KRAS G12C

aka KRAS G12C, G12C, KRAS p.G12C, KRAS c.34G>T, KRAS G12C-mutated

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.

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.

Part ofKRAS· KRASOther readoutsKRAS G12D All readouts

KRAS: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.

Sequencing 4 approval thresholds

What it means for a patient

KRAS G12C is the one KRAS change with approved tablets. In lung cancer sotorasib or adagrasib are on label after a first treatment; in bowel cancer they are given with an EGFR antibody after chemotherapy. Other KRAS mutations (G12D, G12V) do not qualify for these drugs yet, so the exact letter on your report matters.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

The KRAS c.34G>T (p.G12C) substitution detected in tumour tissue or plasma by PCR or sequencing.

“KRAS: KRAS G12C (therascreen KRAS RGQ PCR Kit, Guardant360 CDx, Agilent Resolution ctDx FIRST)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
KRAS G12C	Sotorasib	Non-small-cell lung cancer	FDA	label
KRAS G12C	Sotorasib	Colorectal cancer	FDA	label
KRAS G12C	Adagrasib	Non-small-cell lung cancer	FDA	label
KRAS G12C	Adagrasib	Colorectal cancer	FDA	label

Drugs whose label names it

Sotorasib Adagrasib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
therascreen KRAS RGQ PCR Kit	QIAGEN Manchester	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Sotorasib	P110027/S012 (05/28/2021)
therascreen KRAS RGQ PCR Kit	QIAGEN Manchester	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Adagrasib	P110027/S013 (12/02/2022)
therascreen KRAS RGQ PCR Kit	QIAGEN Manchester	Colorectal Cancer - Tissue	Adagrasib Cetuximab	P110027/S017 (06/21/2024)
therascreen KRAS RGQ PCR Kit	QIAGEN Manchester	Colorectal Cancer - Tissue	Sotorasib Panitumumab	P110027/S018 (01/16/2025)
Guardant360 CDx	Guardant Health	Non-Small Cell Lung Cancer (NSCLC) - Plasma	Sotorasib	P200010/S002 (05/28/2021)
Agilent Resolution ctDx FIRST assay	Resolution Bioscience (Agilent)	Non-Small Cell Lung Cancer (NSCLC) - Plasma	Adagrasib	P210040 (12/12/2022)

Tests that measure it

therascreen KRAS RGQ PCR Kit Guardant360 CDx Agilent Resolution ctDx FIRST Tempus xT and xT CDx FoundationOne CDx FoundationOne Liquid CDx Caris MI Cancer Seek Guardant360 CDx Illumina TruSight Oncology Comprehensive

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.