Ireland
--:--IST
Recruiting Phase 1/2

Dual-Target CAR-NK Cells for Advanced Breast Cancer (HER2+ and TNBC)

NCT07486089 · tracked via the Priya Life Science China tracker
Phase
Phase 1/2
Started
2026-02-02
Last updated
2026-03-20

Condition(s) studied

Breast Cancer (Locally Advanced or Metastatic)HER2-positive Breast CancerTriple-Negative Breast Cancer (TNBC)

Investigational drug(s) / intervention(s)

Dual-target CAR-NK cells (EB-DT-CAR-NK) →Lymphodepleting chemotherapySupportive care

Dual-target CAR-NK cells (EB-DT-CAR-NK): Route: IV infusion. Schedule: single infusion on Day 0; optional second infusion on Day 7 in the absence of dose-limiting toxicity (DLT) and with adequate clinical status.

Lymphodepleting chemotherapy: fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4), prior to CAR-NK infusion.

Supportive care: Premedication per institutional standard (e.g., acetaminophen and antihistamine). Tumor lysis and infection prophylaxis per institutional guidelines.

Study summary

This study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. After a tumor antigen assessment (HER2/ERBB2, MUC1, ROR1, and in some TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.

Eligibility

Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria: * Histologically confirmed breast carcinoma that is locally advanced, unresectable, or metastatic. * Disease subtype: HER2-positive breast cancer or triple-negative breast cancer (TNBC). * Progression after, intolerance to, or ineligibility for standard therapies appropriate for the disease subtype and line of therapy. * At least one measurable lesion per RECIST v1.1. * Tumor antigen assessment available (fresh or archival): expression of at least one candidate target antigen (HER2/ERBB2, MUC1, or ROR1). For TNBC, mesothelin assessment may be performed for exploratory analyses. * ECOG performance status 0-1. * Adequate organ function (example thresholds): ANC ≥ 1.0 x 10\^9/L; platelets ≥ 75 x 10\^9/L; hemoglobin * 8 g/dL; AST/ALT ≤ 3x ULN (≤ 5x with liver metastases); total bilirubin ≤ 1.5x ULN; creatinine clearance * 50 mL/min. * Left ventricular ejection fraction (LVEF) ≥ 45% and no uncontrolled cardiac arrhythmia. * Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception during study treatment and for 6 months after last CAR-NK infusion. * Ability to understand and willingness to sign informed consent. Exclusion Criteria: * Active, untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients with treated CNS metastases may be eligible if clinically stable for ≥ 4 weeks and off high-dose steroids. * Prior gene-modified cellular therapy (e.g., CAR-T or CAR-NK) within 6 months or unresolved grade ≥ 2 toxicity from prior cellular therapy. * Clinically significant active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted). * Uncontrolled infection, including uncontrolled HBV, HCV, or HIV infection (controlled infections may be eligible per investigator). * History of severe hypersensitivity to fludarabine or cyclophosphamide. * Pregnant or breastfeeding. * Concurrent participation in another interventional study that could confound safety or efficacy assessments. * Any condition that, in the investigator's judgment, would make the participant unsuitable for the study (e.g., uncontrolled comorbidity, inability to comply with protocol procedures).

Primary outcome measure(s)

  • Incidence of dose-limiting toxicities (DLTs) — 28 Days
    Incidence of dose-limiting toxicities (DLTs) (including cytokine release syndrome and neurotoxicity) graded by CTCAE v5.0 and ASTCT consensus criteria for CRS/ICANS
  • Safety profile — 12 months
    Safety profile by type, frequency, severity, and relatedness of treatment-emergent adverse events (AEs) and serious AEs.
  • Recommended Phase 2 Dose — 56 days
    Recommended Phase 2 Dose (RP2D) based on DLTs, overall safety, and biologic activity (CAR-NK expansion/persistence).

Trial sites (1)

FacilityCityRegionStatus
Peking University Shenzhen Hospital Shenzhen Guangdong Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07486089 on ClinicalTrials.gov ↗ ← All trials in China