A Phase 4, Multicenter Study to Evaluate Discontinuation and Re-Treatment in Subjects with Tenosynovial Giant Cell Tumor (TGCT) Previously Treated with Pexidartinib

Tenosynovial giant cell tumor (TGCT) is a rare, nonmalignant neoplasm of the
synovium,
bursae, or tendon sheaths that is driven by overexpression of
colony-stimulating factor-1 (CSF-1)
often afflicting adults under 40 years of age. Annual TGCT incidence is
estimated to be 43 cases
per one million individuals, of which approximately 10% are of the diffuse
subtype. Surgical
resection, when feasible, is the standard treatment for TGCT; however,
recurrence of the diffuse
subtype is particularly common. Repeated surgeries often result in increasing
morbidity and
functional limitations of the affected joints. The diffuse disease often has
more extensive
involvement and a poorer likelihood of a successful cure with surgery, and
therefore often may
not be amenable to surgical resection due to the risk of morbidity or high risk
of recurrence in
diffuse disease.Pexidartinib is the first systemic therapy to show a
robust tumor response in TGCT with improved patient symptoms and functional
outcomes;
cholestatic hepatotoxicity has been identified as a risk. Patients with TGCT
diagnosed early in their lives face potentially several decades of daily
treatment. In the real-world setting, subjects and Investigators are faced with
decisions
surrounding patients* activities of daily living and treatment with
pexidartinib for TGCT.
Further data are necessary to fully understand the safe and effective
discontinuation and retreatment with pexidartinib therapy in this patient
population.
The purpose of this Phase 4 multicenter study in subjects with TGCT previously
treated with
pexidartinib are two-fold. At the Screening visit/time of consent, the
Investigators and subjects
are provided the choice to either continue treatment with pexidartinib or
discontinue treatment
with the possibility of re-initiating pexidartinib treatment at a later time.
Findings from this
study will provide important prospective discontinuation and re-treatment data
with pexidartinib
in previously treated subjects with residual disease.
Ultimately, this study will contribute meaningful information to the body of
research on
pexidartinib treatment for patients with TGCT and the safe and effective
discontinuation and retreatment with pexidartinib therapy.

Main objective:

Proportion of subjects who remain treatment-free.


Secondary objectives:

- Change from Baseline in Patient Reported Outcomes (PROs) (PROMIS
PF, EQ-5D-5L)
- Safety: Total number of subjects in the safety analysis set with any AE
collected between Screening and start of re-treatment or final database
lock (whichever occurs first)
- Tumor Assessment: Investigator evaluation of tumor

This is a Phase 4, multicenter study in subjects with TGCT (PVNS or GCT-TS) who
were previously treated with pexidartinib in
one of the following studies: PLX108-10 (ENLIVEN), PLX108-01, PL3397-A-A103,
and PL3397-A U126. At the Screening
visit/time of consent, at the Investigator and subject*s discretion, the
subjects are given the choice to either continue treatment
with pexidartinib or discontinue treatment with the possibility to reinitiate
pexidartinib treatment at a later time.

1. Subjects who choose to continue treatment with pexidartinib will be enrolled
in the Treatment Continuation Cohort.
The assessments from the subject*s *End-of-Treatment visit* (i.e., the visit on
which they received their last dose of
study treatment) from their prior study (eg, tumor assessments, PRO measures,
and safety parameters) will serve as the
Baseline measurements for PL3397-A-U4003 study. These subjects will remain on
their current dosage of pexidartinib
and undergo clinical assessments at 3-month intervals for the duration of the
study.
2. Subjects who choose to discontinue pexidartinib treatment will be enrolled
into the Treatment-Free period of the
Treatment-Free/Re-Treatment Cohort. The assessments from the subject*s
End-of-Treatment visit from their prior
study (eg, tumor assessments, PRO measures, and safety parameters) will serve
as the Baseline measurements for
PL3397-A-U4003 study. Subjects will discontinue pexidartinib treatment and
undergo clinical assessments at 3-month
intervals during the Treatment-Free period. Re-treatment with pexidartinib will
be based on the discretion of the subject
and Investigator. Tumor assessment, subjective and/or functional measures, and
safety will be considered in the
decision-making process. The rationale for discontinuing and restarting
pexidartinib re-treatment will be recorded
accordingly.
Subjects in the Treatment-Free/Re-Treatment Cohort who enter the Re-Treatment
period will be administered
pexidartinib at the dose at which they completed the prior study. Dosing is
required on an empty stomach (at least
1 hour before or 2 hours after a meal or snack), at approximately the same
times of the day, and approximately 12 hours
apart. During the Re-Treatment period, Investigators will ensure weekly liver
monitoring tests for the first 8 weeks
(2 months), then every 2 weeks for 1 month, then once every 3 months or more
frequently as directed by the
Investigator.

In this study the subjects are given the choice to either continue treatment
with pexidartinib or discontinue treatment with the possibility to reinitiate
pexidartinib treatment at a later time.
Participartion in this study might entail more testing than the subject would
usually have. (i.e. blood draws, MRI's).
This study will contribute meaningful information to the body of research on
pexidartinib treatment for patients with TGCT and the safe and effective
discontinuation and retreatment with pexidartinib therapy.