HRYZ-T102 TCR-T Cell for AFP Positive Advanced HCC and Other Solid Tumors

Официальное название

A Phase 1, Single-arm, Open-label, Dose-escalation Study of AFP Specific T Cell Receptor Transduced T Cells Injection（HRYZ-T102）in Patients With AFP Positive Advanced Hepatocellular Carcinoma and Other Solid Tumors

Обзор

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of HRYZ-T102 TCR-T Cell in patients with AFP positive advanced hepatocellular carcinoma and other solid tumors refractory to prior systematic treatments.

Подробное описание

This study plans to enroll 12-24 patients to assess the safety of HRYZ-T102. Subjects who meet the eligibility criteria will receive a single dose of HRYZ-T102 injection .The patient will be followed up 24 months.

Вмешательства

• Биопрепарат AFP Specific T Cell Receptor T Cells
  AFP Specific T Cell Receptor T Cells On day 1, the TCR-T cells will be administered intravenously. Drug: Fludarabine + Cyclophosphamide Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days

Первичные конечные точки

• Adverse events and serious adverse events [Срок оценки: 2 years]
• DLT [Срок оценки: 2 years]

Вторичные конечные точки (8)

• Objective Response Rate（ORR） [Срок оценки: 2 years]
• Disease Control Rate (DCR) [Срок оценки: 2 years]
• Duration of response (DoR) [Срок оценки: 2 years]
• Time to response (TTR) [Срок оценки: 2 years]
• Progression-Free Survival（PFS） [Срок оценки: 2 years]
• Overall Survival (OS) [Срок оценки: 2 years]
• Duration of TCR T cells in-vivo persistence [Срок оценки: 2 years]
• Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ) [Срок оценки: 2 years]

Критерии участия

Критерии включения

• The patient must be willing to sign the informed consent form.
• Age ≥18 years and ≤75 years.
• HLA-A 02:03 allele positive
• Histologically-confirmed AFP positive hepatocellular carcinoma (HCC) or other solid tumor, No benefits from curative surgery or other local therapies are expected ,at least one prior line of systematic treatment at screening, judged by investigators.
• Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained AFP positive or serum AFP ≥400ng/ml.
• Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
• ECOG performance status ≤1.
• Estimated life expectancy ≥4 months.
• Patients must have at least one measurable lesion defined by RECIST 1.1.
• Patients with any organ dysfunction as defined below:

Leukocytes≥3.0 x 10\^9/L; blood platelets ≥75 x 10\^9/L; hemoglobin≥85g/L; Absolute lymphocyte count≥0.8 x 10\^9/L Serum albumin ≥ 30g/L; total bilirubin≤3×ULN; ALT/AST≤3×ULN ; Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN; INR≤1.5×ULN; APTT≤1.5×ULN; LVEF≥50%; SpO2≥92%.

• Subjects with potential fertility must agree to use effective contraceptive methods during the whole trials period and at least 1 year after receiving HRYZ-T102 cell transfusion treatment. HCG test for female with potential fertility must be negative within 7 days before apheresis.

Критерии исключения

• Toxicity of previous treatment has not been mitigated or ≤ Grade 1 at screening.
• Another primary malignancy within 5 years (with some exceptions for completely-resected early-stage tumors)
• With severe cardiovascular disease or presence of clinically-relevant central nervous system (CNS) disorders in six months before screening.
• Systematic autoimmune disorders requiring long-term systematic immunosuppression
• Have a history of hypersensitivity to cyclophosphamide or fludarabine, and it is known that any ingredient used in the treatment of this study will produce allergic reactions.
• Current presence of or previously with hepatic encephalopathy
• Organ transplanters and allogeneic cell transplanters.
• Have a history of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within 3 months before screening
• Hereditary or acquired bleeding (e.g. coagulation dysfunction) or a tendency to clot
• Subject has active infection or unexplained fever during screening and prior to cell transfusion
• Have central nervous system metastasis with symptoms
• Known HIV or syphilis infection, and/or active hepatitis C virus infection.
• HBV infect subjects with HBV-DNA≥2000IU/ml
• Pregnant or lactating female, or those whose HCG test is positive before enrollment.
• Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure

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

• Zhongshan Hospital Affiliated to Fudan University — Шанхай

Идентификаторы

NCT: NCT06515314 · H-T02-C1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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