Patient
VAR-MELANOMA-RELAPSED · 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 |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-KIT | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
| BIO-BRAF-V600E | Excluded (negative) |
Primary current-line option
- 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
- Primary current-line option selected by ALGO-MELANOMA-METASTATIC-2L at step 5.
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-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
- 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
- Current-line alternative presented for HCP consideration
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-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.
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.
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.
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.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Encorafenib + binimetinib (BRAF V600E/K melanoma)
28-day cycles × Continuous until progression or unacceptable toxicity
Standard plan
Induction · Imatinib (KIT-mutant mucosal/acral 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
Standard plan
Induction · Relatlimab + nivolumab (Opdualag, melanoma)
28-day cycles × Until progression or unacceptable toxicity (typical 24 mo cap in trial)
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-HIGH-RISK-BIOLOGY, 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-MELANOMA-TRANSFORMATION-PROGRESSION, 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: 2026-05-13.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT02828202 | Follow-up of a National Cohort of Melanoma Resectable Stage II, Stage III or IV Patients or Unresectable Primary | N/A | RECRUITING | — | Single country | |
| NCT07148245 | Symptoms of Immune Checkpoint Inhibitor Therapy in Cutaneous Melanoma | N/A | RECRUITING | — | Single country | |
| NCT04693377 | Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial | NA | RECRUITING | — | Small N (<50) Single country | |
| NCT07318051 | Sample Collection for Ongoing Research and Product Evaluation Study | N/A | RECRUITING | — | Single country | |
| NCT03340129 | Anti-PD 1 Brain Collaboration + Radiotherapy Extension (ABC-X Study) | PHASE2 | RECRUITING | — | — | |
| NCT06425926 | Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors | PHASE1 / PHASE2 | RECRUITING | — | Single country | |
| NCT06500455 | Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain | PHASE3 | RECRUITING | — | — | |
| NCT06980740 | Video-Tumorboard PLUS | N/A | RECRUITING | — | Single country | |
| NCT06066138 | A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing | PHASE1 | RECRUITING | — | Phase 1 only Small N (<50) Single country | |
| NCT06121180 | Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma | PHASE2 | RECRUITING | — | Small N (<50) 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 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 |
| Standard plan Imatinib (KIT-mutant mucosal/acral melanoma) (REG-IMATINIB-KIT-MELANOMA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Nivolumab + ipilimumab (melanoma, 1L metastatic) (REG-NIVO-IPI-MELANOMA) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| 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 |
| Trial · NCT02828202 Follow-up of a National Cohort of Melanoma Resectable Stage II, Stage III or IV Patients or Unresectable Primary No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07148245 Symptoms of Immune Checkpoint Inhibitor Therapy in Cutaneous Melanoma No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04693377 Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07318051 Sample Collection for Ongoing Research and Product Evaluation Study No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT03340129 Anti-PD 1 Brain Collaboration + Radiotherapy Extension (ABC-X Study) No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06425926 Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06500455 Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06980740 Video-Tumorboard PLUS No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06066138 A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06121180 Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma 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.