Pexidartinib For Advanced Tenosynovial Giant Cell Tumor (Tgct): Long-Term Efficacy And Safety From The Phase 3 Enliven And Phase 1 Plx108-01 (Tgct Cohort) Studies.

11042 Background: TGCT is a rare, locally aggressive neoplasm of the joint/tendon sheath linked to colony-stimulating factor 1 (CSF1) overexpression. Pexidartinib (pex), a selective inhibitor of CSF1 receptor, KIT, and FLT3-ITD, had a compelling tumor response rate in the TGCT cohort of a phase 1 study (NCT01004861) and significant tumor response vs placebo by RECIST v1.1 (39% vs 0%, P< 0.0001) and tumor volume score (TVS) (56% vs 0%, P< 0.0001) in the randomized, 2-part, crossover phase 3 ENLIVEN study (NCT02371369). Updated efficacy and safety with longer treatment are reported. Methods: Patients (pts) were ≥18 y with TGCT that was inoperable or for which surgery would likely be associated with worsening functional limitation or severe morbidity. Best overall response (complete or partial [CR/PR]) and duration of response (DOR) by RECIST and TVS were assessed by independent central review. Data cutoff was Jan 31, 2018, 16-67 mo after pts’ first dose. Results: In both studies 130 pts received pex, 61 ongoing at data cutoff. Median treatment duration was 17 mo (1, 60+). CR/PR rates were high and consistent and, together with DOR, improved with prolongation of treatment (Table). Most frequent adverse events were hair color change (75%), fatigue (60%), nausea (45%), arthralgia (38%), AST increase (30%), and diarrhea (30%). In ENLIVEN part 1, 3 of 61 (5%) pts had reversible ALT and AST ≥3 × ULN with TBil and ALP ≥2 × ULN; all started in the first 8 weeks of treatment, and no new cases emerged with continuation of treatment. Conclusions: Tumor response rate increased with continuation of pex treatment. The safety profile remained similar, with no new mixed or cholestatic hepatotoxicity. Clinical trial information: NCT01004861 and NCT02371369. [Table: see text]