Table 3 Inhibitors of STAT3 in clinical development
From: Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery
Type | Drug names | Phase of trial | Status | Clinical Trial ID | Patients | Ref |
|---|---|---|---|---|---|---|
Direct inhibitors | Â | Â | Â | Â | Â | |
SH2 domain | OPB-51602 (Small molecule) | I | Terminated | Nasopharyngeal carcinoma (n = 9) | NA | |
|  | I | Completed | Advanced cancer (n = 45) | NA | ||
|  | I | Completed | Hematological malignancies (n = 20) | [239] | ||
|  | I | Completed | Malignant solid tumor (n = 51) | [240] | ||
OPB-31121 (Small molecule) | I | Completed | Advanced solid tumors (n = 30) | [241] | ||
|  | I | Unkonwn | Advanced solid tumors (n = 25) | [242] | ||
C188–9 (Small molecule) | I | Recruiting | BC, HNSCC, NSCLC, CRC, melanoma, GAC, advanced cancer (n = 60) | NA | ||
DNA-binding domain | BBI-608 (Napabucasin, small molecule) | I | Completed | Advanced malignancies (n = 87) | NA | |
I | Completed | Healthy volunteers (n = 8) | [243] | |||
III | Completed | CRC (n = 282) | [244] | |||
|  | I/II | Completed | GC (n = 495) | NA | ||
|  | III | Completed | Pancreatic cancer (n = 1132) | [245] | ||
|  | I/II | Terminated | Colorectal cancer (n = 55) | [246] | ||
Other modes | AZD9150(Antisense oligonucleotide) | I | Completed | HCC (n = 58) | NA | |
I/II | Completed | Lymphoma (n = 64) | [247] | |||
|  | I | Completed | NA | Lymphoma, Lung Cancer (n = 25) | [248] | |
STAT3 DECOY (Oligonucleotide) | I | Completed | HNSCC (n = 32) | NA | ||
CpG-STAT3 siRNA | I | Recruiting | Relapsed/Refractory B-Cell NHL (n = 18) | NA | ||
Pyrimethamine (Small molecule) | NA | Completed | NA | CLL (n = 16) | [249] | |
|  | I/II | Recruiting | CLL, SLL (n = 26) | NA | ||
OPB-111077 (Small molecule) | I | Completed | Advanced cancers (n = 145) | NA | ||
|  | I | Terminated | HCC (n = 33) | [250] | ||
Celecoxib (Small molecule) | III | Terminated | CRC (n = 18) | NA | ||
Indirect inhibitors | Â | Â | Â | Â | Â | |
IL-6 | Siltuximab (Anti-IL-6 mAb) | I | Completed | SMM, IMM (n = 30) | NA | |
|  | I | Completed | Prostate cancer (n = 40) | NA | ||
|  | I/II | Completed | Metastatic RCC (n = 68) | [251] | ||
|  | I/II | Completed | Solid tumors (n = 106) | [252] | ||
|  | II | Completed | Multiple myeloma (n = 53) | [253] | ||
|  | II | Completed | Prostate cancer (n = 62) | [254] | ||
|  | II | Terminated | Prostate cancer (n = 106) | [255] | ||
IL-6R | Tocilizumab (Anti-IL-6R mAb) | I | Terminated | B-cell CLL (n = 38) | NA | |
|  | I | Completed | Brest cancer (n = 11) | NA | ||
|  | I/II | Completed | Ovarian cancer (n = 21) | [256] | ||
SRC | Saracatinib | II | Terminated | Osteosarcoma (n = 38) | [257] | |
|  | II | Completed | Melanoma (n = 23) | NA | ||
KX2–391 | II | Completed | Prostate cancer (n = 31) | NA | ||
SRC, ABL | Bosutinib | III | Completed | Leukemia, Myelogenous, Chronic, Breakpoint cluster region-abelson proto-oncogene (BCR-ABL) positive (n = 536) | [258] | |
Dasatinib | II | Completed | Prostate cancer (n = 49) | [259] | ||
|  | III | Completed | Prostate cancer (n = 1930) | [260] | ||
|  | IV | Completed | Chronic Phase Chronic Myeloid Leukemia (n = 39) | [261] | ||
EGFR | Lapatinib | II | Completed | Neoplasms, breast (n = 126) | [262] | |
Cetuximab | II | Completed | Head and neck cancer (n = 238) | NA | ||
Panitumumab | IV | Recruiting | CRC (n = 58) | NA | ||
FGFR | Ponatinib | II | Recruiting | CML (n = 40) | NA | |
VEGFR | Apatinib | II | Unknown | Lung cancer (n = 33) | NA | |
FGFR/VEGFR | ODM 203 | I/IIa | Completed | Advanced or metastatic solid tumors (n = 84) | [263] | |
TLR2, TLR4 | OM-174 | I | Completed | Solid tumors (n = 27) | [264] | |
PDGFR | Sorafenib | IV | Recruiting | HCC (n = 40) | NA | |
IGFR | Figitumumab | I | Completed | NA | Solid tumors (n = 24) | [265] |
JAK1/2 | AZD1480 (Antisense oligonucleotide) | I | Terminated | Solid malignancies (n = 72) | NA | |
I | Terminated | HCC, NSCLC (n = 47) | NA | |||
Ruxolitinib (Small molecule) | II | Completed | AML, ALL, CML (n = 51) | [266] | ||
Momelotinib (Small molecule) | I | Terminated | NSCLC (n = 21) | [267] | ||
|  | III | Terminated | PDAC (n = 25) | NA | ||
INCB018424 | I/II | Completed | Myelofibrosis (n = 153) | [268] | ||
JAK2 | WP1066 (Small molecule) | I | Completed | Brain tumors (n = 8) | NA | |
TQ05105 (Small molecule) | I | Recruiting | Myeloproliferative neoplasms (n = 50) | NA | ||
Fedratinib (Small molecule) | I | Completed | Neoplasm malignant (n = 60) | NA | ||
|  | I | Completed | Myelofibrosis (n = 289) | [269] | ||
|  | II | Completed | Myelofibrosis (n = 97) | [270] | ||
SB1518 (Small molecule) | I/II | Completed | AML, CML, Myelofibrosis (n = 76) | [271] | ||
LY2784544 (Small molecule) | II | Active | Myeloproliferative neoplasms (n = 110) | [272] | ||
Lestaurtinib | II | Completed | Leukemia, Myelofibrosis (N = 27) | [273] | ||
SHP1 | SC-43 | I | Withdrawn | Refractory solid tumor | NA | |