Autologous huMNC2-CAR44 or huMNC2-CAR22 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*)
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ClinicalTrials.gov Identifier: NCT04020575 |
Recruitment Status :
Recruiting
First Posted : July 16, 2019
Last Update Posted : June 18, 2023
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Tracking Information | |||||
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First Submitted Date ICMJE | July 12, 2019 | ||||
First Posted Date ICMJE | July 16, 2019 | ||||
Last Update Posted Date | June 18, 2023 | ||||
Actual Study Start Date ICMJE | January 15, 2020 | ||||
Estimated Primary Completion Date | January 2025 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Incidence of Adverse Events [ Time Frame: Within 35 days after T cell infusion ] To determine the safety and maximally tolerated cell dose (MTD) and recommended phase 2 cell dose (RP2D) of ex vivo expanded autologous huMNC2-CAR44 T cells or huMNC2-CAR22 CAR T cells for patients with advanced MUC1* positive breast cancer using CTCAE version 5.0 and Lee criteria.
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Original Primary Outcome Measures ICMJE |
Incidence of Adverse Events [ Time Frame: Within 35 days after T cell infusion ] To determine the safety and maximally tolerated cell dose (MTD) and recommended phase 2 cell dose (RP2D) of ex vivo expanded autologous huMNC2-CAR44 T cells for patients with advanced MUC1* positive breast cancer using CTCAE version 5.0 and Lee criteria.
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Autologous huMNC2-CAR44 or huMNC2-CAR22 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*) | ||||
Official Title ICMJE | Adoptive Immunotherapy for Advanced MUC1* Positive Breast Cancer With Autologous T Cells Engineered to Express a Chimeric Antigen Receptor, huMNC2-CAR44 or huMNC2-CAR22, Specific for a Cleaved Form of MUC1 (MUC1*) | ||||
Brief Summary | Phase I/II study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express either a chimeric antigen receptor, huMNC2-CAR44 or huMNC2-CAR22, which are specific for a cleaved form of MUC1 (MUC1*). | ||||
Detailed Description | Recent trials have demonstrated that chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) specific for the CD19 molecule can mediate marked tumor regression in a subset of patients with advanced acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). It would be ideal to extend CAR-T cell therapy to common epithelial cancers. However, this poses several challenges, including the identification of molecules expressed on tumor cells that can be targeted safely with CAR-T cells. Minerva Biotechnologies has developed a CAR T product (huMNC2-CAR44 or huMNC2-CAR22) that targets the extra cellular domain of the cleaved form of MUC1 (called MUC1*), which is the form of MUC1 that functions as a growth factor receptor and is present on large percentage of solid tumors, including breast tumors. The antibody targeting head of huMNC2-CAR44 or huMNC2-CAR22 specifically recognizes a cancerous form of MUC1* and does not bind to another form of cleaved MUC1 that is present on some normal tissues that also have a rapid turnover. To be clear, patients will receive either huMNC2-CAR44 or huMNC2-CAR22, but not a combined product. The huMNC2-CAR44 product consists of autologous T cells that are isolated from cancer patients, transduced with a proprietary lentiviral vector backbone manufactured under cGMP and containing sequences for a human CD8 alpha leader sequence, humanized MNC2-scFv (MUC1* targeting head), portions of human CD8 hinge and transmembrane domains, and human 4-1BB and human CD3-zeta costimulatory domains. The huMNC2-CAR44 transduced T cells are antigen-stimulated in vitro, with a synthetic MUC1* extracellular domain peptide. The CAR T cells are then ready for administration to the patient. Alternatively, the CAR T cells can be cryopreserved, then administered to the patient after thaw at bedside. The huMNC2-CAR22 product is comprised of a CD8-α leader sequence, the huMNC2 scFv, a CD28 hinge and transmembrane region, followed by a CD28 co-stimulatory domain and a CD3-ζ signaling domain bearing two Tyrosine to Phenylalanine mutations in each of ITAMs 2 and 3 to minimize CAR T cell exhaustion and increase in vivo persistence. The huMNC2-CAR22 transduced T cells are not antigen-stimulated. The CAR T cells can be cryopreserved, then administered to the patient after thaw at bedside. The investigators propose to evaluate the safety and preliminary anti-tumor activity of adoptively transferred autologous T cells genetically modified to express a CAR that targets MUC1*, huMNC2-CAR44 or huMNC2-CAR22, in Phase I/II clinical trials in patients with metastatic MUC1* positive breast cancers. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Metastatic Breast Cancer | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
69 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | January 15, 2035 | ||||
Estimated Primary Completion Date | January 2025 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Please note that results of tests and/or procedures conducted as per standard of care purposes may be used for research purposes if conducted within the protocol-defined window prior to screening/leukapheresis and/or T-Cell Therapy. Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
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Administrative Information | |||||
NCT Number ICMJE | NCT04020575 | ||||
Other Study ID Numbers ICMJE | 10038 | ||||
Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Minerva Biotechnologies Corporation | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Minerva Biotechnologies Corporation | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | City of Hope Medical Center | ||||
Investigators ICMJE |
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PRS Account | Minerva Biotechnologies Corporation | ||||
Verification Date | June 2023 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |