Study of LM-299 in Subjects Advanced Malignant Tumors

Официальное название

A Phase I/II, Open-label, Dose Escalation and Dose Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of LM-299 Injection as Monotherapy or in Combination With Other Anti-tumor Therapies in Patients With Advanced Solid Tumors

Обзор

For Phase I Dose Escalation Stage, to assess the safety and tolerability of LM-299 in patients with advanced solid tumors,determine the maximum tolerated dose (MTD) or optimal biological dose (OBD), and explorethe recommended dose for expansion (RDE) in patients with advanced solid tumours.. For Phase II Dose Expansion Stage, to assess the antitumor activity of LM-299 in patients with various advanced solid tumors.

Вмешательства

• Препарат LM-299
  Q2W/Q3W,Intravenous Drip

Первичные конечные точки

• Incidence of dose-limitingtoxicity (DLT) [Срок оценки: 53 weeks]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Срок оценки: 53 weeks]
• Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage [Срок оценки: 53 weeks]
• Overall Response Rate (ORR) [Срок оценки: 50 weeks]

Вторичные конечные точки (12)

• PK Parameter: Area Under the Concentration-time Curve(AUClast) [Срок оценки: 103 weeks]
• PK Parameter: Area Under the Concentration-time Curve(AUCtau) [Срок оценки: 103 weeks]
• Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) [Срок оценки: 103 weeks]
• PK Parameter:Time of Maximum Observed Concentration (Tmax) [Срок оценки: 103 weeks]
• PK Parameter: Elimination Half-life (t1/2) [Срок оценки: 103 weeks]
• PK Parameter: Steady State Maximum Concentration(Cmax,ss) [Срок оценки: 103 weeks]
• PK Parameter: Steady State Minimum Concentration(Cmin,ss) [Срок оценки: 103 weeks]
• PK Parameter: Systemic Clearance at Steady State (CLss) [Срок оценки: 103 weeks]
• PK Parameter: Volume of Distribution at Steady-State (Vss) [Срок оценки: 103 weeks]
• PK Parameter: Accumulation Ratio (Rac AUC) [Срок оценки: 103 weeks]
• PK Parameter: Degree of Fluctuation (DF) [Срок оценки: 103 weeks]
• Overall Response Rate (ORR) [Срок оценки: 53 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.
• Participant must be 18- 18 years or the legal age of consent at the time of signing the ICF.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy ≥ 3 months.
• Patients with advanced solid tumors confirmed by histopathological diagnosis who have failed standard treatment, are intolerant to standard treatment, or for whom standard treatment is currently unsuitable.
• Pre-treatment archived tumour tissue (within 5 years) or fresh samples could be provided for biomarker analysis.
• Must have at least one measurable lesion according to RECIST v1.1.
• Adequate organ and bone marrow function as defined by protocol.
• Female subjects of childbearing potential or male subjects with partners of childbearing potential agree to use highly effective contraception.
• Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.

Критерии исключения

• Participate in any other clinical trial within 28 days prior to 1st dosing of LM-299.
• Subjects who have received the anti-tumor treatments within the specified time periods prior to the first dosing of LM-299.
• Any adverse event from prior anti-tumour therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
• Subjects with uncontrolled tumour-related pain.
• Subjects with known central nervous system (CNS) or meningeal metastasis.
• Qualitative urine protein results ≥ 3+.
• Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to 1st dosing of LM-299.
• Any life-threatening bleeding event that occurred within 3 months prior to 1st dosing of LM-299.
• Subjects with esophageal or gastric varices requiring immediate intervention or a history of variceal bleeding .
• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more severe liver cirrhosis.
• Subjects who have clinically uncontrollable third-space fluid accumulatio.
• Radiographic evidence of tumor invading surrounding vital organs or the risk of esophagotracheal fistula or esophagopleural fistula, tumor surrounding or invading the major blood vessels, or presence of intratumoral cavity formation.
• History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of the study drug.
• Patients with complete or incomplete intestinal obstruction within 3 months prior to the first dose of the study drug or patientswho are currently at the risk of intestinal perforation.
• Subjects who are known to be allergic to antibody treatment.
• Subjects who take systemic corticosteroids (≥ 10 mg/day of prednisone or equivalent) for more than 7 days within 2 weeks prior to the first dose of LM-299.
• Subjects with the known history of autoimmune disease.
• Patients with a history of active or previously confirmed inflammatory bowel disease.
• Patients with a history of or currently having interstitial pneumonia requiring systemic corticosteroid treatment.
• Received live vaccines or attenuated live vaccines within 28 days prior to the first dose of the study drug.
• Currently using anticoagulants such as therapeutic doses of heparin or vitamin K antagonists.
• Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-299 (excluding tumour biopsy, puncture, etc.).
• Subjects who have severe cardiovascular and and cerebrovascular diseases.
• Patients with severe infections within 4 weeks prior to the first dose.
• Patients with a history of immunodeficiency.
• Individuals with HIV infection, active HBV or HCV infection .
• Patients with known active tuberculosis (TB). Suspected active TB should be ruled out through clinical examination.
• Patients who have had other malignancies within 5 years prior to the first dose of the study drug.
• Women of childbearing age who test positive for pregnancy within 7 days prior to the first dose of the study drug or are breastfeeding.
• Individuals with known psychiatric disorders or illnesses that may affect adherence to the trial.
• Patients with local or systemic diseases caused by non-malignant tumors.
• 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

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• the first affiliated hospital of Xinxiang medical University — Xinxiang
• Liaocheng people's hospital — Liaocheng
• Zibo municipal hospital — Zibo
• Shanghai Dongfang Hospital (Tongji University Affiliated Dongfang Hospital) — Шанхай
• Shanghai GoBroad Cancer Hospital China Pharmaceutical University — Шанхай

Австралия · 1 центр

• One Clinical Research — Perth

Идентификаторы

NCT: NCT06650566 · LM299-01-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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