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Giant Cell Tumor of Tendon Sheath

Synovitis, Pigmented Villonodular

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Pigmented Villonodular Synovitis

Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily \[BID\]).

400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration)

Pexidartinib

Daiichi Sankyo Contact for Clinical Trial Information

See Central Contact

Global Clinical Leader

This phase 2, multicenter, two-part, open-label, single-arm study will be conducted in Japan and will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of pexidartinib in adult participants with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitation and not amenable to improvement with surgery.

This study will consist of 2 parts. In Part 1, pexidartinib 800 mg/day (400 mg twice a day \[BID\]) will be administered on an empty stomach and tolerability and PK of pexidartinib will be evaluated to determine the initiation of Part 2. In Part 2, pexidartinib 800 mg/day (400 mg BID) will be administered on an empty stomach and efficacy, safety, and PK of pexidartinib will be evaluated.

A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan

A Phase 2, Multicenter, Two-Part, Open-Label Study of Pexidartinib in Adult Subjects With Tenosynovial Giant Cell Tumor in Japan

The number of participants with dose-limiting toxicities will be assessed.

Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma.

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.

AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma.

Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma.

ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.

ORR will be assessed by centrally reviewed MRI scan based on TVS.

Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed.

Mean change from baseline score in the PROMIS Physical Function Scale will be assessed.

Proportion of responders will be assessed based on the BPI Worst Pain NRS item and analgesic use by BPI-30 definition (ie, 30% or more improvement in average NRS).

BOR will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1.

BOR will be assessed by centrally reviewed MRI scan based on TVS.

DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1.

DoR will be assessed by centrally reviewed MRI scan based on TVS.

Daiichi Sankyo Co., Ltd.

Participants receive blinded treatment of 30 mg twice a week (biw) vimseltinib for 24 weeks in Part 1 and continue on 30 mg biw vimseltinib in Part 2

Participants receive blinded treatment of 30 mg twice a week (biw) matching placebo for 24 weeks in Part 1 and have option to receive 30 mg biw vimseltinib in Part 2

vimseltinib

Placebo

This is a multicenter Phase 3 clinical study, which aims to evaluate the effectiveness of an investigational drug called vimseltinib for the treatment of tenosynovial giant cell tumor (TGCT) in cases where surgical removal of the tumor is not an option.

The study consists of two parts. In Part 1, eligible study participants will be assigned to receive either vimseltinib or matching placebo for 24 weeks. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. MRI scans will be used to evaluate the response of the tumors to the treatment. Participants assigned to placebo in Part 1 will have the option to receive vimseltinib for Part 2. Part 2 is a long-term treatment phase in which all participants receive open-label vimseltinib.

Study of Vimseltinib for Tenosynovial Giant Cell Tumor

A Phase 3, Randomized, Placebo-controlled, Double-blind Study of Vimseltinib to Assess the Efficacy and Safety in Patients With Tenosynovial Giant Cell Tumor (MOTION)

Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

Assessed by central read using Tumor Volume Score (TVS). 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.

Mean change from baseline in active ROM of the affected joint, relative to a reference standard at Week 25

Mean change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25

Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score at Week 25

Mean change from baseline in EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25

Proportion of responders, with a response defined as at least a 30% improvement in the mean Brief Pain Inventory (BPI) Worst Pain NRS score without a 30% or greater increase in narcotic analgesic use at Week 25

Deciphera Pharmaceuticals LLC

Participants receive the blinded treatment of ABSK021 for 24 weeks in Part 1 and continue on the open-label Pimicotinib(ABSK021) in Part 2 and Part 3.

Participants receive the blinded treatment of matching placebo for 24 weeks in Part 1 and have option to receive the open-label Pimicotinib(ABSK021) in Part 2.

Pimicotinib(ABSK021)

The goal of this clinical trial is to assess the efficacy and safety of Pimicotinib (ABSK021) in patients with Tenosynovial Giant Cell Tumor (TGCT). The main questions it aims to answer are:

* Whether the Pimicotinib(ABSK021) works well in patients with TGCT.
* Whether the Pimicotinib(ABSK021) is safe in patients with TGCT.

Participants will be asked to complete the study procedures:

* Receive the administration of Pimicotinib(ABSK021) or placebo (a placebo is a look-alike substance that contains no active drug) about 24 weeks in study part 1.
* Receive the administration of Pimicotinib(ABSK021) about 24 weeks in study part 2.
* Receive the administration of Pimicotinib(ABSK021) till study end in study part 3.
* Complete the study procedures speficied in the protocol, which is guided by researchers.

This study consists of part 1 and part 2. Part 1 is a double-blind phase, eligible patients will be randomized to Pimicotinib(ABSK021) treatment group or matching placebo group and will receive Pimicotinib(ABSK021) or matching placebo until completion of Part 1.

Part 2 is an open-label treatment phase, and all patients entering this phase will receive open-label Pimicotinib(ABSK021) until completion of 24 weeks of dosing or withdrawal from the study.

Part 3 is an open-label extension treatment phase, and patients who completed the part 2 and continuted to be eligible, will go to the Part 3. Patients will receive the open-label Pimicotinib(ABSK021) until all patients withdraw from the study, or the sponsor decides to terminate the study, whichever occurs first.

Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study of ABSK021 to Assess the Efficacy and Safety in Patients With Tenosynovial Giant Cell Tumor

Assessed by central read using Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)

Mean change from baseline in ROM of the affected joint

Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score at Week 25. The Worst Stiffness Numeric Rating Scale (NRS) was a 1-item, self-administered questionnaire assessing the "worst" stiffness in the last 24 hours. The NRS for this item ranged from 0 (no stiffness) to 10 (stiffness as bad as you can imagine). Higher scores mean a worse outcomes.

Mean change from baseline in the Worst Pain Numeric Rating Scale (NRS) score at Week 25. The Worst Pain Numeric Rating Scale Score (NRS) was a 1-item, self-administered questionnaire assessing the "worst" pain in the last 24 hours. The NRS for this item ranged from 0 (no pain) to 10 (pain as bad as you can imagine). Higher scores mean a worse outcomes.

Mean change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function score at Week 25. The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess physical function of the upper and lower limbs. The scale ranged 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.

Mean change from baseline in EuroQol visual analogue scale (VAS) score at Week 25. The EuroQol visual analogue scale (VAS) is a Visual Analogue Scale on which the patient rates their current health, with 0 representing the "worst health you can imagine" and 100 representing the "best health you can imagine". Higher scores mean a better outcomes.

Duration of Response as measured by RECIST Version 1.1 and Tumor Volume Score (TVS)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan	NCT04703322	Tenosynovial Gi...	Pexidartinib	20 Years -	Daiichi Sankyo
A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan	NCT04703322	Tenosynovial Gi...	Pexidartinib	20 Years -	Daiichi Sankyo
Study of Vimseltinib for Tenosynovial Giant Cell Tumor	NCT05059262	Tenosynovial Gi... Pigmented Villo... Giant Cell Tumo... Tenosynovial Gi... Tenosynovial Gi...	vimseltinib Placebo	18 Years -	Deciphera Pharmaceuticals LLC
A Study of Pexidartinib in Tenosynovial Giant Cell Tumor in Japan	NCT04703322	Tenosynovial Gi...	Pexidartinib	20 Years -	Daiichi Sankyo
Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)	NCT05804045	Tenosynovial Gi... Pigmented Villo... Giant Cell Tumo...	Pimicotinib(ABS... Placebo	18 Years -	Abbisko Therapeutics Co, Ltd

Spots Global Cancer Trial Database for giant cell tumor of tendon sheath