Treatment for HPV-18 Positive Advanced Solid Tumors

A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of HRYZ-T101 TCR-T Cell for HPV18 Positive Advanced Solid Tumor

This study is testing a new type of cell therapy called HRYZ-T101 to see if it can safely help people with advanced solid tumors that are positive for HPV-18, especially those who have run out of other treatment options.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: HRYZ Biotech Co. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05787535 on ClinicalTrials.gov

What this trial studies

This phase 1 interventional study evaluates the safety, tolerability, and efficacy of HRYZ-T101 TCR-T cell therapy in patients with HPV-18 positive advanced solid tumors. It is a single-center, open-label, single-arm dose escalation study that will assess dose-limiting toxicities associated with HRYZ-T101 TCR-T cell injections. The study includes patients who have previously failed at least one line of treatment and have no effective options left.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with advanced metastatic or recurrent solid tumors confirmed to be HPV-18 positive.

Not a fit: Patients who have not been diagnosed with HPV-18 positive tumors or those with organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced HPV-18 positive solid tumors.

How similar studies have performed: While this approach is novel, similar studies targeting HPV-related cancers have shown promising results in the past.

Eligibility criteria

Inclusion Criteria:

1. The patient must be willing to sign the informed consent form.
2. Age ≥18 years and ≤70 years.
3. Histologically-confirmed advanced metastatic or recurrent solid tumors with confirmed HPV18 infection and HLA-DRB1\*09:01 allele.
4. Subjects who have failed at least first-line treatment in the past and lack effective treatment options.
5. ECOG performance status of 0-1.
6. Estimated life expectancy ≥ 3 months.
7. Patients must have at least one measurable lesion defined by RECIST 1.1.
8. Subjects with potential fertility must agree to use effective contraceptive methods during the whole trials period and at least 6 months after receiving HRYZ-T101 cell transfusion treatment.
9. Patients with any organ dysfunction as defined below:

1) Leukocytes≥3.0 x 10\^9/L; 2) absolute neutrophil count ≤1.5 x 10\^9/L; 3) blood platelets ≥75 x 10\^9/L; 4) hemoglobin≥90g/L; 5) Serum albumin ≥ 3.0g/dL; 6) total bilirubin≤1.5×ULN; ALT/AST≤2.5×ULN; 7) Creatinine clearance ≥50mL/min; 8) INR≤1.5×ULN; APTT≤1.5×ULN; 9) LVEF≥50%; 10) SpO2≥92%.

Exclusion Criteria:

1. Organ transplanters and allogeneic cell transplanters.
2. 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.
3. Those who have undergone major surgery within 4 weeks before enrollment, and those who have received conventional chemotherapy, large-area radiotherapy, targeted therapy, endocrine therapy, immunotherapy or biological therapy, and Chinese herbal medicine and other anti-tumor treatment.
4. Have received live attenuated vaccine within 4 weeks before enrollment.
5. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
6. The subject has active infection or fever more than 38.5 degrees of unknown cause during screening and before cell transfusion.
7. Subjects have any active autoimmune disease or history of autoimmune disease.
8. Subjects with other malignant tumors.
9. Patients with central nervous system metastasis.
10. Active, uncontrolled bacterial or fungal infection requiring systemic treatment.
11. Known HIV or syphilis infection, and/or active hepatitis B virus or hepatitis C virus infection.
12. It is planned to use immunosuppressive agents, or systemic corticosteroids, immunomodulators.
13. Have received any investigational drug within 4 weeks before enrollment, or have participated in another clinical study at the same time.
14. Pregnant or lactating subjects, or those who are unwilling to contraception during the test.
15. Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure.
16. Other serious organic diseases and mental disorders.
17. Have received any gene therapy products before.
18. According to the judgment of the researcher, those who are not suitable for the group, such as poor compliance.

Where this trial is running

Shanghai, Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Jian Zhang, Doctor — Fudan University
• Study coordinator: Xuemin Rao

Conditions Cervical Cancer; Head and Neck Squamous Cell Carcinoma; Oropharyngeal Cancer; Vagina Tumor; Carcinoma of Penis; Anal Carcinoma; Carcinoma of Vulva