HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Official title

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

Overview

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.

Interventions

• Biological HRYZ-T101 Injection
  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

Primary outcome measures

• DLT [Time frame: 28 days]
• Adverse events and serious adverse events [Time frame: 2 years]

Secondary outcome measures (8)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT05952947 · H-T01-C2001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗