Cutaneous neuroendocrine carcinoma

Summary

Cutaneous neuroendocrine carcinoma (MONDO:0019210) is a cancer with 3 cohort genes (3 CIViC-evidence somatic drivers) and 129 clinical trials. Molecularly, CD274 Expression confers sensitivity to Pembrolizumab in Merkel Cell Carcinoma (CIViC Level B); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include avelumab, retifanlimab, and cemiplimab.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 3
• Phenotypes (HPO): 17
• Clinical trials: 129
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

12 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.13	Europe	Validated
Lifetime Prevalence	1-9 / 1 000 000	0.86	Europe	Validated
Point prevalence	1-9 / 100 000	4	Europe	Validated
Annual incidence	1-9 / 100 000	2.7	United States	Validated
Annual incidence	1-9 / 1 000 000	0.22	Denmark	Validated
Annual incidence	1-9 / 1 000 000	0.378	France	Validated
Annual incidence	1-9 / 1 000 000	0.13	United Kingdom	Validated
Annual incidence	1-9 / 100 000	1.8	Australia	Validated
Annual incidence	1-9 / 100 000	2	New Zealand	Validated
Annual incidence	1-9 / 100 000	4	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.27	Worldwide	Not yet validated
Annual incidence	<1 / 1 000 000	0.06	Finland	Not yet validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0030447	Merkel cell skin cancer	Obligate (100%)
HP:0000992	Cutaneous photosensitivity	Frequent (30-79%)
HP:0002730	Chronic noninfectious lymphadenopathy	Frequent (30-79%)
HP:0005374	Cellular immunodeficiency	Frequent (30-79%)
HP:0011356	Regional abnormality of skin	Frequent (30-79%)
HP:0025474	Erythematous plaque	Frequent (30-79%)
HP:0025475	Erythematous macule	Frequent (30-79%)
HP:0200036	Skin nodule	Frequent (30-79%)
HP:0002671	Basal cell carcinoma	Occasional (5-29%)
HP:0005526	Lymphoid leukemia	Occasional (5-29%)
HP:0006739	Squamous cell carcinoma of the skin	Occasional (5-29%)
HP:0006775	Multiple myeloma	Occasional (5-29%)
HP:0100570	Carcinoid tumor	Occasional (5-29%)
HP:0012531	Pain	Excluded (0%)
HP:0012658	Abnormal brain FDG positron emission tomography	Very rare (<1-4%)
HP:0030692	Brain neoplasm	Very rare (<1-4%)
HP:0040095	Neoplasm of the outer ear	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	cutaneous neuroendocrine carcinoma
Mondo ID	MONDO:0019210
MeSH	D015266
Orphanet	79140
ICD-10-CM	C4A
ICD-11	680322043
NCIT	C9231
SNOMED CT	253001006
UMLS	C0007129
MedGen	2843
GARD	0009266
NORD	1947
Is cancer (heuristic)	yes

Also known as: carcinoma of Merkel cell · carcinoma, Merkel cell · cutaneous APUDoma · cutaneous neuroendocrine carcinoma · MCC · Merkel cell cancer · Merkel Cell Carcinoma · Merkel cell carcinoma · Merkel cell tumor · Merkel cell tumour · Merkle tumors · Merkle tumours · neuroendocrine carcinoma of skin · neuroendocrine carcinoma of the skin · neuroendocrine skin carcinoma · trabecular cancer · trabecular skin carcinoma

Data availability: 54 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › neuroendocrine carcinoma › cutaneous neuroendocrine carcinoma

Related subtypes (11): small cell carcinoma, anal canal neuroendocrine neoplasm, large cell neuroendocrine carcinoma, pancreatic endocrine carcinoma, combined lung carcinoma, malignant adrenal gland pheochromocytoma, liver neuroendocrine carcinoma, medullary thyroid gland carcinoma, goblet cell carcinoma, thymic neuroendocrine carcinoma, vulvar neuroendocrine carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 33 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CD274	LoF	DLBCLNOS	CIViC #11335
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	2	18.5×	0.008
Antibody/Immunoglobulin	1	9.7×	0.099

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
lower lobe of lung	1
placenta	1
lateral nuclear group of thalamus	1
oocyte	1
secondary oocyte	1
adrenal tissue	1
calcaneal tendon	1
tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIT	6,087
PIK3CA	5,157
CD274	5,012

Intra-cohort edges

A	B	Sources
KIT	PIK3CA	biogrid_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CA	P42336	135
CD274	Q9NZQ7	76
KIT	P10721	52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 101. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	2	346.1×	0.001	KIT, PIK3CA
Dasatinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Imatinib-resistant KIT mutants	1	3806.7×	0.002	KIT
KIT mutants bind TKIs	1	3806.7×	0.002	KIT
Masitinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Nilotinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Regorafenib-resistant KIT mutants	1	3806.7×	0.002	KIT
Signaling by kinase domain mutants of KIT	1	3806.7×	0.002	KIT
Sunitinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Signaling by juxtamembrane domain KIT mutants	1	3806.7×	0.002	KIT
Sorafenib-resistant KIT mutants	1	3806.7×	0.002	KIT
Drug resistance of KIT mutants	1	3806.7×	0.002	KIT
Signaling by extracellular domain mutants of KIT	1	3806.7×	0.002	KIT
Signaling by SCF-KIT	2	165.5×	0.002	KIT, PIK3CA
Constitutive Signaling by Aberrant PI3K in Cancer	2	84.6×	0.002	KIT, PIK3CA
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	64.5×	0.002	KIT, PIK3CA
PIP3 activates AKT signaling	2	44.5×	0.004	KIT, PIK3CA
RAF/MAP kinase cascade	2	40.7×	0.004	KIT, PIK3CA
MET activates PI3K/AKT signaling	1	634.4×	0.008	PIK3CA
Activated NTRK3 signals through PI3K	1	634.4×	0.008	PIK3CA
Activated NTRK2 signals through PI3K	1	543.8×	0.008	PIK3CA
Signaling by LTK in cancer	1	543.8×	0.008	PIK3CA
PI3K/AKT activation	1	423.0×	0.010	PIK3CA
Regulation of PD-L1(CD274) translation	1	423.0×	0.010	CD274
Signaling by KIT in disease	1	380.7×	0.010	KIT
IRS-mediated signalling	1	346.1×	0.010	PIK3CA
PI3K events in ERBB4 signaling	1	346.1×	0.010	PIK3CA
STAT3 nuclear events downstream of ALK signaling	1	346.1×	0.010	CD274
Co-stimulation by ICOS	1	346.1×	0.010	PIK3CA
Signaling by FGFR4 in disease	1	317.2×	0.010	PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to muscle inactivity	1	5617.3×	0.003	PIK3CA
melanocyte adhesion	1	5617.3×	0.003	KIT
positive regulation of pyloric antrum smooth muscle contraction	1	5617.3×	0.003	KIT
response to butyrate	1	5617.3×	0.003	PIK3CA
negative regulation of tumor necrosis factor superfamily cytokine production	1	5617.3×	0.003	CD274
positive regulation of colon smooth muscle contraction	1	5617.3×	0.003	KIT
positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1	5617.3×	0.003	CD274
positive regulation of vascular associated smooth muscle cell differentiation	1	2808.7×	0.004	KIT
Fc receptor signaling pathway	1	1872.4×	0.004	KIT
Kit signaling pathway	1	1872.4×	0.004	KIT
response to L-leucine	1	1872.4×	0.004	PIK3CA
cellular response to hydrostatic pressure	1	1872.4×	0.004	PIK3CA
melanocyte migration	1	1872.4×	0.004	KIT
obsolete regulation of bile acid metabolic process	1	1872.4×	0.004	KIT
positive regulation of small intestine smooth muscle contraction	1	1872.4×	0.004	KIT
actin cytoskeleton organization	2	52.7×	0.004	KIT, PIK3CA
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	52.2×	0.004	KIT, PIK3CA
mast cell chemotaxis	1	1404.3×	0.005	KIT
hematopoietic stem cell migration	1	1404.3×	0.005	KIT
mast cell differentiation	1	1404.3×	0.005	KIT
negative regulation of CD8-positive, alpha-beta T cell activation	1	1404.3×	0.005	CD274
positive regulation of dendritic cell cytokine production	1	1123.5×	0.005	KIT
positive regulation of mast cell cytokine production	1	1123.5×	0.005	KIT
mast cell proliferation	1	1123.5×	0.005	KIT
positive regulation of mast cell proliferation	1	1123.5×	0.005	KIT
cell migration	2	41.0×	0.005	KIT, PIK3CA
lymphoid progenitor cell differentiation	1	936.2×	0.005	KIT
negative regulation of actin filament depolymerization	1	936.2×	0.005	PIK3CA
erythropoietin-mediated signaling pathway	1	936.2×	0.005	KIT
regulation of cellular respiration	1	936.2×	0.005	PIK3CA

Therapeutics

Drugs indicated for this disease

2 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Avelumab	Approved (phase 4)
Retifanlimab	Approved (phase 4)
Pembrolizumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Carboplatin, Cemiplimab, Cisplatin, Etoposide, Fluorouracil, Ipilimumab, Lanreotide, Lenvatinib, Methotrexate, Nivolumab, Nogapendekin Alfa, Oblimersen Sodium, Paclitaxel, Relatlimab.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 0

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CD274	MOCLOBEMIDE
KIT	PONATINIB
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIT	99	4
PIK3CA	67	4
CD274	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
PONATINIB	4	KIT
FEDRATINIB	4	KIT, PIK3CA
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT, PIK3CA
DASATINIB	4	KIT, PIK3CA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
CD274	525	Binding:520, Functional:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIT	2.7.10.1	receptor protein-tyrosine kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CD274	525
KIT	2,305
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

28 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
MOCLOBEMIDE	4	CD274
PYRVINIUM	4	CD274
RIFABUTIN	4	CD274
PONATINIB	4	KIT
FEDRATINIB	4	KIT, PIK3CA
TIVOZANIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT, PIK3CA
DASATINIB	4	KIT, PIK3CA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CD274, KIT, PIK3CA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 129.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	48
PHASE1	31
PHASE1/PHASE2	25
Not specified	20
PHASE3	4
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03271372	PHASE3	ACTIVE_NOT_RECRUITING	Adjuvant Avelumab in Merkel Cell Cancer
NCT05078047	PHASE3	RECRUITING	Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO
NCT03783078	PHASE3	COMPLETED	Pembrolizumab (MK-3475) as First-line Therapy for Advanced Merkel Cell Carcinoma (MK-3475-913)
NCT04157985	PHASE3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT02479698	PHASE2	RECRUITING	Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus
NCT02978625	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
NCT03071406	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma
NCT03074513	PHASE2	ACTIVE_NOT_RECRUITING	Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors
NCT03228667	PHASE2	ACTIVE_NOT_RECRUITING	QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors
NCT03935893	PHASE2	RECRUITING	Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers
NCT04261855	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy and Avelumab in Merkel Cell Carcinoma
NCT04291885	PHASE2	ACTIVE_NOT_RECRUITING	Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma
NCT04349436	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Investigate the Efficacy and Safety of RP1 in Adult Patients With Organ Transplants and Advanced Skin Malignancies
NCT04792073	PHASE2	ACTIVE_NOT_RECRUITING	Study of Avelumab and/or Radiation Therapy in People With Advanced Merkel Cell Carcinoma
NCT04869137	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel Cell Carcinoma
NCT05086692	PHASE1/PHASE2	RECRUITING	A Beta-only IL-2 ImmunoTherapY Study
NCT05100095	PHASE2	RECRUITING	Hypofractionated Radiation Therapy for Merkel Cell Carcinoma
NCT05120271	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors
NCT05269381	PHASE1/PHASE2	RECRUITING	Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors
NCT05496036	PHASE2	RECRUITING	Neoadjuvant PD-1 Blockade in Resectable Merkel Cell Carcinoma
NCT05583708	PHASE2	RECRUITING	Phase II Study of Peptide Receptor Radionuclide Therapy in Combination With Immunotherapy for Patients With Merkel Cell Cancer
NCT05594290	PHASE2	ACTIVE_NOT_RECRUITING	Chemo-immunotherapy in Patients With Resectable Merkel Cell Carcinoma Prior to Surgery
NCT05864144	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of SNS-101 (Anti VISTA) Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors
NCT05896839	PHASE1/PHASE2	RECRUITING	Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
NCT05947500	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Combination of Two Anticancer Drugs M1774 (Tuvusertib) and Avelumab to Evaluate Their Safety and Effectiveness in Treating Merkel Cell Skin Cancer, MATRiX Trial
NCT05969860	PHASE2	RECRUITING	At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
NCT06047379	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis
NCT06056895	PHASE2	ACTIVE_NOT_RECRUITING	Triple Immune Checkpoint Inhibition for Advanced or Metastatic PD-(L)1 Refractory Merkel Cell Carcinoma
NCT06086288	PHASE2	NOT_YET_RECRUITING	Study of PembrolizumAb combiNeD With Cisplatin or carbOplatin and Etoposide in Treatment naïve Advanced meRkel Cell cArcinoma (MCC)
NCT06151236	PHASE2	RECRUITING	Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma
NCT06223659	PHASE2	RECRUITING	EMLA Topical Cream for Treatment of Pain in Patients Receiving Intra-Dermal Technetium 99 Injections for Lymphoscintigraphy for Skin Cancers
NCT06814496	PHASE1/PHASE2	RECRUITING	Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors
NCT07115043	PHASE1/PHASE2	RECRUITING	A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors
NCT07285044	PHASE2	RECRUITING	The Cancer Connected Access and Remote Expertise Beyond Walls Program to Provide In-Home Cancer Treatment and Improve Treatment Satisfaction in Cancer Patients Living in the Florida Panhandle and Surrounding Areas
NCT07288073	PHASE2	RECRUITING	TIL Therapy in cSCC and MCC
NCT07302347	PHASE1/PHASE2	RECRUITING	A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participants With Merkel Cell Carcinoma (MK-3475-G21/KEYNOTE-G21)
NCT07472322	PHASE1/PHASE2	NOT_YET_RECRUITING	ASTX727 & Retifanlimab-dlwr for Advanced Merkel Cell After Progression on Anti-PD-(L)1
NCT07576725	PHASE2	NOT_YET_RECRUITING	Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial
NCT00003514	PHASE2	WITHDRAWN	Antineoplaston Therapy in Treating Patients With Neuroendocrine Tumor That Is Metastatic or Unlikely to Respond to Surgery or Radiation Therapy
NCT00003549	PHASE2	COMPLETED	S9716: Combination Chemotherapy in Treating Patients With Merkel Cell Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AVELUMAB	4	14
RETIFANLIMAB	4	5
CEMIPLIMAB	4	2
CABOZANTINIB	4	1
COSIBELIMAB	4	1
EDOTREOTIDE GALLIUM GA-68	4	1
IMATINIB	4	1
INDIUM IN 111 PENTETREOTIDE	4	1
LANREOTIDE	4	1
LENVATINIB	4	1
LIFILEUCEL	4	1
LUTETIUM OXODOTREOTIDE LU-177	4	1
OCTREOTIDE ACETATE	4	1
OMEGA-3-ACID ETHYL ESTERS	4	1
PEMBROLIZUMAB	4	1
TALIMOGENE LAHERPAREPVEC	4	1
TARLATAMAB	4	1
TREMELIMUMAB	4	1
NOGAPENDEKIN ALFA	3	4
VATALANIB	3	2
VELIPARIB	3	2
ANTINEOPLASTON A10	3	1
BEMPEGALDESLEUKIN	3	1
L19IL2	3	1
NAVTEMADLIN	3	1
OBLIMERSEN SODIUM	3	1
ONFEKAFUSP ALFA	3	1
PLINABULIN	3	1
RILVEGOSTOMIG	3	1
VUSOLIMOGENE ODERPAREPVEC	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items; also 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
CD274 Expression	Pembrolizumab	Sensitivity/Response	CIViC B	EID1578
PIK3CA P471L	Idelalisib	Sensitivity/Response	CIViC C	EID739