PURPOSE: To evaluate the safety, recommended phase II dose (RP2D) and efficacy 
of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in 
combination with weekly paclitaxel in patients with advanced solid tumors.
PATIENTS AND METHODS: In part 1 of this phase Ib study, 24 patients with 
advanced solid tumors received escalating doses of pexidartinib with weekly 
paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. 
For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 
design. In part 2, 30 patients with metastatic solid tumors were enrolled to 
examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and 
biomarkers were also assessed.
RESULTS: A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at 
least possibly related to either study drug. Grade 3-4 AEs, including anemia 
(26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension 
(11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose 
was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients 
evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 
13 (34%) stable disease, and 17 (45%) progressive disease. No drug-drug 
interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and 
CD14dim/CD16+ monocyte levels decreased by 57-100%.
CONCLUSIONS: The combination of pexidartinib and paclitaxel was generally well 
tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R 
signaling, indicating potential for mitigating macrophage tumor infiltration.