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

Chongqing Precision Biotech Co., Ltd1 site in 1 country36 target enrollmentJanuary 10, 2024

ConditionsOvarian Cancer Cervix Cancer Metastatic Cancer Advanced Cancer Gynecologic Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Ovarian Cancer
Sponsor: Chongqing Precision Biotech Co., Ltd
Enrollment: 36
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 Gynecologic Cancer, 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

January 10, 2024

End Date

December 31, 2027

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;
•Advanced/metastatic gynecological tumor confirmed by histopathology or cytology (paraffin sections or fresh biopsy tumor tissue specimens) (CD70 positive tumor expression (CD70 positive tumor confirmed by histology or pathology (IHC 3+));
•Failure or intolerance after standard treatment (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), and currently no effective treatment;
•According to the RECIST version 1.1 standard, there is at least one measurable diameter and evaluable target lesion. Measurable lesions are defined as: extranodal lesions with CT scan diameter ≥10mm, lymph node lesions with CT scan diameter ≥15mm, scan layer thickness ≤ 5mm, and have not received local treatment;
•ECOG 0 \~ 2 points ;
•Expected survival time is more than 12 weeks;
•No serious mental disorders;
•The functions of important organs are basically normal:
•Hematopoietic function: neutral granules \>1.0×109/L, platelet \>75×109/L, hemoglobin \>80g/L;
•Cardiac function: Echocardiography indicated cardiac ejection fraction ≥50%, and no obvious abnormality was found in electrocardiogram;

Exclusion Criteria

•Received anti-CD70 drug therapy before screening;
•Active/symptomatic central nervous system metastasis or meningeal metastasis at the time of screening; Treated subjects with brain metastases can only be enrolled if no radiographically demonstrated progression is demonstrated ≥4 weeks after the end of treatment.
•Received any of the following treatments prior to screening:
•Participated in other interventional clinical studies before screening, including: the time of last use of unmarketed new drugs less than 3 months from cell transfusion, or the time of last use of marketed drugs less than 5 half-lives from cell transfusion;
•Received anti-tumor therapy such as chemotherapy or targeted therapy within 2 weeks of preapheresis or at least 5 half-lives (whichever is shorter); Received systemic radiation within 4 weeks and local radiation within 2 weeks; Or received radioactive drugs (strontium, samarium) within 8 weeks prior to treatment.
•Systemic corticosteroid therapy with doses greater than 10mg/ day of prednisone (or equivalent doses of other corticosteroids) within 2 weeks of preapheresis (in the absence of active autoimmune disease, inhaled or topical steroid use and adrenocortical replacement with doses greater than 10mg/ day of prednisone efficacy dose are permitted);
•Received live attenuated vaccine within 4 weeks prior to screening;
•There is an active or uncontrolled infection requiring systemic treatment within 1 week prior to screening;
•Had malignancies other than the target tumor within 3 years prior to screening, except for malignancies that had received radical treatment and had no known active disease for ≥3 years prior to enrollment; Or adequately treated non-melanoma skin cancer with no evidence of disease;
•Have any of the following heart conditions:

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

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