RecruitingPhase 1NCT05952947

HRYZ-T101 Injection for HPV18 Positive Solid Tumor

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


Sponsor

HRYZ Biotech Co.

Enrollment

32 participants

Start Date

Nov 1, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria20

  • \. The patient must be willing to sign the informed consent form.
  • \. Age ≥18 years and ≤75 years.
  • \. Metastatic or recurrent solid tumors with confirmed HPV18 infection based on TNM \& FIGO staged histopathological investigation. .
  • \. Subjects who have failed anti-tumor treatment in the past and lack effective treatment options.
  • \. HPV18 positive and HLA-DRB1\*0901 allele.
  • \. ECOG performance status ≤1.
  • \. Estimated life expectancy ≥ 3 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≤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%.
  • \. 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 Criteria20

  • \. 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.
  • \. 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.
  • \. Have received any investigational drug within 4 weeks before apheresis, or have participated in another clinical study at the same time.
  • \. Have received any cell therapy products before.
  • \. Those who have undergone major surgery within 4 weeks before apheresis, or minor surgery within 2 weeks before apheresis.
  • \. Toxicity of previous treatment has not been mitigated or ≤ Grade 1 before apheresis.
  • \. Have received live attenuated vaccine or adenovirus vector vaccine within 4 weeks before apheresis.
  • \. Have central nervous system metastasis with symptoms.
  • \. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
  • \. Subjects with serious or uncontrolled systemic disease or any unstable systemic disease.
  • \. Subjects with active infection requiring systemic treatment with anti-infective drugs within 2 weeks before apheresis.
  • \. Subjects have any active autoimmune disease or history of autoimmune disease.
  • \. Have received immunosuppressive agents, or systemic corticosteroids, immunomodulators within 2 weeks before apheresis.
  • \. 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.
  • \. Subjects with history of thromboembolism ≥ Grade 3 within 6 months before apheresis, or is receiving thrombolytic or anticoagulant for high-risk of thromboembolism.
  • \. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection.
  • \. Organ transplanters and allogeneic cell transplanters.
  • \. Subjects with active pulmonary tuberculosis infection within 1 year or have not received treatment at least 1 year before apheresis.
  • \. Pregnant or lactating female, or those whose HCG test is positive before enrollment.
  • \. According to the judgment of the researcher, those who are not suitable for the group, such as poor compliance.

Interventions

BIOLOGICALHRYZ-T101 Injection

On day 1, the TCR-T cells will be administered intravenously.

DRUGFludarabine + Cyclophosphamide

Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days


Locations(1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

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NCT05952947


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