An Open-label, Dose-escalation, and Dose-expansion Phase I/II Clinical Study of Safety, Tolerability, Pharmacokinetic Profile, and Initial Efficacy of LM-2417 for Injection Alone or in Combination With Other Antitumor Agents in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
This study is to assess the safety and tolerability, obtain the recommended phase 2 dose(RP2D)/or Maximum Tolerated Dose (MTD) for LM-2417 as a single agent or in combination with other anti-tumour agents in subjects with advanced solid tumours.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
- •Aged 18-80 years old (including boundary values) , male or female.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy ≥ 3 months.
- •Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, or currently lack or are intolerant of, standard therapy.
- •Subjects must have Archived Samples or fresh tumor tissue specimens are required for testing.
- •At least one evaluable lesion.
- •Subjects must show appropriate organ and marrow function inlaboratory examinations within 7 days prior to the first dose.
- •Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception prior to study entry, during the study and for 6 months after the last dose of study drug.
- •Subjects who can communicate well with investigators and understand and adhere to the requirements of this study.
- •Single-agent dose of 6mg/kg, 12mg/kg and and combined cohort：Subjects tested positive for biomarkers.
排除标准
- •Previously received with same target therapy.
- •Subjects has participated in any other interventional clinical trial within 28 days prior to the first dosing of LM-
- •Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-2417, including radiotherapy, chemotherapy, endocrine therapy, and immunotherapy, etc.
- •Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.
- •Poorly controlled tumor-related pain.
- •Subjects with symptomatic/active central nervous system (CNS)metastases.
- •Subject who have uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Subjects with known hypersensitivity to antibody therapy;
- •Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) for more than 7 days or other systemic immunosuppressive medications within 2 weeks prior to the first dosing of LM-
- •Previous or current known autoimmune disease.
- •Subject who has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
- •Use of any live vaccine or live attenuated vaccines within 28 days prior to the first dosing of LM-2417.;
- •Subjects who are using therapeutic doses of anticoagulants such as heparin or vitamin K antagonists.
- •Subjects who received major surgery or interventional treatment within28 days prior to the first dosing of LM-
- •Subject who have history of severe cardiovascular disease.
- •Subjects who have uncontrolled or severe illness.
- •HIV infection, active HBV or HCV infection.
- •Subjects who have other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening.
- •Child-bearing potential female who have positive results in pregnancy test or are lactating.
- •Subject who have a known psychiatric diseases or disorders that may affect compliance with the trial.
- •Subject who is judged as not eligible to participate in this study by the investigator.
研究组 & 干预措施
LM-2417 combination expansion
干预措施: LM-2417 (Drug)
LM-2417 combination expansion
干预措施: Docetaxel (Drug)
LM-2417 combination therapy exploratory
干预措施: Docetaxel (Drug)
LM-2417 combination therapy exploratory
干预措施: Toripalimab/Tirelizumab (Drug)
LM-2417 combination therapy exploratory
干预措施: Carboplatin (Drug)
LM-2417 combination expansion
干预措施: Niraparib (Drug)
LM2417 Dose Escalation(Q2W/Q3W)
干预措施: LM-2417 (Drug)
LM-2417 combination therapy exploratory
干预措施: LM-2417 (Drug)
LM-2417 combination therapy exploratory
干预措施: Niraparib (Drug)
LM-2417 combination therapy exploratory
干预措施: Lenvatinib (Drug)
LM-2417 combination expansion
干预措施: Toripalimab/Tirelizumab (Drug)
LM-2417 combination expansion
干预措施: Carboplatin (Drug)
LM-2417 combination expansion
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: 60 weeks
Phase I/II
Incidence of dose-limitingtoxicity (DLT)
时间窗: 60 weeks
Phase I/II
Incidence of serious adverse event (SAE)
时间窗: 60 weeks
Phase I/II
Temperatures
时间窗: 60 weeks
Phase I/II
Pulse in BPM(Beat per Minute)
时间窗: 60 weeks
Phase I/II
Blood Pressure in mmHg
时间窗: 60 weeks
Phase I/II
Weight in Kg
时间窗: 60 weeks
Phase I/II
Laboratory tests-Blood Routine examination
时间窗: 60 weeks
Phase I/II
Laboratory tests-Urine Routine test
时间窗: 60 weeks
Phase I/II
Height in centimeter
时间窗: 60 weeks
Phase I/II
Laboratory tests-Blood biochemistry
时间窗: 60 weeks
Phase I/II
Laboratory tests- Coangulation function
时间窗: 60 weeks
Phase I/II
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
时间窗: 60 weeks
Phase I/II
12-lead electrocardiogram (ECG) in HR
时间窗: 60 weeks
Phase I/II
12-lead electrocardiogram (ECG) in RR
时间窗: 60 weeks
Phase I/II
12-lead electrocardiogram (ECG) in PR
时间窗: 60 weeks
Phase I/II
12-lead electrocardiogram (ECG) in QRS
时间窗: 60 weeks
Phase I/II
12-lead electrocardiogram (ECG) in QT
时间窗: 60 weeks
Phase I/II
ECOG(Eastern Cooperative Oncology Group) score
时间窗: 60 weeks
Phase I/II
Overall Response Rate (ORR)
时间窗: 76 weeks
Phase I/II
12-lead electrocardiogram (ECG) in QTcF
时间窗: 60 weeks
Phase I/II
次要结局
- Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)(112 weeks)
- PK Parameter:Time of Maximum Observed Concentration (Tmax)(112 weeks)
- PK Parameter: Area Under the Concentration-time Curve(AUC)(112 weeks)
- PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss)(112 weeks)
- PK Parameter: Steady State Minimum Concentration(Cmin,ss)(112 weeks)
- PK Parameter: Volume of Distribution at Steady-State (Vss)(112 weeks)
- PK Parameter: Systemic Clearance at Steady State (CLss)(112 weeks)
- PK Parameter: Accumulation Ratio (Rac)(112 weeks)
- PK Parameter: Elimination Half-life (t1/2)(112 weeks)
- PK Parameter: Degree of Fluctuation (DF)(112 weeks)
- Immunogenicity of LM-2417(112 weeks)
- Biomarker correlation(NaPi2b)(112 weeks)
- Duration of Response (DOR) in Month(64 weeks)
- Disease control rate (DCR) in percentage(64 weeks)
- progression-free survival (PFS) in Month(64 weeks)
- Safety: AE/SAE (Number of participants with treatment-related adverse events as Overall survival (OS) in Month(64 weeks)
- Changes of target lesions from baseline in Millimeter(64 weeks)
- AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0) Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)(64 weeks)