Tremelimumab

Summary

Tremelimumab (CHEMBL2108658) is an approved antibody (ATC L01FX20) targeting CTLA4; indicated across 61 conditions including hepatocellular carcinoma and neoplasm; with CIViC clinical evidence for 3 variant-indication associations (e.g. KEAP1 Mutation in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Antibody
• ATC class: L01FX20
• Targets: 1 (CTLA4)
• Indications: 61 conditions
• Clinical trials: 230
• Precision-oncology evidence (CIViC): 3 variant–indication associations

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2108658
Name	Tremelimumab
Type	Antibody
Max phase	4
ATC	L01FX20

Also known as: CP-675,206, CP-675206, Imjudo, PF-06753388, TICILIMUMAB, Tremelimumab, Tremelimumab (genetical recombination), Tremelimumab actl, Tremelimumab astrazeneca, Tremelimumab-actl, TREMELIMUMAB

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CTLA4	cytotoxic T-lymphocyte-associated protein 4 (CD152)	Binding	8.91	0%	P16410

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 1 target gene(s): CTLA4.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Co-stimulation by CD28	1	CTLA4
Co-inhibition by CTLA4	1	CTLA4
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	CTLA4

Dominant GO biological processes

GO term	Targets
adaptive immune response	1
immune response	1
DNA damage response	1
negative regulation of B cell proliferation	1
negative regulation of T cell proliferation	1
positive regulation of apoptotic process	1
negative regulation of regulatory T cell differentiation	1
T cell receptor signaling pathway	1
B cell receptor signaling pathway	1
negative regulation of T cell receptor signaling pathway	1
negative regulation of T cell activation	1
immune system process	1
regulation of T cell proliferation	1

Indications & clinical

Indications

61 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
hepatocellular carcinoma	4	MONDO:0007256	EFO:0000182
neoplasm	4	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	4	MONDO:0005233	EFO:0003060
melanoma	3	MONDO:0005105	EFO:0000756
head and neck squamous cell carcinoma	3	MONDO:0010150	EFO:0000181
metastatic melanoma	3	MONDO:0005191	EFO:0002617
cutaneous melanoma	3	MONDO:0005012	EFO:0000389
renal cell carcinoma	3	MONDO:0005086	EFO:0000681
small cell lung carcinoma	3	MONDO:0008433	EFO:0000702
squamous cell lung carcinoma	3	MONDO:0005097	EFO:0000708
urothelial carcinoma	3	MONDO:0040679	EFO:0008528
clear cell renal carcinoma	3	MONDO:0005005	EFO:0000349
mesothelioma	2	MONDO:0005065	EFO:0000588
breast carcinoma	2	MONDO:0004989	EFO:0000305
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
glioblastoma	2	MONDO:0018177	EFO:0000519
gastric adenocarcinoma	2	MONDO:0005036	EFO:0000503
germ cell tumor	2	MONDO:0005040	EFO:0000514
prostate adenocarcinoma	2	MONDO:0005082	EFO:0000673
sarcoma	2	MONDO:0005089	EFO:0000691
HIV infectious disease	2	MONDO:0005109	EFO:0000764
ovarian carcinoma	2	MONDO:0005140	EFO:0001075
biliary tract neoplasm	2	MONDO:0005304	EFO:0003891
colorectal neoplasm	2	MONDO:0005335	EFO:0004142
upper aerodigestive tract neoplasm	2	MONDO:0005398	EFO:0004284
thyroid gland follicular carcinoma	2	MONDO:0005034	EFO:0000501
thyroid gland papillary carcinoma	2	MONDO:0005075	EFO:0000641
fallopian tube carcinoma	2	MONDO:0006206	EFO:1000251
colorectal adenocarcinoma	2	MONDO:0005008	EFO:0000365
lung neuroendocrine neoplasm	2	MONDO:0005454	EFO:0005220
cholangiocarcinoma	2	MONDO:0019087	EFO:0005221
intrahepatic cholangiocarcinoma	2	MONDO:0003210	EFO:1001961
soft tissue sarcoma	2	MONDO:0018078	EFO:1001968
gastric neoplasm	2	MONDO:0021085	MONDO:0001056
fallopian tube neoplasm	2	MONDO:0021092	MONDO:0002158
seminoma	2	MONDO:0003001	MONDO:0003001
dysgerminoma	2	MONDO:0003002	MONDO:0003002
breast neoplasm	2	MONDO:0021100	MONDO:0007254
ovarian cancer	2	MONDO:0008170	MONDO:0008170
lung neoplasm	2	MONDO:0021117	MONDO:0008903
oral cavity squamous cell carcinoma	2	MONDO:0004958	EFO:0000199
prostate carcinoma	2	MONDO:0005159	EFO:0001663
pancreatic neoplasm	2	MONDO:0021040	EFO:0003860
uveal melanoma	2	MONDO:0006486	EFO:1000616
female reproductive organ cancer	2	MONDO:0001416	EFO:1001331
bile duct neoplasm	2	MONDO:0021662	MONDO:0003059
pancreatic ductal adenocarcinoma	2	MONDO:0005184	MONDO:0005184
lymphoma	1	MONDO:0005062	EFO:0000574
myelodysplastic syndrome	1	MONDO:0018881	EFO:0000198
diffuse large B-cell lymphoma	1	MONDO:0018905	EFO:0000403
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
peritoneal neoplasm	1	MONDO:0006901	EFO:1001100

9 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 230.

Phase distribution

Phase	Trials
PHASE2	118
PHASE1	51
PHASE1/PHASE2	28
PHASE3	20
EARLY_PHASE1	6
Not specified	6
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02453282	PHASE3	ACTIVE_NOT_RECRUITING	Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)
NCT02516241	PHASE3	ACTIVE_NOT_RECRUITING	Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer
NCT02542293	PHASE3	ACTIVE_NOT_RECRUITING	Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)
NCT03043872	PHASE3	ACTIVE_NOT_RECRUITING	Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)
NCT03164616	PHASE3	ACTIVE_NOT_RECRUITING	Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).
NCT03288532	PHASE3	RECRUITING	Renal Adjuvant MultiPle Arm Randomised Trial
NCT03682068	PHASE3	ACTIVE_NOT_RECRUITING	Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
NCT03703297	PHASE3	ACTIVE_NOT_RECRUITING	Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy
NCT04585490	PHASE3	RECRUITING	Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC
NCT04960709	PHASE3	ACTIVE_NOT_RECRUITING	Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin
NCT05301842	PHASE3	ACTIVE_NOT_RECRUITING	Evaluate Durvalumab and Tremelimumab +/- Lenvatinib in Combination With TACE in Patients With Locoregional HCC
NCT05557838	PHASE3	RECRUITING	Study of Durvalumab Plus Tremelimumab as First-line Treatment in Chinese Patients With Unresectable Hepatocellular Carinoma
NCT05883644	PHASE3	ACTIVE_NOT_RECRUITING	Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (HCC)
NCT06109272	PHASE2/PHASE3	RECRUITING	A Study to Assess the Dose, Adverse Events, and Change in Disease Activity of Livmoniplimab as an Intravenous (IV) Solution in Combination With Budigalimab as an IV Solution in Adult Participants With Hepatocellular Carcinoma (HCC)
NCT06921785	PHASE3	RECRUITING	Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma
NCT07166406	PHASE3	RECRUITING	Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial
NCT00257205	PHASE3	COMPLETED	CP-675,206 Versus Either Dacarbazine Or Temozolomide In Patients Without Prior Therapy
NCT02352948	PHASE3	COMPLETED	A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
NCT02369874	PHASE3	COMPLETED	Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer
NCT02551159	PHASE3	COMPLETED	Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer
NCT03084471	PHASE3	COMPLETED	An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.
NCT01843374	PHASE2	ACTIVE_NOT_RECRUITING	Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma
NCT02029001	PHASE2	RECRUITING	Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment
NCT02519348	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma
NCT02571725	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	PARP-inhibition and CTLA-4 Blockade in BRCA-deficient Ovarian Cancer
NCT02888743	PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer
NCT02962063	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab, an Anti-PDLI Antibody, and Tremelimumab, an Anti-CTLA4 Antibody, and Chemoradiation Before Surgery for Esophageal Cancer
NCT03057106	PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC
NCT03158064	PHASE2	ACTIVE_NOT_RECRUITING	Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors
NCT03283605	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Immunotherapy and SBRT for Metastatic Head and Neck Carcinomas
NCT03317158	PHASE1/PHASE2	RECRUITING	Modern Immunotherapy in BCG-Unresponsive, BCG-Relapsing and High Risk BCG-Naive Non-Muscle Invasive Urothelial Carcinoma of the Bladder
NCT03385655	PHASE2	ACTIVE_NOT_RECRUITING	Prostate Cancer Biomarker Enrichment and Treatment Selection
NCT03410615	PHASE2	ACTIVE_NOT_RECRUITING	Cisplatin + Radiotherapy vs Durvalumab + Radiotherapy Followed by Durvalumab vs Durvalumab + Radiotherapy Followed by Tremelimumab + Durvalumab in Intermediate-Risk HPV-Positive Oropharyngeal SCC
NCT03482102	PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
NCT03539822	PHASE1/PHASE2	RECRUITING	Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies
NCT03601455	PHASE2	ACTIVE_NOT_RECRUITING	Radiation Therapy and Durvalumab With or Without Tremelimumab in Treating Participants With Unresectable, Locally Advanced, or Metastatic Bladder Cancer
NCT03606967	PHASE2	RECRUITING	Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer
NCT03704480	PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab + Tremelimumab ± Paclitaxel in Advanced BTC After Platinum Chemotherapy.
NCT03784066	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab With or Without Tremelimumab in Resectable Locally Advanced Squamous Cell Carcinoma of the Oral Cavity
NCT03847649	PHASE2	RECRUITING	A Phase II Study of Durvalumab Treatment - Substudy A: In Patients Who Discontinued Prior Checkpoint Therapy Due to Immune Related Toxicity - Substudy B: For Continued Treatment (+/- Tremelimumab) of Patients Previously Enrolled to Completed CCTG Studies

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
KEAP1 Mutation	Lung Non-small Cell Carcinoma	Sensitivity/Response	Durvalumab Regimen + Chemotherapy + Tremelimumab	CIViC A	EID12419
TMB High	Colorectal Cancer	Sensitivity/Response	Tremelimumab + Durvalumab	CIViC B	EID12042
TMB High	Lung Non-small Cell Carcinoma	Sensitivity/Response	Durvalumab + Tremelimumab	CIViC B	EID12799

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).