CD70 Targeted CAR-T Cells in CD70 Positive Advanced/Metastatic Solid Tumors
Phase I/II Study of CD70 Targeted CAR-T Cell Treatment in CD70 Positive Advanced/Metastatic Solid Tumors
Chinese PLA General Hospital
30 participants
Jul 15, 2023
INTERVENTIONAL
Conditions
Summary
In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety and efficacy of autologous CD70 targeted chimeric antigen receptor modified T (CAR-T) cell therapy will be evaluated in patients with CD70 antigen positive advanced/metastatic solid tumors . In this clinical trial, at least 12 eligible patients in dose escalation period will be enrolled to receive 3 doses of CD70-CAR cell therapy according to the "3+3" principle. In dose expansion period, additional at most 21 eligible patients will be enrolled to receive CD70-CAR-T cell therapy at dose of recommended phase 2 dose(RP2D).
Eligibility
Inclusion Criteria8
- Age 18-75 (inclusive).
- ECOG performance status ≤2 and Estimated life expectancy of more than 3 months.
- Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. CD70 antigen expression level ≥ 30%.
- At least one measurable lesion at baseline per RECIST version 1.1.
- Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor rebiopsy in the process of this study.
- Adequate organ function as defined by the following criteria: ANC≥1.5x10\^9/L; Platelet count ≥75x10\^9/L; Hemoglobin ≥90 g/L;Serum AST and serum ALT, ≤3.0 x ULN (≤5 x ULN for patients with liver cancer or metastases); Total serum bilirubin ≤1.5 x ULN(≤3 x ULN for patients with liver cancer or metastases); Serum creatinine ≤1.5 xULN or creatinine clearance of ≥60 mL/min.
- Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.
- Ability to understand and sign a written informed consent documen.
Exclusion Criteria14
- Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- Received cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives before enrollment;
- Pregnant, lactating, or breastfeeding females;
- Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS);Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV);
- History of allergy or intolerance to study drug components;
- Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation;
- Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.
- Known brain metastases or active central nervous system (CNS).Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
- Previous or concurrent cancer within 5 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors;
- Any serious underlying medical (eg, pulmonary, renal, hepatic,gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements;
- Vaccination within 30 days of study enrollment;
- Previously received CD70-CAR T cell therapy;
- Being participating any other trials or withdraw within 4 weeks;
- Researchers believe that other reasons are not suitable for clinical trials.
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Interventions
Dose escalation: Dose1 (1×10\^6 cells/kg) , Dose 2(3×10\^6 cells/kg) ,Dose 3 (1×10\^7cells/kg); Dose expansion: RP2D Drug: Albumin-bound paclitaxel Administered intravenously at dose of 100-200mg/m2 on day -5; Drug: Cyclophosphamide Administered intravenously at dose of 15-30mg/kg on day -3 and day -2; Drug: Fludarabine Administered intravenously at dose of 30mg/m2 on day -3 and day -2;
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT05947487