Patient
BMA-NRG1_FUSION_PDAC · Algorithm: ALGO-PDAC-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-NRG1-FUSION | NRG1 gene fusion — any fusion partner (RBPMS-NRG1, SLC3A2-NRG1, PMEPA1-NRG1 among most common in PDAC; detected by RNA-seq) | IIA | - SRC-NCCN-PANCREATIC-2025: Level Category 2A (Supports, Sensitivity/Response)
- SRC-ESMO-PANCREATIC-2024: Level B (Supports, Sensitivity/Response)
| NRG1 fusions occur in ~0.5% of pancreatic ductal adenocarcinoma (PDAC) — a rare but actionable subset. Zenocutuzumab (MCLA-128), anti-HER2/HER3 bispecific antibody, FDA accelerated approval (Nov 2024) for NRG1 fusion-positive locally advanced or metastatic NSCLC and pancreatic adenocarcinoma after prior systemic therapy. CRESTONE trial (Schram et al. JCO 2024): NRG1-fusion PDAC cohort — ORR 40%, mDOR 9.1 mo, mPFS 8.7 mo — particularly notable given the ~3 mo mPFS typically seen with 2L-3L chemotherapy in PDAC. NRG1-fusion PDAC is likely KRAS-wild-type in >90% of cases (oncogenic KRAS and NRG1 fusion may be functionally redundant). RNA sequencing required — DNA NGS panels miss most NRG1 fusions. | zenocutuzumab 750 mg IV q2w monotherapy (post-gemcitabine-based or post-FOLFIRINOX; CRESTONE regimen) | - SRC-NCCN-PANCREATIC-2025
- SRC-ESMO-PANCREATIC-2024
|
Treatment options (3 tracks)
- Indication
- IND-PDAC-METASTATIC-1L-FOLFIRINOX
- Regimen
- FOLFIRINOX
- Drugs + NSZU
- Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 every 14d · IV ✓ NSZU covered
- Irinotecan (DRUG-IRINOTECAN) 180 mg/m² (full); 150 mg/m² in modified FOLFIRINOX (mFOLFIRINOX) · IV day 1 · IV ⚠ NSZU — not for this indication
- Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · IV ⚠ NSZU — not for this indication
- 5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h (modified omits bolus to reduce mucositis) · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered
- Reason
- Engine default per algorithm ALGO-PDAC-METASTATIC-1L: {'step': 3, 'outcome': True, 'branch': {'result': 'IND-PDAC-METASTATIC-1L-FOLFIRINOX'}, 'fired_red_flags': ['RF-FITNESS-ECOG-FIT', 'RF-PDAC-FIT-FOR-FOLFIRINOX'], 'winner_red_flag': 'RF-PDAC-FIT-FOR-FOLFIRINOX'}
- Indication
- IND-PDAC-METASTATIC-1L-GEM-NAB-PAC
- Regimen
- Gemcitabine + nab-paclitaxel (MPACT)
- Drugs + NSZU
- Gemcitabine (DRUG-GEMCITABINE) 1000 mg/m² · IV days 1, 8, 15 of 28-d cycle · IV ✓ NSZU covered
- Nab-paclitaxel (albumin-bound paclitaxel) (DRUG-NAB-PACLITAXEL) 125 mg/m² · IV days 1, 8, 15 of 28-d cycle · IV ✓ NSZU covered
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-PDAC-MAINTENANCE-OLAPARIB-BRCA
- Regimen
- Olaparib maintenance (BRCA-mut PDAC post-platinum, POLO)
- Drugs + NSZU
- Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Continuous · PO ⚠ NSZU — not for this indication
- Reason
- Alternative track presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 3 → branch IND-PDAC-METASTATIC-1L-FOLFIRINOX
- RF-FITNESS-ECOG-FIT: Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T).
SRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024
- RF-PDAC-FIT-FOR-FOLFIRINOX ★ winner: Fitness for FOLFIRINOX in metastatic PDAC per PRODIGE-4 / ACCORD-11 inclusion criteria (Conroy NEJM 2011): ECOG 0-1, age ≤75 (≤76 by protocol; convention <=70-75 in real-world), bilirubin ≤1.5× ULN (resolved post-biliary stenting if needed), no significant cardiac comorbidity, adequate hepatic / renal / bone-marrow function. Selects IND-PDAC-METASTATIC-1L-FOLFIRINOX over IND-PDAC-METASTATIC-1L-GEM-NAB-PAC (mOS 11.1 vs 6.8 mo in PRODIGE-4; toxicity tradeoff acceptable in fit patients). Frail / ECOG ≥2 / bilirubin elevated → de-escalate to gem-nab-paclitaxel (MPACT, Von Hoff NEJM 2013).
SRC-NCCN-PANCREATIC-2025SRC-ESMO-PANCREATIC-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-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | standard |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | standard |
| TEST-CT-PET | PET-CT with FDG | Desired | imaging | — | desired (standard) |
| TEST-NGS-COMPREHENSIVE | Comprehensive NGS tumor panel (DNA + RNA, ≥300 genes) | Desired | histology | CSD Lab: M065 | desired (standard) |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Obstructive jaundice / cholangitis in PDAC: total bilirubin ≥3 mg/dL with pancreatic-head mass causing biliary tree dilation, OR active cholangitis (fever + RUQ pain + jaundice). Mandates biliary drainage (ERCP-stent or PTC) BEFORE chemo, which is hepatotoxic and reduces clearance of cytotoxics.
RF-PDAC-BILIARY-OBSTRUCTION-CHOLANGITIS
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-PDAC-METASTATIC-1L-FOLFIRINOX)
- Do NOT initiate without resolved jaundice (bilirubin <1.5-2 ULN) — irinotecan hepatotoxic
- Do NOT use in PS ≥2 — substantial Grade 3-4 toxicity
- Do NOT skip UGT1A1 testing for high-risk populations (preventable severe diarrhea + neutropenia)
Standard plan (IND-PDAC-METASTATIC-1L-GEM-NAB-PAC)
- Do NOT use without addressing biliary obstruction first
- Do NOT continue past Grade 2 functional neuropathy without dose reduction
Aggressive plan (IND-PDAC-MAINTENANCE-OLAPARIB-BRCA)
- Do NOT start without confirmed CR/PR/SD to platinum-induction
- Do NOT skip pre-treatment counseling on long-term MDS/AML risk
- Do NOT use in tumor-only-BRCA without germline confirmation (POLO inclusion was germline)
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · FOLFIRINOX
14-day cycles × 12 cycles (PRODIGE-24 adjuvant); until progression / toxicity (metastatic)
Standard plan
Induction · Gemcitabine + nab-paclitaxel (
28-day cycles × Until progression / unacceptable toxicity
MDT brief
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
skill: molecular_geneticistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Open questions (1, 0 blocking)
Data quality
- Unevaluated RedFlags: RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE, RF-PDAC-BILIARY-OBSTRUCTION-CHOLANGITIS, RF-PDAC-FRAILTY-AGE, RF-PDAC-HIGH-RISK-BIOLOGY, RF-PDAC-INFECTION-SCREENING, RF-PDAC-TRANSFORMATION-PROGRESSION
Skill catalog (2/16 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-PANCREATIC-2024: ESMO Pancreatic Cancer (2024)
- SRC-NCCN-PANCREATIC-2025: NCCN Pancreatic Adenocarcinoma (v.2.2025)
Experimental options (clinical trials)
Last synced: 2026-05-04 · ctgov.
No active trials matched this scenario in ctgov.
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 |
|---|
| Standard plan FOLFIRINOX (REG-FOLFIRINOX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Gemcitabine + nab-paclitaxel (MPACT) (REG-GEM-NAB-PAC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Olaparib maintenance (BRCA-mut PDAC post-platinum, POLO) (REG-OLAPARIB-MAINT-PDAC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.