OpenOnco · Treatment Plan

Treatment plan — DIS-PDAC

PLAN-BMA-KRAS_G12D_PDAC-V1 · v1 · 2026-05-04

Patient

BMA-KRAS_G12D_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-RAS-MUTATION	KRAS A146T	IV	SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS A146T in PDAC — rare; no approved targeted therapy.	—	SRC-NCCN-PANCREATIC-2025
BIO-RAS-MUTATION	KRAS G12D	IIB	SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Better Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12D is the most common PDAC driver (~35-40%). MRTX1133 (Mirati/Bristol) and RMC-9805 are in clinical development; ASTX295 / BI-2865 also active. No FDA approval yet (2026); NCCN flags clinical trial.	—	SRC-NCCN-PANCREATIC-2025
BIO-RAS-MUTATION	KRAS G12V	IV	SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12V in PDAC — second-most common driver. No approved drug 2026; pan-KRAS inhibitors and TCR therapies in trial.	—	SRC-NCCN-PANCREATIC-2025
BIO-RAS-MUTATION	KRAS Q61X	IV	SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Poor Outcome) SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS Q61 in PDAC (rare vs G12) — no approved drug; chemo + clinical trial.	—	SRC-NCCN-PANCREATIC-2025

Treatment options (3 tracks)

Standard plan

★ DEFAULT

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'}

Standard plan

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

Aggressive plan

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)

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

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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	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)

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: 2026-05-04.

NCT	Title	Phase	Status	Sponsor	UA
NCT06922591	Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients	PHASE1 / PHASE2	RECRUITING	Tango Therapeutics, Inc.	—
NCT07020221	A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors	PHASE1 / PHASE2	RECRUITING	Verastem, Inc.	—
NCT07491445	Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma	PHASE3	RECRUITING	Revolution Medicines, Inc.	—
NCT06895031	Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS	PHASE2	RECRUITING	Guangzhou JOYO Pharma Co., Ltd	—
NCT06445062	Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors	PHASE1 / PHASE2	RECRUITING	Revolution Medicines, Inc.	—
NCT05379985	Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS	PHASE1 / PHASE2	RECRUITING	Revolution Medicines, Inc.	—
NCT07349537	Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors	PHASE1	RECRUITING	Revolution Medicines, Inc.	—
NCT07252232	Study of Daraxonrasib (RMC-6236) in Patients With Resected Pancreatic Ductal Adenocarcinoma (PDAC)	PHASE3	RECRUITING	Revolution Medicines, Inc.	—
NCT06128551	Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors	PHASE1 / PHASE2	RECRUITING	Revolution Medicines, Inc.	—

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
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
Trial · NCT06922591 Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07020221 A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07491445 Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06895031 Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06445062 Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05379985 Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07349537 Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07252232 Study of Daraxonrasib (RMC-6236) in Patients With Resected Pancreatic Ductal Adenocarcinoma (PDAC) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06128551 Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors 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: 2026-05-04.

plan_id: PLAN-BMA-KRAS_G12D_PDAC-V1 | version: 1 | generated: 2026-05-04T14:13:16.638466+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.