A Phase I Clinical Study to Assess the Safety and Efficacy of CD70-targeted CAR-T in the Treatment of CD70-positive Refractory or Relapsed Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- CHT101
- Conditions
- Metastatic Tumor
- Sponsor
- Zhejiang University
- Enrollment
- 18
- Primary Endpoint
- Incidence of Adverse events after CD70 UCAR-T cells infusion (Safety and Tolerability)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a single-center, single-arm ，open-label ，dose escalation and dose extension study. In this study we plan to evaluate the safety and efficacy of CD70-targeting UCAR-T cells in the treatment of CD70-positive refractory or relapsed solid tumors, and obtain recommended doses and infusion patterns.
Detailed Description
In the discovery phase, accelerated titration combined with the "3+3" dose escalation principle was adopted, starting from the initial dose of 3×106/kg. If a grade ≥3 AE occurs during DLT observation, the accelerated titration mode will switch to "3+3" dose escalation, at least 12 eligible patients will be enrolled and receive 4 doses of CD70 UCAR-T cell therapy (3 × 10\^6 cells/kg, 6 × 10\^6 cells/kg, 8× 10\^6 cells/kg, 1 × 10\^7 cells/kg). In the dose expansion phase, each group will choose one or two dose groups to verify the safety and efficacy, and plan to recruit about 6 subjects in each dose group. During the clinical study, after the completion of each dose group, the Safety Monitoring Committee (SMC) will determine whether it is possible to continue to increase to the next higher dose group, or add more subjects to the current dose group, or reduce to a lower dose group to continue to explore, or climb to a higher dose after reaching the highest dose (1 × 10\^7 cells/kg). Conditions Relapsed Tumor, Refractory Solid Tumor, Renal Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Ovarian Cancer, Cervix Cancer etal
Investigators
Weijia Fang, MD
Professor
Zhejiang University
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and sign a written informed consent documen；
- •Age ≥18 years old, male or female；
- •Histopathological confirmed advanced or metastatic solid tumors failed to at least second-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy；
- •Histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) diagnosed as advanced/metastatic solid tumor (positive tumor CD70 expression (tumor CD70 positive (IHC 2+) confirmed by histology or pathology));
- •At least one measurable lesion at baseline per RECIST version 1.1；
- •The expected survival time is more than 12 weeks;
- •ECOG 0-1 points;
- •The function of important organs is basically normal:Hematopoietic function:
- •Hematopoietic function: neutrophils ≥ 1.5×109/L, platelets ≥ 90×109/L, hemoglobin ≥ 90g/dL;
- •Renal function: serum creatinine≤1.5×ULN;
Exclusion Criteria
- •Received anti-CD70 drug treatment before screening;
- •Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is longer) before Received;
- •Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to Received；
- •Pregnant, lactating, or breastfeeding females;
- •Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV) RNA titer test is greater than the normal range; human immunodeficiency virus (HIV) antibody positive; syphilis test positive; cytomegalovirus (CMV) DNA test positive;
- •Have any of the following heart conditions:
- •New York Heart Association (NYHA) stage III or IV congestive heart failure; Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment; Clinically significant ventricular arrhythmia, echocardiography showed cardiac ejection fraction\<50%,
- •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;
- •Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation;
- •Vaccination within 14 days of study enrollment;
Arms & Interventions
Anti-CD70 UCAR-T Cell Injection
In the discovery phase, accelerated titration combined with the "3+3" dose escalation principle was adopted, starting from the initial dose of 3×106/kg. If a grade ≥3 AE occurs during DLT observation, the accelerated titration mode will switch to "3+3" dose escalation, at least 12 eligible patients will be enrolled and receive 4 doses of CD70 UCAR-T cell therapy (3 × 10\^6 cells/kg, 6 × 10\^6 cells/kg, 8× 10\^6 cells/kg, 1 × 10\^7 cells/kg). In the dose expansion phase, each group will choose one or two dose groups to verify the safety and efficacy, and plan to recruit about 6 subjects in each dose group.
Intervention: CHT101
Outcomes
Primary Outcomes
Incidence of Adverse events after CD70 UCAR-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)
Secondary Outcomes
- Disease control rate (DCR)(42 days)
- Objective response rate (ORR)(42 days)