Recruiting
Dual-Target CAR-NK Cells for Advanced Breast Cancer (HER2+ and TNBC)
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.
ClinicalTrials.gov IDNCT07486089
PhasePHASE1, PHASE2
Enrollment60
SponsorBeijing Biotech
Age18 Years
SexALL
Conditions studied
Breast Cancer (Locally Advanced or Metastatic), HER2-positive Breast Cancer, Triple-Negative Breast Cancer (TNBC)
About this study
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.
Interventions
- Biological: 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.
- Drug: Lymphodepleting chemotherapy — fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4), prior to CAR-NK infusion.
- Other: Supportive care — Premedication per institutional standard (e.g., acetaminophen and antihistamine).
Tumor lysis and infection prophylaxis per institutional guidelines.
Primary outcomes
- Incidence of dose-limiting toxicities (DLTs) (28 Days)
- Safety profile (12 months)
- Recommended Phase 2 Dose (56 days)
Eligibility information
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).
Study locations
- Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036 China
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-28.