Advanced Solid Tumor Clinical Trial
Official title:
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 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).
Status | Recruiting |
Enrollment | 24 |
Est. completion date | March 2027 |
Est. primary completion date | March 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
China | Shanghai Artemed Hospital | Shanghai | China/Shanghai |
China | Shanghai East Hospital | Shanghai | China/Shanghai |
Lead Sponsor | Collaborator |
---|---|
Shanghai East Hospital | Bio4T2 LLC |
China,
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Blood cytokine levels include interleukin 6 (IL-6), IL-2, IL-4, IL-8, IL-10, TNF-a, and INF-? with ELISA or equivalent method | Concentration and kinetics of multiple blood cytokines including (IL-6), IL-2, IL-4, IL-8, IL-10, TNF-a, and INF-? which have the same unit of measure, and using ELISA or equivalent before and after CAR-T and will be evaluated according to actual blood sampling time points. | Blood sampling for cytokine measurement will be performed at planned time points till 2 years after B4T2-001 CAR-T. | |
Other | H score (0-300) | Explore and evaluate histology before and possibly after CAR-T for expression of BT-001 antigen on the tumor by immunohistochemistry (IHC) to determine the score intensity. "BT-001 positive" refers to a staining of H score of > 150 and preference will be patients with H score of > 200. H score (0-300) will be calculated. High scores are desired. | Planned time points till 2 years after B4T2-001 CAR-T | |
Other | Overall IHC Score (0-4) | Explore and evaluate histology before and possibly after CAR-T for expression of BT-001 antigen on the tumor by IHC to evaluate the score intensity. "BT-001 positive" refers to an IHC score = 3 and preference will be patients with an IHC score of 4. Overall IHC Score (0-4) will be calculated. High scores are desired. | Planned time points till 2 years after B4T2-001 CAR-T | |
Other | The percentage of BT-001 positive stained tumor | Explore and evaluate histology before and possibly after CAR-T for heterogeneity of expression of BT-001 antigen on the tumor. | Planned time points till 2 years after B4T2-001 CAR-T | |
Other | Exploratory tumor biomarker evaluation | Explore and evaluate tumor markers, such as CEA before and possibly after CAR-T. | Planned time points till 2 years after B4T2-001 CAR-T | |
Primary | Safety and tolerability of B4T2-001 CAR-T will be assessed by the incidence of serious adverse events (SAEs), incidence and severity of adverse events (AEs). | Multiple infusions of B4T2-001 CAR-T. | 2 years after B4T2-001 CAR-T | |
Primary | To determine the MTD and RP2D of B4T2-001 CAR-T | The MTD will be determined based on the occurrence of the DLTs according to dose escalation design. RP2D will be defined based on MTD, safety, PK, and preliminary efficacy data. | 2 years after B4T2-001 CAR-T | |
Secondary | PK parameters: maximum concentration (Cmax) | Maximum concentration (Cmax) with the immunoanalytical method. | Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T | |
Secondary | PK parameters: time of peak concentration (Tmax) | Time to peak concentration (Tmax) with the immunoanalytical method. | Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T | |
Secondary | PK parameters: the last measurable time point (Tlast) | The last measurable time point (Tlast) with the immunoanalytical method. | Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T | |
Secondary | PK parameters: area under the curve (AUCs) | Area under the curve (AUCs)with the immunoanalytical method. | Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T | |
Secondary | Overall response rate (ORR) after administration | ORR is defined as the proportion of subjects who achieve CR or PR after treatment via B4T2-001 CAR T, and the objective tumor response rate will be calculated for patients with measurable disease per by RECIST 1.1 (or the latest version) supplemented by iRecist. | 2 years after B4T2-001 CAR-T | |
Secondary | Duration of Response (DOR) after administration | DOR is defined as the time from the first documentation of remission (PR or better) to the first documented disease progression evidence (by RECIST 1.1 (or the latest version) supplemented by iRecist) of the responders (who achieve PR or better response). | 2 years after B4T2-001 CAR-T | |
Secondary | Progress Free Survival (PFS) after administration | PFS is defined as the time from the date of first infusion of the B4T2-001 to the first documented disease progression (according to by RECIST 1.1 (or the latest version) supplemented by iRecist) or death (due to any cause), whichever occurs first. | 2 years after B4T2-001 CAR-T | |
Secondary | Overall Survival (OS) after administration | OS is defined as the time from the date of first infusion of B4T2-001 CAR-T to death of the subject. | 2 years after B4T2-001 CAR-T |
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