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

NCT06072989 | Recruiting Phase 1

• 1 other identifier: B4T2-PRC IIT-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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 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).

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (8)

• PK parameters: maximum concentration (Cmax)

  Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T

• PK parameters: time of peak concentration (Tmax)

  Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T

• PK parameters: the last measurable time point (Tlast)

  Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T

• PK parameters: area under the curve (AUCs)

  Blood sampling for PK will be performed till 2 years after B4T2-001 CAR-T

• Overall response rate (ORR) after administration

  2 years after B4T2-001 CAR-T

Other Outcomes (5)

• 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 2 years after B4T2-001 CAR-T.

• H score (0-300)

  Planned time points till 2 years after B4T2-001 CAR-T

• Overall IHC Score (0-4)

  Planned time points till 2 years after B4T2-001 CAR-T

Study Arms (1)

B4T2-001 CAR T

EXPERIMENTAL

Single Arm and Open Label study consisting of dose escalation study design followed by dose expansion phase at determined MTD.

Biological: B4T2-001 autologous CAR-T

Interventions

B4T2-001 autologous CAR-T BIOLOGICAL

Each subject will receive multiple intravenous infusions of B4T2-001 autologous CAR-T without preparative chemotherapy (lymphodepletion)

B4T2-001 CAR T

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.
• 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.

Sponsors & Collaborators

• Shanghai East Hospital: lead
• Bio4T2 LLC: collaborator

Study Sites (2)

Shanghai East Hospital

Shanghai, China/Shanghai, 200126, China

RECRUITING

Shanghai Artemed Hospital

Shanghai, China/Shanghai, 200131, China

RECRUITING

Related Publications (16)

• 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

• Kershaw MH, Westwood JA, Darcy PK. Gene-engineered T cells for cancer therapy. Nat Rev Cancer. 2013 Aug;13(8):525-41. doi: 10.1038/nrc3565.

  PMID: 23880905 BACKGROUND

• Kochenderfer, J.N., et al., Effective Treatment Of Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma With Autologous T Cells Genetically-Engineered To Express An Anti-CD19 Chimeric Antigen Receptor. Blood, 2013. 122(21): p. 168-168.

  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

• Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 Mar 2.

  PMID: 28271869 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

• Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, Mastronuzzi A, Cefalo MG, Pagliara D, Amicucci M, Li Pira G, Leone G, Bertaina V, Sinibaldi M, Di Cecca S, Guercio M, Abbaszadeh Z, Iaffaldano L, Gunetti M, Iacovelli S, Bugianesi R, Macchia S, Algeri M, Merli P, Galaverna F, Abbas R, Garganese MC, Villani MF, Colafati GS, Bonetti F, Rabusin M, Perruccio K, Folsi V, Quintarelli C, Locatelli F; Precision Medicine Team-IRCCS Ospedale Pediatrico Bambino Gesu. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma. N Engl J Med. 2023 Apr 6;388(14):1284-1295. doi: 10.1056/NEJMoa2210859.

  PMID: 37018492 BACKGROUND

• Qi C, Gong J, Li J, Liu D, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Cao Y, Zhang X, Lu Z, Lu M, Yuan J, Wang Z, Wang Y, Peng X, Gao H, Liu Z, Wang H, Yuan D, Xiao J, Ma H, Wang W, Li Z, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022 Jun;28(6):1189-1198. doi: 10.1038/s41591-022-01800-8. Epub 2022 May 9.

  PMID: 35534566 BACKGROUND

• Gauthier J, Bezerra ED, Hirayama AV, Fiorenza S, Sheih A, Chou CK, Kimble EL, Pender BS, Hawkins RM, Vakil A, Phi TD, Steinmetz RN, Jamieson AW, Bar M, Cassaday RD, Chapuis AG, Cowan AJ, Green DJ, Kiem HP, Milano F, Shadman M, Till BG, Riddell SR, Maloney DG, Turtle CJ. Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies. Blood. 2021 Jan 21;137(3):323-335. doi: 10.1182/blood.2020006770.

  PMID: 32967009 BACKGROUND

• Hines MR, Knight TE, McNerney KO, Leick MB, Jain T, Ahmed S, Frigault MJ, Hill JA, Jain MD, Johnson WT, Lin Y, Mahadeo KM, Maron GM, Marsh RA, Neelapu SS, Nikiforow S, Ombrello AK, Shah NN, Talleur AC, Turicek D, Vatsayan A, Wong SW, Maus MV, Komanduri KV, Berliner N, Henter JI, Perales MA, Frey NV, Teachey DT, Frank MJ, Shah NN. Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome. Transplant Cell Ther. 2023 Jul;29(7):438.e1-438.e16. doi: 10.1016/j.jtct.2023.03.006. Epub 2023 Mar 9.

  PMID: 36906275 BACKGROUND

• Jain MD, Smith M, Shah NN. How I treat refractory CRS and ICANS after CAR T-cell therapy. Blood. 2023 May 18;141(20):2430-2442. doi: 10.1182/blood.2022017414.

  PMID: 36989488 BACKGROUND

• Alvi RM, Frigault MJ, Fradley MG, Jain MD, Mahmood SS, Awadalla M, Lee DH, Zlotoff DA, Zhang L, Drobni ZD, Hassan MZO, Bassily E, Rhea I, Ismail-Khan R, Mulligan CP, Banerji D, Lazaryan A, Shah BD, Rokicki A, Raje N, Chavez JC, Abramson J, Locke FL, Neilan TG. Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T). J Am Coll Cardiol. 2019 Dec 24;74(25):3099-3108. doi: 10.1016/j.jacc.2019.10.038.

  PMID: 31856966 BACKGROUND

• Ghosh AK, Chen DH, Guha A, Mackenzie S, Walker JM, Roddie C. CAR T Cell Therapy-Related Cardiovascular Outcomes and Management: Systemic Disease or Direct Cardiotoxicity? JACC CardioOncol. 2020 Mar 17;2(1):97-109. doi: 10.1016/j.jaccao.2020.02.011. eCollection 2020 Mar.

  PMID: 34396213 BACKGROUND

• Haerizadeh F, Jiang H, Cooper L. Selective recognition of over-expressed self-antigens in solid tumors using calibrated CAR-T therapy. Journal of Clinical Oncology 2023 41:16_suppl, 2540-2540

  BACKGROUND

Study Officials

• Jin Li, MD, PhD

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Li, MD,PhD

CONTACT

+86-13761222111; lijin@csco.org.cn

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: September 25, 2023
• First Posted: October 10, 2023
• Study Start: October 1, 2023
• Primary Completion: March 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)