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

ConditionsBreast Cancer (Locally Advanced or Metastatic)HER2-positive Breast CancerTriple-Negative Breast Cancer (TNBC)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorBeijing Biotech

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

Trial design

Design model

Sequential

Treatments tested in this trial

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

    Biological/Vaccine

    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.

  • Lymphodepleting chemotherapy

    Drug

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

  • Supportive care

    Other intervention

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

Treatment groups

60 Participants
are divided into 4 treatment groups
Group A: Dose Escalation (Part A)Experimental treatment 3 interventions
Group B: Expansion Cohort A (HER2/MUC1)Experimental treatment 3 interventions
Group C: Expansion Cohort B (HER2/ROR1)Experimental treatment 3 interventions
Group D: Expansion Cohort C (MUC1/ROR1; TNBC)Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
28 Days
2

Safety profile

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

Time frame
12 months
3

Recommended Phase 2 Dose

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

Time frame
56 days

Secondary outcomes

1

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

Time frame
12 months
2

Disease control rate (DCR)

Disease control rate (DCR) (CR+PR+SD)

Time frame
12 months
3

Duration of response (DoR).

Time frame
24 months
4

Progression-free survival (PFS)

Time frame
24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Beijing Biotech

Lead sponsor

Source ClinicalTrials.gov
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