EGFR exon 20 insertion

aka EGFR ex20ins, exon 20 insertion, EGFR exon 20 insertion mutation, EGFR ex20ins NSCLC

Exon 20 insertions add amino acids after the C-helix of EGFR and make the kinase resistant to the usual EGFR tablets. They account for about a tenth of EGFR mutations and have their own drugs: amivantamab with chemotherapy and sunvozertinib.

In-frame insertions or duplications in exon 20 (A767_V769dup, D770_N771insSVD and others) are structurally distinct from the classical mutations and do not respond to first- or third-generation TKIs at tolerated doses. Amivantamab is labelled with carboplatin and pemetrexed for first-line NSCLC with EGFR exon 20 insertion mutations (PAPILLON) and alone after platinum chemotherapy; sunvozertinib (Zegfrovy, 2025) is labelled after platinum chemotherapy with the Oncomine Dx Express Test as companion; mobocertinib was withdrawn in 2023. Guardant360 CDx and the Oncomine Dx Target Test carry exon 20 insertion claims for amivantamab. PCR hotspot kits miss many exon 20 insertions, so sequencing is preferred.

Part ofEGFR· EGFROther readoutsEGFR exon 19 deletion EGFR L858R EGFR T790M 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

An exon 20 insertion is an EGFR mutation that the common EGFR tablets do not treat well. The on-label first treatment is amivantamab with chemotherapy; after chemotherapy, amivantamab alone or sunvozertinib. Make sure the mutation was found by sequencing, because older hotspot tests can miss it.

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

An in-frame insertion or duplication within exon 20 of EGFR (excluding T790M) detected by next-generation sequencing of tumour tissue or plasma.

“Exon 20 insertion mutations”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
EGFR exon 20 insertion Rybrevant indications 1.2 and 1.3: with carboplatin and pemetrexed for first-line, and as a single agent after platinum chemotherapy, in NSCLC with EGFR exon 20 insertion mutations as detected by an FDA-approved test.	Amivantamab	Non-small-cell lung cancer	FDA	label

Drugs whose label names it

Amivantamab

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
Guardant360 CDx	Guardant Health	Non-Small Cell Lung Cancer (NSCLC) - Plasma	Amivantamab	P200010/S001 (05/21/2021)
Oncomine Dx Target Test	Life Technologies (Thermo Fisher Scientific)	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Amivantamab	P160045/S027 (12/01/2021)
Oncomine Dx Express Test	Life Technologies (Thermo Fisher Scientific)	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Sunvozertinib	P240040 (07/02/2025)

Tests that measure it

Guardant360 CDx Oncomine Dx Target Test Tempus xT and xT CDx FoundationOne CDx 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.