Status:
RECRUITING
Repeat Intravenous Infusions of B4T2-001 CAR-T Without Lymphodepleting Chemotherapy for Solid Tumors
Lead Sponsor:
Shanghai East Hospital
Collaborating Sponsors:
Bio4T2 LLC
Conditions:
Advanced Solid Tumor
Eligibility:
All Genders
18-70 years
Phase:
PHASE1
Brief Summary
This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of autologous B4T2-001 CAR-T in subjects with advanced solid t...
Detailed Description
This is an open-label dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of lentiviral transduced autologous B4T2-001 CAR-T at up t...
Eligibility Criteria
Inclusion
- The subjects have been fully informed of the possible risks and benefits of participating in this study and have voluntarily signed the informed consent form (ICF).
- Age: 18-70 years (including 18 and 70 years).
- ECOG 0-1.
- With an expected survival of more than 3 months.
- Patients with histologically or cytologically confirmed locally advanced or metastatic "BT-001 positive" solid tumors. IHC should be within 6 months of apheresis, but maybe extended.
- Preference for patients who have failed first- or second-line therapy.
- Having measurable lesions according to RECIST 1.1 (or the latest version).
- Maximum tumor size less than 4 cm according to RECIST 1.1 (or the latest version).
- Having sufficient bone marrow, liver, kidney, and lung functions (based on the normal value of the clinical trial sites).
- ANC and PLT ≥ LLN.
- Without liver metastases, ALT, AST, or ALP ≤ 2.5×upper limit of normal (ULN); with liver metastases, ALT, AST, or ALP ≤ 5×ULN.
- Serum creatinine (ScR) ≤ 1.5×ULN, or creatinine clearance \> 50 mL/min (calculated according to Cockcroft Gault formula).
- International normalized ratio (INR) ≤ 1.5×ULN, APTT ≤ 1.5×ULN.
- Adequate oxygen saturation (≥ 95%) can be maintained without oxygen inhalation.
- Male or female patients of childbearing potential agree to use effective methods of contraception (such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, and intrauterine devices) during the study period and within 1 year after infusion.
Exclusion
- Patients who have received the following anti-tumor treatments prior to apheresis:
- Cytotoxic therapy within 14 days or 28 days (for chemotherapy with high lymphocytic toxicity such as bendamustine, cyclophosphamide, ifosfamide, fludarabine, cladribine, etc.).
- Small molecule targeted therapy within 14 days or at least 5 half-lives, whichever is longer.
- Therapy with monoclonal antibody within 21 days including cetuximab.
- Therapy with immune checkpoint inhibitors and/or Avastin within 30 days of apheresis.
- Immunomodulatory therapy within 14 days.
- Radiotherapy within 14 days of apheresis.
- Traditional Chinese medicine with anti-tumor indications within 14 days of apheresis.
- Investigational agents or treatment within 28 days of apheresis.
- Previously treated with CAR-T/TCR-T cells and/or vaccine within 28 days of apheresis.
- Previously treated with any BT-001-targeted therapy.
- Brain metastases with central nervous system symptoms.
- Pregnant (positive pregnancy test prior to dosing) or breast-feeding.
- Allergic or suspected allergic reaction to any drug and related excipients specified in protocol, e.g., camelid antibody, pre-infusion medication (acetaminophen and diphenhydramine), serum albumin, tocilizumab (or biosimilars of tocilizumab that have been approved for CRS indication), Erbitux/ cetuximab, dimethyl sulfoxide (DMSO), and dextran 40.
- Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \> 100IU/mL or lower limit of the research center \[Only when the detection limit of the research center is higher than 100IU/mL\]), or patients with positive HCV antibody.
- Patients with a history of immunodeficiency, including those who are HIV-positive, or patients with other acquired or congenital immune deficiency, or a history of organ transplantation.
- Patients with concomitant or previous history of interstitial lung disease or interstitial pneumonia; presence of multiple metastatic lesions in the lungs or a single metastatic lesion ≥ 3 cm in length; patients with inflammation in the lungs or have received extensive radiotherapy.
- Patients with uncontrolled active infection based on the investigator's judgment.
- Patients who underwent major surgery within 2 weeks prior to apheresis and not fully recovered.
- The toxicity of previous anti-cancer therapy, including immunotherapy has not returned to less than or equal to Grade 1 as specified in CTCAE v5.0 or the latest version (except for hair loss, Grade 2 peripheral neuropathy, and stable hypothyroidism treated with hormone replacement therapy).
- Patients with a history of acute myocardial infarction, unstable angina pectoris, stroke, or transient ischemic attack within 6 months prior to the enrollment, or with NYHA Class 2 or higher congestive heart failure.
- Patients with chronic diseases requiring treatment with systemic corticosteroids or other immunosuppressants, received systemic corticosteroids (≥ 70 mg prednisone or equivalent dose of other corticosteroids) or other immunosuppressants within 7 days before apheresis, except for the following cases: local, ocular, intra-articular, intranasal, and inhaled glucocorticoid treatment; short term use of glucocorticoids for preventive treatment (such as prevention of contrast medium allergy).
- Patients with autoimmune diseases.
- Patients with Crohn's Disease.
- Patients with a history of uncontrollable mental illness.
- Any condition in which the investigator considers that the subject is not suitable to participate in the study.
Key Trial Info
Start Date :
October 1 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2027
Estimated Enrollment :
24 Patients enrolled
Trial Details
Trial ID
NCT06072989
Start Date
October 1 2023
End Date
March 1 2027
Last Update
October 10 2023
Active Locations (2)
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1
Shanghai East Hospital
Shanghai, China/Shanghai, China, 200126
2
Shanghai Artemed Hospital
Shanghai, China/Shanghai, China, 200131