NCT05952947

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
21mo left

Started Nov 2023

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress59%
Nov 2023Feb 2028

First Submitted

Initial submission to the registry

July 5, 2023

Completed
14 days until next milestone

First Posted

Study publicly available on registry

July 19, 2023

Completed
4 months until next milestone

Study Start

First participant enrolled

November 1, 2023

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2028

Last Updated

February 2, 2024

Status Verified

June 1, 2023

Enrollment Period

4.1 years

First QC Date

July 5, 2023

Last Update Submit

January 31, 2024

Conditions

Cervical CancerHead and Neck Squamous Cell CarcinomaCarcinoma of VaginaCarcinoma of PenisAnal CancerCarcinoma of Vulva

Outcome Measures

Primary Outcomes (2)

  • DLT

    Dose-limiting toxicity

    28 days

  • Adverse events and serious adverse events

    Incidence of adverse events and serious adverse events

    2 years

Secondary Outcomes (8)

  • Objective Response Rate（ORR）

    2 years

  • Disease Control Rate (DCR)

    2 years

  • Duration of response (DoR)

    2 years

  • Time to response (TTR)

    2 years

  • Progression-Free Survival（PFS）

    2 years

  • +3 more secondary outcomes

Other Outcomes (3)

  • Number of Subjects with positive anti-drug antibodies (ADA)

    2 years

  • Number of subjects with replication competent lentivirus (RCL)

    2 years

  • T cell subgroup in peripheral blood

    2 years

Study Arms (1)

HRYZ-T101 Injection

EXPERIMENTAL

Patients will undergo lymphocytapheresis, then treatment with HRYZ-T101 TCR-T cells.

Biological: HRYZ-T101 InjectionDrug: Fludarabine + Cyclophosphamide

Interventions

HRYZ-T101 InjectionBIOLOGICAL

On day 1, the TCR-T cells will be administered intravenously.

HRYZ-T101 Injection
Fludarabine + CyclophosphamideDRUG

Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days

HRYZ-T101 Injection

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. The patient must be willing to sign the informed consent form.
  • \. Age ≥18 years and ≤75 years.
  • \. Metastatic or recurrent solid tumors with confirmed HPV18 infection based on TNM \& FIGO staged histopathological investigation. .
  • \. Subjects who have failed anti-tumor treatment in the past and lack effective treatment options.
  • \. HPV18 positive and HLA-DRB1\*0901 allele.
  • \. ECOG performance status ≤1.
  • \. Estimated life expectancy ≥ 3 months.
  • \. Patients must have at least one measurable lesion defined by RECIST 1.1.
  • \. 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≤1.5×ULN; ALT/AST≤3×ULN or ≤5×ULN for liver metastases;
  • +5 more criteria

You may not qualify if:

  • \. 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.
  • \. 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.
  • \. Have received any investigational drug within 4 weeks before apheresis, or have participated in another clinical study at the same time.
  • \. Have received any cell therapy products before.
  • \. Those who have undergone major surgery within 4 weeks before apheresis, or minor surgery within 2 weeks before apheresis.
  • \. Toxicity of previous treatment has not been mitigated or ≤ Grade 1 before apheresis.
  • \. Have received live attenuated vaccine or adenovirus vector vaccine within 4 weeks before apheresis.
  • \. Have central nervous system metastasis with symptoms.
  • \. Subjects with clinical cardiac symptoms or diseases that cannot be well controlled.
  • \. Subjects with serious or uncontrolled systemic disease or any unstable systemic disease.
  • \. Subjects with active infection requiring systemic treatment with anti-infective drugs within 2 weeks before apheresis.
  • \. Subjects have any active autoimmune disease or history of autoimmune disease.
  • \. Have received immunosuppressive agents, or systemic corticosteroids, immunomodulators within 2 weeks before apheresis.
  • \. 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.
  • \. Subjects with history of thromboembolism ≥ Grade 3 within 6 months before apheresis, or is receiving thrombolytic or anticoagulant for high-risk of thromboembolism.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical NeoplasmsSquamous Cell Carcinoma of Head and NeckVaginal NeoplasmsPenile NeoplasmsAnus NeoplasmsVulvar Neoplasms

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeHead and Neck NeoplasmsVaginal DiseasesGenital Neoplasms, MaleGenital Diseases, MalePenile DiseasesMale Urogenital DiseasesRectal NeoplasmsColorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesAnus DiseasesRectal DiseasesVulvar Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Xiaohua Wu, Doctor

    Fudan University

    PRINCIPAL INVESTIGATOR

  • Jian Zhang, Doctor

    Fudan University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuemin Rao

CONTACT

021-61049928raoxuemin@shhryz.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 5, 2023

First Posted

July 19, 2023

Study Start

November 1, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

February 1, 2028

Last Updated

February 2, 2024

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)