Daraxonrasib shows durable responses in RAS-mutant lung cancer

Daraxonrasib, an oral RAS inhibitor therapy, achieved durable responses in pretreated patients with RAS-mutant non-small cell lung cancer (NSCLC) in a Phase 1/2 trial led by The University of Texas MD Anderson Cancer Center.

The study, published today in The New England Journal of Medicine, was led by David Hong, M.D., deputy chair of Investigational Cancer Therapeutics.

Immunotherapy has improved outcomes for many patients with non-small cell lung cancer, but the majority of these cancers eventually progressAt that point, the few treatment options available to these patients often have modest clinical benefit and substantial toxicities, so these early results are encouraging.”

David Hong, M.D., deputy chair of Investigational Cancer Therapeutics

What is the current standard of care for these patients?

Chemotherapy with docetaxel remains a common standard treatment option for patients with RAS-mutant NSCLC whose disease has progressed after platinum-based chemotherapy and immunotherapy. Historical studies in this setting have reported response rates of 9 to 14%, median progression-free survival (PFS) of 3 to 4.5 months, and median overall survival (OS) of approximately 9 to 12 months. This highlights a significant need for new treatment options for these patients.

How effective was daraxonrasib in this lung cancer trial?

The most clinically relevant results were observed in 38 patients with NSCLC treated with 160-220 mg. of daraxonrasib, the dose range selected for the ongoing Phase 3 RASolve 301 trial. These patients had previously received platinum-based chemotherapy and immunotherapy but had not yet received docetaxel.

In this cohort of patients, the objective response rate was 42% with a median duration of response of 11.5 months. The median PFS was 8.3 months, and median OS was 16 months.

Was daraxonrasib safe in this trial?

While daraxonrasib has notable toxicities, Hong says they should be considered in the context of what patients with this disease are facing and the toxicities associated with chemotherapy.

“Most patients experienced some adverse effects with daraxonrasib, which highlights the importance of dose optimization to minimize these effects,” Hong said. “Still, the toxicities are largely manageable compared to the alternatives available.”

At the recommended Phase 3 dose, 51% of patients experienced an adverse effect at grade 3 or higher, with 71% experiencing dose modifications and 10% having to discontinue treatment. The most common adverse effects were rash, which occurred in 90% of patients (8% grade 3 or above) and gastrointestinal issues, including diarrhea, nausea and vomiting (73%, 62% and 54% respectively overall, each less than 10% grade 3 or above).

What are the next steps for daraxonrasib in lung cancer?

The initial data from this trial, which were presented at the 2025 European Lung Congress, prompted the Phase 3 trial now underway. At UT MD Anderson, that trial is being led by Ferdinandos Skoulidis, M.D.,Ph.D., associate professor of Thoracic/Head and Neck Medical Oncology.