Study of Pimicotinib in Japanese Participants With Tenosynovial Giant Cell Tumor (TGCT) (J-MANEUVER)

Phase 2, Single-arm Study to Investigate the Tolerability, Pharmacokinetics, Efficacy, and Safety of Pimicotinib in Japanese Participants With Tenosynovial Giant Cell Tumor

The primary purpose of this study is to assess the tolerability, pharmacokinetics, and efficacy of pimicotinib in Japanese participants with TGCT

Study Overview

• Status: Recruiting
• Conditions: Tenosynovial Giant Cell Tumor
• Intervention / Treatment: Drug: Pimicotinib

Detailed Description

The purpose of this study is to assess the tolerability, pharmacokinetics (PK), efficacy, and safety of pimicotinib in Japanese participants with TGCT in two cohorts: Safety Run-in and Expansion.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Communication Center; Phone Number: +49 6151 72 5200; Email: service@emdgroup.com

Study Locations

• Japan
  • Fukuoka, Japan
    • Recruiting
    • Kyushu University Hospital - 300173484
  • Nagoya, Japan
    • Recruiting
    • Nagoya University Hospital - 300176284

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Japanese participants with a diagnosis of TGCT that has been histologically confirmed at the local laboratory and is unresectable (that is [i.e.] it is located in a complex anatomical site, extensively invasive, and cannot be completely resected; or a surgical operation may cause dysfunction or serious complications). Symptomatic disease because of active TGCT, defined as a worst pain of greater than or equal to [>=] 4 within 2 weeks prior to enrollment (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine"), and/or a worst stiffness of >= 4 within 2 weeks prior to first dose of pimicotinib (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine")
• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to [<=] 1
• Participants with adequate hepatic, renal hematologic functions
• Other protocol defined inclusion criteria may apply

Exclusion Criteria:

• Known additional malignancy that required active treatment and may affect the participant's participation in the study or affect the outcome of the study as assessed by the Investigator. Exceptions include cured basal cell carcinoma of skin, squamous cell carcinoma of skin, and other carcinoma in situ
• Serious gastrointestinal bleeding within 3 months of first dose of pimicotinib or factors that significantly affected the absorption of oral drug, such as inability to take oral medication or significant nausea and vomiting, malabsorption, external bile duct drainage, massive small-bowel resection, etc.
• Impaired cardiac function or clinically significant cardiac disease, including any one of the following: New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure; prolongation of the rate corrected QT interval based on repeated demonstration of QT interval corrected using Fridericia's formula (QTcF) greater than (>) 480 milliseconds (ms), or history of long QT interval corrected (QTc) syndrome; Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) or below the lower limit of normal, whichever is higher
• Cerebrovascular accident/stroke (within 6 months of first dose of pimicotinib)
• Other protocol defined exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Safety Run-In followed by Expansion Cohort: Pimicotinib

Drug: Pimicotinib; In the Safety Run-in Cohort, participants will receive 50 milligrams (mg) of pimicotinib once daily (QD), orally in 28-day cycles until disease progression (DP), death, discontinuation, or any other reason. The Safety Monitoring Committee (SMC) will monitor and assess tolerability of pimicotinib 50 mg QD during the safety run-in cohort. After making a recommendation about opening the Expansion Cohort based on the assessment in safety run-in cohort, participants will receive 50 mg of pimicotinib monotherapy QD, orally in 28-day cycles until disease progression (DP), death, discontinuation, or any other reason.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety Run-In Cohort: Number of Participants with Dose Limiting Toxicity (DLT)-like events	Day 1 up to Day 28 of Cycle 1 (each cycle is of 28 days)
Safety Run-In Cohort: Pharmacokinetic (PK) Plasma Concentration of Pimicotinib	Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is of 28 days)
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee	Time from first study treatment until progressive disease or death, assessed up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (OR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC)		Time from first study treatment until progressive disease or death, assessed up to approximately 2 years
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator		Time from first study treatment until progressive disease or death, assessed up to approximately 2 years
Mean Change from Baseline in Range of Motion (ROM) at Week 25	The ROM of the affected joint or tumor site will be assessed using a goniometer. Measurements will be recorded in degrees.	Baseline, Week 25
Mean Change from Baseline in Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25		Baseline, Week 25
Mean Change from Baseline in Brief Pain Inventory (BPI)- Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25		Baseline, Week 25
Mean Change from Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Physical Functioning Score at Week 25	The PROMIS Physical Function scale is measured using a series of questions assessing a person's ability to perform various physical tasks, with responses scored on a 5-point Likert scale. The raw score from these responses is then converted to a standardized T-score on a scale of 0 to 100, with a mean of 50 and a standard deviation of 10. The total score is the final T-score.	Baseline, Week 25
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee		Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years
Duration of Response (DOR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC)		Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator		Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years
Mean Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Scale Score at Week 25	The EQ-5D-5L questionnaire is a standardized instrument used as a measure of health outcome. The 5-dimension health status measure evaluates: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: an extreme problem. Higher scores (closer to 5) indicate worse health status.	Baseline, Week 25
Mean Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score at Week 25	The EQ-5D-5L questionnaire is a standardized instrument used as a measure of health outcome. The VAS records the participant's self-rated health on a vertical VAS where the endpoints are labelled 'Worst imaginable health state' and 'Best imaginable health state'. VAS ranges from 0 to 100. Higher scores indicate better perceived health.	Baseline, Week 25
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events		Time from first study treatment, assessed up to approximately 2 years
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pimicotinib		Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is of 28 days)
Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Pimicotinib After Repeated Administration		Pre-dose up to 24 hours post-dose on Cycle 1 Day 15 (each cycle is of 28 days)
Accumulation Ratio of Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC0-24) of Pimicotinib After Repeated Administration		Pre-dose up to 24 hours post-dose on Cycle 1 Day 15 (each cycle is of 28 days)
Plasma Concentration Observed at the End of a Dosing Interval Immediately before Next Dosing (Ctrough) of Pimicotinib		Pre-dose on Cycle 1 Day 15 (each cycle is of 28 days)

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Medical Information Location Map - Med Info Contacts
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2026
• Primary Completion (Estimated): November 22, 2029
• Study Completion (Estimated): November 22, 2029

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Nodular TGCT; diffuse TGCT; giant cell tumor of tendon sheath; colony-stimulating factor 1 receptor (CSF-1R) inhibitor
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Neoplasms; Joint Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Synovitis; Tendinopathy; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath
• Other Study ID Numbers: MS265601_0008; jRCT2071250149 (Other Identifier: Japan Registry of Clinical Trials (JRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union.
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No