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

March 31, 2026 updated by: Beijing Biotech

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 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,TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Natural killer (NK) cells can recognize and kill abnormal cells as part of the innate immune system.

CAR engineering can enhance NK-cell recognition of tumor-associated antigens and may improve anti-tumor activity in solid tumors.

This is a two-part, first-in-program study. Part A uses dose escalation to identify a safe and feasible dose of a dual-target CAR-NK cell product. Part B evaluates preliminary efficacy in biomarker-defined expansion cohorts for HER2-positive breast cancer and triple-negative breast cancer (TNBC).

Target selection is biomarker-guided. A fresh or archival tumor sample is tested by immunohistochemistry (IHC) for HER2/ERBB2, MUC1, and ROR1 expression. Participants are assigned to one of three dual-target CAR-NK constructs based on a predefined algorithm prioritizing highest and most homogeneous target expression. In TNBC, mesothelin testing may be performed to support an exploratory sub-cohort.

All participants receive lymphodepleting chemotherapy (fludarabine + cyclophosphamide) before CAR-NK infusion. The CAR-NK product is an allogeneic, cryopreserved NK-cell therapy engineered to express a dual-specific CAR and an inducible safety switch; the product is administered intravenously.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
Advanced/metastatic breast cancer with measurable disease and expression of at least one target antigen (HER2, MUC1, or ROR1). Participants receive lymphodepletion followed by a single infusion of dual-target CAR-NK (construct chosen by antigen profile)
Other: Supportive care

Premedication per institutional standard (e.g., acetaminophen and antihistamine).

Tumor lysis and infection prophylaxis per institutional guidelines.

Biological: Dual-target CAR-NK cells
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.
Experimental: Expansion Cohort A
HER2-positive breast cancer (HER2 IHC 3+ or IHC 2+ with ISH amplification) with MUC1 expression; receives HER2/MUC1 dual-target CAR-NK at RP2D
Other: Supportive care

Premedication per institutional standard (e.g., acetaminophen and antihistamine).

Tumor lysis and infection prophylaxis per institutional guidelines.

Biological: Dual-target CAR-NK cells
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.
Experimental: Expansion Cohort B
HER2-positive breast cancer or HER2-low disease with high ROR1 expression; receives HER2/ROR1 dual-target CAR-NK at RP2D.
Other: Supportive care

Premedication per institutional standard (e.g., acetaminophen and antihistamine).

Tumor lysis and infection prophylaxis per institutional guidelines.

Biological: Dual-target CAR-NK cells
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.
Experimental: Expansion Cohort C
Triple-negative breast cancer with MUC1 and/or ROR1 expression; receives MUC1/ROR1 dual-target CAR-NK at RP2D. Exploratory TNBC sub-cohort: mesothelin-positive TNBC may be analyzed separately.
Other: Supportive care

Premedication per institutional standard (e.g., acetaminophen and antihistamine).

Tumor lysis and infection prophylaxis per institutional guidelines.

Biological: Dual-target CAR-NK cells
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 days
28 days
Recommended Phase 2 Dose (RP2D) based on overall safety
Time Frame: 56 days
56 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease control rate
Time Frame: 12 months
12 months
Objective response rate (ORR) by RECIST v1.1
Time Frame: 12 months.
12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

April 17, 2028

Study Registration Dates

First Submitted

March 20, 2026

First Submitted That Met QC Criteria

March 31, 2026

First Posted (Actual)

April 6, 2026

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EB-CARNK-BC15

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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