HRYZ-T101 Injection for HPV18 Positive Solid Tumor

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05952947
• Other study ID #: H-T01-C2001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 1, 2023
• Est. completion date: February 2028

Study information

• Verified date: June 2023
• Source: HRYZ Biotech Co.
• Contact: Xuemin Rao
• Phone: 021-61049928
• Email: raoxuemin[@]shhryz.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: February 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms
• Carcinoma
• Cervical Cancer
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Vaginal Neoplasms
• Vulvar Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
HRYZ Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Subjects with positive anti-drug antibodies (ADA)	Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.	2 years
Other	Number of subjects with replication competent lentivirus (RCL)	RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.	2 years
Other	T cell subgroup in peripheral blood	Collect blood samples and analyze for T cell subgroup by flow cytometry at specified intervals before and after treatment with HRYZ-T101.	2 years
Primary	DLT	Dose-limiting toxicity	28 days
Primary	Adverse events and serious adverse events	Incidence of adverse events and serious adverse events	2 years
Secondary	Objective Response Rate(ORR)	The percentage of subjects with PR or CR assessed by RECIST 1.1.	2 years
Secondary	Disease Control Rate (DCR)	The percentage of subjects with a confirmed CR, PR, or stable disease (SD) assessed by RECIST 1.1.	2 years
Secondary	Duration of response (DoR)	Subjects who show a confirmed CR or PR as assessed by RECIST 1.1.	2 years
Secondary	Time to response (TTR)	Time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by RECIST 1.1.	2 years
Secondary	Progression-Free Survival(PFS)	The length of time from enrollment until the time of progression of disease.	2 years
Secondary	Overall Survival (OS)	The interval of time between the date of T-cell infusion and the date of death.	2 years
Secondary	Duration of TCR T cells in-vivo persistence	Blood samples were collected to measure persistence of infused HRYZ-T101.	2 years
Secondary	Concentration of Cytokines (IL-2?IL-6?IL-10?TNFa?IFN?)	Collect blood samples and analyze for presence of cytokines (IL-2?IL-6?IL-10?TNFa?IFN?) at specified intervals before and after treatment with HRYZ-T101.	2 years