OpenOnco · Treatment Plan

Treatment plan — Cutaneous melanoma

PLAN-SHOWCASE-MELANOMA-BRAF-001-V1 · v1 · 2026-06-27

Patient

SHOWCASE-MELANOMA-BRAF-001 · Algorithm: ALGO-MELANOMA-METASTATIC-1L

DiagnosisCutaneous melanoma

MOH / ICD-10C43

ICD-O-38720/3; C44.9

StageIV

Histologycutaneous melanoma

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
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 SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance 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

⚠️ Not included in plan

Biomarker	Status
NRAS	Excluded (negative)
KIT	Excluded (negative)
PD-L1	Not in KB — ask clinician to verify

Primary current-line option

Standard plan

★ DEFAULT

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 4.

Other current-line alternatives (3 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

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

Aggressive plan

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

Standard plan

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

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)

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 (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-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 (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	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-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: 2026-06-27.

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 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 · 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-SHOWCASE-MELANOMA-BRAF-001-V1 | version: 1 | generated: 2026-06-27T09:41:00.175412+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.