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

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