A Phase I Clinical Study to Assess the Safety and Efficacy of CD70-targeted CAR-T in the Treatment of CD70-positive Advanced/Metastatic Solid Tumors

Chongqing Precision Biotech Co., Ltd1 site in 1 country48 target enrollmentNovember 30, 2023

ConditionsRenal Cell Carcinoma Ovarian Cancer Cervix Cancer Metastatic Cancer Advanced Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Renal Cell Carcinoma
Sponsor: Chongqing Precision Biotech Co., Ltd
Enrollment: 48
Locations: 1
Primary Endpoint: Incidence of Adverse events after CD70 CAR-T cells infusion [Safety and Tolerability]
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-center, double-arm, open-label study. this study plans to evaluate the safety and efficacy of CD70-targeting CAR-T cells in the treatment of CD70-positive advanced/metastatic solid tumors, and obtain recommended doses and infusion patterns.

Detailed Description

The research designs to follow 2 groups：Intravenous infusion group and Intraperitoneal injection group；each group sets up 2 phases,the first phase is dose discovery phase to obtain recommended doses,the second phase is dose expansion phase to verify the safety in the recommended doses. In the discovery phase,each group puts up 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CD70-positive advanced/metastatic solid tumors.In the dose expansion phase,each group will choose one or two dose groups to verify the safety and efficacy at this dose,and plan to recruit about 6 subjects in each dose group.

Registry

clinicaltrials.gov

Start Date

November 30, 2023

End Date

September 30, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Chongqing Precision Biotech Co., Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years old, male or female;
•Advanced/metastatic solid tumor confirmed by histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) (positive tumor CD70 expression (tumor CD70 positive (IHC 3+) confirmed by histology or pathology)) ;
•At least after TKI/PARPi, anti-vascular drug treatment is ineffective, there is no available standard treatment plan or standard treatment fails or intolerable (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), There is currently no effective treatment;
•Measurable and evaluable lesions defined by RECIST version 1.1: Measurable disease is defined as at least one lesion that can be accurately measured on at least one level (long diameter needs to be recorded); ), when measured by magnetic resonance imaging (MRI), each lesion must be \>10mm, The lymph node must be \>15mm in the short axis;
•ECOG 0-2 points (Appendix 2);
•The expected survival time is more than 12 weeks;
•No serious mental disorder;
•The functions of important organs are basically normal:
•Hematopoietic function: neutrophils 1.0×109/L, platelets 75×109/L, hemoglobin 80g/L;
•Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;

Exclusion Criteria

•Received anti-CD70 drug treatment before screening;
•Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;
•Received any of the following treatments before screening:
•Participated in other interventional clinical studies before screening, including: the last use of unmarketed new drugs is less than 3 months before cell reinfusion, or the last use of marketed drugs is less than 5 half-lives from cell reinfusion;
•Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is shorter) before apheresis;
•Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to apheresis (inhalation or topical allowed in the absence of active autoimmune disease Use steroids and adrenal corticosteroid replacement at doses greater than 10 mg/day of prednisone);
•Received live attenuated vaccine within 4 weeks before screening;
•Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;
•Malignant tumors other than the target tumor within 3 years before screening, except for the following: malignant tumors that have received radical treatment, and no known active disease within ≥ 3 years before enrollment; or Treated non-melanoma skin cancer with no evidence of disease;
•Suffering from any of the following heart diseases:

Outcomes

Primary Outcomes

Incidence of Adverse events after CD70 CAR-T cells infusion [Safety and Tolerability]

Time Frame: 28 days

Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

Obtain the maximum tolerated dose of CD70 CAR-T cells[Safety and Tolerability]

Time Frame: 28 days

Dose-limiting toxicity after cell infusion

Secondary Outcomes

Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness](2 years)
CMAX of CD70 CAR-T cells [Cell dynamics](3 months)
Disease control rate of CAR-T cell preparations in CD70 positive advanced malignancies [Effectiveness](3 months)
Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness](3 months)
Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness](2 years)
Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness](2 years)
AUCS of CD70 CAR-T cells [Cell dynamics](3 months)
TMAX of CD70 CAR-T cells[Cell dynamics](3 months)
Pharmacodynamics of CD70 CAR-T cells[Cell dynamics](3 months)