KRAS G12D (and other non-G12C KRAS mutations)

aka KRAS G12D, G12D, KRAS G12V, KRAS G13D, KRAS mutant, KRAS codon 12 mutation, KRAS wild-type, RAS wild-type

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.

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.

Part ofKRAS· KRASOther readoutsKRAS G12C 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 2 approval thresholds

What it means for a patient

A KRAS G12D, G12V or G13D result does not yet open a targeted tablet outside a trial, and in bowel cancer it means the EGFR antibodies cetuximab and panitumumab should not be used. In pancreatic cancer, trials of RAS inhibitors are recruiting and are worth asking about. Only a KRAS G12C result qualifies for the approved KRAS drugs.

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

Presence of a KRAS codon 12 or 13 (or exon 3 and 4) mutation other than G12C by PCR or sequencing; for EGFR antibodies the selecting result is the absence of KRAS and NRAS mutations in exons 2, 3 and 4.

“KRAS wild-type (absence of mutations in codons 12 and 13)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
KRAS wild-type (negative selector) FDA companion diagnostic row for the therascreen KRAS RGQ PCR Kit with Erbitux, P110030 (06 July 2012).	Cetuximab	Colorectal cancer	FDA	label
KRAS and NRAS wild-type (negative selector) FDA companion diagnostic rows for FoundationOne CDx and xT CDx with Vectibix.	Panitumumab	Colorectal cancer	FDA	label

Also defined by RASolute 302: daraxonrasib versus chemotherapy in previously treated metastatic pancreatic cancer (ClinicalTrials.gov NCT06625320).

Drugs whose label names it

Cetuximab Panitumumab

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
therascreen KRAS RGQ PCR Kit	QIAGEN Manchester	Colorectal Cancer - Tissue	Cetuximab	P110030 (07/06/2012)
therascreen KRAS RGQ PCR Kit	QIAGEN Manchester	Colorectal Cancer - Tissue	Panitumumab	P110027 (05/23/2014)
FoundationOne CDx	Foundation Medicine	Colorectal Cancer - Tissue (KRAS and NRAS wild-type)	Panitumumab	P170019 (11/30/2017)

Tests that measure it

therascreen KRAS RGQ PCR Kit FoundationOne CDx Tempus xT and xT CDx FoundationOne CDx Caris MI Cancer Seek Guardant360 CDx

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.