Trial Outcomes & Findings for A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan (NCT NCT04703322)

NCT ID: NCT04703322

Last Updated: 2025-03-03

Results Overview

The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)

Results posted on

2025-03-03

Participant Flow

A total of 9 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study. These results are based on Part 1 of the study. All safety and pharmacokinetic primary outcome analysis data for Part 1 are reported. Part 2 of the study was not conducted. Eight patients remain in the study and are being followed until study completion. Only the final safety data of the patients who remain on study will be reported at the final database cut (estimated May 31, 2026).

Participant milestones

Participant milestones
Measure	Pexidartinib Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Overall Study STARTED	9
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Pexidartinib Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Overall Study Ongoing	8
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pexidartinib n=9 Participants Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	35.9 years STANDARD_DEVIATION 11.16 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days)

Population: All DLT TEAEs were assessed in the DLT Evaluable Set.

The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed.

Outcome measures

Outcome measures
Measure	Pexidartinib n=9 Participants Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Dose-limiting Toxicity (DLT) in Part 1 Any Grade DLT TEAE	2 Participants
Dose-limiting Toxicity (DLT) in Part 1 Any Grade Hepatic function abnormal	1 Participants
Dose-limiting Toxicity (DLT) in Part 1 Any Grade Alanine aminotransferase increased	1 Participants
Dose-limiting Toxicity (DLT) in Part 1 Any Grade Aspartate aminotransferase increased	1 Participants
Dose-limiting Toxicity (DLT) in Part 1 Any Grade Blood alkaline phosphatase increased	1 Participants
Dose-limiting Toxicity (DLT) in Part 1 Any Grade Gamma-glutamyltransferase increased	1 Participants

PRIMARY outcome

Timeframe: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days)

Population: Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set.

Pharmacokinetic parameters were assessed using non-compartmental methods. Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.

Outcome measures

Outcome measures
Measure	Pexidartinib n=9 Participants Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 Pexidartinib, C1D1	7920 ng/mL Standard Deviation 1720
Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 Pexidartinib, C1D15	8810 ng/mL Standard Deviation 1110
Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 ZAAD-1006a, C1D1	8000 ng/mL Standard Deviation 1990
Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 ZAAD-1006a, C1D15	11700 ng/mL Standard Deviation 3340

PRIMARY outcome

Timeframe: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days)

Population: Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set.

Pharmacokinetic parameters were assessed using non-compartmental methods. AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of pexidartinib and ZAAD-1006a in plasma.

Outcome measures

Outcome measures
Measure	Pexidartinib n=9 Participants Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of Pexidartinib and ZAAD-1006a (AUClast) in Part 1 Pexidartinib, C1D1	62000 h*ng/mL Geometric Coefficient of Variation 27.3
Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of Pexidartinib and ZAAD-1006a (AUClast) in Part 1 ZAAD-1006a, C1D1	90900 h*ng/mL Geometric Coefficient of Variation 48.4

PRIMARY outcome

Timeframe: Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days)

Population: Pharmacokinetic data were assessed in participants with available data in the Pharmacokinetic Analysis Set.

Pharmacokinetic parameters were assessed using non-compartmental methods. AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.

Outcome measures

Outcome measures
Measure	Pexidartinib n=9 Participants Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1 Pexidartinib, C1D1	8700 h*ng/mL Geometric Coefficient of Variation 28.1
Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1 ZAAD-1006a, C1D1	195000 h*ng/mL Geometric Coefficient of Variation 40.2

PRIMARY outcome

Population: Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set.

Pharmacokinetic parameters were assessed using non-compartmental methods. Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.

Outcome measures

Outcome measures
Measure	Pexidartinib n=9 Participants Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 Pexidartinib, C1D1	2.05 hours Interval 1.97 to 2.1
Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 Pexidartinib, C1D15	2.10 hours Interval 1.92 to 2.15
Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 ZAAD-1006a, C1D1	3.97 hours Interval 1.97 to 7.92
Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 ZAAD-1006a, C1D15	3.83 hours Interval 2.1 to 3.92

PRIMARY outcome

Timeframe: Week 25

Timeframe: Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months

Outcome measures

Outcome data not reported

Adverse Events

Pexidartinib

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Pexidartinib n=9 participants at risk Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily \[BID\]).
Skin and subcutaneous tissue disorders Hair colour changes	77.8% 7/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Skin and subcutaneous tissue disorders Pruritus	44.4% 4/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Skin and subcutaneous tissue disorders Dermatitis	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Skin and subcutaneous tissue disorders Eczema	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Skin and subcutaneous tissue disorders Skin discolouration	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Aspartate aminotransferase increased	77.8% 7/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Alanine aminotransferase increased	44.4% 4/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Blood lactate dehydrogenase increased	33.3% 3/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Gamma-glutamyltransferase increased	33.3% 3/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Blood alkaline phosphatase increased	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Blood bilirubin increased	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Blood creatinine phosphokinase increased	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Blood creatinine increased	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Neutrophil count decreased	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Amylase increased	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Blood cholesterol increased	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Investigations Weight decreased	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
General disorders Pyrexia	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
General disorders Face oedema	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
General disorders Fatigue	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Infections and infestations COVID-19	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Infections and infestations Norovirus infection	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Blood and lymphatic system disorders Anaemia	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Blood and lymphatic system disorders Eosinophilia	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Blood and lymphatic system disorders Leukopenia	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Blood and lymphatic system disorders Neutropenia	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Blood and lymphatic system disorders Thrombocytopenia	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Gastrointestinal disorders Diarrhoea	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Gastrointestinal disorders Nausea	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Hepatobiliary disorders Hepatic function abnormal	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Nervous system disorders Dysgeusia	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Vascular disorders Hypertension	22.2% 2/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Metabolism and nutrition disorders Hypokalaemia	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Musculoskeletal and connective tissue disorders Osteoarthritis	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.1% 1/9 • Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).

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