includes KRAS, NRAS, and HRAS. A RAS mutant cancer has a change, or mutation, in one of these genes that can help drive cancer growth.

What happened?

Daraxonrasib is an oral drug designed to inhibit active RAS across multiple RAS proteins and mutations rather than targeting one specific KRAS variant.

This Phase 1 to 2 study included 136 people with previously treated advanced RAS mutant lung cancer other than KRAS G12C. Across the dose groups studied, confirmed tumor response rates were:

• 31% at doses of 120 mg or less

• 34% at doses of 160 mg to 220 mg

• 37% at 300 mg

Researchers selected 200 mg once daily for Phase 3 development.

What does this mean today?

Daraxonrasib showed antitumor activity in this group of previously treated RAS mutant lung cancers.

Daraxonrasib is not FDA approved for lung cancer.

The drug is FDA approved for a specific group of adults with metastatic pancreatic adenocarcinoma.

A randomized Phase 3 lung cancer trial is recruiting.

Exact RAS mutation, previous treatment, current health, and other eligibility requirements all matter when considering that trial.

One exploratory group helps us understand the next research question

Researchers also performed a post hoc exploratory analysis of 38 people whose treatment history more closely resembled the population being studied in Phase 3.

These 38 people:

• Had received one or two previous lines of treatment

• Had received platinum chemotherapy and PD 1 or PD L1 immunotherapy

• Had not received docetaxel, a chemotherapy

• Received daraxonrasib at doses ranging from 160 mg to 220 mg

This was a selected subgroup within an early phase study. It was not a randomized comparison.

Among these 38 people:

16 of 38, or 42%, had a confirmed tumor response.

34 of 38, or 89%, achieved disease control.

Disease control includes complete response, partial response, or stable disease according to the study criteria. Disease control by itself does not tell us how long that control lasted.

Among people who responded, the median duration of response was 11.5 months.

Median progression free survival was 8.3 months.

Median overall survival was 16.0 months.

Responses in this group were observed in cancers with KRAS G12D, KRAS G12V, KRAS G12A, KRAS G13R, and KRAS Q61H.

The 42% response rate came from people treated across the pooled 160 mg to 220 mg dose range. It is not a response rate established specifically for the 200 mg dose now being studied in Phase 3.

CLARIFY

What does a 42% response rate mean?

A confirmed objective response means the cancer shrank enough on scans to meet established research criteria and that the response was confirmed on a later scan.

It does not mean the cancer disappeared permanently. It does not mean the patient was cured.

In this analysis, 16 of 38 people met the criteria for a confirmed response.

What does an 89% disease control rate mean?

Disease control means the best response was complete response, partial response, or stable disease according to the study criteria.

Disease control and tumor response measure different things.

A person whose cancer remains stable can contribute to the disease control rate without contributing to the objective response rate.

Duration of response and progression free survival provide additional information about how long treatment benefit may last.

Does the 16 month overall survival mean daraxonrasib caused people to live 16 months?

The study observed a median overall survival of 16 months in this particular 38 person exploratory group.

This was not a randomized comparison against another treatment. The study therefore cannot determine how much of that survival resulted from daraxonrasib or whether daraxonrasib improves survival compared with docetaxel.

That is one of the central questions being studied in Phase 3.

What if I have KRAS G12C?

KRAS G12C was excluded from this Phase 1 to 2 lung cancer analysis.

That means these response and survival results cannot be applied directly to someone with KRAS G12C lung cancer.

RASolve 301 also permits eligible patients with G12C, G13, and Q61 mutations. Its primary progression free survival and overall survival analyses focus on RAS G12 mutations excluding G12C.

Previous direct RAS targeted therapy is an exclusion, so eligibility for someone with G12C depends importantly on prior treatment history.

K: Knowledge

Why does this matter?

KRAS G12C changed the treatment landscape because therapies were developed to target that specific KRAS mutation.

Many people with KRAS driven cancers have different variants, including G12D and G12V.

Daraxonrasib takes a broader approach. It inhibits active RAS across multiple mutations and across KRAS, NRAS, and HRAS.

This research is particularly relevant to people with RAS mutations for which there is currently no FDA approved mutation specific targeted therapy in lung cancer.

Who were the patients?

Participants had advanced RAS mutant lung cancer and had generally already received standard treatment.

Almost everyone had previously received:

• Platinum based chemotherapy

• PD 1 or PD L1 immunotherapy

The median number of previous treatment lines for metastatic disease was two.

KRAS G12C was excluded from this lung cancer analysis.

Previous direct RAS targeted therapy was also an important exclusion.

Untreated central nervous system metastases were excluded.

Treatment history matters when deciding how closely these results resemble an individual patient’s situation.

R: Research : What did the RMC 6236 study establish?

The study provides peer reviewed evidence that daraxonrasib has antitumor activity across a group of previously treated RAS mutant non small cell lung cancers other than KRAS G12C.

It also provides more mature information about the duration of some responses than earlier conference reports provided.

This remains Phase 1 to 2 research.

There was no randomized control group.

The investigators did not test whether daraxonrasib was superior to an existing treatment in this study.

Individual KRAS and RAS mutation groups are too small to establish that one variant benefits more than another.

The exploratory 38 person analysis was also selected after the broader study population had been defined and was designed to resemble the population moving into randomized development.

Those limitations matter when interpreting the 42% response rate, progression free survival, and overall survival numbers.

What about side effects?

Treatment benefit needs to be considered together with treatment burden.

Across all 136 people receiving 300 mg or less:

54% experienced a Grade 3 or higher adverse event from any cause.

30% experienced a Grade 3 or higher adverse event considered related to daraxonrasib.

Four Grade 5 adverse events occurred in the overall safety analysis. Investigators did not classify those deaths as treatment related.

At doses of 160 mg to 220 mg, common treatment related side effects included:

• Rash: 90%

• Diarrhea: 66%

• Nausea: 54%

Most treatment related events in this dose range were Grade 1 or Grade 2.

Dose interruptions and dose reductions were part of treatment management and were common enough to be an important consideration when discussing the everyday burden of therapy.

An oral targeted therapy still requires active side effect management, monitoring, and communication with the treatment team.

A: Advocacy What should patients ask?

Knowing only that a cancer is “KRAS positive” is not enough.

Questions to bring to the oncology team may include:

What exact RAS gene and mutation do I have?

Does my treatment history resemble the people included in this study?

Have I received a treatment that could affect eligibility for a daraxonrasib clinical trial?

If I have or previously had brain metastases, how does that affect eligibility?

Is a daraxonrasib trial available near me?

Could a RAS focused second opinion help clarify my current options?

What other treatment and clinical trial options fit my exact cancer, mutation, and treatment history?

S: Survivorship

What might treatment look like in everyday life?

Daraxonrasib is an oral tablet taken once daily.

For patients, treatment decisions involve more than whether a tumor shrinks.

Important considerations include:

• Rash and skin care

• Diarrhea and gastrointestinal symptoms

• Nausea

• Mouth irritation

• Laboratory and clinical monitoring

• Dose interruptions or reductions

• Clinic visits and scans

• Travel if treatment is available only through a clinical trial

Quality of life is part of treatment value.

The ongoing Phase 3 lung cancer study includes quality of life measures, which will provide additional information about how treatment affects daily life over time.

ACCESS: What is available today?

Is daraxonrasib approved for lung cancer?

No, Daraxonrasib remains investigational for lung cancer.

Is there an open Phase 3 lung cancer trial?

Yes. RASolve 301 ClinicalTrials.gov: NCT06881784

RASolve 301 is a global randomized Phase 3 study comparing daraxonrasib with docetaxel in people with previously treated locally advanced or metastatic RAS mutant non small cell lung cancer. The study is currently listed as recruiting.

Current eligibility criteria include documented nonsynonymous mutations in:

• KRAS

• NRAS

• HRAS

At the following codons:

• G12

• G13

• Q61

The trial includes a broader RAS mutant population than the Phase 1 to 2 lung cancer analysis.

Its dual primary efficacy endpoints, progression free survival and overall survival, are being evaluated in people with RAS G12 mutations excluding G12C.

The broader RAS mutant population, including eligible G12C, G13, and Q61 mutations, is also evaluated through secondary endpoints.

Major current eligibility considerations include:

• One or two prior treatment lines

• Previous platinum chemotherapy

• Previous PD 1 or PD L1 immunotherapy

• Measurable disease

• ECOG performance status of 0 or 1

Current exclusion criteria include:

• Previous direct RAS targeted therapy

• Previous docetaxel

• Untreated central nervous system metastases

Additional medical and treatment criteria also apply.

Trial eligibility is individual and can change. Current information needs to be confirmed with the research site before making treatment decisions.

What are we still learning?

Does daraxonrasib improve progression free survival or overall survival compared with docetaxel?

Which KRAS and RAS variants benefit?

How durable will benefit be in a larger population?

How will resistance develop?

What is the best treatment sequence?

How does previous RAS targeted treatment affect future treatment options?

How will treatment affect quality of life over time?

The Phase 3 study is designed to answer several of these questions.

What can I do with this information today?

Start with the biology.

Know the exact RAS gene and exact mutation on the biomarker report.

Then look at the cancer type, treatment history, current treatment options, and clinical trial eligibility together.

A result reported in “RAS mutant lung cancer” becomes useful when a person can answer:

Is this my RAS?

Is this my exact mutation?

Is this my cancer?

Does my treatment history fit?

What can I do with this information now?

That is the purpose of HUB.

HUB

Highlight and Clarify

Knowledge. Research. Advocacy. Survivorship.

Transparency

Editorial Independence

This article was independently written by Terri Conneran for KRAS Kickers. No sponsor, manufacturer, or industry partner had any role in selecting the topic, developing the content, drafting, editing, reviewing, or approving this article.

Clinical accuracy was reviewed by Salman R. Punekar, MD, MSc, Perlmutter Cancer Center at NYU Langone Health.

KRAS Kickers receives sponsorship support from Revolution Medicines and other industry partners. That support did not influence the content or conclusions of this article.

The RMC 6236 001 study was funded by Revolution Medicines, the developer of daraxonrasib.

This is an informational and educational summary developed by KRAS Kickers using the peer reviewed publication, ClinicalTrials.gov information, and FDA sources.

Full author disclosures are available with the New England Journal of Medicine publication.

Sources

Arbour KC, Punekar S, Luo J, et al. Daraxonrasib for Previously Treated RAS Mutant Non Small Cell Lung Cancer. New England Journal of Medicine. 2026;395:882 to 893. DOI: 10.1056/NEJMoa2504059. Clinical trial NCT05379985. ClinicalTrials.gov. RASolve 301. NCT06881784. Recruiting status and eligibility reviewed September 3, 2026.

U.S. Food and Drug Administration. FDA approval of daraxonrasib, RASONQUE, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. August 26, 2026.

Current through September 3, 2026.

This information is provided for education and does not replace discussion with an oncology team. Clinical trial status and eligibility can change.