A Study of the Efficacy and Safety of Pexidartinib in Adult Subjects With TGCT

For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by centrally reviewed MRI scan. Complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; and overall response rate (ORR), defined as CR+PR, are presented.

Time frame: At Week 25 postdose

Population: ORR based on RECIST 1.1 was assessed in the Full Analysis Set.

AUC(0-6h) was calculated using standard non-compartmental analysis. AUC(0-6h) for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.

Time frame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)

Population: AUC(0-6h) was assessed in the Pharmacokinetic Analysis Set.

Best overall response (CR or PR) of pexidartinib based on RECIST 1.1 and TVS are summarized. Tumor categories for RECIST v1.1 were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions; stable disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions; and not evaluable (NE). Tumor categories for TVS were as follows: complete response (CR), disappearance of all target lesions; partial response (PR), at least a 50% decrease in volume score relative to baseline; stable disease (SD), does not meet any of the prior criteria based on score during study; progressive disease (PD), at least a 30% increase in in volume relative to lowest score during the study whether at baseline or some other visit; and not evaluable (NE).

Time frame: From baseline until disease progression or death (whichever occurs first), up to approximately 29 months

Duration of response (DOR) is defined as the date of the first recorded response to the first date of documented disease progression.

Time frame: Time from the date of first documented response until documented disease progression or death from any cause (whichever occurs first), up to approximately 29 months

Cmax was calculated using standard non-compartmental analysis. Cmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.

Time frame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)

Population: Cmax was assessed in the Pharmacokinetic Analysis Set.

The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess the physical function of the upper and lower limbs. The scale ranges from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.

Time frame: At Week 25 postdose

Population: Mean Change From PROMIS was assessed in the Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.

Range of motion (ROM) of the joint was assessed by a qualified, independent, and blinded or third-party assessors at the clinical site. The relative ROM was calculated (expressed in percent) as follows: Relative ROM = 100 x (absolute ROM measured)/(reference ROM standard). The change from baseline in relative ROM at Week 25 was calculated as the difference in relative ROM at Week 25 visit minus relative ROM at Screening visit.

Time frame: At Week 25 postdose

Population: Mean Percent Change From Baseline for Range of Motion (ROM) was assessed in Full Analysis Set; however, participant assessments falling outside the visit window were excluded from the change from baseline analysis.

A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until post-treatment visit (28 ± 7 days after the last dose of study drug).

Time frame: Up to approximately 29 months

For the assessment of tumor response, participants were classified into the best of the following tumor response categories based on Tumor Volume Score (TVS) by centrally reviewed MRI scan. Tumor Volume Score (TVS) is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor. Complete response (CR), disappearance of lesion; partial response (PR), at least 50% decrease in volume score relative to baseline; overall response rate (ORR), defined as CR+PR, are presented.

Time frame: At Week 25 postdose

Population: ORR based on TVS was assessed in the Full Analysis Set.

Tmax was calculated using standard non-compartmental analysis. Tmax for Pexidartinib and primary metabolite, ZAAD-1006a, are presented.

Time frame: Week 3: Cycle 1 Day 1 at pre-dose, 0.5h, 1h, 2h, 4h, and 6h post-dose (each cycle is 28 days)

Population: Tmax was assessed in the Pharmacokinetic Analysis Set.