A drug approved a week earlier for pancreatic cancer has shown activity against advanced lung tumors in an early-stage trial, opening a possible route for patients who currently have no targeted option.
The results, published in the New England Journal of Medicine and reported by the trial's lead center, come from the first-in-human phase 1/2 study of daraxonrasib, sold as Rasonque, in people with previously treated advanced RAS-mutant non-small cell lung cancer. Response rates ranged from 31 percent in the lowest dose group to 37 percent at the highest. In a post-hoc analysis of the dose range chosen for phase 3 testing, 38 patients showed a 42 percent objective response rate, a median duration of response of 11.5 months, median progression-free survival of 8.3 months, and median overall survival of 16 months.
Those numbers matter because of who is left out of current care. RAS mutations are among the most common drivers in lung cancer, appearing in roughly 30 percent of cases. Targeted drugs exist for one specific variant, KRAS G12C. For every other RAS mutation, there is no approved targeted therapy, and patients move to chemotherapy, usually docetaxel, after their first treatments stop working.
The Safety Data Belongs in the Same Sentence as the Response Rate
Nearly every participant had some adverse event. Rash affected 90 percent, diarrhea 73 percent, nausea 62 percent, and vomiting 54 percent. Grade 3 or higher adverse events occurred in 54 percent of participants across all dose levels, and four patients died from adverse events.
That is not a footnote. In a phase 1/2 trial that includes dose escalation, higher doses are given specifically to find the limits of tolerability, so severe events are expected, and the figure spans doses that may not be used going forward. But four deaths in an early trial is information patients and families need alongside the response numbers, and it is the part most likely to be dropped from summaries. David Hong, MD, the MD Anderson oncologist who led the study, said the pattern underscores the importance of dose optimization while noting the toxicities are largely manageable against the alternatives.
The study was funded by Revolution Medicines, which makes the drug. Industry funding does not invalidate a trial, and nearly all oncology drug development is industry-funded. It does mean the results warrant the same scrutiny as any company-sponsored study.
Kathryn C. Arbor, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and the paper's first author, told Healio that the lung cancer data resemble what was seen in pancreatic cancer in how often tumors shrink substantially and how long control lasts, and that the team expects this to translate into a survival benefit. She described the signal as encouraging rather than established and said the optimal dose may differ between diseases and between patients.
An Unusual Way of Hitting a Target Long Considered Undruggable
RAS proteins sat outside the reach of drug developers for decades. Their surface offered no good place for a molecule to grab.
Daraxonrasib works around that. It acts as a molecular glue, first binding a common cellular protein called cyclophilin A. The resulting complex creates a surface that can attach to RAS proteins, blocking them from interacting with the downstream partners they need to drive tumor growth. That mechanism is why the drug is described as multi-selective rather than aimed at a single mutation, and why it can reach RAS variants beyond G12C.
The approach also helps explain the toxicity question. A drug that engages RAS signaling broadly is acting on a pathway that healthy cells use, and the side effect profile reflects that trade-off.
The Gap Between These Results and a Prescription
This drug is not approved for lung cancer, and nothing in this publication changes what a patient can receive today.
The FDA approved Rasonque for metastatic pancreatic adenocarcinoma on August 26, months ahead of its decision deadline, for adults who have had at least one prior systemic therapy or who are not candidates for multiagent therapy. Approval for lung cancer would require results from RASolve 301, the randomized phase 3 trial now underway comparing the drug against standard chemotherapy in previously treated RAS-mutant non-small cell lung cancer. Regulators are likely to want that data before acting, and phase 1/2 response rates frequently look better than what randomized trials confirm. The company's announcement of the publication frames the results as support for that trial rather than as evidence of benefit on their own.
For patients with RAS-mutant lung cancer whose current treatment is failing, the realistic path is a conversation with their oncologist about whether they qualify for the ongoing trial. That conversation should include what the trial involves, whether a site is reachable, and what the known toxicity profile means for someone with their particular health status. Trial participation is not appropriate for everyone, and being randomized to the comparison arm is part of the design.
It is worth being clear about what a 42 percent response rate means, because the figure is easy to misread. It describes the proportion of patients whose tumors shrank by a defined amount on imaging. It does not mean 42 percent of patients were cured, and it does not mean the other 58 percent received no benefit, since disease that stops growing also counts as control. Response rate is an early signal that a drug is doing something, not a measure of how long anyone lives.
Patients should also know whether their tumor has been tested for RAS mutations at all. Comprehensive genomic testing is standard in advanced non-small cell lung cancer but is not universally performed, and knowing the specific mutation determines which options apply. Anyone unsure whether their tumor was sequenced can ask their oncology team directly.
What remains unknown is whether the survival signal holds in a randomized setting, which dose balances benefit against toxicity, and whether particular RAS variants respond better than others. Those answers depend on the phase 3 trial, with initial data expected next year. Until then, this remains a promising early finding in a disease area that badly needs one.
Key Questions Answered
Is this drug approved for lung cancer? No. It is approved for metastatic pancreatic adenocarcinoma. Lung cancer use would require results from the ongoing phase 3 RASolve 301 trial and a separate FDA decision.
What did the trial actually show? Response rates ranged from 31 to 37 percent across dose groups. In a post-hoc subgroup of 38 patients, the response rate was 42 percent, with median progression-free survival of 8.3 months and median overall survival of 16 months.
How serious were the side effects? Nearly all participants had some adverse event, 54 percent had grade 3 or higher events across all dose levels, and four patients died from adverse events.
Who has RAS-mutant lung cancer? RAS mutations appear in roughly 30 percent of non-small cell lung cancer cases. Targeted therapy currently exists only for the KRAS G12C variant, leaving other RAS mutations without an approved targeted option.
How would a patient find out if this applies to them? Comprehensive genomic testing of the tumor identifies RAS mutations. Patients can ask their oncologist whether their tumor was sequenced and what mutation was found.
Can a patient get this drug now for lung cancer? Only through a clinical trial. Patients can ask their oncology team whether they are eligible for RASolve 301 and whether a participating site is accessible.
Who funded the research? Revolution Medicines, which makes the drug, funded the study. Initial results from the phase 3 trial are expected next year.
