Trial Outcomes & Findings for Study to Evaluate Discontinuation and Re-Treatment in Participants With Tenosynovial Giant Cell Tumor (TGCT) Previously Treated With Pexidartinib (NCT NCT04526704)

Last Updated: 2024-12-30

Results Overview

Participants who were not remaining treatment-free were defined as either participants who resumed pexidartinib treatment, death (any cause) or who were receiving systemic therapy or undergoing surgery for the treatment of TGCT, whichever occurs first. The number of participants who remained treatment-free at Month 12 is reported.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

32 participants

Primary outcome timeframe

Baseline up to 12 months after last participant enrolled in Cohort

Results posted on

2024-12-30

Participant Flow

A total of 32 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study.

As specified in the protocol, the study analysis was conducted based on 2 cohorts: Treatment Continuation Cohort and Treatment-Free/Re-Treatment Cohort.

Participant milestones

Participant milestones
Measure	Treatment Continuation Cohort Previously-treated participants with TGCT who continued their current dose of pexidartinib treatment.	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Overall Study STARTED	21	11
Overall Study Resumed Pexidartinib Treatment	0	3
Overall Study COMPLETED	17	11
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Continuation Cohort Previously-treated participants with TGCT who continued their current dose of pexidartinib treatment.	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Overall Study Adverse Event	1	0
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Study to Evaluate Discontinuation and Re-Treatment in Participants With Tenosynovial Giant Cell Tumor (TGCT) Previously Treated With Pexidartinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Continuation Cohort n=21 Participants Previously-treated participants with TGCT who continued their current dose of pexidartinib treatment.	Treatment-Free/Re-Treatment Cohort n=11 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Total n=32 Participants Total of all reporting groups
Age, Continuous	46.2 years STANDARD_DEVIATION 15.7 • n=5 Participants	51.9 years STANDARD_DEVIATION 15.2 • n=7 Participants	48.2 years STANDARD_DEVIATION 15.5 • n=5 Participants
Age, Customized 18 to 40 years	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Age, Customized 41 to 64 years	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized 65 to 74 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Customized 75 to 84 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Customized ≥ 85 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	19 Participants n=5 Participants	8 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Not collected per local regulations	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 12 months after last participant enrolled in Cohort

Population: The number of treatment-free participants was assessed in participants with available data in the Full Analysis Set.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=11 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Number of Treatment-Free Participants at 12 Months In The Treatment-free/Re-treatment Cohort	8 Participants	—

PRIMARY outcome

Timeframe: Baseline up to 24 months after last participant enrolled in Cohort

Population: The number of treatment-free participants was assessed in participants with available data in the Full Analysis Set.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=11 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Number of Treatment-Free Participants at 24 Months In The Treatment-free/Re-treatment Cohort	8 Participants	—

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: PROMIS Physical Function was assessed in participants with available data in the Evaluable Analysis Set.

The PROMIS Physical Function Total Overall Score (includes 11 upper extremity questions and 13 lower extremity questions) ranges from 24 to 120, with each individual question being rated on a 5-point rating scale (where 1 is unable to do and 5 is without any difficulty). Higher PROMIS Physical Function Total Overall Scores indicate a better health state. The change from baseline in PROMIS Physical Function Total Overall Scores is being reported.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=16 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort n=7 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Change From Baseline in PROMIS Physical Function Total Overall Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts	-2.78 score on a scale Standard Deviation 6.42	-1.93 score on a scale Standard Deviation 4.80

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: EQ-5D-5L was assessed in participants with available data in the Evaluable Analysis Set.

The EQ-5D-5L questionnaire assessed a participant's mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The overall health is rated on a scale from 0 to 100, where 0 is worst health you can imagine and 100 is best health you can imagine. The change from baseline in EQ-5D-5L Scale Score is being reported.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=16 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort n=7 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Change From Baseline in EQ-5D-5L Scale Score In The Treatment Continuation and Treatment-free/Re-Treatment Cohorts	-2.4 score on a scale Standard Deviation 13.53	3.4 score on a scale Standard Deviation 7.59

SECONDARY outcome

Timeframe: Month 18 (Re-treatment Period of the Treatment-free/Re-treatment Cohort), Month 24 (Treatment Continuation Cohort)

Population: Tumor assessments were analyzed in participants with available data in the Full Analysis Set.

Tumors were assessed based on the RECIST criteria. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; ≥30% increase in volume relative to lowest score during the study whether at baseline or some other visit.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=16 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort n=3 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Number of Participants With and Without Progressive Disease Not progressive	16 Participants	0 Participants
Number of Participants With and Without Progressive Disease Progressive disease	0 Participants	1 Participants
Number of Participants With and Without Progressive Disease Not evaluable	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

Population: Treatment-emergent adverse events were assessed in participants with available data in the Safety Analysis Set.

Treatment-emergent adverse events (TEAEs) were defined as new adverse events (AEs) or pre-existing conditions that worsen in CTCAE grade after the first dose of study drug and up to 30 days after last dose of study drug.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=21 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Treatment Continuation Cohort	19 Participants	—

SECONDARY outcome

Timeframe: Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

Population: Treatment-emergent adverse events were assessed in participants with available data in the Safety Analysis Set .

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=3 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Number of Participants Who Reported Treatment-Emergent Adverse Events (TEAEs) In The Re-Treatment Period of the Treatment-free/Re-Treatment Cohort	3 Participants	—

SECONDARY outcome

Timeframe: Baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months

Population: Adverse events were assessed in the Safety Analysis Set in participants with available data in the Treatment-free Period of the Treatment-Free/Re-Treatment Cohort.

Adverse events (AEs) were defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment. Participants who were not remaining treatment-free were defined as either participants who resumed pexidartinib treatment, death (any cause) or who were receiving systemic therapy or undergoing surgery for the treatment of TGCT, whichever occurs first.

Outcome measures

Outcome measures
Measure	Treatment-Free/Re-Treatment Cohort n=11 Participants Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free/Re-Treatment Cohort Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).
Number of Patients Reporting AEs (Treatment-free) Any Grade AE	7 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Musculoskeletal/Tissue Disorders	6 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Arthralgia	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Back pain	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Intervertebral disc protrusion	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Joint swelling	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Musculoskeletal pain	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Pain in extremity	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Metabolism and Nutrition Disorders	3 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Hypercholesterolaemia	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Hypertriglyceridaemia	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade General Disorders & Site Conditions	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Asthenia	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Oedema peripheral	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Infections and Infestations	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Cellulitis	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade COVID-19	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade investigations	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Gr Blood creatinine phosphokinase increased	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Blood uric acid increased	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Renal and Urinary Disorders	2 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Renal colic	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Urinary retention	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Injury, Poisoning & Procedural Issues	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Animal bite	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Neoplasms Benign, Malignant & Other	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Lipoma	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Nervous System Disorders	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Sciatica	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Skin and Subcutaneous Tissue Disorders	1 Participants	—
Number of Patients Reporting AEs (Treatment-free) Any Grade Urticaria	1 Participants	—

Adverse Events

Treatment Continuation Cohort

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Re-Treatment Period of Treatment-Free/Re-Treatment Cohort

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Treatment-Free Period of Treatment-Free/Re-treatment Cohort

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Continuation Cohort n=21 participants at risk Previously-treated participants with TGCT who continued their current dose of pexidartinib treatment.	Re-Treatment Period of Treatment-Free/Re-Treatment Cohort n=3 participants at risk Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and had the option to resume pexidartinib treatment at dose of completion of prior study (Re-Treatment Period).	Treatment-Free Period of Treatment-Free/Re-treatment Cohort n=11 participants at risk Previously-treated participants with TGCT who discontinued pexidartinib treatment (Treatment-Free Period) and reported adverse events.
Infections and infestations Creutzfeldt-Jakob disease	4.8% 1/21 • Treatment-emergent adverse events were collected from baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months. TEAEs observed in the Treatment Continuation Cohort and the Re-Treatment Period of the Treatment-free/Re-Treatment Cohort are reported. AEs from the Treatment-free Period of the Treatment-free/Re-Treatment Cohort were captured and are reported as well.	0.00% 0/3 • Treatment-emergent adverse events were collected from baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months. TEAEs observed in the Treatment Continuation Cohort and the Re-Treatment Period of the Treatment-free/Re-Treatment Cohort are reported. AEs from the Treatment-free Period of the Treatment-free/Re-Treatment Cohort were captured and are reported as well.	0.00% 0/11 • Treatment-emergent adverse events were collected from baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months. TEAEs observed in the Treatment Continuation Cohort and the Re-Treatment Period of the Treatment-free/Re-Treatment Cohort are reported. AEs from the Treatment-free Period of the Treatment-free/Re-Treatment Cohort were captured and are reported as well.
Product Issues Device dislocation	4.8% 1/21 • Treatment-emergent adverse events were collected from baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months. TEAEs observed in the Treatment Continuation Cohort and the Re-Treatment Period of the Treatment-free/Re-Treatment Cohort are reported. AEs from the Treatment-free Period of the Treatment-free/Re-Treatment Cohort were captured and are reported as well.	0.00% 0/3 • Treatment-emergent adverse events were collected from baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months. TEAEs observed in the Treatment Continuation Cohort and the Re-Treatment Period of the Treatment-free/Re-Treatment Cohort are reported. AEs from the Treatment-free Period of the Treatment-free/Re-Treatment Cohort were captured and are reported as well.	0.00% 0/11 • Treatment-emergent adverse events were collected from baseline up to 30 days after the start of re-treatment or end of study (whichever occurs first), up to 24 months. TEAEs observed in the Treatment Continuation Cohort and the Re-Treatment Period of the Treatment-free/Re-Treatment Cohort are reported. AEs from the Treatment-free Period of the Treatment-free/Re-Treatment Cohort were captured and are reported as well.

Other adverse events

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place