| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|---|---|---|---|---|---|
| BIO-EGFR-MUTATION | C797S | IIB | Resistance or avoidance signal
Trial or research option
| EGFR C797S is the principal acquired resistance mutation to osimertinib. Cis-configuration with T790M renders all currently approved 3rd-gen EGFR-TKIs ineffective; trans-configuration may respond to combination 1st-gen + osimertinib. Investigational 4th-gen EGFR-TKIs (BLU-945, BBT-176) and amivantamab+chemo (MARIPOSA-2) are active options. | amivantamab + carboplatin + pemetrexed (MARIPOSA-2) platinum-doublet chemotherapy clinical trial of 4th-gen EGFR-TKI |
|
| BIO-EGFR-MUTATION | exon 19 deletion | IA | Resistance or avoidance signal
| EGFR exon 19 deletion in advanced NSCLC: osimertinib 1L improves OS vs first-generation EGFR-TKIs (FLAURA, Soria et al. 2018; Ramalingam 2020). Adjuvant osimertinib post-resection improves DFS (ADAURA, Wu et al. 2020). Exon 19 del is one of two classical sensitizing mutations (with L858R) and predicts the highest TKI response rates. | osimertinib monotherapy osimertinib + pemetrexed/platinum (FLAURA2 regimen) amivantamab + lazertinib (MARIPOSA, 1L alternative) |
|
| BIO-EGFR-MUTATION | exon 20 insertion | IA | Trial or research option
| EGFR exon 20 insertions (excluding A763_Y764insFQEA) are insensitive to classical EGFR-TKIs. Amivantamab (EGFR-MET bispecific) + chemo is 1L standard (PAPILLON, Zhou et al. 2023). Mobocertinib was withdrawn globally 2023-2024 for failed confirmatory trial. Sunvozertinib (China-approved) is an emerging option in 2L. | amivantamab + carboplatin + pemetrexed (PAPILLON 1L) amivantamab monotherapy (2L) platinum-doublet chemotherapy (alternative) |
|
| BIO-EGFR-MUTATION | exon 18 G719X | IB | Trial or research option
| EGFR exon 18 G719X (G719A/C/S) is an "uncommon" sensitizing mutation (~3% of EGFR-mut NSCLC). Afatinib (LUX-Lung pooled analysis, Yang 2015) shows highest activity in G719X; osimertinib also active (UNICORN, Ahn 2022). Often co-occurs with S768I or L861Q. | afatinib monotherapy osimertinib monotherapy |
|
| BIO-EGFR-MUTATION | L858R | IA | EGFR L858R in advanced NSCLC: osimertinib 1L is standard (FLAURA); L858R historically shows somewhat lower TKI response than exon 19 del, prompting interest in combination strategies (FLAURA2 chemo combo; MARIPOSA amivantamab+lazertinib). Adjuvant osimertinib indicated post resection (ADAURA). | osimertinib monotherapy osimertinib + pemetrexed/platinum (FLAURA2) amivantamab + lazertinib (MARIPOSA) |
| |
| BIO-EGFR-MUTATION | T790M | IA | Resistance or avoidance signal | EGFR T790M is the dominant acquired-resistance mechanism after 1st/2nd-gen EGFR-TKI (gefitinib/erlotinib/afatinib). Osimertinib (3rd-gen) is active against T790M and is standard 2L (AURA3, Mok et al. 2017). In the modern era T790M is rarely encountered de novo since osimertinib has moved to 1L; remains relevant after legacy 1L-TKI use. | osimertinib monotherapy |
|
| BIO-PDL1-TPS | (gene-level) | IA |
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) |
|
2IND-NSCLC-EGFR-MUT-MET-1L| 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 | — | 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) | all tracks |
| TEST-BRAIN-MRI-CONTRAST | Brain MRI with contrast | Standard | — | — | all tracks |
| TEST-CT-CAP | CT chest/abdomen/pelvis | Standard | imaging | — | standard |
| TEST-ECG | Electrocardiogram | Standard | clinical_assessment | — | standard |
| # | Owner | Topic | Action |
|---|---|---|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | medical_oncologist | Biomarker status | What is the status of BIO-MET-EX14 (BIO-MET-EX14)? It is required by track(s): IND-NSCLC-MET-EX14-1L-CAPMATINIB. Expected value: MET exon 14 skipping mutation confirmed by NGS (DNA or RNA). |
| 3 | medical_oncologist | Biomarker status | What is the status of BIO-RET-FUSION (BIO-RET-FUSION)? It is required by track(s): IND-NSCLC-RET-FUSION-1L-SELPERCATINIB. Expected value: RET fusion confirmed (CCDC6-RET, KIF5B-RET, NCOA4-RET, or other partner). |
| 4 | molecular_geneticist | Biomarker status | What is the status of ALK rearrangement / fusion (BIO-ALK-FUSION)? It is required by track(s): IND-NSCLC-ALK-MET-1L. Expected value: positive. |
| 5 | molecular_geneticist | Biomarker status | What is the status of BRAF V600E mutation (BIO-BRAF-V600E)? It is required by track(s): IND-NSCLC-BRAF-V600E-1L-DAB-TRAM. Expected value: BRAF V600E confirmed by NGS or validated PCR assay. |
| 6 | 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-NTRK-FUSION-1L-LAROTRECTINIB. Expected value: NTRK1, NTRK2, or NTRK3 gene fusion confirmed. |
| 7 | molecular_geneticist | Biomarker status | What is the status of ROS1 fusion (BIO-ROS1-FUSION)? It is required by track(s): IND-NSCLC-ROS1-1L-REPOTRECTINIB. Expected value: ROS1 rearrangement confirmed (RNA-NGS preferred — captures partner; FISH/IHC acceptable for rapid diagnosis with NGS confirmation). |
| 8 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 9 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|---|---|---|---|---|
BIO-ALK-FUSION | ALK rearrangement / fusion | molecular_geneticist | no | IND-NSCLC-ALK-MET-1L | Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive |
BIO-BRAF-V600E | BRAF V600E mutation | molecular_geneticist | no | IND-NSCLC-BRAF-V600E-1L-DAB-TRAM | Verify result, method, specimen, and report date before sign-off. Expected/constraint: BRAF V600E confirmed by NGS or validated PCR assay |
BIO-MET-EX14 | BIO-MET-EX14 | medical_oncologist | no | IND-NSCLC-MET-EX14-1L-CAPMATINIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: MET exon 14 skipping mutation confirmed by NGS (DNA or RNA) |
BIO-NTRK-FUSION | NTRK1/2/3 gene fusion | molecular_geneticist | no | IND-NSCLC-NTRK-FUSION-1L-LAROTRECTINIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: NTRK1, NTRK2, or NTRK3 gene fusion confirmed |
BIO-RET-FUSION | BIO-RET-FUSION | medical_oncologist | no | IND-NSCLC-RET-FUSION-1L-SELPERCATINIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: RET fusion confirmed (CCDC6-RET, KIF5B-RET, NCOA4-RET, or other partner) |
BIO-ROS1-FUSION | ROS1 fusion | molecular_geneticist | no | IND-NSCLC-ROS1-1L-REPOTRECTINIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: ROS1 rearrangement confirmed (RNA-NGS preferred — captures partner; FISH/IHC acceptable for rapid diagnosis with NGS confirmation) |
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|---|---|---|---|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|---|---|---|---|---|---|---|
| NCT06755684 | Neoadjuvant Befotertinib Combined Bevacizumab or Platinum-based Double Chemotherapy for Resectable Locally-advanced EGFR Mutation-positive Non-Small Cell Lung Cancer | PHASE2 | RECRUITING | Peng Zhang | — | Biomarker: enriched Single country | |
| NCT06102928 | A Clinical Study of the Combination of Anlotinib and Aumolertinib in the First-line Treatment of Advanced NSCLC With EGFR 21L858R Mutation | NA | RECRUITING | Kunming Medical University | — | Biomarker: enriched Small N (<50) Surrogate endpoint only Single country | |
| NCT05800223 | Armatinib Alone or in Combination With SRT for Brain Metastases EGFR-mutated Non-small Cell Lung Cancer | PHASE3 | RECRUITING | Shanghai Cancer Hospital, China | — | Surrogate endpoint only Single country | |
| NCT07174388 | An External Control Arm Study in Non-Small Cell Lung Cancer | N/A | RECRUITING | N-Power Medicine | — | Surrogate endpoint only Single country | |
| NCT05104788 | A Study of Icotinib With Chemotherapy as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer | PHASE2 | RECRUITING | Peking University Cancer Hospital & Institute | — | Biomarker: enriched Small N (<50) Single country | |
| NCT06043973 | Almonertinib Combined With Anlotinib as First-line Treatment for Advanced Non-small Cell Lung Cance | PHASE3 | RECRUITING | Qianfoshan Hospital | — | Biomarker: enriched Surrogate endpoint only Single country | |
| NCT06348927 | Sunvozertinib Plus Anlotinib as 1L Treatment in EGFR-Sensitive Mutations Combined With Co-Mutations Advanced NSCLC | PHASE2 | RECRUITING | Hunan Province Tumor Hospital | — | Biomarker: enriched Surrogate endpoint only Single country | |
| NCT06670196 | A Study of SKB264 in Combination With Osimertinib Versus Osimertinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutations, Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer | PHASE3 | RECRUITING | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | — | Biomarker: enriched Surrogate endpoint only Single country | |
| NCT06080776 | SH-1028 Tablets Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB NSCLC With Sensitizing EGFR Mutations | PHASE3 | RECRUITING | Nanjing Sanhome Pharmaceutical, Co., Ltd. | — | Surrogate endpoint only Single country | |
| NCT06706713 | Study of BEBT-109 in Subjects With EGFR Exon 20 Insertion Mutations Non-Small Cell Lung Cancer | PHASE2 | RECRUITING | BeBetter Med Inc | — | Surrogate endpoint only Single country |
Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|---|---|---|---|
| Standard plan Osimertinib monotherapy (EGFR-mut NSCLC, 1L metastatic OR adjuvant) (REG-OSIMERTINIB-NSCLC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Alectinib monotherapy (ALK+ NSCLC, 1L metastatic OR adjuvant) (REG-ALECTINIB-NSCLC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Repotrectinib monotherapy (TRIDENT-1) — ROS1+ NSCLC (TKI-naive or post-prior ROS1-TKI) (REG-REPOTRECTINIB-NSCLC) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| 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 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 |
| 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 Pembrolizumab monotherapy (NSCLC PD-L1 ≥50%, driver-negative, 1L) (REG-PEMBRO-MONO-NSCLC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Pembrolizumab + carboplatin + pemetrexed (NSCLC non-squamous, 1L) (REG-PEMBRO-CHEMO-NSCLC-NONSQ) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Trial · NCT06755684 Neoadjuvant Befotertinib Combined Bevacizumab or Platinum-based Double Chemotherapy for Resectable Locally-advanced EGFR Mutation-positive Non-Small Cell Lung Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06102928 A Clinical Study of the Combination of Anlotinib and Aumolertinib in the First-line Treatment of Advanced NSCLC With EGFR 21L858R Mutation No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05800223 Armatinib Alone or in Combination With SRT for Brain Metastases EGFR-mutated Non-small Cell Lung Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07174388 An External Control Arm Study in Non-Small Cell Lung Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05104788 A Study of Icotinib With Chemotherapy as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06043973 Almonertinib Combined With Anlotinib as First-line Treatment for Advanced Non-small Cell Lung Cance No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06348927 Sunvozertinib Plus Anlotinib as 1L Treatment in EGFR-Sensitive Mutations Combined With Co-Mutations Advanced NSCLC No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06670196 A Study of SKB264 in Combination With Osimertinib Versus Osimertinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutations, Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06080776 SH-1028 Tablets Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB NSCLC With Sensitizing EGFR Mutations No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06706713 Study of BEBT-109 in Subjects With EGFR Exon 20 Insertion Mutations 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: 2026-06-27.