HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Официальное название

A Multicenter, Single Arm, Open Label, Phase I Clinical Study to Evaluate the Safety, Tolerability and Efficacy of HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Обзор

A multicenter, open label, single arm dose escalation phase I study to evaluate the safety, tolerability, and efficacy of HRYZ-T101 injection for HPV18 positive solid tumor. The study will investigate RP2D of HRYZ-T101 TCR-T cell injection.

Вмешательства

• Биопрепарат HRYZ-T101 Injection
  On day 1, the TCR-T cells will be administered intravenously.
• Препарат Fludarabine + Cyclophosphamide
  Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days

Первичные конечные точки

• DLT [Срок оценки: 28 days]
• Adverse events and serious adverse events [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

• 1\. The patient must be willing to sign the informed consent form.
• 2\. Age ≥18 years and ≤75 years.
• 3\. Metastatic or recurrent solid tumors with confirmed HPV18 infection based on TNM \& FIGO staged histopathological investigation. .
• 4\. Subjects who have failed anti-tumor treatment in the past and lack effective treatment options.
• 5\. HPV18 positive and HLA-DRB1\*0901 allele.
• 6\. ECOG performance status ≤1.
• 7\. Estimated life expectancy ≥ 3 months.
• 8\. Patients must have at least one measurable lesion defined by RECIST 1.1.
• 9\. 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≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases;
• Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN;
• INR≤1.5×ULN; APTT≤1.5×ULN;
• LVEF≥50%;
• SpO2≥92%.
• 10\. Subjects with potential fertility must agree to use effective contraceptive methods during the whole trials period and at least 1 year after receiving HRYZ-T101 cell transfusion treatment. HCG test for female with potential fertility must be negative within 7 days before apheresis.

Критерии исключения

• 1\. 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.
• 2\. Those who have undergone systemic anti-tumor treatment within 4 weeks before apheresis, including who have received conventional chemotherapy, large-area radiotherapy, targeted therapy, immunotherapy or biological therapy, and other anti-tumor treatment. Have received small molecule targeted drugs and oral fluorouracils or Chinese herbal medicine within 2 weeks before apheresis.
• 3\. Have received any investigational drug within 4 weeks before apheresis, or have participated in another clinical study at the same time.
• 4\. Have received any cell therapy products before.
• 5\. Those who have undergone major surgery within 4 weeks before apheresis, or minor surgery within 2 weeks before apheresis.
• 6\. Toxicity of previous treatment has not been mitigated or ≤ Grade 1 before apheresis.
• 7\. Have received live attenuated vaccine or adenovirus vector vaccine within 4 weeks before apheresis.
• 8\. Have central nervous system metastasis with symptoms.
• 9\. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
• 10\. Subjects with serious or uncontrolled systemic disease or any unstable systemic disease.
• 11\. Subjects with active infection requiring systemic treatment with anti-infective drugs within 2 weeks before apheresis.
• 12\. Subjects have any active autoimmune disease or history of autoimmune disease.
• 13\. Have received immunosuppressive agents, or systemic corticosteroids, immunomodulators within 2 weeks before apheresis.
• 14\. Subjects with other malignant tumors. Except for: (1) Carcinoma in situ with curative treatment and no evidence of recurrence for at least 2 years; (2) the primary malignant tumor has been completely resected and achieved CR for ≥ 2 years.
• 15\. Subjects with history of thromboembolism ≥ Grade 3 within 6 months before apheresis, or is receiving thrombolytic or anticoagulant for high-risk of thromboembolism.
• 16\. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection.
• 17\. Organ transplanters and allogeneic cell transplanters.
• 18\. Subjects with active pulmonary tuberculosis infection within 1 year or have not received treatment at least 1 year before apheresis.
• 19\. Pregnant or lactating female, or those whose HCG test is positive before enrollment.
• 20\. According to the judgment of the researcher, those who are not suitable for the group, such as poor compliance.

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

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT05952947 · H-T01-C2001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗