# Zoldonrasib

Source: https://onco.cc/drugs/zoldonrasib/  
OnCo record `zoldonrasib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first drug aimed specifically at KRAS G12D, the single most common mutation in pancreatic cancer. Early combination data in 2026 showed half of previously treated patients responding.

## Summary

Revolution Medicines' covalent tri-complex inhibitor of KRAS G12D(ON). Breakthrough Therapy designation in G12D NSCLC (2025). At ESMO GI 2026, zoldonrasib plus daraxonrasib in previously treated RAS G12D metastatic PDAC (n=60, cutoff 9 Feb 2026): ORR 50% and DCR 97% in second line, median PFS 9.6 months; grade ≥3 treatment-related events 35% (rash, anaemia, stomatitis). First-line combination with gemcitabine/nab-paclitaxel showed high response rates and ctDNA clearance. Phase 3 planning underway.

## Fields

- Kind: Treatment
- Status: phase-2
- Last checked: 2026-09-06
- Code: RMC-9805
- Modality: Small-molecule RAS(ON) G12D-selective inhibitor
- Mechanism: Cyclophilin-A-mediated tri-complex that covalently engages the G12D mutant aspartate and blocks effector binding in the active state.

## Sources

- Revolution Medicines, ESMO GI 2026: https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-phase-12-clinical-data-zoldonrasib
- OncLive report: https://www.onclive.com/view/zoldonrasib-combinations-show-compelling-antitumor-activity-in-ras-g12d-mutant-metastatic-pdac

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [KRAS G12C-mutant colorectal cancer](https://onco.cc/cancers/kras-g12c-colorectal/), [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- drugs: [Daraxonrasib](https://onco.cc/drugs/daraxonrasib/)
- companies: [Revolution Medicines](https://onco.cc/companies/revolution-medicines/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- trials: [Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mu](https://onco.cc/trials/nct07777822/), [Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors](https://onco.cc/trials/nct07397338/), [Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors](https://onco.cc/trials/nct06445062/), [Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors](https://onco.cc/trials/nct06040541/), [Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut](https://onco.cc/trials/nct07805954/), [Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta](https://onco.cc/trials/nct07621718/), [Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients](https://onco.cc/trials/nct06922591/)
- ideas: [RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression](https://onco.cc/ideas/idea-pdac-ras-inhibitor-combinations-and-sequencing/), [RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable](https://onco.cc/ideas/idea-ras-inhibitor-neoadjuvant-pdac/)
- pairings: [G12D-selective + pan-RAS(ON) inhibitor (zoldonrasib + daraxonrasib)](https://onco.cc/pairings/g12d-plus-pan-ras/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)

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