Clinical trial NCT05952947: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cervical Cancer
Head and Neck Squamous Cell Carcinoma
Carcinoma of Vagina
Carcinoma of Penis
Anal Cancer
Carcinoma of Vulva
Lead sponsor: HRYZ Biotech Co.
Sponsor class: INDUSTRY
First posted: 2023-07-19
Enrollment: 32
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: 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 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:

  1. Leukocytes≥3.0 x 10\^9/L;
  2. blood platelets ≥75 x 10\^9/L;
  3. hemoglobin≥85g/L;
  4. Absolute lymphocyte count≥0.8 x 10\^9/L
  5. Serum albumin ≥ 30g/L;
  6. total bilirubin≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases;
  7. Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN;
  8. INR≤1.5×ULN; APTT≤1.5×ULN;
  9. LVEF≥50%;
  10. 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.

Primary outcomes:
measure: DLT
timeFrame: 28 days
measure: Adverse events and serious adverse events
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: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xiaohua Wu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Jian Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: