Status:
NOT_YET_RECRUITING
CD73/AXL Targeted HypoSti.CAR-T Cells in CD73/AXL Positive Advanced/Metastatic Solid Tumors
Lead Sponsor:
Chinese PLA General Hospital
Collaborating Sponsors:
Fudan University
Conditions:
Solid Tumor
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
PHASE2
Brief Summary
In this single-center, single-arm,prospective, open-label, phase 1/2 study, the safety and efficacy of novel autologous hypoxia-activated CAR-T cell therapy targeting CD73 and AXL ( CD73/AXL.HypoSti.C...
Detailed Description
Currently, CAR T-cell therapy still faces significant challenges in its application to solid tumors due to multiple obstacles, including the lack of tumor-specific antigens, the complex immunosuppress...
Eligibility Criteria
Inclusion
- Age 18-75 (inclusive).
- The Eastern Cooperative Oncology Group (ECOG) score ≤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 National Comprehensive Cancer Network (NCCN) guideline recommended standard firstline therapy. Tumor types include but are not limited to:biliary malignancies, pancreatic cancer, lung cancer, breast cancer, head and neck malignancies, gynecological tumors, etc.
- The expression of CD73 or AXL antigen is≥50%.
- 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:
- Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L, Platelet count ≥75 x 10\^9/ L, hemoglobin (Hgb) ≥ 90g/L ;
- Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min;
- Serum aspartate amino transferase (AST) and alanine aminotransferase (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);
- Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings;
- International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN;
- Baseline oxygen saturation \>91% on room air.
- Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to \<= grade 1 toxicity (except for hematological toxicities and clinically non-significant toxicities such as alopecia).
- 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 document.
Exclusion
- 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, immunotherapy, targeted therapy or other anti-tumor therapy within 4 weeks or 5 half-lives before enrollment.
- Pregnant, lactating, or breastfeeding females.
- Known positive test result for human immunodeficiency virus (HIV) or acquired 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.
- Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
- Active bleeding or known hemorrhagic tendency.
- Vaccination within 30 days of study enrollment.
- Being participating any other trials or withdraw within 4 weeks.
- Researchers believe that other reasons are not suitable for clinical trials.
Key Trial Info
Start Date :
May 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
May 1 2028
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT06939270
Start Date
May 1 2025
End Date
May 1 2028
Last Update
April 22 2025
Active Locations (1)
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1
Biotherapeutic Department, Chinese PLA General Hospital
Beijing, Beijing Municipality, China