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Table 1 Completed clinical trials that evaluated TGF-β pathway antagonists in oncology

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   
  1. Summary of completed clinical trials utilizing TGF-β targeting agents in a variety of treatment refractory metastatic solid tumors including breast, esophageal, gastric, biliary, pancreatic, non-small cell lung cancer, melanoma, GBM and head and neck tumors. Nine trials utilized small molecule inhibitors, three utilized antibodies, ten utilized ligand traps, two utilized ASOs, and three utilized vaccination strategies