A Phase I/II, First-in-Human (FIH), Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of LM-364 as a Single Agent or in Combination With Anti-tumor Therapy in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 7
- 主要终点
- Dose limiting toxicity (DLT)
研究概览
简要总结
For Phase I, to assess the safety and tolerability, obtain the recommended phase 2 dose (RP2D)/optimal biologic dose (OBD) and/or Maximum Tolerated Dose (MTD) for LM-364 as a single agent or in combination with tislelizumab in participants with advanced solid tumors.
For Phase II, to assess the preliminary anti-tumor activity of IMP in participants with advanced solid tumors.
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
- •Participants who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
- •Participants must be ≥18 years or the legal age of consent at the time of signing the ICF.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy ≥ 3 months.
- •Adequate organ and bone marrow function as defined by protocol.
- •Participants who are able to communicate well with investigators and understand and adhere to the requirements of this study.
排除标准
- •Participant in any other clinical trial within 28 days prior to 1st dosing of LM-
- •Any adverse event from prior anti-tumour therapy has not yet recovered to ≤ grade 1 of CTCAE v6.
- •Participants with uncontrolled tumour-related pain.
- •Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-
- •Participants who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-
- •Participants who have severe cardiovascular disease.
- •Participants who have uncontrolled or severe illness.
- •Participants who have a history of immunodeficiency disease.
- •Participants with a known history of autoimmune disease.
- •Child-bearing potential female who have positive results in pregnancy test or are lactating.
- •Participants who have psychiatric illness or disorders that may preclude study compliance.
- •Participants who is judged as not eligible to participate in this study by the investigator.
研究组 & 干预措施
LM-364 Monotherapy
干预措施: LM-364 for injection (Drug)
LM-364 Combination Therapy
干预措施: LM-364 for injection (Drug)
LM-364 Combination Therapy
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Dose limiting toxicity (DLT)
时间窗: 78 Weeks
Phase I
Adverse events (AEs)
时间窗: 78 weeks
Phase I
serious adverse events (SAEs)
时间窗: 78 weeks
Phase I
Temperatures
时间窗: 78 weeks
Phase I
Pulse in BPM
时间窗: 78 weeks
Phase I
Blood Pressure in mmHg
时间窗: 78 weeks
Phase I
Weight in Kg
时间窗: 78 weeks
Phase I
Height in centimeter
时间窗: 78 weeks
Phase I
Laboratory examinations--Blood Routine examination
时间窗: 78 weeks
Phase I
Laboratory examinations--Blood biochemistry
时间窗: 78 weeks
Phase I
Laboratory examinations-Urine Routine test
时间窗: 78 weeks
Phase I
Laboratory examinations--Coagulation function
时间窗: 78 weeks
Phase I
Laboratory examinations--Thyroid function
时间窗: 78 weeks
Phase I
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in HR
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in RR
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in PR
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in QRS
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in QT
时间窗: 78 weeks
Phase I
12-lead electrocardiogram (ECG) in QTcF
时间窗: 78 weeks
Phase I
ECOG score-Cooperative Oncology Group score
时间窗: 78 weeks
Phase I
Objective Response Rate (ORR)
时间窗: 52 weeks
Phase II
次要结局
- PK Parameter: Area Under the Concentration-time Curve(AUC)(130 week)
- Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)(130 weeks)
- PK Parameter:Time of Maximum Observed Concentration (Tmax)(130 weeks)
- PK Parameter: Elimination Half-life (T1/2)(130 weeks)
- PK Parameter: Steady State Maximum Concentration(Cmax,ss)(130 weeks)
- PK Parameter: Steady State Minimum Concentration(Cmin,ss)(130 weeks)
- PK Parameter: Systemic Clearance at Steady State (CLss)(130 weeks)
- PK Parameter: Volume of Distribution at Steady-State (Vss)(130 weeks)
- PK Parameter: Accumulation Ratio (Rac)(130 weeks)
- PK Parameter: Degree of Fluctuation (DF)(130 weeks)
- Immunogenicity testing-Anti-drug antibody(130 weeks)
- Immunogenicity testing-neutralizing antibody (Nab)(130 weeks)
- Objective response rate (ORR)(78 weeks)
- Duration of response (DOR)(130 weeks)
- Disease control rate (DCR = CR + PR + SD)(130 weeks)
- Progression free survival according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)(130 weeks)
- Overall survival (OS)(130 weeks)
- Changes of target lesions from baseline in Millimeter(130 weeks)
- To analysis the metabolites of LM-364 if possible(78 weeks)
- QTc-PK relationship -> Correlation concentrations (total antibody, free DXd) vs ΔQTcF (Fridericia's correction)(78 weeks)
- Incidence of adverse events (AEs)(52 weeks)
- Incidence of serious adverse events (SAEs)(52 weeks)
- Temperature (Celsius)(52 weeks)
- Pulse in BPM(Beat per Minute)(52 weeks)
- Blood Pressure in mmHg(52 weeks)
- Weight in Kg(52 weeks)
- Height in centimeters(52 weeks)
- Laboratory examinations--Blood Routine examination(52 weeks)
- Laboratory tests-Urine Routine test(52 weeks)
- Laboratory tests-Blood biochemistry(52 weeks)
- Laboratory tests- Coagulation function(52 weeks)
- Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage(52 weeks)
- 12-lead electrocardiogram (ECG) in HR(52 weeks)
- 12-lead electrocardiogram (ECG) in RR(52 weeks)
- 12-lead electrocardiogram (ECG) in PR(52 weeks)
- 12-lead electrocardiogram (ECG) in QRS(52 weeks)
- 12-lead electrocardiogram (ECG) in QT(52 weeks)
- 12-lead electrocardiogram (ECG) in QTcF(52 weeks)
- Eastern Cooperative Oncology Group score(52 weeks)