A Phase 1, Open-Label, First-in-Human, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-304 in Adults With Advanced HER2-Expressing Solid Tumors
概览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 6
- 主要终点
- Type, incidence and severity of Adverse Events
概览
简要总结
This clinical trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of MT-304 in adults with advanced HER2-expressing solid tumors. The main questions it aims to answer are:
- What is the safety profile of MT-304 when administered alone or with nivolumab?
- What is the recommended Phase 2 dose (RP2D) of MT-304?
Participants will:
- Receive MT-304 alone (every 14 days) or with nivolumab (every 28 days).
- Attend regular clinic visits for assessments and monitoring.
- Continue treatment until disease progression, unacceptable toxicity, or study discontinuation.
详细描述
This multicenter, open-label, Phase 1 trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of MT-304 in adults aged 18 and older with advanced HER2-expressing solid tumors.
The study consists of two treatment modules:
- Module 1 (Monotherapy): Participants receive MT-304 every 14 days for 28-day cycles, with dosing adjustments based on clinical benefit and safety evaluations.
- Module 2 (Combination Therapy): Participants receive MT-304 in combination with nivolumab, administered every 14 days and 28 days, respectively, also allowing for dosing adjustments.
The Bayesian Optimal Interval (BOIN) design will guide dose escalation, overseen by a Safety Review Committee to establish the recommended Phase 2 dose (RP2D).
Regular assessments, including vital signs and laboratory tests, will monitor safety and efficacy throughout the trial, with follow-up visits for up to 2 years post-treatment.
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
- •Aged 18 years or above
- •Histologically confirmed diagnosis of metastatic or advanced epithelial cancer expressing HER2 (Note: Participants with other tumor types expressing HER2 may be considered pending discussion with the Medical Monitor).
- •Measurable lesion per RECIST 1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or
- •Adequate Organ function
排除标准
- •Known active CNS metastasis and/or carcinomatous meningitis.
- •Any acute illness including fever.
- •History of symptomatic congestive heart failure
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites
- •Active autoimmune disease not related to prior therapy for primary malignancy that has required systemic therapy in the last 1 year.
研究组 & 干预措施
MT-304 Monotherapy
Participants receive MT-304 administered intravenously once every 14 days (Q14D) in escalating dose levels.
干预措施: MT-304 (Drug)
MT-304 + Nivolumab Combination Therapy
Participants receive MT-304 administered intravenously once every 14 days (Q14D) in combination with nivolumab as "per local label" administered once every 28 days (Q28D).
干预措施: MT-304 + Nivolumab (Drug)
结局指标
主要结局
Type, incidence and severity of Adverse Events
时间窗: Up to 90 days from the last dose of Investigational Medicinal Product (IMP)
Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.
Number of Participants With Change From Baseline in Vital Signs (Composite Safety Outcome)
时间窗: Up to 30 days from the last dose of IMP
Body temperature, body weight, pulse rate, and blood pressure (systolic and diastolic) assessed collectively; participants with clinically significant changes in any vital sign parameter will be summarized as a composite safety outcome.
Number of Participants With Abnormal Clinical Laboratory Parameters (Composite Safety Outcome)
时间窗: Up to 30 days from the last dose of IMP
Hematology, clinical chemistry, coagulation, virology testing, and urinalysis assessed collectively; participants with abnormalities in any laboratory parameter will be summarized as a composite safety outcome.
Number of Participants With Change From Baseline in ECG Parameters (Composite Safety Outcome)
时间窗: Screening through Day 28, with assessments performed on Screening, Day 1 (pre-dose), and Day 28.
PR interval, QRS duration, QT interval, corrected QT interval (QTc), and heart rate assessed collectively from 12-lead ECG recordings; participants with clinically significant changes in any ECG parameter will be summarized as a composite safety outcome.
Maximum Tolerated Dose (MTD)
时间窗: 28 days from the last dose of IMP
The MTD in Module 1 (monotherapy) will be determined based on dose-limiting toxicities (DLTs).
Optimal Biological Dose (OBD)
时间窗: 28 days from the last dose of IMP
The OBD in Module 2 (combination) will be identified based on dose-limiting toxicities (DLTs).
次要结局
- To assess adverse events of special interest (AESI) by measuring infusion reaction(Upto 90 days from the last dose of IMP)
- To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS)(Upto 90 days from the last dose of IMP)
- To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS)(Upto 90 days from the last dose of IMP)
- To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction(Upto 90 days from the last dose of IMP)
- To assess the incidence of second primary malignancies reported as adverse events of special interest (AESI) occurring during the study treatment period and long-term follow-up.(From first dose of Investigational Medicinal Product (IMP) through end of study and follow-up (up to 2 years))
- Pharmacokinetics (PK)(From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).)