A Phase I/II Study of LM-2417 in Subjects With Advanced Solid Tumours

Официальное название

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

Обзор

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.

Вмешательства

• Препарат LM-2417
  Q2W/Q3W,Intravenous Drip
• Препарат Docetaxel
  Q3W,Intravenous Drip
• Препарат Toripalimab/Tirelizumab
  Q3W,Intravenous Drip
• Препарат Carboplatin
  Q3W,Intravenous Drip
• Препарат Niraparib
  QD,Oral Administration
• Препарат Lenvatinib
  QD,Oral Administration

Первичные конечные точки

• Incidence of adverse events (AEs) [Срок оценки: 60 weeks]
• Incidence of dose-limitingtoxicity (DLT) [Срок оценки: 60 weeks]
• Incidence of serious adverse event (SAE) [Срок оценки: 60 weeks]
• Temperatures [Срок оценки: 60 weeks]
• Pulse in BPM(Beat per Minute) [Срок оценки: 60 weeks]
• Blood Pressure in mmHg [Срок оценки: 60 weeks]
• Weight in Kg [Срок оценки: 60 weeks]
• Height in centimeter [Срок оценки: 60 weeks]
• Laboratory tests-Blood Routine examination [Срок оценки: 60 weeks]
• Laboratory tests-Urine Routine test [Срок оценки: 60 weeks]

Вторичные конечные точки (12)

• Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) [Срок оценки: 112 weeks]
• PK Parameter:Time of Maximum Observed Concentration (Tmax) [Срок оценки: 112 weeks]
• PK Parameter: Area Under the Concentration-time Curve(AUC) [Срок оценки: 112 weeks]
• PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss) [Срок оценки: 112 weeks]
• PK Parameter: Steady State Minimum Concentration(Cmin,ss) [Срок оценки: 112 weeks]
• PK Parameter: Systemic Clearance at Steady State (CLss) [Срок оценки: 112 weeks]
• PK Parameter: Accumulation Ratio (Rac) [Срок оценки: 112 weeks]
• PK Parameter: Elimination Half-life (t1/2) [Срок оценки: 112 weeks]
• PK Parameter: Volume of Distribution at Steady-State (Vss) [Срок оценки: 112 weeks]
• PK Parameter: Degree of Fluctuation (DF) [Срок оценки: 112 weeks]
• Immunogenicity of LM-2417 [Срок оценки: 112 weeks]
• Biomarker correlation(NaPi2b) [Срок оценки: 112 weeks]

Критерии участия

Критерии включения

• 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 0-1.
• 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.

Критерии исключения

• 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-2417.
• 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 v5.0.
• 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-2417.
• 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-2417.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• FuDan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06682780 · LM2417-01-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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