Table 1. Summary of clinical trials for TGFβ inhibitory drugs.
| Drug; company |
Type | Targets | Disease applications |
Stage | Clinical trial identifiers |
Summary of results | Refs |
|---|---|---|---|---|---|---|---|
| Trabedersen (AP12009); Antisense Pharma |
Antisense oligo | TGFβ2 ligand |
Glioblastoma | Phase I/IIb | NCT00431561 | Safe | 70,73,74 |
| Pancreatic cancer, MetM, colon cancer |
Phase I | NCT00844064 | Pancreatic cancer trials continue |
84 | |||
| Glioblastoma | Phase III | NCT00761280 | Glioblastoma trials stopped in March 2012 owing to advances in standard of care and neurosurgery (Box 4) |
||||
| Belagen- pumatucel-L (Lucanix); NovaRx |
Antisense gene-modified allogeneic tumour cell vaccine |
TGFβ2 | NSCLC | Phase III | NCT00676507 | Well tolerated in 75 patients; survival advantage justifies further Phase III evaluation |
85-87 |
| Disitertide (P144); Digna Biotech |
Peptide | Peptide based on TβRIIIthat blocks ligand binding to receptors |
Skin fibrosis in systemic sclerosis |
Phase II |
NCT00574613, NCT00781053 |
Preclinical efficacy in peritoneal fibrosis associated with peritoneal dialysis, renal and cardiac fibrosis, corneal haze and retinal AMD; safety and efficacy in Phase IIa clinical trial for scleroderma/ skin fibrosis |
75-78 |
| Lerdelimumab (CAI-152); Cambridge Antibody Technology |
Humanized antibody |
TGFβ2 ligand |
Reduction of scarring after glaucoma surgery |
Phase III (complete) | Safe; ineffective in reducing scarring in Phase III trial |
88,89 | |
| Metelimumab (CAI-192); Cambridge Antibody Technology |
Humanized Antibody |
TGFβ1 ligand |
Diffuse systemic sclerosis |
Phase I/II | NCT00043706 | Ineffective when systemically administered in doses up to 10 mg per kg |
90 |
| Fresolimumab (GC-1008); Cambridge Antibody Technology/ Genzyme/ Sanofi |
Humanized antibody |
TGFβ1, TGFβ2 and TGFβ3 ligands |
Focal segmental glomerulosclerosis |
Phasel | NCT00464321 | Completed and safe; plans to progress |
92 |
| Systemic sclerosis | Phasel | NCT01284322 | Still recruiting | - | |||
| Study ongoing | - | ||||||
| Completed, no results | - | ||||||
| Myelofibrosis | Phasel | NCT01291784 | See Box 4 | 93 | |||
| TPF | Phasel | NCT00125385 | See Box 4 | 93 | |||
| Renal cell carcinoma |
Phasel | NCT00356460 | See Box 4 | 93 | |||
| Malignant melanoma |
Phasel | NCT00356460 | See Box 4 | 81 | |||
| Metastatic breast cancer (with radiotherapy) |
Phasel | NCT01401062 | Active and recruiting patients | - | |||
| Relapsed malignant pleural, mesothelioma |
Phase II | NCT01112293 | Ongoing but not recruiting participants |
- | |||
| LY2382770; Eli Lilly |
Humanized Antibody |
TGFβ1 | Diabetic kidney disease (fibrosis) |
Phase II | NCT01113801 | Safety and efficacy in protecting kidney function in patients with diabetic kidney disease; still recruiting |
- |
| SIX-100; Stromedix |
Antibody | aVβ6 integrin | Fibrosis | Phase II | NCT01371305 | Significant antifibrotic activity in preclinical models of lung, kidney and liver disease |
168 |
| LY2157299; Eli Lilly |
Small molecule | TβRI kinase |
Advanced-stage melanoma |
Phase II | NCI10038320 | See Box 4 | 82 |
| Recurrent glioblastoma |
Phase II | NCT01582269 | Recruiting; LY2157299 alone or with lomustine therapy versus lomustine alone in recurrent glioblastoma |
213 | |||
| Glioblastoma | Phase II | NCT01220271 | Recruiting; LY2157299 with temozolomide-based radiochemotherapy in newly diagnosed malignant glioma |
212 | |||
| Hepato cellular carcinoma |
Phase II | NCT01246986 | Recruiting | - | |||
| Advanced pancreatic carcinoma |
Phase II | NCT01373164 | Recruiting; comparison of gemcitabine with gemcitabine plus LY2157299 |
- | |||
| Dominant negative TGFBR2-modified CILs |
Recombinant T cells |
TβRII | Adoptive transfer of T cells expressing HER2 and ΔNTGFBR2 for lung cancer (HERCREEM) |
Phasel | NCT00889954 | No update on clinical trials | - |
| Dominant negative TGFBR2-modified CILs |
Recombinant T cells (a clinical grade retrovirus vector encoding dominant negative TβRII) |
TβRII | TGFβ-resistant LMP2A-specific CILs for EBV-positive lymphoma |
Phasel | NCT00368082 | Preclinical efficacy in tumour killing of TGFβ-secreting EBV-positive lymphoma; no update on clinical trials |
107 |
| Avotermin (Juvista); Renova |
Recombinant protein |
TGFβ3 | Scarring | Phase II | NCT004322111, NCT00656227 |
Thejuvista Phase II trial had not reached its primary or secondary efficacy end points as of February 2011 |
214 |
| Pirfenidone; lnterMune |
Small molecule, not TGFβ-specific |
IPF, glomerulosclerosis and diabetic kidney disease, pathological skin scarring |
Phase III | Multiple trials | First drug approved for IPF in Europe |
162 | |
| Losartan; Merck and Co. |
Small molecule, not TGFβ-specific |
AT1 | Marfan syndrome (MFS) |
Phase I/II |
NCT00723801, NCT00763893, NCT00782327 |
Reduction of aortic aneurysm in mouse model of MFS; clinical trials in progress to reduce aortic root dilation and cardiac muscle stiffness in patients with MFS |
12,182 |
| Tranilast; Kissei Pharmaceuticals |
Small molecule, not TGFβ-specific |
Unknown | Corneal primary pterygium |
Phase III | NCT01003613 | Tranilast reduces myofibroblast proliferation of corneal myofibroblasts in vitro and may be a novel adjuvant therapy for corneal keloid |
185, 215,216 |
| IMC-TR1; lmClone Systems/ Eli Lilly |
Humanized antibody |
TβRII | Mammary and colon cancer |
Phasel | NCT01646203 | Preclinical efficacy against primary tumour growth and metastasis through multiple effects on tumour, stroma and immune cells |
94 |
AMD, age-related macular degeneration; AT1, angiotensin II type 1 receptor; CTL, cytotoxic T lymphocyte; EBV, Epstein–Barrvirus; IPF, idiopathic pulmonary fibrosis; LMP2A, an EBV-specific antigen; MetM, metastatic melanoma; NSCLC, non-small-cell lung cancer; oligo, oligonucleotide; Tβ3R, TGFβ3 receptor; TGFβ, transforming growth factor-β; TGFBR2, gene encoding TβRII.