Phase 3 Randomized Double-Blind Placebo-Controlled Study of Vimseltinib in Patients with Tenosynovial Giant Cell Tumor

Trial ID: 2024-513624-42-00
Protocol: DCC-3014-03-001
Sponsor: Deciphera Pharmaceuticals Inc.

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Diseases & Conditions

Myasthenia gravis

Objectives

The primary objective of this Phase 3, randomized, placebo-controlled, double-blind study is to evaluate the **anti-tumor activity** of vimseltinib in patients with Tenosynovial Giant Cell Tumor. This is assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 through a blinded independent radiological review (IRR). The clinical relevance of this objective lies in determining the efficacy of vimseltinib as a potential therapeutic option for this condition, which could lead to improved management and outcomes for patients.

Secondary objectives include:

Assessing the anti-tumor activity of vimseltinib using tumor volume score (TVS) and modified RECIST (mRECIST) by blinded IRR.
Evaluating the effects of vimseltinib on range of motion (ROM).
Assessing the effects of vimseltinib on physical function, worst stiffness, worst pain, and quality of life (QoL) using patient-reported outcome (PRO) measures.
Evaluating the safety and tolerability of vimseltinib.

Participants

The clinical trial involves a total of **44 participants** diagnosed with **Tenosynovial Giant Cell Tumor**. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on their ability to understand and comply with the protocol, as well as their willingness to complete patient-reported outcome assessments electronically. The trial population is characterized by individuals with symptomatic disease, experiencing at least moderate pain or stiffness, and having measurable disease per RECIST v1.1 criteria. Participants are required to have adequate organ function and bone marrow reserve, as indicated by specific laboratory assessments. The study includes individuals for whom surgical resection could potentially lead to worsening functional limitations or severe morbidity. Participants must maintain a stable analgesic regimen, if applicable, and be able to take oral medication. The trial also considers lifestyle factors such as the ability to complete 14 consecutive days of questionnaires during the screening period. The study population includes vulnerable individuals, ensuring a comprehensive evaluation of the investigational treatment's efficacy and safety.

Plans and Procedures

The clinical trial is a **Phase 3**, randomized, placebo-controlled, double-blind study designed to assess the efficacy and safety of **vimseltinib** in patients with **Tenosynovial Giant Cell Tumor** (TGCT). The trial consists of two parts: Part 1 is double-blinded, and Part 2 is an open-label study. The primary objective is to evaluate the anti-tumor activity of vimseltinib using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, assessed by a blinded independent radiological review. The trial is expected to conclude by July 2026, with recruitment having commenced in January 2023.

Participants will be involved in the study for a maximum treatment period of 48 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be adults aged 18 years or older with a histologically confirmed diagnosis of TGCT, among other health and compliance criteria. Participants must also have measurable disease per RECIST v1.1 and adequate organ function.

Study visits are structured to ensure comprehensive monitoring and data collection. The screening visit involves a thorough assessment to confirm eligibility, including histological confirmation of TGCT and baseline measurements. Follow-up visits occur at regular intervals to evaluate the objective response rate (ORR) and other secondary endpoints, such as changes in joint range of motion and patient-reported outcomes. The end-of-study visit will finalize data collection and assess the duration of response and any treatment-emergent adverse events.

Participant involvement may be terminated early if there is disease progression, unacceptable toxicity, or withdrawal of consent. The study drug, vimseltinib, is administered orally in a hard capsule form, with a maximum daily dose of 30 mg and a total dose not exceeding 720 mg. The trial's design ensures rigorous assessment of both efficacy and safety, with primary endpoints measured at Week 25, including ORR per RECIST v1.1. Secondary endpoints include changes in physical function and pain scores, as well as the incidence of adverse events.

Treatment

The clinical trial involves the administration of **DCC-3014**, a hard capsule formulation containing the active substance **vimseltinib**. Vimseltinib is a chemical compound with the chemical name 2-(isopropylamino)-3-methyl-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one. The medication is administered orally, with a maximum daily dose of 30 mg and a total maximum dose of 720 mg over a treatment period of up to 48 weeks. The primary objective of the trial is to evaluate the anti-tumor activity of vimseltinib in patients with Tenosynovial Giant Cell Tumor, using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent radiological review.

The study also includes a **placebo** group, where participants receive a placebo designed to match the appearance of DCC-3014. The placebo is administered in the same pharmaceutical form and via the same oral route as the experimental medication. This placebo-controlled design ensures that the effects of vimseltinib can be accurately assessed by comparing outcomes between the treatment and placebo groups. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

Efficacy

The efficacy of the investigational drug **vimseltinib** in the treatment of Tenosynovial Giant Cell Tumor (TGCT) will be assessed using several parameters. The primary endpoint for evaluating efficacy is the Objective Response Rate (ORR), which includes complete response (CR) and partial response (PR) as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, assessed at Week 25. This evaluation will be conducted through a blinded independent radiological review.

Secondary endpoints include the ORR per Tumor Volume Score (TVS) at Week 25, changes from baseline in active range of motion (ROM) of the affected joint, and changes in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25. Additional secondary measures include changes in the Worst Stiffness numeric rating scale (NRS) score, EQ-VAS (EuroQol Visual Analogue Scale), and the Brief Pain Inventory (BPI) Worst Pain NRS score, all assessed at Week 25. The duration of response (DOR) will also be evaluated, defined as the time from first PR or CR to disease progression or death, using RECIST v1.1, TVS, and modified RECIST (mRECIST).

These efficacy parameters will be measured and collected at specified timepoints, primarily at Week 25, using validated scales and imaging techniques. The analysis will be conducted in accordance with the trial protocol to ensure the reliability and validity of the results. The trial will also monitor the incidence of treatment-emergent adverse events (TEAEs) and changes from baseline in laboratory parameters, electrocardiograms (ECGs), and vital signs to assess the safety profile of the treatment.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female participants ≥18 years of age
Histologically confirmed diagnosis of TGCT (formerly known as pigmented villonodular synovitis [PVNS] or giant cell tumor of the tendon sheath [GCT-TS]). Tumor biopsy to confirm TGCT diagnosis will be required if no histology/pathology is available. a. Participants should have TGCT in a single joint and must have TGCT in joints where ROM can be assessed
Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity as judged by surgical consultation or a multidisciplinary tumor board
Symptomatic disease with 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
Participant should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements outlined in Protocol Table 4
An analgesic regimen, if used, needs to be stable( ie, no change in dose) as judged by the Investigator for at least 2 weeks prior to the first dose of study drug
Measurable disease per RECIST v1.1 with at least one lesion having a minimum size of 2 cm as assessed from magnetic resonance imaging (MRI) scans by a central radiologist
Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 21 days prior to the first dose of study drug: a. Bone marrow function: absolute neutrophil count (ANC) ≥1500/μL; hemoglobin ≥10 g/dL; platelet count ≥lower limit of normal (LLN). b. Hepatic function: total serum bilirubin ≤upper limit of normal (ULN); serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ULN. c. Renal function: creatinine clearance ≥50 mL/min based either on urine collection or Cockcroft-Gault estimation. d. Electrolytes ≥LLN for: potassium, magnesium, and calcium
Able to take oral medication
Participants of reproductive potential must: a. Have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening (female participants). b. Agree to follow the contraception requirements outlined in the protocol
The participant is capable of understanding and complying with the protocol and has signed the informed consent form (ICF). A signed ICF must be obtained before any study-specific procedures are performed.
Willing and able to complete the PRO assessments on an electronic device

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Exclusion Criteria

Previous use of systemic therapy (investigational or approved) targeting CSF1 or CSF1R including vimseltinib; previous therapy with imatinib and nilotinib is allowed
Treatment for TGCT, including investigational therapy, during the screening period. NOTE: Participants may not be part of an ongoing or have prior participation in a non TGCT investigational drug study within 30 days of screening. Ongoing participation in a noninterventional study (including observational studies) is permitted
Known metastatic TGCT or other active cancer that requires concurrent treatment (exceptions will be considered on a case-by-case basis depending on tumor type, stage, location, planned treatment, and expected recovery after discussion and approval by Sponsor)
Baseline prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome
Receive concurrent treatment with any prohibited medications • Acetaminophen usage exceeding 3 g/day • Proton-pump inhibitors taken within 4 days prior to the first dose of study drug • Medications that are breast cancer resistance protein (BCRP) or organic cation transporter 2 (OCT2) substrates taken within at least 4 days or 5×half-life (whichever is longer) prior to the first dose of study drug • Medications with a known risk of prolonging the QT interval within at least 14 days or 5×half-life (whichever is longer) prior to the first dose of study drug (see Appendix 1) • Prophylactic use of myeloid growth factors (eg, granulocyte colonystimulating factor [G-CSF], granulocyte macrophage-colony-stimulating factor [GM-CSF])
Major surgery within 14 days of the first dose of study drug; following major surgeries >14 days prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence
Any clinically significant comorbidities, such as significant concomitant arthropathy not related to TGCT in the affected joint, or any other serious medical or psychiatric condition(s), known current alcohol abuse, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the participant to safety risks
Active liver or biliary disease including non-alcoholic steatohepatitis (NASH), or cirrhosis
Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator
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

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Recruiting	10 Jan 2023	20
Germany	Not Recruiting	10 Jan 2023	8
Italy	Not Recruiting	10 Jan 2023	17
The Netherlands	Not Recruiting	10 Jan 2023	—
Norway	Not Recruiting	10 Jan 2023	3
Poland	Not Recruiting	10 Jan 2023	2
Spain	Not Recruiting	10 Jan 2023	15
Netherlands	—	—	14