Dual-target CAR-NK therapy for advanced HER2-positive and triple-negative breast cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This two-part, first-in-program study uses tumor biomarker testing (IHC on fresh or archival tissue) to select one of three dual-target CAR-NK products matched to each patient's antigen profile. Part A uses dose escalation to identify a safe and feasible dose and Part B enrolls biomarker-defined expansion cohorts for HER2-positive disease and TNBC to look for preliminary anti-tumor activity. All participants receive short-course lymphodepleting chemotherapy (fludarabine plus cyclophosphamide) before a single intravenous infusion of an allogeneic, cryopreserved dual-specific CAR-NK product that includes an inducible safety switch. Safety, tolerability, and early signals of efficacy will be measured through clinical exams, imaging per RECIST v1.1, and laboratory monitoring.

Why it matters

Who can join: the full rules

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).

Where it's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: Seni S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.