Condition or disease | Intervention/treatment | Phase |
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Metastatic Breast Cancer | Biological: huMNC2-CAR44 CAR T cells Biological: huMNC2-CAR44 CAR T cells @ RP2D | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 69 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Adoptive Immunotherapy for Advanced MUC1* Positive Breast Cancer With Autologous T Cells Engineered to Express a Chimeric Antigen Receptor, huMNC2-CAR44 Specific for a Cleaved Form of MUC1 (MUC1*) |
Actual Study Start Date : | January 15, 2020 |
Estimated Primary Completion Date : | January 2023 |
Estimated Study Completion Date : | January 15, 2035 |
Arm | Intervention/treatment |
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Experimental: Dose Escalation
Dose escalation or de-escalation is tested in cohorts of 3 patients each using standard "3+3" dose-finding.
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Biological: huMNC2-CAR44 CAR T cells
huMNC2-CAR44 T cells are an autologous T cell product transduced with a proprietary lentiviral vector backbone coding for humanized MNC2-scFv (the targeting head).
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Experimental: Luminal
Dose Expansion - 15 patients will be enrolled with luminal (hormone receptor positive, HER2 negative) metastatic breast cancer.
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Biological: huMNC2-CAR44 CAR T cells @ RP2D
huMNC2-CAR44 T cells are an autologous T cell product transduced with a proprietary lentiviral vector backbone coding for humanized MNC2-scFv (the targeting head) @ RP2D
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Experimental: HER2+
Dose Expansion - 15 patients will be enrolled with HER2+ metastatic breast cancer.
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Biological: huMNC2-CAR44 CAR T cells @ RP2D
huMNC2-CAR44 T cells are an autologous T cell product transduced with a proprietary lentiviral vector backbone coding for humanized MNC2-scFv (the targeting head) @ RP2D
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Experimental: Triple Negative
Dose Expansion - 15 patients will be enrolled with triple negative metastatic breast cancer.
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Biological: huMNC2-CAR44 CAR T cells @ RP2D
huMNC2-CAR44 T cells are an autologous T cell product transduced with a proprietary lentiviral vector backbone coding for humanized MNC2-scFv (the targeting head) @ RP2D
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients must have received standard metastatic systemic therapy per NCCN guidelines or institutional practice which are known to confer benefit. No maximum on number of prior systemic treatment regimens.
Patients must have measurable disease by at least one of the criteria below:
Exclusion Criteria:
Major organ dysfunction defined as:
i. NYHA class III or IV congestive heart failure, ii. clinically significant hypotension, iii. uncontrolled symptomatic coronary artery disease, or iv. a documented ejection fraction of <45%. Any patient with an EF of 45-49% must receive clearance by a cardiologist to be eligible for the trial.
Contact: Jennifer Specht, MD | 206-606-4668 | immunotherapy@seattlecca.org |
United States, Washington | |
Fred Hutchinson Cancer Research Center | Recruiting |
Seattle, Washington, United States, 98109 | |
Principal Investigator: Jennifer M Specht, MD |
Principal Investigator: | Jennifer M Specht, MD | Fred Hutchinson Cancer Research Center |
Tracking Information | |||||
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First Submitted Date ICMJE | July 12, 2019 | ||||
First Posted Date ICMJE | July 16, 2019 | ||||
Last Update Posted Date | January 28, 2020 | ||||
Actual Study Start Date ICMJE | January 15, 2020 | ||||
Estimated Primary Completion Date | January 2023 (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 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 | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Autologous huMNC2-CAR44 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 Specific for a Cleaved Form of MUC1 (MUC1*) | ||||
Brief Summary | Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 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 (huMNC2-CAR44) 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 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. 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. 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, in a phase I clinical trial in patients with metastatic MUC1* positive breast cancer. | ||||
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 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
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 | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04020575 | ||||
Other Study ID Numbers ICMJE | 10038 | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Minerva Biotechnologies Corporation | ||||
Study Sponsor ICMJE | Minerva Biotechnologies Corporation | ||||
Collaborators ICMJE | Fred Hutchinson Cancer Research Center | ||||
Investigators ICMJE |
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PRS Account | Minerva Biotechnologies Corporation | ||||
Verification Date | January 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |