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 trial will test a dual-target CAR-NK cell therapy in adults with advanced HER2-positive or triple-negative breast cancer who have progressed on or cannot receive standard treatments.
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 | NCT07510802 on ClinicalTrials.gov |
What this trial studies
This two-part, first-in-program trial gives adults with advanced HER2-positive or triple-negative breast cancer a biomarker-guided, dual-target CAR-NK cell therapy after short-course lymphodepleting chemotherapy. Tumor samples are tested for HER2, MUC1, and ROR1 (and mesothelin in some TNBC cases) to select one of three CAR-NK products matched to each patient’s dominant antigen profile. Part A uses dose escalation to identify a safe and feasible dose, and Part B enrolls biomarker-defined expansion cohorts to look for preliminary anti-tumor activity. The allogeneic, cryopreserved NK product is engineered with a dual-specific CAR and an inducible safety switch and is administered intravenously.
Who should consider this trial
Good fit: Ideal candidates are adults with histologically confirmed locally advanced or metastatic HER2-positive or triple-negative breast cancer, measurable disease, ECOG 0–1, adequate organ function, expression of at least one target antigen on tumor testing, and prior progression on or intolerance to standard therapies.
Not a fit: Patients unlikely to benefit include those whose tumors lack the tested target antigens, those with poor performance status or organ dysfunction, pregnancy, uncontrolled cardiac disease, or those unable to undergo lymphodepleting chemotherapy.
Why it matters
Potential benefit: If successful, this approach could provide a new targeted cell therapy option that shrinks tumors for patients with HER2-positive or triple-negative breast cancer who have exhausted standard treatments.
How similar studies have performed: Related CAR-NK approaches have shown promising early activity in blood cancers, but dual-target CAR-NK for solid tumors like breast cancer remains largely experimental with limited prior success.
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: shan 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.