A Clinical Study to Evaluate B4T2-001 CAR T Cells in the Treatment of Advanced Solid Tumors

NCT05621486 | Active Not Recruiting Phase 1

• 1 other identifier: B4T2-PRC-IIT-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This is a first in human (FIH), open-label, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of B4T2-001 Autologous CAR T cells 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).

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of serious adverse events (SAEs), incidence and severity of adverse events (AEs)

  Safety and tolerability of B4T2-001 CAR T cells

  Minimum 2 years after B4T2-001 CAR T infusion

• To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of B4T2-001 CAR T cells

  The MTD will be determined based on the occurrence of the Dose-Limiting Toxicities (DLTs) according to the accelerated titration design and 3+3 dose escalation design. RP2D will be defined based on MTD, safety, PK, and preliminary efficacy data.

  2 years after B4T2-001 CAR T infusion

Secondary Outcomes (7)

• Pharmacokinetics (PK): Area Under Curve (AUC)

  Blood sampling for PK will be performed at planned time points till the end of the study

• Pharmacokinetics (PK): maximum concentration (Cmax)

  Blood sampling for PK will be performed at planned time points till the end of the study

• Pharmacokinetics (PK): Time to Cmax (Tmax)

  Blood sampling for PK will be performed at planned time points till the end of the study

• Overall response rate (ORR) after administration

  Minimum 2 years after B4T2-001 CAR T infusion

• Duration of Response (DOR) after administration

  Minimum 2 years after B4T2-001 CAR T infusion

Other Outcomes (4)

• Blood cytokine levels include interleukin 6 (IL-6), IL-2, IL-4, IL-8, IL-10, TNF-α, and INF-γ with ELISA or equivalent method

  Blood sampling for cytokine measurement will be performed at planned time points till 90 days after B4T2-001 CAR T infusion

• H score (0-300)

  Minimum 2 years after B4T2-001 CAR T infusion

• Overall IHC Score (0-4)

  Minimum 2 years after B4T2-001 CAR T infusion

Study Arms (1)

B4T2-001 CAR T cells

EXPERIMENTAL

Single Arm and Open Label study consisting of dose escalation study design followed by dose expansion phase at determined MTD. Treatment follows a lymphodepleting chemotherapy regimen

Biological: B4T2-001 Autologous CAR T cells

Interventions

B4T2-001 Autologous CAR T cells BIOLOGICAL

Each subject will receive infusion with B4T2-001 autologous CAR T Cells

B4T2-001 CAR T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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;
• Histologically or cytologically confirmed locally advanced or metastatic BT-001 positive malignant solid tumors (including but not limited to gastric or gastroesophageal junction adenocarcinoma, pancreatic cancer, non-small cell lung cancer and breast cancer), who have failed standard treatment, or for whom standard treatment is not available or applicable at this stage;
• Having measurable or evaluable lesions according to RECIST 1.1 or the latest version;
• Having sufficient bone marrow, liver and kidney functions (based on the normal value of the clinical trial site):
• Absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 75×109/L;
• Total serum bilirubin ≤ 1.5×upper limit of normal (ULN);
• Without liver metastases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) ≤ 2.5×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 must 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;
• Small molecule targeted therapy within 14 days or at least 5 half-lives, whichever is longer;
• Therapy with monoclonal antibody within 21 days;
• Immunomodulatory therapy within 7 days;
• Radiotherapy within 14 days;
• Traditional Chinese medicine with anti-tumor indications within 14 days;
• Investigational agents or treatment within 28 days.
• Previously treated with CAR-T/TCR-T cells therapy against any target or other cell therapies or therapeutic tumor vaccine;
• 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 women;
• Allergic reaction to any drug and related excipients specified in protocol, e.g., lymphodepletion regimen (cyclophosphamide and fludarabine) and pre-infusion medication (acetaminophen and diphenhydramine), human serum albumin, tocilizumab, Erbitux/cetuximab, dimethyl sulfoxide (DMSO), and dextran 40;
• Patients with active hepatitis B (hepatitis B surface antigen (HBsAg) is positive and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \> 500IU/ml or lower limit of the research center \[Only when the detection limit of the research center is higher than 500IU/ml\]), or active hepatitis C (patients with positive HCV antibody but HCV-RNA \< lower limit of detection at the site are allowed), but patients receiving prophylactic antiviral therapy other than interferon are allowed;
• 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;

Sponsors & Collaborators

• Shanghai East Hospital: lead
• Bio4T2 LLC: collaborator

Study Sites (2)

Shanghai East Hospital

Shanghai, China/Shanghai, 200126, China

Location

Shanghai Artemed Hospital

Shanghai, China/Shanghai, 200131, China

Location

Related Publications (5)

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Thompson JA, Schneider BJ, Brahmer J, Achufusi A, Armand P, Berkenstock MK, Bhatia S, Budde LE, Chokshi S, Davies M, Elshoury A, Gesthalter Y, Hegde A, Jain M, Kaffenberger BH, Lechner MG, Li T, Marr A, McGettigan S, McPherson J, Medina T, Mohindra NA, Olszanski AJ, Oluwole O, Patel SP, Patil P, Reddy S, Ryder M, Santomasso B, Shofer S, Sosman JA, Wang Y, Zaha VG, Lyons M, Dwyer M, Hang L. Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Apr;20(4):387-405. doi: 10.6004/jnccn.2022.0020.

  PMID: 35390769 BACKGROUND

• Jo Y, Ali LA, Shim JA, Lee BH, Hong C. Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield. Cancers (Basel). 2020 Jul 28;12(8):2087. doi: 10.3390/cancers12082087.

  PMID: 32731404 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.

  PMID: 30592986 BACKGROUND

Study Officials

• Jin Li, MD, PhD

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 18, 2022
• Study Start: September 14, 2022
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 12, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)