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.
Patients must have histologically or cytologically confirmed, HER2 negative metastatic breast cancer that is historically GD2 expressing (e.g., triple negative breast cancer, metaplastic breast cancer, high grade 3 estrogen positive breast cancer at initial diagnosis) with available archival tissue. Well differentiated neuroendocrine tumor (NETs) are not eligible for this trial since GD2 expression is unknown. GD2 expression is not required for eligibility but a primary tumor paraffin block is required at enrollment for assessment of GD2 expression
Patients must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for the evaluation of measurable disease
Patients must have received at least one prior treatment for metastatic disease and progressed on treatment or been intolerant to treatment
Female or male >=18 years
Patients who within 3 weeks prior to study enrollment who have received chemotherapy, investigational agents, or radiation
Patients with active brain metastases or leptomeningeal metastases are excluded from this clinical trial because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients with treated brain metastases are eligible if there is no magnetic resonance imaging (MRI) evidence of progression for 6 months after treatment is complete and within 28 days prior to the first dose of trial drug. Patients requiring immunosuppressive doses of systemic corticosteroids (> 10mg/day prednisone equivalent) for palliation are excluded
Patients with a history of another invasive malignancy < 3 years prior to enrollment (patients with non-melanoma skin cancers, carcinoma in situ of the breast or cervix are eligible)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
Sequential
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan
Gemcitabine
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Naxitamab
Biological/VaccineGiven IV
Universal Donor Expanded TGF-beta-imprinted NK Cells
Biological/VaccineGiven IV
Incidence of adverse events
Will be summarized descriptively with reporting of any dose limiting toxicities (DLTs) in these initial patients. In addition, to DLTs, serious adverse events (SAEs) and immune related adverse events of interest will be reported. Will be summarized descriptively and graphically, with reporting the outcome measures indicated along with two-tailed 95% confidence intervals (CIs). Number and frequency of patients experiencing each adverse event (AE) type and grade will tabulated, among patients evaluable for toxicity. The number (%) of patients experiencing at least one grade 3 to 5 AE will be reported with 95% CI.
Objective response rate
Will be estimated in each arm using two-sided 80% and 95% CI about the observed percentages of response (PR+CR).
Transforming growth factor beta imprinted natural killer (TGFBi NK) cell detection
TGFBi NK cell persistence will be defined as the presence (detectable donor TGFBi NK cells) or the absence (no detectable donor TGFBi NK cells). Data will be described numerically as percentage of donor cells in blood and will be correlated to clinical outcomes.
Progression free survival
Will be estimated using a Kaplan-Meier curve and the median PFS will be reported along with a 95% confidence interval, separately by arm, based on the patients who are enrolled in the evaluation of clinical response.
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Margaret Gatti-Mays
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
