Ignite Creation Date:
2025-12-24 @ 6:51 PM
Ignite Modification Date:
2026-01-04 @ 12:01 AM
Study NCT ID:
NCT06026657
Status:
RECRUITING
Last Update Posted:
2025-07-08
First Post:
2023-08-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Gemcitabine and Ex Vivo Expanded Allogenic Universal Donor, TGFβi Natural Killer (NK) Cells With or Without Naxitamab (Danyelza) for the Treatment of Patients With Metastatic, GD2 Expressing, HER2 Negative Breast Cancer
Sponsor:
Margaret Gatti-Mays
Organization:
Study Overview
Official Title:
Phase 1b/2 Study of Naxitamab (Danyelza), Gemcitabine and Ex Vivo Expanded Allogenic Universal Donor, TGFβi Natural Killer (NK) Cells in Advanced GD2-expressing Breast Cancers (DiG NKs)
Status:
RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib/II trial tests the safety, best dose and how well gemcitabine and ex vivo expanded allogenic universal donor TGFBi NK cells with or without naxitamab work for the treatment of patients with GD2 expressing, HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. TGFBi NK cells are manufactured cells that are a part of your natural immunity. NK cells can recognize missing or incorrect proteins on tumor cells and then eliminate these tumor cells and TGFBi NK cells are created to be able to better kill the tumor cells. Naxitamab is a monoclonal antibody that targets GD2, which is a protein or sugar present on tumor cells but not very commonly found on normal cells. This antibody helps draw the attention of the immune system to the tumor cells that have GD2 to help attack the tumor cells. Giving gemcitabine and TGFBi NK cells with or without naxitamab may kill more tumor cells in patients with metastatic GD2 expressing, HER2 negative breast cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the safety of gemcitabine plus transforming growth factor beta imprinted natural killer (TGFBi NKs) +/- naxitamab in metastatic breast cancer.
II. To evaluate the objective response rate of gemcitabine plus TGFB NKs +/- naxitamab in metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To determine if TGFB NK cells are detectable in the peripheral blood 5 days following infusion (C1D21).
II. To determine if gemcitabine plus TGFB NKs +/- naxitamab improves median progression-free survival (PFS) in metastatic breast cancer over historical controls for gemcitabine alone.
EXPLORATORY OBJECTIVES:
I. Peripheral blood mononuclear cells (PBMCs) Ia. Real-time blood immune profiling Ib. Antigen specific immune responses II. Plasma/Serum IIa. TCR clonality IIb. Cytokines (IFNy, IL-10, IL-12, IL-2, IL4, etc) and chemokines IIc. Antigen specific immune responses III. Archival tissue IIIa. GD2 expression on tumor IIIb. Immunohistochemistry/multispectral imaging IIIc. Tumor mutational burden
OUTLINE: Patients are assigned to 1 of 4 arms.
ARM I: Patients receive gemcitabine intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 of cycle 1.
ARM II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 and 18 of cycle 1.
ARM III: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle followed by naxitamab IV over 30-60 minutes on days 1, 4, and 8 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 of cycle 1.
ARM IV: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle followed by naxitamab IV over 30-60 minutes on days 1, 4, and 8 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 and 18 of cycle 1.
Patients undergo computed tomography and blood sample collection and may undergo magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up within 30 days of stopping treatment and every 3 months for 1 year.
I. To evaluate the safety of gemcitabine plus transforming growth factor beta imprinted natural killer (TGFBi NKs) +/- naxitamab in metastatic breast cancer.
II. To evaluate the objective response rate of gemcitabine plus TGFB NKs +/- naxitamab in metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To determine if TGFB NK cells are detectable in the peripheral blood 5 days following infusion (C1D21).
II. To determine if gemcitabine plus TGFB NKs +/- naxitamab improves median progression-free survival (PFS) in metastatic breast cancer over historical controls for gemcitabine alone.
EXPLORATORY OBJECTIVES:
I. Peripheral blood mononuclear cells (PBMCs) Ia. Real-time blood immune profiling Ib. Antigen specific immune responses II. Plasma/Serum IIa. TCR clonality IIb. Cytokines (IFNy, IL-10, IL-12, IL-2, IL4, etc) and chemokines IIc. Antigen specific immune responses III. Archival tissue IIIa. GD2 expression on tumor IIIb. Immunohistochemistry/multispectral imaging IIIc. Tumor mutational burden
OUTLINE: Patients are assigned to 1 of 4 arms.
ARM I: Patients receive gemcitabine intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 of cycle 1.
ARM II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 and 18 of cycle 1.
ARM III: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle followed by naxitamab IV over 30-60 minutes on days 1, 4, and 8 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 of cycle 1.
ARM IV: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 of each cycle followed by naxitamab IV over 30-60 minutes on days 1, 4, and 8 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive TGFBi NK cells IV over 10-30 minutes on day 16 and 18 of cycle 1.
Patients undergo computed tomography and blood sample collection and may undergo magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up within 30 days of stopping treatment and every 3 months for 1 year.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2023-06508 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View |