Table 1. Summary of TGFβ inhibitors in clinical development.
| Drug; company | Type | Targets | Disease applications | Stage | Clinical trial identifiers | Summary of results |
|---|---|---|---|---|---|---|
| Trabedersen (AP12009); Antisense Pharma | Antisense oligonucleotide | TGFβ2 ligand | Monotherapy vs. SOC in refractory GBM or anaplastic astrocytoma | Phase III | NCT00761280 | Non significant OS benefit (terminated due to low patient recruitment) |
| Monotherapy in melanoma | Phase I/II | NCT00844064 | Preliminary evidence of improved OS | |||
| Belagenpumatucel-L (Lucanix); NovaRx | Antisense gene-modified allogeneic tumour cell vaccine | TGFβ2 | Monotherapy as maintenance therapy in NSCLC | Phase III | NCT00676507 | OS benefit in patients with prior radiotherapy and/or randomized within 12 weeks of chemotherapy completion |
| Monotherapy as maintenance in high-risk ovarian cancer | Phase II/III | NCT02346747 | Preliminary evidence of improved relapse-free survival | |||
| Monotherapy vs. gemcitabine + docetaxel in Ewing’s sarcoma | Phase IIb | NCT02511132 | Ongoing | |||
| Combination with nivolumab in NSCLC after platinum-based therapy | Phase III | NCT02639234 | Ongoing | |||
| Combination with nivolumab for advanced or metastatic melanoma | Phase I | NCT02574533 | Ongoing | |||
| Combination with durvalumab for advanced women’s cancers | Phase II | NCT02725489 | Enrolling | |||
| Fresolimumab (GC-1008); Cambridge Antibody Technology/Genzyme/Sanofi | Humanized monoclonal antibody | TGFβ1, TGFβ2 and TGFβ3 ligands | Monotherapy in melanoma and renal cell carcinoma | Phase Ib | NCT00356460 | Preliminary evidence of antitumor activity |
| Relapsed malignant pleural, mesothelioma | Phase II | NCT01112293 | No partial or complete responses observed | |||
| Combination with RT in metastatic breast cancer | Phase II | NCT01401062 | High dose fresolimumab resulted in improved OS | |||
| Combination with RT in early stage NSCLC | Phase I/II | NCT02581787 | Recruiting | |||
| Galunisertib (LY2157299); Eli Lilly | Small molecule | TGFβRI kinase | LY2157299 alone or with lomustine therapy versus lomustine alone in recurrent glioblastoma | Phase II | NCT01582269 | No improved OS compared to lomustine alone |
| LY2157299 with temozolomide-based radiochemotherapy in newly diagnosed malignant glioma | Phase II | NCT01220271 | Ongoing | |||
| Monotherapy and in combination with sorafenib in hepatocellular carcinoma | Phase II | NCT01246986 | OS benefit in patients with >20% decrease in TGFβ1, AFP, and CDH1 levels from baseline; combination ongoing | |||
| Galunisertib + gemcitabine vs. gemcitabine in metastatic pancreatic cancer | Phase II | NCT01373164 | Trend to OS benefit | |||
| Combination with nivolumab in glioblastoma, NSCLC and hepatocellular carcinoma | Phase Ib | NCT02423343 | Ongoing | |||
| Combination with durvalumab in metastatic pancreatic cancer | Phase Ib | NCT02734160 | Ongoing | |||
| Combination with RT in metastatic breast cancer | Phase II | NCT02538471 | Ongoing | |||
| IMC-TR1; ImClone Systems/Eli Lilly | Humanized monoclonal antibody | TGFβRII | Advanced solid tumors | Phase I | NCT01646203 | Safe |
| M7824; EMD Serono | Humanized monoclonal bifunctional antibody | TGFβRII and PD-L1 | Advanced non-small cell lung cancer | Phase II | NCT03631706 | Ongoing |
Table compiled from the following sources: Akhurst and Hata 2012, Kang, Demaria et al. 2016, de Gramont, Faivre et al. 2017, Tolcher, Berlin et al. 2017, Formenti, Lee et al. 2018. GBM, glioblastoma multiforme; NSCLC, non-small cell lung cancer; SOC, standard of care; OS, overall survival.