A Phase 1 Open-label, Multicenter Dose Escalation and Expansion Study of MT-5111 in Subjects With Previously Treated Advanced HER2-positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 28
- 主要终点
- To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
研究概览
简要总结
This will be a Phase 1b, first in human, open-label, dose escalation and expansion study of MT-5111 (a recombinant fusion protein) given as monotherapy in subjects with HER2-positive solid tumors
详细描述
This study will be conducted in two parts:
Part A (Dose Escalation): The purpose of Part A is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D). Part A will include any type of HER2-positive solid cancer.
Part B (Dose Expansion): The purpose of Part B is to confirm the safety and tolerability of MT-5111 doses selected from those explored in Part A including the MTD or RP2D. Part B will include 3 types of HER2-positive solid cancers in the following 3 expansion groups: Group B1: Breast cancer; Group B2: gastric or gastroesophageal adenocarcinomas (GEA); and Group B3: Other HER2-positive solid cancers.
The Breast Cancer cohort will start enrolling in parallel to Part A.
Up to 178 eligible subjects will be identified and treated through competitive enrollment at multiple study centers globally
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically confirmed, unresectable, locally advanced or metastatic solid cancers:
- •Part A (Dose-Escalation): All HER2-positive solid cancers are eligible
- •Part B (Dose-Expansion): Any type of HER2-positive solid cancer, including breast cancer, and gastric or gastroesophageal adenocarcinomas (GEA).
- •HER2-positive in the latest tumor sample tested for HER2 (testing to be done on a metastatic lesion in cases of metastatic cancers).
- •Relapsed or refractory to or intolerant of existing therapy(ies)
- •At least 1 measurable or evaluable lesion according to RECIST 1.1 (Subjects with evaluable disease only may be included in the dose escalation phase)
- •ECOG performance score of ≤ 1
- •Adequate Bone marrow function as determined by:
- •Absolute neutrophil count (ANC) ≥ 1,000/mm3
- •Platelet count ≥ 75,000 mm³ and
- •Hemoglobin ≥ 8.0 g/dL
- •Red blood cell transfusion within 2 weeks of study treatment start is allowed if hemoglobin levels remain stable
- •Kidney function:
- •Creatinine clearance (CLcr) ≥ 50 mL/min either measured or estimated using the Cockcroft-Gault formula
- •Cardiac Function:
- •Left ventricular ejection fraction (LVEF) ≥ 55% on the echocardiogram (ECHO) assessment (preferred), or multigated acquisition (MUGA) scan, and QTcF ≤ 480 ms for women and QTcF ≤ 450 ms for men [average from three QTcF values on the triplicate 12-lead electrocardiogram (ECG)] at baseline
- •Hepatic function:
- •Total bilirubin ≤ 1.5 x ULN, or ≤ 3 x ULN for subjects with Gilbert's Syndrome and
- •AST ≤ 3 x ULN (or ≤ 5 x ULN if liver metastasis) and ALT ≤ 3 x ULN (or ≤ 5 x ULN if liver metastasis)
排除标准
- •History or current evidence of another tumor that is histologically distinct from the tumor under study
- •Current evidence of new or growing CNS metastases during screening
- •Subjects with known CNS metastases will be eligible if they meet protocol specified criteria
- •Evidence of CTCAE Grade >1 toxicity before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria
- •History or evidence of significant cardiovascular disease
- •Current evidence of active, uncontrolled hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV) (evidenced by detectable viral load by PCR) or acquired immunodeficiency syndrome (AIDS) related illness
- •Current evidence of ≥ grade 2 underlying pulmonary disease
- •Certain exclusionary prior treatments
研究组 & 干预措施
Part A- Dose Escalation
Part A- Dose Escalation in patients with previously treated advanced HER2-positive solid tumors.
The assigned dose level of MT-5111 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e., on day 1, day 8 and day 15 of each cycle).
干预措施: MT-5111 (experimental study drug) (Drug)
Part B- Dose Expansion
Part B - Dose Expansion in previously treated HER2-positive breast, GEA and other HER2-positive solid cancers
Part B will include 3 expansion groups: Group B1 (Breast Cancer) will begin enrolling while Part A is being conducted following the completion of Cohort 7 and Subsequent cohort of subjects in group B1 may enroll into higher doses that are tolerated in Part A. Group B2 (GEA) and Group B3 (Other HER-2 positive solid cancer groups) will begin enrollment after the MTD or RP2D is determined in Part A.
The assigned dose level of MT-5111 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e., on day 1, day 8 and day 15 of each cycle).
干预措施: MT-5111 (experimental study drug) (Drug)
结局指标
主要结局
To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
时间窗: 21 day cycle
Evaluation of safety of MT-5111 as measured by number of subjects with adverse events using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
时间窗: 21 day cycle
Evaluation of tolerability of MT-5111 as measured by number of subjects with dose limiting toxicities (DLTs)
次要结局
- PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC])(Day 1, Day 8, and Day 15 in Each 21-Day cycle)
- To evaluate the immunogenicity of MT-5111(Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit)
- PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax])(Day 1, Day 8, and Day 15 in Each 21-Day cycle)
- PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax])(Day 1, Day 8, and Day 15 in Each 21-Day cycle)
- To evaluate the tumor response to MT-5111(Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose)