EGFR T790M

aka T790M, EGFR T790M mutation, gatekeeper mutation EGFR, EGFR exon 20 T790M

T790M is the gatekeeper mutation that lung cancers acquire to escape first- and second-generation EGFR inhibitors. Finding it, in tissue or blood, is the historic gate for osimertinib after an earlier EGFR drug.

The c.2369C>T (T790M) substitution in exon 20 enlarges the ATP-binding pocket's affinity for ATP and confers resistance to erlotinib, gefitinib and afatinib; it arose in about half of patients progressing on those drugs. Osimertinib's 2015 accelerated approval (AURA) was for metastatic EGFR T790M-positive NSCLC after an EGFR TKI, detected by the cobas EGFR Mutation Test v2 in tissue or plasma, the first plasma companion diagnostic. That indication remains on the label, though first-line osimertinib has made acquired T790M uncommon. FoundationOne CDx and Guardant360 CDx also list T790M in their EGFR claims.

Part ofEGFR· EGFROther readoutsEGFR exon 19 deletion EGFR exon 20 insertion EGFR L858R All readouts

EGFR: 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 · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.

Sequencing 1 approval threshold

What it means for a patient

If your lung cancer grew on erlotinib, gefitinib or afatinib and a T790M mutation is found, osimertinib is the on-label next step. The mutation can often be detected in a blood sample; if the blood test is negative the tumour should be biopsied, because blood misses it in a fair share of patients.

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 EGFR exon 20 c.2369C>T (p.T790M) substitution detected in tumour tissue or plasma cell-free DNA; a negative plasma result should prompt tissue testing.

“EGFR exon 19 deletions, EGFR exon 21 L858R, and T790M”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
EGFR T790M after prior EGFR TKI Indication 1.4 of the osimertinib label: metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy.	Osimertinib	Non-small-cell lung cancer	FDA	label

Drugs whose label names it

Osimertinib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
cobas EGFR Mutation Test v2	Roche Molecular Systems	Non-Small Cell Lung Cancer (NSCLC) - Plasma	Osimertinib	P150044 (09/28/2016)

Tests that measure it

cobas EGFR Mutation Test v2 FoundationOne CDx FoundationOne Liquid CDx 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.