From: Novel therapies emerging in oncology to target the TGF-β pathway
Study NCT Registry Number | Agent | Target(s) | Study Population | Number of Patients | Phase | Clinical Efficacy | Most Frequent Adverse Events |
---|---|---|---|---|---|---|---|
Small molecule receptor kinase inhibitors | |||||||
NCT02160106 | Vactosertib | TGF-β RI | Solid tumors | 29 | I | Pharmacokinetics | |
(TEW-7197) | 35 | I | Dosing model | ||||
NCT01682187 | Galunisertib (LY2157299) | TGF-β RI | Advanced solid tumors | 65 | I | Glioma population ORR 14% | Thrombocytopenia thrombosis, dyspnea |
NCT01582269 | Galunisertib ± Lomustine | TGF-β RI | Refractory glioma | 180 | II | mOS: Galunisertib 8 m, Lomustine 7 m, Both 6.5 m | Fatigue, nausea, vomiting |
NCT01220271 | Temozolomide RT ± Galunisertib | CT/RT TGF-β RI | GBM | 75 | Ib/II | mOS 18.2 vs. 17.9 m | Fatigue, nausea constipation |
NCT01373164 | Galunisertib ± Gemcitabine | TGF-β RI Chemotherapy | Inoperable or metastatic pancreatic | 170 | I/II | mOS 8.9 vs. 7.1 m | Neutropenia, thrombocytopenia |
NCT02154646 | Galunisertib + Gemcitabine | TGF-β RI Chemotherapy | Inoperable or metastatic pancreatic cancer | 9 | I | ORR 0% | Elevated liver enzymes |
NCT02734160 | Galunisertib + Durvalumab | TGF-β RI PD-L1 | Metastatic pancreatic cancer | 32 | I | ORR 3% mPFS 1.9 | Elevated liver enzymes neutropenia |
NCT02240433 | Galunisertib + Sorafenib | TGF-β RI TKI, Angiogenesis | Metastatic HCC | 14 | I | ORR 9% | Hypophosphatemia Hand-foot syndrome |
NCT01246986 | Galunisertib | TGF-β RI | Metastatic HCC | 147 | II | mPFS: 2.7 m (part A) 4.2 m (part B) | Neutropenia |
Antibodies | |||||||
NCT00356460 | Fresolimumab | TGF-β1, β2, β3 | Advanced melanoma Renal cell cancer | 29 | I | ORR 3 and 5% mPFS 2.75 m | Keratoacanthomas hyperkeratosis |
NCT01472731 | Fresolimumab RT | TGF-β1, β2, β3 | Glioma | 23 | II | ORR 0% | Fatigue, anemia keratoacanthomas |
NCT01646203 | LY3022859 | TGF-β RII | Advanced solid Tumors | 14 | I | Not reported | CRS |
Ligand Traps | |||||||
NCT04296942 | Bintrafusp alfa, BN-Brachyury, Entinostat, Adotrastuzumab Emtansine | TGF-β RII and PD-L1 | Advanced Stage Breast cancer | 19 | I | ORR 21% | Bullous pemphigoid increased lipase, colitis |
NCT03427411 | Bintrafusp alfa | TGF-β RII and PD-L1 | HPV-positive advanced solid tumors | 120 (estimated enrollment) | II | ORR 39% | Colitis, hypokalemia gastroparesis |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Pre-treated cervical tumors | 25 | I | ORR 28% | Hypokalemia |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Refractory head and neck cancer | 32 | I | ORR 22% | Keratoacanthomas hyperglycemia |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Pre-treated NSCLC | 80 | II | PD-L1 > 1%, ORR 40% PD-L1 > 80%,ORR 71% | Keratoacanthomas |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Pre-treated esophageal adenocarcinoma | 30 | I | ORR 20% | Anemia, pain |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Pre-treated gastric cancer | 31 | I | ORR 22% | Anemia, diarrhea, rash |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Pre-treated biliary tract cancer | 30 | I | ORR 23% | ILD |
NCT02517398 | Bintrafusp alfa | TGF-β RII and PD-L1 | Refractory colorectal cancer | 29 | I | ORR 3.4% | Anemia, fatigue enteritis |
NCT02631070 | Luspatercept | ActRIIb IgG1 | Very low, low or intermediate risk MDS | 229 | III | Transfusion independent > 8 weeks asthenia, nausea, 38% vs. 13% | Fatigue, diarrhea, |
Antisense nucleotides | |||||||
NCT00431561 | Trabedersen vs. Temozolomide/ Lomustine | TGF-β2 mRNA | Recurrent/ Refractory glioma | 142 | IIb | 6 m tumor control rate: Trabedersen 10uM: 33% Trabedersen 80uM: 20% Chemotherapy: 27% | Nervous disorders |
NCT00844064 | Trabedersen | TGF-β2 mRNA | Advanced tumors known to overproduce TGF-β2 | 62 | I | ||
Vaccines | |||||||
NCT01058785 | Belagenpumatucel-L | TGF-β2 Inhibition | NSCLC | 75 | II | ORR 15% | Pain, anemia fatigue |
NCT00676507 | Belagenpumatucel-L | TGF-β2 Inhibition | Inoperable or metastatic NSCLC | 532 | III | mOS 20 vs 17 m | Allergic reactions |
NCT02574533 | Vigil + Pembrolizumab | Vaccine Anti-PD-1 | Advanced melanoma | 2 | I |