Table 2:
Inhibitors of TGFβ signaling in various cancers that are in clinical trial.
| Target molecule | Drug Name | Clinical trial phase | Cancer Type | Result |
|---|---|---|---|---|
| TGF-β1, 2 ligands | Fresolimum ab (GC-1008) (Human monoclonal-antibody) | Phase I NCT00356460 | Advanced malignant melanoma or renal cell carcinoma (metastatic or non-resectable with at least one previous therapy) | Well tolerated. Preliminary antitumor activity needing further studies. |
| Phase I, II NCT02581787 | Non-small cell lung carcinoma (Stage IA, IB, non-operable, high surgical risk or patient refuses surgery) | With stereotactic ablative radiotherapy. Result not yet posted. | ||
| Phase II NCT01401062 | Metastatic breast cancer (persistent or recurrent with at least one failed therapy (endocrine or chemotherapy) | With local radiation therapy. Well tolerated. Showed higher systemic immune response and OS. | ||
| Phase II NCT0112293 | Relapsed malignant pleural mesothelioma (1-2 previous systemic therapies, at least one therapy with pemetrexed) | Result not yet posted. | ||
| ALK1 (type 1 subclass of TGF-β receptor) | PF-03446962 (Human monoclonal-antibody) | Phase II NCT01486368 | Advanced malignant pleural mesothelioma (disease progression after treatment with one line of platinum-based doublet chemotherapy) | Well tolerated but failed to show efficacy. |
| Phase I NCT01911273 | Advanced hepatocellular carcinoma (disease progression or intolerance after treatment with VEGFR-TKIs) | Well tolerated with modest single agent antitumor activity, support further evaluation. | ||
| Phase I NCT00557856 | Advanced solid tumors (treatment refractory or no available treatment) | Well tolerated. Single agent antitumor activity. | ||
| TGFβRI | Galunisertib (LY-2157299) (Small molecule inhibitor) | Phase II NCT01582269 | Recurrent intracranial glioblastoma (Grade IV) | With lomustine. Combination failed to show improved OS. |
| Phase I, II NCT03470350 | Metastatic colorectal cancer (chemotherapy resistant activated TGF-β signature like) | With capecitabine. Result not yet verified. | ||
| Phase I NCT02154646 | Advanced or metastatic pancreatic cancer (tumors not manageable by resection) | With gemcitabine. Well tolerated. Combination showed efficacy. Further investigation needed. | ||
| Phase I NCT02734160 | Recurrent metastatic pancreatic adenocarcinoma (disease progression, refractory or intolerant to <2 systemic regimens) | With durvalumab. Result not yet posted. | ||
| Phase I NCT02240433 | Unresectable hepatocellular carcinoma | With Sorafenib. Well tolerated, Promising antitumor activity | ||
| Phase I NCT02906397 | Advanced hepatocellular carcinoma (inoperable, not eligible, failed or discontinued sorafenib therapy) | With stereotactic body radiotherapy. Result not yet posted |
Abbreviations: OS= Overall survival