HRYZ-T101 injection for HPV18 positive solid tumors

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

This study is testing a new injection called HRYZ-T101 to see if it can safely help people with solid tumors that are positive for HPV18.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: HRYZ Biotech Co. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05952947 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, single-arm Phase 1 study aimed at evaluating the safety, tolerability, and efficacy of HRYZ-T101 injection in patients with HPV18 positive solid tumors. The study will involve a dose escalation approach to determine the recommended phase 2 dose (RP2D) of the HRYZ-T101 TCR-T cell injection. Participants will receive HRYZ-T101 along with Fludarabine and Cyclophosphamide as part of their treatment regimen.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with metastatic or recurrent solid tumors confirmed to be HPV18 positive.

Not a fit: Patients with solid tumors that are not HPV18 positive or those who have not failed prior anti-tumor treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with HPV18 positive solid tumors who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in targeting HPV18 positive tumors, similar immunotherapy strategies have shown promise in other cancer types.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Xiaohua Wu, Doctor — Fudan University
• Study coordinator: Xuemin Rao

Conditions: Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Carcinoma of Vagina, Carcinoma of Penis, Anal Cancer, Carcinoma of Vulva