Infusions of B4T2-001 CAR-T for advanced solid tumors without chemotherapy

A Single Arm, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of B4T2-001 CAR-T in Patients With Advanced Solid Tumors

This study is testing a new CAR-T therapy for people with advanced solid tumors to see if it can help them without needing chemotherapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai East Hospital (Academic / other)
• Drugs / interventions: cetuximab, tocilizumab, CAR-T, chemotherapy, immunotherapy, cyclophosphamide, fludarabine, prednisone
• Locations: 2 sites (Shanghai, China/Shanghai and 1 other locations)
• Trial ID: NCT06072989 on ClinicalTrials.gov

What this trial studies

This open-label, dose escalation and expansion study evaluates the safety, tolerability, pharmacokinetics, and antitumor activity of autologous B4T2-001 CAR-T in patients with advanced solid tumors, including gastric, pancreatic, lung, colorectal, and metastatic breast cancers. Participants will receive multiple intravenous infusions of B4T2-001 CAR-T every 21 days without the need for preparative chemotherapy. The study aims to determine the appropriate dosing levels based on the occurrence of dose-limiting toxicities during the treatment cycles. The trial builds on previous findings from a pilot study to explore the potential of this innovative CAR-T therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with advanced solid tumors that test positive for the BT-001 target antigen and have failed prior therapies.

Not a fit: Patients with tumors that do not express the BT-001 target antigen or those with significant liver metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in the context of solid tumors without lymphodepleting chemotherapy, previous CAR-T studies have shown promising results in hematological malignancies.

Eligibility criteria

Inclusion Criteria:

1. 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).
2. Age: 18-70 years (including 18 and 70 years).
3. ECOG 0-1.
4. With an expected survival of more than 3 months.
5. 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.
6. Preference for patients who have failed first- or second-line therapy.
7. Having measurable lesions according to RECIST 1.1 (or the latest version).
8. Maximum tumor size less than 4 cm according to RECIST 1.1 (or the latest version).
9. 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.
10. 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 Criteria:

1. Patients who have received the following anti-tumor treatments prior to apheresis:

   1. Cytotoxic therapy within 14 days or 28 days (for chemotherapy with high lymphocytic toxicity such as bendamustine, cyclophosphamide, ifosfamide, fludarabine, cladribine, etc.).
   2. Small molecule targeted therapy within 14 days or at least 5 half-lives, whichever is longer.
   3. Therapy with monoclonal antibody within 21 days including cetuximab.
   4. Therapy with immune checkpoint inhibitors and/or Avastin within 30 days of apheresis.
   5. Immunomodulatory therapy within 14 days.
   6. Radiotherapy within 14 days of apheresis.
   7. Traditional Chinese medicine with anti-tumor indications within 14 days of apheresis.
   8. Investigational agents or treatment within 28 days of apheresis.
   9. Previously treated with CAR-T/TCR-T cells and/or vaccine within 28 days of apheresis.
2. Previously treated with any BT-001-targeted therapy.
3. Brain metastases with central nervous system symptoms.
4. Pregnant (positive pregnancy test prior to dosing) or breast-feeding.
5. 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.
6. 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.
7. 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.
8. 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.
9. Patients with uncontrolled active infection based on the investigator's judgment.
10. Patients who underwent major surgery within 2 weeks prior to apheresis and not fully recovered.
11. 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).
12. 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.
13. 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).
14. Patients with autoimmune diseases.
15. Patients with Crohn's Disease.
16. Patients with a history of uncontrollable mental illness.
17. Any condition in which the investigator considers that the subject is not suitable to participate in the study.

Where this trial is running

Shanghai, China/Shanghai and 1 other locations

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

Study contacts

• Principal investigator: Jin Li, MD, PhD — Shanghai East Hospital
• Study coordinator: Jin Li, MD,PhD

Conditions Advanced Solid Tumor