EGFR exon 20 insertion — heterogeneous in-frame insertions that sterically block 1st/2nd/...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-NSCLC-EGFR-EX20INS-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-CHRYSALIS-PARK-2021` `SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	EGFR exon 20 insertion — heterogeneous in-frame insertions that sterically block 1st/2nd/3rd-gen EGFR-TKI binding. Targeted by amivantamab (EGFR-MET bispecific; CHRYSALIS / PAPILLON) and mobocertinib (where available). PAPILLON established 1L amivantamab + carboplatin/pemetrexed; CHRYSALIS supports 2L+ amivantamab monotherapy.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L, ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "egfr_exon20_insertion",
      "value": true
    },
    {
      "finding": "egfr_ex20ins",
      "value": "positive"
    },
    {
      "finding": "egfr_mutation",
      "value": "exon20_insertion"
    }
  ],
  "type": "biomarker"
}

Notes

~5-10% of EGFR-mutant NSCLC. NGS strongly preferred over PCR for detection (PCR misses non-canonical insertions). Standard EGFR-TKI (osimertinib, erlotinib) inactive — do not treat as classic EGFR mutation. Amivantamab IV q-weekly induction → q-2-weekly maintenance (rapid infusion-reaction premedication required). Mobocertinib voluntarily withdrawn in some markets due to OS data.

Used By

Algorithms

ALGO-NSCLC-METASTATIC-1L - ALGO-NSCLC-METASTATIC-1L
ALGO-NSCLC-METASTATIC-2L - ALGO-NSCLC-METASTATIC-2L