Drug intelligence / Profile preview

pexidartinib + paclitaxel

Development stage
Unknown
Lead developer
Daiichi Sankyo
Modality
Nucleic Acid-Directed Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Classical Binding Small Molecules → Small Molecules
Administration
Oral, Intravenous
01

Overview

This is a combination of **pexidartinib**, a small molecule tyrosine kinase inhibitor of colony-stimulating factor 1 receptor (CSF-1R), FMS-like tyrosine kinase 3 (FLT3), and c-Kit (KIT), and **paclitaxel**, a microtubule-stabilizing chemotherapeutic agent. The combination has been studied in clinical trials for advanced solid tumors and high-risk early-stage breast cancer. Pexidartinib blocks CSF-1R signaling, reducing tumor-associated macrophage infiltration, which may help mitigate tumor growth and immune evasion. Paclitaxel disrupts cell division by stabilizing microtubules, leading to apoptosis of rapidly dividing cells. The pairing is based on preclinical evidence that CSF-1R inhibition can decrease immunosuppressive macrophages and enhance cytotoxic chemotherapy effects. In phase Ib/II studies, the combination showed manageable toxicity, notable hematologic and hepatic adverse events, and some partial and complete responses in advanced solid tumor patients. However, a trial in high-risk early-stage breast cancer found limited efficacy and concerns regarding serious hepatic toxicity[1][3][4][5].

Other names
pexidartinib and paclitaxelPLX3397 and paclitaxelPLX-3397 and paclitaxelPLX 3397 and paclitaxel
02

Targets

KIT (c-KIT proto-oncogene receptor tyrosine kinase)FLT3-ITD (Fms-like tyrosine kinase 3 with internal tandem duplication)CSF1R (Macrophage colony-stimulating factor receptor)TUBB (Tubulin (alpha and beta subunits))

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