OpenOnco · Treatment Plan

Treatment plan — Cutaneous melanoma

PLAN-VAR-MELANOMA-RELAPSED-V1 · v1 · 2026-06-27

Patient

VAR-MELANOMA-RELAPSED · Algorithm: ALGO-MELANOMA-METASTATIC-2L

DiagnosisCutaneous melanoma

MOH / ICD-10C43

ICD-O-38720/3; C44.9

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

⚠️ Not included in plan

Biomarker	Status
BIO-KIT	BIO definition in KB; no ESCAT BMA entry — verify with clinician
BIO-BRAF-V600E	Excluded (negative)

Primary current-line option

Standard plan

★ DEFAULT

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.

Standard plan

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

Aggressive plan

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

Standard plan

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)

OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist

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-BAP1-CONFIRMED-CARRIER, RF-ENVIRONMENTAL-OUTDOOR-UV-SKIN-PREVENTION, RF-FAMMM-CONFIRMED-CARRIER, RF-LIFESTYLE-UV-EXPOSURE-PREVENTION, 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-OCC-FIREFIGHTER-PREVENTION, 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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	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: 2026-06-27.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT04045691	Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment	N/A	RECRUITING	Pierre Fabre Pharma GmbH	—	Surrogate endpoint only
NCT07230613	Neo-adjuvant Immunotherapy in Patients With Localized Melanoma	PHASE2	RECRUITING	UNICANCER	—	Single country
NCT05779423	Cryoablation+Ipilimumab+Nivolumab in Melanoma	PHASE2	RECRUITING	Massachusetts General Hospital	—	Small N (<50) Single country
NCT00722228	Autologous and Allogeneic Whole Cell Cancer Vaccine for Metastatic Tumors	PHASE1 / PHASE2	RECRUITING	Hadassah Medical Organization	—	Single country
NCT00040352	Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma	N/A	RECRUITING	National Cancer Institute (NCI)	—	Single country
NCT06630611	Evaluation of a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer (PragmaTIL)	PHASE2	RECRUITING	Vall d'Hebron Institute of Oncology	—	Small N (<50) Single country
NCT05296564	Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers	PHASE1 / PHASE2	RECRUITING	Hadassah Medical Organization	—	Small N (<50) Single country
NCT05029791	Variations of Immune Infiltrate and Cell Plasticity Markers in Treated Metastatic Melanoma Patients	NA	RECRUITING	Hospices Civils de Lyon	—	Single country
NCT05307289	Study of Alterations in Tumor Metabolism Associated With the Development of Immunotherapy Resistance in Melanoma	NA	RECRUITING	Centre Hospitalier Universitaire de Nice	—	Small N (<50) Single country
NCT07223424	Patient Preference for Subcutaneous vs. Intravenous Immune Therapy	PHASE2	RECRUITING	Diwakar Davar	—	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 · NCT04045691 Binimetinib Plus Encorafenib Real Life Investigation of Next Generation Melanoma Treatment No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07230613 Neo-adjuvant Immunotherapy in Patients With Localized Melanoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05779423 Cryoablation+Ipilimumab+Nivolumab in Melanoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT00722228 Autologous and Allogeneic Whole Cell Cancer Vaccine for Metastatic Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT00040352 Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06630611 Evaluation of a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer (PragmaTIL) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05296564 Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05029791 Variations of Immune Infiltrate and Cell Plasticity Markers in Treated Metastatic Melanoma Patients No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05307289 Study of Alterations in Tumor Metabolism Associated With the Development of Immunotherapy Resistance in Melanoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07223424 Patient Preference for Subcutaneous vs. Intravenous Immune Therapy 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.

plan_id: PLAN-VAR-MELANOMA-RELAPSED-V1 | version: 1 | generated: 2026-06-27T09:41:01.834918+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.