OpenOnco · Treatment Plan

Treatment plan — DIS-NSCLC

PLAN-BMA-NRG1_FUSION_NSCLC-V1 · v1 · 2026-05-04

Patient

BMA-NRG1_FUSION_NSCLC · Algorithm: ALGO-NSCLC-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 (CD74-NRG1 most common in lung mucinous adenocarcinoma; ATP1B1-NRG1, SLC3A2-NRG1; detected by RNA-seq or FISH)	IIA	SRC-NCCN-NSCLC-2025: Level Category 2A (Supports, Sensitivity/Response) SRC-ESMO-NSCLC-METASTATIC-2024: Level B (Supports, Sensitivity/Response)	NRG1 fusions (~0.2% NSCLC; enriched in invasive mucinous adenocarcinoma, never-smokers) drive tumor growth via HER3 activation and downstream PI3K/AKT signaling. Zenocutuzumab (MCLA-128), an anti-HER2/HER3 bispecific antibody that blocks NRG1 binding to HER3, received 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 NSCLC cohort — ORR 33% (RECIST), mDOR 7.4 mo, mPFS 8.1 mo in previously treated patients; disease control rate 73%. NRG1 fusions are mutually exclusive with EGFR, ALK, ROS1, KRAS G12C in the vast majority of cases. Standard NTRK/RET/MET panel may miss NRG1 — RNA-based sequencing required.	zenocutuzumab 750 mg IV q2w monotherapy (post-platinum or post-ICI; CRESTONE regimen)	SRC-NCCN-NSCLC-2025 SRC-ESMO-NSCLC-METASTATIC-2024

Treatment options (9 tracks)

Aggressive plan

★ DEFAULT

Indication

IND-NSCLC-PDL1-LOW-NONSQ-MET-1L

Regimen

Pembrolizumab + carboplatin + pemetrexed (NSCLC non-squamous, 1L)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3 weeks · Continuous up to 2 years · IV ⚠ NSZU — not for this indication
Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Cycles 1-4 · IV ✓ NSZU covered
Pemetrexed (DRUG-PEMETREXED) 500 mg/m² IV · Cycles 1-4 + maintenance until progression · IV ✓ NSZU covered

Reason

Engine default per algorithm ALGO-NSCLC-METASTATIC-1L: {'step': 9, 'outcome': False, 'branch': {'result': 'IND-NSCLC-PDL1-LOW-NONSQ-MET-1L', 'notes': 'PD-L1 TPS <50% or unknown: pembrolizumab + platinum + pemetrexed (non-squamous; KEYNOTE-189) or pembrolizumab + carboplatin + paclitaxel/nab-paclitaxel (squamous; KEYNOTE-407). TMB-high (≥10 mut/Mb) may support pembro mono even at low TPS.\n'}, 'fired_red_flags': [], 'winner_red_flag': None}

Standard plan

Indication

IND-NSCLC-EGFR-MUT-MET-1L

Regimen

Osimertinib monotherapy (EGFR-mut NSCLC, 1L metastatic OR adjuvant)

Drugs + NSZU

Osimertinib (DRUG-OSIMERTINIB) 80 mg PO once daily · Continuous · PO ⚠ NSZU — not for this indication

Reason

Alternative track presented for HCP consideration

Standard plan

Indication

IND-NSCLC-ALK-MET-1L

Regimen

Alectinib monotherapy (ALK+ NSCLC, 1L metastatic OR adjuvant)

Drugs + NSZU

Alectinib (DRUG-ALECTINIB) 600 mg PO BID with food · Continuous · PO ⚠ NSZU — not for this indication

Reason

Alternative track presented for HCP consideration

Aggressive plan

Indication

IND-NSCLC-ROS1-1L-REPOTRECTINIB

Regimen

Repotrectinib monotherapy (TRIDENT-1) — ROS1+ NSCLC (TKI-naive or post-prior ROS1-TKI)

Drugs + NSZU

Repotrectinib (DRUG-REPOTRECTINIB) 160 mg PO once daily x14 days, then 160 mg PO BID continuous (lead-in mitigates CNS-AE) · Lead-in then continuous · PO ✗ Not registered in UA

Reason

Alternative track presented for HCP consideration

IND-NSCLC-MET-EX14-1L-CAPMATINIB

Indication: IND-NSCLC-MET-EX14-1L-CAPMATINIB
Regimen: —
Reason: Alternative track presented for HCP consideration

IND-NSCLC-RET-FUSION-1L-SELPERCATINIB

Indication: IND-NSCLC-RET-FUSION-1L-SELPERCATINIB
Regimen: —
Reason: Alternative track presented for HCP consideration

IND-NSCLC-BRAF-V600E-1L-DAB-TRAM

Indication: IND-NSCLC-BRAF-V600E-1L-DAB-TRAM
Regimen: —
Reason: Alternative track presented for HCP consideration

Standard plan

Indication

IND-NSCLC-NTRK-FUSION-1L-LAROTRECTINIB

Regimen

Larotrectinib monotherapy (NAVIGATE / SCOUT) — NTRK fusion+ solid tumors (tumor-agnostic, incl. NSCLC)

Drugs + NSZU

Larotrectinib (DRUG-LAROTRECTINIB) 100 mg PO BID (adults); pediatric 100 mg/m² BID · Continuous · PO ⚠ Out-of-pocket

Reason

Alternative track presented for HCP consideration

Standard plan

Indication

IND-NSCLC-PDL1-HIGH-MET-1L

Regimen

Pembrolizumab monotherapy (NSCLC PD-L1 ≥50%, driver-negative, 1L)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3 weeks (or 400 mg q6 weeks) · Continuous until progression OR 2 years · IV ⚠ NSZU — not for this indication

Reason

Alternative track presented for HCP consideration

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	—	aggressive, standard
TEST-CECT-CAP	CECT chest/abdomen/pelvis	Critical	imaging	—	aggressive, standard
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	aggressive
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	aggressive, standard
TEST-NSCLC-NGS-PANEL	NSCLC comprehensive NGS panel (DNA + RNA fusion)	Critical	—	CSD Lab: M081 CSD Lab: M065	aggressive, standard
TEST-PDL1-IHC	PD-L1 IHC (TPS for NSCLC)	Critical	—	CSD Lab ✓ (code TBC)	aggressive, standard
Brain MRI (NSCLC brain met screening — larotrectinib has CNS activity)	Brain MRI (NSCLC brain met screening — larotrectinib has CNS activity)	Standard	—	—	standard
NTRK fusion NGS (RNA-NGS preferred; DNA-NGS may miss some fusions)	NTRK fusion NGS (RNA-NGS preferred; DNA-NGS may miss some fusions)	Standard	—	—	standard
TEST-BRAIN-MRI-CONTRAST	Brain MRI with contrast	Standard	—	—	aggressive, standard
TEST-CT-CAP	TEST-CT-CAP	Standard	—	—	standard

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

ROS1 fusion (CD74-ROS1, EZR-ROS1, others) — ~1-2% of NSCLC adenocarcinoma; never-smoker enriched. Treatment-defining: entrectinib (CNS-active) or repotrectinib (TRIDENT-1, including post-crizotinib resistance) preferred 1L; crizotinib historic option. RF-NSCLC-ROS1-FUSION-ACTIONABLE

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-NSCLC-ROS1-1L-REPOTRECTINIB)

Do NOT skip lead-in dosing (14 days at 160 mg daily before BID) — direct BID sharply worsens CNS-AE.
Do NOT ignore vestibular AE counseling — patients must understand that dizziness ~60% usually adapts in 4-8 weeks.
Do NOT combine with strong CYP3A4 inhibitors or inducers without dose modification.
Do NOT ignore long-term skeletal fracture monitoring — bone density q-yearly.
Do NOT stop for reversible Grade 1-2 dizziness — usually adapts; reduction to 120 mg BID for Grade 3.
Do NOT confirm plan without funding pathway — repotrectinib not registered in Ukraine.
Do NOT use in baseline severe vestibular dysfunction — additive CNS toxicity.

Standard plan (IND-NSCLC-NTRK-FUSION-1L-LAROTRECTINIB)

Не призначати при NTRK мутації без фузії — тільки фузійні NTRK є показанням
Не застосовувати з сильними CYP3A4 індукторами (рифампіцин тощо)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Pembrolizumab + carboplatin +

21-day cycles × 4 cycles induction; then pembro + pemetrexed maintenance until progression OR 2 years total pembro

Standard plan

Induction · Osimertinib monotherapy (EGFR-

28-day cycles × Continuous until progression (metastatic) OR 3 years (ADAURA adjuvant)

Standard plan

Induction · Alectinib monotherapy (ALK+ NS

28-day cycles × Continuous until progression (metastatic) OR 2 years (ALINA adjuvant)

Aggressive plan

Induction · Repotrectinib monotherapy (TRI

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Larotrectinib monotherapy (NAV

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Pembrolizumab monotherapy (NSC

21-day cycles × Up to 2 years (35 cycles q3w) — KEYNOTE-024 protocol

MDT brief

Skills (recommended) — for consideration (3)

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
Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
skill: social_worker_case_managerv0.1.0reviewed 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-NSCLC-ALK-FUSION-ACTIONABLE, RF-NSCLC-BRAF-V600E-ACTIONABLE, RF-NSCLC-BRAIN-METS-EMERGENCY, RF-NSCLC-CORD-COMPRESSION, RF-NSCLC-EGFR-C797S-RESISTANCE, RF-NSCLC-EGFR-EX19DEL-ACTIONABLE, RF-NSCLC-EGFR-EX20INS-ACTIONABLE, RF-NSCLC-EGFR-T790M-ACTIONABLE, RF-NSCLC-FRAILTY-AGE, RF-NSCLC-HER2-MUT-ACTIONABLE, RF-NSCLC-HER3-HIGH-PATRITUMAB-CANDIDATE, RF-NSCLC-HIGH-RISK-BIOLOGY, RF-NSCLC-INFECTION-SCREENING, RF-NSCLC-KRAS-G12C-ACTIONABLE, RF-NSCLC-MALIGNANT-EFFUSION, RF-NSCLC-MET-AMP-ACTIONABLE, RF-NSCLC-MET-EX14-ACTIONABLE, RF-NSCLC-NRG1-FUSION-ZENO-CANDIDATE, RF-NSCLC-NTRK-FUSION-ACTIONABLE, RF-NSCLC-ORGAN-DYSFUNCTION, RF-NSCLC-PDL1-50-PLUS, RF-NSCLC-RET-FUSION-ACTIONABLE, RF-NSCLC-ROS1-FUSION-ACTIONABLE, RF-NSCLC-SVC-SYNDROME, RF-NSCLC-TRANSFORMATION-PROGRESSION, RF-NSCLC-TROP2-DATO-CANDIDATE

Skill catalog (3/16 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-NSCLC-METASTATIC-2024: ESMO Clinical Practice Guideline on Metastatic Non-Small Cell Lung Cancer (2024)
SRC-KEYNOTE-024-RECK-2016: Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer (2016)
SRC-KEYNOTE-189-GANDHI-2018: Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer (2018)
SRC-NCCN-NSCLC-2025: NCCN Clinical Practice Guidelines — Non-Small Cell Lung Cancer (2025.v8)
SRC-TRIDENT1-DRILON-2024: Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer (TRIDENT-1) (2024)

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	Eligibility (excerpt)
NCT07361562	A Study of a Selective ERBB2 Inhibitor (CGT4255), in Patients With Advanced Solid Tumors	PHASE1	RECRUITING	Cogent Biosciences, 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
Aggressive plan Pembrolizumab + carboplatin + pemetrexed (NSCLC non-squamous, 1L) (REG-PEMBRO-CHEMO-NSCLC-NONSQ)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Osimertinib monotherapy (EGFR-mut NSCLC, 1L metastatic OR adjuvant) (REG-OSIMERTINIB-NSCLC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Alectinib monotherapy (ALK+ NSCLC, 1L metastatic OR adjuvant) (REG-ALECTINIB-NSCLC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Repotrectinib monotherapy (TRIDENT-1) — ROS1+ NSCLC (TKI-naive or post-prior ROS1-TKI) (REG-REPOTRECTINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
IND-NSCLC-MET-EX14-1L-CAPMATINIB — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
IND-NSCLC-RET-FUSION-1L-SELPERCATINIB — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
IND-NSCLC-BRAF-V600E-1L-DAB-TRAM — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
Standard plan Larotrectinib monotherapy (NAVIGATE / SCOUT) — NTRK fusion+ solid tumors (tumor-agnostic, incl. NSCLC) (REG-LAROTRECTINIB-PANTUMOR) 1/1 component drug(s) not on NSZU formulary	✓ registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Pembrolizumab monotherapy (NSCLC PD-L1 ≥50%, driver-negative, 1L) (REG-PEMBRO-MONO-NSCLC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT07361562 A Study of a Selective ERBB2 Inhibitor (CGT4255), in Patients With Advanced 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-NRG1_FUSION_NSCLC-V1 | version: 1 | generated: 2026-05-04T14:13:16.669956+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.