58MO Evaluation of three pexidartinib doses in a global phase IV clinical study of patients with tenosynovial giant cell tumor (TGCT) who chose to continue treatment

In 2019, pexidartinib was US FDA-approsssved (800 mg/day TDD) for TGCT patients with severe morbidity or functional limitations not amenable to improvement with surgery. Per label, dose modifications are recommended in certain scenarios, yet long-term data at dosages <800 mg/day are lacking. We evaluated efficacy and safety of 3 doses in a phase 4 study designed to evaluate pexidartinib discontinuation/rechallenge in patients with TGCT. This multicenter, open-label, nonrandomized study (NCT04526704) enrolled adults with TGCT from 4 prior pexidartinib trials (NCT02371369; NCT01004861; NCT02734433; NCT03291288). After the prior trials' end-of-treatment (EOT) visits, patients could choose to enter the Treatment Continuation Cohort (TCC; same dose as EOT) or Treatment-Free/Re-Treatment Cohort (TF/RTC; discontinue pexidartinib with choice to re-initiate at the investigator's/patient's discretion). This secondary analysis studied the proportion of progressive disease (PD) by investigator-assessed RECIST v1.1 and safety of 3 pexidartinib doses (800 mg, 600 mg, 400 mg) utilized in the TCC. From Oct 2020-Apr 2021, 32 patients enrolled; 21/32 chose the TCC with a median age of 47 (range: 21-78) years, 57% (12/21) were female, and 48% (10/21) had knee tumors. In the TCC, 10 (48%), 6 (29%) and 5 (24%) patients were treated at daily doses of 800 mg, 600 mg, and 400 mg, respectively. Patient characteristics were well-balanced across dose, with a median of 10.8 (range: 4.6-32.6) years since diagnosis and a median of 55.3 (range: 26.7-91.0) months of historical pexidartinib treatment. Four of the 21 patients (19%) discontinued this study early due to AE (n = 1; 800 mg), patient withdrawal (n = 2; 800 mg), or physician decision (n = 1; 400 mg). In an average 22.4±4.4 months of follow-up, no TCC patients showed RECIST PD. 19 TCC patients (10 [100%], 6 [100%], 3 [60%] on 800 mg, 600 mg, and 400 mg, respectively) had TEAEs. Patients who continued pexidartinib experienced disease control with a manageable safety profile across 3 doses. Further evaluation of long-term pexidartinib activity following dose modification is warranted.