A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 139
- 试验地点
- 4
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this Phase I/II study is to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and to evaluate the safety, antitumor activity and pharmacokinetic (PK) profile of MAK683 in patients with advanced malignancies such as Diffuse Large B cell Lymphoma (DLBCL), nasopharyngeal carcinoma (NPC) or other advanced solid tumors for whom no further effective standard treatment is available.
详细描述
The purpose phase I of this trial is to characterize safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MAK683.
The purpose of the phase II of this trial is to evaluate the anti-tumor activity of MAK683. Phase II part will not be opened.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Eastern Cooperative Oncology Group (ECOG): 0 to 2
- •Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014)
- •Advanced or recurrent/metastatic solid tumor, including nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma and sarcoma, with measurable disease as determined by RECIST 1.1.
排除标准
- •Other malignant diseases than the ones being treated in this study
- •Severe and/or uncontrolled medical conditions that in the investigator's opinion could affect the safety of individual or impair the assessment of study result.
- •B-cell lymphoma patients who have received prior allogeneic stem cell transplant
- •Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment
- •Symptomatic central nervous system (CNS) involvement which are neurologically unstable or requiring increasing doses of steroids to control.
- •Patient having out of range laboratory values defined as:
- •Insufficient bone marrow function at screening:
- •Platelets ≤ 50,000/mm3
- •Hemoglobin (Hgb) ≤ 80 g/L
- •Absolute neutrophil count (ANC) ≤ 1000/mm3 2) Insufficient hepatic and renal function at screening:
- •ALP, ALT, and AST > 3 x ULN (>5 x ULN if subject has liver metastases)
- •Total bilirubin >1.5 x ULN
- •Serum creatinine > 1.5 x ULN and/or creatinine clearance ≤ 50 mL/min
研究组 & 干预措施
Phase I - All
advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.
干预措施: MAK683 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: up to 28 days
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety and tolerability
时间窗: up to approximately 3 years
Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions
次要结局
- Area Under the Plasma Concentration (AUC) Time Curve of MAK683(30 months)
- Half-Life of MAK683(30 months)
- Overall Response Rate (ORR)(up to 30 months)
- Peak Plasma Concentration (Cmax) of MAK683(30 months)
- H3K27 tri methylation level in PBMC(up to day 15)
- Progression-free survival (PFS)(up to 30 months)
- Duration of overall response (DOR)(up to 30 months)
- Best Overall Response (BOR)(up to 30 months)