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NCT Number: NCT07499362

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

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

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Key information

Conditions

Tenosynovial Giant Cell Tumor Giant Cell Tumor of Tendon Sheath Giant Cell Tumors Joint Diseases Muscular Diseases Musculoskeletal Diseases Neoplasms Neoplasms by Histologic Type Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Synovitis Tendinopathy

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Cancer Center Hospital, Chūōku, Japan

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pimicotinib

Drug

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.

Primary outcomes

  1. Safety Run-In Cohort: Number of Participants with Dose Limiting Toxicity (DLT)-like events

    Time frame: Day 1 up to Day 28 of Cycle 1 (each cycle is of 28 days)

  2. Safety Run-In Cohort: Pharmacokinetic (PK) Plasma Concentration of Pimicotinib

    Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is of 28 days)

  3. Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee

    Time frame: Time from first study treatment until progressive disease or death, assessed up to approximately 2 years

Secondary outcomes

  1. Objective Response (OR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC)

    Time frame: Time from first study treatment until progressive disease or death, assessed up to approximately 2 years

  2. Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator

    Time frame: Time from first study treatment until progressive disease or death, assessed up to approximately 2 years

  3. Mean Change from Baseline in Range of Motion (ROM) at Week 25

    Time frame: Baseline, Week 25

    The ROM of the affected joint or tumor site will be assessed using a goniometer. Measurements will be recorded in degrees.

  4. Mean Change from Baseline in Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25

    Time frame: Baseline, Week 25

  5. Mean Change from Baseline in Brief Pain Inventory (BPI)- Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25

    Time frame: Baseline, Week 25

  6. Mean Change from Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Physical Functioning Score at Week 25

    Time frame: Baseline, 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.

  7. 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 frame: Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years

  8. Duration of Response (DOR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC)

    Time frame: Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years

  9. Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator

    Time frame: Time from first documentation of objective response until progressive disease (PD) or death, assessed approximately up to 2 years

  10. Mean Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Scale Score at Week 25

    Time frame: Baseline, 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.

  11. Mean Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score at Week 25

    Time frame: Baseline, 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.

  12. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events

    Time frame: Time from first study treatment, assessed up to approximately 2 years

  13. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Pimicotinib

    Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is of 28 days)

  14. Accumulation Ratio for Maximum Observed Plasma Concentration [Racc(Cmax)] of Pimicotinib After Repeated Administration

    Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15 (each cycle is of 28 days)

  15. Accumulation Ratio of Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC0-24) of Pimicotinib After Repeated Administration

    Time frame: Pre-dose up to 24 hours post-dose on Cycle 1 Day 15 (each cycle is of 28 days)

  16. Plasma Concentration Observed at the End of a Dosing Interval Immediately before Next Dosing (Ctrough) of Pimicotinib

    Time frame: Pre-dose on Cycle 1 Day 15 (each cycle is of 28 days)

Study contacts

Contact information is provided by the study sponsor or research team.

Communication Center

CONTACT

[email protected]

+49 6151 72 5200

Sponsors and collaborators

Lead sponsor

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Mar 30, 2026
Registry last updated
Jul 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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