Early-Phase Data Support Further Evaluation of Daraxonrasib in RAS-Mutant Non-Small Cell Lung Cancer

Clinical Summary: 

• Design/Population: This phase 1/2 dose-escalation and dose-expansion study evaluated oral daraxonrasib in patients with previously treated advanced RAS-mutant non-small cell lung cancer (NSCLC).
• Key Outcomes: Objective responses were observed in more than 30% of patients across evaluated dose levels, with response rates increasing numerically at higher doses. Grade ≥3 adverse events were common, including pneumonia, diarrhea, rash, and anemia, and 4 fatal adverse events were reported.
• Clinical Relevance: These findings demonstrate early clinical activity with daraxonrasib in previously treated RAS-mutant NSCLC and support continued development of RAS(ON) inhibition in a molecularly defined population with limited targeted treatment options.

Results from a phase 1/2 study demonstrated antitumor activity with daraxonrasib, an oral RAS(ON) multiselective inhibitor, in patients with previously treated advanced RAS-mutant non-small cell lung cancer (NSCLC).

In this dose-escalation and dose-expansion study, 136 patients received once daily daraxonrasib at doses ranging from 10 mg to 400 mg in 21-day cycles. The primary end point was safety. A key secondary end point was investigator-assessed objective response rate (ORR), as assessed via RECIST version 1.1.

At analysis, ORR was 31% among patients treated with doses of ≤120 mg, 34% among those treated with doses of 160 mg to 220 mg, and 37% among those receiving 300 mg, demonstrating antitumor activity across evaluated dose levels.

Adverse events of any grade occurred in 99% of patients. The most frequently reported adverse events occurring in ≥30% of patients included rash, diarrhea, nausea, vomiting, and mucositis or stomatitis.

Grade ≥3 adverse events occurred in 54% of patients. The most common severe events included pneumonia, diarrhea, rash, and anemia. Four fatal adverse events were reported.

Overall, these early-phase findings demonstrate clinical activity with daraxonrasib in previously treated advanced RAS-mutant NSCLC, with objective responses observed across dose levels. The safety profile, including the frequency of grade ≥3 adverse events, will remain an important consideration as daraxonrasib advances in clinical development.

Source: 

Arbour KC, Punekar S, Luo J, et al. Daraxonrasib for previously treated RAS-mutant non-small cell lung cancer. N Engl J Med. Published online: September 2, 2026. doi: 10.1056/NEJMoa2504059