NCT07486089

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
22mo left

Started Feb 2026

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress14%
Feb 2026Mar 2028

Study Start

First participant enrolled

February 2, 2026

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

March 17, 2026

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 20, 2026

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 14, 2027

Expected
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 17, 2028

Last Updated

March 20, 2026

Status Verified

March 1, 2026

Enrollment Period

1 year

First QC Date

March 17, 2026

Last Update Submit

March 17, 2026

Conditions

HER2-positive Breast CancerTriple-Negative Breast Cancer (TNBC)Breast Cancer (Locally Advanced or Metastatic)

Keywords

CAR-NK; dual targetingdoptive cellular immunotherapyHER2 / ERBB2MUC1ROR1mesothelinsolid tumorbiomarker-guided cohort assignmentLymphodepletionfludarabinecyclophosphamide

Outcome Measures

Primary Outcomes (3)

  • Incidence of dose-limiting toxicities (DLTs)

    Incidence of dose-limiting toxicities (DLTs) (including cytokine release syndrome and neurotoxicity) graded by CTCAE v5.0 and ASTCT consensus criteria for CRS/ICANS

    28 Days

  • Safety profile

    Safety profile by type, frequency, severity, and relatedness of treatment-emergent adverse events (AEs) and serious AEs.

    12 months

  • Recommended Phase 2 Dose

    Recommended Phase 2 Dose (RP2D) based on DLTs, overall safety, and biologic activity (CAR-NK expansion/persistence).

    56 days

Secondary Outcomes (5)

  • Objective response rate (ORR) by RECIST v1.1 (and iRECIST, if immunotherapy response patterns are suspected).

    12 months

  • Disease control rate (DCR)

    12 months

  • Duration of response (DoR).

    24 months

  • Progression-free survival (PFS)

    24 months

  • Overall survival (OS)

    24 months

Study Arms (4)

Dose Escalation (Part A)

EXPERIMENTAL

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).

Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK)Drug: Lymphodepleting chemotherapyOther: Supportive care

Expansion Cohort A (HER2/MUC1)

EXPERIMENTAL

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.

Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK)Drug: Lymphodepleting chemotherapyOther: Supportive care

Expansion Cohort B (HER2/ROR1)

EXPERIMENTAL

HER2-positive breast cancer or HER2-low disease with high ROR1 expression; receives HER2/ROR1 dual-target CAR-NK at RP2D.

Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK)Drug: Lymphodepleting chemotherapyOther: Supportive care

Expansion Cohort C (MUC1/ROR1; TNBC)

EXPERIMENTAL

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.

Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK)Drug: Lymphodepleting chemotherapyOther: Supportive care

Interventions

Dual-target CAR-NK cells (EB-DT-CAR-NK)BIOLOGICAL

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.

Also known as: EB-DT-CAR-NK (Essen Biotech Dual-Target CAR-NK)
Dose Escalation (Part A)Expansion Cohort A (HER2/MUC1)Expansion Cohort B (HER2/ROR1)Expansion Cohort C (MUC1/ROR1; TNBC)
Lymphodepleting chemotherapyDRUG

fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4), prior to CAR-NK infusion.

Also known as: Fludarabine (Fludara®)
Dose Escalation (Part A)Expansion Cohort A (HER2/MUC1)Expansion Cohort B (HER2/ROR1)Expansion Cohort C (MUC1/ROR1; TNBC)
Supportive careOTHER

Premedication per institutional standard (e.g., acetaminophen and antihistamine). Tumor lysis and infection prophylaxis per institutional guidelines.

Also known as: Cyclophosphamide (Cytoxan®)
Dose Escalation (Part A)Expansion Cohort A (HER2/MUC1)Expansion Cohort B (HER2/ROR1)Expansion Cohort C (MUC1/ROR1; TNBC)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • g/dL; AST/ALT ≤ 3x ULN (≤ 5x with liver metastases); total bilirubin ≤ 1.5x ULN; creatinine clearance
  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Breast NeoplasmsNeoplasm MetastasisTriple Negative Breast Neoplasms

Interventions

fludarabinefludarabine phosphatePalliative CareCyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Patient CareTherapeuticsHealth ServicesHealth Care Facilities Workforce and ServicesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030Seni-Lu@beijing-biotech.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
Open-label design; no blinding of participants, investigators, or outcome assessors.
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Part A: 3+3 dose-escalation across 3 planned dose levels. Part B: biomarker-guided, non-randomized expansion cohorts based on tumor antigen expression with cohort-specific Simon two-stage stopping rules for futility.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 17, 2026

First Posted

March 20, 2026

Study Start

February 2, 2026

Primary Completion (Estimated)

February 14, 2027

Study Completion (Estimated)

March 17, 2028

Last Updated

March 20, 2026

Record last verified: 2026-03

Locations

CN(1)