The primary purpose of this study is to assess the tolerability, pharmacokinetics, and efficacy of pimicotinib in Japanese participants with TGCT
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
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)
Single group
Pimicotinib
DrugIn 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.
Safety Run-In Cohort: Number of Participants with Dose Limiting Toxicity (DLT)-like events
Safety Run-In Cohort: Pharmacokinetic (PK) Plasma Concentration of Pimicotinib
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee
Objective Response (OR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC)
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Investigator
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.
Mean Change from Baseline in Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25
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Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Lead sponsor
Merck KGaA, Darmstadt, Germany
Collaborator