OpenOnco · Treatment Plan

Treatment plan — Non-small cell lung cancer

PLAN-NSCLC-RET-FUSION-2L-001-V1 · v1 · 2026-08-17

Patient

NSCLC-RET-FUSION-2L-001 · Algorithm: ALGO-NSCLC-METASTATIC-2L

DiagnosisNon-small cell lung cancer

MOH / ICD-10C34

ICD-O-38046/3; C34.9

StageIV

Histologyadenocarcinoma

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
ESCAT: clinical review pendingBIO-PDL1-TPS	(gene-level)	IA	SRC-KEYNOTE-024-RECK-2016 SRC-KEYNOTE-042-MOK-2019 SRC-KEYNOTE-189-GANDHI-2018 SRC-KEYNOTE-407-PAZ-ARES-2018 SRC-NCCN-NSCLC-2025 SRC-ESMO-NSCLC-METASTATIC-2024 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	PD-L1 Tumor Proportion Score (TPS) is the primary predictive biomarker for pembrolizumab selection in metastatic NSCLC without driver alterations. Three threshold-stratified eligibility bands: TPS ≥50% — pembrolizumab monotherapy 1L preferred (KEYNOTE-024; mPFS 10.3 vs 6.0 mo, HR 0.50); TPS ≥1% — pembrolizumab + carboplatin + pemetrexed (non-sq, KEYNOTE-189) or pembrolizumab + carboplatin + paclitaxel/nab-paclitaxel (sq, KEYNOTE-407); TPS 1-49% — chemo-IO combination preferred over pembro mono. Testing by IHC 22C3 pharmDx mandatory on FFPE specimen. Threshold-gated indication selection is performed by the algorithm layer (ALGO-NSCLC, IND-NSCLC-PDL1-HIGH-MET-1L, IND-NSCLC-PDL1-LOW-NONSQ-MET-1L); this BMA entry surfaces ESCAT tier context only.	pembrolizumab monotherapy (TPS≥50% 1L per SRC-KEYNOTE-024-RECK-2016, SRC-NCCN-NSCLC-2025) pembrolizumab + carboplatin + pemetrexed (TPS≥1% non-sq 1L per SRC-KEYNOTE-189-GANDHI-2018) pembrolizumab + carboplatin + paclitaxel/nab-paclitaxel (TPS≥1% sq 1L per SRC-KEYNOTE-407-PAZ-ARES-2018)	SRC-KEYNOTE-024-RECK-2016 SRC-KEYNOTE-042-MOK-2019 SRC-KEYNOTE-189-GANDHI-2018 SRC-KEYNOTE-407-PAZ-ARES-2018 SRC-NCCN-NSCLC-2025 SRC-ESMO-NSCLC-METASTATIC-2024
ESCAT: clinical review pendingBIO-RET	CCDC6-RET fusion	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Sensitivity/Response) Resistance or avoidance signal SRC-CIVIC: Level C ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response)	CCDC6-RET fusion is the second-most common RET fusion in NSCLC (~10-20%). Response to selective RET-TKIs (selpercatinib LIBRETTO-001, pralsetinib ARROW) is comparable to KIF5B-RET — fusion-partner identity does not currently modify treatment selection.	selpercatinib monotherapy pralsetinib monotherapy	SRC-NCCN-NSCLC-2025 SRC-ESMO-NSCLC-METASTATIC-2024
ESCAT: clinical review pendingBIO-RET	fusion (gene-level — KIF5B-RET, CCDC6-RET, NCOA4-RET et al.)	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Sensitivity/Response) Resistance or avoidance signal SRC-CIVIC: Level C ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response)	RET fusion in advanced NSCLC (~1-2% of adenocarcinoma): selpercatinib (LIBRETTO-001 Drilon 2020 — ORR 64% prior-tx / 85% TKI-naive; LIBRETTO-431 1L vs platinum-pemetrexed) and pralsetinib (ARROW Gainor 2021 — ORR 70%) are highly selective RET-TKIs with deep, durable responses including in CNS. Multikinase TKIs (cabozantinib, vandetanib) are inferior and toxic.	selpercatinib monotherapy (1L preferred per LIBRETTO-431) pralsetinib monotherapy	SRC-NCCN-NSCLC-2025 SRC-ESMO-NSCLC-METASTATIC-2024
ESCAT: clinical review pendingBIO-RET	KIF5B-RET fusion	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B (Supports, Sensitivity/Response) Resistance or avoidance signal SRC-CIVIC: Level C ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response)	KIF5B-RET is the most common RET fusion in NSCLC (~70% of RET+ NSCLC). Treatment is identical to gene-level RET fusion: selpercatinib (LIBRETTO-001 / LIBRETTO-431) and pralsetinib (ARROW). Deep CNS penetrance with selpercatinib (intracranial ORR 82%).	selpercatinib monotherapy pralsetinib monotherapy	SRC-NCCN-NSCLC-2025 SRC-ESMO-NSCLC-METASTATIC-2024

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-NSCLC-2L-RET-FUSION-SELPERCATINIB

Regimen

Selpercatinib monotherapy (LIBRETTO-001) — RET fusion+ NSCLC

Drugs + NSZU

Selpercatinib (DRUG-SELPERCATINIB) 160 mg PO BID with food (≥50 kg); 120 mg BID (<50 kg) · Continuous · PO ✗ Not registered in UA

Reason

Primary current-line option selected by ALGO-NSCLC-METASTATIC-2L at step 13; branch-driving red flag: RF-NSCLC-RET-FUSION-ACTIONABLE.

Other current-line alternatives (14 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Aggressive plan

Indication

IND-NSCLC-2L-EGFR-POST-OSI-AMI-LAZ

Regimen

Amivantamab + Lazertinib (MARIPOSA-2) — 2L EGFR-mut NSCLC post-osimertinib

Drugs + NSZU

Amivantamab (DRUG-AMIVANTAMAB) 1050 mg IV (<80 kg) OR 1400 mg IV (≥80 kg); SC formulation 1600 mg / 2240 mg available (PALOMA-3) · Cycle 1 split day 1+2, then weekly weeks 2-4, then every 2 weeks · IV ✗ Not registered in UA
Lazertinib (DRUG-LAZERTINIB) 240 mg PO once daily · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-EGFR-EX20INS-AMIVANTAMAB

Regimen

Amivantamab monotherapy (CHRYSALIS) — 2L EGFR Exon 20 insertion NSCLC

Drugs + NSZU

Amivantamab (DRUG-AMIVANTAMAB) 1050 mg IV (<80 kg) OR 1400 mg IV (≥80 kg); SC formulation 1600 / 2240 mg also approved · Cycle 1 split day 1+2, then weekly weeks 2-4, then every 2 weeks · IV ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-NSCLC-ALK-2L-LORLATINIB

Regimen

Lorlatinib monotherapy (ALK+ NSCLC, 1L OR post-2G TKI)

Drugs + NSZU

Lorlatinib (DRUG-LORLATINIB) 100 mg PO once daily · Continuous · PO ⚠ Out-of-pocket

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-ROS1-POST-CRIZ-ENTRECTINIB

Regimen

Entrectinib monotherapy (STARTRK-2) — ROS1+ NSCLC (CNS-active)

Drugs + NSZU

Entrectinib (DRUG-ENTRECTINIB) 600 mg PO once daily · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-NSCLC-2L-ROS1-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

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-KRAS-G12C-SOTORASIB

Regimen

Sotorasib monotherapy (KRAS G12C+ NSCLC, 2L+)

Drugs + NSZU

Sotorasib (DRUG-SOTORASIB) 960 mg PO once daily · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-NSCLC-2L-KRAS-G12C-ADAGRASIB

Regimen

Adagrasib monotherapy (KRYSTAL-1) — 2L+ KRAS G12C+ NSCLC

Drugs + NSZU

Adagrasib (DRUG-ADAGRASIB) 600 mg PO BID · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-MET-EX14-CAPMATINIB

Regimen

Capmatinib monotherapy (GEOMETRY mono-1) — MET ex14 NSCLC

Drugs + NSZU

Capmatinib (DRUG-CAPMATINIB) 400 mg PO BID with food · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-MET-EX14-TEPOTINIB

Regimen

Tepotinib monotherapy (VISION) — MET ex14 NSCLC

Drugs + NSZU

Tepotinib (DRUG-TEPOTINIB) 450 mg PO once daily with food · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-MET-AMP-CAPMATINIB

Regimen

Capmatinib monotherapy (GEOMETRY mono-1) — MET ex14 NSCLC

Drugs + NSZU

Capmatinib (DRUG-CAPMATINIB) 400 mg PO BID with food · Continuous · PO ✗ Not registered in UA

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-BRAF-V600E-DAB-TRAM

Regimen

Dabrafenib + trametinib (BRAF V600E+ NSCLC)

Drugs + NSZU

Dabrafenib (DRUG-DABRAFENIB) 150 mg PO BID · Continuous · PO ⚠ NSZU — not for this indication
Trametinib (DRUG-TRAMETINIB) 2 mg PO once daily · Continuous · PO ⚠ NSZU — not for this indication

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-NTRK-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

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-HER2-MUT-T-DXD

Regimen

Trastuzumab deruxtecan (DESTINY-Lung01/02) — HER2-mutant NSCLC 2L+

Drugs + NSZU

Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 5.4 mg/kg IV · Day 1 of every 21-day cycle · IV ⚠ NSZU — not for this indication

Supportive care

SUP-GCSF-NEUTROPENIA

Reason

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-NSCLC-2L-PD-L1-POST-IO-DOCETAXEL

Regimen

Docetaxel + Ramucirumab (REVEL) — 2L+ NSCLC post-platinum / post-ICI

Drugs + NSZU

Docetaxel (DRUG-DOCETAXEL) 75 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
Ramucirumab (DRUG-RAMUCIRUMAB) 10 mg/kg · IV day 1 of each 21-day cycle · IV ⚠ Out-of-pocket

Supportive care

SUP-GCSF-NEUTROPENIA

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 13 → branch IND-NSCLC-2L-RET-FUSION-SELPERCATINIB

RF-NSCLC-RET-FUSION-ACTIONABLE ★ winner: RET fusion (KIF5B-RET, CCDC6-RET, others) — ~1-2% of NSCLC adenocarcinoma. Selpercatinib (LIBRETTO-001 — ORR 85% TKI-naive) and pralsetinib (ARROW) are FDA-approved selective RET-TKIs; preferred 1L over multikinase (cabo, vandetanib). SRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024SRC-LIBRETTO001-DRILON-2020SRC-ARROW

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-CECT-CAP	CECT chest/abdomen/pelvis	Critical	imaging	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-FISH-PANEL	FISH (Fluorescence In Situ Hybridization)	Critical	genomic	CSD Lab ✓ (code TBC)	desired (aggressive)
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks
TEST-NSCLC-NGS-PANEL	NSCLC comprehensive NGS panel (DNA + RNA fusion)	Critical	—	CSD Lab: M081 CSD Lab: M065	all tracks
TEST-PDL1-IHC	PD-L1 IHC (TPS for NSCLC)	Critical	—	CSD Lab ✓ (code TBC)	desired (aggressive, standard)
TEST-BRAIN-MRI-CONTRAST	Brain MRI with contrast	Standard	—	—	all tracks
TEST-ECHO	Echocardiography	Standard	imaging	—	standard

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

ALK rearrangement / fusion (typically EML4-ALK) — ~5% of NSCLC adenocarcinoma; never-smoker / younger enriched. Treatment-defining: alectinib (ALEX — mPFS 34.8 mo) or lorlatinib (CROWN — 5-y PFS 60%) preferred 1L over crizotinib. Adjuvant alectinib 2 y after resection (ALINA).
Detection: RNA-NGS (preferred for fusion partners) OR FISH break-apart OR IHC (D5F3) screen. Crizotinib effectively obsolete 1L. Lorlatinib has the deepest CNS penetration but most CNS / lipid toxicity; alectinib is the most balanced 1L…
RF-NSCLC-ALK-FUSION-ACTIONABLESRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024SRC-CROWN-SOLOMON-2021
NSCLC with symptomatic brain metastases requiring emergency intervention: focal deficit, new seizure, raised intracranial pressure, or impending herniation. Asymptomatic / oligometastatic brain disease handled separately
Symptomatic brain mets in NSCLC ~20-30% at presentation. Per NCCN-NSCLC: dexamethasone 4-16 mg/day depending on edema; SRS for ≤4 lesions or WBRT for diffuse; surgical resection for large solitary or herniation-risk. Systemic therapy…
RF-NSCLC-BRAIN-METS-EMERGENCYSRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024
NSCLC with malignant epidural spinal cord compression (MESCC): new motor deficit, sensory level, bowel/bladder dysfunction, severe back pain with vertebral metastasis on imaging — neurosurgical/radiation emergency
Per NCCN-NSCLC + NCCN supportive-care: dexamethasone 10 mg IV bolus + 4 mg q6h, urgent MRI whole spine, neurosurgery/radiation oncology consult within 24 h. Surgical decompression + RT if surgical candidate (Patchell criteria); RT alone…
RF-NSCLC-CORD-COMPRESSIONSRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024
EGFR C797S — covalent-binding-site mutation that confers acquired resistance to osimertinib (~20% of post-osimertinib progression). 3L+ treatment shifts to amivantamab + lazertinib + chemo (MARIPOSA-2) or chemotherapy. Trans-allelic C797S/T790M relative to the sensitizing mutation predicts whether 1st/3rd-gen EGFR-TKI rotation can recover response.
Allele context matters: cis-C797S/T790M (same allele) — no available EGFR-TKI restores response, switch to amivantamab + lazertinib + chemo or chemo + bev. Trans-C797S/T790M (different alleles) — combination of 1st-gen + 3rd-gen EGFR-TKI…
RF-NSCLC-EGFR-C797S-RESISTANCESRC-NCCN-NSCLC-2025SRC-MARIPOSA2-PASSARO-2024
EGFR exon 19 deletion is the most common actionable EGFR-sensitizing mutation in NSCLC adenocarcinoma (~45-50% of EGFR-mutant cases). FDA/EMA-approved 1L targeted therapy is osimertinib (FLAURA — mPFS 18.9 vs 10.2 mo, OS 38.6 vs 31.8 mo); MARIPOSA-2 establishes 2L amivantamab + lazertinib + chemo post-osimertinib progression.
Routes 1L → osimertinib 80 mg PO daily (FLAURA). Acquired-resistance surveillance: ctDNA at progression for T790M (rare on osimertinib), C797S (~20% of post-osimertinib resistance), MET amplification, histologic transformation. 2L…
RF-NSCLC-EGFR-EX19DEL-ACTIONABLESRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024SRC-FLAURA-SORIA-2018
Acquired EGFR T790M (gatekeeper) mutation at progression on 1st/2nd-gen EGFR-TKI (gefitinib, erlotinib, afatinib, dacomitinib) — drives 2L switch to osimertinib (AURA3 — mPFS 10.1 vs 4.4 mo with platinum-pem). Detected on ctDNA NGS or tissue re-biopsy.
T790M presence at first progression on older TKI = osimertinib 2L with established benefit. With osimertinib used 1L (FLAURA standard), T790M is a rare resistance mechanism — most progression on osimertinib shows alternate mechanisms…
RF-NSCLC-EGFR-T790M-ACTIONABLESRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024SRC-FLAURA-SORIA-2018
Age ≥75 + ECOG ≥2 + significant comorbidity — concurrent CRT and platinum-doublet chemo poorly tolerated; consider sequential CRT, weekly chemo + ICI, or single-agent / best-supportive-care for fragile patients.
Geriatric assessment (G8 / CGA) recommended pre-treatment for ≥70. PD-L1≥50% driver-negative elderly: pembrolizumab mono is the best-tolerated option preserving OS benefit.
RF-NSCLC-FRAILTY-AGESRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-EARLY-2024
NSCLC with symptomatic malignant pleural / pericardial effusion: dyspnea at rest, hypoxia, hemodynamic compromise (effusion-driven hypotension or tamponade physiology)
Per NCCN-NSCLC: thoracentesis ± indwelling pleural catheter ± talc pleurodesis for symptomatic relief before / parallel to systemic therapy. Pericardial effusion: window or pericardiocentesis depending on tamponade status. Note: malignant…
RF-NSCLC-MALIGNANT-EFFUSIONSRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024
NSCLC with superior vena cava syndrome: facial/upper-extremity edema, distended neck/chest veins, dyspnea, plethora, headache — most often right-upper-lobe / bulky mediastinal NSCLC
SVC syndrome occurs in ~5-10% of NSCLC at presentation. Per NCCN-NSCLC: emergency endovascular SVC stenting OR urgent palliative RT (30 Gy/10 fx) is first-line stabilization; chemoradiation begun in parallel for limited-stage; systemic…
RF-NSCLC-SVC-SYNDROMESRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024
Symptomatic CNS metastases OR superior vena cava (SVC) syndrome OR rapid radiographic progression on therapy — emergency / aggressive-progression flag requiring brain imaging, RT/surgical consult, and treatment intensification or sequencing change.
CNS-active TKI options critical for ALK / EGFR / ROS1 mets — alectinib / lorlatinib / brigatinib / osimertinib all have CNS efficacy. SVC syndrome: emergent RT or stenting; systemic therapy proceeds in parallel.
RF-NSCLC-TRANSFORMATION-PROGRESSIONSRC-NCCN-NSCLC-2025SRC-ESMO-NSCLC-METASTATIC-2024

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-NSCLC-2L-RET-FUSION-SELPERCATINIB)

Do NOT confirm RET fusion on a DNA-only hotspot panel basis — RNA-NGS mandatory.
Do NOT ignore baseline + serial hypertension monitoring — class effect ~40%; antihypertensives proactive.
Do NOT ignore baseline + serial LFTs (q2 weeks first 3 mo) — boxed hepatotoxicity AE.
Do NOT combine with QT-prolonging drugs without careful review — QTc class effect.
Do NOT combine with strong CYP3A4 inhibitors / inducers — exposure shifts.
Do NOT confirm plan without funding pathway — selpercatinib not registered in Ukraine.
Do NOT ignore hemorrhage risk — Grade ≥3 bleeding requires dose-modification or discontinuation.

Aggressive plan (IND-NSCLC-2L-EGFR-POST-OSI-AMI-LAZ)

Do NOT initiate without post-osimertinib re-biopsy or ctDNA NGS — small-cell transformation (~5-15%) requires etoposide/platinum, not EGFR-targeted.
Do NOT skip DOAC prophylactic anticoagulation for the first 4 months — VTE rate ~30% with ami+lazertinib combination.
Do NOT prescribe at ECOG ≥2 — IRR + cumulative toxicity intolerable.
Do NOT use IV formulation without full premedication protocol — IRR ~65% baseline; SC formulation strongly preferred.
Do NOT ignore baseline + serial ILD monitoring (CT chest) — pneumonitis risk; permanent discontinuation Grade ≥3.
Do NOT confirm plan without funding pathway — neither amivantamab nor lazertinib registered in Ukraine; access requires named-patient or cross-border.
Do NOT prescribe in known historic VTE (DVT/PE) without gastroenterology consult — anticoagulation triple-therapy risk.

Standard plan (IND-NSCLC-2L-EGFR-EX20INS-AMIVANTAMAB)

Do NOT prescribe osimertinib or other 1G/2G/3G EGFR-TKI for EGFR Ex20ins — ORR <25%, not active.
Do NOT use mobocertinib — FDA approval withdrawn 2023 (negative confirmatory trial).
Do NOT confirm Ex20ins on hotspot PCR basis — DNA-NGS mandatory (variable insertion sites).
Do NOT use IV without full premedication protocol — IRR ~65% cycle 1; SC formulation preferred.
Do NOT confirm plan without funding pathway — amivantamab not registered in Ukraine.
Do NOT ignore baseline + serial ILD monitoring (CT chest).
Do NOT prescribe at ECOG 3-4 — IRR + AE profile intolerable.

Aggressive plan (IND-NSCLC-ALK-2L-LORLATINIB)

Do NOT initiate without NGS resistance profiling — some resistance mutations respond better to repotrectinib or specific re-challenge.
Do NOT ignore CNS imaging — lorlatinib chosen partly for CNS penetration; baseline brain MRI mandatory.
Do NOT skip lipid panel + diabetes screen — hypercholesterolemia + hypertriglyceridemia >90% (statin management).
Do NOT ignore cognitive AE — Grade 2 (memory, mood) requires hold + dose reduction; patient counseling pre-start.
Do NOT combine with strong CYP3A4 inhibitors or inducers without dose modification — exposure shifts significant.
Do NOT confirm plan without funding pathway — lorlatinib not registered in Ukraine; off-label international referral required.
Do NOT discontinue therapy at reversible cognitive AE — dose-dependent; usually returns at 75 mg → 50 mg.

Standard plan (IND-NSCLC-2L-ROS1-POST-CRIZ-ENTRECTINIB)

Do NOT initiate without NGS resistance profiling — G2032R requires repotrectinib, not entrectinib.
Do NOT ignore baseline brain MRI — entrectinib chosen partly for CNS penetration.
Do NOT combine with strong CYP3A4 inhibitors or inducers without dose modification.
Do NOT ignore cardiomyopathy / LVEF monitoring — class effect TKI.
Do NOT confirm plan without funding pathway — entrectinib not registered in Ukraine.
Do NOT prescribe at ECOG 3-4 without careful assessment — TRK-class CNS AE may worsen frail pts.
Do NOT use crizotinib re-challenge — biologically unreasonable after progression.

Aggressive plan (IND-NSCLC-2L-ROS1-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% but usually adapts in 4-8 weeks.
Do NOT combine with strong CYP3A4 inhibitors or inducers without dose modification — exposure shifts significant.
Do NOT ignore long-term skeletal fracture monitoring — bone density q-yearly.
Do NOT confirm plan without funding pathway — repotrectinib not registered in Ukraine.
Do NOT use at baseline severe vestibular dysfunction — additive CNS toxicity.
Do NOT discontinue for reversible Grade 1-2 dizziness — usually adapts; reduction to 120 mg BID at Grade 3.

Standard plan (IND-NSCLC-2L-KRAS-G12C-SOTORASIB)

Do NOT ignore baseline + serial LFTs (q-cycle) — hepatotoxicity ~25% transaminase elevation, dose-limiting.
Do NOT prescribe at baseline transaminases >5× ULN — toxicity risk cumulative.
Do NOT use at ECOG 3-4 — limited benefit and toxicity profile.
Do NOT confirm plan without funding pathway — sotorasib not registered in Ukraine.
Do NOT use together with proton-pump inhibitors or H2-blockers — absorption suppressed (administer with cola for acidification if PPI required).
Do NOT combine with strong CYP3A4 inhibitors — exposure increased.
Do NOT prescribe in active untreated brain metastases without considering adagrasib alternative.

Aggressive plan (IND-NSCLC-2L-KRAS-G12C-ADAGRASIB)

Do NOT ignore baseline ECG + electrolytes — QTc prolongation class effect; correct K/Mg pre-start.
Do NOT combine with QT-prolonging drugs (ondansetron, ciprofloxacin, methadone) without careful review.
Do NOT combine with strong CYP3A4 inhibitors — exposure increased.
Do NOT ignore baseline + serial LFTs and renal function — multi-organ toxicity.
Do NOT confirm plan without funding pathway — adagrasib not registered in Ukraine.
Do NOT use at baseline QTc >480 ms — contraindicated.
Do NOT ignore aggressive antiemetic prophylaxis — N/V dominantly limits adherence.

Standard plan (IND-NSCLC-2L-MET-EX14-CAPMATINIB)

Do NOT confirm MET ex14 on a DNA-only hotspot panel basis — RNA-NGS mandatory for catching splice-site variants.
Do NOT ignore baseline + serial LFTs — hepatotoxicity Grade ≥3 requires hold.
Do NOT ignore peripheral edema — proactive diuretics + compression; reduce dose if persistent G≥2.
Do NOT combine with strong CYP3A4 inhibitors / inducers — exposure shifts.
Do NOT confirm plan without funding pathway — capmatinib not registered in Ukraine.
Do NOT use at baseline pneumonitis or severe lung disease — additive ILD risk.
Do NOT discontinue for isolated mild edema — manageable with conservative measures.

Standard plan (IND-NSCLC-2L-MET-EX14-TEPOTINIB)

Do NOT confirm MET ex14 on a DNA-only hotspot panel basis — RNA-NGS mandatory.
Do NOT ignore baseline + serial LFTs — hepatotoxicity Grade ≥3.
Do NOT ignore peripheral edema — diuretics + compression; reduce to 225 mg if persistent.
Do NOT combine with strong CYP3A4 inhibitors / inducers.
Do NOT confirm plan without funding pathway — tepotinib not registered in Ukraine.
Do NOT use in ILD or severe lung disease.
Do NOT discontinue for isolated mild edema.

Standard plan (IND-NSCLC-2L-MET-AMP-CAPMATINIB)

Do NOT use capmatinib at low-level MET amplification (GCN 5-9) — minimal benefit of monotherapy.
Do NOT confirm MET amplification on IHC alone — FISH or NGS confirmation mandatory.
Do NOT ignore baseline + serial LFTs — hepatotoxicity ≥G3 requires hold.
Do NOT ignore peripheral edema — proactive diuretics + compression; reduce dose if persistent G≥2.
Do NOT combine with strong CYP3A4 inhibitors / inducers — exposure shifts.
Do NOT confirm plan without funding pathway — capmatinib not registered in Ukraine; off-label MET-amp use complicates EAP.
Do NOT use at baseline pneumonitis or severe lung disease — additive ILD risk.
Do NOT discontinue for isolated mild edema — manageable with conservative measures.

Standard plan (IND-NSCLC-2L-BRAF-V600E-DAB-TRAM)

Do NOT prescribe in non-V600 BRAF mutations (V600K often responsive, V600D variable, fusion / class-2 / class-3 NOT responsive).
Do NOT ignore pyrexia management protocol — hold both drugs, antipyretics, restart when afebrile; not permanent discontinuation for reversible pyrexia.
Do NOT ignore baseline + serial LVEF (echo q3 mo) — MEK inhibitor cardiomyopathy.
Do NOT combine with strong CYP3A4 inhibitors / inducers.
Do NOT use at baseline LVEF <50% or severe HF.
Do NOT ignore dermatologic surveillance — secondary skin malignancies (SCC, KA) possible class effect.
Do NOT confirm plan without funding — partial NSZU coverage; may require co-pay or charity.

Standard plan (IND-NSCLC-2L-NTRK-LAROTRECTINIB)

Do NOT confirm NTRK fusion on pan-TRK IHC alone — confirm by RNA-NGS (IHC less sensitive for NTRK3).
Do NOT discontinue larotrectinib abruptly — withdrawal symptoms described; taper if possible.
Do NOT combine with strong CYP3A4 inhibitors / inducers without dose modification.
Do NOT ignore baseline + serial LFTs.
Do NOT confirm plan without funding pathway — larotrectinib not registered in Ukraine.
Do NOT use at baseline severe cognitive dysfunction — TRK class CNS-AE (less than entrectinib).
Do NOT ignore NGS-based resistance characterization at progression — repotrectinib active for G595R / G667C.

Standard plan (IND-NSCLC-2L-HER2-MUT-T-DXD)

Do NOT confirm HER2 mutation status on IHC alone — IHC useful for amplification/overexpression, NOT for kinase-domain mutations; NGS mandatory.
Do NOT ignore baseline + monthly CT chest — pneumonitis ~12% any-grade, ~3% G≥3, ~1% fatal.
Do NOT continue T-DXd at any confirmed ILD ≥G2 — permanent discontinuation.
Do NOT ignore baseline + serial LVEF (echo q3 mo) — cardiomyopathy risk lower than naked trastuzumab but exists.
Do NOT skip aggressive antiemetic prophylaxis — high emetogenicity (NK1+5HT3+dex regimen).
Do NOT prescribe at baseline ILD or severe lung disease — additive pneumonitis risk.
Do NOT confirm UA-funding pathway on the basis of breast registration — NSCLC indication outside NSZU; funding requires explicit charity / off-label / DEC pathway citing FDA NSCLC label.

Standard plan (IND-NSCLC-2L-PD-L1-POST-IO-DOCETAXEL)

Do NOT prescribe without comprehensive NGS panel (≥9 driver genes) — driver-positive disease requires targeted, not cytotoxic 2L.
Do NOT prescribe at baseline Grade ≥2 peripheral neuropathy — taxane toxicity cumulative.
Do NOT initiate within 28 days of major surgery — perforation / dehiscence risk with ramucirumab.
Do NOT continue ramucirumab with uncontrolled HTN >160/100 — cerebrovascular risk.
Do NOT use in active hemoptysis or recent GI bleeding — fatal hemorrhages possible.
Do NOT skip dexamethasone premedication for docetaxel — fluid retention + hypersensitivity.
Do NOT prescribe at ECOG 3-4 — toxicity profile doc+ram exceeds frail patient tolerance; consider single-agent docetaxel or best supportive care.
Do NOT confirm ramucirumab without funding — single-agent docetaxel or doc+nintedanib (adenocarcinoma) are valid alternatives in UA.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Selpercatinib monotherapy (LIBRETTO-001) — RET fusion+ NSCLC

28-day cycles × Continuous until progression or unacceptable toxicity

Aggressive plan

Induction · Amivantamab + Lazertinib (MARIPOSA-2) — 2L EGFR-mut NSCLC post-osimertinib

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Amivantamab monotherapy (CHRYSALIS) — 2L EGFR Exon 20 insertion NSCLC

28-day cycles × Continuous until progression or unacceptable toxicity

Aggressive plan

Induction · Lorlatinib monotherapy (ALK+ NSCLC, 1L OR post-2G TKI)

28-day cycles × Continuous until progression

Standard plan

Induction · Entrectinib monotherapy (STARTRK-2) — ROS1+ NSCLC (CNS-active)

28-day cycles × Continuous until progression or unacceptable toxicity

Aggressive plan

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

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Sotorasib monotherapy (KRAS G12C+ NSCLC, 2L+)

28-day cycles × Continuous until progression

Aggressive plan

Induction · Adagrasib monotherapy (KRYSTAL-1) — 2L+ KRAS G12C+ NSCLC

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Capmatinib monotherapy (GEOMETRY mono-1) — MET ex14 NSCLC

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Tepotinib monotherapy (VISION) — MET ex14 NSCLC

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Dabrafenib + trametinib (BRAF V600E+ NSCLC)

28-day cycles × Continuous until progression

Standard plan

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

28-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Trastuzumab deruxtecan (DESTINY-Lung01/02) — HER2-mutant NSCLC 2L+

21-day cycles × Continuous until progression or unacceptable toxicity

Standard plan

Induction · Docetaxel + Ramucirumab (REVEL) — 2L+ NSCLC post-platinum / post-ICI

21-day cycles × Until progression or unacceptable toxicity (typically 6+ cycles for responders)

MDT brief

Discussion questions (10, 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-ALK-FUSION
What is the status of ALK rearrangement / fusion (BIO-ALK-FUSION)? It is required by track(s): IND-NSCLC-ALK-2L-LORLATINIB. Expected value: ALK rearranged (FISH OR IHC OR NGS).
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.
→ molecular_geneticist
OQ-BIOMARKER-BRAF-V600E
What is the status of BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-NSCLC-2L-BRAF-V600E-DAB-TRAM. Expected value: BRAF V600E confirmed by NGS or PCR.
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.
→ molecular_geneticist
OQ-BIOMARKER-EGFR-MUTATION
What is the status of EGFR mutation status (NSCLC actionable) (BIO-EGFR-MUTATION)? It is required by track(s): IND-NSCLC-2L-EGFR-POST-OSI-AMI-LAZ, IND-NSCLC-2L-EGFR-EX20INS-AMIVANTAMAB. Expected value: Activating EGFR mutation (ex19del OR L858R) confirmed at diagnosis; status reassessed for resistance mutations at progression.
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.
→ molecular_geneticist
OQ-BIOMARKER-HER2-SOLID
What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-NSCLC-2L-HER2-MUT-T-DXD. Expected value: HER2-activating mutation confirmed by NGS (kinase-domain insertion most common — Y772_A775dup; also G776 / V777 / L755 / S310 hotspots).
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
OQ-BIOMARKER-KRAS-G12C
What is the status of KRAS G12C mutation (BIO-KRAS-G12C)? It is required by track(s): IND-NSCLC-2L-KRAS-G12C-SOTORASIB, IND-NSCLC-2L-KRAS-G12C-ADAGRASIB. Expected value: KRAS G12C mutation confirmed by NGS or allele-specific PCR.
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.
→ molecular_geneticist
OQ-BIOMARKER-MET
What is the status of MET alterations (exon 14 skipping or amplification) (BIO-MET)? It is required by track(s): IND-NSCLC-2L-MET-EX14-CAPMATINIB, IND-NSCLC-2L-MET-EX14-TEPOTINIB. Expected value: MET exon 14 skipping mutation confirmed by NGS (RNA-NGS preferred — captures splice-site variants outside hotspots).
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.
→ molecular_geneticist
OQ-BIOMARKER-MET-AMPLIFICATION
What is the status of MET amplification (high-level copy-number gain) (BIO-MET-AMPLIFICATION)? It is required by track(s): IND-NSCLC-2L-MET-AMP-CAPMATINIB. Expected value: High-level MET amplification (MET/CEP7 ≥4.0 OR mean GCN ≥10) confirmed by FISH OR NGS with assay-specific high-amp 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.
→ molecular_geneticist
OQ-BIOMARKER-NTRK-FUSION
What is the status of NTRK1/2/3 gene fusion (BIO-NTRK-FUSION)? It is required by track(s): IND-NSCLC-2L-NTRK-LAROTRECTINIB. Expected value: NTRK1/2/3 fusion confirmed by RNA-NGS (preferred — captures partner) or pan-TRK IHC ≥1+ confirmed by NGS/FISH.
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.
→ molecular_geneticist
OQ-BIOMARKER-ROS1-FUSION
What is the status of ROS1 fusion (BIO-ROS1-FUSION)? It is required by track(s): IND-NSCLC-2L-ROS1-POST-CRIZ-ENTRECTINIB, IND-NSCLC-2L-ROS1-REPOTRECTINIB. Expected value: ROS1 rearrangement confirmed (RNA-NGS preferred OR FISH).
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.
→ molecular_geneticist

MDT talk tree (12 steps)

#	Owner	Topic	Action
1	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
2	molecular_geneticist	Biomarker status	What is the status of ALK rearrangement / fusion (BIO-ALK-FUSION)? It is required by track(s): IND-NSCLC-ALK-2L-LORLATINIB. Expected value: ALK rearranged (FISH OR IHC OR NGS).
3	molecular_geneticist	Biomarker status	What is the status of BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-NSCLC-2L-BRAF-V600E-DAB-TRAM. Expected value: BRAF V600E confirmed by NGS or PCR.
4	molecular_geneticist	Biomarker status	What is the status of EGFR mutation status (NSCLC actionable) (BIO-EGFR-MUTATION)? It is required by track(s): IND-NSCLC-2L-EGFR-POST-OSI-AMI-LAZ, IND-NSCLC-2L-EGFR-EX20INS-AMIVANTAMAB. Expected value: Activating EGFR mutation (ex19del OR L858R) confirmed at diagnosis; status reassessed for resistance mutations at progression.
5	molecular_geneticist	Biomarker status	What is the status of KRAS G12C mutation (BIO-KRAS-G12C)? It is required by track(s): IND-NSCLC-2L-KRAS-G12C-SOTORASIB, IND-NSCLC-2L-KRAS-G12C-ADAGRASIB. Expected value: KRAS G12C mutation confirmed by NGS or allele-specific PCR.
6	molecular_geneticist	Biomarker status	What is the status of MET alterations (exon 14 skipping or amplification) (BIO-MET)? It is required by track(s): IND-NSCLC-2L-MET-EX14-CAPMATINIB, IND-NSCLC-2L-MET-EX14-TEPOTINIB. Expected value: MET exon 14 skipping mutation confirmed by NGS (RNA-NGS preferred — captures splice-site variants outside hotspots).
7	molecular_geneticist	Biomarker status	What is the status of MET amplification (high-level copy-number gain) (BIO-MET-AMPLIFICATION)? It is required by track(s): IND-NSCLC-2L-MET-AMP-CAPMATINIB. Expected value: High-level MET amplification (MET/CEP7 ≥4.0 OR mean GCN ≥10) confirmed by FISH OR NGS with assay-specific high-amp threshold.
8	molecular_geneticist	Biomarker status	What is the status of NTRK1/2/3 gene fusion (BIO-NTRK-FUSION)? It is required by track(s): IND-NSCLC-2L-NTRK-LAROTRECTINIB. Expected value: NTRK1/2/3 fusion confirmed by RNA-NGS (preferred — captures partner) or pan-TRK IHC ≥1+ confirmed by NGS/FISH.
9	molecular_geneticist	Biomarker status	What is the status of ROS1 fusion (BIO-ROS1-FUSION)? It is required by track(s): IND-NSCLC-2L-ROS1-POST-CRIZ-ENTRECTINIB, IND-NSCLC-2L-ROS1-REPOTRECTINIB. Expected value: ROS1 rearrangement confirmed (RNA-NGS preferred OR FISH).
10	pathologist	Biomarker status	What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-NSCLC-2L-HER2-MUT-T-DXD. Expected value: HER2-activating mutation confirmed by NGS (kinase-domain insertion most common — Y772_A775dup; also G776 / V777 / L755 / S310 hotspots).
11	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
12	social_worker_case_manager	Specialist review	Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.

Skills (recommended) — for consideration (3)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-ALK-FUSION, OQ-BIOMARKER-BRAF-V600E, OQ-BIOMARKER-EGFR-MUTATION, OQ-BIOMARKER-KRAS-G12C, OQ-BIOMARKER-MET, OQ-BIOMARKER-MET-AMPLIFICATION, OQ-BIOMARKER-NTRK-FUSION, OQ-BIOMARKER-ROS1-FUSION
Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.

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: 1/10 known (10%), 9 missing, 0 default-track gaps
Unevaluated RedFlags: RF-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION, RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-ENVIRONMENTAL-AIR-POLLUTION-LUNG-PREVENTION, RF-ENVIRONMENTAL-ARSENIC-WATER-PREVENTION, RF-ENVIRONMENTAL-FRYING-EMISSIONS-PREVENTION, RF-ENVIRONMENTAL-SECONDHAND-SMOKE-LUNG-PREVENTION, RF-IATROGENIC-BLEOMYCIN-LATE-PREVENTION, RF-IATROGENIC-PRIOR-RADIATION-PREVENTION, RF-LIFESTYLE-TOBACCO-CANCER-PREVENTION, 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-ROS1-FUSION-ACTIONABLE, RF-NSCLC-SVC-SYNDROME, RF-NSCLC-TRANSFORMATION-PROGRESSION, RF-NSCLC-TROP2-DATO-CANDIDATE, RF-OCC-ASBESTOS-MALIGNANCY-PREVENTION, RF-OCC-DIESEL-EXHAUST-PREVENTION, RF-OCC-FIREFIGHTER-PREVENTION, RF-OCC-IONIZING-RADIATION-PREVENTION, RF-OCC-PAH-PREVENTION, RF-OCC-PAINTERS-PREVENTION, RF-OCC-SILICA-PREVENTION, RF-RADON-MALIGNANCY-PREVENTION, RF-SCLERODERMA-LUNG-PREVENTION

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-ALK-FUSION`	ALK rearrangement / fusion	molecular_geneticist	no	IND-NSCLC-ALK-2L-LORLATINIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: ALK rearranged (FISH OR IHC OR NGS)
`BIO-BRAF-V600E`	BRAF V600E mutation	molecular_geneticist	no	IND-NSCLC-2L-BRAF-V600E-DAB-TRAM	Verify result, method, specimen, and report date before sign-off. Expected/constraint: BRAF V600E confirmed by NGS or PCR
`BIO-EGFR-MUTATION`	EGFR mutation status (NSCLC actionable)	molecular_geneticist	no	IND-NSCLC-2L-EGFR-POST-OSI-AMI-LAZ, IND-NSCLC-2L-EGFR-EX20INS-AMIVANTAMAB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: Activating EGFR mutation (ex19del OR L858R) confirmed at diagnosis; status reassessed for resistance mutations at progression
`BIO-HER2-SOLID`	HER2 status (solid tumors — gastric/GEJ/CRC scoring)	pathologist	no	IND-NSCLC-2L-HER2-MUT-T-DXD	Verify result, method, specimen, and report date before sign-off. Expected/constraint: HER2-activating mutation confirmed by NGS (kinase-domain insertion most common — Y772_A775dup; also G776 / V777 / L755 / S310 hotspots)
`BIO-KRAS-G12C`	KRAS G12C mutation	molecular_geneticist	no	IND-NSCLC-2L-KRAS-G12C-SOTORASIB, IND-NSCLC-2L-KRAS-G12C-ADAGRASIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: KRAS G12C mutation confirmed by NGS or allele-specific PCR
`BIO-MET`	MET alterations (exon 14 skipping or amplification)	molecular_geneticist	no	IND-NSCLC-2L-MET-EX14-CAPMATINIB, IND-NSCLC-2L-MET-EX14-TEPOTINIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: MET exon 14 skipping mutation confirmed by NGS (RNA-NGS preferred — captures splice-site variants outside hotspots)
`BIO-MET-AMPLIFICATION`	MET amplification (high-level copy-number gain)	molecular_geneticist	no	IND-NSCLC-2L-MET-AMP-CAPMATINIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: High-level MET amplification (MET/CEP7 ≥4.0 OR mean GCN ≥10) confirmed by FISH OR NGS with assay-specific high-amp threshold
`BIO-NTRK-FUSION`	NTRK1/2/3 gene fusion	molecular_geneticist	no	IND-NSCLC-2L-NTRK-LAROTRECTINIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: NTRK1/2/3 fusion confirmed by RNA-NGS (preferred — captures partner) or pan-TRK IHC ≥1+ confirmed by NGS/FISH
`BIO-ROS1-FUSION`	ROS1 fusion	molecular_geneticist	no	IND-NSCLC-2L-ROS1-POST-CRIZ-ENTRECTINIB, IND-NSCLC-2L-ROS1-REPOTRECTINIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: ROS1 rearrangement confirmed (RNA-NGS preferred OR FISH)

Technical MDT skill metadata (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-BRF113928-PLANCHARD-2016: Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, multicentre phase 2 trial (BRF113928) (2016)
SRC-CHRYSALIS-PARK-2021: Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study (2021)
SRC-CODEBREAK200-JOHNSON-2023: Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial (CodeBreaK 200) (2023)
SRC-DESTINY-BREAST03-CORTES-2022: Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer (2022)
SRC-DESTINYLUNG01-LI-2022: Trastuzumab Deruxtecan in Previously Treated HER2-Mutant Lung Cancer (DESTINY-Lung01) (2022)
SRC-DESTINYLUNG02-GOTO-2023: Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial (2023)
SRC-ESMO-NSCLC-METASTATIC-2024: ESMO Clinical Practice Guideline on Metastatic Non-Small Cell Lung Cancer (2024)
SRC-GEOMETRY-WOLF-2020: Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer (GEOMETRY mono-1) (2020)
SRC-KRYSTAL1-JANNE-2022: Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS G12C Mutation (KRYSTAL-1) (2022)
SRC-LIBRETTO001-DRILON-2020: Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer (LIBRETTO-001) (2020)
SRC-LUMELUNG1-RECK-2014: Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial (2014)
SRC-MARIPOSA2-PASSARO-2024: Amivantamab plus Lazertinib in Osimertinib-Relapsed EGFR-Mutated Advanced Non-Small Cell Lung Cancer (MARIPOSA-2) (2024)
SRC-NAVIGATE-DRILON-2018: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children (NAVIGATE / SCOUT pooled) (2018)
SRC-NCCN-NSCLC-2025: NCCN Clinical Practice Guidelines — Non-Small Cell Lung Cancer (2025.v8)
SRC-REVEL-GARON-2014: Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial (2014)
SRC-STARTRK2-DRILON-2020: Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials (2020)
SRC-TRIDENT1-DRILON-2024: Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer (TRIDENT-1) (2024)
SRC-VISION-PAIK-2020: Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations (VISION) (2020)

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: 2026-08-17.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT01639508	Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity	PHASE2	RECRUITING	Memorial Sloan Kettering Cancer Center	—	Biomarker: enriched Surrogate endpoint only Single country
NCT05059951	Chemotherapy With or Without Immune Checkpoint Inhibitors for Lung Cancer	N/A	RECRUITING	Hunan Province Tumor Hospital	—	Surrogate endpoint only Single country
NCT06563999	Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.	PHASE2	RECRUITING	Sun Yat-sen University	—	Biomarker: enriched Single country
NCT04302025	A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)	PHASE2	RECRUITING	Genentech, Inc.	—	Single country
NCT07704658	Pralsetinib DDI Study in Patients With Advanced or Metastatic Solid Tumors	PHASE4	RECRUITING	Rigel Pharmaceuticals	—	Small N (<50) Single country
NCT07696832	Efficacy and Safety of Ivonescimab Monotherapy as First-Line Treatment for PD-L1-Positive, Driver Gene-Negative, Locally Advanced or Metastatic NSCLC: A Multicenter, Prospective, Real-World Cohort Study	N/A	RECRUITING	Guangdong Association of Clinical Trials	—	Surrogate endpoint only Single country
NCT04683250	Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities	PHASE1 / PHASE2	RECRUITING	Taiho Pharmaceutical Co., Ltd.	—	Biomarker: enriched Surrogate endpoint only
NCT05451602	HEC169096 in Participants With Advanced Solid Tumors	PHASE1 / PHASE2	RECRUITING	Sunshine Lake Pharma Co., Ltd.	—	Biomarker: enriched Surrogate endpoint only Single country
NCT07613424	A Study of MET Concordance and Gene Profiling in 1L NSCLC (Genomet)	NA	RECRUITING	AstraZeneca	—	Single country
NCT05142189	Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer	PHASE1	RECRUITING	BioNTech SE	—	Biomarker: enriched Phase 1 only

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 Selpercatinib monotherapy (LIBRETTO-001) — RET fusion+ NSCLC (REG-SELPERCATINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Amivantamab + Lazertinib (MARIPOSA-2) — 2L EGFR-mut NSCLC post-osimertinib (REG-AMIVANTAMAB-LAZERTINIB-NSCLC-2L) 2/2 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Amivantamab monotherapy (CHRYSALIS) — 2L EGFR Exon 20 insertion NSCLC (REG-AMIVANTAMAB-MONO-NSCLC-EX20INS) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Lorlatinib monotherapy (ALK+ NSCLC, 1L OR post-2G TKI) (REG-LORLATINIB-NSCLC) 1/1 component drug(s) not on NSZU formulary	✓ registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Entrectinib monotherapy (STARTRK-2) — ROS1+ NSCLC (CNS-active) (REG-ENTRECTINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
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
Standard plan Sotorasib monotherapy (KRAS G12C+ NSCLC, 2L+) (REG-SOTORASIB-KRAS) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan Adagrasib monotherapy (KRYSTAL-1) — 2L+ KRAS G12C+ NSCLC (REG-ADAGRASIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Capmatinib monotherapy (GEOMETRY mono-1) — MET ex14 NSCLC (REG-CAPMATINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Tepotinib monotherapy (VISION) — MET ex14 NSCLC (REG-TEPOTINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Capmatinib monotherapy (GEOMETRY mono-1) — MET ex14 NSCLC (REG-CAPMATINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Standard plan Dabrafenib + trametinib (BRAF V600E+ NSCLC) (REG-DABRAFENIB-TRAMETINIB-NSCLC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
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 Trastuzumab deruxtecan (DESTINY-Lung01/02) — HER2-mutant NSCLC 2L+ (REG-T-DXD-NSCLC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Docetaxel + Ramucirumab (REVEL) — 2L+ NSCLC post-platinum / post-ICI (REG-DOCETAXEL-RAMUCIRUMAB) 1/2 component drug(s) not on NSZU formulary	✓ registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT01639508 Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05059951 Chemotherapy With or Without Immune Checkpoint Inhibitors for Lung Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06563999 Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations. No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04302025 A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07704658 Pralsetinib DDI Study in Patients With Advanced or Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07696832 Efficacy and Safety of Ivonescimab Monotherapy as First-Line Treatment for PD-L1-Positive, Driver Gene-Negative, Locally Advanced or Metastatic NSCLC: A Multicenter, Prospective, Real-World Cohort Study No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04683250 Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05451602 HEC169096 in Participants With Advanced Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07613424 A Study of MET Concordance and Gene Profiling in 1L NSCLC (Genomet) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05142189 Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer 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: 2026-08-17.

plan_id: PLAN-NSCLC-RET-FUSION-2L-001-V1 | version: 1 | generated: 2026-08-17T08:06:31.088581+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.