ClinicalTrials.gov record NCT06026657
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
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)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This phase 1b/2 treatment study tests gemcitabine together with ex vivo expanded allogeneic TGF‑β‑imprinted natural killer (TGFBi NK) cells, given with or without naxitamab (Danyelza), in people with metastatic GD2‑expressing, HER2‑negative breast cancer. The trial looks for safe dose(s) and measures tumor responses. Treatments are given by IV in repeating 28‑day cycles; the NK‑cell infusion(s) occur during the first cycle. Participants will have imaging and blood samples taken during treatment and be followed after stopping therapy.
What it is studying. The study is testing the safety and appropriate dose of combining gemcitabine with donor TGFBi NK cells, and whether adding naxitamab affects tumor response. It will measure objective tumor responses and track whether the infused donor NK cells can be detected in the blood after infusion. Secondary and exploratory goals include estimating progression‑free survival versus historical data and studying immune and tumor markers in blood and archival tissue.
What the researchers hope to learn. Scientific goals are to evaluate safety and dose-limiting toxicities, estimate objective response rates in each treatment arm, determine whether donor TGFBi NK cells persist in the blood after infusion, and estimate progression‑free survival compared with historical controls. Exploratory analyses will profile immune responses and examine tumor GD2 expression and other tumor markers.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Gemcitabine
- Biological
- Naxitamab
- Universal Donor Expanded TGF-beta-imprinted NK Cells
- Procedure
- Biospecimen Collection
- Computed Tomography
- Magnetic Resonance Imaging
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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
Exclusion criteria
- 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
- Uncontrolled intercurrent illness including, but not limited to, ongoing active infection that requires systemic treatment with ongoing antibiotics (eligible if can stop antibiotics on day of enrollment), unexplained fever (temperature > 38.1˚celcius [C]) within 7 days of initial treatment, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that in the opinion of the primary investigator would prohibit the patient from complying with study requirements
- Patients with bone metastases who have initiated denosumab or a bisphosphonate therapy within 28 days prior to or after cycle 1 day 1 due to the potential for flu-like symptoms and mild cytokine release syndrome with the initial dose. However, continuation of prior therapy is allowed
- Patients should have no evidence of being immunocompromised as listed below:
- Active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger in the opinion of the primary investigator
- Altered immune function that in the judgement of the PI that may affect a patient's ability to adequately engage the immune system and respond to the immunotherapy agents being administered, including but not limited to: inflammatory bowel disease; active infectious enteritis; eosinophilic enteritis; lupus erythematous; ankylosing spondylitis; scleroderma; multiple sclerosis. These criteria do not include all disease with an immune-related component but are not autoimmune in nature or have a primary alteration in the general immune function that may interfere with the vaccine mechanism of action, for example celiac disease
- Immunosuppressive therapy post-organ transplant
- Concurrent use of chronic use of systemic steroids, except for physiologic doses of systemic steroids for replacement, defined as 10mg of prednisone per day or equivalent, or local (topical, nasal, ophthalmic or inhaled) steroid use or prior concomitant use with chemotherapy. Systemic steroids must have been discontinued >2 weeks prior to trial start. Prior use of corticosteroids in short-term schemes (duration shorter than 3 days) for indications such as prophylaxis of reactions to intravenous contrast for imaging studies or chemotherapy-related adverse events (AEs) are not considered part of this exclusion. Prior use of corticosteroids for brain metastasis ending at least 14 days prior to enrollment is not considered part of this exclusion criteria
- Pregnant and breastfeeding women are excluded from this study because of the potential for teratogenic or abortifacient effects with all of the agents involved in this trial. Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods. Women of childbearing potential must agree to use two methods of adequate contraception at study entry be used for the duration of study participation and for at least 7 months for women and 6 months for men after the final dose of any study-related medications
- Clinically significant cardiomyopathy, coronary disease, myocardial infarction, chronic heart failure (CHF) (New York Heart Association class III or IV or hospitalization for CHF), ejection fraction < 50% or cerebrovascular accident within 6 months prior to enrollment
- Patients with a history of myocarditis are excluded due to the potential of myocarditis with anti-PD-L1 antibodies or other immunotherapies
- Patients who have received any live vaccines within 30 days prior to enrollment (inactivated vaccines including COVID vaccines are allowed)
- Any other condition, which would, in the opinion of the principal investigator the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained
- Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 90% and/or abnormal pulmonary function tests within 28 days of C1D1 if these assessments are clinically indicated.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive intravenous gemcitabine on days 1, 8 and 15 of each 28‑day cycle for up to 1 year, and one or two IV infusions of donor TGFBi NK cells in the first cycle (day 16 and possibly day 18). In some arms they also receive IV naxitamab on days 1, 4 and 8 of each cycle. Study visits include treatment infusions (30–60 minutes for drugs; 10–30 minutes for NK cells), CT scans and blood draws regularly, and possible MRIs. After stopping treatment there is a safety visit within 30 days and follow‑up visits every 3 months for 1 year.
How the study is structured. Interventional, non‑randomized treatment study with four sequential arms. All participants receive gemcitabine IV in 28‑day cycles (days 1, 8, 15) for up to one year; some arms also receive naxitamab IV on specified days. Universal donor TGFBi NK cells are given by IV infusion during the first cycle (one or two infusions depending on arm). Participants undergo CT scans, blood draws, and may have MRI; there is a safety follow‑up about 30 days after treatment and clinical follow‑up every 3 months for one year.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry lists this study under Anatomic Stage IV Breast Cancer AJCC v8; HER2-Negative Breast Carcinoma. Does it apply to my diagnosis?
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Gaucher disease
Important dates
- Study start
- Apr 2, 2024
- Primary completion
- Dec 31, 2026 (estimated)
- Study completion
- Dec 31, 2026 (estimated)
- Target enrollment
- 42 participants (estimated)
- Last updated on registry
- Jul 8, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Margaret Gatti-Mays
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- The Ohio State University Comprehensive Cancer Center 📞 800-293-5066 ✉ OSUCCCClinicaltrials@osumc.edu
- Amanda Kabetso 📞 614-257-2400 ✉ amanda.kabetso@osumc.edu
Participating sites (1)
- Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, 43210 · United States
- Margaret E. Gatti-Mays, MD, MPH · 614-293-0066
- Margaret E. Gatti-Mays, MD, MPH
Terms used on this page · explanations by MedicalUpdates.ai
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- prior treatment
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- Glomerular filtration rate
- A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
- Women of childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- half-life
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- investigational
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- magnetic resonance imaging
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- cytokine release syndrome
- A reaction in which the immune system releases a large amount of signalling proteins at once, causing fever and sometimes low blood pressure or breathing problems. It can occur after some immune therapies, such as CAR-T cells or bispecific antibodies.
- exclusion criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- principal investigator
- The doctor or scientist responsible for running the study at a site or overall.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- progression-free survival
- The length of time during and after treatment that a person lives without the condition getting worse, as defined by the study.
- computed tomography
- An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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