NTRK1/2/3 gene fusion — pan-tumor actionable driver; <1% in NSCLC. Larotrectinib (NAVIGAT...

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

ID	`RF-NSCLC-NTRK-FUSION-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NAVIGATE-DRILON-2018` `SRC-NCCN-NSCLC-2025` `SRC-STARTRK2-DRILON-2020`

Red Flag Origin

Definition	NTRK1/2/3 gene fusion — pan-tumor actionable driver; <1% in NSCLC. Larotrectinib (NAVIGATE — ORR 75% pan-tumor) and entrectinib (STARTRK-2) are FDA tissue-agnostic TRK inhibitors. Treatment-defining if detected.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L, ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "ntrk_fusion",
      "value": true
    },
    {
      "finding": "ntrk_status",
      "value": "fusion_positive"
    },
    {
      "finding": "ntrk1_fusion",
      "value": true
    },
    {
      "finding": "ntrk2_fusion",
      "value": true
    },
    {
      "finding": "ntrk3_fusion",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Detection: pan-TRK IHC screen → confirm by RNA-NGS or FISH (IHC less sensitive for NTRK3). Acquired-resistance solvent-front mutations (NTRK1 G595R, NTRK3 G623R) addressed by next-gen TRK-TKI repotrectinib / selitrectinib. Class neurologic toxicity (dizziness, paresthesias, weight gain) — tropomyosin-receptor-mediated.

Used By

Algorithms

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