MAGE-A4-directed TCR-T in the Treatment Amongst Subjects With Advanced Solid Tumors

Официальное название

A Single-arm, Open-label, Dose Exploratory Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous Humanized MAGE-A4-directed T Cell Receptor Engineered T Cell (JWTCR001) in Patients With Advanced Solid Tumors

Обзор

A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.

Подробное описание

This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic treatments.

Вмешательства

• Препарат TCR-MAGE-A4 T-Cells
  * Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses * MAGE-A4-directed T cell receptor-engineered T Cells

Первичные конечные точки

• Rate of dose-limiting toxicities (DLTs) [Срок оценки: 28 days]
• Rate and severity of adverse events (AEs) and severe adverse events (SAEs) [Срок оценки: 2 years]
• Rate and severity of clinically-significant abnormalities in laboratory testings [Срок оценки: 2 years]

Вторичные конечные точки (8)

• Copy number of the vector transgene of JWTCR001 in peripheral blood [Срок оценки: 2 years]
• MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood [Срок оценки: 2 years]
• Antitumor efficacy-Progression-free survival (PFS) [Срок оценки: 2 years]
• Antitumor efficacy-Duration of response (DOR) [Срок оценки: 2 years]
• Antitumor efficacy-Time to response (TTR) [Срок оценки: 2 years]
• Antitumor efficacy-Overall survival (OS) [Срок оценки: 2 years]
• Antitumor efficacy-Objective response rate (ORR) [Срок оценки: 2 years]
• Antitumor efficacy-Disease control rate (DCR) [Срок оценки: 2 years]

Критерии участия

Критерии включения

• 18-75 year-old, male or female
• Voluntarily willing to participate in the study and sign the written informed consent form
• Life expectation ≥12 weeks
• European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion
• Histologically-confirmed recurrent/metastatic advanced solid tumors
• Radiologically-confirmed progression disease after at least one prior line of systematic treatment and no available standard of care at screening, judged by investigators
• Fresh or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained MAGE-A4 positive
• Human leukocyte antigen (HLA)-A\*02 allele matched
• Per response evaluation criteria in solid tumors (RECIST) version 1.1, at least one measurable lesion
• Adequate organ functions
• Adequate venous access for APH
• Non-hematological adverse events induced by previous treatment must have recovered to Grade ≤1 according to Common Terminology Criteria for Adverse Events (CTCAE), except for alopecia and peripheral neuropathy
• Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1 year post infusion, and sperm donation is prohibited during the study
• Women of childbearing potential must have negative serum human chorionic gonadotropin β (β-hCG) test result at screening and 48 hours prior to lymphodepletion

Критерии исключения

• Pregnant or lactating women
• Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19)
• Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH
• Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
• Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators
• Systematic autoimmune disorders requiring long-term systematic treatment
• Previously treated with any genetically engineered modified T cell therapy or other cell and gene therapy (CGT)
• History of organ transplant
• Uncontrolled or active infection within 72 hours prior to screening, APH, LD, or within 5 days prior to infusion
• Subjects with other serious diseases that may restrict them from participating in this study
• Clinically significant CNS disorders, such as epilepsy, stroke, Parkinson disease, etc
• Grade ≥ 2 hemorrhage within 30 days prior to screening, or in need of longterm anticoagulants
• Active digestive ulcer or gastrointestinal (GI) bleeding within 3 months prior to screening
• Not satisfying wash-out period for APH
• Previously allergic or intolerable to JWTCR001 or its components
• Unable or unwilling to comply with the study protocol, judged by the investigators
• Other situations implying that the subject might not be appropriate to participate in the study

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 · 1 центр

• Department of GI Oncology,Peking University Cancer Hospital — Пекин

Идентификаторы

NCT: NCT06170294 · JWTCR001001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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