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)

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Trial Details

Sponsor: Margaret Gatti-Mays (other)

Phase: 1/2

Start date: April 2, 2024

Planned enrollment: 42

Trial ID: NCT06026657
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: GEM/DOX + TGFBi expanded NK cells (TGF-beta imprinted NK cells)

TrialFetch AI Analysis

Goal: Assess safety, determine a recommended dosing approach, and obtain preliminary efficacy of gemcitabine combined with ex vivo expanded universal-donor TGFβ-imprinted NK cells with or without the anti-GD2 antibody naxitamab in metastatic, GD2-expressing, HER2-negative breast cancer.

Patients: Adults ≥18 years with histologically or cytologically confirmed HER2-negative metastatic breast cancer, historically GD2-expressing subtypes favored (e.g., triple-negative, metaplastic, high-grade ER+), measurable disease by RECIST 1.1, prior therapy for metastatic disease, ECOG 0–1, adequate marrow, renal, and hepatic function. GD2 expression is not required for eligibility, but archival primary tumor tissue is required for GD2 assessment. Key exclusions include active or untreated CNS disease, recent systemic therapy or radiation within 3 weeks, significant cardiac disease, active autoimmune disease requiring systemic therapy, significant immunosuppression, and pregnancy or breastfeeding.

Design: Phase 1b/2, open-label, non-randomized, multi-arm study with four experimental cohorts exploring one versus two TGFBi NK-cell infusions and the addition of naxitamab to gemcitabine. Planned enrollment is 42 patients. Safety and objective response are co-primary objectives across arms, with serial imaging and correlative immune assays.

Treatments: All arms include gemcitabine IV on days 1, 8, and 15 of 28-day cycles for up to 1 year if no progression or unacceptable toxicity. TGFBi NK cells are infused IV in cycle 1 on day 16 (Arms I and III) or days 16 and 18 (Arms II and IV). Arms III and IV also administer naxitamab IV on days 1, 4, and 8 each cycle. TGFβ-imprinted NK cells are an investigational, off-the-shelf, universal-donor NK-cell product expanded ex vivo in the presence of TGF-β to generate a phenotype resistant to TGF-β–mediated suppression and capable of heightened proinflammatory cytokine production; early clinical development is ongoing in other indications with no definitive human efficacy or safety results reported to date. Naxitamab is a monoclonal antibody targeting GD2 to facilitate immune-mediated tumor cell killing; it is approved in neuroblastoma and is being repurposed here to enhance ADCC against GD2-expressing breast cancer cells. Gemcitabine is a cytotoxic nucleoside analog commonly used in metastatic breast cancer salvage settings.

Outcomes: Primary outcomes: incidence of adverse events including dose-limiting toxicities, serious and immune-related adverse events; objective response rate (CR+PR) by RECIST 1.1 in each arm. Secondary outcomes: peripheral blood detection and persistence of donor TGFBi NK cells at day 5 post-infusion; progression-free survival estimated by Kaplan-Meier with median PFS and 95% CI. Exploratory endpoints include immune profiling of PBMCs, plasma/serum cytokines and chemokines, TCR clonality, antigen-specific responses, and archival tumor analyses including GD2 expression, immunohistochemistry/multispectral imaging, and tumor mutational burden.

Burden on patient: Moderate to high. Patients receive frequent IV infusions within each 28-day cycle (gemcitabine days 1, 8, 15; naxitamab days 1, 4, 8 in two arms; NK-cell infusion(s) on day 16 ± 18 in cycle 1), necessitating multiple clinic visits and infusion chair time. Safety labs and correlative blood draws are required, including specific sampling around NK-cell infusion to assess persistence, which adds venipunctures beyond standard care. Serial CT imaging and potential MRIs increase visit frequency. There are no mandated tumor biopsies beyond archival tissue, which lowers procedural burden, but early-phase monitoring and immune therapy infusions with potential premedications and observation periods raise time and travel demands. Overall, participation requires substantial clinic attendance and monitoring typical of a phase 1b/2 cell therapy–antibody combination study.

Last updated: Oct 2025

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Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

No email / 614-293-0066

Status: Recruiting