Table 2.
CSF1R tyrosine kinase inhibitors in clinical development
|
Code
|
Generic
|
Phase I Trial
|
Phase Ib Trial
|
|||
|
DLT
|
MTD, mg/d
|
RP2D, mg/d
|
Response
|
ICI Partner
|
||
| ARRY382[24] | CK, pyrexia, AST | 400 | 400 | None | Pembrolizumab | |
| BLZ945[26] | Amylase, lipase, AST, ALP, sudden death | 1200 | 1200 | 1 PR in GBM | Spartalizumab (1 PR in HNSCC) | |
| DCC3014[28] | Lipase, hypocalcemia | 1 PR in TGCT | Avelumab | |||
| JNJ40346527[29] | Edicotinib | None | None | None | 1 CR in HL | |
| PLX3397*[30,31] | Pexidartinib | None | None | 1000 | 12 PRs in TGCT[12] | Durvalumab Pembrolizumab |
ALP: alkaline phosphatase; AST: aspartate aminotransferase; CK: creatinine kinase; CR: complete response; CSF1R: colony-stimulating factor 1 receptor; DLT: dose-limiting toxicity; FLT3: fms-like tyrosine kinase 3; GBM: glioblastoma multiforme; HL: Hodgkin lymphoma; HNSCC: head and neck squamous cell carcinoma; ICI: immune checkpoint inhibitor; MTD: maximum tolerated dose; PR: partial response; RP2D: recommended phase II dose; TGCT: tenosynovial giant cell tumor.
*
PLX3397 (pexidartinib) is a CSF1, KIT, FLT3 inhibitor.