Daraxonrasib for previously treated metastatic pancreatic cancer: what RASolute 302 showed

On April 13, 2026, Revolution Medicines announced positive results from the international randomized Phase 3 RASolute 302 trial. The study evaluated daraxonrasib (RMC-6236), an oral RAS(ON) inhibitor, in patients with previously treated metastatic pancreatic ductal adenocarcinoma. Daraxonrasib was compared not with placebo but with standard intravenous cytotoxic chemotherapy of investigator’s choice. According to the company, the endpoints for progression-free survival and overall survival are considered final. Detailed efficacy and safety data are expected to be presented at the ASCO plenary session on May 31, 2026.

Key points

• Daraxonrasib demonstrated an overall survival benefit compared with standard chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma.
• The trial met primary endpoints for progression-free survival and overall survival in patients with RAS G12-mutated tumors.
• Daraxonrasib is not yet approved by FDA or EMA. The FDA previously granted it Breakthrough Therapy Designation and Orphan Drug status for previously treated metastatic pancreatic cancer with G12 mutations.

Key study numbers

In RASolute 302, daraxonrasib was administered orally at 300 mg once daily. The control arm received standard intravenous cytotoxic chemotherapy of investigator’s choice. Randomization was 1:1.

Key data currently available:

• Population: previously treated metastatic pancreatic ductal adenocarcinoma.
• Line of therapy: after prior treatment; the study design focused on patients after one prior line of therapy in the metastatic setting.
• Primary analysis population: tumors with RAS G12 mutations, including G12D, G12V, and G12R.
• Also enrolled: patients with a broader spectrum of RAS variants and patients without detected RAS mutations.
• Overall survival: 13.2 months vs 6.7 months in the chemotherapy arm (HR 0.40; p < 0.0001).
• Progression-free survival: the study met this endpoint, but median PFS was not disclosed in the press release.
• Safety: the company reported the drug was generally well tolerated with a manageable safety profile.

Why this matters for practice

Pancreatic cancer remains one of the most challenging tumors for systemic therapy. After progression on first line, treatment options are often limited, and tolerability of repeat chemotherapy can be difficult. That is why an overall survival benefit in a Phase 3 study is an important signal.

The clinically meaningful part of this news is about RAS. In pancreatic cancer, RAS mutations are extremely common but were long considered a difficult therapeutic target. Daraxonrasib belongs to a new class of RAS(ON) inhibitors — drugs that target the active form of RAS proteins. This differs from narrower inhibitors of specific KRAS variants.

If subsequent regulatory decisions confirm the use of daraxonrasib, this may change treatment selection after first-line progression in metastatic pancreatic cancer. It will be especially important to understand the tumor’s molecular profile — whether a RAS mutation is present, which specific variant, whether extended molecular testing has been done, and what treatment options have already been used.

For patients, this means molecular testing in metastatic pancreatic ductal adenocarcinoma becomes an even more important element of treatment planning. A second opinion may be useful when it is necessary to understand whether new data applies to your specific situation, especially after progression on first line.

Limitations — what does not change yet

These data do not apply to all patients with pancreatic cancer. RASolute 302 enrolled patients with metastatic pancreatic ductal adenocarcinoma who had already received prior therapy. Daraxonrasib remains an investigational drug. It is not approved by regulators as standard therapy, including in the United States and Europe. Orphan Drug and Breakthrough Therapy Designations accelerate development and review but do not equal approval and do not mean automatic availability in Russia.

Preliminary company data have been released, not a full peer-reviewed publication. Detailed results are needed: median progression-free survival, response rate, subgroup data for RAS G12D, G12V, G12R, outcomes in patients without RAS mutations, adverse event rates, quality-of-life impact, and the proportion of patients requiring dose modifications.

Therefore these data cannot be automatically applied to every patient. Treatment decisions should take into account stage, performance status, prior therapy, chemotherapy tolerability, tumor molecular profile, drug or trial availability, and treatment goals.

When a second opinion is especially helpful

• when metastatic pancreatic cancer is confirmed but the post-first-line strategy is unclear;
• when disease progresses on FOLFIRINOX, gemcitabine with nab-paclitaxel, or another first-line regimen;
• when molecular testing has not been done or is incomplete;
• when a KRAS/RAS mutation is known but its impact on therapy or trial eligibility is unclear;
• when the patient wants to understand whether RASolute 302 data apply to their specific situation.

What to prepare for the consultation

• histology report;
• records of prior treatment;
• CT, MRI, or PET-CT scans with serial imaging;
• molecular testing results, ideally including KRAS/RAS, BRCA1/2, MSI/MMR, NTRK, and other identified markers;
• biomarker data if already tested;
• recent blood tests including complete blood count and biochemistry;
• list of comorbidities and current medications.

Frequently asked questions

More answers on the FAQ page.