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Advanced/metastatic gastric or GE-junction adenocarcinoma with PD-L1 combined positive sc...

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

IDRF-GASTRIC-PDL1-CPS-1-PLUS
TypeRed flag
Statusreviewed 2026-04-27 | pending_clinical_signoff
DiseasesDIS-GASTRIC
SourcesSRC-CHECKMATE-649-JANJIGIAN-2022 SRC-ESMO-GASTRIC-2024 SRC-NCCN-GASTRIC-2025

Red Flag Origin

DefinitionAdvanced/metastatic gastric or GE-junction adenocarcinoma with PD-L1 combined positive score (CPS) ≥1 by 22C3 IHC. CheckMate-649 (Janjigian Lancet 2021; final OS 2024) established nivolumab + chemo (FOLFOX or XELOX) over chemo alone for CPS ≥5 (mOS 14.4 vs 11.1 mo, HR 0.71) with continued benefit at CPS ≥1 (HR 0.78). FDA approved nivolumab + chemo for HER2-negative gastric/GEJ adenocarcinoma 1L regardless of CPS; EMA restricts to CPS ≥5. NCCN/ESMO 2024 favor adding nivolumab to FOLFOX/XELOX for CPS ≥1 (with stronger preference at CPS ≥5).
Clinical directionintensify
Categoryhigh-risk-biology
Shifts algorithmALGO-GASTRIC-METASTATIC-1L

Trigger Logic

{
  "any_of": [
    {
      "comparator": ">=",
      "finding": "pdl1_cps",
      "threshold": 1
    },
    {
      "comparator": ">=",
      "finding": "pdl1_cps_22c3",
      "threshold": 1
    },
    {
      "comparator": ">=",
      "finding": "BIO-PDL1-CPS",
      "threshold": 1
    }
  ],
  "type": "biomarker"
}

Notes

Two-tier CPS approach: CPS ≥5 = strong evidence (CheckMate-649 primary endpoint, EMA-approved cutoff); CPS 1-4 = secondary subgroup, FDA- approved but EMA restricts. Pembrolizumab (KEYNOTE-859) approved similarly for CPS ≥1 with chemo. HER2 testing precedes PD-L1 in the algorithm — HER2+ disease routes to trastuzumab + chemo (KEYNOTE-811 established pembrolizumab + trastuzumab + chemo for HER2+ CPS ≥1). MSI-H gastric (~5%) overrides PD-L1 (KEYNOTE-859 MSI-H subset shows exceptional response — single-agent pembrolizumab acceptable). EBV-positive gastric (~10%) is also IO-responsive but no biomarker threshold established. Detection: 22C3 IHC, central or local laboratory; Dako 28-8 (used in CheckMate-649) and 22C3 are interchangeable for gastric CPS in clinical practice. Jurisdictional split (canonical home: known_controversies block on IND-GASTRIC-METASTATIC-1L-PDL1-CHEMO-ICI; RedFlag schema does not define a known_controversies field — recorded here in notes for cross-reference): - FDA: nivolumab + chemo approved regardless of CPS (overall CheckMate-649 ITT benefit basis). - EMA: restricts to CPS ≥5 (primary-endpoint stratum, HR 0.71). - NCCN v3.2025: favours adding nivolumab at CP...

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