Clinical trial NCT06515314: HRYZ-T102 TCR-T Cell for AFP Positive Advanced HCC and Other Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Cell Carcinoma
Lead sponsor: HRYZ Biotech Co.
Sponsor class: INDUSTRY
First posted: 2024-07-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. The patient must be willing to sign the informed consent form.
2. Age ≥18 years and ≤75 years.
3. HLA-A 02:03 allele positive
4. 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.
5. Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained AFP positive or serum AFP ≥400ng/ml.
6. Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
7. ECOG performance status ≤1.
8. Estimated life expectancy ≥4 months.
9. Patients must have at least one measurable lesion defined by RECIST 1.1.
10. 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%.
11. 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Adverse events and serious adverse events
timeFrame: 2 years
measure: DLT
timeFrame: 2 years
Secondary outcomes:
measure: Objective Response Rate（ORR）
timeFrame: 2 years
measure: Disease Control Rate (DCR)
timeFrame: 2 years
measure: Duration of response (DoR)
timeFrame: 2 years
measure: Time to response (TTR)
timeFrame: 2 years
measure: Progression-Free Survival（PFS）
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Duration of TCR T cells in-vivo persistence
timeFrame: 2 years
measure: Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ)
timeFrame: 2 years
Other outcomes:
measure: Number of Subjects with positive anti-drug antibodies (ADA)
timeFrame: 2 years
measure: Number of subjects with replication competent lentivirus (RCL)
timeFrame: 2 years
measure: T cell subgroup in peripheral blood
timeFrame: 2 years
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Study Principal Investigator
name: Xiaowu Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: