Study of Vimseltinib for Tenosynovial Giant Cell Tumor

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Tenosynovial Giant Cell Tumor, Pigmented Villonodular Synovitis, Giant Cell Tumor of Tendon Sheath, Tenosynovial Giant Cell Tumor, Diffuse, Tenosynovial Giant Cell Tumor, Localized

Intervention / Treatment
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* Drug: vimseltinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years of age TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening) Symptomatic disease as defined as at least moderate pain or at least moderate stiffness (defined as a score of 4 or more, with 10 describing the worst condition) within the screening period and documented in the medical record Participants should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements as outlined in study protocol Must have stable analgesic regimen, as judged by the investigator, for at least 2 weeks prior to first dose of study drug Must have measurable disease, as per RECIST Version 1.1, with at least one lesion having a minimum size of 2cm Adequate organ and bone marrow function If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements Must provide signed consent to participate in the study and is willing to comply with study-specific procedures Willing and able to complete the patient-reported outcome (PRO) assessments on an electronic device Exclusion Criteria: Previous use of systemic therapy (investigational or approved) targeting colony stimulating factor 1 (CSF1) or CSFR1 receptor (CSF1R); previous therapy with imatinib and nilotinib is allowed Received therapy for TGCT, including investigational therapy during the screening period. Participated in a non-TGCT investigational drug study within 30 days of screening. Known metastatic TGCT or other active cancer that requires concurrent treatment (exceptions will be considered on a case-by-case basis) QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome Concurrent treatment with any study-prohibited medications Major surgery within 14 days of the first dose of study drug Any clinically significant comorbidities Active liver or biliary disease including nonalcoholic steatohepatitis (NASH) or cirrhosis Malabsorption syndrome or other illness that could affect oral absorption Known active human immunodeficiency virus (HIV), acute or chronic hepatitis B, acute or chronic hepatitis C, or known active mycobacterium tuberculosis infection If female, the participant is pregnant or breastfeeding Known allergy or hypersensitivity to any component of the study drug Contraindication to MRI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1/Part 2 - vimseltinib/vimseltinib<br>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 | Drug: vimseltinib<br>* CSF1R inhibitor<br>* Other names: DCC-3014;|
| Placebo Comparator: Part 1/Part 2 - placebo/vimseltinib<br>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 | Drug: vimseltinib<br>* CSF1R inhibitor<br>* Other names: DCC-3014;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR= complete response [CR]+partial response [PR]) per RECIST Version 1,1 | Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Baseline to Week 25 (Cycle 7, Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR per Tumor Volume Score (TVS) | 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. | Baseline to Week 25 (Cycle 7, Day 1) | 
| Range of motion (ROM) | Mean change from baseline in active ROM of the affected joint, relative to a reference standard at Week 25 | Baseline to Week 25 (Cycle 7, Day 1) | 
| Physical function | Mean change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25 | Baseline to Week 25 (Cycle 7, Day 1) | 
| Worst stiffness | Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score at Week 25 | Baseline to Week 25 (Cycle 7, Day 1) | 
| Quality of life (QoL) | Mean change from baseline in EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25 | Baseline to Week 25 (Cycle 7, Day 1) | 
| Worst pain | 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 | Baseline to Week 25 (Cycle 7, Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TGCT, PVNS