OpenOnco · DIS-NSCLC · Relapsed / 2nd line
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OpenOnco · Treatment Plan
Treatment plan — Non-small cell lung cancer
PLAN-VAR-NSCLC-RELAPSED-V1 · v1 · 2026-05-13
Patient
VAR-NSCLC-RELAPSED · Algorithm: ALGO-NSCLC-METASTATIC-2L
DiagnosisNon-small cell lung cancer
MOH / ICD-10C34
ICD-O-38046/3; C34.9

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
✅ Covered biomarkers (matched in KB)
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-BRAF-V600EV600EIA
Molecular evidence option
  • SRC-CIVIC: Level A (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level B (Supports, Poor Outcome)
Resistance or avoidance signal
Trial or research option
  • SRC-CIVIC: Level C (Supports, Sensitivity/Response)
  • SRC-CIVIC: Level D (Supports, Sensitivity/Response)
BRAF V600E in advanced NSCLC (≈1-2% of adenocarcinomas): dabrafenib + trametinib gives ORR ~64% in 1L (Planchard et al. Lancet Oncol 2017) and is FDA/EMA-approved across lines. Encorafenib + binimetinib (PHAROS, Riely et al. JCO 2023) ORR 75% in treatment-naïve, 46% pretreated — also FDA-approved 2023.dabrafenib + trametinib
encorafenib + binimetinib
  • SRC-NCCN-NSCLC-2025
  • SRC-ESMO-NSCLC-METASTATIC-2024
BIO-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
⚠️ Not included in plan
BiomarkerStatus
BIO-ALK-FUSIONExcluded (negative)
BIO-EGFR-MUTATIONExcluded (negative)
BIO-NTRK-FUSIONExcluded (negative)
BIO-ROS1-FUSIONExcluded (negative)

Primary current-line option

Aggressive plan
★ DEFAULT
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
Primary current-line option per algorithm ALGO-NSCLC-METASTATIC-2L: selected default was filtered; promoted first remaining current-line track

Other current-line alternatives (13 tracks)

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

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-CBCComplete Blood Count with DifferentialCriticallaball tracks
TEST-CECT-CAPCECT chest/abdomen/pelvisCriticalimagingall tracks
TEST-CMPComprehensive Metabolic PanelCriticallaball tracks
TEST-FISH-PANELFISH (Fluorescence In Situ Hybridization)CriticalgenomicCSD Lab ✓ (code TBC)desired (aggressive)
TEST-LFTLiver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)Criticallaball tracks
TEST-NSCLC-NGS-PANELNSCLC comprehensive NGS panel (DNA + RNA fusion)CriticalCSD Lab: M081
CSD Lab: M065
all tracks
TEST-PDL1-IHCPD-L1 IHC (TPS for NSCLC)CriticalCSD Lab ✓ (code TBC)desired (aggressive, standard)
TEST-BRAIN-MRI-CONTRASTBrain MRI with contrastStandardall tracks
TEST-ECHOEchocardiographyStandardimagingstandard

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). RF-NSCLC-ALK-FUSION-ACTIONABLE
  • NSCLC with symptomatic brain metastases requiring emergency intervention: focal deficit, new seizure, raised intracranial pressure, or impending herniation. Asymptomatic / oligometastatic brain disease handled separatelyRF-NSCLC-BRAIN-METS-EMERGENCY
  • 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 emergencyRF-NSCLC-CORD-COMPRESSION
  • 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. RF-NSCLC-EGFR-C797S-RESISTANCE
  • 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. RF-NSCLC-EGFR-EX19DEL-ACTIONABLE
  • 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. RF-NSCLC-EGFR-T790M-ACTIONABLE
  • 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.RF-NSCLC-FRAILTY-AGE
  • NSCLC with symptomatic malignant pleural / pericardial effusion: dyspnea at rest, hypoxia, hemodynamic compromise (effusion-driven hypotension or tamponade physiology)RF-NSCLC-MALIGNANT-EFFUSION
  • NSCLC with superior vena cava syndrome: facial/upper-extremity edema, distended neck/chest veins, dyspnea, plethora, headache — most often right-upper-lobe / bulky mediastinal NSCLCRF-NSCLC-SVC-SYNDROME
  • 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.RF-NSCLC-TRANSFORMATION-PROGRESSION

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-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-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.
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.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

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 · Selpercatinib monotherapy (LIBRETTO-001) — RET fusion+ NSCLC
28-day cycles × Continuous until progression or unacceptable toxicity

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

MDT brief

Discussion questions (6, 0 blocking)

MDT talk tree (8 steps)

#OwnerTopicAction
1hematologistStaging / disease burden What is the current LDH? Marker of tumor burden and transformation.
2molecular_geneticistBiomarker 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.
3molecular_geneticistBiomarker 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).
4molecular_geneticistBiomarker 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.
5molecular_geneticistBiomarker status What is the status of RET alterations (fusion or activating point mutation) (BIO-RET)? It is required by track(s): IND-NSCLC-2L-RET-FUSION-SELPERCATINIB. Expected value: RET fusion confirmed by RNA-NGS (preferred) or FISH; KIF5B-RET most common partner in NSCLC.
6pathologistBiomarker 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).
7clinical_pharmacistSpecialist review Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
8social_worker_case_managerSpecialist 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-KRAS-G12C, OQ-BIOMARKER-MET, OQ-BIOMARKER-MET-AMPLIFICATION, OQ-BIOMARKER-RET
  • 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: 5/10 known (50%), 5 missing, 0 default-track gaps
  • Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, 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
Missing biomarkerLabelMDT ownerDefault trackRequired byNext action
BIO-HER2-SOLIDHER2 status (solid tumors — gastric/GEJ/CRC scoring)pathologistnoIND-NSCLC-2L-HER2-MUT-T-DXDVerify 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-G12CKRAS G12C mutationmolecular_geneticistnoIND-NSCLC-2L-KRAS-G12C-SOTORASIB, IND-NSCLC-2L-KRAS-G12C-ADAGRASIBVerify result, method, specimen, and report date before sign-off. Expected/constraint: KRAS G12C mutation confirmed by NGS or allele-specific PCR
BIO-METMET alterations (exon 14 skipping or amplification)molecular_geneticistnoIND-NSCLC-2L-MET-EX14-CAPMATINIB, IND-NSCLC-2L-MET-EX14-TEPOTINIBVerify 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-AMPLIFICATIONMET amplification (high-level copy-number gain)molecular_geneticistnoIND-NSCLC-2L-MET-AMP-CAPMATINIBVerify 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-RETRET alterations (fusion or activating point mutation)molecular_geneticistnoIND-NSCLC-2L-RET-FUSION-SELPERCATINIBVerify result, method, specimen, and report date before sign-off. Expected/constraint: RET fusion confirmed by RNA-NGS (preferred) or FISH; KIF5B-RET most common partner in NSCLC
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).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

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: 2026-05-13.
NCTTitlePhaseStatusSponsorUASignalsEligibility (excerpt)
NCT06734182Neoadjuvant Envafolimab Plus Disitamab Vedotin and Carboplatin in Resectable HER2-Mutant Non-Small-Cell Lung CancerPHASE2RECRUITINGGuangdong Provincial People's HospitalSmall N (<50) Single country
NCT05477979The Associations of Psychological Stress With Therapy Efficacy and Prognosis of Lung Cancer (STRESS-LUNG)N/ARECRUITINGSecond Xiangya Hospital of Central South UniversitySurrogate endpoint only Single country
NCT05473156A Study to Investigate the Safety, Pharmacokinetics, and Clinical Activity of AP203 in Patients with Locally Advanced or Metastatic Solid Tumors, and Expansion to Selected MalignanciesPHASE1 / PHASE2RECRUITINGAP Biosciences Inc.Surrogate endpoint only Single country
NCT05288205Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C MutationPHASE1 / PHASE2RECRUITINGAllist Pharmaceuticals, Inc.Single country
NCT06634979Selective Lymph Node Resection for Invasive Non-small Cell Lung Cancer With the CTR of 0.5-1 and the Diameter of ≤ 2 cmNARECRUITINGFudan UniversitySurrogate endpoint only Single country
NCT05802186Stereotactic Body Radiation Therapy Planning With Artificial Intelligence-Directed Dose Recommendation for Treatment of Primary or Metastatic Lung Tumors, RAD-AI StudyNARECRUITINGNorthwestern UniversitySingle country
NCT05624996Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-Small Cell Lung CancerPHASE3RECRUITINGNRG Oncology
NCT05198154ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLCN/ARECRUITINGFang WuSurrogate endpoint only Single country
NCT04165070KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)PHASE1 / PHASE2RECRUITINGMerck Sharp & Dohme LLCUASurrogate endpoint only
NCT07320105Postoperative Radiotherapy for Postoperative N2 Metastases of NSCLC in the Immunotherapy Era (Phase II)PHASE4RECRUITINGFujian Cancer HospitalSurrogate endpoint only Single country

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).
OptionUA registrationNSZUCost orientationAccess pathway
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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot 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 pathwaynot recorded
Standard plan
Dabrafenib + trametinib (BRAF V600E+ NSCLC) (REG-DABRAFENIB-TRAMETINIB-NSCLC)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
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 pathwaynot 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 pathwaynot recorded
Standard plan
Trastuzumab deruxtecan (DESTINY-Lung01/02) — HER2-mutant NSCLC 2L+ (REG-T-DXD-NSCLC)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Trial · NCT06734182
Neoadjuvant Envafolimab Plus Disitamab Vedotin and Carboplatin in Resectable HER2-Mutant Non-Small-Cell Lung Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05477979
The Associations of Psychological Stress With Therapy Efficacy and Prognosis of Lung Cancer (STRESS-LUNG)
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05473156
A Study to Investigate the Safety, Pharmacokinetics, and Clinical Activity of AP203 in Patients with Locally Advanced or Metastatic Solid Tumors, and Expansion to Selected Malignancies
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05288205
Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06634979
Selective Lymph Node Resection for Invasive Non-small Cell Lung Cancer With the CTR of 0.5-1 and the Diameter of ≤ 2 cm
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05802186
Stereotactic Body Radiation Therapy Planning With Artificial Intelligence-Directed Dose Recommendation for Treatment of Primary or Metastatic Lung Tumors, RAD-AI Study
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05624996
Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-Small Cell Lung Cancer
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05198154
ctDNA Analysis to Monitor the Risk of Progression After First-line Immunotherapy in Patients With Advanced NSCLC
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04165070
KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)
UA site available — verify enrollment status with site
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07320105
Postoperative Radiotherapy for Postoperative N2 Metastases of NSCLC in the Immunotherapy Era (Phase II)
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: 2026-05-13.