Rasonque (daraxonrasib): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat metastatic pancreatic cancerWording from FDA's list of novel approvals.
FDA review
Priority reviewOrphan drug
Company
Revolution Medicines
Application
NDA 220910
Specialty
Oncology
At a glance
Rasonque is the first RAS(ON) multi-selective inhibitor, approved for metastatic pancreatic cancer after earlier systemic therapy. In the phase 3 RASolute 302 trial it roughly doubled median overall survival compared with second-line chemotherapy (13.2 versus 6.7 months; hazard ratio 0.40), with fewer severe adverse events and far fewer stops for toxicity.
What it is and how it works
More than 90% of pancreatic adenocarcinomas carry an activating RAS mutation, mostly at KRAS G12. Daraxonrasib, taken by mouth, first binds cyclophilin A inside the cell; that pair then locks onto RAS in its active, GTP-bound state and blocks its signaling. It works across mutant KRAS, NRAS and HRAS and wild-type RAS, unlike KRAS G12C inhibitors, which fit only one mutation that is rare in pancreatic cancer.
500 patients with metastatic pancreatic adenocarcinoma that progressed after one prior regimen (fluoropyrimidine- or gemcitabine-based), ECOG performance status 0 or 1; 92% had KRAS G12 mutations and 70% had liver metastases.
Compared with
Chemotherapy of the investigator's choice: modified FOLFIRINOX, gemcitabine plus nab-paclitaxel, FOLFOX, or liposomal irinotecan with 5-FU and leucovorin.
Primary endpoint
Overall survival and progression-free survival in patients with RAS G12 mutations (dual primary end points).
Result
Median overall survival 13.2 versus 6.6 months in the RAS G12 group and 13.2 versus 6.7 months overall (hazard ratio 0.40 in both; P<0.001).
Other results
Median progression-free survival 7.3 versus 3.5 months in the RAS G12 group (hazard ratio 0.45) and 7.2 versus 3.6 months overall (hazard ratio 0.49); P<0.001 for both.
Safety in the trial
Grade 3 or higher adverse events 61.8% versus 69.6%; treatment-related events leading to discontinuation 1.2% versus 11.2%.
How does Rasonque (daraxonrasib) compare with the alternatives (Liposomal irinotecan with 5-FU and leucovorin, FOLFOX or modified FOLFIRINOX, Gemcitabine plus nab-paclitaxel) for metastatic pancreatic cancer? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
Almost every patient had an adverse event in both groups, but grade 3 or higher events were less common with daraxonrasib (61.8%) than with chemotherapy (69.6%), and treatment-related events led to stopping treatment in 1.2% versus 11.2%. See the label for the specific warnings and monitoring.
What it competes with
Second-line treatment of metastatic pancreatic cancer has been chemotherapy chosen by what the patient received first: a fluoropyrimidine regimen after gemcitabine, or gemcitabine-based treatment after FOLFIRINOX. RASolute 302 compared daraxonrasib with those choices.
Liposomal irinotecan with 5-FU and leucovorinStandard second line after gemcitabine-based treatment.
FOLFOX or modified FOLFIRINOXFluoropyrimidine regimens used second line.
Gemcitabine plus nab-paclitaxelUsual second line after FOLFIRINOX.
KRAS G12C inhibitorsCover only the small G12C subset of pancreatic cancers.
Bottom line for clinicians
For metastatic pancreatic adenocarcinoma that has progressed on one line of treatment, or in patients who can't take multiagent chemotherapy, daraxonrasib is a new standard of care: a 6-month gain in median survival is large for this disease, and the drug was better tolerated than chemotherapy. Results were the same in the RAS G12 group and in the whole trial, which also included tumors with other RAS mutations or none detected.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 27, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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