Patient
GASTRIC-HER2-TOGA-001 · Algorithm: ALGO-GASTRIC-METASTATIC-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| BIO-HER2-SOLID | amplification / overexpression — IHC 3+ or (IHC 2+ + ISH amplified, HER2/CEP17 ≥2.0); ~15-20% of gastric/GEJ adenocarcinoma | IA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Sensitivity/Response)
| HER2-positive gastric/GEJ adenocarcinoma (~15-20%): trastuzumab + chemotherapy is standard 1L (ToGA Bang Lancet 2010 — mOS 13.8 vs 11.1 mo, HR 0.74). Pembrolizumab + trastuzumab + chemo is FDA-approved 1L for HER2-positive PD-L1 CPS ≥1 metastatic gastric/GEJ disease per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024 (KEYNOTE-811). Trastuzumab deruxtecan (T-DXd) is FDA-approved 2L+ for HER2-positive (IHC 3+ or 2+) advanced gastric/GEJ adenocarcinoma based on DESTINY-Gastric01 (Shitara NEJM 2020 — ORR 51% vs 14% with chemotherapy). | trastuzumab + fluoropyrimidine + platinum (1L per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024)
pembrolizumab + trastuzumab + fluoropyrimidine + platinum (1L HER2+ PD-L1 CPS ≥1 per SRC-NCCN-GASTRIC-2025)
trastuzumab deruxtecan (2L+ post-trastuzumab progression per SRC-NCCN-GASTRIC-2025) | - SRC-NCCN-GASTRIC-2025
- SRC-ESMO-GASTRIC-2024
|
| BIO-PDL1-CPS | (gene-level) | IA | - SRC-NCCN-GASTRIC-2025
- SRC-ESMO-GASTRIC-2024
- SRC-CHECKMATE-649-JANJIGIAN-2022
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap. | PD-L1 CPS is a continuous IHC score used as an eligibility threshold for ICI-containing regimens in metastatic gastric/GEJ adenocarcinoma. Thresholds vary by regimen: CPS ≥5 — nivolumab + fluoropyrimidine + platinum (CheckMate-649; mOS 14.4 vs 11.1 mo, HR 0.71 in CPS≥5 subgroup); CPS ≥1 — nivolumab + chemo as broader population (CM-649); CPS ≥1 — pembrolizumab + trastuzumab + chemo for HER2+ disease (KEYNOTE-811, covered separately in BMA-HER2-AMP-GASTRIC). Per NCCN and ESMO 2024, PD-L1 CPS testing by IHC 22C3 pharmDx is mandatory prior to 1L treatment selection. Threshold-gated indication selection is performed by the algorithm layer (IND-GASTRIC-METASTATIC-1L-PDL1-CHEMO-ICI); this BMA entry surfaces ESCAT tier context for tumor-board discussion only. | nivolumab + fluoropyrimidine + platinum (CPS≥5, 1L per SRC-NCCN-GASTRIC-2025, SRC-ESMO-GASTRIC-2024)
nivolumab + FOLFOX/XELOX (CPS≥1 broader population per SRC-CHECKMATE-649-JANJIGIAN-2022) | - SRC-NCCN-GASTRIC-2025
- SRC-ESMO-GASTRIC-2024
- SRC-CHECKMATE-649-JANJIGIAN-2022
|
| Biomarker | Status |
|---|
| BIO-MSI-STATUS | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-GASTRIC-METASTATIC-1L-HER2-TOGA
- Regimen
- Trastuzumab + capecitabine + cisplatin (TOGA / KEYNOTE-811)
- Drugs + NSZU
- Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading then 6 mg/kg q3w · IV day 1 every 21d · IV ✓ NSZU covered
- Capecitabine (DRUG-CAPECITABINE) 1000 mg/m² PO BID days 1-14 · PO days 1-14 · PO ✓ NSZU covered
- Cisplatin (DRUG-CISPLATIN) 80 mg/m² · IV day 1 q3w · IV ⚠ NSZU — not for this indication
- Reason
- Primary current-line option selected by ALGO-GASTRIC-METASTATIC-1L at step 1; branch-driving red flag: RF-GASTRIC-HIGH-RISK-BIOLOGY.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-GASTRIC-METASTATIC-1L-CLDN18-2-ZOLBETUXIMAB
- Regimen
- Zolbetuximab + mFOLFOX6 (SPOTLIGHT) — 1L CLDN18.2-positive HER2-negative gastric/GEJ
- Drugs + NSZU
- Zolbetuximab (DRUG-ZOLBETUXIMAB) Loading 800 mg/m² IV cycle 1 day 1; maintenance 600 mg/m² IV q2w · IV q2w (with mFOLFOX6 backbone) · IV ✗ Not registered in UA
- Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² IV day 1 · IV day 1 q2w · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² IV day 1 · IV day 1 q2w · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus day 1, then 2400 mg/m² IV continuous infusion over 46 h · IV q2w · IV ✓ NSZU covered
- Supportive care
- SUP-ANTIEMETIC-PREMED
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-GASTRIC-METASTATIC-1L-FGFR2B-BEMARITUZUMAB
- Regimen
- Bemarituzumab + mFOLFOX6 (FORTITUDE-101) — 1L FGFR2b-overexpressing HER2-non-positive gastric/GEJ
- Drugs + NSZU
- Bemarituzumab (DRUG-BEMARITUZUMAB) 15 mg/kg IV q2w; cycle 1 day 8 additional 7.5 mg/kg loading dose (FORTITUDE-101 protocol) · IV q2w (with mFOLFOX6 backbone) + cycle 1 day 8 booster dose · IV ✗ Not registered in UA
- Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² IV day 1 · IV day 1 q2w · IV ✓ NSZU covered
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² IV day 1 · IV day 1 q2w · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus day 1, then 2400 mg/m² IV continuous infusion over 46 h · IV q2w · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 1 → branch IND-GASTRIC-METASTATIC-1L-HER2-TOGA
- RF-GASTRIC-HIGH-RISK-BIOLOGY ★ winner: Treatment-defining biomarkers in metastatic gastric/GEJ adenocarcinoma: HER2+ (IHC 3+ OR 2+/ISH+) → trastuzumab+chemo TOGA / T-DXd 2L+; CLDN18.2+ (≥75% of tumor cells with 2+ membranous staining) → zolbetuximab+chemo SPOTLIGHT/GLOW; MSI-H → pembrolizumab mono; EBV+ subtype (TCGA molecular class) — distinct biology, ICI-favorable.
SRC-NCCN-GASTRIC-2025SRC-ESMO-GASTRIC-2024
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-HER2-IHC-ISH-IF-RAS-WT | HER2 IHC + reflex ISH (gastric scoring criteria) | Standard | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | desired (aggressive) |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- 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.
RF-GASTRIC-CLDN18-2-ACTIONABLE
- Treatment-defining biomarkers in metastatic gastric/GEJ adenocarcinoma: HER2+ (IHC 3+ OR 2+/ISH+) → trastuzumab+chemo TOGA / T-DXd 2L+; CLDN18.2+ (≥75% of tumor cells with 2+ membranous staining) → zolbetuximab+chemo SPOTLIGHT/GLOW; MSI-H → pembrolizumab mono; EBV+ subtype (TCGA molecular class) — distinct biology, ICI-favorable.
RF-GASTRIC-HIGH-RISK-BIOLOGY
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-GASTRIC-METASTATIC-1L-HER2-TOGA)
- Do NOT use without baseline LVEF — trastuzumab cardiotoxic (q3-mo echo monitoring)
- Do NOT combine with anthracycline (cumulative cardiotoxicity)
- Do NOT initiate during ongoing GI bleed / obstruction
Aggressive plan (IND-GASTRIC-METASTATIC-1L-CLDN18-2-ZOLBETUXIMAB)
- Do not start zolbetuximab without confirmed CLDN18.2 ≥75% 2+/3+ by VENTANA RxDx — outside this range benefit is not proven.
- Do not prescribe zolbetuximab in HER2+ patients — TOGA trastuzumab+chemo takes priority.
- Do not prescribe zolbetuximab in MSI-H patients 1L — pembrolizumab (KEYNOTE-859) takes preference.
- Do not start without triplet antiemetic prophylaxis (5-HT3 + NK1-RA + dex) for cycle 1 — nausea/vomiting severe without it.
- Do not combine with ipilimumab/ICI outside of trials — combination safety unknown.
- Do not confirm the plan without funding pathway — zolbetuximab not registered in UA.
Aggressive plan (IND-GASTRIC-METASTATIC-1L-FGFR2B-BEMARITUZUMAB)
- Do not start bemarituzumab without confirmed FGFR2b IHC 2+/3+ ≥10% by validated IIIb-isoform-selective antibody — outside this range benefit is not proven.
- Do not use pan-FGFR2 IHC instead of FGFR2b-selective — IIIb isoform is the target; pan-FGFR2 does not differentiate isoforms.
- Do not prescribe in HER2+ patients — TOGA trastuzumab+chemo takes priority.
- Do not prescribe in MSI-H patients — pembrolizumab (KEYNOTE-859) takes preference.
- Do not start without baseline ophthalmology exam + serial monitoring plan — corneal events ~70% any-grade, ~25% grade ≥3.
- Do not confirm the plan without funding pathway — bemarituzumab not registered; access via named-patient / clinical-trial only.
- Do not combine with other FGFR-selective inhibitors or CLDN18.2-targeted therapy outside trials.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Trastuzumab + capecitabine + cisplatin (TOGA / KEYNOTE-811)
21-day cycles × Until progression / unacceptable toxicity (chemo backbone often capped at 6-8 cycles, trastuzumab continues mono)
Aggressive plan
Induction · Zolbetuximab + mFOLFOX6 (SPOTLIGHT) — 1L CLDN18.2-positive HER2-negative gastric/GEJ
14-day cycles × Until progression / unacceptable toxicity (oxaliplatin commonly capped at 8-12 cycles for cumulative neuropathy; zolbetuximab + 5-FU/LV maintenance continues)
Aggressive plan
Induction · Bemarituzumab + mFOLFOX6 (FORTITUDE-101) — 1L FGFR2b-overexpressing HER2-non-positive gastric/GEJ
14-day cycles × Until progression / unacceptable toxicity (oxaliplatin commonly capped at 8-12 cycles for cumulative neuropathy; bemarituzumab + 5-FU/LV maintenance continues; FORTITUDE-101 protocol allows oxaliplatin discontinuation per investigator with bemarituzumab + 5-FU/LV continued)
MDT brief
Discussion questions (2, 0 blocking)
OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
OQ-BIOMARKER-FGFR2B-IHC
What is the status of FGFR2b protein expression by IHC (membranous staining) (BIO-FGFR2B-IHC)? It is required by track(s): IND-GASTRIC-METASTATIC-1L-FGFR2B-BEMARITUZUMAB. Expected value: FGFR2b 2+/3+ membranous staining in ≥10% of tumor cells (FIGHT / FORTITUDE-101 threshold).
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | pathologist | Biomarker status | What is the status of FGFR2b protein expression by IHC (membranous staining) (BIO-FGFR2B-IHC)? It is required by track(s): IND-GASTRIC-METASTATIC-1L-FGFR2B-BEMARITUZUMAB. Expected value: FGFR2b 2+/3+ membranous staining in ≥10% of tumor cells (FIGHT / FORTITUDE-101 threshold). |
| 3 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (recommended) — for consideration (1)
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 2/3 known (67%), 1 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-BREAST-CDH1-LOBULAR-CANDIDATE, RF-GASTRIC-CLDN18-2-ACTIONABLE, RF-GASTRIC-EMERGENCY-BLEED-OBSTRUCTION, RF-GASTRIC-FRAILTY-AGE, RF-GASTRIC-INFECTION-SCREENING, RF-GASTRIC-TRANSFORMATION-PROGRESSION, RF-OLIGOMET-DEFINITION
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-FGFR2B-IHC | FGFR2b protein expression by IHC (membranous staining) | pathologist | no | IND-GASTRIC-METASTATIC-1L-FGFR2B-BEMARITUZUMAB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: FGFR2b 2+/3+ membranous staining in ≥10% of tumor cells (FIGHT / FORTITUDE-101 threshold) |
Technical MDT skill metadata (1/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-ESMO-GASTRIC-2024: ESMO Gastric Cancer (2024)
- SRC-FORTITUDE-101: Bemarituzumab (BEMA) plus chemotherapy for advanced or metastatic FGFR2b-overexpressing gastric or gastroesophageal junction cancer (G/GEJC): FORTITUDE-101 phase 3 study results ()
- SRC-NCCN-GASTRIC-2025: NCCN Gastric Cancer (v.3.2025)
Experimental options (clinical trials)
Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-12.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT04389632 | A Study of Sigvotatug Vedotin in Advanced Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: enriched Phase 1 only | |
| NCT06157892 | A Study of Disitamab Vedotin With Other Anticancer Drugs in Solid Tumors | PHASE2 | RECRUITING | — | Surrogate endpoint only | |
| NCT06364410 | Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors | PHASE1 | RECRUITING | — | Biomarker: enriched Phase 1 only Small N (<50) Single country | |
| NCT06330064 | A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02) | PHASE2 | RECRUITING | — | Surrogate endpoint only | |
| NCT05059444 | ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation | N/A | RECRUITING | — | — | |
Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.
Option availability in Ukraine
Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Aggressive plan Trastuzumab + capecitabine + cisplatin (TOGA / KEYNOTE-811) (REG-TRASTUZUMAB-CHEMO-TOGA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Zolbetuximab + mFOLFOX6 (SPOTLIGHT) — 1L CLDN18.2-positive HER2-negative gastric/GEJ (REG-ZOLBETUXIMAB-CHEMO) 1/4 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Bemarituzumab + mFOLFOX6 (FORTITUDE-101) — 1L FGFR2b-overexpressing HER2-non-positive gastric/GEJ (REG-BEMARITUZUMAB-MFOLFOX6) 1/4 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Trial · NCT04389632 A Study of Sigvotatug Vedotin in Advanced Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06157892 A Study of Disitamab Vedotin With Other Anticancer Drugs in Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06364410 Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06330064 A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02) No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05059444 ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-12.