Repeat Intravenous Infusions of B4T2-001 CAR-T Without Lymphodepleting Chemotherapy for Solid Tumors

Recruiting now · Phase 1

Conditions studied: Advanced Solid Tumor

In brief

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 tumors including but not limited to advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, advanced pancreatic cancer, advanced non-small cell lung cancer (NSCLC), colorectal cancers (CRC) and metastatic breast cancer that tests positive for BT-001 target antigen according to Immunohistochemistry (IHC). The trial builds off first-in-human results from pilot study per clinicaltrials.gov ID: NCT05621486 to administer multiple infusions of B4T2-001 CAR-T without the need to give preparative chemotherapy (lymphodepletion).

Key facts

Study ID

NCT06072989

Run by

Shanghai East Hospital

People needed

24

Starts

2023-10-01

Expected to finish

2027-03-01

Last updated by the study team

2023-10-10

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Shanghai East Hospital — Shanghai, China/Shanghai, China (enrolling)
• Shanghai Artemed Hospital — Shanghai, China/Shanghai, China (enrolling)

Full record on ClinicalTrials.gov

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