# KRAS G12C

Source: https://onco.cc/biomarkers/kras-g12c/  
OnCo record `kras-g12c` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KRAS G12C swaps glycine 12 for cysteine and was the first KRAS mutation a drug could grip. Sotorasib and adagrasib are approved for it in lung cancer, and with an EGFR antibody in bowel cancer.

## Summary

The c.34G>T (G12C) substitution is found in about 13 percent of lung adenocarcinomas and 3 to 4 percent of colorectal cancers. Sotorasib and adagrasib are labelled as single agents for KRAS G12C-mutated locally advanced or metastatic NSCLC after at least one prior systemic therapy, and in colorectal cancer sotorasib with panitumumab and adagrasib with cetuximab after prior chemotherapy, each 'as determined by an FDA-approved test'. The therascreen KRAS RGQ PCR Kit, Guardant360 CDx, Agilent Resolution ctDx FIRST and FoundationOne CDx carry the claims. G12C is the only KRAS mutation with an approved drug; the other codon 12 and 13 mutations are used as negative selectors for EGFR antibodies in colorectal cancer.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: KRAS G12C; G12C; KRAS p.G12C; KRAS c.34G>T; KRAS G12C-mutated
- Tags: biomarker; kras

## Notes

- Pancreatic ductal adenocarcinoma: G12C is 1 to 2% of cases, about 1.2% of KRAS-mutant MSK-IMPACT samples (cBioPortal). CodeBreaK 100 treated 38 previously treated patients with sotorasib for 8 confirmed responses (21%), progression-free survival 4.0 months and overall survival 6.9 months (Strickler 2023); KRYSTAL-1 gave 7 responses in 21 pancreatic patients (33.3%) with adagrasib (Bekaii-Saab 2023). Neither drug has a pancreatic approval, and the threshold is simply the presence of the allele on a tumour panel or plasma test.
- Colorectal cancer: G12C is about 7% of KRAS mutation records and about 3% of all colorectal cancers (cBioPortal), or 145 of 839 KRAS-mutant patients (17%) in an Italian series where it carried shorter overall survival than other KRAS alleles (hazard ratio 1.32) and more lung and liver metastases (Schirripa 2020). The threshold is the presence of the allele on a tumour panel or plasma test. Unlike in lung cancer the inhibitor must be paired with an EGFR antibody, because blocking G12C alone triggers adaptive EGFR reactivation: that is the design of CodeBreaK 300 (sotorasib plus panitumumab) and of the adagrasib plus cetuximab arm of KRYSTAL-1.
- Lung cancer: 41 to 51% of KRAS mutation records and about 13% of all adenocarcinomas, the highest share of any common cancer, because the G to T transversion that produces it is the tobacco carcinogen signature (Alexandrov 2016; cBioPortal). Unlike in colorectal cancer, a G12C inhibitor has single-agent activity in lung cancer without an EGFR antibody alongside it. What modifies the outcome is the co-mutation: STK11 and KEAP1 loss, present in about a fifth of these tumours each, predict poor benefit from checkpoint blockade in this KRAS-mutant population specifically (Ricciuti 2022).

## Sources

- LUMAKRAS prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c80a362c-7ac3-4894-a076-0691e68ef8c1
- KRAZATI prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0b8bf078-34c2-4f45-9012-38a8ac082b01

## Connected records

- biomarkers: [BRAF V600E (and V600K)](https://onco.cc/biomarkers/braf-v600e/), [KRAS G12D (and other non-G12C KRAS mutations)](https://onco.cc/biomarkers/kras-g12d/), [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/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [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: [Adagrasib](https://onco.cc/drugs/adagrasib/), [Cetuximab](https://onco.cc/drugs/cetuximab/), [Divarasib](https://onco.cc/drugs/divarasib/), [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/), [Olomorasib](https://onco.cc/drugs/olomorasib/), [Panitumumab](https://onco.cc/drugs/panitumumab/), [Sotorasib](https://onco.cc/drugs/sotorasib/), [therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)](https://onco.cc/drugs/therascreen-cdx/)
- terms: [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- key papers: [CodeBreaK 100: sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer](https://onco.cc/key-papers/paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023/), [CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer](https://onco.cc/key-papers/paper-codebreak-300-nejm-2023/), [Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer](https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/), [Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer](https://onco.cc/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/), [KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population](https://onco.cc/key-papers/paper-schirripa-kras-g12c-metastatic-colorectal-clin-colorectal-cancer-2020/), [KRYSTAL-1: adagrasib in advanced solid tumours harbouring a KRAS G12C mutation, including pancreatic cancer](https://onco.cc/key-papers/paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023/), [KRYSTAL-1: adagrasib with or without cetuximab in KRAS G12C-mutated colorectal cancer](https://onco.cc/key-papers/paper-krystal-1-crc-yaeger-nejm-2023/), [Mutational signatures associated with tobacco smoking in human cancer](https://onco.cc/key-papers/paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016/), [Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers](https://onco.cc/key-papers/paper-singhi-targeted-genome-profiling-3594-pdac-gastroenterology-2019/), [STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma](https://onco.cc/key-papers/paper-kras-nsclc-cancer-discov-2018/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/)
- targets: [KRAS](https://onco.cc/targets/kras/)

---
JSON: https://onco.cc/api/v1/entities/kras-g12c.json