A Multicenter Phase 1/2, Open-Label Study of DCC-3014 to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 46
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a multicenter, open-label Phase 1/2 study of vimseltinib in patients with malignant solid tumors and tenosynovial giant cell tumor (TGCT). There will be 2 distinct parts in this study: Dose Escalation (Phase 1) and Expansion (Phase 2). Phase 1 will enroll both malignant solid tumor and TGCT patients. Phase 2 will comprise two cohorts (Cohort A and Cohort B) and will only enroll TGCT patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dose Escalation Phase:
- •Patients ≥18 years of age
- •Patients must have:
- •advanced malignant solid tumors; or
- •symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)
- •Malignant solid tumor patients only: Able to provide a tumor tissue sample
- •Must have 1 measurable lesion according to RECIST Version 1.1
- •Malignant solid tumor patients only: Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Adequate organ and bone marrow function
- •If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
- •Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.
- •Expansion Phase (Cohorts A and B)
- •Patients ≥18 years of age
- •Patients must have symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)
- •a) Expansion Cohort B: patients must have prior systemic treatment with anti-CSF1 or anti-CSF1R therapy, with the exception of imatinib or nilotinib
- •Adequate organ and bone marrow function
- •Must have at least 1 measurable lesion according to RECIST Version 1.1
- •If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
- •Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.
排除标准
- •Dose Escalation Phase:
- •Received anticancer therapy or therapy for TGCT, including investigational therapy, within 2 weeks or 28 days for therapies with half-life (t1/2) longer than 3 days prior to the administration of study drug.
- •Unresolved toxicity (Grade >1 or baseline) from previous anticancer therapy or TGCT therapy, excluding alopecia.
- •Known active central nervous system (CNS) metastases.
- •History or presence of clinically relevant cardiovascular abnormalities.
- •Systemic arterial or venous thrombotic or embolic events.
- •QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome.
- •Left ventricular ejection fraction (LVEF) <50%.
- •Concurrent treatment with proton-pump inhibitor(s).
- •Major surgery within 2 weeks of the first dose of study drug.
- •Malabsorption syndrome or other illness that could affect oral absorption.
- •Known human immunodeficiency virus, active hepatitis B, active hepatitis C, or active mycobacterium tuberculosis infection.
- •If female, the patient is pregnant or lactating.
- •Known allergy or hypersensitivity to any component of the study drug.
- •Any other clinically significant comorbidities.
- •Expansion Phase (Cohorts A and B)
- •Expansion Cohort A: received systemic therapy targeting CSF1 or CSF1R; previous therapy with imatinib and nilotinib is allowed.
- •Expansion Cohort B: discontinued systemic therapy targeting anti-CSF1 or anti-CSF1R due to drug-induced liver injury.
- •Treatment with therapy for TGCT, including investigational therapy, within 2 weeks or 28 days for therapies with a t1/2 longer than 3 days prior to the administration of the study drug.
- •Known metastatic TGCT or other active cancer that requires concurrent treatment.
- •QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome.
- •Left ventricular ejection fraction (LVEF) <55%.
- •Concurrent treatment with proton-pump inhibitor(s).
- •Major surgery within 2 weeks of the first dose of study drug.
- •Any clinically significant comorbidities
- •Malabsorption syndrome or other illness that could affect oral absorption.
- •Known human immunodeficiency virus (HIV), active or chronic hepatitis B, active or chronic hepatitis C, or active mycobacterium tuberculosis infection.
- •If female, the patient is pregnant or lactating.
- •Known allergy or hypersensitivity to any component of the study drug.
- •Contraindication for MRI
- •Active liver or biliary disease, including evidence of fatty liver, nonalcoholic steatohepatitis (NASH), or cirrhosis
研究组 & 干预措施
Experimental Treatment
Dose Escalation Phase: Increasing doses of vimseltinib beginning at 10 milligram (mg) once daily (QD) for 28 day cycles until disease progression or unacceptable toxicity.
Expansion Phase: Dosing of different patient cohorts at the dose level determined from the Dose Escalation Phase of the study.
干预措施: Vimseltinib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Day 1 - Day 28 of Cycle 1 for each dose level tested
Determine the maximum tolerated dose.
Duration of response rate (DOR) (Expansion Phase only)
时间窗: Date from PR or CR to disease progression or death (Estimated up to 24 months)
Measure time from partial response (PR) or complete response (CR) to disease progression or death.
Number of Patients with Dose-Limiting Toxicities (DLTs)
时间窗: Day 1- Day 28 of Cycle 1 for each dose level tested
Identify the number of patients with DLTs for each dose level tested.
Area under the concentration-time curve (AUC) of Vimseltinib
时间窗: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
Measure the AUC of vimseltinib.
Time to maximum observed concentration of Vimseltinib
时间窗: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
Measure the time to maximum plasma concentration of vimseltinib in patients.
Trough observed concentration of Vimseltinib
时间窗: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
Measure the observed trough concentration of vimseltinib in patients.
Maximum observed concentration of Vimseltinib
时间窗: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
Measure the maximum observed concentration of vimseltinib in patients.
Objective response rate (ORR= complete response [CR]+partial response [PR]) (Expansion Phase only)
时间窗: At Week 25 (Cycle 7, Day 1)
Assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
Half life of Vimseltinib
时间窗: Cycle 1 Day 1 and Day 8, and Cycle 2 Day 1 (pre-dose and at multiple time points (up to 8 hours) post-dose)
Measure half life of vimseltinib in patients.
次要结局
- Worst Stiffness Numeric Rating Scale (NRS) Score (Expansion Phase only)(Baseline to Week 25 (Cycle 7, Day 1))
- Range of Motion (ROM) (Expansion Phase only)(Baseline to Week 25 (Cycle 7, Day 1))
- Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Score (Expansion Phase only)(Baseline to Week 25 (Cycle 7, Day 1))
- Response rate (Expansion Phase only)(At Week 25 (Cycle 7, Day 1))
- Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) Score (Expansion Phase only)(Baseline to Week 25 (Cycle 7, Day 1))