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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Safety Run-In Cohort: Number of Participants with Dose Limiting Toxicity (DLT)-like events [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Time from first study treatment until progressive disease or death, assessed up to approximately 2 years]

Вторичные конечные точки (12)

• Objective Response (OR) According to Tumor Volume Score (TVS) as Assessed by Independent Review Committee (IRC) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline, Week 25]
• Mean Change from Baseline in Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25 [Срок оценки: Baseline, Week 25]
• Mean Change from Baseline in Brief Pain Inventory (BPI)- Worst-Stiffness-Numeric Rating Scale (NRS) Score at Week 25 [Срок оценки: Baseline, Week 25]
• Mean Change from Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Physical Functioning Score at Week 25 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline, Week 25]
• Mean Change From Baseline in EQ-5D-5L Visual Analog Scale (VAS) Score at Week 25 [Срок оценки: Baseline, Week 25]
• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events [Срок оценки: Time from first study treatment, assessed up to approximately 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Япония · 3 центра

• National Cancer Center Hospital — Chūōku
• Kyushu University Hospital - 300173484 — Fukuoka
• Nagoya University Hospital - 300176284 — Nagoya

Идентификаторы

NCT: NCT07499362 · MS265601_0008 · jRCT2071250149

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗