Dual-target CAR-NK therapy for advanced HER2-positive and triple-negative breast cancer
Phase 1/2, Biomarker-guided, Open-label Study of Allogeneic Dual-target CAR-NK Cells Directed Against HER2/ERBB2, MUC1, and/or ROR1 in Patients With Advanced or Metastatic Breast Cancer (Including HER2-positive and Triple-negative Disease).
This test gives a personalized dual-target CAR-NK cell infusion after short-course chemo to see if it is safe and can shrink tumors in adults with advanced HER2-positive or triple-negative breast cancer whose tumors express HER2, MUC1, or ROR1.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, cyclophosphamide, fludarabine, chimeric antigen receptor, chemotherapy |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07486089 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults with histologically confirmed locally advanced or metastatic HER2-positive breast cancer or TNBC who have progressed on or cannot receive standard therapies, have ECOG 0–1, measurable disease, and tumor antigen expression (HER2, MUC1, or ROR1) are the intended participants.
Not a fit: Patients whose tumors lack the target antigens, who have poor organ function, uncontrolled cardiac disease, ECOG >1, or who are pregnant are unlikely to qualify or benefit from this therapy.
Why it matters
Potential benefit: If successful, the approach could provide a new targeted cell therapy option that safely reduces tumor burden for patients with advanced HER2-positive or triple-negative breast cancer who express the selected antigens.
How similar studies have performed: Allogeneic CAR-NK approaches have shown early promise in hematologic cancers, but dual-target CAR-NK for breast cancer is experimental with very limited clinical data to date.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Shenzhen, Guangdong
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.