OncoMatch/Clinical Trials/Zoldonrasib

Zoldonrasib (RMC-9805) Clinical Trials

Zoldonrasib (RMC-9805) is an oral RAS(ON) inhibitor from Revolution Medicines that is selective for the KRAS G12D mutation — the most common single KRAS variant in pancreatic cancer — in contrast to the same company’s daraxonrasib, which targets multiple RAS variants. It is investigational and has not been approved by the FDA. It holds Breakthrough Therapy Designation, granted January 8, 2026, for adults with locally advanced or metastatic non-small cell lung cancer harboring KRAS G12D who have previously received anti-PD-(L)1 treatment and platinum-containing chemotherapy; that designation speeds review and is not an approval, and it covers lung cancer while most zoldonrasib trials are in pancreatic cancer. In the phase 1 RMC-9805-001 study, preliminary results presented at the 2025 ASCO Gastrointestinal Cancers Symposium and the 2025 AACR Annual Meeting reported tumor responses in 11 of 18 evaluable patients with KRAS G12D lung cancer treated at 1,200 mg once daily, and in 30% of 40 patients with KRAS G12D pancreatic cancer who had been enrolled at least 14 weeks before the data cutoff; these are small, early, selected groups rather than trial-wide results. The most common treatment-related side effects at that dose were nausea (27%), diarrhea (20%), vomiting (15%) and rash (10%), each reported as mild or moderate, with no dose-limiting toxicities; those are the most frequent effects reported, not the full safety profile. Zoldonrasib has since moved into phase 3 — alone with chemotherapy, and combined with daraxonrasib as first-line treatment for metastatic pancreatic cancer — and those trials generally require a documented KRAS G12D mutation, though requirements vary by study and cohort.