Inclusion Criteria:
* Age ≥ 18 years (Age ≥ 20 years in Taiwan).
* A diagnosis of TGCT (i) that has been histologically confirmed by a pathologist and (ii) associated with severe morbidity or functional limitations and not amenable to improvement with surgery determined consensually by qualified personnel (eg, 2 surgeons or a multi-disciplinary tumor board).
* Measurable disease as defined by RECIST 1.1 (except that a minimal size of 2 cm is required), assessed from MRI scan by a central radiologist.
* Stable prescription of analgesic regimen during the 2 weeks prior to enrollment.
* Women of childbearing potential must have a negative serum pregnancy test within the 14-day period prior to enrollment (Where demanded by local regulations, this test may be required within 72 hours of enrollment).
* Females of reproductive potential should be advised to use an effective, non-hormonal method of contraception during treatment with pexidartinib and for 1 month after the last dose. Males with female partners of reproductive potential should be advised to use an effective method of contraception during treatment with pexidartinib and for 1 month after the last dose. Female partners of male participants should concurrently use effective contraceptive methods (hormonal or non-hormonal). Women of nonchildbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year. Women who have documentation of at least 12 months of spontaneous amenorrhea and have a follicle stimulating hormone level \> 40 mIU/mL will be considered postmenopausal.
* Adequate hematologic, hepatic, and renal function, defined by:
* Absolute neutrophil count ≥ 1.5 × 10\^9/L
* Hemoglobin \> 10 g/dL
* Platelet count ≥ 100 × 10\^9/L
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.0 × upper limit of normal (ULN)
* Total bilirubin and direct bilirubin ≤ 1.0 × ULN
* Alkaline phosphatase ≤ 1.0 × ULN
* Creatinine clearance (CLcr) \> 15 mL/min
* Willingness and ability to complete the PROMIS Physical Function Scale.
* Willingness and ability to use a diary.
* Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.
Exclusion Criteria:
* Investigational drug/device use within 28 days of enrolment.
* Previous use of pexidartinib or any biologic treatment targeting colony stimulating factor 1 (CSF-1) or the CSF-1 receptor; previous use of oral tyrosine kinase inhibitors are allowed (eg, imatinib or nilotinib).
* Active cancer except for tumor for which a participant is enrolled in the study, (either concurrent or within the last year of starting study drug) that requires therapy (eg, surgical, chemotherapy, or radiation therapy), with the exception of adequately treated basal or squamous cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix or breast, or prostate carcinoma with a prostate-specific antigen value \< 0.2 ng/mL.
* Known metastatic TGCT.
* Active or chronic infection with hepatitis C or known positive hepatitis B surface antigen, or known active or chronic infection with human immunodeficiency virus.
* Active liver or biliary tract disease
* Known active tuberculosis.
* Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator's opinion, would likely interfere with a participant's study participation or the interpretation of his or her results.
* Use of strong Cytochrome P450 (CYP) 3A inducers, including St John's wort, proton pump inhibitors (PPIs), and other products known to cause hepatotoxicity.
* Women who are breastfeeding.
* A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women).
* MRI contraindications.
* History of hypersensitivity to any excipients in the investigational product.
* Inability to swallow capsules.
