Malignant pleural mesothelioma

Summary

Malignant pleural mesothelioma (MONDO:0005112) is a disease with 5 cohort genes and 113 clinical trials. Molecularly, MDM2 EXPRESSION is associated with resistance to Pemetrexed + Cisplatin in Malignant Pleural Mesothelioma (CIViC Level B); 6 further subtype–drug associations are mapped below. Top therapeutic interventions include sodium thiosulfate, celecoxib, and nintedanib.

At a glance

• Cohort genes: 5
• Clinical trials: 113
• Precision-medicine evidence (CIViC): 7 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	malignant pleural mesothelioma
Mondo ID	MONDO:0005112
EFO	EFO:0000770
DOID	DOID:7474
NCIT	C7376
SNOMED CT	254645002
UMLS	C0812413
MedGen	208810
GARD	0024150
Anatomy (UBERON)	UBERON:0000977
Is cancer (heuristic)	no

Also known as: malignant mesothelioma of pleura · malignant mesothelioma of the pleura · malignant pleural mesothelioma · pleura mesothelioma · pleural diffuse malignant mesothelioma · pleural malignant mesothelioma

Data availability: 87 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › mesothelial neoplasm › mesothelioma › pleural mesothelioma › malignant pleural mesothelioma

Related subtypes (1): pleural adenomatoid tumor

Subtypes (2): pleural epithelioid mesothelioma, pleural sarcomatoid mesothelioma

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: 21 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF2	Orphanet:528084	Non-specific syndromic intellectual disability
ERCC1	Orphanet:1466	COFS syndrome
ERCC1	Orphanet:90322	Cockayne syndrome type 2
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma
MDM2	Orphanet:524	Li-Fraumeni syndrome
MDM2	Orphanet:99970	Dedifferentiated liposarcoma
MDM2	Orphanet:99971	Well-differentiated liposarcoma
NRAS	Orphanet:146	Differentiated thyroid carcinoma
NRAS	Orphanet:2612	Linear nevus sebaceus syndrome
NRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
NRAS	Orphanet:389	Langerhans cell histiocytosis
NRAS	Orphanet:626	Large/giant congenital melanocytic nevus
NRAS	Orphanet:648	Noonan syndrome
NRAS	Orphanet:86834	Juvenile myelomonocytic leukemia

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF2	HGNC:10061	ENSG00000121481	Q99496	E3 ubiquitin-protein ligase RING2	civic_evidence
ERCC1	HGNC:3433	ENSG00000012061	P07992	DNA excision repair protein ERCC-1	civic_evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	civic_evidence
MDM2	HGNC:6973	ENSG00000135679	Q00987	E3 ubiquitin-protein ligase Mdm2	civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF2	E3 ubiquitin-protein ligase RING2	E3 ubiquitin-protein ligase that mediates monoubiquitination of ‘Lys-119’ of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation.
ERCC1	DNA excision repair protein ERCC-1	Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5’-incision during DNA repair.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
MDM2	E3 ubiquitin-protein ligase Mdm2	E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.2

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	1	5.5×	0.252
Transcription factor	2	3.3×	0.252
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
ERCC1	Other/Unknown	no		ERCC1/RAD10/SWI10, RuvA_2-like, Restrct_endonuc-II-like
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
MDM2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RanBP2, SWIB_MDM2_domain
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
primordial germ cell in gonad	1
apex of heart	1
parotid gland	1
right atrium auricular region	1
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1
adrenal tissue	1
calcaneal tendon	1
ventricular zone	1
epithelium of nasopharynx	1
gingival epithelium	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF2	178	ubiquitous	marker	primordial germ cell in gonad, cortical plate, ganglionic eminence
ERCC1	285	ubiquitous	marker	apex of heart, parotid gland, right atrium auricular region
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
MDM2	274	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MDM2	9,892
NRAS	7,598
ALK	4,792
RNF2	3,814
ERCC1	2,085

Intra-cohort edges

A	B	Sources
ALK	NRAS	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MDM2	Q00987	147
ALK	Q9UM73	79
NRAS	P01111	35
RNF2	Q99496	15
ERCC1	P07992	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 142. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Drug resistance of ALK mutants	1	2284.0×	0.006	ALK
ASP-3026-resistant ALK mutants	1	2284.0×	0.006	ALK
NVP-TAE684-resistant ALK mutants	1	2284.0×	0.006	ALK
alectinib-resistant ALK mutants	1	2284.0×	0.006	ALK
brigatinib-resistant ALK mutants	1	2284.0×	0.006	ALK
ceritinib-resistant ALK mutants	1	2284.0×	0.006	ALK
crizotinib-resistant ALK mutants	1	2284.0×	0.006	ALK
lorlatinib-resistant ALK mutants	1	2284.0×	0.006	ALK
Signaling by ALK in cancer	2	108.8×	0.006	ALK, MDM2
Signaling by ALK fusions and activated point mutants	2	60.1×	0.006	ALK, MDM2
Signaling by RAS GAP mutants	1	761.3×	0.014	NRAS
Signaling by RAS GTPase mutants	1	761.3×	0.014	NRAS
Oxidative Stress Induced Senescence	2	36.2×	0.014	RNF2, MDM2
MDK and PTN in ALK signaling	1	571.0×	0.018	ALK
Activation of RAS in B cells	1	456.8×	0.020	NRAS
RAS signaling downstream of NF1 loss-of-function variants	1	326.3×	0.020	NRAS
Estrogen-stimulated signaling through PRKCZ	1	326.3×	0.020	NRAS
SOS-mediated signalling	1	285.5×	0.020	NRAS
Activated NTRK3 signals through RAS	1	253.8×	0.020	NRAS
EGFR Transactivation by Gastrin	1	228.4×	0.020	NRAS
SHC-related events triggered by IGF1R	1	228.4×	0.020	NRAS
Activated NTRK2 signals through RAS	1	228.4×	0.020	NRAS
MET activates RAS signaling	1	207.6×	0.020	NRAS
Signaling by FGFR4 in disease	1	190.3×	0.020	NRAS
Activated NTRK2 signals through FRS2 and FRS3	1	190.3×	0.020	NRAS
Constitutive Signaling by Overexpressed ERBB2	1	190.3×	0.020	NRAS
ALK mutants bind TKIs	1	190.3×	0.020	ALK
p38MAPK events	1	175.7×	0.020	NRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	175.7×	0.020	NRAS
Signaling by PDGFRA extracellular domain mutants	1	175.7×	0.020	NRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to vitamin B1	1	3370.4×	0.011	MDM2
response to formaldehyde	1	3370.4×	0.011	MDM2
response to environmental enrichment	1	1685.2×	0.011	ALK
response to ether	1	1123.5×	0.011	MDM2
response to water-immersion restraint stress	1	1123.5×	0.011	MDM2
pyrimidine dimer repair by nucleotide-excision repair	1	842.6×	0.011	ERCC1
obsolete syncytium formation	1	842.6×	0.011	ERCC1
traversing start control point of mitotic cell cycle	1	842.6×	0.011	MDM2
regulation of dopamine receptor signaling pathway	1	842.6×	0.011	ALK
telomeric DNA-containing double minutes formation	1	842.6×	0.011	ERCC1
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	842.6×	0.011	MDM2
positive regulation of t-circle formation	1	842.6×	0.011	ERCC1
negative regulation of protection from non-homologous end joining at telomere	1	842.6×	0.011	ERCC1
swimming behavior	1	674.1×	0.011	ALK
cellular response to alkaloid	1	674.1×	0.011	MDM2
cellular response to UV-C	1	674.1×	0.011	MDM2
mitotic recombination	1	561.7×	0.011	ERCC1
negative regulation of telomere maintenance	1	561.7×	0.011	ERCC1
post-embryonic hemopoiesis	1	561.7×	0.011	ERCC1
response to stress	1	481.5×	0.011	ALK
cellular response to antibiotic	1	481.5×	0.011	MDM2
fibroblast activation	1	481.5×	0.011	MDM2
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	481.5×	0.011	MDM2
atrial septum development	1	421.3×	0.012	MDM2
peptidyl-tyrosine autophosphorylation	1	374.5×	0.013	ALK
response to magnesium ion	1	280.9×	0.014	MDM2
t-circle formation	1	280.9×	0.014	ERCC1
phosphorylation	1	259.3×	0.014	ALK
UV-damage excision repair	1	259.3×	0.014	ERCC1
atrioventricular valve morphogenesis	1	240.7×	0.014	MDM2

Therapeutics

Drugs indicated for this disease

2 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Nivolumab	Approved (phase 4)
Pemetrexed	Approved (phase 4)
Atezolizumab	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Nadofaragene Firadenovec	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)
Vorinostat	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dasatinib Anhydrous, Defactinib, Dovitinib, Doxorubicin, Everolimus, Lenvatinib, Lurbinectedin, Methotrexate, Nintedanib, Pegargiminase, Porfimer Sodium, Regramostim, Tivantinib, Toripalimab, Trabectedin, Trabedersen.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 2

Druggability breadth: 5 of 5 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
ALK	CERITINIB
MDM2	NITROFURANTOIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALK	61	4
MDM2	14	4
NRAS	1	1
RNF2	0	0
ERCC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
NITROFURANTOIN	4	MDM2
APOMORPHINE	4	MDM2
CYTARABINE	4	MDM2
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1
MDM2	1,007	Binding:979, Functional:28
ERCC1	28	Binding:28
NRAS	18	Binding:18
RNF2	16	Binding:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNF2	2.3.2.27	RING-type E3 ubiquitin transferase
ALK	2.7.10.1	receptor protein-tyrosine kinase
MDM2	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ALK	1,815
MDM2	1,007

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
NITROFURANTOIN	4	MDM2
APOMORPHINE	4	MDM2
CYTARABINE	4	MDM2
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	ALK, MDM2
B	Phased (≥1) drug, not yet approved	1	NRAS
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	RNF2, ERCC1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF2	16	—
ERCC1	28	—

Clinical trials & evidence

Clinical trials

Clinical trials: 113.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	41
PHASE1	26
Not specified	22
PHASE1/PHASE2	19
PHASE3	4
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01098266	PHASE3	COMPLETED	NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed
NCT03710876	PHASE3	COMPLETED	Efficacy & Safety of rAd-IFN Administered With Celecoxib & Gemcitabine in Patients With Malignant Pleural Mesothelioma
NCT04158141	PHASE3	TERMINATED	Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma
NCT04334759	PHASE3	COMPLETED	DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
NCT01064648	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma
NCT02535312	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin
NCT03074513	PHASE2	ACTIVE_NOT_RECRUITING	Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors
NCT03126630	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma
NCT04400539	PHASE2	RECRUITING	The IMmunotherapy Pleural 5-ALA PDT
NCT05425576	PHASE2	NOT_YET_RECRUITING	OT-101 in Combination With Pembrolizumab in Subjects With Malignant Pleural Mesothelioma Failing to Respond to Checkpoint Inhibition
NCT05765084	PHASE1/PHASE2	RECRUITING	Integration of the PD-L1 Inhibitor Atezolizumab and WT1/DC Vaccination Into Platinum/Pemetrexed-based First-line Treatment for Epithelioid Malignant Pleural Mesothelioma
NCT06318286	PHASE2	RECRUITING	Study of Pembrolizumab Plus Chemotherapy With Lenvatinib for Malignant Pleural Mesothelioma
NCT07510815	PHASE1/PHASE2	RECRUITING	Dual-Target MSLN/FAP CAR-NK Cells for Pleural and Peritoneal Mesothelioma
NCT00165503	PHASE2	TERMINATED	Pleurectomy/Decortication With Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin With Sodium Thiosulfate
NCT00165516	PHASE2	COMPLETED	Extrapleural Pneumonectomy With Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin With Amifostine and Sodium Thiosulfate
NCT00272558	PHASE2	COMPLETED	Study of Carboplatin and Vinorelbine in Malignant Pleural Mesothelioma
NCT00386815	PHASE2	COMPLETED	Safety Confirmation Study of Pemetrexed Plus Cisplatin in Patients With Malignant Pleural Mesothelioma
NCT00484276	PHASE2	COMPLETED	Study of NGR-hTNF as Single Agent in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma
NCT00700336	PHASE1/PHASE2	COMPLETED	Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II)
NCT00738582	PHASE2	COMPLETED	An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma
NCT00797719	PHASE1/PHASE2	COMPLETED	Short Neoadjuvant Hemithoracic IMRT for MPM
NCT00886028	PHASE2	UNKNOWN	Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma
NCT01024946	PHASE2	COMPLETED	Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity
NCT01112293	PHASE2	COMPLETED	Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma
NCT01211275	PHASE1/PHASE2	COMPLETED	Standard Chemotherapy With of Without Axitinib in Malignant Mesothelioma
NCT01243632	PHASE2	COMPLETED	Gemcitabine in Long Infusion and Cisplatin for Malignant Pleural Mesothelioma Treatment
NCT01265433	PHASE2	COMPLETED	Galinpepimut-S (WT-1 Analog Peptide) Vaccine in Malignant Pleural Mesothelioma After Combined Modality Therapy
NCT01279967	PHASE2	UNKNOWN	A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma
NCT01353482	PHASE1/PHASE2	WITHDRAWN	A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma
NCT01358084	PHASE2	COMPLETED	Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
NCT01486368	PHASE2	COMPLETED	A Phase II Study of PF-03446962 in Patients With Advanced Malignant Pleural Mesothelioma
NCT01644994	PHASE1/PHASE2	COMPLETED	Intracavitary Cisplatin-Fibrin Localized Chemotherapy After P/D or EPP for Malignant Pleural Mesothelioma
NCT01721018	PHASE1/PHASE2	COMPLETED	Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma.
NCT01769547	PHASE2	TERMINATED	A Phase II Study of Single-agent DOVitinib in Advanced Malignant PlEural Mesothelioma Which Has Progressed Following Prior Platinum-Antifolate Chemotherapy
NCT01869023	PHASE2	UNKNOWN	Phase II Study of Six Hours Low Dose Gemcitabine Plus Cisplatin in the Treatment for Advanced Pleural Mesothelioma
NCT01870609	PHASE2	TERMINATED	Placebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma
NCT02004028	PHASE2	TERMINATED	Window of Opportunity Study of VS-6063 (Defactinib) in Surgical Resectable Malignant Pleural Mesothelioma Participants
NCT02049060	PHASE1/PHASE2	COMPLETED	Study of the Combination of Tivantinib Plus Pemetrexed and Carboplatin
NCT02194231	PHASE2	COMPLETED	ATREUS - Phase II Study on the Activity of Trabectedin in Patients With Malignant Pleural Mesothelioma (MPM)
NCT02347917	PHASE1/PHASE2	COMPLETED	A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SODIUM THIOSULFATE	4	4
CELECOXIB	4	2
NINTEDANIB	4	2
AMIFOSTINE	4	1
AXITINIB	4	1
DURVALUMAB	4	1
IPILIMUMAB	4	1
TRABECTEDIN	4	1
VORINOSTAT	4	1
DEFACTINIB	3	4
CEDIRANIB MALEATE	3	1
DOVITINIB	3	1
GALINPEPIMUT-S	3	1
NADOFARAGENE FIRADENOVEC	3	1
NAPABUCASIN	3	1
PEGARGIMINASE	3	1
PLATINUM	3	1
REGRAMOSTIM	3	1
TIVANTINIB	3	1
METHOXYAMINE	2	2
AMATUXIMAB	2	1
ANETUMAB RAVTANSINE	2	1
ASCRINVACUMAB	2	1
CBP-501	2	1
FRESOLIMUMAB	2	1
TETRAHYDROURIDINE	2	1
APG-2449	1	1
ELIMUSERTIB	1	1
CHEMBL3753202	0	4
CHEMBL5412235	0	4

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 7 predictive associations from 7 curated evidence items; also 2 prognostic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
MDM2 EXPRESSION	Pemetrexed + Cisplatin	Resistance	CIViC B	EID827
EML4::ALK Fusion	Alectinib	Sensitivity/Response	CIViC C	EID9228
EML4::ALK Fusion AND ALK I1171N AND ALK L1196M	Lorlatinib	Sensitivity/Response	CIViC C	EID11113
EML4::ALK Fusion AND ALK G1202R AND ALK I1171N AND ALK L1196M	Lorlatinib	Resistance	CIViC C	EID11114
EML4::ALK Fusion AND ALK I1171N AND ALK L1196M	Alectinib	Resistance	CIViC C	EID11115
BAP1 Loss	EPZ011989	Sensitivity/Response	CIViC D	EID8329
BAP1 Mutation	CDK4/6 Inhibition	Sensitivity/Response	CIViC D	EID12008