NCT05952947RecruitingPhase 1
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
HRYZ Biotech Co.1 site in 1 country32 target enrollmentStarted: November 1, 2023Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- DLT
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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 ≤
- •Estimated life expectancy ≥ 3 months.
- •Patients must have at least one measurable lesion defined by RECIST 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;
- •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
- •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.
Arms & Interventions
HRYZ-T101 Injection
Experimental
Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells.
Intervention: Fludarabine + Cyclophosphamide (Drug)
HRYZ-T101 Injection
Experimental
Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells.
Intervention: HRYZ-T101 Injection (Biological)
Outcomes
Primary Outcomes
DLT
Time Frame: 28 days
Dose-limiting toxicity
Adverse events and serious adverse events
Time Frame: 2 years
Incidence of adverse events and serious adverse events
Secondary Outcomes
- Objective Response Rate（ORR）(2 years)
- Progression-Free Survival（PFS）(2 years)
- Duration of response (DoR)(2 years)
- Overall Survival (OS)(2 years)
- Disease Control Rate (DCR)(2 years)
- Time to response (TTR)(2 years)
- Duration of TCR T cells in-vivo persistence(2 years)
- Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ)(2 years)
Investigators
Study Sites (1)
Loading locations...
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