Patient
MELANOMA-BRAF-V600-NIVOIPI-001 · Algorithm: ALGO-MELANOMA-METASTATIC-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| BIO-BRAF-V600E | V600E | IA | 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 (and V600K) in cutaneous melanoma is the prototypical driver: combination BRAF + MEK inhibition (dabrafenib + trametinib; encorafenib + binimetinib; vemurafenib + cobimetinib) yields high ORR (~65-70%) and improves OS vs single-agent BRAFi (COMBI-d/v, coBRIM, COLUMBUS). Adjuvant dabrafenib + trametinib improves RFS in resected stage III (COMBI-AD). Triplet with anti-PD-1 (atezolizumab + vemurafenib + cobimetinib; IMspire150) extends PFS over doublet. | dabrafenib + trametinib
encorafenib + binimetinib
vemurafenib + cobimetinib
atezolizumab + vemurafenib + cobimetinib (triplet) | - SRC-NCCN-MELANOMA-2025
- SRC-ESMO-MELANOMA-2024
|
| BIO-BRAF-V600E | V600K | IA | 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 V600K (~10-20% of BRAF-mutant melanomas) shares all BRAF/MEKi approvals with V600E. Slightly lower ORR in pooled analyses (COMBI-d/v subgroup) but PFS/OS benefit preserved. Companion-diagnostic kits (cobas, THxID) detect both V600E and V600K. | dabrafenib + trametinib
encorafenib + binimetinib
vemurafenib + cobimetinib | - SRC-NCCN-MELANOMA-2025
- SRC-ESMO-MELANOMA-2024
|
| Biomarker | Status |
|---|
| BIO-NRAS | Not in KB — ask clinician to verify |
| BIO-KIT | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-MELANOMA-METASTATIC-1L-NIVO-IPI
- Regimen
- Nivolumab + ipilimumab (melanoma, 1L metastatic)
- Drugs + NSZU
- Nivolumab (DRUG-NIVOLUMAB) 1 mg/kg IV induction → 480 mg flat IV q4w maintenance · Induction with ipi cycles 1-4 · IV ✓ NSZU covered
- Ipilimumab (DRUG-IPILIMUMAB) 3 mg/kg IV (higher than RCC) · Days 1 of cycles 1-4 · IV ✓ NSZU covered
- Reason
- Primary current-line option selected by ALGO-MELANOMA-METASTATIC-1L at step 3.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-MELANOMA-ADJUVANT-PEMBRO-STAGE-III
- Regimen
- Pembrolizumab adjuvant (resected stage III/IV melanoma; KEYNOTE-054)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w (or 400 mg IV q6w) · Day 1 every 3 weeks (or q6w), for up to 18 cycles (~12 months total) starting within 12 weeks of definitive surgery · IV ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-MELANOMA-BRAF-METASTATIC-1L-DABRA-TRAME
- Regimen
- Dabrafenib + trametinib (BRAF V600E+ NSCLC)
- Drugs + NSZU
- Dabrafenib (DRUG-DABRAFENIB) 150 mg PO BID · Continuous · PO ✓ NSZU covered
- Trametinib (DRUG-TRAMETINIB) 2 mg PO once daily · Continuous · PO ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-MELANOMA-METASTATIC-1L-PEMBRO-MONO
- Regimen
- Pembrolizumab monotherapy (advanced/metastatic melanoma, 1L; KEYNOTE-006)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w (or 400 mg IV q6w) · Day 1 every 3 weeks (or q6w), for up to 35 cycles (~2 years) or until progression / unacceptable toxicity · IV ✓ NSZU covered
- 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 2 → branch 3
- RF-MELANOMA-BRAF-V600-ACTIONABLE ★ winner: BRAF V600E or V600K activating mutation in metastatic / unresectable melanoma — ~40-50% prevalence cutaneous melanoma. Treatment-defining: BRAFi + MEKi doublet (dabrafenib + trametinib, encorafenib + binimetinib — COLUMBUS, vemurafenib + cobimetinib). Sequencing with anti-PD-1 (CheckMate-067, DREAMseq) — IO-first preferred in low-volume disease; BRAF+MEK first in symptomatic / high-LDH disease.
SRC-NCCN-MELANOMA-2025SRC-ESMO-MELANOMA-2024SRC-COLUMBUS-DUMMETT-2018SRC-CHECKMATE-067-LARKIN-2019
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | all tracks |
| TEST-LDH | Lactate Dehydrogenase | Critical | lab | — | standard |
| TEST-BRAIN-MRI-CONTRAST | Brain MRI with contrast | Standard | — | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- LDH >2x ULN OR severe hepatic dysfunction — predictor of inferior ICI outcomes.RF-MELANOMA-ORGAN-DYSFUNCTION
- Symptomatic CNS metastases — ICI doublet (nivo+ipi) intracranially active; BRAFi+MEKi for visceral crisis.RF-MELANOMA-TRANSFORMATION-PROGRESSION
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-MELANOMA-ADJUVANT-PEMBRO-STAGE-III)
- Do not start adjuvant IO without negative baseline brain MRI with contrast — occult cerebral metastases are a frequent finding.
- Do not skip baseline TSH / cortisol / glucose — endocrine irAE are the most frequent, and pre-existing endocrinopathies change management.
- Do not start later than 12 weeks from surgery — KEYNOTE-054 window is shorter; benefit poorly characterized after that.
- Do not continue with gr ≥3 irAE without reassessing benefit/risk — adjuvant is curative intent, threshold for permanent discontinuation lower than metastatic.
- Do not combine with immunosuppression or live vaccines.
- Do not skip pre-treatment counseling — irAE may be permanent (endocrinopathies) and impact quality of life more than relapse in some scenarios.
Standard plan (IND-MELANOMA-METASTATIC-1L-PEMBRO-MONO)
- Do not start pembrolizumab without baseline TSH / cortisol / glucose — endocrine irAE are the most frequent.
- Do not ignore active autoimmune disease — relative contraindication, assess risk/benefit with rheumatologist.
- Do not skip baseline brain MRI with contrast — cerebral metastases are often asymptomatic in melanoma.
- Do not continue with gr ≥3 irAE without high-dose steroids (1-2 mg/kg prednisolone-equivalent) — delay in management can be fatal.
- Do not combine with immunosuppressants / live vaccines during treatment.
- Do not prescribe with ECOG ≥3 — limited data, palliative approach more appropriate.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Nivolumab + ipilimumab (melanoma, 1L metastatic)
21-day cycles × 4 induction; nivo maintenance until progression OR 2 years
Standard plan
Induction · Pembrolizumab adjuvant (resected stage III/IV melanoma; KEYNOTE-054)
21-day cycles × 18 cycles (~12 months) per KEYNOTE-054 protocol
Aggressive plan
Induction · Dabrafenib + trametinib (BRAF V600E+ NSCLC)
28-day cycles × Continuous until progression
Standard plan
Induction · Pembrolizumab monotherapy (advanced/metastatic melanoma, 1L; KEYNOTE-006)
21-day cycles × Up to 35 cycles (~2 years) or until progression
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 3 | molecular_geneticist | Specialist review | Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed. |
Skills (recommended) — for consideration (2)
- 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.
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: 1/1 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-MELANOMA-BRAF-V600-ACTIONABLE, RF-MELANOMA-INFECTION-SCREENING, RF-MELANOMA-IO-RESISTANT, RF-MELANOMA-KIT-MUT-ACTIONABLE, RF-MELANOMA-NF1-MUT-CANDIDATE, RF-MELANOMA-ORGAN-DYSFUNCTION, RF-MELANOMA-STAGE-III-RESECTED, RF-UVEAL-MELANOMA-BAP1-MUT-CANDIDATE
Technical MDT skill metadata (2/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | 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 |
Sources cited
- SRC-CHECKMATE-067-LARKIN-2019: Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma (2019)
- SRC-CHECKMATE-238-WEBER-2017: Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma (2017)
- SRC-COMBI-D-LONG-2014: Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma (2014)
- SRC-ESMO-MELANOMA-2024: ESMO Cutaneous Melanoma (2024)
- SRC-KEYNOTE-006-ROBERT-2015: Pembrolizumab versus Ipilimumab in Advanced Melanoma (2015)
- SRC-KEYNOTE-054-EGGERMONT-2018: Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma (2018)
- SRC-NCCN-MELANOMA-2025: NCCN Cutaneous Melanoma (2025.v2)
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.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06906822 | PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients | PHASE2 | RECRUITING | — | Surrogate 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).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Standard plan Nivolumab + ipilimumab (melanoma, 1L metastatic) (REG-NIVO-IPI-MELANOMA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Pembrolizumab adjuvant (resected stage III/IV melanoma; KEYNOTE-054) (REG-PEMBRO-ADJUVANT-MELANOMA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Dabrafenib + trametinib (BRAF V600E+ NSCLC) (REG-DABRAFENIB-TRAMETINIB-NSCLC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Pembrolizumab monotherapy (advanced/metastatic melanoma, 1L; KEYNOTE-006) (REG-PEMBRO-MONO-MELANOMA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Trial · NCT06906822 PLUG-IN: Pembrolizumab Combined With Enfortumab Vedotin for Advanced Melanoma Patients 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.