# KRAS G12D (and other non-G12C KRAS mutations)

Source: https://onco.cc/biomarkers/kras-g12d/  
OnCo record `kras-g12d` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

G12D is the commonest KRAS mutation, especially in pancreatic cancer, and has no approved drug yet. In bowel cancer any KRAS or NRAS mutation is a reason not to give EGFR antibodies, which is where the approvals sit.

## Summary

KRAS G12D (c.35G>A) drives about 40 percent of pancreatic and 12 percent of colorectal cancers; G12V and G13D follow. No G12D-selective drug is approved: zoldonrasib (RMC-9805) and the pan-RAS(ON) inhibitor daraxonrasib are in trials (RASolute 302, NCT06625320, is the phase 3 in pancreatic cancer). The approvals that turn on non-G12C KRAS status are negative ones: cetuximab and panitumumab are labelled for KRAS wild-type (and RAS wild-type) metastatic colorectal cancer, with the therascreen KRAS RGQ PCR Kit, cobas KRAS test, FoundationOne CDx and Tempus xT CDx listed as companion diagnostics for detecting the absence of codon 12 and 13 mutations.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: KRAS G12D; G12D; KRAS G12V; KRAS G13D; KRAS mutant; KRAS codon 12 mutation
- Tags: biomarker; kras

## Notes

- Pancreatic ductal adenocarcinoma: G12D is the commonest allele, about 40% of KRAS mutations, and carries the worst prognosis, 6 months against 9 for other alleles (hazard ratio 1.47) in 219 advanced patients (Bournet 2016) and 15.3 months after resection (Qian 2018). RASolute 302 randomised on RAS G12, G13 or Q61 mutation or none identified rather than on a single allele, with daraxonrasib giving overall survival 13.2 against 6.6 months (hazard ratio 0.40) in the G12 population (O'Reilly 2026); G12D-selective inhibitors such as zoldonrasib and MRTX1133 are in trials.
- Colorectal cancer: G12D is the commonest KRAS allele here, about 29% of KRAS mutation records (cBioPortal), and the one with no approved inhibitor, which is why it appears on the cancer record's open problems. Like every RAS mutation it predicts no benefit from cetuximab or panitumumab (Karapetis 2008, Douillard 2013). G13D, almost unique to colorectal cancer among the common RAS-driven tumours at about 18% of records, is treated the same way: the retrospective suggestion that G13D tumours might still respond to cetuximab has never been confirmed prospectively.
- Lung cancer: G12D is 12.2% of KRAS mutation records and G12V 14.9%, so the non-G12C alleles together are more than half of KRAS-mutant lung adenocarcinoma and none of them has an approved inhibitor (cBioPortal). G12D is relatively enriched in never smokers, where it leads the short list of KRAS alleles, which is the inverse of the smoking-driven G12C pattern (Alexandrov 2016).

## Sources

- FDA: List of FDA-Authorized Companion Diagnostic Devices: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools

## Connected records

- biomarkers: [KRAS G12C](https://onco.cc/biomarkers/kras-g12c/), [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/), [STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma](https://onco.cc/biomarkers/stk11-keap1-loss/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [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/)
- drugs: [Cetuximab](https://onco.cc/drugs/cetuximab/), [Panitumumab](https://onco.cc/drugs/panitumumab/), [therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)](https://onco.cc/drugs/therascreen-cdx/)
- terms: [KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer](https://onco.cc/terms/kras-allelic-imbalance/), [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/), [Wild-type (WT)](https://onco.cc/terms/wild-type/)
- key papers: [Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018/), [Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer](https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/), [Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer](https://onco.cc/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/), [K-ras mutations and benefit from cetuximab in advanced colorectal cancer](https://onco.cc/key-papers/paper-karapetis-kras-cetuximab-colorectal-nejm-2008/), [KRAS G12D mutation subtype is a prognostic factor for advanced pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016/), [Mutational signatures associated with tobacco smoking in human cancer](https://onco.cc/key-papers/paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016/), [Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)](https://onco.cc/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/)
- targets: [KRAS](https://onco.cc/targets/kras/)

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