Pancreatic Cancer Drug Rasonque Shows 42% Response Rate in Lung Cancer Trial

Written by Vytautas Valinskas

Key takeaways

• The FDA approved Rasonque (daraxonrasib) for metastatic pancreatic adenocarcinoma on 26 August 2026, six and a half months before the user fee deadline.
• In the phase 3 RASolute 302 trial of 500 adults, median overall survival was 13.2 months on the drug against 6.7 months on chemotherapy, a hazard ratio of 0.40.
• The lung cancer results published a week later come from a phase 1/2 study of 136 patients with no control arm, where response rates ran from 31% to 37% depending on dose.
• The widely quoted 42% response rate applies to a subgroup of 38 patients who had not yet received docetaxel, at the dose range chosen for the phase 3 trial.
• Rasonque carries a US list price of $39,800 for a 30-day supply, roughly $477,000 a year before discounts, and it is not approved for lung cancer anywhere.

Two results, one week apart, and very different evidence

On 26 August the US Food and Drug Administration approved Rasonque, the brand name for daraxonrasib, for adults with metastatic pancreatic adenocarcinoma who have already had one systemic therapy or cannot take combination chemotherapy. One week later, the New England Journal of Medicine published early results for the same drug in lung cancer.

The two events are being reported as a single narrative: a drug that beat pancreatic cancer is now beating lung cancer. That framing flattens a distinction that matters to anyone deciding what to believe. The pancreatic approval rests on a randomised phase 3 trial with a chemotherapy comparator. The lung data comes from a first-in-human dose-finding study with no control arm at all.

Both are real. Only one is proof.

What the pancreatic approval actually showed

RASolute 302 randomised 500 adults with previously treated metastatic pancreatic adenocarcinoma to either 300 mg of daraxonrasib once daily or the investigator's choice of four standard chemotherapy regimens. Median overall survival was 13.2 months on the drug and 6.7 months on chemotherapy, with a hazard ratio of 0.40 and a confidence interval running from 0.30 to 0.53. Median progression-free survival was 7.2 months against 3.6.

The trial also tracked how patients felt. Time to deterioration of global health status was 5.7 months on daraxonrasib and 2.6 months on chemotherapy; time to worsening of clinically relevant pain was 9.2 months against 3.8. Those endpoints carry weight in a disease where, according to the FDA's own approval announcement, roughly 67,000 Americans are diagnosed each year and 90 to 95 percent of those cases are adenocarcinoma.

Angelo de Claro, who directs the FDA's Oncology Center of Excellence, described the drug as showing “unprecedented results in an area of high unmet need”. The agency cleared it six and a half months early, using a Commissioner's National Priority Voucher on top of breakthrough therapy and orphan drug designations. The label requires no companion diagnostic: patients qualify whether or not a RAS mutation has been identified in their tumour.

The molecular glue that made RAS druggable

RAS proteins act as switches. Oncogenic mutations jam them in the active, GTP-bound state, and that state has no obvious pocket for a small molecule to grip. Researchers spent decades calling RAS undruggable for exactly this reason.

Daraxonrasib gets around the problem by not binding RAS first. It attaches to cyclophilin A, a chaperone protein already present inside the cell, and the resulting pair then clamps onto active RAS across the switch I and switch II interface, physically blocking the effector proteins that carry the growth signal onward. Chemists call this a tri-complex; oncologists tend to call it a molecular glue.

Because the mechanism targets the active conformation rather than one specific mutant, one molecule covers KRAS, NRAS and HRAS, mutant and wild-type alike. The first-generation drugs sotorasib and adagrasib only reach KRAS G12C, which accounts for a minority of RAS-driven tumours. That breadth is why the pancreatic label does not need a mutation test, and it is why the lung cancer question came up at all.

The lung data, and its limits

The phase 1/2 trial known as RMC-6236-001 was the first study of daraxonrasib in non-small cell lung cancer. It enrolled 136 previously treated patients whose tumours carried RAS mutations other than G12C, most of whom had already had platinum chemotherapy and immunotherapy. Investigator-assessed response rates rose with dose: 31 percent at 120 mg or below, 34 percent between 160 and 220 mg, and 37 percent at 300 mg.

The 42 percent figure that headlined much of the coverage is narrower than that. It describes 38 patients treated at 160 to 220 mg who had not yet received docetaxel. In that group, median duration of response was 11.5 months, median progression-free survival 8.3 months, and median overall survival 16.0 months.

Those numbers look strong against docetaxel, which is the usual next step for these patients. But nobody in this trial received docetaxel as a comparator. The benchmark comes from historical studies, which MD Anderson summarised alongside the publication as response rates of 9 to 14 percent, progression-free survival of 3 to 4.5 months, and overall survival of roughly 9 to 12 months. Comparing a 38-patient single-arm subgroup with a pooled historical average is a reasonable way to decide whether to run a phase 3 trial. It is not a reasonable way to decide that a drug works.

David Hong of MD Anderson, one of the study leads, put it plainly: for patients whose disease has progressed past immunotherapy, “these early results are encouraging”. Kathryn Arbour of Memorial Sloan Kettering, the paper's first author, led the trial at that centre. The study was funded by Revolution Medicines, the company that makes the drug.

The randomised test is under way. RASolve 301 compares daraxonrasib directly with docetaxel in previously treated RAS-mutant lung cancer, at the 160 to 220 mg dose range, with initial data expected in 2027.

How the three datasets compare

Tumours shrank, then some of them grew back

Several patients in the lung study responded and then progressed. Arbour has said the resistance mechanisms are still being worked out. A separate analysis of pancreatic cancer patients, published in Nature Medicine, sequenced more than 800 genes in paired blood samples from 44 people before and after treatment. It found no acquired secondary KRAS mutations, which distinguishes daraxonrasib from the G12C inhibitors, but did find KRAS and MYC amplification and upregulation of receptor tyrosine kinases. Those findings come from pancreatic tumours, not lung, and should not be transferred across without care.

The side effects are substantial

Dermatologic toxicity occurred in 86 percent of pancreatic trial patients, 10 percent at grade 3. Stomatitis affected 57 percent, diarrhoea 63 percent. Gastrointestinal perforation occurred in 0.9 percent and interstitial lung disease or pneumonitis in 2.4 percent, each with one fatal event. Serious adverse reactions occurred in 30 percent of patients, though only 2.9 percent stopped treatment permanently.

In the lung trial, 51 percent of patients at the recommended phase 3 dose had a grade 3 or higher adverse effect, 71 percent needed a dose adjustment, and 10 percent discontinued. Memorial Sloan Kettering reports 54 percent with significant side effects across the whole trial population; the two figures use different denominators and both are accurate. Rash reached 90 percent at the phase 3 dose. The label now builds prophylaxis into the regimen: topical corticosteroids, emollients, sunscreen, and consideration of oral antibiotics before the first dose.

What it costs, and what happens next

Revolution Medicines set the wholesale acquisition cost at $39,800 for a 30-day supply, which works out to roughly $477,000 a year. Analysts had expected something between $25,000 and $30,000 a month; BioPharma Dive's reporting on the launch pricing notes the annual figure is more than double the list price of Keytruda. The company's chief financial officer projected gross-to-net discounts of 20 to 30 percent, and eligible commercially insured patients may pay nothing through a copay programme. Evercore ISI raised its sales estimate to $2.4 billion next year on the pancreatic indication alone.

Outside the United States daraxonrasib remains investigational, with the European Medicines Agency running a phased review. For lung cancer it is investigational everywhere, and the only route to it is a clinical trial.

The honest summary is that a drug class written off for forty years now has an approval, a survival curve to defend it, and a plausible second indication that has not yet been tested against anything. The 2027 readout of RASolve 301 will settle the second part. Until then, 42 percent is a reason to run the trial, not a result from it.

Sources

• US Food and Drug Administration – FDA Approves First in Class Targeted Therapy for Metastatic Pancreatic Cancer: https://www.fda.gov/news-events/press-announcements/fda-approves-first-class-targeted-therapy-metastatic-pancreatic-cancer
• US Food and Drug Administration – FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daraxonrasib-metastatic-pancreatic-adenocarcinoma
• Revolution Medicines – U.S. FDA Approves RASONQUE (daraxonrasib), the First Broad RAS-Targeted Medicine in Metastatic Pancreatic Cancer: https://ir.revmed.com/news-releases/news-release-details/us-fda-approves-revolution-medicines-rasonquetm-daraxonrasib
• MD Anderson Cancer Center – Daraxonrasib demonstrates initial antitumor activity in RAS-mutant lung cancer: https://www.mdanderson.org/newsroom/research-newsroom/daraxonrasib-demonstrates-initial-antitumor-activity-in-ras-mutant-lung-cancer-in-NSCLC.h00-159858501.html
• Memorial Sloan Kettering Cancer Center – Potential New Treatment for Lung Cancer: Daraxonrasib Aimed at RAS Mutations: https://www.mskcc.org/news/potential-new-treatment-for-lung-cancer-daraxonrasib-aimed-at-ras-mutations
• New England Journal of Medicine – Arbour KC et al., Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer: https://www.nejm.org/doi/full/10.1056/NEJMoa2504059
• Nature Medicine – Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer: https://www.nature.com/articles/s41591-026-04537-w
• BioPharma Dive – Revolution pancreatic cancer drug should quickly become a blockbuster, analysts say: https://www.biopharmadive.com/news/revolution-rasonque-price-pancreatic-cancer-drug-launch-sales/828918/
• Targeted Oncology – Daraxonrasib Shows Antitumor Activity in RAS-Mutant NSCLC: https://www.targetedonc.com/view/daraxonrasib-shows-antitumor-activity-in-ras-mutant-nsclc