Study of Autologous CAR-T Cells Targeting B7-H3 in TNBC iC9-CAR.B7-H3 T Cells

July 27, 2026 updated by: UNC Lineberger Comprehensive Cancer Center

Study of Administration of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors and Containing the Inducible Caspase 9 Safety Switch in Subjects With Triple Negative Breast Cancer

This phase 1, single-center, open-label study explores the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells in subjects with relapsed/refractory triple-negative breast cancer (TNBC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9-CAR.B7-H3 T cells) treatment is experimental and has not been approved by the Food and Drug Administration. The safety of iC9-CAR.B7-H3 T cells will be investigated using a modified 3+3 design. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD) and additional factors such as the ability to manufacture sufficient cells for infusion.

Subjects with TNBC who meet procurement eligibility criteria will have cells collected to manufacture iC9-CAR.B7-H3 T cells. Eligible subjects will receive lymphodepletion with cyclophosphamide and fludarabine.

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • 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 Contact Backup

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina
        • Contact:
        • Principal Investigator:
          • Yara Abdou, MD
        • Sub-Investigator:
          • Claire E Dees, MD, MSc

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:

Unless otherwise noted, subjects must meet all of the following criteria to participate in in all phases of the study:

  1. Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative.
  2. Age ≥ 18 years at the time of consent.
  3. Karnofsky score of > 60% (see APPENDIX VI- Karnofsky Scale))

  4. Histologically confirmed TNBC (ER-, PR-, HER2-negative)

    1. ER- and PR-negative: defined as < 1% staining by immunohistochemistry (IHC)
    2. HER2-negative: defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio < 2.0

Exclusion Criteria:

  1. Patients with a history of symptomatic CNS involvement or multiple metastases requiring whole-brain radiation.
  2. Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  3. Subject does not have a measurable and or evaluable disease as defined by RECIST 1.1

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: iC9-CAR.B7-H3 T cells
Specimen will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.
Biological: iC9-CAR.B7-H3 T Cell Therapy
iC9-CAR.B7-H3 T cells will then be administered intravenously
Other Names:
  • iC9-CAR.B7-H3 T cells
Drug: cyclophosphamide
cyclophosphamide 300 mg/m2 IV will be given.
Other Names:
  • Cytoxan
Drug: fludarabine
fludarabine 30 mg/m2 IV will be given.
Other Names:
  • Fludara
  • Fludarabine Phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS)
Time Frame: Up to 4 weeks

Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria.

Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Up to 4 weeks
Toxicity: NCI-CTCAE
Time Frame: Up to 4 weeks

Toxicity will be graded as the Number of participants with adverse events (AE)s

AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Up to 4 weeks
Toxicity: Cytokine Release Syndrome (CRS)
Time Frame: Up to 8 weeks after infusion of Biological/Vaccine
CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death
Up to 8 weeks after infusion of Biological/Vaccine

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 2 years
OS will be measured from the first day of lymphodepleting chemotherapy prior to iC9-CAR.B7-H3 T cell infusion to the date of death for any cause.
Up to 2 years
The recommended phase 2 dose (RP2D) NCI-CTCAE v5.
Time Frame: Up to 4 weeks
The RP2D of iC9-CAR.B7-H3 T cells will be determined based on modified 3+3 dose finding rules and the tolerability of iC9-CAR.B7-H3 T cells will be assessed by NCI-CTCAE v5 criteria.
Up to 4 weeks
The recommended phase 2 dose (RP2D) CRS Grading
Time Frame: Up to 4 weeks
The RP2D of iC9-CAR.B7-H3 T cells will be determined based on modified 3+3 dose finding rules and the tolerability of iC9-CAR.B7-H3 T cells will be assessed byASTCT Consensus CRS Grading Criteria.
Up to 4 weeks
The recommended phase 2 dose (RP2D)
Time Frame: Up to 4 weeks
The RP2D of iC9-CAR.B7-H3 T cells will be determined based on modified 3+3 dose finding rules and the tolerability of iC9-CAR.B7-H3 T cells will be assessed by ASTCT Consensus ICANS Grading Criteria.
Up to 4 weeks
Objective response rate
Time Frame: Up to 2 years

Objective response rate is defined as the percentage of subjects achieving a confirmed partial response (PR) or better (≥ PR) based on RECIST 1.1 criteria.

Complete response - Disappearance of all target lesions. Any pathological lymph node (LN) must be <10mm. Partial response: At least a 30% decrease in the sum of the largest distance (LD) of the target lesions. Progressive Disease (PD): At least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started including baseline if that is the smallest in the study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions also constitutes PD. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.
Up to 2 years
Progression Free Survival (PFS)
Time Frame: Up to 2 years
PFS will be measured from the first day of lymphodepletion chemotherapy prior to iC9-CAR.B7-H3 T cell infusion to progression per RECIST 1.1 or death.
Up to 2 years
Duration of Response (DOR)
Time Frame: Up to 2 years
DOR is time from the first immune Complete Response (iCR) or immune Partial Response (iPR) until progressive disease (iCPD) per immune Response Evaluation Criteria in Solid Tumors (iRECIST), criteria or death, whichever occurs first. Per iRECIST) responses are assessed by imaging as follows: iCR: Disappearance of all lesions, with pathological lymph nodes <10 mm. iPR: ≥30% decrease in target lesions from baseline. Immune Stable Disease (iSD): Neither sufficient shrinkage for iPR nor sufficient increase. Immune Unconfirmed Progressive Disease (iUPD): Initial evidence of progression based on RECIST 1.1, including growth of existing lesions and/or new lesions; requires confirmation. Immune Confirmed Progressive Disease (iCPD): Progression confirmed at a subsequent assessment following iUPD per iRECIST. New lesions are recorded separately and do not automatically constitute treatment failure. Progression must be confirmed after iUPD to establish iCPD.
Up to 2 years

Collaborators and Investigators

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

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

M.D. Anderson Cancer Center
National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Yara Abdou, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

June 27, 2024

Primary Completion (Estimated)

May 22, 2028

Study Completion (Estimated)

May 1, 2030

Study Registration Dates

First Submitted

March 22, 2024

First Submitted That Met QC Criteria

March 28, 2024

First Posted (Actual)

April 4, 2024

Study Record Updates

Last Update Posted (Actual)

July 28, 2026

Last Update Submitted That Met QC Criteria

July 27, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC2128-ATL
  • P50CA058223-29A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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