A Single-center, Single-arm, Dose-escalation Exploratory Clinical Trial of the Safety, Efficacy, and Pharmacokinetics of XKDCT293 (Nectin-4-CAR-T) in Nectin-4-positive Advanced Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- XKDCT293
- Conditions
- Advanced Breast Cancer
- Sponsor
- Shenzhen Celconta Life Science Co., Ltd.
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Dose limiting toxicity (DLT)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
A single-center, single-arm, dose-escalation exploratory clinical trial of the safety, efficacy, and pharmacokinetics of XKDCT 293 (Nectin-4-CAR-T) in Nectin-4-positive advanced breast cancer
Detailed Description
This study is a prospective, single-arm, open-label, single-dose dose-finding study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy characteristics of XKDCT 293 (Nectin-4-CAR-T) cell preparation in subjects with Nectin-4-positive advanced breast cancer. The study will enroll subjects with pathologically confirmed advanced breast cancer, positive Nectin-4 expression, who have previously received standard treatment, failed treatment or cannot tolerate it. Imaging examinations show evaluable tumor lesions. The study included screening period, PBMC collection, baseline, lymphocyte pre-depletion chemotherapy , rest evaluation, cell transfusion, hospitalization observation period, routine follow-up period, and long-term follow-up period. The study set up three dose groups, and adopted the classic 3+3 experimental design for dose escalation. Main purpose: (1)the safety and tolerability of XKDCT 293 in the treatment of nectin-4-positive advanced breast cancer Secondary Purpose: 1. the cellular metabolic kinetics and pharmacodynamics of XKDCT 293 in the treatment of nectin-4 -positive advanced breast cancer ; 2. To preliminarily evaluate the efficacy of XKDCT 293 cell preparations in patients with advanced Nectin-4-positive breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •·You must meet all of the following conditions to be eligible for the group：
- •Understand and voluntarily sign the informed consent form;
- •Age at screening ranged from 18 to 75 years (including the cutoff value), regardless of gender;
- •Locally advanced or metastatic breast cancer that is unresectable as confirmed by histology or cytology, including triple-negative breast cancer, Her-2-positive, and HR-positive breast cancer;
- •Histological or cytological tumor specimens were confirmed by immunohistochemistry to have moderate to high expression of nectin-4 (expression intensity ≥2+ and tumor cell positive rate ≥50%);
- •Patients who have received standard systemic treatment for breast cancer recommended by the Breast Cancer Diagnosis and Treatment Guidelines (2022 Edition) and have had imaging or other objective evidence of disease progression after receiving standard treatment; or patients with refractory breast cancer who cannot tolerate standard treatment or have contraindications to standard treatment, and who have at least one measurable lesion (according to RECIST version 1.1, the long diameter of the measurable lesion on spiral CT scan is ≥10mm or the short diameter of the enlarged lymph node is ≥15mm, see Appendix 1 for RECIST version 1.1); Note: Treatment failure is defined as disease progression during treatment or recurrence after treatment.
- •Definition of intolerance : the occurrence of grade ≥ IV hematological toxicity, grade ≥ III non-hematological toxicity, or grade ≥ III damage to major organs such as heart, liver, and kidney during treatment (refer to NCI-CTCAE v5.0 standards), or a comprehensive assessment by the investigator.
- •The expected survival time at enrollment was greater than 12 weeks;
- •During screening, laboratory tests must meet the following requirements:
- •White blood cell count ≥3.0×10\^9 /L;
Exclusion Criteria
- •·Anyone who has any of the following conditions cannot be selected as a subject：
- •Pregnant or breastfeeding women;
- •Those who have a history of allergy to any component of the cell product ;
- •Suffering from other malignant tumors, except for the following: cured non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, superficial bladder cancer, and other malignant tumors with a disease-free survival period of more than 5 years;
- •Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive, and HBV DNA copy number positive; Hepatitis C antibody (HCV-Ab) positive; Anti-Treponema pallidum antibody (TP-Ab) positive; Human immunodeficiency virus antibody (HIV-Ab) positive; Those who meet any of the following conditions;
- •Previous anti-tumor treatment or clinical trial participation:
- •Previously received CAR-T therapy or other gene-edited cell therapy;
- •Participated in other clinical studies within 28 days before reinfusion;
- •Received local radiotherapy within 7 days or at least 5 half-lives (whichever is longer) before apheresis or small molecule chemotherapy drugs;
- •Daily use of systemic glucocorticoids ≥ 15 mg within 7 days before apheresis, excluding inhaled corticosteroids;
Arms & Interventions
Autologous targeted Nectin4 chimeric antigen receptor T cell injection
Autologous targeted Nectin4 chimeric antigen receptor T cell injection
Intervention: XKDCT293
Autologous targeted Nectin4 chimeric antigen receptor T cell injection
Autologous targeted Nectin4 chimeric antigen receptor T cell injection
Intervention: CAR-T cell
Outcomes
Primary Outcomes
Dose limiting toxicity (DLT)
Time Frame: 28 days of single infusion
Dose limiting toxicity (DLT) in the dose escalation phase
Incidence of Treatment Related adverse events (AEs)
Time Frame: 1 year
Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs)
Maximum tolerated dose (MTD)
Time Frame: 28 days of single infusion
Maximum tolerated dose (MTD) in the dose escalation phase
Secondary Outcomes
- Cellular metabolic kinetics indicators(1 year)
- objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS)(1 year)