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)
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
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count \>= 1,500/mcL (\> 1.5 X 10\^6/L)
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 mg/dL (transfusion to obtain hemoglobin \>= 9 mg/dL within 24 hours prior to dosing is allowed)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance (CrCl) \>= 60 mL/min for participant with creatinine levels \> 1.5 X institutional upper limit of normal (ULN) (Glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl)
• Patients must have adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 3 X ULN and total bilirubin \< 1.5 X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin =\< 5 mg/dL will be permitted. Gilbert's syndrome will be defined as elevated unconjugated bilirubin, with conjugated (direct) bilirubin within the normal range and less than 20% of the total. Total bilirubin will be permitted up to 5 mg/dL, if patients have historical readings consistent with the definition of Gilbert's syndrome prior to entering study. Adequate hepatic function for patients with known liver metastases is defined as AST and ALT levels ≤ 5 X ULN
• The effects of the trial agents on the developing human fetus are unknown. However, gemcitabine is known to have negative fetal effects. For this reason: Women of childbearing potential must agree to use adequate contraception at study entry, for the duration of study participation and for 7 months after the last dose of study medication based upon estimated half-life or receptor occupancy. Adequate contraception is defined as 2 highly effective methods of contraception (including a physical barrier). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men should refrain from fathering a child using adequate contraception or donating sperm during the study and for 6 months after the last dose of study medications. Adequate contraception is defined as 2 highly effective methods of contraception (including a physical barrier)
• Patients with well-controlled human immunodeficiency virus (HIV) infection are eligible for trial as long as:
‣ On an effective anti-retroviral therapy (ART) ˃ 4 weeks and with evidence of viral-suppression as defined as HIV viral load ˂ 400 copies/mL within the last 3 months
⁃ CD4 \> 200 cells/µL within the last 3 months; and
⁃ No reported opportunistic infections within 6 months prior to enrollment, except for the following which will be allowed:
• Esophageal candidiasis treated within last 6 months or currently improving with antifungal treatment.
∙ Oral and/or genital herpes simplex virus (HSV) treated within last 6 months or currently improving with antiviral treatment.
∙ Mycobacterium avium infection in last 6 months or that has been treated for at least 1 month
• Patients with evidence of chronic hepatitis B virus (HBV) infection are eligible for trial as long as the HBV viral load is undetectable on suppressive therapy, if indicated.
‣ Patients with history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable or unquantifiable HCV ribonucleic acid (RNA) 12 weeks or longer after definitive treatment completion.
⁃ Patients must be able to understand and willing to sign a written informed consent document
• Any adverse events subjects have experienced from prior therapy must have resolved to =\< grade 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5