A Study of MRG006A in the Treatment of Patients With Advanced Solid Tumors

Официальное название

A Phase I/II, Open-label, Multi-center, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Efficacy and Pharmacokinetics of MRG006A in Patients With Advanced Solid Tumors

Обзор

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG006A in patients with advanced solid tumors.

Подробное описание

This study consists of two parts. Phase I is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG006A. Phase II is a dose expansion study to further assess the efficacy, safety, pharmacokinetics and immunogenicityof MRG006A at confirmed RP2D.

Вмешательства

• Препарат MRG006A
  Administrated intravenously

Первичные конечные точки

• Maximum Tolerated Dose (MTD) - Phase I [Срок оценки: Baseline to the end of the first treatment cycle (each cycle is 21 days).]
• Recommended Phase II Dose (RP2D) - Phase I [Срок оценки: Baseline to study completion (up to 24 months).]
• Adverse Events (AEs) - Phase I [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• Serious Adverse Events (SAEs) - Phase I [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• Objective Response Rate (ORR)- Phase II [Срок оценки: Baseline to study completion (up to 24 months).]

Вторичные конечные точки (12)

• Objective Response Rate (ORR) - Phase I [Срок оценки: Baseline to study completion (up to 24 months).]
• Overall Survive (OS)- Phase II [Срок оценки: Baseline to study completion (up to 24 months).]
• Duration of Response (DoR) [Срок оценки: Baseline to study completion (up to 24 months).]
• Disease Control Rate (DCR) [Срок оценки: Baseline to study completion (up to 24 months).]
• Progression Free Survival (PFS) [Срок оценки: Baseline to study completion (up to 24 months).]
• Cmax [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• Tmax [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• AUC0-t [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• Incidence of anti-drug antibody (ADA) [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• QT interval corrected by Fridericia's formula（QTcF） [Срок оценки: Baseline to 15 days after the third dose of study treatment.]
• Adverse Events (AEs) - Phase II [Срок оценки: Baseline to 30 days after the last dose of study treatment.]
• Serious Adverse Events (SAEs) - Phase II [Срок оценки: Baseline to 30 days after the last dose of study treatment.]

Критерии участия

Критерии включения

• Understand and provide written informed consent and comply with the requirements set forth in the protocol.
• age ≥ 18 years, ≤ 75 years.
• Expected survival ≥ 3 months.
• For patients with stage I and II disease, tumor tissue samples for GPC3 and P53 testing must be provided.
• Patients with histologically or cytologically confirmed advanced solid tumors.
• At least one measurable lesion according to RECISTv1.1 and mRECIST (HCC patients).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Organ function must meet basic requirements.
• Women who are pregnant or breastfeeding are not included in this study.
• Female and male patients of childbearing potential must agree to take adequate measures.

Критерии исключения

• Moderate and above thoracoabdominal pelvic fluid and pericardial effusion with clinical symptoms.
• History of liver failure and hepatic encephalopathy.
• Portal vein tumor thrombus involving both the main portal vein and left and right branches, or involving both the main portal vein and mesenteric vein needs to be excluded. The tumor involves the vena cava, or has formed a vena cava tumor thrombus.
• Residual toxicity due to previous anti-tumor therapy or clinically significant laboratory abnormalities higher than grade 1 (CTCAEv5.0).
• For liver cancer, previous or current central nervous system metastases and/or meningeal metastases. Patients with treated stable brain metastases from non-hepatic cancers may participate.
• Patients at high risk of bleeding.
• Severe cardiac insufficiency within 6 months prior to enrollment.
• Pulmonary embolism or deep venous thrombosis within 3 months before the first study drug treatment;
• History of gastrointestinal perforation, fistula, and bowel obstruction, extensive bowel resection, Crohn 's disease, ulcerative colitis, or chronic diarrhea for the past 6 months.
• Patients with double cancer and multiple cancer.
• Uncontrolled or poorly controlled disease.
• History of ventricular tachycardia or torsades de pointes.
• Previous or combined interstitial pneumonia, severe chronic obstructive pulmonary disease with respiratory failure, severe pulmonary insufficiency, symptomatic bronchospasm and other medical history;
• Allergic reactions to any component or excipient of MRG006A, or known Grade ≥ 3 allergic reactions to other prior anti-GPC3 or other monoclonal antibodies.
• Acute or chronic active hepatitis B or C infection.
• Active or clinically poorly controlled serious infection.
• Receiving anti-tuberculosis treatment or receiving anti-tuberculosis treatment within 1 year before the first dose.
• People infected with human immunodeficiency virus (HIV), known syphilis infection requiring treatment.
• Use of systemic corticosteroids within 4 weeks prior to first treatment.
• Use of strong CYP3A4 inducers, strong CYP3A4 inhibitors within 14 days or 5 times the half-life prior to the first dose.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• Zhongshan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT07093970 · MRG006A-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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