CLDN18.2 expression positive (≥75% of tumor cells with 2+/3+ membranous staining on VENTA...

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

ID	`RF-GASTRIC-CLDN18-2-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-30 \| pending_clinical_signoff
Diseases	`DIS-GASTRIC`
Sources	`SRC-ESMO-GASTRIC-2024` `SRC-NCCN-GASTRIC-2025`

Red Flag Origin

Definition	CLDN18.2 expression positive (≥75% of tumor cells with 2+/3+ membranous staining on VENTANA CLDN18 (43-14A) RxDx) in HER2-negative metastatic / unresectable gastric or GEJ adenocarcinoma — eligibility for zolbetuximab + fluoropyrimidine/oxaliplatin 1L (SPOTLIGHT mFOLFOX6 mOS 18.2 vs 15.5 mo HR 0.75; GLOW CAPOX mOS 14.4 vs 12.2 mo HR 0.77). Treatment-defining for the ~38% of HER2-negative gastric cohort. Hierarchy: HER2+ trastuzumab supersedes; MSI-H pembrolizumab supersedes; otherwise CLDN18.2+ → zolbetuximab.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-GASTRIC-METASTATIC-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "cldn18_2_status",
      "value": "positive"
    },
    {
      "finding": "cldn18_2_ihc_2_3_pct",
      "operator": ">=",
      "value": 75
    },
    {
      "finding": "claudin_18_2",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Companion diagnostic VENTANA CLDN18 (43-14A) RxDx required (FDA- approved alongside zolbetuximab Oct 2024). Cutoff: ≥75% of tumor cells with 2+/3+ membranous staining. Major toxicity: nausea/vomiting (~70% any grade — severe in cycle 1, mitigated by aggressive prophylaxis + slow infusion + post-cycle 1 desensitization). Trial source stubs SPOTLIGHT (Shitara 2023) and GLOW (Shah 2023) not yet in KB — flagged for source-ingestion follow-up.

Used By

Algorithms

ALGO-GASTRIC-METASTATIC-1L - ALGO-GASTRIC-METASTATIC-1L