Patient
MELANOMA-NIVO-RELATLIMAB-001 · Algorithm: ALGO-MELANOMA-METASTATIC-2L
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-2L-RELATLIMAB-NIVOLUMAB
- Regimen
- Relatlimab + nivolumab (Opdualag, melanoma)
- Drugs + NSZU
- Relatlimab (DRUG-RELATLIMAB) 160 mg (fixed-dose co-formulation with nivolumab 480 mg) · IV q4w, over 30 min · IV ✗ Not registered in UA
- Nivolumab (DRUG-NIVOLUMAB) 480 mg (fixed-dose co-formulation with relatlimab 160 mg) · IV q4w, over 30 min · IV ✓ NSZU covered
- Reason
- Primary current-line option selected by ALGO-MELANOMA-METASTATIC-2L at step 5; branch-driving red flag: RF-MELANOMA-FRAILTY-AGE.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-MELANOMA-2L-KIT-IMATINIB
- Regimen
- Imatinib (KIT-mutant mucosal/acral melanoma)
- Drugs + NSZU
- Imatinib (DRUG-IMATINIB) 400 mg PO BID with food + large glass of water (Carvajal 2011 trial dose) · Continuous · PO ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-MELANOMA-2L-POST-IO-BRAFI-MEKI
- Regimen
- Encorafenib + binimetinib (BRAF V600E/K melanoma)
- Drugs + NSZU
- Encorafenib (DRUG-ENCORAFENIB) 450 mg PO once daily, with or without food · Continuous · PO ⚠ Out-of-pocket
- Binimetinib (DRUG-BINIMETINIB) 45 mg PO BID, with or without food · Continuous · PO ✗ Not registered in UA
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-MELANOMA-2L-POST-BRAFI-IPI-NIVO
- 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
- 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 4 → branch 41
- 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
Step 5 → branch IND-MELANOMA-2L-RELATLIMAB-NIVOLUMAB
- RF-MELANOMA-FRAILTY-AGE ★ winner: Age ≥80 + ECOG ≥2 — nivo+ipi prohibitive; nivo+rela or pembro mono. SRC-NCCN-MELANOMA-2025SRC-ESMO-MELANOMA-2024
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-LDH | Lactate Dehydrogenase | Critical | lab | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-PREGNANCY | Beta-HCG | Critical | lab | — | all tracks |
| 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
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-2L-RELATLIMAB-NIVOLUMAB)
- Do not prescribe if the patient already received anti-PD-1 1L — this buys nothing new beyond additional LAG-3 blockade with minimal benefit post-PD-1.
- Do not ignore baseline troponin + ECG — myocarditis ~1.7% (higher than nivo mono); serial monitoring with symptoms.
- Do not give >10 mg/day prednisolone before start — reduces ICI efficacy.
- Do not use in baseline active autoimmune disease on systemic immunosuppression — irAE risk.
- Do not confirm plan without verified funding pathway — relatlimab not registered in Ukraine; pathway = named-patient import.
- Do not give live vaccines during or for 3 months after.
Standard plan (IND-MELANOMA-2L-KIT-IMATINIB)
- Do not prescribe in KIT amplification without point mutation — non-predictive (Carvajal 2011).
- Do not prescribe in non-mucosal/non-acral melanoma without NGS-documented KIT mutation — low pre-test probability + false-positives.
- Do not continue >12 weeks without objective response (PR/CR) — early switch to ICI or BRAFi+MEKi if BRAF-co-mutated.
- Do not forget off-label justification for MDT — imatinib is licensed for CML/GIST/Ph+ALL, not melanoma.
- Do not ignore baseline + monthly LFTs — hepatotoxicity is a defined AE.
- Do not give with warfarin without monitoring INR — CYP3A4 substrate interaction.
Standard plan (IND-MELANOMA-2L-POST-IO-BRAFI-MEKI)
- Do not prescribe without verified BRAF V600E or V600K — non-V600 BRAF alterations do not respond to BRAFi+MEKi doublet.
- Do not ignore baseline + serial ECHO (LVEF) — binimetinib cardiomyopathy ~7%, mandatory monitoring q2-3 mo.
- Do not skip baseline + symptom-driven ophthalmology — RPED, RVO, uveitis class effect MEKi.
- Do not use in BRAF-WT — toxic, ineffective; pseudo-paradoxical activation of MAPK in BRAF-WT cells.
- Do not forget dermatology q3 mo — new SCC + primary melanomas class effect BRAFi (although less than vemurafenib mono).
- Do not prescribe in IO-naive (without 1L anti-PD-1) — DREAMseq showed that IO-first sequence is superior to targeted-first for OS.
- Do not confirm plan without verified funding pathway — ENCO+BINI out-of-pocket in Ukraine.
Aggressive plan (IND-MELANOMA-2L-POST-BRAFI-IPI-NIVO)
- Do not prescribe in baseline active autoimmune disease on systemic immunosuppression — irAE can be fatal (myocarditis, hepatitis).
- Do not ignore baseline TFTs, cortisol, LFTs, troponin — irAE monitoring is foundational.
- Do not give >10 mg/day prednisolone before start — reduces ICI efficacy.
- Do not continue ipi+nivo with Grade ≥3 irAE — switch to nivo maintenance or stop.
- Do not prescribe in pre-BRAFi setting in BRAF V600+ — DREAMseq showed that IO-first gives better OS in BRAF-mut patients (exception: visceral crisis requires BRAFi for rapid response).
- Do not give live vaccines during or for 3 months after completion.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Relatlimab + nivolumab (Opdualag, melanoma)
28-day cycles × Until progression or unacceptable toxicity (typical 24 mo cap in trial)
Standard plan
Induction · Imatinib (KIT-mutant mucosal/acral melanoma)
28-day cycles × Continuous until progression or unacceptable toxicity
Standard plan
Induction · Encorafenib + binimetinib (BRAF V600E/K melanoma)
28-day cycles × Continuous until progression or unacceptable toxicity
Aggressive plan
Induction · Nivolumab + ipilimumab (melanoma, 1L metastatic)
21-day cycles × 4 induction; nivo maintenance until progression OR 2 years
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (4 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. |
| 4 | 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.
- 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: 2/2 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 (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 | 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-CARVAJAL-KIT-MELANOMA-2013: KIT as a therapeutic target in metastatic melanoma (2011)
- SRC-CHECKMATE-067-LARKIN-2019: Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma (2019)
- SRC-COLUMBUS-DUMMETT-2018: Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial (2018)
- SRC-ESMO-MELANOMA-2024: ESMO Cutaneous Melanoma (2024)
- SRC-NCCN-MELANOMA-2025: NCCN Cutaneous Melanoma (2025.v2)
- SRC-RELATIVITY-047-TAWBI-2022: Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma (2022)
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: 2026-05-12.
| 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 Relatlimab + nivolumab (Opdualag, melanoma) (REG-RELATLIMAB-NIVOLUMAB-MELANOMA) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Imatinib (KIT-mutant mucosal/acral melanoma) (REG-IMATINIB-KIT-MELANOMA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Encorafenib + binimetinib (BRAF V600E/K melanoma) (REG-ENCORAFENIB-BINIMETINIB-MELANOMA) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Nivolumab + ipilimumab (melanoma, 1L metastatic) (REG-NIVO-IPI-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: 2026-05-12.