HER3 (ERBB3) high-expression / actionability surrogate in EGFR-mutant NSCLC progressing o...

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

ID	`RF-NSCLC-HER3-HIGH-PATRITUMAB-CANDIDATE`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	HER3 (ERBB3) high-expression / actionability surrogate in EGFR-mutant NSCLC progressing on prior EGFR-TKI — patritumab deruxtecan (HER3-DXd) is a HER3-directed deruxtecan antibody-drug conjugate. HERTHENA-Lung01 (Yu 2023) phase-2 single-arm in EGFR-mutant NSCLC post-osimertinib + platinum chemo (n=225): ORR 29.8%, mPFS 5.5 mo, mOS 11.9 mo independent of HER3 IHC level — biomarker-unselected enrollment. FDA accelerated-approval review pending. Candidate RF until BIO-HER3-EXPRESSION lands and pivotal trial-Source SRC-HERTHENA-LUNG01-YU-2024 ingested.
Clinical direction	investigate
Category	high-risk-biology

Trigger Logic

{
  "all_of": [
    {
      "finding": "egfr_mutation",
      "value": "positive"
    },
    {
      "finding": "prior_egfr_tki_progression",
      "value": true
    },
    {
      "finding": "prior_platinum_chemo",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Candidate RF — multiple prerequisites missing. (a) BIO-HER3-EXPRESSION not yet authored on master (W7d emerging-targeted bio chunk pending); (b) HERTHENA-Lung01 trial-Source SRC-HERTHENA-LUNG01-YU-2024 not yet ingested. clinical_direction = investigate (not intensify) because HERTHENA-Lung01 was biomarker-unselected — HER3 IHC not a gating criterion in pivotal data; eligibility is post-osimertinib + platinum-progressed EGFR-mutant. Priority 90 placed conservatively to avoid over-firing while awaiting confirmatory FDA approval (delay signal as of 2024-2025). When trigger fires the engine should surface patritumab-DXd as a candidate option for MDT discussion; not auto-route. Toxicity: thrombocytopenia (~21% G≥3), neutropenia, ILD class warning per deruxtecan platform. Promote to draft:false + clinical_direction:intensify after FDA accelerated approval + trial-Source ingestion.

Used By

No reverse references found in the YAML corpus.