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The first immune brake ever targeted for cancer; releasing it won a Nobel Prize and cures a fraction of melanomas. This dossier gathers the 10 products (3 approved), 145 trials, 3 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Competes with CD28 for B7 ligands during T-cell priming; also depletes regulatory T cells via Fc effector function.
| Modality | Approved | Phase 3 | Phase 2 |
|---|---|---|---|
| Antibody 7 | |||
| Bispecific antibody 2 | - | ||
| fusion protein or cytokine 1 | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
| 3 | Active | A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer | - | ||
CheckMate 8HW NCT04008030 | 3 | Positive | MSI-H/dMMR metastatic colorectal cancer, all lines: nivolumab + ipilimumab vs nivolumab vs chemotherapy | First-line PFS 54.1 vs 5.9 months (HR 0.21); combination vs nivolumab PFS HR 0.62. | |
CheckMate 9DW NCT04039607 | 3 | Positive | First-line unresectable HCC: nivolumab + ipilimumab vs lenvatinib or sorafenib | OS 23.7 vs 20.6 months, HR 0.79; ORR 36% vs 13%. | |
COMPASSION-16 / AK104-303 NCT04982237 | 3 | Positive | Persistent, recurrent, or metastatic cervical cancer, first line (China): cadonilimab (PD-1×CTLA-4 bispecific) + platinum-paclitaxel ± bevacizumab vs placebo + chemotherapy ± bevacizumab | OS HR 0.64; PFS HR 0.62. | |
NADINA NCT04949113 | 3 | Positive | Resectable macroscopic stage III melanoma: two cycles neoadjuvant ipilimumab + nivolumab then surgery (adjuvant only if incomplete response) vs surgery then 12 cycles adjuvant nivolumab | 12-month EFS 83.7% vs 57.2%; HR 0.32. | |
CheckMate 915 NCT03068455 | 3 | Negative | Resected stage IIIB to IV melanoma: adjuvant nivolumab plus low-dose ipilimumab against nivolumab alone | Nivolumab plus low-dose ipilimumab did not improve recurrence-free survival over nivolumab alone after resection of stage III to IV melanoma. | |
COSMIC-313 NCT03937219 | 3 | Mixed | Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab | PFS HR 0.73; OS HR 1.02 (no benefit). | |
HIMALAYA NCT03298451 | 3 | Positive | First-line unresectable HCC: STRIDE (single priming dose tremelimumab + durvalumab) vs sorafenib | OS HR 0.78; 5-year OS 19.6% vs 9.4%. | |
| 3 | Active | A Phase III, Randomized, Multi-Center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Patients With Metastatic Non Small-Cell Lung Cancer (NSCLC) (POSEIDON) | Durvalumab with chemotherapy improved progression-free survival (5.5 against 4.8 months, hazard ratio 0.74, p=0.0009) but not significantly overall survival; adding a limited course of tremelimumab improved both (overall survival 14.0 against 11.7 months, hazard ratio 0.77, p=0.0030). | ||
| 3 | Active | A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC). | - | ||
CheckMate 648 NCT03143153 | 3 | Positive | First-line advanced oesophageal squamous cell carcinoma: nivolumab + chemotherapy, or nivolumab + ipilimumab (chemotherapy-free), vs chemotherapy | PD-L1 ≥1%: OS 15.4 vs 9.1 months (nivo + chemo, HR 0.54); 13.7 vs 9.1 months (nivo + ipi, HR 0.64). | |
DREAMseq (ECOG-ACRIN EA6134) NCT02224781 | 3 | Positive | Untreated BRAF V600 metastatic melanoma: nivolumab + ipilimumab then dabrafenib + trametinib at progression, vs the reverse sequence | 2-year OS 71.8% vs 51.5%. | |
| 3 | Negative | Previously treated stage 4 squamous non-small-cell lung cancer with no matching biomarker and no prior immunotherapy: nivolumab plus ipilimumab against nivolumab alone | Nivolumab plus ipilimumab did not improve survival over nivolumab alone; the trial closed for futility. | ||
| 3 | Active | A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Cancer | - | ||
CheckMate 743 NCT02899299 | 3 | Positive | Unresectable pleural mesothelioma, first line: nivolumab + ipilimumab vs platinum-pemetrexed | OS 18.1 vs 14.1 months, HR 0.74; 5-year OS 14% vs 6%. | |
CheckMate 9LA NCT03215706 | 3 | Positive | Treatment-naive stage IV or recurrent non-small-cell lung cancer of any PD-L1 level: nivolumab 360 mg every three weeks with ipilimumab 1 mg/kg every six weeks plus two cycles of histology-based platinum doublet chemotherapy, versus four cycles of chemotherapy alone, with overall survival as the primary endpoint | Median overall survival 14.1 against 10.7 months at the interim analysis (hazard ratio 0.69, p=0.00065), and 15.6 against 10.9 months with longer follow-up. | |
CASPIAN NCT03043872 | 3 | Positive | First-line extensive-stage SCLC: platinum-etoposide + durvalumab (± tremelimumab) vs platinum-etoposide | OS 13.0 vs 10.3 months, HR 0.73; 3-year OS 17.6% vs 5.8%. | |
CheckMate 227 NCT02477826 | 3 | Positive | Untreated stage IV or recurrent non-small-cell lung cancer without EGFR or ALK alterations: nivolumab plus ipilimumab, nivolumab plus chemotherapy or nivolumab alone against platinum chemotherapy, analysed by PD-L1 expression | Nivolumab plus ipilimumab improved overall survival over chemotherapy in PD-L1-positive advanced non-small-cell lung cancer; approved in the United States in May 2020. | |
| 3 | Active | A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC)(MYSTIC). | - | ||
CheckMate 214 NCT02231749 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + ipilimumab vs sunitinib | 8-year OS HR 0.72 (ITT), 0.69 (intermediate/poor risk). | |
CheckMate 238 NCT02388906 | 3 | Positive | Resected stage IIIB, IIIC or IV melanoma: one year of adjuvant nivolumab versus ipilimumab 10 mg/kg | 12-month recurrence-free survival 70.5% vs 60.8% (HR 0.65); 4-year recurrence-free survival 51.7% vs 41.2%; no overall survival difference. | |
CheckMate 067 NCT01844505 | 3 | Positive | Untreated advanced melanoma: nivolumab + ipilimumab vs nivolumab vs ipilimumab | 10-year OS 43% vs 37% vs 19%. | |
KEYNOTE-006 NCT01866319 | 3 | Positive | Advanced melanoma, ≤1 prior systemic therapy: pembrolizumab (two schedules) vs ipilimumab | 10-year OS 34.0% vs 23.6%. | |
CA184-043 NCT00861614 | 3 | Negative | Metastatic castration-resistant prostate cancer with at least one bone metastasis, progressing after docetaxel: bone-directed radiotherapy of 8 Gy in one fraction followed by ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses, then maintenance every 3 months, with overall survival as the primary endpoint | Median overall survival 11.2 against 10.0 months (hazard ratio 0.85, 95 percent confidence interval 0.72 to 1.00, p=0.053), missing significance; hazard ratio 1.46 in the first 5 months and 0.60 beyond 12 months. Grade 3 to 4 immune-related adverse events 26 against 3 percent, with four treatment-related deaths. | |
| 3 | Active | A Double-Blind Placebo-Controlled Comparative Randomized Clinical Study of the Efficacy and Safety of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma | - | ||
| 3 | Recruiting | A Randomized, Double-blind, Phase III Clinical Study Comparing the Efficacy and Safety of Cadonilimab Plus Oxaliplatin and Tegafur-Gimeracil-Oteracil Potassium (SOX) Versus Placebo Plus SOX as Perioperative Treatment for Patients With Resectable Gastric and Gastroesophageal Junction (G/GEJ) Adenocarcinoma | - | ||
| 3 | Recruiting | A Randomized, Double-blind, Phase III Clinical Study on the Efficacy and Safety of AK104 Versus Placebo as Adjuvant Therapy for Hepatocellular Carcinoma With High Risk of Recurrence After Curative Resection | - | ||
| 3 | Recruiting | A Randomized, Double-blind, Multicenter Phase III Study to Evaluate the Consolidation Therapy of AK104 Versus Sugemalimab in Patients With Unresectable Locally Advanced Non-Small Cell Lung Cancer Who Have Not Progressed After Concurrent or Sequential Chemoradiotherapy | - | ||
| 3 | Active | A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate AK104 Combined With Chemoradiotherapy For The Treatment of Locally Advanced Cervical Cancer | - |
No recorded escape route names this target.
How T cells decide to attack. A T cell needs to see the target (TCR-MHC) and get a 'go' signal (CD28). PD-1 and CTLA-4 are 'stop' signals; tumours exploit them. Checkpoint inhibitors remove the stop.
Which nodes have drugs →Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.
Which nodes have drugs →A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.
Which nodes have drugs →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| MSI by PCR (Promega MSI Analysis System and equivalents) Promega and others · LDT | PCR | Instability at two or more of five markers (MSI-high); NGS panels report MSI from hundreds of loci |
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"CTLA-4" OR ABSTRACT:"CTLA-4" OR TITLE:"CTLA4" OR ABSTRACT:"CTLA4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CTLA-4, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/ctla4.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/ctla4.json. Licence CC BY-NC 4.0.